[Improvement of Lower Urinary Tract Symptoms in Patients with Prostate Cancer Treated with Maximal Androgen Blockade]

Zhong Nan Da Xue Xue Bao. Yi Xue Ban = Journal of Central South University. Medical Sciences. Sep, 2011  |  Pubmed ID: 21946203

To investigate the timing of reaching maximum improvement of the lower urinary tract symptoms (LUTS) in patients with advanced prostate cancer treated with maximal androgen blockade(MAB), and to provide guidelines for the treatment program.

Apolipoprotein A-I Mimetic Peptide D-4F Promotes Human Endothelial Progenitor Cell Proliferation, Migration, Adhesion Though ENOS/NO Pathway

Molecular Biology Reports. Sep, 2011  |  Pubmed ID: 21947883

Circulating endothelial progenitor cells (EPCs) have a critical role in endothelial maintenance and repair. Apolipoprotein A-I mimetic peptide D-4F has been shown to posses anti-atherogenic properties via sequestration of oxidized phospholipids, induction of remodeling of high density lipoprotein and promotion of cholesterol efflux from macrophage-derived foam cells. In this study, we test the effects of D-4F on EPC biology. EPCs were isolated from the peripheral venous blood of healthy male volunteers and characterized by 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine-labeled acetylated LDL uptake and ulex europaeus agglutinin binding and flow cytometry. Cell proliferation, migration, adhesion, nitric oxide production and endothelial nitric oxide synthase (eNOS) expression in the absence and presence of D-4F or simvastatin (as a positive control), were assayed. We demonstrated that D-4F significantly enhanced EPC proliferation, migration and adhesion in a dose-dependent manner compared with vehicle. However, all of the favorable effects of D-4F on EPCs were dramatically attenuated by preincubation with NOS inhibitor L-NAME. Further, D-4F also increased nitric oxide production in culture supernatant and the levels of eNOS expression and phosphorylation. The stimulatory effects of D-4F (10 μg/ml) on EPC biology were comparable to 0.5 μM simvastatin. These results suggest that eNOS/NO pathway mediates the functional modulation of EPC biology in response to D-4F treatment and support the notion that the beneficial role of D-4F on EPCs may be one of the important components of its anti-atherogenic potential.

[Application of Circular Staplers in Cervical Esophagogastric Anastomosis After Esophageal Cancer Resection]

Zhonghua Wei Chang Wai Ke Za Zhi = Chinese Journal of Gastrointestinal Surgery. Sep, 2011  |  Pubmed ID: 21948534

To evaluate safety and feasibility of circular staplers in cervical esophagogastrostomy after esophageal cancer resection.

Kinetics and Mechanism of Conformational Changes in a G-quadruplex of Thrombin-binding Aptamer Induced by Pb2+

The Journal of Physical Chemistry. B. Nov, 2011  |  Pubmed ID: 21950308

It has been shown that guanine-rich DNA can fold into a G-quadruplex with certain metal cations. The spectral characteristics, thermostability, and kinetics for the formation of a Pb(2+)-driven G-quadruplex of thrombin-binding aptamer (TBA) were measured in the current work using a combination of ultraviolet (UV) and circular dichroism (CD) spectroscopy along with stopped-flow technique. CD spectra demonstrated that TBA could fold into a unique G-quadruplex with a strong positive peak at 312 nm. Analysis of the titration data reveals that the binding stoichiometry is 1:1 for the titration of TBA with Pb(NO(3))(2), which is in accordance with the localization of the Pb(2+) ion between the adjacent G-quartets. Thermal denaturation profiles indicate that the Pb(2+)-induced intramolecular G-quadruplex is more stable than those driven by Na(+) or K(+) ions. Kinetic studies suggest that the Pb(2+)-induced folding G-quadruplex of TBA probably proceeds through the rapid formation of an intermediate Pb(2+)-TBA complex, which then isomerizes to the fully folded structure. Conformational changes transpire after the addition of Pb(NO(3))(2) to the Na(+)- or K(+)-induced G-quadruplexes, which may be attributed to the replacement of Na(+) or K(+) ions by Pb(2+) ions and the generation of a more compact structure of the Pb(2+)-TBA structure. The relaxation time, τ, of folding the G-quadruplex is reduced from 1.05 s in the presence of Pb(2+) ions alone to 0.34 s under the cooperation of initially added Na(+) ions, while τ is increased to 8.33 s under the competition of initially added K(+) ions.

Design Optimization of Scaffold Microstructures Using Wall Shear Stress Criterion Towards Regulated Flow-induced Erosion

Journal of Biomechanical Engineering. Aug, 2011  |  Pubmed ID: 21950901

Tissue scaffolds aim to provide a cell-friendly biomechanical environment for facilitating cell growth. Existing studies have shown significant demands for generating a certain level of wall shear stress (WSS) on scaffold microstructural surfaces for promoting cellular response and attachment efficacy. Recently, its role in shear-induced erosion of polymer scaffold has also drawn increasing attention. This paper proposes a bi-directional evolutionary structural optimization (BESO) approach for design of scaffold microstructure in terms of the WSS uniformity criterion, by downgrading highly-stressed solid elements into fluidic elements and/or upgrading lowly-stressed fluidic elements into solid elements. In addition to this, a computational model is presented to simulate shear-induced erosion process. The effective stiffness and permeability of initial and optimized scaffold microstructures are characterized by the finite element based homogenization technique to quantify the variations of mechanical properties of scaffold during erosion. The illustrative examples show that a uniform WSS is achieved within the optimized scaffold microstructures, and their architectural and biomechanical features are maintained for a longer lifetime during shear-induced erosion process. This study provides a mathematical means to the design optimization of cellular biomaterials in terms of the WSS criterion towards controllable shear-induced erosion.

IsoLasso: a LASSO Regression Approach to RNA-Seq Based Transcriptome Assembly

Journal of Computational Biology : a Journal of Computational Molecular Cell Biology. Nov, 2011  |  Pubmed ID: 21951053

The new second generation sequencing technology revolutionizes many biology-related research fields and poses various computational biology challenges. One of them is transcriptome assembly based on RNA-Seq data, which aims at reconstructing all full-length mRNA transcripts simultaneously from millions of short reads. In this article, we consider three objectives in transcriptome assembly: the maximization of prediction accuracy, minimization of interpretation, and maximization of completeness. The first objective, the maximization of prediction accuracy, requires that the estimated expression levels based on assembled transcripts should be as close as possible to the observed ones for every expressed region of the genome. The minimization of interpretation follows the parsimony principle to seek as few transcripts in the prediction as possible. The third objective, the maximization of completeness, requires that the maximum number of mapped reads (or ?expressed segments? in gene models) be explained by (i.e., contained in) the predicted transcripts in the solution. Based on the above three objectives, we present IsoLasso, a new RNA-Seq based transcriptome assembly tool. IsoLasso is based on the well-known LASSO algorithm, a multivariate regression method designated to seek a balance between the maximization of prediction accuracy and the minimization of interpretation. By including some additional constraints in the quadratic program involved in LASSO, IsoLasso is able to make the set of assembled transcripts as complete as possible. Experiments on simulated and real RNA-Seq datasets show that IsoLasso achieves, simultaneously, higher sensitivity and precision than the state-of-art transcript assembly tools.

Cyclospora Papionis, Cryptosporidium Hominis, and Human-pathogenic Enterocytozoon Bieneusi in Captive Baboons in Kenya

Journal of Clinical Microbiology. Dec, 2011  |  Pubmed ID: 21956988

Cyclospora papionis, Cryptosporidium hominis, and Enterocytozoon bieneusi were detected in 42 (17.9%), 6 (2.6%), and 29 (12.3%) of 235 newly captured baboons in Kenya, respectively. Most C. hominis subtypes and E. bieneusi genotypes found have been detected in humans in the area, suggesting that cross-species transmission of cryptosporidiosis and microsporidiosis is possible.

Growth of the Pancreatic Cancer Cell Line PANC-1 is Inhibited by Protein Phosphatase 2A Inhibitors Through Overactivation of the C-Jun N-terminal Kinase Pathway

European Journal of Cancer (Oxford, England : 1990). Nov, 2011  |  Pubmed ID: 21958460

Protein phosphatase 2A (PP2A) is a multimeric serine/threonine phosphatase that can dephosphorylate multiple kinases. It is generally considered to be a cancer suppressor as its inhibition can induce phosphorylation and activation of substrate kinases that mainly accelerate growth. We previously reported that cantharidin, an active constituent of a traditional Chinese medicine, potently and selectively inhibited PP2A, yet efficiently repressed the growth of pancreatic cancer cells through activation of the c-Jun N-terminal kinase (JNK) pathway. This suggested that activation of kinase pathways might also be a potential strategy for cancer therapy. In this study, we have confirmed that the basal activity of the phospatidylinositol 3-kinase (PI3K)/JNK/activator protein 1 (AP-1) pathway promoted pancreatic cancer cell growth when stimulated by growth factors. Interestingly, although treatment with the PP2A inhibitors, cantharidin or okadaic acid (OA), amplified the PI3K-dependent activation of JNK, cell growth was repressed. We therefore hypothesised that a specific level of activity of the JNK pathway might be required to maintain the promitogenic function, as both repression and overactivation of JNK could inhibit cell proliferation. It was found that the JNK-dependent growth inhibition was independent of the activation of AP-1, but dependent on the repression of Akt. Although the PP2A inhibitors triggered overactivation of JNK and inhibited cell growth, excessively activated protein kinase C (PKC) improved cell survival. Combined treatment with a PP2A inhibitor and a PKC inhibitor produced a synergistic effect, which indicates a potentially promising therapeutic approach to pancreatic cancer treatment.

Determination of Hymexazol in Cucumber and Soil Samples by Derivatization Using GC-FPD

Bulletin of Environmental Contamination and Toxicology. Dec, 2011  |  Pubmed ID: 21959994

A sensitive and effective analytical method for the determination of hymexazol in cucumber and soil samples by gas chromatography with a flame photometric detector was developed. This method was validated with fortified at three different levels of 0.2, 1.0 and 5.0 mg/kg. Average recoveries obtained from cucumber and soil samples at three fortified levels were 94.0%-107.8% with relative standard deviations (RSDs) of less than 11.4%. Limits of quantification (LOQ) in cucumber and soil were 0.2 mg/kg. The method was successfully applied to determine hymexazol in real samples of cucumber and soil under open fields.

Incident Dementia in a Defined Older Chinese Population

PloS One. 2011  |  Pubmed ID: 21966372

Current knowledge about incident dementia is mainly derived from studies undertaken in the West, showing that dementia is related to older age, low socio-economic status, lack of social network, depression and cardiovascular disease risk factors. We know little about incidence and predictors of dementia in China, where the prevalence is increasing and the patterns of risk factors are different.

Infectious Bursal Disease Virus-induced Activation of JNK Signaling Pathway is Required for Virus Replication and Correlates with Virus-induced Apoptosis

Virology. Nov, 2011  |  Pubmed ID: 21968197

The Jun NH2-terminal kinase (JNK) which serves as an important component of cellular signal transduction pathways has been shown to regulate many viral infections. The present study demonstrated for the first time that infectious bursal disease virus (IBDV), the causative agent of a highly contagious disease in chickens, can activate JNK1/2 pathway in IBDV-infected cells dependent upon viral replication. IBDV-induced JNK1/2 activation causes its downstream target c-Jun phosphorylation, which kinetically paralleled JNK1/2 activation. Investigations into the mechanism of JNK1/2 regulation revealed that inhibition of JNK1/2 activation leads to reduced viral progeny release, which is associated with decreased viral transcription and lower virus protein expression, and thereby limiting apoptotic cell death as evidenced by blockage of Bax activation, cytochrome c release, and caspase activation. These data suggest that the JNK pathway plays an important role in the IBDV replication and contributes to virus-mediated changes in host cells.

[The Effects of Inoculation Route and Adjuvant Type on the Immunizing Potency of CVB3 VP1 Protein]

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi = Chinese Journal of Cellular and Molecular Immunology. Oct, 2011  |  Pubmed ID: 21968309

To explore the effects of inoculation route and adjuvant type on the immunizing potency of coxsackievrus B type 3 (CVB3) VP1 protein.

Core-shell Ag@SiO2@mSiO2 Mesoporous Nanocarriers for Metal-enhanced Fluorescence

Chemical Communications (Cambridge, England). Nov, 2011  |  Pubmed ID: 21968454

A novel mesoporous nanocarrier consisting of a silver core, a silica spacer with controlled thickness and a fluorophores-loaded mesoporous silica shell was fabricated for the metal-enhanced fluorescence (MEF) and Förster resonance energy transfer (FRET) effects.

The Dissipation of Ethofenprox in Cabbage and Soil Under Open Conditions

Environmental Monitoring and Assessment. Oct, 2011  |  Pubmed ID: 21968878

The dissipation of ethofenprox in cabbage and soil under open conditions was investigated at two primary cabbage-growing regions, Beijing and Kunming in China. Samples were extracted with acetonitrile and determined by ultra-performance liquid chromatography with a single quadrupole detector. Dissipation of ethofenprox from cabbage and soil can be best explained by a first-order decay process. The half-lives of ethofenprox were 1.9 and 2.3 days in cabbage and 20.0 and 13.0 days in soil at Beijing and Kunming, respectively. The concentration of ethofenprox residue was reduced by 90% taking 7 and 60 days in cabbage and soil. Dissipation rates in cabbage and soil at two geographically separated experimental fields differed, suggesting that this was affected by complicated factors, such as local climate and soil characteristics. These data could provide guidance for the proper and safe use of this pesticide on cabbage in China.

MBD 4--a Potential Substrate for Protein Kinase X

Acta Biochimica Et Biophysica Sinica. Nov, 2011  |  Pubmed ID: 21971312

Secreted Heat Shock Protein-90 (Hsp90) in Wound Healing and Cancer

Biochimica Et Biophysica Acta. Sep, 2011  |  Pubmed ID: 21982864

Extracellular Hsp90 proteins, including "membrane-bound", "released" and "secreted", were first reported more than two decades ago. Only studies of the past 7years have begun to reveal a picture for when, how and why Hsp90 gets exported by both normal and tumor cells. Normal cells secrete Hsp90 in response to tissue injury. Tumor cells have managed to constitutively secrete Hsp90 for tissue invasion. In either case, sufficient supply of the extracellular Hsp90 can be guaranteed by its unusually abundant storage inside the cells. A well-characterized function of secreted Hsp90α is to promote cell motility, a crucial event for both wound healing and cancer. The reported targets for extracellular Hsp90α include MMP2, LRP-1, tyrosine kinase receptors and possibly more. The pro-motility activity of secreted Hsp90α resides within a fragment, called 'F-5', at the boundary between linker region and middle domain. Inhibition of its secretion, neutralization of its extracellular action or interruption of its signaling through LRP-1 block wound healing and tumor invasion in vitro and in vivo. In normal tissue, topical application of F-5 promotes acute and diabetic wound healing far more effectively than US FDA-approved conventional growth factor therapy in mice. In cancer, drugs that selectively target the F-5 region of secreted Hsp90 by cancer cells may be more effective and less toxic than those that target the ATPase of the intracellular Hsp90. This article is part of a Special Issue entitled: Heat Shock Protein 90 (HSP90).

Lamin A/C Deficiency is Associated with Fat Infiltration of Muscle and Bone

Mechanisms of Ageing and Development. Nov-Dec, 2011  |  Pubmed ID: 21982926

Sarcopenia and osteopenia are two common components of the frailty syndrome that may share a common underlying mechanism. Since frailty has been associated with increased fat infiltration in muscle and bone, we hypothesized that lamin A/C, a protein of the nuclear envelope that regulates adipose differentiation, could be associated with the pathophysiology of both osteo and sarcopenia in the frailty syndrome. Four-week-old lamin A/C null (Lmna(-/-)), heterozygous (Lmna(+/-)) and wild type (WT) mice were sacrificed and their mid-thigh analyzed for fat infiltration using invasive (histology) and non-invasive (μCT) methods. Lmna(-/-) mice showed a significant increase in inter- (~4-fold) and intra-myofiber (~2.5-fold) fat and marrow fat infiltration (~40-fold), with a significant decrease in muscle volume (-42.8%) and bone volume (-21.8%), as compared with WT controls. Furthermore, fat infiltration happened concomitantly with a significant decline in muscle and bone strength in Lmna(-/-) mice. From a mechanistic approach, high levels of pro-adipogenic factors PPARγ and C/EBPα were associated with a reduction in myogenic and osteogenic factors from the Wnt-10b/β-catenin signalling pathway in Lmna(-/-) mice. In conclusion, lamin A/C could constitute the determinant factor in the pathogenesis and potential treatment of both sarcopenia and osteopenia, which are commonly observed in the frailty syndrome.

Peptide-conjugated PAMAM Dendrimer As a Universal DNA Vaccine Platform to Target Antigen-presenting Cells

Cancer Research. Dec, 2011  |  Pubmed ID: 21987727

DNA-based vaccines hold promise to outperform conventional antigen-based vaccines by virtue of many unique features. However, DNA vaccines have thus far fallen short of expectations, due in part to poor targeting of professional antigen-presenting cells (APC) and low immunogenicity. In this study, we describe a new platform for effective and selective delivery of DNA to APCs in vivo that offers intrinsic immune-enhancing characteristics. This platform is based on conjugation of fifth generation polyamidoamine (G5-PAMAM) dendrimers, a DNA-loading surface, with MHC class II-targeting peptides that can selectively deliver these dendrimers to APCs under conditions that enhance their immune stimulatory potency. DNA conjugated with this platform efficiently transfected murine and human APCs in vitro. Subcutaneous administration of DNA-peptide-dendrimer complexes in vivo preferentially transfected dendritic cells (DC) in the draining lymph nodes, promoted generation of high affinity T cells, and elicited rejection of established tumors. Taken together, our findings show how PAMAM dendrimer complexes can be used for high transfection efficiency and effective targeting of APCs in vivo, conferring properties essential to generate effective DNA vaccines.

Differential Pair Distribution Function Study of the Structure of Arsenate Adsorbed on Nanocrystalline γ-alumina

Environmental Science & Technology. Nov, 2011  |  Pubmed ID: 21988151

Structural information is important for understanding surface adsorption mechanisms of contaminants on metal (hydr)oxides. In this work, a novel technique was employed to study the interfacial structure of arsenate oxyanions adsorbed on γ-alumina nanoparticles, namely, differential pair distribution function (d-PDF) analysis of synchrotron X-ray total scattering. The d-PDF is the difference of properly normalized PDFs obtained for samples with and without arsenate adsorbed, otherwise identically prepared. The real space pattern contains information on atomic pair correlations between adsorbed arsenate and the atoms on γ-alumina surface (Al, O, etc.). PDF results on the arsenate adsorption sample on γ-alumina prepared at 1 mM As concentration and pH 5 revealed two peaks at 1.66 Å and 3.09 Å, corresponding to As-O and As-Al atomic pair correlations. This observation is consistent with those measured by extended X-ray absorption fine structure (EXAFS) spectroscopy, which suggests a first shell of As-O at 1.69 ± 0.01 Å with a coordination number of ~4 and a second shell of As-Al at ~3.13 ± 0.04 Å with a coordination number of ~2. These results are in agreement with a bidentate binuclear coordination environment to the octahedral Al of γ-alumina as predicted by density functional theory (DFT) calculation.

Single Turnover of Substrate-bound Ferric Cysteine Dioxygenase with Superoxide Anion: Enzymatic Reactivation, Product Formation, and a Transient Intermediate

Biochemistry. Nov, 2011  |  Pubmed ID: 21992268

Cysteine dioxygenase (CDO) is a non-heme mononuclear iron enzyme that catalyzes the O(2)-dependent oxidation of L-cysteine (Cys) to produce cysteine sulfinic acid (CSA). In this study we demonstrate that the catalytic cycle of CDO can be "primed" by one electron through chemical oxidation to produce CDO with ferric iron in the active site (Fe(III)-CDO, termed 2). While catalytically inactive, the substrate-bound form of Fe(III)-CDO (2a) is more amenable to interrogation by UV-vis and EPR spectroscopy than the 'as-isolated' Fe(II)-CDO enzyme (1). Chemical-rescue experiments were performed in which superoxide (O(2)(•-)) anions were introduced to 2a to explore the possibility that a Fe(III)-superoxide species represents the first intermediate within the catalytic pathway of CDO. In principle, O(2)(•-) can serve as a suitable acceptor for the remaining 3-electrons necessary for CSA formation and regeneration of the active Fe(II)-CDO enzyme (1). Indeed, addition of O(2)(•-) to 2a resulted in the rapid formation of a transient species (termed 3a) observable at 565 nm by UV-vis spectroscopy. The subsequent decay of 3a is kinetically matched to CSA formation. Moreover, a signal attributed to 3a was also identified using parallel mode X-band EPR spectroscopy (g ~ 11). Spectroscopic simulations, observed temperature dependence, and the microwave power saturation behavior of 3a are consistent with a ground state S = 3 from a ferromagnetically coupled (J ~ -8 cm(-1)) high-spin ferric iron (S(A) = 5/2) with a bound radical (S(B) = 1/2), presumably O(2)(•-). Following treatment with O(2)(•-), the specific activity of recovered CDO increased to ~60% relative to untreated enzyme.

An Efficient Linear Scaling Procedure for Constructing Localized Orbitals of Large Molecules Based on the One-particle Density Matrix

The Journal of Chemical Physics. Oct, 2011  |  Pubmed ID: 21992282

We have developed a linear-scaling algorithm for obtaining the Boys localized molecular orbitals from the one-particle density matrix. The algorithm is made up of two steps: the Cholesky decomposition of the density matrix to obtain Cholesky molecular orbitals and the subsequent Boys localization process. Linear-scaling algorithms have been proposed to achieve linear-scaling calculations of these two steps, based on the sparse matrix technique and the locality of the Cholesky molecular orbitals. The present algorithm has been applied to compute the Boys localized orbitals in a number of systems including α-helix peptides, water clusters, and protein molecules. Illustrative calculations demonstrate that the computational time of obtaining Boys localized orbitals with the present algorithm is asymptotically linear with increasing the system size.

The Melatonin MT1 Receptor Axis Modulates Mutant Huntingtin-mediated Toxicity

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Oct, 2011  |  Pubmed ID: 21994366

Melatonin mediates neuroprotection in several experimental models of neurodegeneration. It is not yet known, however, whether melatonin provides neuroprotection in genetic models of Huntington's disease (HD). We report that melatonin delays disease onset and mortality in a transgenic mouse model of HD. Moreover, mutant huntingtin (htt)-mediated toxicity in cells, mice, and humans is associated with loss of the type 1 melatonin receptor (MT1). We observe high levels of MT1 receptor in mitochondria from the brains of wild-type mice but much less in brains from HD mice. Moreover, we demonstrate that melatonin inhibits mutant htt-induced caspase activation and preserves MT1 receptor expression. This observation is critical, because melatonin-mediated protection is dependent on the presence and activation of the MT1 receptor. In summary, we delineate a pathologic process whereby mutant htt-induced loss of the mitochondrial MT1 receptor enhances neuronal vulnerability and potentially accelerates the neurodegenerative process.

General Boundary Mapping Method and Its Application in Designing an Arbitrarily Shaped Perfect Electric Conductor Reshaper

Optics Express. Sep, 2011  |  Pubmed ID: 21996916

A general boundary mapping method is proposed to enable the designing of various transformation devices with arbitrary shapes by reducing the traditional space-to-space mapping to boundary-to-boundary mapping. The method also makes the designing of complex-shaped transformation devices more feasible and flexible. Using the boundary mapping method, an arbitrarily shaped perfect electric conductor (PEC) reshaping device, which is called a "PEC reshaper," is demonstrated to visually reshape a PEC with an arbitrary shape to another arbitrary one. Unlike the previously reported simple PEC reshaping devices, the arbitrarily shaped PEC reshaper designed here does not need to share a common domain. Moreover, the flexibilities of the boundary mapping method are expected to inspire some novel PEC reshapers with attractive new functionalities.

The Crystal Structure of a Munc13 C-terminal Module Exhibits a Remarkable Similarity to Vesicle Tethering Factors

Structure (London, England : 1993). Oct, 2011  |  Pubmed ID: 22000513

Unc13/Munc13s play a crucial function in neurotransmitter release through their MUN domain, which mediates the transition from the Syntaxin-1/Munc18-1 complex to the SNARE complex. The MUN domain was suggested to be related to tethering factors, but no MUN-domain structure is available to experimentally validate this notion and address key unresolved questions about the interactions and minimal structural unit required for Unc13/Munc13 function. Here we identify an autonomously folded module within the MUN domain (MUN-CD) and show that its crystal structure is remarkably similar to several tethering factors. We also show that the activity in promoting the Syntaxin-1/Munc18-1 to SNARE complex transition is strongly impaired in MUN-CD. These results show that MUN domains and tethering factors indeed belong to the same family and may have a common role in membrane trafficking. We propose a model whereby the MUN-CD module is central for Munc13 function but full activity requires adjacent sequences.

Zinc Deficiency Exacerbates Diabetic Down-regulation of Akt Expression and Function in the Testis: Essential Roles of PTEN, PTP1B and TRB3

The Journal of Nutritional Biochemistry. Oct, 2011  |  Pubmed ID: 22000581

Since zinc (Zn) plays an important role in the spermatogenesis and Zn deficiency exacerbated diabetes-induced testicular apoptosis, the present study investigated the effect of Zn deficiency on diabetes-induced testicular Akt-mediated glucose metabolism changes and inflammation. Zn deficiency was induced by chronic treatment of normal and diabetic mice with the Zn chelator N,N,N',N', tetrakis (2-pyridylmethyl) ethylenediaminepentaethylene (TPEN). After diabetes onset induced by streptozotocin, both diabetic and age-matched control mice were given TPEN intraperitoneally for 4 months. Western blotting assay revealed that Akt-mediated glucose metabolism signaling was down-regulated in the diabetic testis and was further decreased in diabetic mice with Zn deficiency, reflected by reduced phosphorylation of both Akt and GSK-3β and increased phosphorylation of glycogen synthase along with a disarrangement of fatty acid metabolism (increased expression of PPAR-α and decreased adenosine-monophosphate-activated protein kinase phosphorylation). Testicular expressions of plasminogen activator inhibitor-1 and intracellular adhesion molecule-1 as inflammatory factors were increased in the TPEN or diabetes-alone group, but not additive in the group of diabetes with Zn deficiency. A mechanistic study showed that Akt negative regulators phosphatase and tensin homology deleted on chromosome 10 (PTEN), protein tyrosine phosphatases 1B and Tribbles 3 all increased in diabetic testis and further increased in the testis of diabetic mice with Zn deficiency. These studies suggest that Zn deficiency significantly exacerbated diabetic down-regulation of Akt expression and function, most likely by up-regulation of Akt negative regulators. Therefore, prevention of Zn deficiency for diabetic patients is important in order to avoid the exacerbation of diabetic inhibition of glucose metabolism in the testis.

Learning Image Context for Segmentation of Prostate in CT-guided Radiotherapy

Medical Image Computing and Computer-assisted Intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention. 2011  |  Pubmed ID: 22003745

Segmentation of prostate is highly important in the external beam radiotherapy of prostate cancer. However, it is challenging to localize prostate in the CT images due to low image contrast, prostate motion, and both intensity and shape changes of bladder and rectum around the prostate. In this paper, an online learning and patient-specific classification method based on location-adaptive image context is proposed to precisely segment prostate in the CT image. Specifically, two sets of position-adaptive classifiers are respectively placed along the two coordinate directions, and further trained with the previous segmented treatment images to jointly perform the prostate segmentation. In particular, each location-adaptive classifier is recursively trained with different image context collected at different scales and orientations for better identification of each prostate region. The proposed learning-based prostate segmentation method has been extensively evaluated on a large set of patients, achieving very promising results.

[Herbs for Calming Liver and Suppressing Yang in Treatment of Hyperthyroidism with Hyperactive Liver Yang: Herbal Effects on Lymphocyte Protein Expression]

Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica. Jul, 2011  |  Pubmed ID: 22016976

To observe the herbal effects on hyperthyroidism patients with syndrome of hyperactivity of liver-Yang by method for calming the liver and suppressing Yang and investigate its effects on the lymphocyte protein expression. This approach may lay a foundation for the further investigation of the curative mechanisms of calming the liver and suppressing Yang treatment.

A Fragment of Secreted Hsp90α Carries Properties That Enable It to Accelerate Effectively Both Acute and Diabetic Wound Healing in Mice

The Journal of Clinical Investigation. Nov, 2011  |  Pubmed ID: 22019588

Wounds that fail to heal in a timely manner, for example, diabetic foot ulcers, pose a health, economic, and social problem worldwide. For decades, conventional wisdom has pointed to growth factors as the main driving force of wound healing; thus, growth factors have become the center of therapeutic developments. To date, becaplermin (recombinant human PDGF-BB) is the only US FDA-approved growth factor therapy, and it shows modest efficacy, is costly, and has the potential to cause cancer in patients. Other molecules that drive wound healing have therefore been sought. In this context, it has been noticed that wounds do not heal without the participation of secreted Hsp90α. Here, we report that a 115-aa fragment of secreted Hsp90α (F-5) acts as an unconventional wound healing agent in mice. Topical application of F-5 peptide promoted acute and diabetic wound closure in mice far more effectively than did PDGF-BB. The stronger effect of F-5 was due to 3 properties not held by conventional growth factors: its ability to recruit both epidermal and dermal cells; the fact that its ability to promote dermal cell migration was not inhibited by TGF-β; and its ability to override the inhibitory effects of hyperglycemia on cell migration in diabetes. The discovery of F-5 challenges the long-standing paradigm of wound healing factors and reveals a potentially more effective and safer agent for healing acute and diabetic wounds.

Secoiridoid Glucosides and Related Compounds from Syringa Reticulata and Their Antioxidant Activities

Bioorganic & Medicinal Chemistry Letters. Nov, 2011  |  Pubmed ID: 21955940

A 70% EtOH extract from the bark of Syringareticulata has shown significant antioxidant activity. Chemical study on the extract resulted in the isolation of seventeen compounds (1-17), including a novel oleoside-type secoiridoid glucoside, reticuloside (1), and the structures were elucidated on the basis of extensive spectroscopic analyses. Among the isolated compounds, jaspolyoside (2), oleuropein (4) and 2-(3,4-dihydroxy)-phenylethyl-β-d-glucopyranoside (17), showed the most potent superoxide anion scavenging activity with the EC(50) values of 4.97, 2.57 and 4.97μM, respectively. The structure-activity relationship indicated that the presence of 2-(3,4-dihydroxyphenyl)-ethoxy group is important for exhibiting the activity.

Transient Protection from Heat-stress Induced Apoptotic Stimulation by Metastasis-associated Protein 1 in Pachytene Spermatocytes

PloS One. 2011  |  Pubmed ID: 22022494

Deregulated thermal factors have been frequently implicated in the pathogenesis of male infertility, but the molecular basis through which certain responses are directed remain largely unknown. We previously reported that overexpression of exogenous Metastasis-associated protein 1 (MTA1) protects spermatogenic tumor cells GC-2spd (ts) against heat-induced apoptosis. To further dissect the underlying mechanism, we addressed here the fine coordination between MTA1 and p53 in pachytene spermatocytes upon hyperthermal stimulation.

Hsp27 Participates in the Maintenance of Breast Cancer Stem Cells Through Regulation of Epithelial-mesenchymal Transition and Nuclear Factor-κB

Breast Cancer Research : BCR. Oct, 2011  |  Pubmed ID: 22023707

ABSTRACT: INTRODUCTION: Heat shock proteins (HSPs) are normally induced under environmental stress to serve as chaperones for maintenance of correct protein folding but they are often overexpressed in many cancers, including breast cancer. The expression of Hsp27, an ATP-independent small HSP, is associated with cell migration and drug resistance of breast cancer cells. Breast cancer stem cells (BCSCs) have been identified as a subpopulation of breast cancer cells with markers of CD24-CD44+ or high intracellular aldehyde dehydrogenase activity (ALDH+) and proved to be associated with radiation resistance and metastasis. However, the involvement of Hsp27 in the maintenance of BCSC is largely unknown. METHODS: Mitogen-activated protein kinase antibody array and Western blot were used to discover the expression of Hsp27 and its phosphorylation in ALDH + BCSCs. To study the involvement of Hsp27 in BCSC biology, siRNA mediated gene silencing and quercetin treatment were used to inhibit Hsp27 expression and the characters of BCSCs, which include ALDH+ population, mammosphere formation and cell migration, were analyzed simultaneously. The tumorigenicity of breast cancer cells after knockdown of Hsp27 was analyzed by xenograftment assay in NOD/SCID mice. The epithelial-mesenchymal transition (EMT) of breast cancer cells was analyzed by wound-healing assay and Western blot of snail, vimentin and E-cadherin expression. The activation of nuclear factor kappa B (NF-κB) was analyzed by luciferase-based reporter assay and nuclear translocation. RESULTS: Hsp27 and its phosphorylation were increased in ALDH+ BCSCs in comparison with ALDH- non-BCSCs. Knockdown of Hsp27 in breast cancer cells decreased characters of BCSCs, such as ALDH+ population, mammosphere formation and cell migration. In addition, the in vivo CSC frequency could be diminished in Hsp27 knockdown breast cancer cells. The inhibitory effects could also be observed in cells treated with quercetin, a plant flavonoid inhibitor of Hsp27, and it could be reversed by overexpression of Hsp27. Knockdown of Hsp27 also suppressed EMT signatures, such as decreasing the expression of snail and vimentin and increasing the expression of E-cadherin. Furthermore, knockdown of Hsp27 decreased the nuclear translocation as well as the activity of NF-κB in ALDH + BCSCs, which resulted from increasing expression of IκBα. Restored activation of NF-κB by knockdown of IκBα could reverse the inhibitory effect of Hsp27 siRNA in suppression of ALDH+ cells. CONCLUSIONS: Our data suggest that Hsp27 regulates the EMT process and NF-κB activity to contribute the maintenance of BCSCs. Targeting Hsp27 may be considered as a novel strategy in breast cancer therapy.

Gene Regulation in Giardia Lambia Involves a Putative MicroRNA Derived from a Small Nucleolar RNA

PLoS Neglected Tropical Diseases. Oct, 2011  |  Pubmed ID: 22028939

Two core microRNA (miRNA) pathway proteins, Dicer and Argonaute, are found in Giardia lamblia, a deeply branching parasitic protozoan. There are, however, no apparent homologues of Drosha or Exportin5 in the genome. Here, we report a 26 nucleotide (nt) RNA derived from a 106 nt Box C/D snoRNA, GlsR2. This small RNA, designated miR5, localizes to the 3' end of GlsR2 and has a 75 nt hairpin precursor. GlsR2 is processed by the Dicer from Giardia (GlDcr) and generated miR5. Immunoprecipitation of the Argonaute from Giardia (GlAgo) brought down miR5. When a Renilla Luciferase transcript with a 26 nt miR5 antisense sequence at the 3'-untranslated region (3' UTR) was introduced into Giardia trophozoites, Luciferase expression was reduced ∼25% when synthetic miR5 was also introduced. The Luciferase mRNA level remained, however, unchanged, suggesting translation repression by miR5. This inhibition was fully reversed by introducing also a 2'-O-methylated antisense inhibitor of miR5, suggesting that miR5 acts by interacting specifically with the antisense sequence in the mRNA. A partial antisense knock down of GlDcr or GlAgo in Giardia indicated that the former is needed for miR5 biogenesis whereas the latter is required for miR5-mediated translational repression. Potential targets for miR5 with canonical seed sequences were predicted bioinformatically near the stop codon of Giardia mRNAs. Four out of the 21 most likely targets were tested in the Luciferase reporter assay. miR5 was found to inhibit Luciferase expression (∼20%) of transcripts carrying these potential target sites, indicating that snoRNA-derived miRNA can regulate the expression of multiple genes in Giardia.

Toxicity Identification and High-efficiency Treatment of Aging Chemical Industrial Wastewater from the Hangu Reservoir, China

Journal of Environmental Quality. Nov-Dec, 2011  |  Pubmed ID: 22031553

The Hangu Reservoir, located in Binhai New Area, Tianjin, China, receives mixed wastewater from a chemical industrial park. The aging chemical industrial wastewater is less biodegradable and contains complex hazardous substances, thus having an adverse effect on local ecological service function of the reservoir and on local economic and social development. In this study, key toxicants in the aging chemical industrial wastewater from the Hangu Reservoir were systematically identified by the toxicity identification evaluations (TIEs), and the treatment efficiency of the aging chemical industrial wastewater was examined and optimized by a municipal wastewater treatment process simulated in a laboratory. According to the TIE results using and wheat seeds as tested organisms, Cl, Cu, Pb, and Zn were identified as key toxicants in the aging chemical industrial wastewater, with concentrations of 7349.11, 0.01, 0.07, and 0.07 mg L, respectively, which were confirmed by subsequent spiking approaches. Based on the TIE results, the aging chemical industrial wastewater could be classified as high-salinity wastewater. The co-treatment of the aging chemical industrial wastewater and municipal wastewater may be an effective and low-cost method. The treatment efficiency of the mixed wastewater increased with an increase in the volume ratio of municipal wastewater to aging chemical industrial wastewater. When the volume ratio was 10:1, the best removal efficiencies of chemical oxygen demand, total N, and total P were up to 85.1, 89.3, and 96.5%, respectively, whereas the toxicity unit of the treated wastewater was reduced to 0.50.

[Enriching Blood Effect Comparison in Three Kinds of Blood Deficiency Model After Oral Administration of Drug Pair of Angelicae Sinensis Radix and Chuanxiong Rhizoma and Each Single Herb]

Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica. Jul, 2011  |  Pubmed ID: 22032150

Through establishing different blood deficiency animal model, to evaluate enriching blood effect changes of the drug pair of Angelicae Sinensis Radix and Chuanxiong Rhizoma and each single herb, and to explore the effect characteristics of their compatibility.

A MicroRNA Derived from an Apparent Canonical Biogenesis Pathway Regulates Variant Surface Protein Gene Expression in Giardia Lamblia

RNA (New York, N.Y.). Dec, 2011  |  Pubmed ID: 22033329

We have previously shown that a snoRNA-derived microRNA, miR2, in Giardia lamblia potentially regulates the expression of 22 variant surface protein (VSP) genes. Here, we identified another miRNA, miR4, also capable of regulating the expression of several VSPs but derived from an unannotated open reading frame (ORF) rather than a snoRNA, suggesting a canonical miRNA biogenesis pathway in Giardia. miR4 represses expression of a reporter containing two miR4 antisense sequences at the 3' UTR without causing a corresponding decrease in the mRNA level. This repression requires the presence of the Giardia Argonaute protein (GlAgo) and is reversed by 2' O-methylated antisense oligo to miR4, suggesting an RNA-induced silencing complex (RISC)-mediated mechanism. Furthermore, in vivo and in vitro evidence suggested that the Giardia Dicer protein (GlDcr) is required for miR4 biogenesis. Coimmunoprecipitation of miR4 with GlAgo further verified miR4 as a miRNA. A total of 361 potential target sites for miR4 were bioinformatically identified in Giardia, out of which 69 (32.7%) were associated with VSP genes. miR4 reduces the expression of a reporter containing two copies of the target site from VSP (GL50803_36493) at the 3' UTR. Sixteen of the 69 VSP genes were further found to contain partially overlapping miR2 and miR4 targeting sites. Expression of a reporter carrying the two overlapping sites was inhibited by either miR2 or miR4, but the inhibition was neither synergistic nor additive, suggesting a complex mechanism of miRNA regulation of VSP expression and the presence of a rich miRNAome in Giardia.

[Modern Documentary Research on Disease Menu of Acupuncture-moxibustion for Mental and Behavioral Disorder]

Zhongguo Zhen Jiu = Chinese Acupuncture & Moxibustion. Oct, 2011  |  Pubmed ID: 22043692

Dominant disease menu of mental and behavioral disorder of acupuncture therapy was summarized and obtained in this article.

[Whey Protein Improves Insulin Resistance Via the Increase of Antioxidant Capacity in Model Rats]

Wei Sheng Yan Jiu = Journal of Hygiene Research. Sep, 2011  |  Pubmed ID: 22043714

To investigate the effects of whey protein on insulin resistance in model rats.

Expression of ABCB5 Gene in Hematological Malignances and Its Significance

Leukemia & Lymphoma. Dec, 2011  |  Pubmed ID: 22044138

We examined ABCB5 gene expression using real-time polymerase chain reaction (PCR) in leukemia cells from 29 patients with acute lymphoblastic leukemia (ALL), 24 patients with chronic lymphocytic leukemia (CLL), 42 with acute myeloid leukemia (AML), 22 with chronic myeloid leukemia (CML), 17 with lymphoma and 10 with multiple myeloma (MM). It was confirmed that expression of the ABCB5 gene is highly increased in B-precursor ALL and French-American-British (FAB) M1 and M2 types of AML and lymphoma. The ABCB5 gene is expressed more highly in patients with relapsed or refractory disease than in patients with drug sensitive acute leukemia. Furthermore, there was an evident positive correlation between ABCB5 mRNA expression and MDR1 mRNA expression, but no correlation with MRP mRNA expression or BCRP mRNA expression. Quantification of the ABCB5 gene by real-time PCR offers particular promise as a prognostic marker and a marker for drug resistance in acute leukemia. Our findings raise the possibility that ABCB5 may be responsible for both the progression and chemotherapeutic refractoriness of advanced acute leukemia, and that ABCB5-targeted approaches might therefore represent novel and translationally relevant therapeutic strategies for drug resistance in leukemia.

Reliability of a New Biokinetic Model of Zirconium in Internal Dosimetry: Part I, Parameter Uncertainty Analysis

Health Physics. Dec, 2011  |  Pubmed ID: 22048485

The reliability of biokinetic models is essential in internal dose assessments and radiation risk analysis for the public, occupational workers, and patients exposed to radionuclides. In this paper, a method for assessing the reliability of biokinetic models by means of uncertainty and sensitivity analysis was developed. The paper is divided into two parts. In the first part of the study published here, the uncertainty sources of the model parameters for zirconium (Zr), developed by the International Commission on Radiological Protection (ICRP), were identified and analyzed. Furthermore, the uncertainty of the biokinetic experimental measurement performed at the Helmholtz Zentrum München-German Research Center for Environmental Health (HMGU) for developing a new biokinetic model of Zr was analyzed according to the Guide to the Expression of Uncertainty in Measurement, published by the International Organization for Standardization. The confidence interval and distribution of model parameters of the ICRP and HMGU Zr biokinetic models were evaluated. As a result of computer biokinetic modelings, the mean, standard uncertainty, and confidence interval of model prediction calculated based on the model parameter uncertainty were presented and compared to the plasma clearance and urinary excretion measured after intravenous administration. It was shown that for the most important compartment, the plasma, the uncertainty evaluated for the HMGU model was much smaller than that for the ICRP model; that phenomenon was observed for other organs and tissues as well. The uncertainty of the integral of the radioactivity of Zr up to 50 y calculated by the HMGU model after ingestion by adult members of the public was shown to be smaller by a factor of two than that of the ICRP model. It was also shown that the distribution type of the model parameter strongly influences the model prediction, and the correlation of the model input parameters affects the model prediction to a certain extent depending on the strength of the correlation. In the case of model prediction, the qualitative comparison of the model predictions with the measured plasma and urinary data showed the HMGU model to be more reliable than the ICRP model; quantitatively, the uncertainty model prediction by the HMGU systemic biokinetic model is smaller than that of the ICRP model. The uncertainty information on the model parameters analyzed in this study was used in the second part of the paper regarding a sensitivity analysis of the Zr biokinetic models.

Reliability of a New Biokinetic Model of Zirconium in Internal Dosimetry: Part II, Parameter Sensitivity Analysis

Health Physics. Dec, 2011  |  Pubmed ID: 22048486

The reliability of biokinetic models is essential for the assessment of internal doses and a radiation risk analysis for the public and occupational workers exposed to radionuclides. In the present study, a method for assessing the reliability of biokinetic models by means of uncertainty and sensitivity analysis was developed. In the first part of the paper, the parameter uncertainty was analyzed for two biokinetic models of zirconium (Zr); one was reported by the International Commission on Radiological Protection (ICRP), and one was developed at the Helmholtz Zentrum München-German Research Center for Environmental Health (HMGU). In the second part of the paper, the parameter uncertainties and distributions of the Zr biokinetic models evaluated in Part I are used as the model inputs for identifying the most influential parameters in the models. Furthermore, the most influential model parameter on the integral of the radioactivity of Zr over 50 y in source organs after ingestion was identified. The results of the systemic HMGU Zr model showed that over the first 10 d, the parameters of transfer rates between blood and other soft tissues have the largest influence on the content of Zr in the blood and the daily urinary excretion; however, after day 1,000, the transfer rate from bone to blood becomes dominant. For the retention in bone, the transfer rate from blood to bone surfaces has the most influence out to the endpoint of the simulation; the transfer rate from blood to the upper larger intestine contributes a lot in the later days; i.e., after day 300. The alimentary tract absorption factor (fA) influences mostly the integral of radioactivity of Zr in most source organs after ingestion.

The Impact of Renin-angiotensin-aldosterone System Blockade on Heart Failure Outcomes and Mortality in Patients Identified to Have Aortic Regurgitation: a Large Population Cohort Study

Journal of the American College of Cardiology. Nov, 2011  |  Pubmed ID: 22051330

The aim of this study was to investigate the effect of renin-angiotensin system blockade on outcomes in patients with aortic regurgitation (AR).

Chemical Constituents from Sambucus Adnata and Their Protein-tyrosine Phosphatase 1B Inhibitory Activities

Chemical & Pharmaceutical Bulletin. 2011  |  Pubmed ID: 22041077

The MeOH extract from the whole plants of Sambucus adnata has shown significant protein-tyrosine phosphatase 1B (PTP1B) inhibitory activity. Chemical study on the extract resulted in the isolation of thirteen compounds, including a novel triterpene (1). The structure of 1 was determined to be 1α,3β-dihydroxy-urs-12-en-11-one-3-yl palmitate on the basis of extensive spectroscopic analyses. Among the isolated compounds, ursolic acid, oleanolic acid and (±)-boehmenan showed the most potent PTP1B inhibitory activity in vitro with the IC(50) values of 4.1, 14.4 and 43.5 µm, respectively. The kinetic analysis indicated that (±)-boehmenan inhibits PTP1B activity in a competitive manner.

Inhibition of α Folate Receptor Resulting in a Reversal of Taxol Resistance in Nasopharyngeal Carcinoma

Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-Head and Neck Surgery. Oct, 2011  |  Pubmed ID: 22041223

Objective. To further determine the role of FOLR1 in taxol resistance of nasopharyngeal carcinoma (NPC) and whether inhibition of FOLR1 expression reverses the taxol-resistant phenotype.Study Design. Correlation study between gene expression and cancer cell survival.Setting. University hospital.Subjects and Methods. Three taxol-resistant sub-cell lines with a different resistant index were established from the parental CNE-1 NPC cell line. The correlation between FOLR1 expression and taxol sensitivity was statistically analyzed. Inhibition of FOLR1 expression was carried out by RNA interference and by a FOLR1-specific monoclonal antibody, and taxol sensitivity was examined by colony formation assays. FOLR1 expression was also examined in 72 NPC patient specimens by immunohistochemistry.Results. The levels of FOLR1 expression were positively and significantly correlated with a taxol resistance phenotype (P < .05). Inhibition of FOLR1 expression resulted in a significantly increased sensitivity of taxol to taxol-resistant NPC cells (P < .05). An increase of FOLR1 expression by gene transfection caused a taxol-resistant phenotype in parental NPC cells. The level of FOLR1 expression was found to be related to clinical stage in NPC tissue samples.Conclusion. These results suggest that FOLR1 plays an important role in taxol resistance of NPC cells.

Superb Fluoride and Arsenic Removal Performance of Highly Ordered Mesoporous Aluminas

Journal of Hazardous Materials. Dec, 2011  |  Pubmed ID: 22061441

Highly ordered mesoporous aluminas and calcium-doped aluminas were synthesized through a facile and reproducible method. Their fluoride adsorption characteristics, including adsorption isotherms, adsorption kinetics, the effect of pH and co-existing anions were investigated. These materials exhibited strong affinity to fluoride ions and extremely high defluoridation capacities. The highest defluoridation capacity value reached 450 mg/g. These materials also showed superb arsenic removal ability. 1g of mesoporous alumina was able to treat 200 kg of arsenic contaminated water with a pH value of 7, reducing the concentration of arsenate from 100 ppb to 1 ppb.

Novel Phenoxyalkylcarboxylic Acid Derivatives As Hypolipidaemic Agents

Journal of Enzyme Inhibition and Medicinal Chemistry. Nov, 2011  |  Pubmed ID: 22085137

Novel phenoxyalkylcarboxylic acid derivatives based on the natural scaffolds, flavonoids, or resveratrol were designed, synthesized, and evaluated for hypolipidaemic activity. Among the compounds, 30b lowered the triglycerides by 48.5% (P?

High Glucose Promotes Pancreatic Cancer Cell Proliferation Via the Induction of EGF Expression and Transactivation of EGFR

PloS One. 2011  |  Pubmed ID: 22087246

Multiple lines of evidence suggest that a large portion of pancreatic cancer patients suffer from either hyperglycemia or diabetes, both of which are characterized by high blood glucose level. However, the underlying biological mechanism of this phenomenon is largely unknown. In the present study, we demonstrated that the proliferative ability of two human pancreatic cancer cell lines, BxPC-3 and Panc-1, was upregulated by high glucose in a concentration-dependent manner. Furthermore, the promoting effect of high glucose levels on EGF transcription and secretion but not its receptors in these PC cell lines was detected by using an EGF-neutralizing antibody and RT-PCR. In addition, the EGFR transactivation is induced by high glucose levels in concentration- and time-dependent manners in PC cells in the presence of the EGF-neutralizing antibody. These results suggest that high glucose promotes pancreatic cancer cell proliferation via the induction of EGF expression and transactivation of EGFR. Our findings may provide new insight on the links between high glucose level and PC in terms of the molecular mechanism and reveal a novel therapeutic strategy for PC patients who simultaneously suffer from either diabetes or hyperglycemia.

Clinical Utility of Automated Platelet Clump Count in the Screening for Ethylene Diamine Tetraacetic Acid-dependent Pseudothrombocytopenia

Chinese Medical Journal. Oct, 2011  |  Pubmed ID: 22088534

Platelet (PLT) clumping occurring in pseudothrombocytopenia (PTCP) can result in inaccurate PLT. Automated platelet clump count (APCC) is a quantitative parameter of platelet aggregation. In this study, we evaluated the clinical utility of APCC in the screening for platelet aggregation related ethylene diamine tetraacetic acid (EDTA)-dependent PTCP (EDTA-PTCP).

Association of Six Single Nucleotide Polymorphisms with Gestational Diabetes Mellitus in a Chinese Population

PloS One. 2011  |  Pubmed ID: 22096510

To investigate whether the candidate genes that confer susceptibility to type 2 diabetes mellitus are also correlated with gestational diabetes mellitus (GDM) in pregnant Chinese women.

[Clinical Study on Intervention of Spleen-restoring Decoction Integrating with Dormancy Hygiene Education on Subhealthy Insomnia of Deficiency of Both Heart and Spleen Pattern]

Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica. Aug, 2011  |  Pubmed ID: 22097346

To appraise the clinical efficacy, safety and compliance of the intervention of spleen-restoring decoction combined with dormancy hygiene education and the intervention of spleen-restoring decoction alone on sub-healthy insomnia of deficiency of both the heart and spleen pattern.

Kinetics of Nanochain Formation in a Simplified Model of Amelogenin Biomacromolecules

Biophysical Journal. Nov, 2011  |  Pubmed ID: 22098749

We show that the kinetics of nanochain formation of amelogenin molecules is well described by a combination of translational and rotational diffusion of a simplified anisotropic bipolar model consisting of hydrophobic spherical colloid particles and a point charge located on each particle surface. The colloid particles interact via a standard depletion attraction whereas the point charges interact through a screened Coulomb repulsion. We study the kinetics via a Brownian dynamics simulation of both translational and rotational motions and show that the anisotropy brought in by the charge dramatically affects the kinetic pathway of cluster formation and our simple model captures the main features of the experimental observations.

NSD2 Links Dimethylation of Histone H3 at Lysine 36 to Oncogenic Programming

Molecular Cell. Nov, 2011  |  Pubmed ID: 22099308

The histone lysine methyltransferase NSD2 (MMSET/WHSC1) is implicated in diverse diseases and commonly overexpressed in multiple myeloma due to a recurrent t(4;14) chromosomal translocation. However, the precise catalytic activity of NSD2 is obscure, preventing progress in understanding how this enzyme influences chromatin biology and myeloma pathogenesis. Here, we show that dimethylation of histone H3 at lysine 36 (H3K36me2) is the principal chromatin-regulatory activity of NSD2. Catalysis of H3K36me2 by NSD2 is sufficient for gene activation. In t(4;14)-positive myeloma cells, the normal genome-wide and gene-specific distribution of H3K36me2 is obliterated, creating a chromatin landscape that selects for a transcription profile favorable for myelomagenesis. Catalytically active NSD2 confers xenograft tumor formation upon t(4;14)-negative cells and promotes oncogenic transformation of primary cells in an H3K36me2-dependent manner. Together, our findings establish H3K36me2 as the primary product generated by NSD2 and demonstrate that genomic disorganization of this canonical chromatin mark by NSD2 initiates oncogenic programming.

Epoxidation of Alkenes Catalyzed by Phenyl Group-modified, Periodic Mesoporous Organosilica-entrapped, Dimeric Manganese-salen Complexes

ChemSusChem. Dec, 2011  |  Pubmed ID: 22105943

A series of reusable, recoverable, diamine-bridged dimeric manganese-salen complexes were prepared by the encapsulation of homogeneous dimeric Mn(salen) complexes into nanocages of a 3D periodic mesoporous organosilica (PMO) support followed by silylation of the support with organosilane. The composition, structure, morphology, and textural properties of the prepared PMO-entrapped dimeric Mn(salen) complexes were characterized, and their catalytic performances were tested in the epoxidation of alkenes (styrene, cyclohexene, and 1-phenylcyclohexene), with NaClO as an oxygen source and 4-phenylpyridine-N-oxide as an axial ligand. Furthermore, the influences of the textural and morphological properties of the entrapped dimeric Mn(salen) complexes and the key reaction parameters on the catalytic activity and selectivity are discussed. Finally, the reusability of the supported dimeric Mn(salen) complexes was evaluated over three catalytic runs.

Total Isovolumic Time Relates to Exercise Capacity in Patients with Transposition of the Great Arteries Late After Atrial Switch Procedures

Cardiology in the Young. Nov, 2011  |  Pubmed ID: 22068048

BACKGROUND: Systemic right ventricular systolic dysfunction is common late after atrial switch surgery for transposition of the great arteries. Total isovolumic time is the time that the ventricle is neither ejecting nor filling and is calculated without relying on geometric assumptions. We assessed resting total isovolumic time in this population and its relationship to exercise capacity. METHODS: A total of 40 adult patients with transposition of the great arteries after atrial switch - and 10 healthy controls - underwent transthoracic echocardiography and cardiopulmonary exercise testing from January, 2006 to January, 2009. Resting total isovolumic time was measured in seconds per minute: 60 minus total ejection time plus total filling time. RESULTS: The mean age was 31.6 plus or minus 7.6 years, and 38.0% were men. There were 16 patients (40%) who had more than or equal to moderate systolic dysfunction of the right ventricle. Intra- and inter-observer agreement was good for total isovolumic time, which was significantly prolonged in patients compared with controls (12.0 plus or minus 3.9 seconds per minute versus 6.0 plus or minus 1.8 seconds per minute, p-value less than 0.001) and correlated significantly with peak oxygen consumption (r equals minus 0.63, p-value less than 0.001). The correlation strengthened (r equals minus 0.73, p-value less than 0.001) after excluding seven patients with exercise-induced cyanosis. No relationship was found between exercise capacity and right ventricular ejection fraction or long-axis amplitude.ConclusionResting isovolumic time is prolonged after atrial switch for patients with transposition of the great arteries. It is highly reproducible and relates well to exercise capacity.

Effect of Ionic Products of Dicalcium Silicate Coating on Osteoblast Differentiation and Collagen Production Via TGF-β1 Pathway

Journal of Biomaterials Applications. Nov, 2011  |  Pubmed ID: 22071351

In this work, the medium containing ionic products of dicalcium silicates (Ca(2)SiO(4)) for culturing MG63 cells was prepared by immersing a titanium alloy plate with the plasma sprayed Ca(2)SiO(4) coatings in DMEM solution. The effect of the ionic products on cellular differentiation, collagen production, and local growth factors (prostaglandin E(2) [PGE(2)] and transforming growth factor-β [TGF-β1]) of osteoblast-like MG63 cells were investigated. The normal DMEM was also used to culture MG63 cells as the control group. Differentiation of cell was evaluated by detecting alkaline phosphatase (ALP) activity and osteocalcin (OC) synthesis as well as their gene expression. Collagen production was analyzed by Sircol assay. The levels of PGE(2) and TGF-β1 in culture medium were measured using enzyme-linked immunosorbent assay (ELISA). The gene expressions of TGF-β receptors (TGF-β RI and TGF-β RII) were also measured by real-time PCR technology. MG63 cells cultured in DMEM containing ionic products of Ca(2)SiO(4) coating showed enhanced differentiation and increased collagen production. The results obtained from ELISA showed that the levels of PGE(2) and TGF-β1 in experimental group were higher than that in control. The gene expression of TGF-β receptors was upregulated, indicating that more TGF-β1 bonded to their receptors which produce more effects on the osteoblastic activity, leading to enhanced differentiation and synthetic activity of osteoblast. It is concluded that ionic products of Ca(2)SiO(4) coating may enhance cellular differentiation and collagen production by influencing TGF-β1 pathway.

MR Spectroscopy and Micro-CT in Evaluation of Osteoporosis Model in Rabbits: Comparison with Histopathology

European Radiology. Nov, 2011  |  Pubmed ID: 22101829

PURPOSE: To explore the evidence of regular alteration of bone quality in osteoporosis dynamically examined by MRS and micro-CT, comparing with histopathology. METHODS: Forty rabbits were allocated into two groups. Group A were used as sham. Group B underwent bilateral ovariectomy (OVX) combined with daily intramuscular methylprednisolone, underwent MR spectroscopy, micro-CT, and histopathology of L5 at 2, 4, 8, and 10 weeks after operation. RESULTS: Fat fraction as shown by MRS in Group B was significantly increased over the time course of osteoporosis development with significant difference between two groups at 4, 8, and 10 weeks after OVX. Continuous deterioration of cancellous bone architecture in Group B, was first detected at week4. FF value in group B correlated with micro-CT parameters. Marrow fat as measured by MR and CT was positively correlated with both the mean density and diameter of adipocytes (both of which increased over time). CONCLUSIONS: Marrow adipogenesis occurs in synchrony with deterioration of trabecular microarchitecture.MRS may be valuable to assess the pathophysiological changes of bone marrow in osteoporosis in early stage. KEY POINTS: • MRS revealed gradually increasing bone marrow fat in rabbits rendered osteoporotic • Marrow adipogenesis occurs in synchrony with deterioration of trabecular microarchitecture • Pathology revealed an early increase in number of marrow adipocytes in osteoporosis. • MRS may help assess early pathophysiological bone marrow changes in osteoporosis.

Using Rice Straw Fermentation Liquor to Produce Bioflocculants During an Anaerobic Dry Fermentation Process

Bioresource Technology. Nov, 2011  |  Pubmed ID: 22142504

In this study, fermentation liquor from rice straw was used to produce bioflocculants during a dry fermentation process. Acetic acid and butyric acid were the predominant VFAs during the process. A compound bioflocculant producing inoculum, F(+) was inoculated into compound media in which fermentation liquor and conventional bioflocculants medium at different ratios. The maximum flocculation activity, 92.45% was achieved when 100-day fermentation liquor and conventional bioflocculants medium were mixed at an equal ratio. Furthermore, 454-pyrosequencing technology was used to measure bacterial diversity on the 25th day of operation, which was a period of rapid VFA accumulating. A total of 2110 sequences were obtained, and were found to be affiliated with 8 phylogenetic groups, including Actinobacteria, Acidobacteria, Bacteroidetes, Firmicutes, Proteobacteria, Chloroflexi, Spirochaetes and Synergistetes. Notably, Firmicutes (92.3%) was the dominant microbial population, followed by Actinobacteria (2.37%) and Proteobacteria (1.04%).

Cardioprotective Effect of a Hemoglobin-based Oxygen Carrier on Cold Ischemia/reperfusion Injury

Cardiology. 2011  |  Pubmed ID: 22143256

The etiology of myocardial ischemia/reperfusion (I/R) injury is multifactorial, but activation of the innate immune system and the resulting inflammatory response are important components of I/R injury. The aim of this study was to investigate the protective effect of a hemoglobin-based oxygen carrier (HBOC) on cold I/R heart and to explore the underlying mechanisms.

Microstructure and Mechanical Properties of Glass-infiltrated Al(2)O (3)/ZrO (2) Nanocomposites

Journal of Materials Science. Materials in Medicine. Dec, 2011  |  Pubmed ID: 22143906

This work was to investigate the effect of zirconia nanoparticles content on microstructure and mechanical properties of glass-infiltrated alumina/zirconia composites (AZGs). A series of slip-cast zirconia-toughened alumina (ZTA) compacts containing 10, 20, 30 wt% nano-zirconia, respectively, were partially sintered at 1,250°C for 2 h, then infiltrated with lanthanum borosilicate glass of lower thermal expansion at 1,180°C for 4 h. A porosity ranging from 21 to 25% mainly with submicron pore size was demonstrated in the partially-sintered ZTAs. Homogeneous distribution and micro-crystallization of intergranular glass phase was showed in the AZGs. The mechanical strength and fracture toughness of AZGs increased with zirconia content, the maximum (633.5 ± 41.7, 6.7 ± 0.6 MPa m(0.5)) were obtained in 30 wt% zirconia group, which were significantly higher than those in 10 wt% zirconia group (P < 0.05). The improved mechanical performance of AZGs containing 30 wt% zirconia was attributed to their larger zirconia content as well as thinner intergranular glass film.

Snailase Preparation of Ginsenoside M1 from Protopanaxadiol-type Ginsenoside and Their Protective Effects Against CCl4-induced Chronic Hepatotoxicity in Mice

Molecules (Basel, Switzerland). 2011  |  Pubmed ID: 22146371

To investigate the protective effects of protopanaxadiol-type ginsenoside (PDG) and its metabolite ginsenoside M1 (G-M1) on carbon tetrachloride (CCl(4))-induced chronic liver injury in ICR mice, we carried out conversion of protopanaxadiol-type ginsenosides to ginsenoside M1 using snailase. The optimum time for the conversion was 24 h at a constant pH of 4.5 and an optimum temperature of 50 °C. The transformation products were identified by high-performance liquid chromatography and electrospray ion-mass spectrometry. Subsequently, most of PDG was decomposed and converted into G-M1 by 24 h post-reaction. During the study on hepatoprotective in a mice model of chronic liver injury, PDG or G-M1 supplement significantly ameliorated the CCl(4)-induced liver lesions, lowered the serum levels of select hepatic enzyme markers (alanine aminotransferase, ALT, and aspartate aminotransferase, AST) and malondialdehyde and increased the activity of superoxide dismutase in liver. Histopathology of the liver tissues showed that PDG and G-M1 attenuated the hepatocellular necrosis and led to reduction of inflammatory cell infiltration. Therefore, the results of this study show that PDG and G-M1 can be proposed to protect the liver against CCl(4)-induced oxidative injury in mice, and the hepatoprotective effect might be attributed to amelioration of oxidative stress.

Xuhuai Goat H-FABP Gene Clone, Subcellular Localization of Expression Products and the Preparation of Transgenic Mice

DNA and Cell Biology. Dec, 2011  |  Pubmed ID: 22149926

The aim of this study was to clone the heart-type fatty acid binding protein (H-FABP) gene of Xuhuai goat, to explore it bioinformatically, and analyze the subcellular localization using enhanced green fluorescent protein (EGFP). The results showed that the coding sequence (CDS) length of Xuhuai goat H-FABP gene was 402 bp, encoding 133 amino acids (GenBank accession number AY466498.1). The H-FABP cDNA coding sequence was compared with the corresponding region of human, chicken, brown rat, cow, wild boar, donkey, and zebrafish. The similarity were 89%, 76%, 85%, 84%, 93%, 91%, 70%, respectively. For the corresponding amino acid sequences, the similarity were 90%, 79%, 88%, 97%, 95%, 94%, 72%, respectively. This study did not find the signal peptide region in the H-FABP protein; it revealed that H-FABP protein might be a nonsecreted protein. H-FABP expression was detected in vitro by reverse transcription-polymerase chain reaction (RT-PCR), and the EGFP-H-FABP fusion protein was localized to the cytoplasm. The gene could also be transiently and permanently expressed in mice.

Molecular Features of the Complementarity Determining Region 3 Motif of the T Cell Population and Subsets in the Blood of Patients with Chronic Severe Hepatitis B

Journal of Translational Medicine. 2011  |  Pubmed ID: 22152113

T cell receptor (TCR) reflects the status and function of T cells. We previously developed a gene melting spectral pattern (GMSP) assay, which rapidly detects clonal expansion of the T cell receptor β variable gene (TCRBV) in patients with HBV by using quantitative real-time reverse transcription PCR (qRT-PCR) with DNA melting curve analysis. However, the molecular profiles of TCRBV in peripheral blood mononuclear cells (PBMCs) and CD8+, CD8- cell subsets from chronic severe hepatitis B (CSHB) patients have not been well described.

Two Novel Steroidal Alkaloid Glycosides from the Seeds of Lycium Barbarum

Chemistry & Biodiversity. Dec, 2011  |  Pubmed ID: 22162165

Two novel steroidal alkaloid glycosides, lycioside A (1) and lycioside B (2) were isolated from the seeds of Lycium barbarum. Their structures were determined by various spectroscopic analyses. Compounds 1 and 2 showed inhibitory activities with the IC(50) values of 75.3 and 72.8 μM against rat intestinal sucrase, and 63.4 and 59.1 μM against rat intestinal maltase.

[Study on Surveillance and Early-warning System of Schistosomiasis in First Phase of East Route of South-to-North Water Diversion Project. III. Indexes of Surveillance and Early-warning and Risk Assessment]

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi = Chinese Journal of Schistosomiasis Control. Feb, 2011  |  Pubmed ID: 22164372

To establish the index system of surveillance and early-warning on schistosomiasis and to provide the scientific basis for risk assessment and emergency plan in first phase of east route of South-to-North Water Diversion Project.

[Technology of Preventing Oncomelania Snail Diffusion in East Route of South-to-North Water Diversion Project. I. Field Test of Blocking Diffusion of Oncomelania Snails with Blocking Network Via Collecting Water from Middle Layer]

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi = Chinese Journal of Schistosomiasis Control. Jun, 2011  |  Pubmed ID: 22164501

To evaluate the effectiveness of blocking diffusion of Oncomelania snails with the blocking network via collecting water from middle layer.

[Surveillance of Oncomelania Hupensis Snails in Baoying and Gaoyou Sections of Li Canal in East Route of South-to-North Water Diversion Project]

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi = Chinese Journal of Schistosomiasis Control. Aug, 2011  |  Pubmed ID: 22164860

To understand the distribution and diffusion of Oncomelania hupensis snails in the Baoying and Gaoyou sections of the Li Canal in the east route of the South-to-North Water Diversion Project.

[Molecular Diagnosis of Toxoplasmosis]

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi = Chinese Journal of Schistosomiasis Control. Aug, 2011  |  Pubmed ID: 22164871

This paper reviews the domestic and foreign literatures regarding molecular diagnosis of toxoplasmosis. The nucleic acid molecule hybridization and Toxoplasma gondii gene sequences for polymerase chain reaction (PCR), common and conventional PCR, nested PCR, real-time quantitative PCR, immune PCR, in-situ PCR, loop-mediated isothermal amplification technology are introduced.

[Study on Corrosion Resistance of Three Non-noble Porcelain Alloys]

Hua Xi Kou Qiang Yi Xue Za Zhi = Huaxi Kouqiang Yixue Zazhi = West China Journal of Stomatology. Oct, 2011  |  Pubmed ID: 22165115

To study the electrochemical corrosion behavior of Co-Cr, Ni-Cr and Ni-Cr-Be based porcelain alloys in NaCl solution.

[Biological Characteristics of Denitrifying Polyphosphate-accumulating Organisms]

Huan Jing Ke Xue= Huanjing Kexue / [bian Ji, Zhongguo Ke Xue Yuan Huan Jing Ke Xue Wei Yuan Hui "Huan Jing Ke Xue" Bian Ji Wei Yuan Hui.]. Sep, 2011  |  Pubmed ID: 22165243

A denitrifying phosphate-accumulating organisms (DNPAOs), which was called Q-hrb05, was isolated in the special medium from the anaerobic/aerobic/anoxic SBR reactor. Strain Q-hrb05 was identified by 16SrDNA gene analysis, and the accession number of 16SrDNA gene sequence of strain Q-hrb05 in GenBank was GU214826. Effects of the different pH values, temperature, carbon source of medium on nitrogen and phosphorus removal of strain Q-hrb05 were investigated. The result showed that strain Q-hrb05 belonged to Bacillus sp.. Meanwhile, extracellular exopolymers of strain Q-hrb05 was based on protein, about 120.6 mg x mL(-1), and it had 23.05 microg x mL(-1) nucleic acid, but little polysaccharide. There was no significant adsorption of phosphate. So phosphorus removal was mainly due to intracellular uptake. And when pH value was kept as 7, temperature was kept as 30 degrees C, and carbon source was kept sodium acetate, the highest nitrogen and phosphorus removal efficiency was achieved. Phosphorus uptake rate was averaged at 88%, and the denitrification rate reached 81%.

Regulation of Microglia by Ionotropic Glutamatergic and GABAergic Neurotransmission

Neuron Glia Biology. Dec, 2011  |  Pubmed ID: 22166726

Recent studies have indicated that constitutive functions of microglia in the healthy adult central nervous system (CNS) involve immune surveillance, synapse maintenance and trophic support. These functions have been related to the ramified structure of 'resting' microglia and the prominent motility in their processes that provide extensive coverage of the entire extracellular milleu. In this review, we examine how external signals, and in particular, ionotropic neurotransmission, regulate features of microglial morphology and process motility. Current findings indicate that microglial physiology in the healthy CNS is constitutively and reciprocally regulated by endogenous ionotropic glutamatergic and GABAergic neurotransmission. These influences do not act directly on microglial cells but indirectly via the activity-dependent release of ATP, likely through a mechanism involving pannexin channels. Microglia in the 'resting' state are not only dynamically active, but also constantly engaged in ongoing communication with neuronal and macroglial components of the CNS in a functionally relevant way.

Cardiovascular Magnetic Resonance Tagging of the Right Ventricular Free Wall for the Assessment of Long Axis Myocardial Function in Congenital Heart Disease

Journal of Cardiovascular Magnetic Resonance : Official Journal of the Society for Cardiovascular Magnetic Resonance. Dec, 2011  |  Pubmed ID: 22168638

ABSTRACT: BACKGROUND: Right ventricular ejection fraction (RV-EF) has traditionally been used to measure and compare RV function serially over time, but may be a relatively insensitive marker of change in RV myocardial contractile function. We developed a cardiovascular magnetic resonance (CMR) tagging-based technique with a view to rapid and reproducible measurement of RV long axis function and applied it in patients with congenital heart disease. METHODS: We studied 84 patients: 56 with repaired Tetralogy of Fallot (rTOF); 28 with atrial septal defect (ASD): 13 with and 15 without pulmonary hypertension (RV pressure >40mmHG by echocardiography). For comparison, 20 healthy controls were studied. CMR acquisitions included an anatomically defined four chamber cine followed by a cine gradient echo-planar sequence in the same plane with a labelling pre-pulse giving a tag line across the basal myocardium. RV tag displacement was measured with automated registration and tracking of the tag line together with standard measurement of RV-EF. RESULTS: Mean RV displacement was higher in the control (26+/-3mm) than in rTOF (16+/-4mm) and ASD with pulmonary hypertension (18+/-3mm) groups, but lower than in the ASD group without (30+/-4mm), P<0.001. The technique was reproducible with inter-study bias+/-95% limits of agreement of 0.7+/-2.7mm. While RV-EF was lower in rTOF than in controls (49+/-9% versus 57+/-6%, P<0.001), it did not differ between either ASD group and controls. CONCLUSIONS: Measurements of RV long axis displacement by CMR tagging showed more differences between the groups studied than did RV-EF, and was reproducible, quick and easy to apply. Further work is needed to assess its potential use for the detection of longitudinal changes in RV myocardial function.

[Knowledge on Drinking Water of Adults in Four Cities of China]

Zhonghua Yu Fang Yi Xue Za Zhi [Chinese Journal of Preventive Medicine]. Aug, 2011  |  Pubmed ID: 22169686

To understand the status on knowledge of drinking water among adults aged 18 - 60 yrs in Beijing, Shanghai, Chengdu and Guangzhou of China.

Real-time PCR and High Resolution Melt Analysis for Rapid Detection of Mycobacterium Leprae Drug Resistance Mutations and Strain Types

Journal of Clinical Microbiology. Dec, 2011  |  Pubmed ID: 22170923

Drug resistance surveillance and strain typing of Mycobacterium leprae are necessary to investigate ongoing transmission of leprosy in endemic regions. To enable wider implementation of these molecular analyses, novel real time-PCR-high resolution melt (RT-PCR-HRM) assays without allele specific primers or probes and post PCR sample handling were developed. For the detection of mutations within drug resistance determining regions (DRDRs) of folP1, rpoB and gyrA, targets for dapsone, rifampicin and fluoroquinolones, real-time PCR-HRM assays were developed. A reference panel of wild type and drug resistant mouse foot pad derived strains which included three folP1, two rpoB and one gyrA mutation types were tested. RT-PCR-HRM correctly distinguished the wild type from the mutant strains. In addition, RT-PCR HRM analyses aided in recognizing samples with mixed or minor alleles and also a mislabeled sample. When tested in 121 sequence characterized clinical strains, HRM identified all the folP1 mutants representing two mutation types, including one not within the reference panel. The false positives (<5%) could be attributed to low DNA concentration or PCR inhibition. A second set of RT-PCR HRM assays for identification of three previously reported SNPs that have been used for strain typing were developed and validated in 22 reference and 25 clinical strains. Real-time PCR-HRM is a sensitive, simple, rapid and high throughput tool for routine screening known DRDR mutants in new and relapsed cases, SNP typing and detection of minor mutant alleles in wild type background at lower costs than current methods and with potential for quality control in leprosy investigations.

Characterization of PpGalNAc-T18, a Member of the Vertebrate-specific Y Subfamily of UDP-N-acetyl-α-D-galactosamine: Polypeptide N-acetylgalactosaminyltransferases

Glycobiology. Dec, 2011  |  Pubmed ID: 22171061

The first step of mucin-type O-glycosylation is catalyzed by members of the UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferase (ppGalNAc-T, EC 2.4.1.41) family. Each member of this family has unique substrate specificity and expression profiles. In this report, we describe a new subfamily of ppGalNAc-Ts, designated the Y subfamily. The Y subfamily consists of four members, ppGalNAc-T8, -T9, -T17 and -T18, in which the conserved YDX(5)WGGENXE sequence in the Gal/GalNAc-T motif of ppGalNAc-Ts is mutated to LDX(5)YGGENXE. Phylogenetic analysis revealed that the Y subfamily members only exist in vertebrates. All four Y subfamily members lack the in vitro GalNAc-transferase activity towards classical substrates possibly because of the UDP-GalNAc binding pocket mutants. However, ppGalNAc-T18, the newly identified defining member, was localized in the endoplasmic reticulum (ER) rather than the Golgi apparatus in lung carcinoma cells. Knockdown of ppGalNAc-T18 altered cell morphology, proliferation potential, and changed cell O-glycosylation. ppGalNAc-T18 can also modulate in vitro GalNAc-transferase activity of ppGalNAc-T2 and -T10, suggesting it may be a chaperone-like protein. These findings suggest that the new Y subfamily of ppGalNAc-Ts plays important role in protein glycosylation; characterizing their functions will provide new insight into the role of ppGalNAc-Ts.

An Essential Role for the Id1/PI3K/Akt/NFkB/survivin Signalling Pathway in Promoting the Proliferation of Endothelial Progenitor Cells in Vitro

Molecular and Cellular Biochemistry. Dec, 2011  |  Pubmed ID: 22139302

The enhancement of re-endothelialisation is a critical therapeutic option for repairing injured blood vessels. Endothelial progenitor cells (EPCs) are the major source of cells that participate in endothelium repair and contribute to re-endothelialisation by reducing neointima formation after vascular injury. The over-expression of the inhibitor of differentiation or DNA binding 1 (Id1) significantly improved EPC proliferation. This study aimed to investigate the effects of Id1 on the phosphatidylinositol-3-kinase (PI3K)/Akt/nuclear factor kappa B (NFκB)/survivin signalling pathway and its significance in promoting EPC proliferation in vitro. Spleen-derived EPCs were cultured as previously described. Id1 was presented at low levels in EPCs, and was rapidly up-regulated by stimulation with vascular endothelial growth factor. We demonstrated that transient transfection of Id1 into EPCs activated the PI3K/Akt/NFκB/survivin signalling pathway and promoted EPC proliferation. The proliferation of EPCs was extensively inhibited by silencing of endogenous Id1, and knockdown of Id1 expression led to suppression of PI3K/Akt/NFκB/survivin signalling pathway in EPCs. In addition, blockade by the PI3K-specific inhibitor LY294002, Akt inhibitor, the NFκB inhibitor BAY 11-7082, the survivin inhibitor Curcumin, or the survivin inhibitor YM155 reduced the effects of Id1 transfection. These results suggest that the Id1/PI3K/Akt/NFκB/survivin signalling pathway plays a critical role in EPC proliferation. The Id1/PI3K/Akt/NFκB/survivin signalling pathway may represent a novel therapeutic target in the prevention of restenosis after vascular injury.

Relationship Between Aberrant Methylation of FAS Promoter and Biological Behavior of Bladder Urothelial Carcinoma

Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban. Dec, 2011  |  Pubmed ID: 22173501

This study examined the promoter methylation of APO-1/CD95 (Fas) gene in bladder urothelial carcinoma and analyzed the relationship between the Fas promoter methylation and the biological behavior of bladder cancer. Promoter methylation of Fas gene was detected by methylation-specific PCR (MSP) in 4 bladder cancer cell lines, 50 human bladder urothelial carcinoma samples and l0 normal bladder tissue samples. Correlation of the aberrant methylation of Fas promoter with the clinicopathological parameters was statistically analyzed. The results showed that Fas was down-regulated at both mRNA and protein level in bladder cancer cell lines and tissue samples of bladder urothelial carcinoma. The positive rate of Fas protein expression in bladder urothelial carcinoma was 34.0% (17/50), significantly lower than that in normal bladder tissues (70.0%, 7/10) (P<0.01). Fas promoter methylation was detected, and the positive rate of Fas promoter methylation in bladder urothelial carcinoma was 42.0% (21/50), which was obviously higher than that in normal bladder tissues (0.0%, 0/10) (P<0.01). The aberrant methylation of Fas promoter was reversely correlated with Fas protein expression (P<0.05). Furthermore, the positive rates of Fas promoter methylation in high-grade and low-grade bladder urothelial carcinoma were 73.3% (11/15) and 34.2% (12/35), respectively, with significant difference shown (P<0.05). No statistical significance was found in the Fas promoter methylation among different clinical stages of bladder cancer. It was concluded that Fas promoter hypermethylation plays an important role in the pathogenesis of bladder urothelial carcinoma and may serve as a prognostic indicator of bladder urothelial carcinoma.

Effect of Human Cytomegalovirus on Invasive Capability of Early Pregnant Extravillous Cytotrophoblasts

Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban. Dec, 2011  |  Pubmed ID: 22173505

The effect of human cytomegalovirus (HCMV) on invasive capability of early pregnant extravillous cytotrophoblasts (EVTs) was investigated in vitro. Primary EVTs were obtained by complex phosphoesterasum digestion and gradient centrifugation from villous tissue aseptically taken from healthy pregnant women. Cytokeratin7 (CK7), vimentin (Vim) and c-erbB-2 were immunocytochemically detected to identify source of cells, and HCMVpp65 antigen was assayed to determine the infection state of primary EVTs by immunocytochemical staining. The EVTs were divided into two groups: control group and HCMV group, and the expression of c-erbB-2, matrix metalloproteinase-2 (MMP-2) and MMP-9 proteins was detected in two groups by immunocytochemistry and Western blotting. Enzymic activity changes of MMP-2 and MMP-9 were tested by gelatin zymography in primary EVTs infected with HCMV. The invasion of primary EVTs was detected by cell invasion assay in vitro after they were infected by HCMV. The cell source identification showed that the cells obtained were highly-pure primary EVTs, and primary EVTs could be infected by HCMV. Primary EVTs could express c-erbB-2, MMP-2 and MMP-9 proteins, and as compared with control group, the protein expression was decreased significantly in HCMV groups (P<0.05). Primary EVTs could secrete active MMP-2 and MMP-9 in vitro, and the activity of two MMPs was decreased significantly in HCMV groups (P<0.05). The in vitro cell invasion assay showed that the number of primary EVTs permeating Matrigel in HCMV group was decreased (P<0.05). We are led to conclude that HCMV can infect primary EVTs and inhibit their invasion capability, suggesting that the impaired EVT's invasion capability might be related to the abnormal expression of c-erbB-2, MMP-2 and MMP-9 proteins.

[Population and Distribution of Western Black Crested Gibbon (Nomascus Concolor) at Ailao Mountain, Xinping, Yunnan]

Dong Wu Xue Yan Jiu = Zoological Research / "Dong Wu Xue Yan Jiu" Bian Ji Wei Yuan Hui Bian Ji. Dec, 2011  |  Pubmed ID: 22184029

The western black crested gibbon (Nomascus concolor) is mainly distributed in Yunnan, China. Ailao Mountain is located in central Yunnan and divided into three prefectures and six counties. This mountain forms the principle distribution range for western black crested gibbon; however, there are no published data on the gibbon population inhabiting the Xinping administrative. Take the interview results conducted in 2007 and 2009 with local people as the reference, this study conducted an extensive field survey covering all possible habitats from November 2009 to January 2010 using call surveys. Among the one hundred and twenty-four gibbon groups which were confirmed across the Ailao Mountain, the largest known population of western black crested gibbons yet, 85 groups inhabit the national nature reserve and adjacent national forest, 30 groups inhabit the provincial nature reserve and nine groups inhabit the collective forest located outside the reserve and national forest. We found that the western black crested gibbons here have a patchy distribution pattern and occur at higher densities in certain areas. Moreover, the population distribution density and elevation gradient distribution decline from north to south. The results also demonstrated the importance of Ailao Mountain in the western black crested gibbon protection.

Melanocortin-4 Receptor in the Medial Amygdala Regulates Emotional Stress-induced Anxiety-like Behaviour, Anorexia and Corticosterone Secretion

The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (CINP). Dec, 2011  |  Pubmed ID: 22176700

The central melanocortin system has been implicated in emotional stress-induced anxiety, anorexia and activation of the hypothalamo-pituitary-adrenal (HPA) axis. However, the underlying neural substrates have not been identified. The medial amygdala (MeA) is highly sensitive to emotional stress and expresses high levels of the melanocortin-4 receptor (MC4R). This study investigated the effects of activation and blockade of MC4R in the MeA on anxiety-like behaviour, food intake and corticosterone secretion. We demonstrate that MC4R-expressing neurons in the MeA were activated by acute restraint stress, as indicated by induction of c-fos mRNA expression. Infusion of a selective MC4R agonist into the MeA elicited anxiogenic-like effects in the elevated plus-maze test and decreased food intake. In contrast, local MeA infusion of SHU 9119, a MC4R antagonist, blocked restraint stress-induced anxiogenic and anorectic effects. Moreover, plasma corticosterone levels were increased by intra-MeA infusion of the MC4R agonist under non-stressed conditions and restraint stress-induced elevation of plasma corticosterone levels was attenuated by pretreatment with SHU 9119 in the MeA. Thus, stimulating MC4R in the MeA induces stress-like anxiogenic and anorectic effects as well as activation of the HPA axis, whereas antagonizing MC4R in this region blocks such effects induced by restraint stress. Together, our results implicate MC4R signalling in the MeA in behavioural and endocrine responses to stress.

Financial Factor Influence on Scaling and Memory of Trading Volume in Stock Market

Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics. Oct, 2011  |  Pubmed ID: 22181232

We study the daily trading volume volatility of 17 197 stocks in the US stock markets during the period 1989-2008 and analyze the time return intervals τ between volume volatilities above a given threshold q. For different thresholds q, the probability density function P_{q}(τ) scales with mean interval 〈τ〉 as P_{q}(τ)=〈τ〉^{-1}f(τ/〈τ〉), and the tails of the scaling function can be well approximated by a power law f(x)∼x^{-γ}. We also study the relation between the form of the distribution function P_{q}(τ) and several financial factors: stock lifetime, market capitalization, volume, and trading value. We find a systematic tendency of P_{q}(τ) associated with these factors, suggesting a multiscaling feature in the volume return intervals. We analyze the conditional probability P_{q}(τ|τ_{0}) for τ following a certain interval τ_{0}, and find that P_{q}(τ|τ_{0}) depends on τ_{0} such that immediately following a short (long) return interval a second short (long) return interval tends to occur. We also find indications that there is a long-term correlation in the daily volume volatility. We compare our results to those found earlier for price volatility.

[Relationship Between Single Nucleotide Polymorphisms in IL28B Gene and Response to Interferon Treatment in Chronic Hepatitis B Patients]

Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University. Dec, 2011  |  Pubmed ID: 22200702

To explore the relationship between the single nucleotide polymorphisms (SNPs) of rs12979860 and rs8099917 in IL28B gene and the response to interferon treatment in hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B patients.

The Use of Calcium Phosphate-based Biomaterials in Implant Dentistry

Journal of Materials Science. Materials in Medicine. Dec, 2011  |  Pubmed ID: 22201031

Since calcium phosphates (CaPs) were first proposed, a wide variety of formulations have been developed and continuously optimized, some of which (e.g. calcium phosphate cements, CPCs) have been successfully commercialized for clinical applications. These CaP-based biomaterials have been shown to be very attractive bone substitutes and efficient drug delivery vehicles across diverse biomedical applications. In this article, CaP biomaterials, principally CPCs, are addressed as alternatives/complements to autogenous bone for grafting in implant dentistry and as coating materials for enhancing the osteoinductivity of titanium implants, highlighting their performance benefits simultaneously as carriers for growth factors and as scaffolds for cell proliferation, differentiation and penetration. Different strategies for employing CaP biomaterials in dental implantology aim to ultimately reach the same goal, namely to enhance the osseointegration process for dental implants in the context of immediate loading and to augment the formation of surrounding bone to guarantee long-term success.

The Nuclear Factor-kappaB Inhibitor Pyrrolidine Dithiocarbamate Reduces Polyinosinic-polycytidilic Acid-induced Immune Response in Pregnant Rats and the Behavioral Defects of Their Adult Offspring

Behavioral and Brain Functions : BBF. Dec, 2011  |  Pubmed ID: 22208616

ABSTRACT: BACKGROUND: Epidemiological studies have indicated that maternal infection during pregnancy may lead to a higher incidence of schizophrenia in the offspring. It is assumed that the maternal infection increases the immune response, leading to neurodevelopmental disorders in the offspring. Maternal polyinosinic-polycytidilic acid (PolyI:C) treatment induces a wide range of characteristics in the offspring mimicking some schizophrenia symptoms in humans. These observations are consistent with the neurodevelopmental hypothesis of schizophrenia. METHODS: We examined whether suppression of the maternal immune response could prevent neurodevelopmental disorders in adult offspring. PolyI:C or saline was administered to early pregnant rats to mimic maternal infection, and the maternal immune response represented by tumor necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) levels was determined by enzyme-linked immunosorbent assays (ELISA). The NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC) was used to suppress the maternal immune response. Neurodevelopmental disorders in adult offspring were examined by prepulse inhibition (PPI), passive avoidance, and active avoidance tests. RESULTS: PolyI:C administration to early pregnant rats led to elevated serum cytokine levels as shown by massive increases in serum TNF-alpha and IL-10 levels. The adult offspring showed defects in prepulse inhibition, and passive avoidance and active avoidance tests. PDTC intervention in early pregnant rats suppressed cytokine increases and reduced the severity of neurodevelopmental defects in adult offspring. CONCLUSIONS: Our findings suggest that PDTC can suppress the maternal immune response induced by PolyI:C and partially prevent neurodevelopmental disorders of adult offspring.

Occurrence and Exposure to Polycyclic Aromatic Hydrocarbons and Their Derivatives in a Rural Chinese Home Through Biomass Fuelled Cooking

Environmental Pollution (Barking, Essex : 1987). Dec, 2011  |  Pubmed ID: 22209516

The concentration and composition of PAHs emitted from biomass cooking fuel were characterized in a rural non-smoking household in northern China. Twenty-two parent PAHs (pPAHs), 12 nitro-PAHs (nPAHs), and 4 oxy-PAHs (oPAHs) were measured in the kitchen, bedroom, and outdoors during both summer and winter. The most severe contamination occurred in the kitchen in the winter, where the daily mean concentrations of pPAHs, nPAHs, and oPAHs were 7500 ± 4100, 38 ± 29, and 8400 ± 9200 ng/m(3), respectively. Our results suggest that the nPAHs were largely from secondary formation in ambient air while oPAHs were either from primary emission of biomass burning or secondary formation from pPAHs in the kitchen. The daily mean benzo(a)pyrene equivalent exposure concentration was as high as 200 ± 160 ng/m(3) in the winter for the housewife who did the cooking compared to 59 ± 37 ng/m(3) for the control group that did not cook.

Metabolism of Cholesterol, Vitamin D3 and 20-hydroxyvitamin D3 Incorporated into Phospholipid Vesicles by Human CYP27A1

The Journal of Steroid Biochemistry and Molecular Biology. Dec, 2011  |  Pubmed ID: 22210453

CYP27A1 is a mitochondrial cytochrome P450 which can hydroxylate vitamin D3 and cholesterol at carbons 25 and 26, respectively. The product of vitamin D3 metabolism, 25-hydroxyvitamin D3, is the precursor to the biologically active hormone, 1α,25-dihydroxyvitamin D3. CYP27A1 is attached to the inner mitochondrial membrane and substrates appear to reach the active site through the membrane phase. We have therefore examined the ability of bacterially expressed and purified CYP27A1 to metabolize substrates incorporated into phospholipid vesicles which resemble the inner mitochondrial membrane. We also examined the ability of CYP27A1 to metabolize 20-hydroxyvitamin D3 (20(OH)D3), a novel non-calcemic form of vitamin D derived from CYP11A1 action on vitamin D3 which has anti-proliferative activity on keratinocytes, leukemic and myeloid cells. CYP27A1 displayed high catalytic activity towards cholesterol with a turnover number (k(cat)) of 9.8min(-1) and K(m) of 0.49mol/mol phospholipid (510μM phospholipid). The K(m) value of vitamin D3 was similar for that of cholesterol, but the k(cat) was 4.5-fold lower. 20(OH)D3 was metabolized by CYP27A1 to two major products with a k(cat)/K(m) that was 2.5-fold higher than that for vitamin D3, suggesting that 20(OH)D3 could effectively compete with vitamin D3 for catalysis. NMR and mass spectrometric analyses revealed that the two major products were 20,25-dihydroxyvitamin D3 and 20,26-dihydroxyvitamin D3, in almost equal proportions. Thus, the presence of the 20-hydroxyl group on the vitamin D3 side chain enables it to be metabolized more efficiently than vitamin D3, with carbon 26 in addition to carbon 25 becoming a major site of hydroxylation. Our study reports the highest k(cat) for the 25-hydroxylation of vitamin D3 by any human cytochrome P450 suggesting that CYP27A1 might be an important contributor to the synthesis of 25-hydroxyvitamin D3, particularly in tissues where it is highly expressed.

Sarcoidosis Mimicking Recurrent Lymphoma

American Journal of Hematology. Dec, 2011  |  Pubmed ID: 22213376

[Probe of Classification of Adult Acute Lymphoblastic Leukemia]

Zhonghua Xue Ye Xue Za Zhi = Zhonghua Xueyexue Zazhi. Jul, 2011  |  Pubmed ID: 22213861

To investigate the biologic features of adult acute lymphoblastic leukemia (ALL), and reclassified our ALL patients according to the 2008 WHO classification.

[Protective Effects of Lycium Barbarum Extract Against MPP(+) -induced Neurotoxicity in Caenorhabditis Elegans and PC12 Cells]

Zhong Yao Cai = Zhongyaocai = Journal of Chinese Medicinal Materials. Aug, 2011  |  Pubmed ID: 22233040

To investigate the neuroprotective effects of Lycium barbarum extract against MPP(+) -induced neurotoxicity in Caenorhabditis elegans and PC12 cells and its mechanism. Methods: Pretreated MPP(+) -induced nearotoxicity in C. elegans and PC12 cells with Lycium barbarum at different dosages. The viability and DA neurodegeneration was assessed in C. elegans selectively expressing green fluorescent protein (GFP) in DA neurons. PC12 cell damage was measured using MTT and nuclear morphology. Intracellular reactive oxygen species (ROS), mitochondrial membrane potential and total GSH were assessed.

[Isolation and Analysis of a New Phytoecdysteroid from Cyanotis Arachnoidea C. B. Clarke]

Se Pu = Chinese Journal of Chromatography / Zhongguo Hua Xue Hui. Sep, 2011  |  Pubmed ID: 22233087

Cyanotis arachnoidea is a plant with plenty of phytoecdysteroid. To study the active compound in it, a new phytoecdysteroid with 5alpha-cholesta skeleton, was isolated from the whole plant of Cyanotis arachnoidea C. B. Clarke by using various chromatographic methods (alumina column chromatography, silica gel column chromatography, octadecyl silane (ODS) column chromatography, thin layer chromatography (TLC) and high performance liquid chromatography (HPLC)). Its structure was analyzed on the basis of 1D and 2D nuclear magnetic resonances (NMR), electrospray ionization mass spectrometry (ESI-MS) methods. It is a compound with structure of 3beta,14alpha, 14alpha,20R,22R,25-hexahydroxy-5alpha-cholest-7-en-6-one, which is a rare phytoecdysteroid with 5alpha-H.

[Progress in Regulative Mechanism of EBV Lytic Replication Cycle]

Bing Du Xue Bao = Chinese Journal of Virology / [bian Ji, Bing Du Xue Bao Bian Ji Wei Yuan Hui]. Nov, 2011  |  Pubmed ID: 22263278

[Clinical Application of Imiquimod for the Treatment of Infantile Hemangiomas]

Zhonghua Zheng Xing Wai Ke Za Zhi = Zhonghua Zhengxing Waike Zazhi = Chinese Journal of Plastic Surgery. Nov, 2011  |  Pubmed ID: 22292400

To explore the clinical application of imiquimod for the treatment of infantile hemangiomas (IH).

[To Observe Postoperative Analgesia and Preemptive Analgesia of Tramadol Hydrochloride Sustained Release Tablets for Nasal Endoscopic Operation]

Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi = Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery. Nov, 2011  |  Pubmed ID: 22303699

To observe postoperative analgesia and preemptive analgesia of Tramadol hydrochloride sustainged release tablets for nasal endoscopic operation.

[Study of the Physical Properties of SnS Thin Films Deposited by Ultrasonic Spray Pyrolysis Method]

Guang Pu Xue Yu Guang Pu Fen Xi = Guang Pu. Oct, 2011  |  Pubmed ID: 22250530

In the present paper, SnS thin films were deposited by ultrasonic spray pyrolysis method. The influence of the three different precursor concentrations on the properties of SnS thin films was compared. XRD shows that when precursor solution is thiourea (0.5 mol x L(-1)) + tin tetrachloride (0.5 mol x L(-1)) + deionized water, there are SnS and SnO2 mixed phases; when precursor solution is thiourea (0.6 mol x L(-1)) + tin tetrachloride (0.5 mol x L(-1)) + deionized water, SnS phase is the dominant diffraction peak, although a certain amount of SnO2 phase is contained; when precursor solution is thiourea (0.7 mol x L(-1)) + tin tetrachloride (0.5 mol x L(-1)) + deionized water, thin film after being annealed is single SnS thin film with orthorhombic structure. SEM shows that films are uniform and dense. Furthermore, the particles of films are bigger when thiourea concentration is higher. Transmittance spectrum shows that the influence of precursor concentration on transmittance of thin films is less. Dark I-V and C-V tests of the devices show that junction characteristics of the devices were similar when prepared by three different concentrations of precursor solution, and as the thiourea concentration is higher, the carrier concentration is relatively larger.

[Clinical Significances of Serum NO and OxLDL in Obstructive Sleep Apnea-hypopnea Syndrome]

Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi = Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery. Nov, 2011  |  Pubmed ID: 22260075

To study the correlation between the serum levels of nitrogen oxide (NO) and oxidized low density lipoprotein (oxLDL) in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS).

Simultaneous Determination of Evodiamine and Rutecarpine in Rabbit Plasma by LC-ESI-MS and Its Application to Pharmacokinetics

Die Pharmazie. Dec, 2011  |  Pubmed ID: 22312694

A sensitive and selective liquid chromatography-mass spectrometry (LC-MS) method for the determination of evodiamine and rutecarpine in rabbit plasma was developed and validated. The analytes and internal standard (IS) are extracted from plasma by one-step protein precipitation with acetonitrile, and separated on a Zorbax SB-C18 column (2.1 mm x 50 mm, 3.5 microm) using acetonitrile-0.1% formic acid as mobile phase with gradient elution. Electrospray ionization (ESI) source was applied and operated in positive ion mode, and selective ion monitoring (SIM) mode used to quantify evodiamine and rutecarpine. The assay is linear over the range of 2-1600 ng/mL for evodiamine and rutecarpine, with a lower limit of quantification (LLOQ) of 5 ng/mL both for evodiamine and rutecarpine. Intra-day and inter-day precision are less than 12% and the accuracy are in the range of 90.9-104.3%. Furthermore, the newly developed method is successfully used for the determination of evodiamine and rutecarpine in rabbit plasma for pharmacokinetic study.

[Neoadjuvant Chemotherapy with Paclitaxel and Cisplantin or Carboplatin for Patients with Locally Advanced Uterine Cervical Cancer]

Zhonghua Zhong Liu Za Zhi [Chinese Journal of Oncology]. Aug, 2011  |  Pubmed ID: 22325224

To investigate the efficacy and toxicity of neoadjuvant chemotherapy with paclitaxel and carboplatin or cisplatin for patients with locally advanced cervical cancer.

[Nimotuzumab in Combination with Chemotherapy in Patients with Advanced Non-small Cell Lung Cancer]

Zhonghua Zhong Liu Za Zhi [Chinese Journal of Oncology]. Aug, 2011  |  Pubmed ID: 22325226

To evaluate the role of nimotuzumab in combination with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC).

[USMM Technology Application in Extraction and Separation of Salvia Miltiorrhiza]

Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica. Nov, 2011  |  Pubmed ID: 22375387

To investigate USMM coupled techniques applied in active ingredient extraction and separation of Salvia.

Polymer-assisted Deposition of Co-doped Zinc Oxide Thin Films for the Detection of Aromatic Organic Compounds

Journal of Nanoscience and Nanotechnology. Dec, 2011  |  Pubmed ID: 22409004

Co-doped Zinc oxide thin films are deposited onto SiO2/Si substrate by polymer-assisted deposition method. The surface morphology, structures and chemical states of the thin films are examined by scanning electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The gas-sensing properties of the thin films upon exposure to aromatic organic compound vapors are also investigated. Co-doping is shown to be very effective in enhancing the response of ZnO thin film to aromatic organic compound.

Fabrication and Structure Characterization of Te Butterfly Nanostructures

Journal of Nanoscience and Nanotechnology. Dec, 2011  |  Pubmed ID: 22409051

Te nanowires and butterfly nanostructures have been fabricated by template-free electrodeposition (TFED) in aqueous solution. By high-resolution transmission electron microscopy (HRTEM) study, the favored growth directions of the nanowires and the wings of the butterfly nanostructures were determined to be along the [0001] direction of trigonal Te, and the twinning plane of the butterfly nanostructures was (11-22). The cathodoluminescence measurements carried out at different positions of the butterfly nanostructure indicated that the twin boundaries influenced the photoemission efficiency.

Characterization and Optimization of Fe(II)Cit-No Reduction by Pseudomonas Sp

Environmental Technology. Dec, 2011  |  Pubmed ID: 22439583

Biological reduction of nitric oxide (NO), chelated by ferrous L (L: chelate reagent), to N2 is one of the core processes in a chemical absorption-biological reduction integrated technique for nitrogen oxide (NOx) removal from flue gases. In this study, a newly isolated strain, Pseudomonas sp., was used to reduce NO chelated by Fe(II)Cit (Cit: citrate) as Fe(II)Cit-NO, and some factors were investigated. The results showed that, at the NO concentration of 670 mg/m3, 65.9% of NO was totally reduced within 25 h under anaerobic conditions, and the optimal conditions for the bioreduction of NO were found. The strain of Pseudomonas sp. could efficiently use glucose as the carbon source for Fe(II)Cit-NO reduction. Though each complex could be reduced by its own dedicated bacterial strain, Fe(III)Cit could also be reduced by the strain of Pseudomonas sp. The nitrite ion, NO2-, could inhibit cell growth and thus affect the Fe(III) reduction process. These findings provide some useful data for Fe(II)Cit-NO reduction, scrubber solution regeneration and NOx removal process design.

[Outcome of Acute Promyelocytic Leukemia with Homoharringtonine (HHT) and ATRA]

Zhonghua Xue Ye Xue Za Zhi = Zhonghua Xueyexue Zazhi. Nov, 2011  |  Pubmed ID: 22339911

To assess complete remission (CR), the overall survival (OS), event-free survival (EFS) and adverse events of newly diagnosed acute promyelocytic leukemia (APL) with homoharringtonine (HHT) plus ATRA, to evaluate the therapeutic effect by comparing HHT plus ATRA with daunorubicin plus ATRA as induction regimen (HA with DA as post-remission regimen).

[Expression of Cdc7 and Mcm2 As a Marker for Proliferation and Prognosis in Diffuse Large B Cell Lymphoma]

Zhonghua Zhong Liu Za Zhi [Chinese Journal of Oncology]. Dec, 2011  |  Pubmed ID: 22340100

The aim of this study was to assess the expression of cell division cycle 7 (Cdc7) kinase and minichromosome maintenance protein 2 (MCM2) in diffuse large B cell lymphoma (DLBCL) and explore their relationship with prognosis of DLBCL patients.

Hydrogen Sulfide Regulates Vascular Endoplasmic Reticulum Stress in Apolipoprotein E Knockout Mice

Chinese Medical Journal. Nov, 2011  |  Pubmed ID: 22340159

Atherosclerosis is an important cardiovascular disease, becoming a major and increasing health problem in developed countries. However, the possible underlying mechanisms were not completely clear. In 2009, our research group first discovered that hydrogen sulfide (H(2)S) as a novel gastrotransmitter played an important anti-atherosclerotic role. The study was designed to examine the regulatory effect of hydrogen sulfide (H(2)S) on endoplasmic reticulum stress (ERS) in apolipoprotein E knockout (apoE(-/-)) mice fed a Western type diet.

Gastrointestinal Stromal Tumor with Synchronous Isolated Parenchymal Splenic Metastasis of Ovarian Cancer

Chinese Medical Journal. Dec, 2011  |  Pubmed ID: 22340419

Gastrointestinal stromal tumor (GIST) represents the most common intramural mesenchymal tumor of the gastrointestinal tract, but the synchronous occurrence of GIST in the stomach and gynecological cancer is rare. We present a unique case of a 56-year-old female patient who was diagnosed with the synchronous development of GIST and an isolated parenchymal splenic metastasis of ovarian cancer. She underwent a wide local excision of gastric lesions with splenectomy. A morphological (histological and immunohistochemical) study established a spindle-cell type of gastrointestinal tumor that expressed CD117, and a parenchymal recurrence of ovarian papillary serous adenocarcinoma. The patient has remained alive and disease-free for 30 months since the last operation. A small GIST concomitant with an isolated parenchymal splenic metastasis of ovarian cancer is rarely encountered. The coexistence of GIST with other malignancies constitutes an intriguing oncologic model. Surgeons are advised to be alert against possible primary GIST accompanying other neoplasms.

[Anti-reflux Effects of Reverse Stapling with Nissen Fundoplication for Esophagogastric Anastomoses]

Zhonghua Yi Xue Za Zhi. Dec, 2011  |  Pubmed ID: 22333203

To explore the anti-reflux effects of esophagogastric anastomoses by reverse stapling with Nissen fundoplication (RSNF).

[Role and Mechanism of Purkinje Fiber in the Initiation and Maintenance of Ventricular Arrhythmias]

Zhonghua Xin Xue Guan Bing Za Zhi. Nov, 2011  |  Pubmed ID: 22336466

[Clinical and Cytogenetic Features and Their Influencing Factors of Core Binding Factor Acute Myeloid Leukemia]

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae. Oct, 2011  |  Pubmed ID: 22338135

To discuss the clinical and cytogenetic features of core binding factor (CBF) acute myeloid leukemia (AML) patients and the main factors that influence the prognosis.

Riboflavin Alleviates Cardiac Failure in Type I Diabetic Cardiomyopathy

Heart International. Sep, 2011  |  Pubmed ID: 22355488

Heart failure (HF) is a common and serious comorbidity of diabetes. Oxidative stress has been associated with the pathogenesis of chronic diabetic complications including cardiomyopathy. The ability of antioxidants to inhibit injury has raised the possibility of new therapeutic treatment for diabetic heart diseases. Riboflavin constitutes an essential nutrient for humans and animals and it is an important food additive. Riboflavin, a precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), enhances the oxidative folding and subsequent secretion of proteins. The objective of this study was to investigate the cardioprotective effect of riboflavin in diabetic rats. Diabetes was induced in 30 rats by a single injection of streptozotocin (STZ) (70 mg /kg). Riboflavin (20 mg/kg) was orally administered to animals immediately after induction of diabetes and was continued for eight weeks. Rats were examined for diabetic cardiomyopathy by left ventricular (LV) remadynamic function. Myocardial oxidative stress was assessed by measuring the activity of superoxide dismutase (SOD), the level of malondialdehyde (MDA) as well as heme oxygenase-1 (HO-1) protein level. Myocardial connective tissue growth factor (CTGF) level was measured by Western blot in all rats at the end of the study. In the untreated diabetic rats, left ventricular systolic pressure (LVSP) rate of pressure rose (+dp/dt), and rate of pressure decay (-dp/dt) were depressed while left ventricular end-diastolic pressure (LVEDP) was increased, which indicated the reduced left ventricular contractility and slowing of left ventricular relaxation. The level of SOD decreased, CTGF and HO-1 protein expression and MDA content rose. Riboflavin treatment significantly improved left ventricular systolic and diastolic function in diabetic rats, there were persistent increases in significant activation of SOD and the level of HO-1 protein, and a decrease in the level of CTGF. These results suggest that riboflavin treatment ameliorates myocardial function and improves heart oxidant status, whereas raising myocardial HO-1 and decreasing myocardial CTGF levels have beneficial effects on diabetic cardiomyopathy.

[Impact of Simulation Operation High Water Level on Oncomelania Hupensis Natural Growth in Water Diversion Rivers of East Route of South-to-North Water Diversion Project]

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi = Chinese Journal of Schistosomiasis Control. Dec, 2011  |  Pubmed ID: 22379822

To verify the impact of operation high water level on Oncomelania hupensis natural growth in the water diversion rivers of the east route of South-to-North Water Diversion Project.

In Vitro Evaluation of Cytotoxicity and Oxidative Stress Induced by Multiwalled Carbon Nanotubes in Murine RAW 264.7 Macrophages and Human A549 Lung Cells

Biomedical and Environmental Sciences : BES. Dec, 2011  |  Pubmed ID: 22365394

To investigate in vitro cytotoxicity and oxidative stress response induced by multiwalled carbon nanotubes (MWCNTs).

[Construction and Sequence Analysis of Recombinant HCV-1b Replicon by Replacing NS5A Region]

Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University. Jan, 2012  |  Pubmed ID: 22366003

To construct the recombinant HCV-1b replicon by replacing NS5A region using serum samples from patients with chronic hepatitis C (CHC) in South China and explore the biological characteristics of NS5A protein in response to antiviral therapy.

Development of Multifunctional Hyaluronan-coated Nanoparticles for Imaging and Drug Delivery to Cancer Cells

Biomacromolecules. Apr, 2012  |  Pubmed ID: 22372739

Currently, there is high interest in developing multifunctional theranostic platforms for cancer monitoring and chemotherapy. Herein, we report hyaluronan (HA)-coated superparamagnetic iron oxide nanoparticles (HA-SPION) as a promising system for targeted imaging and drug delivery. When incubated with cancer cells, HA-SPIONs were rapidly taken up and the internalization of HA-SPION by cancer cells was much higher than the NPs without HA coating. The high magnetic relaxivity of HA-SPION coupled with enhanced uptake enabled magnetic resonance imaging of cancer cells. Furthermore, doxorubicin (DOX) was attached onto the nanoparticles through an acid responsive linker. While HA-SPION was not toxic to cells, DOX-HA-SPION was much more potent than free DOX to kill not only drug-sensitive but also multi-drug-resistant cancer cells. This was attributed to differential uptake mechanisms and cellular distributions of free DOX and DOX-HA-SPION in cancer cells.

Surface-Engineered Gold Nanorods: Promising DNA Vaccine Adjuvant for HIV-1 Treatment

Nano Letters. Feb, 2012  |  Pubmed ID: 22372996

With the intense international response to the AIDS pandemic, HIV vaccines have been extensively investigated but have failed due to issues of safety or efficacy in humans. Adjuvants for HIV/AIDS vaccines are under intense research but a rational design approach is still lacking. Nanomaterials represent an obvious opportunity in this field due to their unique physicochemical properties. Gold nanostructures are being actively studied as a promising and versatile platform for biomedical application. Herein, we report novel surface-engineered gold nanorods (NRs) used as promising DNA vaccine adjuvant for HIV treatment. We have exploited the effects of surface chemistry on the adjuvant activity of the gold nanorod by placing three kinds of molecules, that is, cetyltrimethylammonium bromide (CTAB), poly(diallydimethylammonium chloride) (PDDAC), and polyethyleneimine (PEI) on the surface of the nanorod. These PDDAC- or PEI-modified Au NRs can significantly promote cellular and humoral immunity as well as T cell proliferation through activating antigen-presenting cells if compared to naked HIV-1 Env plasmid DNA treatment in vivo. These findings have shed light on the rational design of low-toxic nanomaterials as a versatile platform for vaccine nanoadjuvants/delivery systems.

Effects of the Transparent Cathode on the Performance of a Relativistic Magnetron with Axial Radiation

The Review of Scientific Instruments. Feb, 2012  |  Pubmed ID: 22380113

Experimental investigation of the transparent cathode used in a relativistic magnetron with axial radiation is reported in this paper. The transparent cathode is composed of six separate stalks with the diameter of 6 mm. Under the working condition of 549 kV and ∼0.38 T, the relativistic magnetron with the transparent cathode experimentally produces a 550 MW microwave. The radiation mode is TE(11) at the frequency of 2.35 GHz. The total efficiency is 16.7%. The variations of the relative positions between the separate stalks and the anode blocks can perform the maximum difference of 4 ns in microwave duration. Compared with the conventional solid cathode, the transparent cathode provides faster startup time of 12 ns, relatively wider pulse duration of 35% and relatively higher efficiency of 10.6%.

[Expression of Hsa-miR-20a in Human Glioma Tissues and Its Effect on the Proliferation of Human Glioma Cells in Vitro]

Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University. Feb, 2012  |  Pubmed ID: 22381757

To investigate miR-20a expression in human glioma and normal brain tissues and its effect on the proliferation of glioma cells in vitro.

The U-box/ARM E3 Ligase PUB13 Regulates Cell Death, Defense and Flowering Time in Arabidopsis1

Plant Physiology. Mar, 2012  |  Pubmed ID: 22383540

The components in plant signal transduction pathways are intertwined and affect each other to coordinate plant growth, development and defenses to stresses. The role of ubiquitination in connecting these pathways, particularly plant innate immunity and flowering, is largely unknown. Here we report the dual roles for the Arabidopsis (Arabidopsis thaliana) Plant U-Box protein 13 (PUB13) in defense and flowering time control. In vitro ubiquitination assays indicated that PUB13 is an active E3 ubiquitin ligase and the intact U-box domain is required for the E3 ligase activity. Disruption of PUB13 gene by T-DNA insertion results in spontaneous cell death, accumulation of H2O2 and salicylic acid (SA), and elevated resistance to biotrophic pathogens but increased susceptibility to necrotrophic pathogens. The cell death, H2O2 accumulation, and resistance to necrotrophic pathogens in pub13 are enhanced when plants are pre-treated with high humidity. Importantly, pub13 also shows early flowering under middle- and long-day conditions in which the expression of SOC1 and FT is induced while FLC expression is suppressed. Finally, we found that two components involved in SA-mediated signaling pathway, SID2 and PAD4, are required for the defense and flowering time phenotypes caused by loss of function of PUB13. Taken together, our data demonstrate that PUB13 acts as an important node connecting SA-dependent defense signaling and flowering time regulation in Arabidopsis.

Reducing Developmental Risk for Emotional/behavioral Problems: a Randomized Controlled Trial Examining the Tools for Getting Along Curriculum

Journal of School Psychology. Apr, 2012  |  Pubmed ID: 22386118

Researchers have demonstrated that cognitive-behavioral intervention strategies - such as social problem solving - provided in school settings can help ameliorate the developmental risk for emotional and behavioral difficulties. In this study, we report the results of a randomized controlled trial of Tools for Getting Along (TFGA), a social problem-solving universally delivered curriculum designed to reduce the developmental risk for serious emotional or behavioral problems among upper elementary grade students. We analyzed pre-intervention and post-intervention teacher-report and student self-report data from 14 schools, 87 classrooms, and a total of 1296 students using multilevel modeling. Results (effect sizes calculated using Hedges' g) indicated that students who were taught TFGA had a more positive approach to problem solving (g=.11) and a more rational problem-solving style (g=.16). Treated students with relatively poor baseline scores benefited from TFGA on (a) problem-solving knowledge (g=1.54); (b) teacher-rated executive functioning (g=.35 for Behavior Regulation and .32 for Metacognition), and proactive aggression (g=.20); and (c) self-reported trait anger (g=.17) and anger expression (g=.21). Thus, TFGA may reduce risk for emotional and behavioral difficulties by improving students' cognitive and emotional self-regulation and increasing their pro-social choices.

Predicting Sustained Viral Response to Hepatitis C Using a Rapid and Simple IL28B Rs8099917 Genotyping Assay

Antiviral Research. Feb, 2012  |  Pubmed ID: 22387386

Recent studies showed that two single nucleotide polymorphisms (SNPs) (rs12979860 and rs8099917) near the gene IL28B coding for IFNλ3 were associated with the antiviral treatment response of the combination therapy of pegIFN plus RBV. We established the use of tetra-primer amplification refractory mutation system polymerase chain reaction (ARMS-PCR) for detecting IL28B rs8099917 genotype (T>G) in 56 Chinese chronic hepatitis C patients infected with Hepatitis C Virus (HCV) genotype 1. The new assay showed 98.2% specificity, and was confirmed by direct sequencing. Among the 56 samples, TT genotype and TG genotype accounted for 80.4% (45/56) and 19.6% (11/56), respectively. GG genotype was not found. The proportion of responders in TT group was higher than that in TG group (68.9% vs. 27.3%, p=0.029). For HCV clinical decision-making, using the new assay, rs8099917 genotyping could provide similar information to rs12979860 genotyping due to a strong association between the two SNPs in Chinese patients. The assay system in this study can be implemented using basic laboratory equipments, making it convenient for clinical and research purposes.

Neural Bases of Falsification in Conditional Proposition Testing: Evidence from an FMRI Study

International Journal of Psychophysiology : Official Journal of the International Organization of Psychophysiology. Mar, 2012  |  Pubmed ID: 22387620

The ability of testing the validity of a conditional statement is important in our everyday life. However, the brain mechanisms underlying this process, especially falsification process which is important in daily life, but especially crucial to scientific reasoning and research is not as yet completely clear. Therefore, in the present study, we used event-related functional magnetic resonance imaging (fMRI) to examine the neural bases of the falsification process in testing the validity of a conditional statement as used in Wason's (1966) selection task. Our fMRI results showed that: (1) compared with the baseline condition, both Falsification (by using Modus Ponens, and Modus Tollens) and Non-Falsification conditions (affirming the consequent, and denying the antecedent) activated the left frontal areas (BA44/45, or BA6), and basal ganglia, the areas previously found in the rule-guided conditional reasoning operations; the parietal area (BA40, BA7) for recruiting cognitive resources to represent and maintain the different evidential information in working memory. (2) The left middle frontal gyrus (BA9) and cerebellum were shown to be activated in the contrast of Falsification condition versus Non-Falsification condition and in the contrast of MT versus Non-Falsification condition. These results indicated that the left middle frontal gyrus (BA9) might be the key brain region involved in the falsification process of conditional statement for which abstracting and integrating logical relationships, and inhibiting the distraction of the irrelevant information were the essential processes. Moreover, the cerebellum was found to be responsible for constructing an internal working model. In addition, our brain imaging results might support the dual-process theory of reasoning.

Impaired Long-term Potentiation and Long-term Memory Deficits in XCT-deficient Sut Mice

Bioscience Reports. Jun, 2012  |  Pubmed ID: 22394266

xCT is the functional subunit of the cystine/glutamate antiporter system xc-, which exchanges intracellular glutamate with extracellular cystine. xCT has been reported to play roles in the maintenance of intracellular redox and ambient extracellular glutamate, which may affect neuronal function. To assess a potential role of xCT in the mouse hippocampus, we performed fear conditioning and passive avoidance for long-term memories and examined hippocampal synaptic plasticity in wild-type mice and xCT-null mutants, sut mice. Long-term memory was impaired in sut mice. Normal basal synaptic transmission and short-term presynaptic plasticity at hippocampal Schaffer collateral-CA1 synapses were observed in sut mice. However, LTP (long-term potentiation) was significantly reduced in sut mice compared with their wild-type counterparts. Supplementation of extracellular glutamate did not reverse the reduction in LTP. Taken together, our results suggest that xCT plays a role in the modulation of hippocampal long-term plasticity.

Fragmentation Investigation of Seven Arylnaphthalide Lignans Using Liquid Chromatography/tandem Quadrupole Time-of-flight Mass Spectrometry

Rapid Communications in Mass Spectrometry : RCM. Apr, 2012  |  Pubmed ID: 22396032

The combination of fragmentation patterns in positive and negative ion modes could be helpful in understanding the structural features of these arylnaphthalide lignans.

Single Enzyme Studies Reveal the Existence of Discrete Func-tional States for Monomeric Enzymes and How They Are "se-lected" by Allosteric Interactions

Journal of the American Chemical Society. Apr, 2012  |  Pubmed ID: 22489643

Allosteric regulation of enzymatic activity forms the basis for controlling a plethora of vital cellular processes. While the mechanism underlying regulation of multimeric enzymes is generally well understood and proposed to primarily operate via conformational selection, the mechanism underlying allosteric regulation of monomeric enzymes is poorly understood. Here we monitored for the first time allosteric regulation of enzymatic activity at the single molecule level. We measured single stochastic catalytic turnovers of a monomeric metabolic enzyme (Thermomyces Lanuginosus Lipase) while titrating its proximity to a lipid membrane that acts as an allosteric effector. These measurements revealed the existence of discrete binary functional states that were intuitively assumed to exist but remained hidden in mac-roscopic ensemble measurements. The discrete functional states correlate with the enzyme's major conformational states, and are redistributed in the presence of the regulatory effector. Thus our data support allosteric regulation of monomeric en-zymes to operate via selection of preexisting functional states and not via induction of new ones.

Vitamin D Receptor Genetic Polymorphisms and Tuberculosis Among Chinese Han Ethnic Group

Chinese Medical Journal. Mar, 2012  |  Pubmed ID: 22490597

In epidemiological studies, tuberculosis (TB) appears intimately with vitamin D insufficiency whereas its relationship with vitamin D receptor (VDR) polymorphism caused by radical difference remains unspecified. This study aimed to investigate the relationship between vitamin D genetic polymorphism and tuberculosis in Han ethnic group.

Identification of Links Between Small Molecules and MiRNAs in Human Cancers Based on Transcriptional Responses

Scientific Reports. 2012  |  Pubmed ID: 22355792

The use of small molecules to target miRNAs is a new type of therapy for human diseases, particularly cancers. We proposed a novel high-throughput approach to identify the biological links between small molecules and miRNAs in 23 different cancers and constructed the Small Molecule-MiRNA Network (SMirN) for each cancer to systematically analyze the properties of their associations. In each SMirN, we partitioned small molecules (miRNAs) into modules, in which small molecules (miRNAs) were connected with one miRNA (small molecule). Almost all of the miRNA modules comprised miRNAs that had similar target genes and functions or were members of the same miRNA family. Most of the small molecule modules involved compounds with similar chemical structures, modes of action, or drug interactions. These modules can be used to identify drug candidates and new indications for existing drugs. Therefore, our approach is valuable to drug discovery and cancer therapy.

Concurrent Prophylactic Placement of Inferior Vena Cava Filter in Gastric Bypass and Adjustable Banding Operations in the Bariatric Outcomes Longitudinal Database

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Feb, 2012  |  Pubmed ID: 22360915

INTRODUCTION: Postoperative pulmonary embolism (PE) is a leading cause of morbidity and mortality after bariatric surgery. However, the concurrent prophylactic placement of an inferior vena cava filter (CPIVCF) in patients undergoing bariatric operations remains controversial. This study used the Bariatric Outcomes Longitudinal Database (BOLD) to establish associated characters and determine outcomes of CPIVCF for patients undergoing Roux-en-Y gastric bypass (GB) and adjustable gastric banding (AB) surgeries. METHODS: We analyzed BOLD, a database of bariatric surgery patient information. GB and AB operations were categorized into open and laparoscopic approaches. Univariate logistic regressions were used to compare between non-CPIVCF and concurrent CPIVCF groups. Significant variables (P < .05) were subsequently input into multivariate regression models: CPIVCF was retained in each model. RESULTS: A total of 322 CPIVCFs (0.33%) were identified from 97,218 GB and AB operations performed between 2007 and 2010 in this retrospective registry study. Significant differences were identified in male gender (21.1% vs 31.4%; P < .001), preoperative body mass index (BMI; 44.5 ± 6.6 vs 45.3 ± 7; P < .001), and African-American race (10.5% vs 18%; P < .001) between non-CPIVCF and CPIVCF groups. The CPIVCF group had more patients with previous nonbariatric surgery (50% vs 43.6%; P = .02), a history of venous thromboembolism (VTE; 21.4% vs 3.1%; P < .001), impairment of functional status (7.8% vs 3.1%; P < .001), lower extremity edema (47.2% vs 27.1%; P < .001), obesity hypoventilation syndrome (7.1% vs 2.1%; P < .001), obstructive sleep apnea syndrome (58.1% vs 43.3%; P < .001), and pulmonary hypertension (13% vs 4.1%; P < .001). Patients in the CPIVCF group were more likely to receive GB than gastric banding (77% vs 58.1%; P < .001) and an open surgical approach (21.4% vs 4.8%; P < .001). Operative duration was longer in the CPIVCF group (119 ± 67 vs 89 ± 52 minutes; P < .001). The CPIVCF group also had a longer length of hospital stay (3 ± 2 vs 2 ± 6 days; P = .048), was associated with higher incidence of deep venous thrombosis (DVT; 0.93% vs 0.12%; P < .001), and a higher mortality (0.31% vs 0.03%; P = .003) from PE and indeterminate causes. In multivariate analysis, male gender, African-American race, previous nonbariatric surgery, a high BMI, obesity hypoventilation syndrome, history of VTE, lower extremity edema, and pulmonary hypertension were preoperative factors associated with CPIVCF. CONCLUSION: CPIVCF was associated with specific clinical features, increased health care resource utilization, and a higher mortality in patients undergoing bariatric operations. Although selected patient characteristics influence surgeons to perform CPIVCF, this study was unable to establish an outcome benefit for CPIVCF.

Polymorphisms in the Vitamin D Receptor Gene and Type 1 Diabetes Mellitus Risk: An Update by Meta-analysis

Molecular and Cellular Endocrinology. May, 2012  |  Pubmed ID: 22361322

Four well known polymorphisms (BsmI, FokI, ApaI, TaqI) in the VDR gene have been implicated in susceptibility to type 1 diabetes mellitus (T1DM), but the results to date have been inconclusive. The aim of this study was to investigate the association between polymorphisms in the VDR gene and T1DM risk by meta-analysis. A total of 57 case-control studies in 26 published studies were included. The results indicated that the BsmI polymorphism is associated with increased risk of T1DM (BB+Bb vs. bb: OR=1.30, 95% CI=1.03-1.63), while the FokI, ApaI and TaqI polymorphisms were not. In the subgroup analysis by ethnicity, the increased risk of T1DM remained in the Asian subgroup for the BsmI polymorphism; whereas no significant association was found in other populations for other polymorphisms. Results from the current study suggest that the BsmI polymorphism is associated with increased risk of T1DM, especially in Asians. Further studies are needed to confirm our results.

Enantioselective Synthesis of β-Pyrazole-Substituted Alcohols Through an Asymmetric Ring-Opening Reaction of Meso-Epoxides

Chemistry (Weinheim an Der Bergstrasse, Germany). Mar, 2012  |  Pubmed ID: 22362613

An efficient and practical synthesis of optically pure β-pyrazole-substituted alcohols was achieved by an asymmetric ring-opening reaction of meso-epoxides with pyrazole derivatives as the nucleophile. In the presence of 1 mol % of an N,N'-dioxide-Sc(OTf)(3) complex, excellent enantioselectivity and yields were obtained from meso-epoxides. The process could also be used for a mixture of cis- and trans-stilbene oxides. A proposed transition-state model is provided.

The Potential Role of ORM2 in the Development of Colorectal Cancer

PloS One. 2012  |  Pubmed ID: 22363757

Colorectal cancer (CRC) is the third most common malignancy in the world. The risk of death is closely correlated to the stage of CRC at the time of primary diagnosis. Therefore, there is a compelling need for the identification of blood biomarkers that can enable early detection of CRC. We used a quantitative proteomic approach with isobaric labeling (iTRAQ) to examine changes in the plasma proteome of 10 patients with CRC compared to healthy volunteers. Enzyme-Linked Immunosorbnent Assay (ELISA) and Western blot were used for further validation. In our quantitative proteomics analysis, we detected 75 human plasma proteins with more than 95% confidence using iTRAQ labeling in conjunction with microQ-TOF MS. 9 up-regulated and 4 down-regulated proteins were observed in the CRC group. The ORM2 level in plasma was confirmed to be significantly elevated in patients suffering from CRC compared with the controls. ORM2 expression in CRC tissues was significantly increased compared with that in corresponding adjacent normal mucous tissues (P<0.001). ITRAQ together with Q-TOF/MS is a sensitive and reproducible technique of quantitative proteomics. Alteration in expression of ORM2 suggests that ORM2 could be used as a potential biomarker in the diagnosis of CRC.

A Marine Secondary Producer Respires and Feeds More in a High CO(2) Ocean

Marine Pollution Bulletin. Apr, 2012  |  Pubmed ID: 22364924

Climate change mediates marine chemical and physical environments and therefore influences marine organisms. While increasing atmospheric CO(2) level and associated ocean acidification has been predicted to stimulate marine primary productivity and may affect community structure, the processes that impact food chain and biological CO(2) pump are less documented. We hypothesized that copepods, as the secondary marine producer, may respond to future changes in seawater carbonate chemistry associated with ocean acidification due to increasing atmospheric CO(2) concentration. Here, we show that the copepod, Centropages tenuiremis, was able to perceive the chemical changes in seawater induced under elevated CO(2) concentration (>1700μatm, pH<7.60) with avoidance strategy. The copepod's respiration increased at the elevated CO(2) (1000μatm), associated acidity (pH 7.83) and its feeding rates also increased correspondingly, except for the initial acclimating period, when it fed less. Our results imply that marine secondary producers increase their respiration and feeding rate in response to ocean acidification to balance the energy cost against increased acidity and CO(2) concentration.

[Necessity of No.13 Lymph Node Dissection in Advanced Gastric Carcinoma]

Zhonghua Wei Chang Wai Ke Za Zhi = Chinese Journal of Gastrointestinal Surgery. Feb, 2012  |  Pubmed ID: 22368021

To investigate the feasibility and necessity of No.13 lymph node dissection for advanced gastric carcinoma.

Generation of Dopaminergic Neurons Directly from Mouse Fibroblasts and Fibroblast-derived Neural Progenitors

Cell Research. Apr, 2012  |  Pubmed ID: 22370632

Transmissible Gastroenteritis Virus Infection Induces Apoptosis Through FasL- and Mitochondria-mediated Pathways

Veterinary Microbiology. Jan, 2012  |  Pubmed ID: 22341312

Transmissible gastroenteritis virus (TGEV) has been reported to induce apoptosis in swine testis (ST) cells. However, the mechanisms underlying TGEV-induced apoptosis are still unclear. In this study we observed that TGEV infection induced apoptosis in porcine kidney (PK-15) cells in a time- and dose-dependent manner. TGEV infection up-regulated FasL, activated FasL-mediated apoptotic pathway, leading to activation of caspase-8 and cleavage of Bid. In addition, TGEV infection down-regulated Bcl-2, up-regulated Bax expression, promoted translocation of Bax to mitochondria, activated mitochondria-mediated apoptotic pathway, which in turn caused the release of cytochrome c and the activation of caspase-9. Both extrinsic and intrinsic pathways activated downstream effector caspase-3, followed by the cleavage of PARP, resulting in cell apoptosis. Moreover, TGEV infection did not induce significant DNA fragmentation in ammonium chloride (NH(4)Cl) pretreated PK-15 cells or cells infected with UV-inactivated TGEV. In turn, block of caspases activation also did not affect TGEV replication. Taken together, this study demonstrates that TGEV-induced apoptosis is dependent on viral replication in PK-15 cells and occurs through activation of FasL- and mitochondria-mediated apoptotic pathways.

Learning Image Context for Segmentation of the Prostate in CT-guided Radiotherapy

Physics in Medicine and Biology. Mar, 2012  |  Pubmed ID: 22343071

Accurate segmentation of the prostate is the key to the success of external beam radiotherapy of prostate cancer. However, accurate segmentation of the prostate in computer tomography (CT) images remains challenging mainly due to three factors: (1) low image contrast between the prostate and its surrounding tissues, (2) unpredictable prostate motion across different treatment days and (3) large variations of intensities and shapes of the bladder and rectum around the prostate. In this paper, an online-learning and patient-specific classification method based on the location-adaptive image context is presented to deal with all these challenging issues and achieve the precise segmentation of the prostate in CT images. Specifically, two sets of location-adaptive classifiers are placed, respectively, along the two coordinate directions of the planning image space of a patient, and further trained with the planning image and also the previous-segmented treatment images of the same patient to jointly perform prostate segmentation for a new treatment image (of the same patient). In particular, each location-adaptive classifier, which itself consists of a set of sequential sub-classifiers, is recursively trained with both the static image appearance features and the iteratively updated image context features (extracted at different scales and orientations) for better identification of each prostate region. The proposed learning-based prostate segmentation method has been extensively evaluated on 161 images of 11 patients, each with more than nine daily treatment three-dimensional CT images. Our method achieves the mean Dice value 0.908 and the mean ± SD of average surface distance value 1.40 ± 0.57 mm. Its performance is also compared with three prostate segmentation methods, indicating the best segmentation accuracy by the proposed method among all methods under comparison.

Radiosensitization of Normoxic and Hypoxic H1339 Lung Tumor Cells by Heat Shock Protein 90 Inhibition is Independent of Hypoxia Inducible Factor-1α

PloS One. 2012  |  Pubmed ID: 22347438

Ionizing irradiation is a commonly accepted treatment modality for lung cancer patients. However, the clinical outcome is hampered by normal tissue toxicity and tumor hypoxia. Since tumors often have higher levels of active heat shock protein 90 (Hsp90) than normal tissues, targeting of Hsp90 might provide a promising strategy to sensitize tumors towards irradiation. Hsp90 client proteins include oncogenic signaling proteins, cell cycle activators, growth factor receptors and hypoxia inducible factor-1α (HIF-1α). Overexpression of HIF-1α is assumed to promote malignant transformation and tumor progression and thus might reduce the accessibility to radiotherapy.

[Consistency of the Subjective Evaluation of Malocclusion Severity by the Chinese Orthodontic Experts]

Beijing Da Xue Xue Bao. Yi Xue Ban = Journal of Peking University. Health Sciences. Feb, 2012  |  Pubmed ID: 22353910

To assess the consistency of the subjective evaluation of malocclusion severity by the Chinese orthodontic experts.

[Agreement Analysis of Subjective Evaluation of Orthodontic Treatment Outcome]

Beijing Da Xue Xue Bao. Yi Xue Ban = Journal of Peking University. Health Sciences. Feb, 2012  |  Pubmed ID: 22353911

To investigate the agreement of subjective evaluation of orthodontic treatment outcome and to analyze possible factors that may be related to it.

Merlin: a Tumour Suppressor with Functions at the Cell Cortex and in the Nucleus

EMBO Reports. Feb, 2012  |  Pubmed ID: 22354087

Inhibition of proliferation by cell-to-cell contact is essential for tissue organization, and its disruption contributes to tumorigenesis. The FERM domain protein Merlin, encoded by the NF2 tumour suppressor gene, is an important mediator of contact inhibition. Merlin was thought to inhibit mitogenic signalling and activate the Hippo pathway by interacting with diverse target-effectors at or near the plasma membrane. However, recent studies highlight that Merlin pleiotropically affects signalling by migrating into the nucleus and inducing a growth-suppressive programme of gene expression through its direct inhibition of the CRL4(DCAF1) E3 ubiquitin ligase. In addition, Merlin promotes the establishment of epithelial adhesion and polarity by recruiting Par3 and aPKC to E-cadherin-dependent junctions, and by ensuring the assembly of tight junctions. These recent advances suggest that Merlin acts at the cell cortex and in the nucleus in a similar, albeit antithetic, manner to the oncogene β-catenin.

Effect of Statins on Total Cholesterol Concentrations and Cardiovascular Outcomes in Patients with Diabetes Mellitus: a Population-based Cohort Study

European Journal of Clinical Pharmacology. Feb, 2012  |  Pubmed ID: 22354153

BACKGROUND: In the UK, clinicians usually make treatment decisions based on total cholesterol (TC) at the same time supplemented with high-density lipoprotein cholesterol (HDL-C) measurements. We evaluated statin-associated TC concentration change and its impact on cardiovascular (CV) risk reduction in diabetic patients in the setting of usual care. METHODS: In a population-based cohort study using a record-linkage database in Tayside, Scotland. we studied 6,697 diabetic patients who had at least two separate TC measurements between 1993 and 2007. Patients were categorized into statin-exposed and statin-unexposed groups according to statin use status during the follow-up. The main outcomes were TC concentration change from baseline, CV events, and all-cause mortality during the follow-up. Multivariate Cox regression models with a time-dependent variable for statins were employed to assess outcome risk. RESULTS: Statin-associated TC concentrations decreased by 1.64 mmol/L (28%) in patients without CV disease (CVD) (5,984) and 1.19 mmol/L (23%) in patients with CVD (713) from 5.90 mmol/L and 5.20 mmol/L at baselines, respectively. Statin use reduced incident and recurrent CV events by 39% and 41%, respectively [adjusted hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.57-0.66; 0.59 95% CI 0.47-0.76) per millimole of TC reduction. For all-cause mortality, the adjusted HRs were 0.39 (95% CI 0.32-0.47) in primary prevention and 0.58 (95% CI 0.42-0.80) in secondary prevention. CONCLUSION: Statin use was as effective in diabetic patients in the setting of usual care, as in the clinical trials, in both primary and secondary prevention. TC changes can be used as a measure of statin efficacy in the absence of low-density lipoprotein cholesterol (LDL-C) in diabetic patients.

Over-expression of PDGFR-β Promotes PDGF-induced Proliferation, Migration, and Angiogenesis of EPCs Through PI3K/Akt Signaling Pathway

PloS One. 2012  |  Pubmed ID: 22355314

The proliferation, migration, and angiogenesis of endothelial progenitor cells (EPCs) play critical roles in postnatal neovascularization and re-endothelialization following vascular injury. Here we evaluated whether the over-expression of platelet-derived growth factor receptor-β (PDGFR-β) can enhance the PDGF-BB-stimulated biological functions of EPCs through the PDGFR-β/phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. We first confirmed the expression of endogenous PDGFR-β and its plasma membrane localization in spleen-derived EPCs. We then demonstrated that the PDGFR-β over-expression in EPCs enhanced the PDGF-BB-induced proliferation, migration, and angiogenesis of EPCs. Using AG1295 (a PDGFR kinase inhibitor), LY294002 (a PI3K inhibitor), and sc-221226 (an Akt inhibitor), we further showed that the PI3K/Akt signaling pathway participates in the PDGF-BB-induced proliferation, migration, and angiogenesis of EPCs. In addition, the PI3K/Akt signaling pathway is required for PDGFR-β over-expression to enhance these PDGF-BB-induced phenotypes.

Mitochondrial Reactive Oxygen Species and Calcium Uptake Regulate Activation of Phagocytic NADPH Oxidase

American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. Mar, 2012  |  Pubmed ID: 22442197

Production of superoxide (O(2)(•)) by NADPH oxidases contributes to the development of hypertension and atherosclerosis. Factors responsible for activation of NADPH oxidases are not well understood; interestingly, cardiovascular disease is associated with both altered NADPH oxidase activity and age-associated mitochondrial dysfunction. We hypothesized that mitochondrial dysfunction may contribute to activation of NADPH oxidase. The effect of mitochondrial inhibitors on phagocytic NADPH oxidase in human lymphoblasts and whole blood was measured at the basal state and upon protein kinase C (PKC)-dependent stimulation with phorbol 12-myristate 13-acetate (PMA) using extracellular 1-hydroxy-2,2,6,6-tetramethyl¬piperidin-4-yl-trimethyl¬ammonium or mitochondria-targeted 1-hydroxy-4-[2-triphenylphosphonio)-acetamido]-2,2,6,6-tetramethyl¬piperidine spin probes and electron spin resonance (ESR). Intracellular cytosolic calcium [Ca(2+)](i) was measured spectrofluorometrically using FURA-2 AM. Incubation of lymphoblasts with the mitochondrial inhibitors rotenone, antimycin A, carbonyl cyanide 3-chlorophenylhydrazone (CCCP) or ruthenium red (an inhibitor of mitochondrial Ca(2+) uniporter) did not significantly change basal activity of NADPH oxidase. In contrast, preincubation with the mitochondrial inhibitors prior to PMA stimulation of lymphoblasts resulted in 2-3 fold increase of NADPH oxidase activity compared to stimulation with PMA alone. Most notably, the intracellular Ca(2+) chelating agent BAPTA-AM abolished the effect of mitochondrial inhibitors on NADPH oxidase activity. Cytosolic Ca(2+) measurements with FURA-2AM showed that the mitochondrial inhibitors increased [Ca(2+)](i) while BAPTA-AM abolished the increase in [Ca(2+)](i). Furthermore, depletion of cellular Ca(2+) with thapsigargin attenuated CCCP- and antimycin A-mediated activation of NADPH oxidase in the presence of PMA by 42% and 31%, correspondingly. Our data suggest that mitochondria regulate PKC-dependent activation of phagocytic NADPH oxidase. In summary, increased mitochondrial O(2)(•) and impaired buffering of cytosolic Ca(2+) by dysfunctional mitochondria result in enhanced NADPH oxidase activity which may contribute to the development of cardiovascular diseases.

Aging-associated Changes in Cellular Immunity Based on the SENIEUR Protocol

Scandinavian Journal of Immunology. Mar, 2012  |  Pubmed ID: 22443369

To investigate aging-associated changes in cellular immunity, we recruited three groups of healthy subjects based on SENIEUR protocol criteria. In addition, 10 subjects were randomly selected from each group to isolate their T cells from peripheral blood mononuclear cells (PBMC); T cell proliferation after phytohemagglutinin (PHA) stimulation was determined by MTT assays. There were no marked differences in the absolute numbers of peripheral blood T cells, NK cells, or B cells among the three groups (P>0.05). Also, no significant differences were noted in the numbers of CD4(+) cells, CD8(+) cells, or the CD4(+) /CD8(+) ratios (P>0.05). After PHA stimulation, T cell proliferation was markedly increased, with the highest level in Group C and the lowest level in Group A (P<0.05). CIK tumoricidal activities were also dramatically increased, with the highest activity in Group C and the lowest activity in Group A (P<0.05). Our findings suggest that the numbers of immune cells remain unchanged with advanced age. However, there is a trend for decreased cellular immunity with an increase in age.

Effects of Variation in Retinol Binding Protein 4 Gene and Adipose Specific Expression of Gestational Diabetes in Beijing, China

Diabetes Research and Clinical Practice. Mar, 2012  |  Pubmed ID: 22444425

OBJECTIVE: To investigate the clinical features of GDM in China and the effects of RBP4 genetic variants, and also to identify RBP4 expression changes in mRNA and protein levels. RESEARCH DESIGN AND METHODS: 1595 Chinese pregnant women were included in this study. Four known RBP4 single nucleotide polymorphisms (SNPs) were genotyped in 505 cases and 687 controls. Expression levels of adipose specific RBP4 mRNA and protein were detected in 41 samples of subcutaneous adipose tissue. RESULTS: The estimated indices of insulin resistance were gradually increased from NGT, GIGT to GDM. Two single SNPs were associated with GDM (rs3758539 G vs A, OR=1.446, P=0.009; rs3758539 GG vs AG+AA, OR=1.532, P=0.006; rs12265684C vs G, OR=1.296, P=0.038) and a haplotype of 3 common SNPs [G-G-T] was increased in subjects with GDM and GIGT (OR=1.322, 95% CI 1.054-1.659, P=0.016). RBP4 mRNA expression in adipose tissue of GDM patients was significantly increased in comparison to control subjects (1.438±0.187 vs 1.034±0.062, p=0.025). CONCLUSION: This finding suggests that impaired insulin sensitivity has an early onset in mild gestational intolerance. Two single SNPs were associated with GDM in the case-control study while a haplotype of 3 common SNPs [G-G-T] was increased in glucose intolerance subjects.

Discovery of Flavonoid Derivatives As Anti-HCV Agents Via Pharmacophore Search Combining Molecular Docking Strategy

European Journal of Medicinal Chemistry. Mar, 2012  |  Pubmed ID: 22445328

Common feature based pharmacophore and structure-based docking approaches have been employed in the identification of novel anti-HCV candidates from our in-house database. A total of 31 hits identified in silico were screened in vitro assay. 20 Compounds demonstrated anti-HCV activities (EC(50)<50μM), including two naturally occurring flavones apigenin (21) and luteolin (22) with low micromole EC(50) values and three compounds (23, 24 and 25) of novel scaffolds with moderate potencies. In addition, pharmacophore refinement was also conducted based on the current knowledge of flavone-derived anti-HCV candidates and the results of combined in silico and in vitro assays.

Effects of Dapagliflozin, a Sodium-Glucose Cotransporter-2 Inhibitor, on Hemoglobin A1c, Body Weight, and Hypoglycemia Risk in Patients With Type 2 Diabetes Inadequately Controlled on Pioglitazone Monotherapy

Diabetes Care. Mar, 2012  |  Pubmed ID: 22446170

OBJECTIVETo examine the safety and efficacy of dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, added on to pioglitazone in type 2 diabetes inadequately controlled on pioglitazone.RESEARCH DESIGN AND METHODSTreatment-naive patients or those receiving metformin, sulfonylurea, or thiazolidinedione entered a 10-week pioglitazone dose-optimization period with only pioglitazone. They were then randomized, along with patients previously receiving pioglitazone ≥30 mg, to 48 weeks of double-blind dapagliflozin 5 (n = 141) or 10 mg (n = 140) or placebo (n = 139) every day plus open-label pioglitazone. The primary objective compared hemoglobin A1c (HbA1c) change from baseline with dapagliflozin plus pioglitazone versus placebo plus pioglitazone at week 24. Primary analysis was based on ANCOVA model using last observation carried forward; all remaining analyses used repeated-measures analysis.RESULTSAt week 24, the mean reduction from baseline in HbA1c was -0.42% for placebo versus -0.82 and -0.97% for dapagliflozin 5 and 10 mg groups, respectively (P = 0.0007 and P < 0.0001 versus placebo). Patients receiving pioglitazone alone had greater weight gain (3 kg) than those receiving dapagliflozin plus pioglitazone (0.7-1.4 kg) at week 48. Through 48 weeks: hypoglycemia was rare; more events suggestive of genital infection were reported with dapagliflozin (8.6-9.2%) than placebo (2.9%); events suggestive of urinary tract infection showed no clear drug effect (5.0-8.5% for dapagliflozin and 7.9% for placebo); dapagliflozin plus pioglitazone groups had less edema (2.1-4.3%) compared with placebo plus pioglitazone (6.5%); and congestive heart failure and fractures were rare.CONCLUSIONSIn patients with type 2 diabetes inadequately controlled on pioglitazone, the addition of dapagliflozin further reduced HbA1c levels and mitigated the pioglitazone-related weight gain without increasing hypoglycemia risk.

Response Surface Modeling and Optimization of Accelerated Solvent Extraction of Four Lignans from Fructus Schisandrae

Molecules (Basel, Switzerland). 2012  |  Pubmed ID: 22447025

A new method based on accelerated solvent extraction (ASE) combined with response surface methodology (RSM) modeling and optimization has been developed for the extraction of four lignans in Fructus Schisandrae (the fruits of Schisandra chinensis Baill). The RSM method, based on a three level and three variable Box-Behnken design (BBD), was employed to obtain the optimal combination of extraction condition. In brief, the lignans schizandrin, schisandrol B, deoxyschizandrin and schisandrin B were optimally extracted with 87% ethanol as extraction solvent, extraction temperature of 160 °C, static extraction time of 10 min, extraction pressure of 1,500 psi, flush volume of 60% and one extraction cycle. The 3D response surface plot and the contour plot derived from the mathematical models were applied to determine the optimal conditions. Under the above conditions, the experimental value of four lignans was 14.72 mg/g, which is in close agreement with the value predicted by the model.

Determination of Rutin in Cigarette Tobacco, Filters, Mainstream Smoke and Burned Ash of Different Branded Cigarettes by High Performance Liquid Chromatography

Molecules (Basel, Switzerland). 2012  |  Pubmed ID: 22450684

Tobacco consists of at least 3,800 chemical constituents. Among them, rutin is an important polyphenolic secondary metabolite in tobacco, which has positive actions such as antiallergic, anti-inflammatory and vasoactive, antitumor, antibacterial, antiviral and anti-protozoal properties. A high performance liquid chromatography method was used to analyze rutin in tobacco and filters, mainstream smoke, and burned ash of ten varieties of cigarettes made in China. The chromatographic analysis was performed on a Hypersil ODS2 column with a gradient elution of acetonitrile and water at a flow rate of 1.0 mL/min. Detection was carried out at 350 nm using a photodiode array detector. The calibration curves for the determination of analytes showed good linearity over the investigated ranges (R2 > 0.9998). Precision and reproducibility were evaluated by six replicated analyses, and the R.S.D. values were less than 0.59% and 1.53%. The recoveries were between 98.47 and 100.84%. Under the optimized conditions, namely 45 mL/g of solvent to solid ratio, 30 min of extraction time and 200 W of ultrasound power, the concentrations of rutin in tobacco and filter, mainstream smoke, burned ash of different brands cigarettes were 10.20-63.98, 0.10-0.32, 0.06-0.16 and 0 μg/per cigarette, respectively.

Autophagy Genes Function Sequentially to Promote Apoptotic Cell Corpse Degradation in the Engulfing Cell

The Journal of Cell Biology. Apr, 2012  |  Pubmed ID: 22451698

Apoptotic cell degradation is a fundamental process for organism development, and impaired clearance causes inflammatory or autoimmune disease. Although autophagy genes were reported to be essential for exposing the engulfment signal on apoptotic cells, their roles in phagocytes for apoptotic cell removal are not well understood. In this paper, we develop live-cell imaging techniques to study apoptotic cell clearance in the Caenorhabditis elegans Q neuroblast lineage. We show that the autophagy proteins LGG-1/LC3, ATG-18, and EPG-5 were sequentially recruited to internalized apoptotic Q cells in the phagocyte. In atg-18 or epg-5 mutants, apoptotic Q cells were internalized but not properly degraded; this phenotype was fully rescued by the expression of autophagy genes in the phagocyte. Time-lapse analysis of autophagy mutants revealed that recruitment of the small guanosine triphosphatases RAB-5 and RAB-7 to the phagosome and the formation of phagolysosome were all significantly delayed. Thus, autophagy genes act within the phagocyte to promote apoptotic cell degradation.

Retene Emission from Residential Solid Fuels in China and Evaluation of Retene As a Unique Marker for Soft Wood Combustion

Environmental Science & Technology. Apr, 2012  |  Pubmed ID: 22452486

Retene (1-methyl-7-isopropylphenanthrene) is often used as a marker for softwood combustion and for polycyclic aromatic hydrocarbon (PAH) source apportionment. The emission factors of retene (EF(RET)s) from 11 crop residues, 27 firewood fuels, and 5 coals were measured using traditional rural Chinese stoves. Retene was measured in combustion emissions from all of the residential fuels tested and EF(RET)s varied significantly among the fuels due to the differences in fuel properties and combustion conditions. EF(RET)s for pine (0.34 ± 0.08 mg/kg) and larch (0.29 ± 0.22 mg/kg) were significantly higher than those of other wood types, including fir and cypress (0.081 ± 0.058 mg/kg). However, EF(RET)s for crop residues varied from 0.048 ± 0.008 to 0.37 ± 0.14 mg/kg and were not significantly lower than those for softwood (0.074 ± 0.026 to 0.34 ± 0.08 mg/kg). The EF(RET)s for coal were very high and ranged from 2.2 ± 1.5 (anthracite briquette) to 187 ± 113 mg/kg (raw bituminous chunk). EF(RET) was positively correlated with EFs of coemitted particulate matter (EF(PM)) and phenanthrene (EF(PHE)) for crop residue and coal, but not for wood. In addition, the ratios of EF(PHE)/EF(RET) and EF(PM)/EF(RET) for coals were much lower than those for crop residues and wood. These data suggest that retene is not a unique PAH marker for softwood combustion and that coal combustion, in particular, should be taken into account when retene is used for PAH source apportionment.

Utility of Three-dimensional Echocardiography for Assessment of Double-orifice Mitral Valve

European Heart Journal Cardiovascular Imaging. Mar, 2012  |  Pubmed ID: 22453718

A Refined Cluster-in-molecule Local Correlation Approach for Predicting the Relative Energies of Large Systems

Physical Chemistry Chemical Physics : PCCP. Mar, 2012  |  Pubmed ID: 22456726

A refined cluster-in-molecule (CIM) method for local correlation calculations of large molecules is presented. In the present work, two new strategies are introduced to further improve the CIM approach: (1) Some medium-range electron correlation energies, which are neglected in the previous CIM approach, are taken into account. (2) A much simpler procedure using only a distance threshold is used to construct various clusters. To cover the medium-range correlation effect as much as possible, some two-atom-centered clusters are built, in addition to one-atom-centered clusters. Our test calculations at the second order perturbation theory (MP2) level show that the refined CIM method can recover about 99.9% of the conventional MP2 correlation energy using an appropriate distance threshold. The accuracy of the present CIM method is capable of providing reliable relative energies of medium-sized systems such as polyalanines with 10 residues, and water molecules with 50 water molecules. For polyalanines with up to 30 residues, we have demonstrated that the computational cost of the CIM-MP2 calculation increases linearly with the molecular size, but the required memory and disc-space do not need to increase for large systems. The improved CIM method has been used to compute the relative energy of ice-like (H(2)O)(96) clusters (with 2400 basis functions) and to predict the dimerization energy of a double-helical foldamer (with 2330 basis functions). The present CIM method is expected to be a practical local correlation method for describing the relative energies of large systems.

Alterations of TP53 Are Associated with a Poor Outcome for Patients with Hepatocellular Carcinoma: Evidence from a Systematic Review and Meta-analysis

European Journal of Cancer (Oxford, England : 1990). Mar, 2012  |  Pubmed ID: 22459764

BACKGROUND: The prognostic significance of p53 aberration in hepatocellular carcinoma (HCC) remains inconclusive. This systematic review and meta-analysis aimed to provide comprehensive evidence on the association of p53 alterations with recurrence-free survival (RFS) and overall survival (OS) in HCC patients. METHODS: Systematic literature searches were conducted until July 2010. Meta-analysis was performed to estimate prognostic effects of p53 alterations on patient outcomes in HCC. Sensitivity and subgroup analyses were also conducted in the meta-analysis. RESULTS: Thirty-seven studies (7 tumour p53 mutation, 23 tumour p53 expression and 7 serum anti-p53 antibodies) were included in the systematic review and meta-analysis. The average percentages of p53 mutation, p53 expression upregulation and anti-p53 antibody level elevation in HCC patients were 31.5%, 35.0% and 23.8%, respectively. Tumour p53 alterations were associated significantly with poor patient outcomes in HCC: the summary hazard ratio (HR) of mutant p53 versus wild type p53 phenotype was 2.58 [95% confidence interval (CI): 1.96-3.41] for OS and 3.19 [95% CI: 2.21-4.60] for RFS, respectively; and the summary HR of upregulated p53 expression versus low/undetectable p53 expression was 1.68 [95% CI: 1.49-1.90] for OS and 1.89 [95% CI: 1.34-2.66] for RFS, respectively. However, elevated serum anti-p53 antibody was only associated with poor OS in HCC group with a high proportion of (⩾50%) of hepatitis C virus (HCV) infection [HR: 1.92; 95% CI: 1.30-2.85]. Moreover, sensitivity analyses showed that the results of meta-analyses were not altered. CONCLUSION: HCC patients with p53 mutation and upregulated expression in tumour tissue have a shorter OS and RFS than patients with wild type p53 and low/undetectable p53 expression. However, the prognostic value of serum anti-p53 antibody is required to be further examined.

Elastic Response and Length Change of Single DNA Molecules Induced by a Combination of Cisplatin and Transplatin

Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics. Feb, 2012  |  Pubmed ID: 22463255

Magnetic tweezers were employed to investigate the interactions between DNA and cisplatin (transplatin). Cisplatin shortened DNA and reduced its persistence length more significantly than transplatin due to the formation of many more diadducts than those formed by transplatin. Interestingly, the presence of transplatin could enhance the ability of cisplatin in shortening DNA. An optimal concentration ratio of transplatin to cisplatin existed at which cisplatin showed the highest ability in shortening DNA. Moreover, abrupt length changes were also observed when DNA was treated with a mixture of cisplatin and transplatin at high concentrations. A model was proposed to qualitatively explain well these results.

Effects of Panax Notoginseng Flower Extract on the TGF-β/Smad Signal Transduction Pathway in Heart Remodeling of Human Chymase Transgenic Mice

Molecular Medicine Reports. Apr, 2012  |  Pubmed ID: 22469817

Panax notoginseng is a common Chinese herb extensively used in Chinese medical practice for the treatment of cardiovascular diseases. The present study aimed to evaluate the effects of Panax notoginseng flower extract (PNFE) on the TGF-β/Smad signal transduction pathway in heart remodeling of human chymase transgenic mice. After treatment with PNFE and soybean trypsin inhibitor (SBTI), the left ventricular mass indexes (LVMIs) of transgenic and normal C57 BL/6 mice were analyzed. The mRNA expression of chymase, TGF-β1, Smad2, Smad3 and Smad7 in myocardium was assessed with RT-PCR, while the protein expression in myocardium was detected by western blotting. The results showed that PNFE and SBTI treatment led to a significant reduction in LVMIs in transgenic mice, indicating a beneficial effect on left ventricular remodeling. Mechanistically, PNFE and SBTI treatment attenuated the mRNA expression of chymase, TGF-β1, Smad2 and Smad3, as well as the protein expression in the myocardium tissues of the transgenic mouse model. By contrast, PNFE and SBTI treatment markedly up-regulated the mRNA and protein expression of Smad7. It was concluded that PNFE was able to improve the ventricular hypertrophy state in human chymase transgenic mice through regulation of the expression of mRNA and protein of TGF-β/Smad in ventricular tissues.

Novel Materials Which Possess the Ability to Target Liver Cells

Expert Opinion on Drug Delivery. Apr, 2012  |  Pubmed ID: 22480167

Introduction: Hepatic-targeted drug delivery systems are designed to treat diseases of the liver. However, since there are several different types of liver diseases that are caused by different cells, it is important to select the proper materials to target these different cells. Areas covered: This review addresses novel materials that possess the ability to target liver cells via receptor-ligand processes and offers an insight into the aspects of formulation design. It also discusses several approaches used to enhance the targeting efficiency of drug delivery systems to receptors in the liver cells. In addition, the delivery efficiency and therapeutic efficacy of these materials in the treatment of acute or chronic liver diseases is highlighted. Expert opinion: Further research into the use of clinical materials and the design of smart materials for multi-drug delivery to different organelles is important for future studies on these new materials. It is hoped that these targeted therapeutics will benefit patients with liver disorders in the near future.

Merlin: a Tumour Suppressor with Functions at the Cell Cortex and in the Nucleus

EMBO Reports. Mar, 2012  |  Pubmed ID: 22482125

Inhibition of proliferation by cell-to-cell contact is essential for tissue organization, and its disruption contributes to tumorigenesis. The FERM domain protein Merlin, encoded by the NF2 tumour suppressor gene, is an important mediator of contact inhibition. Merlin was thought to inhibit mitogenic signalling and activate the Hippo pathway by interacting with diverse target-effectors at or near the plasma membrane. However, recent studies highlight that Merlin pleiotropically affects signalling by migrating into the nucleus and inducing a growth-suppressive programme of gene expression through its direct inhibition of the CRL4DCAF1 E3 ubiquitin ligase. In addition, Merlin promotes the establishment of epithelial adhesion and polarity by recruiting Par3 and aPKC to E-cadherin-dependent junctions, and by ensuring the assembly of tight junctions. These recent advances suggest that Merlin acts at the cell cortex and in the nucleus in a similar, albeit antithetic, manner to the oncogene β-catenin.

Multiple Releases of Polyplexes of Plasmids VEGF and BFGF from Electrospun Fibrous Scaffolds Towards Regeneration of Mature Blood Vessels

Acta Biomaterialia. Apr, 2012  |  Pubmed ID: 22484697

Key challenges associated with the outcomes of vascular grafting, for example to get fully vascularized in engineered tissues and regenerate promptly blood vessel substitutes, remain unsolved. The local available of angiogenic growth factors is highly desirable for tissue regeneration, and the plasmid loading in scaffolds represents a powerful alternative for the local production of tissue-inductive factors. Up to now no attempt has been made to clarify the efficacy of electrospun fibers with the loading of multiple plasmids to promote tissue regeneration. In current study core-sheath electrospun fibers with the encapsulation of polyplexes of basic fibroblast growth factor-encoding plasmid (pbFGF) and vascular endothelial growth factor-encoding plasmid (pVEGF) were evaluated to promote the generation of mature blood vessels. In vitro release indicated a sustained release of pDNA for around 4 weeks with as low as about 10% of initial burst release, and the release patterns from the single and two plasmids-loaded systems coincided. In vitro investigations on human umbilical vein endothelial cells showed that the sustained release of pDNA from fibrous mats promoted cell attachment and viability, cell transfection and protein expression, and extracellular secretion of collagen IV and laminin. The acceleration of angiogenesis was assessed in vivo after subcutaneous implantation of fibrous scaffolds, and the explants were evaluated after 1, 2 and 4 week treatment through histological and immunohistochemical staining. Compared with pDNA polyplex infiltrated fibrous mats, the pDNA polyplex encapsulated fibers alleviated the inflammation reaction, and enhanced the generation of microvessels. Although there was no significant difference in the total number of microvessels, the density of mature vessels was significantly enhanced by the combined treatment with both pbFGF and pVEGF as compared with those incorporating individual pDNA. The integration of core-sheath structure, DNA condensation and multiple delivery strategies provided a potential platform for scaffold fabrication to regenerate functional tissues.

Increased Frequencies of Th22 Cells As Well As Th17 Cells in the Peripheral Blood of Patients with Ankylosing Spondylitis and Rheumatoid Arthritis

PloS One. 2012  |  Pubmed ID: 22485125

T-helper (Th) 22 is involved in the pathogenesis of inflammatory diseases. The roles of Th22 cells in the pathophysiological of ankylosing spondylitis (AS) and rheumatoid arthritis (RA) remain unsettled. So we examined the frequencies of Th22 cells, Th17 cells and Th1 cells in peripheral blood (PB) from patients with AS and patients with RA compared with both healthy controls as well as patients with osteoarthritis.

Major Biological Activities of the Skin Secretion of the Chinese Giant Salamander, Andrias Davidianus

Zeitschrift Für Naturforschung. C, Journal of Biosciences. Jan-Feb, 2012  |  Pubmed ID: 22486045

Amphibian skin can produce abundant secretion which contains many bioactive compounds. In this work, skin secretion of the Chinese giant salamander (Andrias davidianus) was obtained by mild electrical stimulation of the dorsal skin surface, and the main physiopathological properties of the secretion were described. Intraperitoneal administration of the skin secretion caused lethal effects in mice. Low doses of the skin secretion induced significant systemic and local effects like edema and nociception in mice. The activities of phospholipase A2 and proteolytic enzyme were likely related to the physiopathological activities observed. The work proved the complex toxic effects of the Chinese giant salamander skin secretion and provided clues to study its physiological function further.

Palladium(II)-Catalyzed Oxidative CH/CH Cross-Coupling Between Two Structurally Similar Azoles

Chemistry (Weinheim an Der Bergstrasse, Germany). Apr, 2012  |  Pubmed ID: 22488979

Power of two: A widely functional-group tolerant, selective and rapid oxidative cross-coupling between two structurally similar azoles has been carried out by using a palladium/copper co-catalytic twofold CH activation method.

Recent Patents on Oligonucleotide Synthesis and Gene Synthesis

Recent Patents on DNA & Gene Sequences. Apr, 2012  |  Pubmed ID: 22208678

Gene synthesis is an emerging field which has widespread implications in synthetic biology and molecular biology. The field is constantly evolving which has led to key advances in oligonucleotide synthesis and gene synthesis technologies, with simplicity, cost effectiveness and high throughput. The miniaturization, multiplexing, microfluidic processing and the integrated microchip engineering will drive down cost and increase productivity without compromising DNA synthesis fidelity, whereas the gigantic amount of genome information provides infinite source of DNA elements and genes as raw material for synthetic biology. This article describes some of the recent patents on oligonucleotide synthesis and gene synthesis.

Block Copolymer Micelles for Nanomedicine

Nanomedicine (London, England). Feb, 2012  |  Pubmed ID: 22339128

Novel Tubulin Polymerization Inhibitors Overcome Multidrug Resistance and Reduce Melanoma Lung Metastasis

Pharmaceutical Research. Mar, 2012  |  Pubmed ID: 22410804

PURPOSE: To evaluate abilities of 2-aryl-4-benzoyl-imidazoles (ABI) to overcome multidrug resistance (MDR), define their cellular target, and assess in vivo antimelanoma efficacy. METHODS: MDR cell lines that overexpressed P-glycoprotein, MDR-associated proteins, and breast cancer resistance protein were used to evaluate ABI ability to overcome MDR. Cell cycle analysis, molecular modeling, and microtubule imaging were used to define ABI cellular target. SHO mice bearing A375 human melanoma xenograft were used to evaluate ABI in vivo antitumor activity. B16-F10/C57BL mouse melanoma lung metastasis model was used to test ABI efficacy to inhibit tumor lung metastasis. RESULTS: ABIs showed similar potency to MDR cells compared to matching parent cells. ABIs were identified to target tubulin on the colchicine binding site. After 31 days of treatment, ABI-288 dosed at 25 mg/kg inhibited melanoma tumor growth by 69%; dacarbazine at 60 mg/kg inhibited growth by 52%. ABI-274 dosed at 25 mg/kg showed better lung metastasis inhibition than dacarbazine at 60 mg/kg. CONCLUSIONS: This new class of antimitotic compounds can overcome several clinically important drug resistant mechanisms in vitro and are effective in inhibiting melanoma lung metastasis in vivo, supporting their further development.

Efficient Delivery of Antitumor Drug to the Nuclei of Tumor Cells by Amphiphilic Biodegradable Poly(L-Aspartic Acid-co-Lactic Acid)/DPPE Co-Polymer Nanoparticles

Small (Weinheim an Der Bergstrasse, Germany). Mar, 2012  |  Pubmed ID: 22411637

The use of biodegradable polymeric nanoparticles (NPs) for controlled drug delivery has shown significant therapeutic potential. Polyaspartic acid and polylactic acid are the most intensively studied biodegradable polymers. In the present study, novel amphiphilic biodegradable co-polymer NPs, poly(L-aspartic acid-co-lactic acid) with 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) (poly(AA-co-LA)/DPPE) is synthesized and subsequently used to encapsulate an antitumor drug doxorubicin (DOX). The formulation parameters of the NPs are optimized to improve encapsulation efficiency. The resulting drug-loaded NPs possess better size homogeneity (polydispersity) and exhibit pH-responsive drug release profiles. Cellular viability assays indicate that the poly(AA-co-LA)/DPPE NPs did not induce cell death, whereas doxorubicin encapsulated NPs were cytotoxic to various types of tumor cells. In addition, the free NPs could not enter the cell nuclei after internalized in tumor cells. The DOX-loaded NPs exhibit efficient intracellular delivery in tumor cells with co-localization in lysosome and delay entering into the nucleus, which suggests a time- and pH-dependent drug release profile within cells. When applied to deliver chemotherapeutics to a mouse xenograft model of human lung adenocarcinoma, DOX-loaded NPs have a comparable antitumor activity with free DOX, and greatly reduce systemic toxicity and mortality. The delivery of cytotoxic drugs directly to the nucleus specifically within tumor cells is of great interest. These results demonstrate the feasibility of the application of the amphiphilic polyaspartic acid derivative, poly(AA-co-LA)/DPPE, as a nanocarrier for cell nuclear delivery of potent antitumor drugs.

Stereoselective Dissipation of Epoxiconazole in Grape (Vitis Viniferacv. Kyoho) and Soil Under Field Conditions

Chemosphere. May, 2012  |  Pubmed ID: 22414382

Stereoselective dissipation of epoxiconazole had been studied in grape and soil during plant growing under field conditions in this paper. A sensitive and rapid chiral method was developed and validated for the determination of epoxiconazole stereoisomers in grape and soil based on liquid chromatography coupled with triple quadrupole mass spectrometry (LC-MS/MS). Phenomenex Lux Cellulose-1 column was used for enantioseparation with a mixture of acetonitrile/water (90/10, v/v) as mobile phase at flow rate of 0.3mLmin(-1). Fortified recoveries in grape and soil samples ranged from 76.0% to 91.9% and relative standard deviations were less than 11.4% with fortified levels of 0.025-1.0mgkg(-1). The limits of detection and quantification were 0.005mgkg(-1) and 0.025mgkg(-1), respectively, with linear calibration curves extending up to 5.0mgkg(-1). The field experimental results showed that dissipations of epoxiconazole stereoisomers in grape followed first-order kinetics (R(2)>0.92) and stereoselectivity occurred in 2h after spraying. The (-)-stereoisomer with half-life of 9.3d degraded faster than (+)-stereoisomer with that of 13.2d, and resulted in relative enrichment of (+)-stereoisomer. However, the stereoisomeric dissipations in soil were triphasic ("increase-decrease-steady") with lower dissipation rates, and also occurred with preferential degradation of (-)-stereoisomer under field condition. The results for stereoselective dissipations can be applied for food and environmental assessments of chiral pesticides.

Bak Deficiency Inhibits Liver Carcinogenesis: A Causal Link Between Apoptosis and Carcinogenesis

Journal of Hepatology. Mar, 2012  |  Pubmed ID: 22414765

BACKGROUND & AIMS: Hepatocyte apoptosis is a key feature of chronic liver disease including viral hepatitis and steatohepatitis. A previous study demonstrated that absence of the Bcl-2 family protein Mcl-1 led to increased hepatocyte apoptosis and development of liver tumors in mice. Since Mcl-1 not only inhibits the mitochondrial pathway of apoptosis but can also inhibit cell cycle progression and promote DNA repair, it remains to be proven whether the tumor suppressive effects of Mcl-1 are mediated by prevention of apoptosis. METHODS: We examined liver tumor development, fibrogenesis, and oxidative stress in livers of hepatocyte-specific knockout (KO) of Mcl-1 or Bcl-xL, another key antagonist of apoptosis in hepatocytes. We also examined the impact of additional KO of Bak, a downstream molecule of Mcl-1 towards apoptosis but not the cell cycle or DNA damage pathway, on tumor development, hepatocyte apoptosis, and inflammation. RESULTS: Bcl-xL KO led to a high incidence of liver tumors in 1.5-year-old mice, similar to Mcl-1 KO. Bcl-xL- or Mcl-1-deficient livers showed higher levels of TNF-α production and oxidative stress than wild-type livers at as early as 6weeks of age and oxidative DNA damage at 1.5years. Deletion of Bak significantly inhibited hepatocyte apoptosis in Mcl-1 KO mice and reduced the incidence of liver cancer, coinciding with reduction of TNF-α production, oxidative stress, and oxidative DNA damage in non-cancerous livers. CONCLUSIONS: Our findings strongly suggest that chronically increased apoptosis in hepatocytes is carcinogenic and offer genetic evidence that inhibition of apoptosis may suppress liver carcinogenesis in chronic liver disease.

Characterization of the MiRNA Profile in UVB-irradiated Normal Human Keratinocytes

Experimental Dermatology. Apr, 2012  |  Pubmed ID: 22417313

The aim of this study was to assess the effects of ultraviolet B (UVB) irradiation on microRNA (miRNA) expression in normal human keratinocytes. Global miRNA expression profiles of primary cultures of normal human keratinocytes 4 and 24 h postirradiation were studied using miRNA microarray with further confirmation by real-time PCR. We found that upon 30 or 60 mJ/cm(2) of UVB radiation, the expression of 44 miRNAs was up- or downregulated more than twofold compared with non-irradiated keratinocytes. MiRNAs were either up- or downregulated after 4 h and then either returned to normal levels or remained affected after 24 h, resulting in four distinct patterns of miRNA expression change. It appears that acute exposure of keratinocytes to UVB radiation results in several specific patterns of miRNA response.

Pimarane Diterpenes from the Fungus Epicoccum Sp. HS-1 Associated with Apostichopus Japonicus

Bioorganic & Medicinal Chemistry Letters. Apr, 2012  |  Pubmed ID: 22418279

Three new pimarane diterpenes (1, 2 and 3) as well as a known compound 4, were isolated from the marine-derived fungus HS-1 from Apostichopus japonicus. Their structures and relative stereochemistry of 1-3 were elucidated using a combination of NMR spectroscopy and CD. In the primary bioassay, compounds 1, 2 and 4 inhibited the growth of KB and KBv200 with IC(50) of 3.51, 2.34μg/mL, 20.74, 14.47μg/mL, and 3.86, 6.52μg/mL, respectively.

In Vitro Percutaneous Absorption Enhancement of Granisetron by Chemical Penetration Enhancers

Drug Development and Industrial Pharmacy. Mar, 2012  |  Pubmed ID: 22424279

Granisetron (GRN), a potent antiemetic agent, is frequently used to prevent nausea and vomiting induced by cancer cytotoxic chemotherapy and radiation therapy. Objective: As part of our efforts to further modify the physicochemical properties of this market drug, with the ultimate goal to formulate a better dosage form for GRN, this work was carried out to improve its permeability in vitro. Methods: The permeation behavior of GRN in isopropyl myristate (IPM) was investigated across excised rabbit abdominal skin and the enhancing activities of three novel O-acylmenthol derivatives synthesized in our laboratory as well as five well-known chemical enhancers were evaluated. Results: It was found that the steady-state flux of granisetron free base (GRN-B) was about 26-fold higher than that of granisetron hydrochloride (GRN-H). The novel enhancer, 2-isopropyl-5-methylcyclohexyl heptanoate (M-HEP), was observed to provide the most significant enhancement for the absorption of GRN-B. When incorporated in the donor solution with the optimal enhancer M-HEP, the steady-state flux of GRN-B increased from (196.44 ± 12.03) μg·cm(-2)·h(-1) to (1044.95 ± 71.99) μg·cm(-2)·h(-1) (P < 0.01). Conclusion: These findings indicated that the application of chemical enhancers was an effective approach to increase the percutaneous absorption of GRN in vitro.

Hepatitis C Virus Amino Acid Sequence Diversity Correlates with the Outcome of Combined Interferon/ribavirin Therapy in Chinese Patients with Chronic Hepatitis C

Archives of Virology. Mar, 2012  |  Pubmed ID: 22426896

Evidence has shown that the p7, NS2 and NS3 genes affect the outcome of pegylated-IFN-α/ribavirin (PEG-IFN/RBV) combination therapy in different populations with HCV infections. Here, we test the hypothesis that diversity in the p7, NS2 and NS3 genes influences the probability of obtaining either a sustained (SVR) or non-sustained (non-SVR) viral response in Chinese patients with genotype 1b chronic hepatitis C. There were significantly more unique variations in the p7, NS2 and NS3 genes in the sequences from SVR than non-SVR patients. Inter-patient variations related to treatment outcome in NS3 were concentrated in the protease domain. There were no significant differences in the frequency of variations in the core, E1 and E2 proteins between the groups. In conclusion, increased amino acid sequence diversity in the p7, NS2 and NS3 genes is associated with an SVR to PEG-IFN/RBV therapy in Chinese patients with genotype 1b chronic hepatitis C.

Structural and Functional Insights into the Heme-binding Domain of the Human Soluble Guanylate Cyclase α2 Subunit and Heterodimeric α2β1

Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry. Mar, 2012  |  Pubmed ID: 22426988

Soluble guanylate cyclase (sGC) mediates NO signaling for a wide range of physiological effects in the cardiovascular system and the central nervous system. The α1β1 isoform is ubiquitously distributed in cytosolic fractions of tissues, whereas α2β1 is mainly found in the brain. The major occurrence and the unique characteristic of human sGC α2β1 indicate a special role in the mediation of neuronal communication. We have efficiently purified and characterized the recombinant heme-binding domain of the human sGC α2 subunit (hsGC α2(H)) and heterodimeric α2β1 (hsGC β1(H)-α2(H)) by UV-vis spectroscopy, circular dichrosim spectroscopy, EPR spectroscopy, and homology modeling. The heme dissociation and related NO/CO binding/dissociation of both hsGC α2(H) and hsGC β1(H)-α2(H) were investigated. The two truncated proteins interact with heme noncovalently. The CO binding affinity of hsGC α2(H) is threefold greater than that of human sGC α1(H), whereas the dissociation constant k (1) for dissociation of NO from hsGC α2(H) is sevenfold larger than that for dissociation of NO from hsGC α1(H), although k (2) is almost identical. The results indicate that in comparison with the α1β1 isoform, the brain α2β1 isoform exhibits a distinctly different CO/NO affinity and binding rate in favor of NO signaling, and this is consistent with its physiological role in the activation and desensitization. Molecular modeling and sequence alignments are consistent with the hypothesis that His105 contributes to the different CO/NO binding properties of different isoforms. This valuable information is helpful to understand the molecular mechanism by which human sGC α2β1 mediates NO/CO signaling.

Immunogenicity Study of Plasmid DNA Encoding Mouse Cysteine-Rich Secretory Protein-1 (mCRISP1) As a Contraceptive Vaccine

American Journal of Reproductive Immunology (New York, N.Y. : 1989). Mar, 2012  |  Pubmed ID: 22429321

PROBLEM: To examine the immunocontraceptive properties of the plasmid pcDNA-mCRISP1 and compare them to the corresponding recombinant mCRISP1 (r-mCRISP1). METHOD OF STUDY: RT-PCR and indirect immunofluorescence were performed to observe the mCRISP1 protein expression in COS-7 cells. Three groups of mice received three injections of r-mCRISP1, pcDNA-mCRISP1 or pcDNA vector, respectively. ELISA and Western blot were used to examine the immune responses and immunoreactivity of antisera. Sperm-egg penetration assay was performed to examine the effect of anti-mCRISP1 antibodies in vitro fertilization of mouse oocytes. Fertility and mean litter size were analysed by natural mating. Histological analysis was carried out to look for potential immunopathologic effects of the antibodies. RESULTS: COS-7 cells transfected with pcDNA-mCRISP1 present the expression of mCRISP1. Both r-mCRISP1 and pcDNA-mCRISP1 raised an immune response against r-mCRISP1 protein and native CRISP1 in mouse sperm. The titres of anti-mCRISP1 antibodies from DNA immunized mice were significantly lower than that of r-mCRISP1 immunized mice, but it lasted relatively longer. Male and female pcDNA-mCRISP1 injected animals presented a statistically significant reduction in their fertility with no signs of immunopathologic effects. CONCLUSION: These studies demonstrated the feasibility of generating an immune response to mCRISP1 protein by DNA vaccine and pcDNA-mCRISP1 plasmid causing significant anti-fertility potential.

Towards Personalized Medicine with a Three-dimensional Micro-scale Perfusion-based Two-chamber Tissue Model System

Biomaterials. Jun, 2012  |  Pubmed ID: 22429982

A three-dimensional micro-scale perfusion-based two-chamber (3D-μPTC) tissue model system was developed to test the cytotoxicity of anticancer drugs in conjunction with liver metabolism. Liver cells with different cytochrome P450 (CYP) subtypes and glioblastoma multiforme (GBM) brain cancer cells were cultured in two separate chambers connected in tandem. Both chambers contained a 3D tissue engineering scaffold fabricated with biodegradable poly(lactic acid) (PLA) using a solvent-free approach. We used this model system to test the cytotoxicity of anticancer drugs, including temozolomide (TMZ) and ifosfamide (IFO). With the liver cells, TMZ showed a much lower toxicity to GBM cells under both 2D and 3D cell culture conditions. Comparing 2D, GBM cells cultured in 3D had much high viability under TMZ treatment. IFO was used to test the CYP-related metabolic effects. Cells with different expression levels of CYP3A4 differed dramatically in their ability to activate IFO, which led to strong metabolism-dependent cytotoxicity to GBM cells. These results demonstrate that our 3D-μPTC system could provide a more physiologically realistic in vitro environment than the current 2D monolayers for testing metabolism-dependent toxicity of anticancer drugs. It could therefore be used as an important platform for better prediction of drug dosing and schedule towards personalized medicine.

Synchronous Bilateral Pleomorphic Adenomas of the Parotid Gland

Journal of Investigative and Clinical Dentistry. Mar, 2012  |  Pubmed ID: 22431298

Bilateral pleomorphic adenomas of the parotid gland are extremely rare, accounting for less than 0.2% of all parotid gland tumors. We present a rare case of a patient with synchronous bilateral pleomorphic adenomas of the parotid gland. A 27-year-old woman presented with a 5-month history of a slowly-growing, painless swelling of the right parotid gland. After a thorough bilateral parotid examination and magnetic resonance imaging evaluation, bilateral tumors of the parotid gland were found. The patient underwent surgical excision of the bilateral tumors in one surgical setting. Histopathological examination showed that both tumors were pleomorphic adenomas. The patient has been followed for 24 months without recurrence of tumors. Careful preoperative examination and radiological evaluation of bilateral parotid glands might be necessary for the early diagnosis of synchronous bilateral tumors. We suggest that treatment be individualized depending on the sizes and locations of tumors, and the surgical and neurological risks.

Advanced Glycation End Products Induce a Prothrombotic Phenotype in Mice Via Interaction with Platelet CD36

Blood. Mar, 2012  |  Pubmed ID: 22431576

Diabetes mellitus has been associated with platelet hyper-reactivity, which plays a central role in hyperglycemia related prothrombotic phenotype. The mechanisms responsible for this phenomenon are not established. Here, we investigated the role of CD36, a class B scavenger receptor in this process. Using both in vitro and in vivo mouse models, we demonstrated direct and specific interactions of platelet CD36 with advanced glycation end products (AGE) generated under hyperglycemic conditions. AGE bound to platelet CD36 in a specific and dose dependent manner, and binding was inhibited by a high affinity CD36 ligand NO(2)LDL. CD36 null platelets did not bind AGE. Using diet and drug induced mouse diabetes models we showed that cd36 null mice had delayed time to formation of occlusive thrombi in a FeCl(3)-induced carotid artery injury model compared with wild type. Cd36 null mice had similar level of hyperglycemia and similar level of plasma AGE compared with WT mice under this condition, but WT mice had more AGE incorporated into thrombi. Mechanistic studies revealed that CD36-dependent JNK2 activation is involved in this pro-thrombotic pathway. Thus, this study couples vascular complications in diabetes mellitus with AGE-CD36-mediated platelet signaling and hyper-reactivity.

Fractalkine As a Marker for Assessment of Severe Acute Pancreatitis

Journal of Digestive Diseases. Apr, 2012  |  Pubmed ID: 22435508

  The aim of this study was to study the role of fractalkine (FKN) in the development of severe acute pancreatitis (SAP) in animal model.

The Mutation Profiles of Common Oncogenes Involved in Melanoma in Southern China

The Journal of Investigative Dermatology. Mar, 2012  |  Pubmed ID: 22437319

Quantitative Unit Classification of Ventral Tegmental Area Neurons In Vivo

Journal of Neurophysiology. Feb, 2012  |  Pubmed ID: 22378178

Neurons in the ventral tegmental area (VTA) synthesize several major neurotransmitters, including dopamine (DA), GABA, and glutamate. To classify VTA single-unit neural activity from freely-moving rats, we used hierarchical agglomerative clustering and probability distributions as quantitative methods. After examining many parameters, a firing rate of 10 Hz emerged as a transition frequency between clusters of low-firing and high-firing neurons. To form a subgroup identified as high-firing neurons with GABAergic characteristics, the high-firing classification was sorted by spike duration. To form a subgroup identified as putative DA neurons, the low-firing classification was sorted by their DA D2-type receptor pharmacological responses to quinpirole and eticlopride. Putative DA neurons were inhibited by the D2-type receptor agonist, quinpirole, and returned to near baseline firing rates or higher following the D2-type receptor antagonist, eticlopride. Other neuron types showed different responses to these D2-type receptor drugs. A multidimensional comparison of neural properties indicated that these subgroups often clustered independently of each other with minimal overlap. Firing pattern variability reliably distinguished putative DA neurons from other neuron types. A combination of phasic burst properties and a low skew in the interspike interval distribution produced a neural population that was comparable to the one sorted by D2 pharmacology. These findings provide a quantitative statistical approach for the classification of VTA neurons in unanesthetized animals.

Bismuth 2,6-pyridinedicarboxylates: Assembly of Molecular Units into Coordination Polymers, CO(2) Sorption and Photoluminescence

Dalton Transactions (Cambridge, England : 2003). Apr, 2012  |  Pubmed ID: 22378230

Six inorganic-organic bismuth 2,6-pyridinedicarboxylate (pdc) compounds, [Bi(2,6-pdc)(3)]·3(dma), 1, [Bi(2,6-pdc)(3)]·3(dma)·2(H(2)O), 2, [Bi(2,6-pdc)(2)(dmf)]·(dma), 3, Bi(2,6-pdc)(2,6-pdcme)(MeOH), 4, [LiBi(2,6-pdc)(3)(H(2)O)]·2(dma), 5, and Li(5)Bi(2,6-pdc)(4)(H(2)O)(2), 6 (where dma = dimethyl ammonium cation, dmf = dimethylformamide and 2,6-pdcme = 6-methyl-oxycarbonyl pyridine 2-carboxylate) have been synthesized under solvothermal conditions and their structures determined by single crystal X-ray diffraction. Compounds 1-4 have molecular structures whereas compounds 5 and 6 form one- and three-dimensional frameworks, respectively. Compounds 1 and 2, both having similar monomeric bismuth coordination units, which are connected non-covalently into a (4,4)-connected square lattice by H-bonding interactions through dma cations. Compounds 3 and 4, both have a similar dimeric bismuth coordination unit. In 3, the dimers are connected into a one-dimensional chain by H-bonding interactions through dma cations. In the partially esterified and neutral 4, there was no such H-bonding interactions due to the absence of any dma cations. Compounds 5 and 6 have a similar monomeric bismuth coordination unit to that seen in 1 and 2. In 5, the monomers are connected through lithium cations into one-dimensional chains, which further interact non-covalently by H-bonding interactions through dma cations. In the lithium-rich 6, the monomers are connected by the lithium cations and 2,6-pdc anions into a three dimensional structure with intramolecular H-bonding interactions involving the water molecules. The non-porous 5 and 6 exhibit a reasonable amount of H(2) and CO(2) sorptions, respectively. Tb(3+)- and Eu(3+)-doped and co-doped 4 and 5 emit characteristic sensitized green/red/yellow-orange luminescence.

Emodin Potentiates the Antitumor Effects of Gemcitabine in PANC-1 Pancreatic Cancer Xenograft Model in Vivo Via Inhibition of Inhibitors of Apoptosis

International Journal of Oncology. Jun, 2012  |  Pubmed ID: 22378302

Pancreatic cancer is a highly aggressive malignant disease. Gemcitabine is currently the standard first-line chemotherapeutic agent for pancreatic cancer. As members of apoptosis inhibitors, Survivin and XIAP play an important role in chemotherapy resistance in pancreatic cancer. Emodin has therapeutic potential against cancers. This study was designed to investigate whether combination therapy with gemcitabine and emodin enhanced antitumor efficacy in pancreatic cancer. The application of the combination therapy triggered significantly higher frequency of pancreatic cancer cell apoptosis. Our research demonstrated that the combination of emodin and gemcitabine resulted in significantly reduced tumor volumes compared to gemcitabine or emodin treatment alone. Immunohistochemistry and western immunoblot analyses showed that Survivin and XIAP expression were downregulated in emodin and the combination groups compared to the other two groups. Reverse transcriptase polymerase chain reaction analyses showed that Survivin and XIAP mRNA expression in emodin and the combination groups were downregulated significantly compared to the other two groups. Furthermore, the expression of the nuclear transcription factor κB (NF-κB) protein and NF-κB mRNA were downregulated in the emodin and the combination groups. DNA-binding activity of NF-κB was inhibited in emodin and combination groups compared to the other groups. This study suggests that emodin potentiates the antitumor effects of gemcitabine in PANC-1 cell xenografts via promotion of apoptosis and IAP suppression.

Emission Factors, Size Distributions, and Emission Inventories of Carbonaceous Particulate Matter from Residential Wood Combustion in Rural China

Environmental Science & Technology. Apr, 2012  |  Pubmed ID: 22380753

Published emission factors (EFs) often vary significantly, leading to high uncertainties in emission estimations. There are few reliable EFs from field measurements of residential wood combustion in China. In this study, 17 wood fuels and one bamboo were combusted in a typical residential stove in rural China to measure realistic EFs of particulate matter (PM), organic carbon (OC), and elemental carbon (EC), as well as to investigate the influence of fuel properties and combustion conditions on the EFs. Measured EFs of PM, OC, and EC (EF(PM), EF(OC), and EF(EC), respectively) were in the range of 0.38-6.4, 0.024-3.0, and 0.039-3.9 g/kg (dry basis), with means and standard derivation of 2.2 ± 1.2, 0.62 ± 0.64, and 0.83 ± 0.69 g/kg, respectively. Shrubby biomass combustion produced higher EFs than tree woods, and both species had lower EFs than those of indoor crop residue burning (p < 0.05). Significant correlations between EF(PM), EF(OC), and EF(EC) were expected. By using a nine-stage cascade impactor, it was shown that size distributions of PM emitted from tree biomass combustions were unimodal with peaks at a diameter less than 0.4 μm (PM(0.4)), much finer than the PM from indoor crop residue burning. Approximately 79.4% of the total PM from tree wood combustion was PM with a diameter less than 2.1 μm (PM(2.1)). PM size distributions for shrubby biomasses were slightly different from those for tree fuels. On the basis of the measured EFs, total emissions of PM, OC, and EC from residential wood combustion in rural China in 2007 were estimated at about 303, 75.7, and 92.0 Gg.

Novel Dual-control Poly(N-isopropylacrylamide-co-chlorophyllin) Nanogels for Improving Drug Release

Nanomedicine (London, England). Mar, 2012  |  Pubmed ID: 22385198

How to overcome insufficient drug release is an important issue in the drug-delivery system.

Mutasynthesis of a Potent Anticancer Sibiromycin Analogue

ACS Chemical Biology. Mar, 2012  |  Pubmed ID: 22390171

Pursuit of the actinomycete pyrrolobenzodiazepine natural product sibiromycin as a chemotherapeutic agent has been limited by its cardiotoxicity. Among pyrrolobenzodiazepines, cardiotoxicity is associated with hydroxylation at position 9. Deletion of the methyltransferase gene sibL abolishes the production of sibiromycin. Supplementation of growth media with 4-methylanthranilic acid can substitute for its native 3-hydroxy congener. Cultures grown in this fashion yielded 9-deoxysibiromycin. In this study, we characterize the structure and biological activity of sibiromycin and 9-deoxysibiromycin methyl carbinolamines. Preliminary in vitro evidence suggests that 9-deoxysibiromycin exhibits reduced cardiotoxicity while gaining antitumor activity. These results strongly support further exploration of the production and evaluation of monomeric and dimeric glycosylated pyrrolobenzodiazepine analogues of sibiromycin.

Swainsonine Activates Mitochondria-mediated Apoptotic Pathway in Human Lung Cancer A549 Cells and Retards the Growth of Lung Cancer Xenografts

International Journal of Biological Sciences. 2012  |  Pubmed ID: 22393311

Swainsonine (1, 2, 8-trihyroxyindolizidine, SW), a natural alkaloid, has been reported to exhibit anti-cancer activity on several mouse models of human cancer and human cancers in vivo. However, the mechanisms of SW-mediated tumor regression are not clear. In this study, we investigated the effects of SW on several human lung cancer cell lines in vitro. The results showed that SW significantly inhibited these cells growth through induction of apoptosis in different extent in vitro. Further studies showed that SW treatment up-regulated Bax, down-regulated Bcl-2 expression, promoted Bax translocation to mitochondria, activated mitochondria-mediated apoptotic pathway, which in turn caused the release of cytochrome c, the activation of caspase-9 and caspase-3, and the cleavage of poly (ADP-ribose) polymerase (PARP), resulting in A549 cell apoptosis. However, the expression of Fas, Fas ligand (FasL) or caspase-8 activity did not appear significant changes in the process of SW-induced apoptosis. Moreover, SW treatment inhibited Bcl-2 expression, promoted Bax translocation, cytochrome c release and caspase-3 activity in xenograft tumor cells, resulting in a significant decrease of tumor volume and tumor weight in the SW-treated xenograft mice groups in comparison to the control group. Taken together, this study demonstrated for the first time that SW inhibited A549 cancer cells growth through a mitochondria-mediated, caspase-dependent apoptotic pathway in vitro and in vivo.

20-Hydroxyvitamin D3 Inhibits Proliferation of Cancer Cells with High Efficacy While Being Non-toxic

Anticancer Research. Mar, 2012  |  Pubmed ID: 22399586

Aim: To define the potential utility of 20-hydroxyvitamin D(3) (20(OH)D(3)) as a tumorostatic agent, we assessed its in vitro antiproliferative activity and its in vivo toxicity.

An NMR-based Metabonomic Investigation of the Subacute Effects of Melamine in Rats

Journal of Proteome Research. Apr, 2012  |  Pubmed ID: 22401608

The subacute toxic effects of 28 days of exposure to three dosages (250, 500, 1000 mg/kg/day) of melamine on Wistar rats were investigated using nuclear magnetic resonance spectra, histopathological examination, and biochemical analysis. Rats treated with melamine developed adverse health effects compared to the controls, including decrease in body weight and kidney damage. Blood biochemical analysis showed that the blood urea nitrogen and creatinine increased distinctly compared to the control group. Urinary metabonomic analysis indicated that melamine caused an increase in succinate and citrate. Serum metabonomic analysis showed that the lowest dose led to an increase in dimethylglycine, N-acetylglycoprotein (NAC), accompanied by a decrease in taurine and glucose. Rats treated with the highest dose developed high levels of serum choline and 3-hydroxybutyrate (3-HB) together with low lactate levels. Metabonomic analysis of liver tissue indicated that melamine caused an increase in NAC, choline, and creatine, accompanied by a decrease in lactate, trimethylamine-N-oxide, glutamate, and glucose. All three dosages resulted in an increase in glutamate, lactate, choline, glucose, and animo acids and a decrease in 3-HB and pyruvate in aqueous kidney extract. These results indicate that melamine not only caused renal disfunction but also disturbed the liver's glucose, protein, and nitrogen metabolism.

Design, Synthesis, and Biological Action of 20R-Hydroxyvitamin D3

Journal of Medicinal Chemistry. Mar, 2012  |  Pubmed ID: 22404326

The non-naturally occurring 20R epimer of 20-hydroxyvitamin D3 is synthesized based on chemical design and hypothesis. The 20R isomer is separated by semipreparative HPLC, and its structure is characterized. A comparison of 20R isomer to its 20S counterpart in biological evaluation demonstrates that they have different behaviors in antiproliferative and metabolic studies.

A Short Note on the Horizontal and Vertical Movements of a Whale Shark, Rhincodon Typus, Tracked by Satellite Telemetry in the South China Sea

Integrative Zoology. Mar, 2012  |  Pubmed ID: 22405452

Whale sharks, a global migratory species, are often reported entangled in fishing nets in coastal areas of China. The effectiveness of conservation measures has been constrained by very limited knowledge on their movements and preferred habitats in the coastal areas of China. For the first time, we tracked the movements of 2 whale sharks by satellite telemetry in Mainland China. The tracking results of 1 whale shark revealed that it travelled in the South China Sea in a south-eastern direction, parallel to the eastern coast of Vietnam. Total distance travelled was 1018 km, in approximately 74 days, with a mean speed of 14 km per day. It appeared to head towards the cool upwelling zones in southern Vietnam at the time of the tag's detachment. In our study, it was observed that this whale shark was a surface dweller and spent approximately 45% of its time above 10 m water depth and 90% of its time above 50 m depth. It also tended to stay in water temperatures between 27 and 30 °C, and was rarely recorded in water below 20 °C. This preliminary study indicates the importance of shallow waters as the foraging habitat for whale sharks, and has implications for their management and conservation.

Mutation Analysis of the NRXN1 Gene in a Chinese Autism Cohort

Journal of Psychiatric Research. Mar, 2012  |  Pubmed ID: 22405623

Autism is a brain developmental disorder characterized by impaired social interaction and communication, as well as restricted and repetitive behaviors. The neurexin-1(NRXN1) gene mapped on chromosome 2p16.3 encodes neurexin, a cell adhesion molecule and receptor in the vertebrate nervous system. Rare de novo alterations and copy number variations (CNVs) suggested neurexin-1 as a candidate gene for the pathogenesis of autism, but data on the gene mutation of neurexin-1 in Chinese Han population with autism are limited. By direct sequencing, we analyzed the entire coding regions and associated splice junctions of neurexin-1 in 313 Chinese autism patients. For exons in which non-synonymous variants were identified, sequencing was performed in 500 healthy controls. We identified 22 variants in the neurexin-1 coding regions, including 7 missense variants, 3 deletions, and 12 synonymous mutations. Among them, 3 missense and 3 synonymous variants were not reported in the dbSNP database and absent in 500 control subjects; whereas 4 missense variants, 3 deletions and 3 synonymous mutations were not reported in the dbSNP database but were identified in the control subjects. However, there is no significant association of these mutations with autism risk. Interestingly, there was a statistically significant association of neurexin-1 SNP P300P (rs2303298) with risk of autism (26.2% vs. 13.8%; χ(2) = 22.487; p = 3.45E-006; OR = 2.152 (1.559-2.970)). Our data suggest a possible association of neurexin-1 with autism risk in Chinese Han population, warranting further large-scale study on this gene.

New Cytotoxic Quinolone Alkaloids from Fruits of Evodia Rutaecarpa

Fitoterapia. Mar, 2012  |  Pubmed ID: 22406451

Three new quinolone alkaloids, 1-methyl-2-[7-hydroxy-(E)-9-tridecenyl]-4(1H)-quinolone (1), 1-methyl-2-[(Z)-4-nonenyl]-4(1H)-quinolone (2), 1-methyl-2-[(1E,5Z)-1,5-undecadienyl]-4(1H)-quinolone (3) and one new natural product, 1-methyl-2-[(E)-1-undecenyl]-4(1H)-quinolone (4), were isolated from the dried and nearly ripe fruits of Evodia rutaecarpa (Juss.) Benth., along with thirteen known compounds (5-17). In addition, one new artificial product, 1-methyl-2-[7-carbonyl-(E)-9-tridecenyl]-4(1H)-quinolone (1A) was also obtained. The structures of these compounds were determined by spectroscopic analyses. The cytotoxic activities of all of the compounds against the human cancer cell lines HL-60, N-87, H-460, and Hep G(2) cells were evaluated by MTT assay. The results showed that these alkaloids inhibited cell proliferation with IC(50) values between 14μM and 22μM.

Loss-of-function Mutations in Filaggrin Gene Associate with Psoriasis Vulgaris in Chinese Population

Human Genetics. Mar, 2012  |  Pubmed ID: 22407025

Loss-of-function mutations in filaggrin gene (FLG; OMIM #135940) have been reported to cause the semi-dominant keratinizing disorders such as ichthyosis vulgaris (IV; OMIM #146700) and atopic dermatitis (AD; OMIM #605803). Recent linkage analysis and immunohistochemical studies suggest the possible contribution of FLG to psoriatic susceptibility. However, no susceptibility variant in FLG gene associated with psoriasis (OMIM #177900) has been identified. In this study, we identified a non-sense mutation of FLG (p.K4022X) in a Chinese psoriasis/IV coexisting family. The homozygous p.K4022X mutation was detected in a psoriasis patient, whereas the heterozygous p.K4022X mutation was identified in two IV patients and four apparently normal family members. We also genotyped p.K4022X variant in 441 sporadic Chinese psoriasis patients and found homozygous mutation in two patients, while no homozygous variant was found in 500 control individuals. After sequencing the entire coding region of FLG gene in 441 psoriasis patients, we identified another five mutations (p.R826X, p.W2583X, c.7945delA, c.3321delA and p.Q2417X). Although all six FLG mutations as a whole was not significantly associated with psoriasis (P = 0.105), mutation p.K4022X was significantly associated with psoriasis (P < 0.05). Our data thus indicates an association of FLG with psoriasis in Chinese population.

Characterization and Expression Analysis of Hsp70 Gene from Ulva Prolifera J. Agardh (Chlorophycophyta, Chlorophyceae)

Marine Genomics. Mar, 2012  |  Pubmed ID: 22325722

In the Yellow Sea of China, large-scale green tides have broken out consecutively from 2007 to 2011. Ulva prolifera, the causative species of green tide, showed great ability to acclimate to adverse circumstance. To explore the mechanisms of rapid growth and stress resistance during the bloom, we characterized and analyzed hsp70 from U. prolifera. The results showed that hsp70 gene had 6 exons and 5 introns. The promoter-like region contained multiple cis-acting elements. The transcription of hsp70 was up-regulated by UV irradiation, heat treatment and salinities induction, but less influenced by desiccation. In vitro expression of HSP70 protein and western blot was also conducted, and the recombinant protein will be used in detecting the interaction between HSP70 and related functional proteins in the future. The study suggested that hsp70 could be used in prediction of stress tolerance in algae and monitoring environmental changes.

Antioxidant Treatment Reduces Blast-induced Cochlear Damage and Hearing Loss

Hearing Research. Feb, 2012  |  Pubmed ID: 22326291

Exposure to blast overpressure has become one of the hazards of both military and civilian life in many parts of the world due to war and terrorist activity. Auditory damage is one of the primary sequela of blast trauma, affecting immediate situational awareness and causing permanent hearing loss. Protecting against blast exposure is limited by the inability to anticipate the timing of these exposures, particularly those caused by terrorists. Therefore a therapeutic regimen is desirable that is able to ameliorate auditory damage when administered after a blast exposure has occurred. The purpose of this study was to determine if administration of a combination of antioxidants 2,4-disulfonyl α-phenyl tertiary butyl nitrone (HPN-07) and N-acetylcysteine (NAC) beginning 1 h after blast exposure could reduce both temporary and permanent hearing loss. To this end, a blast simulator was developed and the operational conditions established for exposing rats to blast overpressures comparable to those encountered in an open-field blast of 14 pounds per square inch (psi). This blast model produced reproducible blast overpressures that resulted in physiological and physical damage to the auditory system that was proportional to the number and amplitude of the blasts. After exposure to 3 consecutive 14 psi blasts 100% of anesthetized rats had permanent hearing loss as determined at 21 days post exposure by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) testing. Animals treated with HPN-07 and NAC after blast exposure showed a significant reduction in ABR threshold shifts and DPOAE level shifts at 2-16 kHz with significant reduction in inner hair cell (IHC) and outer hair cell (OHC) loss across the 5-36 kHz region of the cochlea compared with control animals. The time course of changes in the auditory system was documented at 3 h, 24 h, 7 day and 21 day after blast exposure. At 3 h after blast exposure the auditory brainstem response (ABR) threshold shifts were elevated by 60 dB in both treated and control groups. A partial recovery of to 35 dB was observed at 24 h in the controls, indicative of a temporary threshold shift (TTS) and there was essential no further recovery by 21 days representing a permanent threshold shift of about 30 dB. Antioxidant treatment increased the amount of both TTS and PTS recovery relative to controls by 10 and 20 dB respectively. Distortion product otoacoustic emission (DPOAE) reached a maximum level shift of 25-30 dB measured in both control and treated groups at 3 h after blast exposure. These levels did not change by day 21 in the control group but in the treatment group the level shifts began to decline at 24 h until by day 21 they were 10-20 dB below that of the controls. Loss of cochlear hair cells measured at 21 day after blast exposure was mostly in the outer hair cells (OHC) and broadly distributed across the basilar membrane, consistent with the distribution of loss of frequency responses as measured by ABR and DPOAE analysis and typical of blast-induced damage. OHC loss progressively increased after blast exposure reaching an average loss of 32% in the control group and 10% in the treated group at 21 days. These findings provide the first evidence that a combination of antioxidants, HPN-07 and NAC, can both enhance TTS recovery and prevent PTS by reducing damage to the mechanical and neural components of the auditory system when administered shortly after blast exposure.

Oral Vaccination with Attenuated Salmonella Enterica Serovar Typhimurium Expressing Cap Protein of PCV2 and Its Immunogenicity in Mouse and Swine Models

Veterinary Microbiology. Jan, 2012  |  Pubmed ID: 22326539

Attenuated Salmonella enterica serovar Typhimurium (S. typhimurium) was selected as a transgenic vehicle for the development of oral vaccines against Porcine circovirus type 2 (PCV2). The Cap-encoding gene of PCV2 was amplified by PCR and cloned into expression vector pYA3341. The recombinant plasmid pYA3341-Cap was transformed into attenuated S. typhimurium X4550. BALB/c mice were inoculated orally with various doses of attenuated S. typhimurium X4550/pYA3341-Cap. The bacterium was safe to mice at dose of 2×10(9)cfu and eventually eliminated in the spleen and mesenteric lymph nodes at 4 weeks post-immunization. The flow cytometry analysis showed that the percentage of CD4(+) T cells and CD4(+)/CD8(+) ratio were increased significantly in mice immunized with attenuated S. typhimurium X4550/pYA3341-Cap. Vaccine tests in swine showed that the oral immunization with attenuated S. typhimurium X4550/pYA3341-Cap could elicit significantly higher Cap antibody titers in the treated swine than the control groups. Virus neutralization test showed that serum from the swine treated with attenuated S. typhimurium X4550/pYA3341-Cap had significant levels of neutralization activities. The swine lymphocyte proliferative responses indicated that attenuated S. typhimurium X4550/pYA3341-Cap could induce obvious cellular immune response. An in vivo challenge study showed the swine treated with attenuated S. typhimurium X4550/pYA3341-Cap had significantly lower PCV2-associated lesions and PCV2 viremia than the control groups. The results indicated that attenuated S. typhimurium X4550/pYA3341-Cap can be a potential vaccine against PCV2 infections.

Muscle Injury Induced by Different Types of Contractions in Dystrophic Mdx Mice

Journal of Muscle Research and Cell Motility. Feb, 2012  |  Pubmed ID: 22327507

Studies on comparing the effect of lengthening, isometric and shortening contractions on dystrophin-deficient muscles are unavailable. We hypothesized that different types of contractions lead to different extents to which dystrophin-deficient muscles are injured. For this purpose, we developed protocols for different types of contraction-induced injury to mdx muscles in vitro. Force deficits and percentages of procion orange dye positive fibers were employed to assess the extent of injury to each muscle. Our results revealed that both the lengthening and isometric contractions resulted in significantly greater injury to extensor digitorum longus (EDL) muscles of mdx mice than to that of control (C57BL/6) mice. In contrast, the shortening contractions induced very mild and identical injury to EDL muscles of mdx and C57BL/6 mice. Then another protocol was carried out in vivo to ascertain the effect of shortening contractions on mdx muscles by achillotenotomy. Histological assessment revealed that the triceps surae muscles with excised Achilles tendon (EAT) displayed little and significantly milder injury than the normal ones did. In conclusions, the unloaded shortening contractions induce little injury to mdx muscles. The in vitro protocol for different types of contraction-induced injury is sensitive and reliable.

Interferon Gamma Inhibits Adipogenesis in Vitro and Prevents Marrow Fat Infiltration in Oophorectomized Mice

Stem Cells (Dayton, Ohio). Feb, 2012  |  Pubmed ID: 22331815

Interferon gamma (IFNγ) has been reported to induce osteoblastogenesis from mesenchymal stem cells (MSC) both in vitro and in vivo. With ageing, adipocytes outnumber osteoblasts within the bone microenvironment leading to a decrease in bone formation. Since both osteoblasts and adipocytes are of mesenchymal origin we hypothesized that IFNγ treatment might negatively affect adipogenesis while stimulates osteoblastogenesis in human MSC. To test this hypothesis, human MSC were induced to differentiate into adipocytes in the presence or absence of osteogenic doses of IFNγ (1, 10, 100 ng/ml). IFNγ-treated MSC showed a decrease in adipocyte differentiation and lipid deposition as compared with vehicle-treated controls. Additionally, adipogenic markers were significantly decreased by IFNγ treatment at the same doses that have been reported to have a strong osteogenic effect in vitro. Furthermore, DNA binding of PPARγ was significantly lower in IFNγ-treated differentiating MSC. Subsequently, ovariectomized C57BL6 mice were treated with osteogenic doses of IFNγ three times a week for 6 weeks. In distal femur, treated mice showed significantly higher hematopoiesis concomitant with lower levels of fat volume/total volume, adipocyte number and expression of adipogenic markers as compared with the vehicle-treated mice. Together, these findings demonstrate that, at osteogenic doses, IFNγ also acts as an inhibitor of adipogenesis in vitro and prevents marrow fat infiltration while favors hematopoiesis in ovariectomized mice.

Pharmacokinetic Study of Unbound Forsythiaside in Rat Blood and Bile by Microdialysis Coupled with HPLC Method

European Journal of Drug Metabolism and Pharmacokinetics. Feb, 2012  |  Pubmed ID: 22314894

In the present study, an in vivo microdialysis sampling method coupled to HPLC was applied for the determination of unbound forsythiaside in rat blood and bile. Microdialysis probes were inserted into the jugular vein and bile duct of rats, and then blood and bile dialysates were collected at regular time intervals after intravenous administration of forsythiaside (50 mg/kg). Dialysates were directly injected into HPLC system. Forsythiaside was separated on a C(18) column eluted with the mobile phase of acetonitrile-water-formic acid (16:84:0.2, v/v/v) at a flow rate of 0.8 mL/min. The wavelength of the ultraviolet detector was set at 332 nm. The lowest limit of quantification was 0.2 μg/mL for forsythiaside. Excellent linearity was found to be over a concentration range of 0.2-100 μg/mL. The main pharmacokinetic parameters of unbound forsythiaside in rat blood and bile were obtained. Furthermore, the bile-to-blood distribution ratio (AUC(bile)/AUC(blood)) of forsythiaside was 0.32 ± 0.06. The results indicated that forsythiaside went through hepatobiliary excretion.

Netrin-1 Simultaneously Suppresses Corneal Inflammation and Neovascularization

Investigative Ophthalmology & Visual Science. Feb, 2012  |  Pubmed ID: 22323486

Purpose:To investigate the effect of netrin-1 on alkali-burn induced corneal inflammation and neovascularization.Methods:The expression of netrin-1 and its receptor UNC5A, UNC5B, UNC5C, UNC5D, A2BAR, DCC and neogenin in normal and alkali-burned rat cornea were determined by RT-PCR and/or Western Blot, or immunostaining. Topical netrin-1 protein was applied to treat rat corneal alkali-burn injury for 14 consecutive days, started right after the injury or 10 days post-injury. Corneal inflammation and neovascularization were observed under slit lamp microscope. The apoptosis of corneal cells was determined by terminal deoxynucleotidyl transferase-mediated nick end labeling assay. Corneal inflammatory cell infiltration was evaluated by immunostaining of anti-PMN and anti-ED1 antibodies. The expression of EGF, VEGF, and PEDF in rat cornea was determined by Western Blot.Results:Netrin-1 and its receptor UNC5B were expressed in normal rat corneal epithelium and stromal cells, and their expression decreased after corneal alkali burn. Exogenous netrin-1 administered on rat ocular surfaces resolved alkali burn-induced corneal inflammation, at the meanwhile, suppressed corneal neovascularization. Furthermore, netrin-1 could reverse neovascularization in alkali-burned cornea. We found that netrin-1 executed the functions through various mechanisms, including upregulating EGF expression, accelerating epithelial wound healing, inhibiting neutrophil and macrophage infiltration, reducing corneal cell apoptosis, and restoring the equilibrium of VEGF and PEDF in the wounded cornea.Conclusions:Netrin-1 could dampen inflammation, inhibit and reverse neovascularization in alkali burned cornea.

Right Ventricular Long-axis Response to Different Chronic Loading Conditions: Its Relevance to Clinical Symptoms

International Journal of Cardiology. Jan, 2012  |  Pubmed ID: 22261688

BACKGROUND: The intervention timing in atrial septal defect (ASD) or pulmonary valvular stenosis (PVS) is more dependent on symptoms than right ventricular (RV) damage in clinical practice. RV long-axis function is sensitive in revealing RV myocardial dysfunction. We evaluate the impact of different chronic loading conditions on RV long-axis function and its relationship to patients' symptoms in ASD or PVS. METHODS: Transthoracic echocardiography was performed in normals (n=39) and patients with isolated secundum ASD (n=45) or PVS (n=38). RV volume- and pressure-overloading were defined as the ratio of RV/left ventricular end-diastolic dimension ≥0.5 and RV systolic pressure ≥40mmHg, respectively. RV long-axis dysfunction was defined as M-mode tricuspid annular plane systolic excursion (TAPSE) <1.6cm. New York Heart Association (NYHA) functional class and other symptoms (decreased exercise tolerance, palpitation and chest pain) were recorded. RESULTS: Thirty-nine (32.0%) had normal loading (Group 1; 39 normals); 24 (19.6%) had isolated volume-overloading (Group 2; all ASDs); 21 (17.2%) had isolated pressure-overloading (Group 3; 21 PVSs) and 38 (31.1%) had both overloading conditions (Group 4; 21 ASDs and 17 PVSs). RV long-axis dysfunction in abnormal loading groups were zero (0%, Group 2), 21 (100%, Group 3) and 22 (57.8%, Group 4) (χ(2)=45.9, p<0.001). Group 3 were more symptomatic (NYHA functional class 2.5±0.6 versus 1.6±0.5, p<0.05) and had lower TAPSE (1.6±0.4 versus 3.0±0.7cm, p<0.05) than Group 2. RV long-axis dysfunction was the strongest predictor of the presence of symptoms (odds ratio=9.298, p<0.001). CONCLUSION: Chronic volume-overloading accentuates while pressure-overloading attenuates RV long-axis excursion and its impairment was associated with the presence of symptoms.

New Insights About the Early Diagnosis of Fertility Impairment in Varicoceles: The DNA Repair Gene Example

Medical Hypotheses. Feb, 2012  |  Pubmed ID: 22305334

Of all men consulted for infertility, around 30% appear to have a varicocele, therefore, this male dysfunction has been considered as a potential cause of infertility in many patients. Emerging studies point out spermatozoa progressive motility as the most important predictor of fertility provided that the analysis was carried out with infertility duration, thus leaving unsolved problem to evaluate the spontaneous testicular damage during the very early phase in varicoceles. Given the deterioration of testicular function caused by varicoceles is progressive, the early and efficient evaluation of testicular damage would be of great importance for the future medical intervention in this population. The resultant mechanism by which varicoceles affect testicular function remains unclear, but the increase in testicular temperature is most commonly accepted aetiology. In this context, we hypothesize that metastasis-associated protein 1 (MTA1), an intrinsic DNA damage response component, possessing transient protective effect in primary spermatocytes against heat stress, bears the potential to be a diagnostic biomarker for the assessment of early testicular damage in varicoceles. The facet that the decrease of MTA1 expression appears much earlier than the beginning of apoptotic wave after heat stress warrants its theoretical rationality and technical accessibility for biochemical application. Basically, MTA1 participates in the maintenance of early apoptotic balance induced by hyperthermal stimulation by elevating the deacetylation level of p53, a master regulator responsible for the initial phase of germ cell apoptosis induced by hyperthermia. These knowledges collectively promote our belief that information from future experiments designed to further study MTA1 during spermatogenesis will provide a scientific basis for the development of a novel biomarker for early diagnosis of testicular detriment in varicoceles, which should lead to improved outcomes in this progressive pathology.

Highly Z-Selective Asymmetric Conjugate Addition of Alkynones with Pyrazol-5-ones Promoted by N,N'-Dioxide-Metal Complexes

Angewandte Chemie (International Ed. in English). Feb, 2012  |  Pubmed ID: 22307768

Highly selective: The title reaction is achieved with high enantiomeric and geometric control and thermodynamically unstable (Z)-enone derivatives are obtained as the major products. The procedure tolerates a wide range of substrates to generate optically active pyrazolones with vinyl-substituted quaternary stereocenters.

Linear Psoriasis

CMAJ : Canadian Medical Association Journal = Journal De L'Association Medicale Canadienne. Feb, 2012  |  Pubmed ID: 22311943

Oridonin Induces Apoptosis and Senescence by Increasing Hydrogen Peroxide and Glutathione Depletion in Colorectal Cancer Cells

International Journal of Molecular Medicine. Apr, 2012  |  Pubmed ID: 22294162

We recently demonstrated that oridonin could induce apoptosis and senescence of colon cancer cells in vitro and in vivo. However, the underlying mechanism remains unknown. In this study, the involvement of reactive oxygen species in oridonin-induced cell death and senescence was investigated in colon adenocarcinoma-derived SW1116 cells. Oridonin increased intracellular hydrogen peroxide levels and reduced the glutathione content in a dose-dependent manner. N-acetylcysteine, a reactive oxygen species scavenger, not only blocked the oridonin-induced increase in hydrogen peroxide and glutathione depletion, but also blocked apoptosis and senescence induced by oridonin, as evidenced by the decrease in Annexin V and senescence-associated β-galactosidase- positive cells and the inhibition of oridonin-induced upregulation of p53 and p16 and downregulation of c-Myc. Moreover, exogenous catalase could inhibit the increase in hydrogen peroxide and apoptosis induced by oridonin, but not the glutathione depletion and senescence. Furthermore, thioredoxin reductase (TrxR) activity was reduced by oridonin in vitro and in cells, which may cause the increase in hydrogen peroxide. In conclusion, the increase in hydrogen peroxide and glutathione depletion account for oridonin-induced apoptosis and senescence in colorectal cancer cells, and TrxR inhibition is involved in this process. Given the importance of TrxR as a novel cancer target in colon cancer, oridonin would be a promising clinical candidate. The mechanism of oridonin-induced inhibition of TrxR warrants further investigation.

[Observation on Therapeutic Effect of Acupuncture Combined with Medicine on Mild Cognition Disorders in Patients with Post-stroke]

Zhongguo Zhen Jiu = Chinese Acupuncture & Moxibustion. Jan, 2012  |  Pubmed ID: 22295811

To explore the curative effect and safety of acupuncture for mild cognitive disorders after stroke.

Early Prediction of Response to Vorinostat in an Orthotopic Rat Glioma Model

NMR in Biomedicine. Feb, 2012  |  Pubmed ID: 22302519

Glioblastoma is the most common primary brain tumor and is uniformly fatal despite aggressive surgical and adjuvant therapy. As survival is short, it is critical to determine the value of therapy early on in treatment. Improved early predictive assessment would allow neuro-oncologists to personalize and adjust or change treatment sooner to maximize the use of efficacious therapy. During carcinogenesis, tumor suppressor genes can be silenced by aberrant histone deacetylation. This epigenetic modification has become an important target for tumor therapy. Suberoylanilide hydroxamic acid (SAHA, Vorinostat, Zolinza) is an orally active, potent inhibitor of histone deacetylase (HDAC) activity. A major shortcoming of the use of HDAC inhibitors in the treatment of patients with brain tumors is the lack of reliable biomarkers to predict and determine response. Histological evaluation may reflect tumor viability following treatment, but is an invasive procedure and impractical for glioblastoma. Another problem is that response to SAHA therapy is associated with tumor redifferentiation and cytostasis rather than tumor size reduction, thus limiting the use of traditional imaging methods. A noninvasive method to assess drug delivery and efficacy is needed. Here, we investigated whether changes in (1) H MRS metabolites could render reliable biomarkers for an early response to SAHA treatment in an orthotopic animal model for glioma. Untreated tumors exhibited significantly elevated alanine and lactate levels and reduced inositol, N-acetylaspartate and creatine levels, typical changes reported in glioblastoma relative to normal brain tissues. The (1) H MRS-detectable metabolites of SAHA-treated tumors were restored to those of normal-like brain tissues. In addition, reduced inositol and N-acetylaspartate were found to be potential biomarkers for mood alteration and depression, which may also be alleviated with SAHA treatment. Our study suggests that (1) H MRS can provide reliable metabolic biomarkers at the earliest stage of SAHA treatment to predict the therapeutic response. Copyright © 2012 John Wiley & Sons, Ltd.

Discovery of Common Variants Associated with Low TSH Levels and Thyroid Cancer Risk

Nature Genetics. Jan, 2012  |  Pubmed ID: 22267200

To search for sequence variants conferring risk of nonmedullary thyroid cancer, we focused our analysis on 22 SNPs with a P < 5 × 10(-8) in a genome-wide association study on levels of thyroid stimulating hormone (TSH) in 27,758 Icelanders. Of those, rs965513 has previously been shown to associate with thyroid cancer. The remaining 21 SNPs were genotyped in 561 Icelandic individuals with thyroid cancer (cases) and up to 40,013 controls. Variants suggestively associated with thyroid cancer (P < 0.05) were genotyped in an additional 595 non-Icelandic cases and 2,604 controls. After combining the results, three variants were shown to associate with thyroid cancer: rs966423 on 2q35 (OR = 1.34; P(combined) = 1.3 × 10(-9)), rs2439302 on 8p12 (OR = 1.36; P(combined) = 2.0 × 10(-9)) and rs116909374 on 14q13.3 (OR = 2.09; P(combined) = 4.6 × 10(-11)), a region previously reported to contain an uncorrelated variant conferring risk of thyroid cancer. A strong association (P = 9.1 × 10(-91)) was observed between rs2439302 on 8p12 and expression of NRG1, which encodes the signaling protein neuregulin 1, in blood.

Impairment of Cellular Immunity is Associated with Overexpression of Heat Shock Protein 70 in Neonatal Pigs with Intrauterine Growth Retardation

Cell Stress & Chaperones. Jan, 2012  |  Pubmed ID: 22270614

Neonates with intrauterine growth retardation (IUGR) are susceptible to decreases in cellular immunity. In recent years, a growing body of evidence indicates that Hsp70 may serve as a danger signal to the innate immune system and promote receptor-mediated apoptosis. Using neonatal pigs with IUGR, we investigated immune function of pigs and expression of heat shock protein 70 (Hsp70), nuclear factor-kappa B (NF-κB), and forkhead box O 3a (FoxO3a) in the intestinal tract. Samples from the blood, duodenum, jejunum, and ileum of normal body weight (NBW) piglets and IUGR piglets were collected at day 7 after birth. Furthermore, to test whether Hsp70 is associated with regulation of NF-κB and FoxO3a, Hsp70 was silenced using small RNA interference (siRNA) in IEC-6 cells. Body and intestinal weights were lower in IUGR piglets than in NBW piglets (p < 0.05). Proliferation of peripheral blood lymphocytes was decreased (p < 0.05) in IUGR piglets. Cytokine concentrations (IFN-γ, IL-4, IL-10, IL-1, and IL-8) were lower in serum of IUGR piglets. The levels of IFN-γ and IL-10 were decreased (p < 0.05) in the ileum of IUGR piglets, but IL-4 was increased (p < 0.05). The expressions of Hsp70 and FoxO3a were increased, and NF-κB activity was downregulated in IUGR piglets (p < 0.05). Furthermore, siRNA-mediated Hsp70 downregulation increased NF-κB activity, inhibited expression of FoxO3a, and decreased cell apoptosis. In contrast, overexpression of Hsp70 inhibited NF-κB activation. In conclusion, IUGR impairs immune functions in neonatal pigs. An inefficient immunity in IUGR piglets is associated with overexpression of Hsp70, which impairs NF-κB signaling and upregulates FoxO3a expression.

Genetic Analysis of the P1 Region of Human Enterovirus 71 Strains and Expression of the 55 F StrainVP1 Protein

Virologica Sinica. Feb, 2012  |  Pubmed ID: 22270802

Enterovirus 71 (EV71) is a member of the Entero-virus genus of the Picornaviridae family and is the major cause of Hand, foot, and mouth disease (HFMD) in children. Different strains from Gansu were cloned and the P1 protein was sequenced and analysed. Results indicate that there are three kinds of EV71 infections prevalent in Gansu. The VP1 protein from one of these strains, 55F, was expressed. The recombinant protein was expressed with high level and reacted specifically with the EV71 patient antibody, the recombinant protein was also applied to raise antiserum in rabbits and after the fourth injection a high titer of antiserum was detected by ELISA assay. These data are useful for further clarification of prevalent EV71 strains in the north of China at the molecular level and provide a basis for EV71 diagnosis.

Highly Ordered Mesoporous Silica Films with Perpendicular Mesochannels by a Simple Stöber-Solution Growth Approach

Angewandte Chemie (International Ed. in English). Jan, 2012  |  Pubmed ID: 22271504

A simple solution: In the simple approach to silica films with perpendicular mesochannels presented herein, the substrate is immersed into a Stöber solution in which the silica precursors are hydrolyzed, cross-linked by an ammonia catalyst, and assembled with a surfactant on the substrate to form hexagonal mesostructures perpendicular to the substrate surface.

Rapid Conversion of Human ESCs into Mouse ESC-like Pluripotent State by Optimizing Culture Conditions

Protein & Cell. Jan, 2012  |  Pubmed ID: 22271597

The pluripotent state between human and mouse embryonic stem cells is different. Pluripotent state of human embryonic stem cells (ESCs) is believed to be primed and is similar with that of mouse epiblast stem cells (EpiSCs), which is different from the naïve state of mouse ESCs. Human ESCs could be converted into a naïve state through exogenous expression of defined transcription factors (Hanna et al., 2010). Here we report a rapid conversion of human ESCs to mouse ESC-like naïve states only by modifying the culture conditions. These converted human ESCs, which we called mhESCs (mouse ESC-like human ESCs), have normal karyotype, allow single cell passage, exhibit domed morphology like mouse ESCs and express some pluripotent markers similar with mouse ESCs. Thus the rapid conversion established a naïve pluripotency in human ESCs like mouse ESCs, and provided a new model to study the regulation of pluripotency.

The Healing Process of Intracorporeally and in Situ Devitalized Distal Femur by Microwave in a Dog Model and Its Mechanical Properties in Vitro

PloS One. 2012  |  Pubmed ID: 22276207

Limb-salvage surgery has been well recognized as a standard treatment and alternative to amputation for patients with malignant bone tumors. Various limb-sparing techniques have been developed including tumor prosthesis, allograft, autograft and graft-prosthesis composite. However, each of these methods has short- and long-term disadvantages such as nonunion, mechanical failures and poor limb function. The technique of intracorporeal devitalization of tumor-bearing bone segment in situ by microwave-induced hyperthermia after separating it from surrounding normal tissues with a safe margin is a promising limb-salvage method, which may avoid some shortcomings encountered by the above-mentioned conventional techniques. The purpose of this study is to assess the healing process and revitalization potential of the devitalized bone segment by this method in a dog model. In addition, the immediate effect of microwave on the biomechanical properties of bone tissue was also explored in an in vitro experiment.

Identification of Liguzinediol Metabolites in Rats by Ultra Performance Liquid Chromatography/quadrupole-time-of-flight Mass Spectrometry

Journal of Pharmaceutical and Biomedical Analysis. Jan, 2012  |  Pubmed ID: 22277354

Ultra performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC/QTOF MS) was employed to investigate the in vivo metabolism of liguzinediol. Urine, bile, feces and plasma samples were collected after intravenous administration of 10mg/kg liguzinediol to healthy rats. Altogether seven metabolites were detected and tentatively identified based on the characteristics of their protonated ions. The metabolites were mainly transformed by four main metabolic pathways including oxidation, sulfation, glycine conjugation and glucuronidation.

Applicability of Accelerated Solvent Extraction for Synthetic Colorants Analysis in Meat Products with Ultrahigh Performance Liquid Chromatography-photodiode Array Detection

Analytica Chimica Acta. Feb, 2012  |  Pubmed ID: 22284887

Accelerated solvent extraction (ASE) coupled with ultrahigh performance liquid chromatography (UHPLC) with photodiode array detection (PDA) has been used for the quantitative determination of synthetic colorants in meat products. Samples were extracted with ethanol-water-ammonia with a ratio of 75:24:1 (v/v/v) using ASE instrument at 85°C. As a result, all the colorants in meat products were separated using an optimized gradient elution within 3.5min. Detection and quantification limits of synthetic colorants were in the ranges of 0.01-0.02mgkg(-1) and 0.05mgkg(-1), respectively. The intra-day and inter-day precision of the synthetic colorants were ranged between 1.7% (E123) to 5.2% (E124) and 3.2% (E124) to 6.0% (E129), respectively. The intra-day and inter-day recoveries of the synthetic colorants were ranged between 76.9% (E124) to 84.9% (E102) and 76.3% (E124) to 84.3% (E127), respectively. The method has been applied for the determination of seven synthetic colorants in meat products.

Dl-3n-butylphthalide Promotes Angiogenesis Via the Extracellular Signal-regulated Kinase 1/2 and Phosphatidylinositol 3-kinase /Akt- Endothelial Nitric Oxide Synthase Signaling Pathways

Journal of Cardiovascular Pharmacology. Jan, 2012  |  Pubmed ID: 22286127

ABSTRACT: We have previously demonstrated that dl-3n-butylphthalide (NBP) has a potential angiogenic activity. In this study, we investigated the angiogenic effect of NBP and the molecular mechanisms underlying NBP-mediated angiogenesis. Zebrafish embryos and human umbilical vein endothelial cells (HUVEC) were treated with various doses of NBP and several signaling pathway inhibitors. NBP induced ectopic subintestinal vessel production in zebrafish embryos and induced invasion, migration and endothelial cell tube formation of HUVEC in a dose-dependent manner. These NBP-induced angiogenic effects were partially suppressed by SU5402, a fibroblast growth factor receptor 1 (FGFR-1) inhibitor; U0126, an extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor; LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor; 1L6-hydroxymethyl-chiro-inositol-2-(R)-2-O-methyl-3-O-octadecyl-sn-glycerocarbonate, an Akt inhibitor; Cavtratin, an eNOS inhibitor and completely inhibited by a combination of U0126 and LY294002. NBP enhanced phosphorylation of ERK1/2 and FGF-2 expression, which were inhibited by U0126. NBP increased phosphorylation of Akt and endothelial nitric oxide synthase at serine 1177, which were blocked by LY294002. NBP stimulated nitric oxide production, which was reduced by LY294002. Our data demonstrated that 1) NBP promoted angiogenesis and 2) the angiogenic effects of NBP were mediated by the ERK1/2 and PI3K/Akt-eNOS signaling pathways. Our findings suggest that NBP could be a novel agent for therapeutic angiogenesis in ischemic diseases.

Cluster Randomised Trials of Prescription Medicines or Prescribing Policy- Public and General Practitioner Opinions in Scotland

British Journal of Clinical Pharmacology. Jan, 2012  |  Pubmed ID: 22288609

Aims:  To understand public and general practitioner (GP) opinion on the acceptability of randomised policy design (RPD) studies (cluster randomised trials) of prescription medicines in Scotland. Methods:  We surveyed public opinion on the concept of RPD studies in a sample of 1,040 adults to determine acceptability and understand how people feel when changes are made to their medicines. We also surveyed GPs (n=1,034) about the concept of RPD studies as a tool for improving understanding of comparative effectiveness and safety of medicines in the 'usual care' setting. Results:  30% of people would be happy to receive a letter about randomised policy changes to their therapy, 31% would not mind or had no opinion and 39% would be unhappy. This view was sensitive to the reason for change; effectiveness and safety reasons were most acceptable (96%) and cost saving least acceptable (39%). Only 19% thought randomised policy change was not an acceptable method of determining the best treatments. 81% of respondents were willing for their medical data to be followed up to compare drug treatments (further 10% undecided). Participants reporting long-term medical conditions and those reporting previous changes to drug therapy were more in favour of RPD studies than other participants. 33% (n=341) of GPs responded to our survey. 45% were in favour of RPD studies, 19% were undecided and 36% not in favour. Conclusions:  The public in Scotland is broadly supportive of the concept of randomised policy design studies of medicines, while there is a spread of opinion among GPs. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Magnetic Spherical Cores Partly Coated with Periodic Mesoporous Organosilica Single Crystals

Nanoscale. Jan, 2012  |  Pubmed ID: 22290196

Core-shell structured materials are of special significance in various applications. Until now, most reported core-shell structures have polycrystalline or amorphous coatings as their shell layers, with popular morphologies of microspheres or quasi-spheres. However, the single crystals, either mesoscale or atomic ones, are still rarely reported as shell layers. If single crystals can be coated on core materials, it would result in a range of new type core-shell structures with various morphologies, and probably more potential applications. In this work, we demonstrate that periodic mesoporous organosilica (PMO) single crystals can partly grow on magnetic microspheres to form incomplete Fe(3)O(4)@nSiO(2)@PMO core-shell materials in aqueous solution, which indeed is the first illustration that mesoporous single-crystal materials can be used as shell layers for preparation of core-shell materials. The achieved materials have advantages of high specific surface areas, good magnetic responses, embedded functional groups and cubic mesopore channels, which might provide them with various application conveniences. We suppose the partial growth is largely decided by the competition between growing tendency of single crystals and the resistances to this tendency. In principle, other single crystals, including a range of atomic single crystals, such as zeolites, are able to be developed into such core-shell structures.

Caveolin Targeting to Late Endosome/Lysosomal Membranes is Induced by Perturbations of Lysosomal PH and Cholesterol Content

Molecular Biology of the Cell. Jan, 2012  |  Pubmed ID: 22238363

Caveolin-1 is an integral membrane protein of plasma membrane caveolae. Here we report that caveolin-1 collects at the cytosolic surface of lysosomal membranes when cells are serum starved. This is due to an elevation of the intra-lysosomal pH since ionophores and proton pump inhibitors that dissipate the lysosomal pH gradient also trapped caveolin-1 on late endosome/lysosomes. Accumulation is both saturable and reversible. At least a portion of the caveolin-1 goes to the plasma membrane upon reversal. Several studies suggest that caveolin-1 is involved in cholesterol transport within the cell. Strikingly, we find that blocking cholesterol export from lysosomes with progesterone or U18666A or treating cells with low concentrations of cyclodextrin also caused caveolin-1 to accumulate on late endosome/lysosomal membranes. Under these conditions however, live cell imaging shows cavicles actively docking with lysosomes, suggesting these structures may be involved in delivering caveolin-1. Targeting of caveolin-1 to late endosome/lysosomes is not observed normally and the degradation rate of caveolin-1 is not altered by any of these conditions indicating that caveolin-1 accumulation is not a consequence of blocked degradation. We conclude that caveolin-1 normally traffics to and from the cytoplasmic surface of lysosomes during intracellular cholesterol trafficking.

MiR-200a is Involved in Rat Epididymal Development by Targeting β-catenin MRNA

Acta Biochimica Et Biophysica Sinica. Jan, 2012  |  Pubmed ID: 22240259

The expression of 350 microRNAs (miRNAs) in epididymis of rat from postnatal development to adult (from postnatal days 7-70) was profiled with home-made miRNA microarray. Among them, 48 miRNAs changed significantly, in which the expression of miR-200a increased obviously with time, in a good agreement with that obtained from northern blot analysis. The real-time quantitative-polymerase chain reaction result indicated that temporal expression of rat β-catenin was exactly inversed to that of miR-200a during rat epididymal development, implying that miR-200a might also target β-catenin mRNA in rat epididymis as reported by Saydam et al. in humans. The bioinformatic analysis indicated that 3' untranslated region of rat β-catenin mRNA did contain a putative binding site for miR-200a. Meanwhile, it was found that the sequence of this binding site was different from that of human β-catenin mRNA with a deletion of two adjacent nucleotides (U and C). But the results of luciferase targeting assay in HEK 293T cells and the overexpression of miR-200a in rat NRK cells demonstrated that miR-200a did target rat β-catenin mRNA and cause the suppression of its expression. All these results show that miR-200a should be involved in rat epididymal development by targeting β-catenin mRNA of rat and suppressing its expression.

Kinetics and Mechanism of G-quadruplex Formation and Conformational Switch in a G-quadruplex of PS2.M Induced by Pb2+

Nucleic Acids Research. Jan, 2012  |  Pubmed ID: 22241774

DNA sequences with guanine repeats can form G-quartets that adopt G-quadruplex structures in the presence of specific metal ions. Using circular dichroism (CD) and ultraviolet-visible (UV-Vis) spectroscopy, we determined the spectral characteristics and the overall conformation of a G-quadruplex of PS2.M with an oligonucleotide sequence, d(GTG(3)TAG(3)CG(3)TTG(2)). UV-melting curves demonstrate that the Pb(2+)-induced G-quadruplex formed unimolecularly and the highest melting temperature (T(m)) is 72°C. The analysis of the UV titration results reveals that the binding stoichiometry of Pb(2+) ions to PS2.M is two, suggesting that the Pb(2+) ions coordinate between adjacent G-quartets. Binding of ions to G-rich DNA is a complex multiple-pathway process, which is strongly affected by the type of the cations. Kinetic studies suggest that the Pb(2+)-induced folding of PS2.M to G-quadruplex probably proceeds through a three-step pathway involving two intermediates. Structural transition occurs after adding Pb(NO(3))(2) to the Na(+)- or K(+)-induced G-quadruplexes, which may be attributed to the replacement of Na(+) or K(+) by Pb(2+) ions and the generation of a more compact Pb(2+)-PS2.M structure. Comparison of the relaxation times shows that the Na(+)→Pb(2+) exchange is more facile than the K(+)→Pb(2+) exchange process, and the mechanisms for these processes are proposed.

Novel Tfap2-mediated Control of SoxE Expression Facilitated the Evolutionary Emergence of the Neural Crest

Development (Cambridge, England). Feb, 2012  |  Pubmed ID: 22241841

Gene duplication has been proposed to drive the evolution of novel morphologies. After gene duplication, it is unclear whether changes in the resulting paralogs' coding-regions, or in their cis-regulatory elements, contribute most significantly to the assembly of novel gene regulatory networks. The Transcription Factor Activator Protein 2 (Tfap2) was duplicated in the chordate lineage and is essential for development of the neural crest, a tissue that emerged with vertebrates. Using a tfap2-depleted zebrafish background, we test the ability of available gnathostome, agnathan, cephalochordate and insect tfap2 paralogs to drive neural crest development. With the exception of tfap2d (lamprey and zebrafish), all are able to do so. Together with expression analyses, these results indicate that sub-functionalization has occurred among Tfap2 paralogs, but that neo-functionalization of the Tfap2 protein did not drive the emergence of the neural crest. We investigate whether acquisition of novel target genes for Tfap2 might have done so. We show that in neural crest cells Tfap2 directly activates expression of sox10, which encodes a transcription factor essential for neural crest development. The appearance of this regulatory interaction is likely to have coincided with that of the neural crest, because AP2 and SoxE are not co-expressed in amphioxus, and because neural crest enhancers are not detected proximal to amphioxus soxE. We find that sox10 has limited ability to restore the neural crest in Tfap2-deficient embryos. Together, these results show that mutations resulting in novel Tfap2-mediated regulation of sox10 and other targets contributed to the evolution of the neural crest.

Growth Mechanisms of Fluorescent Silver Clusters Regulated by Polymorphic DNA Templates: a DFT Study

The Journal of Physical Chemistry. B. Feb, 2012  |  Pubmed ID: 22242908

The aggregation behaviors of silver atoms modulated by polymorphic DNA templates involving i-motif, G-quadruplex, and the Watson-Crick duplex, were investigated by using the density functional theory (DFT) calculations, combining with the experimental characterizations of CD, UV, fluorescence measurements and TEM, in order to understand the reason in the molecular level that polymorphic DNA templates affect the fluorescence emitting species of Ag nanomaterials. First, the affinity sites of silver ions on different DNA templates were analyzed by using DFT calculations, and the conformational variations of DNA templates caused by silver ions and atoms were disclosed. Second, the aggregation behaviors of silver atoms constrained by the polymorphic DNA templates were studied by DFT modeling, and distinct fluorescence property of nanosilvers templated by polymorphic DNA were evaluated using the time-dependent DFT calculations. It is illustrated that with the DNA template adopting i-motif or the duplex the silver atoms tend to aggregate inside the encapsulated spaces of nucleobases, and the formed silver nanoclusters are positively charged with high fluorescent spectral features; whereas with the template of the G-quadruplex the silver atoms are preferential to aggregate outside of the G-tetrad, which results in the formation of larger silver crystals without fluorescence property. The results obtained here are useful to explore the nucleation and growth mechanism of silver nanomaterials regulated by the structure-specific DNA templates, which is important to rational design of desirable fluorescent emitters for sensing in the field from biology to nanoscience.

Effect of Statins on Total Cholesterol Concentrations, Cardiovascular Morbidity, and All-cause Mortality in Chronic Obstructive Pulmonary Disease: a Population-based Cohort Study

Clinical Therapeutics. Feb, 2012  |  Pubmed ID: 22244052

The benefit of statin use on total cholesterol (TC) concentration has not been studied previously in patients with chronic obstructive pulmonary disease (COPD).

Novel Polymer-Layered Silicate Intercalated Composite Beads for Drug Delivery

Journal of Biomaterials Science. Polymer Edition. Jan, 2012  |  Pubmed ID: 22244298

Core-shell structured beads were fabricated from chitosan (CS)/organic rectorite (OREC) composites and alginate (ALG) in Ca(2+) aqueous solutions with different mixing ratios by a cross-linking process. The mechanical properties, surface and internal morphology, intercalation structure between CS and OREC, porosity and pore size distribution, bovine serum albumin (BSA) encapsulation efficiency and its controllable release ability were investigated. Optical microscopy, scanning electron microscopy and transmission electron microscopy showed that the core-shell structure was generated in the beads. The Fourier transform infrared spectra results implied the presence of electrostatic and hydrogen-bonding interaction between CS and OREC. The energy-dispersive X-ray and X-ray photoelectron spectroscopy results verified the existence of OREC in the beads. Small-angle X-ray diffraction results confirmed that the interlayer of OREC was intercalated by CS chains successfully, and the interlayer distance increased from 2.42 to 2.60 nm. The BSA encapsulation and release test indicated that the beads released the drug continuously. OREC could not only avoid the burst release phenomenon in the first period bust also improve the utilization efficacy of the drug. When the ratio of CS/OREC was 6:1 and CS-OREC/ALG was 2:1, the beads were better for drug released in stomach, and when CS/OREC was 12:1 and CS-OREC/ALG was 2:1, the beads were better for drug released in stomach than in intestine.

Meta-analysis for Cyclin E in Lung Cancer Survival

Clinica Chimica Acta; International Journal of Clinical Chemistry. Jan, 2012  |  Pubmed ID: 22244930

BACKGROUND: To assess the prognosis value of cyclin E expression in survival of patients with lung cancer (LC), we performed a systematic review of the literature with meta-analysis. METHODS: Electronic databases were used to identify published studies before August 2011. Pooled hazard ratio (HR) with 95% confidence interval (95% CI) was used to estimate the strength of the association of cyclin E expression with survival of LC patients. Heterogeneity and publication bias were also assessed. RESULTS: Fourteen studies (2606 cases) were eligible and subjected to analysis. Cyclin E over-expression was found to be a strong predictor of poor prognosis in LC patients (HR: 1.38, 95% CI: 1.07-1.79; P=0.014). When only non-small cell lung cancer (NSCLC) was considered, the combined HR was 1.53 (95% CI: 1.19-1.97, P=0.001). A significant association was also evident when the analysis was limited to studies involving adenocarcinoma (AD), but not squamous cell carcinoma (SQ). Publication bias was absent. Sensitivity analyses suggested that the summary statistics obtained should approximate the actual average.

Induction of Activation of the Antioxidant Response Element and Stabilization of Nrf2 by 3-(3-pyridylmethylidene)-2-indolinone (PMID) Confers Protection Against Oxidative Stress-induced Cell Death

Toxicology and Applied Pharmacology. Jan, 2012  |  Pubmed ID: 22245129

The antioxidant response elements (ARE) are a cis-acting enhancer sequence located in regulatory regions of antioxidant and detoxifying genes. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a member of the Cap 'n' Collar family of transcription factors that binds to the ARE and regulates the transcription of specific ARE-containing genes. Under oxidative stress, Nrf2/ARE induction is fundamental to defense against reactive oxygen species (ROS) and serves as a key factor in the protection against toxic xenobiotics. 3-(3-Pyridylmethylidene)-2-Indolinone (PMID) is a derivative of 2-indolinone compounds which act as protein kinase inhibitors and show anti-tumor activity. However, the role of PMID in the oxidative stress remains unknown. In the present study, we showed that PMID induced the activation of ARE-mediated transcription, increased the DNA-binding activity of Nrf2 and then up-regulated the expression of antioxidant genes such as HO-1, SOD, and NQO1. The level of Nrf2 protein was increased in cells treated with PMID by a post-transcriptional mechanism. Under CHX treatment, the stability of Nrf2 protein was enhanced by PMID with decreased turnover rate. We showed that PMID reduced the ubiquitination of Nrf2 and disrupted the Cullin3 (Cul3)-Keap1 interaction. Furthermore, cells treated with PMID showed resistance to cytotoxicity by H(2)O(2) and pro-oxidant 6-OHDA. PMID also up-regulated the antioxidant level in BALB/c mice. Taken together, the compound PMID induces the ARE-mediated gene expression through stabilization of Nrf2 protein and activation of Nrf2/ARE pathway and protects against oxidative stress-mediated cell death.

Marital Status, Education, and Risk of Acute Myocardial Infarction in Mainland China: The INTER-HEART Study

Journal of Epidemiology / Japan Epidemiological Association. Jan, 2012  |  Pubmed ID: 22245707

Background: We investigated the effects of marital status and education on the risk of acute myocardial infarction (AMI) in a large-scale case-control study in China.Methods: This study was part of the INTER-HEART China case-control study. The main outcome measure was first AMI. Incident cases of AMI and control patients with no past history of heart disease were recruited. Controls were matching by age (±5 years) and sex. Marital status was combined into 2 categories: single and not single. Education level was classified into 2 categories: 8 years or less and more than 8 years.Results: From 1999 to 2002, we recruited 2909 cases and 2947 controls from 17 cities. After adjustment for age, sex, BMI, psychosocial factors, lifestyle, other factors, and mutually for other risk factors, the odds ratio (OR) for AMI associated with being single was 1.51 (95% confidence interval: 1.18-1.93) overall, 1.19 (0.84-1.68; P = 0.072) in men and 2.00 (1.39-2.86; P < 0.0001) in women. The interaction of sex and marital status was statistically significant (P = 0.045). Compared with a high education level, a low education level increased the risk of AMI (1.45, 1.26-1.67); the odds ratios in men and women were 1.29 (1.09-1.52) and 1.55 (1.16-2.08), respectively. Single women with a low education level had a high risk of AMI (2.95, 1.99-4.37).Conclusions: Being single was consistently associated with an increased risk for AMI, particularly in women. In addition, as compared with high education level, low education level was associated with a higher risk of AMI in both men and women.

Epidemiology of 1974 Burn Patients at a Major Burn Center in Beijing: A 9-Year Study

Journal of Burn Care & Research : Official Publication of the American Burn Association. Jan, 2012  |  Pubmed ID: 22245803

To date, little epidemiological data are available on burns in China. This study describes the characteristics of burn patients admitted to a major burn center in Beijing to show trends in admission and outcomes in burned patients to share information about the current state of care for burned patients in our burn center. A retrospective study on 1974 burn patients admitted to Jishuitan Hospital in Beijing was conducted during the 9-year period from 2000 to 2008, and data were collected on age, gender, TBSA, etiology, length of hospital stay, mortality, and inhalation injury. The male:female ratio of the burn population was 2.41:1 and did not differ significantly over the study period (P > .05). The mean age of admission was 36 ± 16.3 years, and most patients were 30 to 39 years old (24.0%) or 20 to 29 years old (23.8%). The mean TBSA of burn was 14.7 ± 3.4%, ranging from 1 to 100%, and the mean size/age did not change significantly over the course of the study (P > .05). The incidence in burn injury decreased over the study period (P < .05). The most common cause of burn was flame (67.9%) followed by electrical (16.1%) and scald (9.5%). The mean length of hospital stay was 33.2 ± 3.5 days, extending from 1 to 413 days, and it did not differ significantly over the study period (P > .05). The mortality and inhalation injury rate were 2.8 and 6.9%, respectively. Annual mortality rate did not differ significantly over the study period (P > .05). This retrospective review of the specific epidemiological features of burn patients will provide important information for the development of proper control programs to reduce the incidence of burns and burn-related deaths.

Changes in T Lymphocyte Subsets and Intracellular Cytokines After Transfer of Chemically Extracted Acellular Nerve Allografts

Molecular Medicine Reports. Apr, 2012  |  Pubmed ID: 22245851

The aim of the present study was to observe the immune mechanism underlying the rejection of chemically extracted acellular nerve allografts for use in clinical applications. A total of 128 BALB/c mice were randomly divided into a negative contrast group (NC, 32 mice), a fresh autograft group (AG, 32 mice), a fresh allogeneic nerve group (FN, 32 mice) and a chemically extracted acellular allogeneic nerve group (CEN, 32 mice). Various types of nerve grafts were implanted into the thigh muscle of BALB/C mice in the corresponding groups. At 3, 7, 14 and 28 days post-operation, the mice (8 cases from each group) were sacrificed and their spleens were extracted. The spleens were ground into paste. The erythrocytes and other cells were lysed using distilled water and the T lymphocytes were collected. Monoclonal antibodies (CD3, CD4, CD8, CD25, IL-2, IFN-γ and TNF-α) were then added to the solution. The Facial Action Coding System was used to determine the positive rates of the cells combined with the monoclonal antibodies above. No significant statistical differences were observed between the CEN, NC and AG groups. However, some data of the FN group were significantly higher than those of the other groups at the corresponding time. No obvious immune rejections were observed among the chemically extracted acellular nerve allografts compared with fresh nerve autograft.

Transcriptional Regulation of Arabidopsis MIR168a and ARGONAUTE1 Homeostasis in ABA and Abiotic Stress Responses

Plant Physiology. Jan, 2012  |  Pubmed ID: 22247272

The accumulation of a number of small RNAs in plants is affected by abscisic acid (ABA) and abiotic stresses, but the underlying mechanisms are poorly understood. The miR168-mediated feedback regulatory loop regulates ARGONAUTE1 (AGO1) homeostasis, which is crucial for gene expression modulation and plant development. Here we revealed a transcriptional regulatory mechanism by which MIR168 controls AGO1 homeostasis during ABA treatment and abiotic stress responses in Arabidopsis thaliana. Plants overexpressing MIR168a and the AGO1 loss-of-function mutant (ago1-27) display ABA hypersensitivity and drought tolerance, while the mir168a-2 mutant shows ABA hyposensitivity and drought hypersensitivity. Both the precursor and mature miR168 were induced under ABA and several abiotic stress treatments, but no obvious decrease for the target of miR168, AGO1, was shown under the same conditions. However, promoter activity analysis indicated that AGO1 transcription activity was increased under ABA and drought treatments, suggesting that transcriptional elevation of MIR168a is required for maintaining a stable AGO1 transcript level during the stress response. Furthermore, we showed both in vitro and in vivo that the transcription of MIR168a is directly regulated by four ABA-responsive element (ABRE) binding factors (ABF1-4), which bind to the ABRE cis-element within the MIR168a promoter. This ABRE motif is also found in the promoter of MIR168a homologs in diverse plant species. Our findings suggest that transcriptional regulation of miR168 and post-transcriptional control of AGO1 homeostasis may play an important and conserved role in stress response and signal transduction in plants.

Design and Synthesis of 2-Iminothiazolidin-4-one Moiety-Containing Compounds As Potent Antiproliferative Agents

Archiv Der Pharmazie. Jan, 2012  |  Pubmed ID: 22223396

A new series of 2,5-diaryliminothiazolidin-4-ones were designed and synthesized as potent antiproliferative agents. The antiproliferative activities of the 25 target compounds were evaluated against three cancer cell lines (A549, H460 and HT29) by MTT assay. Pharmacological data indicated that most of the compounds possessed moderate activity, some showed remarkable activity against one or more cell lines. As the most promising compound, 8s (with IC(50) values of 1.1, 0.01 and 1.3 µM against the A549, H460 and HT29 cell lines) was 1.1- to 270-fold more potent than the reference drug sorafenib. Furthermore, preliminary structure-activity relationships (SARs) were summarized to provide guidance for further design and discovery of 2-iminothiazolidin-4-one-based antiproliferative agents.

Serum Levels of Interleukin (IL)-18, IL-23 and IL-17 in Chinese Patients with Multiple Sclerosis

Journal of Neuroimmunology. Feb, 2012  |  Pubmed ID: 22230485

It has been reported that cytokines play an important role in the pathogenesis of multiple sclerosis (MS). The aim of this study was to evaluate the serum levels of interleukin (IL)-18, IL-23 and IL-17 in Chinese patients with MS. We compared the serum concentrations of pro-inflammatory cytokines IL-18, IL-23 and IL-17 in 39 patients with MS and 39 healthy controls matched with sex and age. Serum cytokines were measured by FlowCytomix, a kind of cytometric bead-based assay. Correlations between the serum levels of the three cytokines and disability (expanded disability status scale, EDSS), disease duration, current age and age at onset were examined. Serum concentrations of all IL-18, IL-23 and IL-17 were significantly higher in MS patients than healthy controls. There were no significant differences of the three cytokines' levels between female and male healthy controls, while the serum IL-18 level was observed significantly higher (P=0.049) in male MS patients than female MS patients. No significant correlations were observed between any of the three cytokines' levels and EDSS, disease duration and current age. However, IL-23 was found negatively correlated with age at onset in male MS patients (r(s)=-0.775, P=0.041). Our data suggest that all IL-18, IL-23 and IL-17 may be involved in the pathogenesis of MS. However, the relationships of the three cytokines and clinical characteristics of MS need to be further investigated in the future.

Dioscin Induces Cancer Cell Apoptosis Through Elevated Oxidative Stress Mediated by Downregulation of Peroxiredoxins

Cancer Biology & Therapy. Feb, 2012  |  Pubmed ID: 22231406

Dioscin has been shown to promote anti-cancer activity against several forms of cancers. However, its detailed molecular mechanisms have not been clearly clarified.In this study, we demonstrate that dioscin induces apoptosis in cancer cells through the induction of oxidative stress. Treatment with cancer cells in vitro with dioscin resulted in rapid generation of reactive oxygen species (ROS) and the induction of mitochondrial pathway apoptosis in human esophageal cancer cell line Kyse510. Inhibition of oxidative stress by the antioxidant N-acetylcysteine blocked the induction of apoptosis by dioscin, indicating that ROS generation is the primary mechanism responsible for the proapoptotic activity of dioscin. Proteomic analysis and Western blotting further revealed peroxiredoxins 1and 6 (PRDX 1 and 6), which are implicated in ROS metabolism and apoptosis, were associated with the anti-cancer effects of dioscin. Meanwhile, overexpression of PRDX 1 and 6 significantly blocked the elevated ROS and apoptosis induced by dioscin. In conclusion, we suggest that PRDX1 and PRDX6 are key targets in the process of dioscin-induced apoptosis that involves intracellular elevated ROS.

General and Controllable Synthesis of Novel Mesoporous Magnetic Iron Oxide@carbon Encapsulates for Efficient Arsenic Removal

Advanced Materials (Deerfield Beach, Fla.). Jan, 2012  |  Pubmed ID: 22213225

A facile ammonia-atmosphere pre-hydrolysis post-synthetic route that can uniformly and selectively deposit Fe(2) O(3) nanoparticles in the predefined mesopores (5.6 nm) of a bimodal (2.3, 5.6 nm) mesoporous carbon matrix is demonstrated. The mesoporous magnetic Fe(2) O(3) @C encapsulates show excellent performance for arsenic capture with remarkable adsorption capacity, fast uptake rate, easy magnetic separation, and good cyclic stability.

Hyperglycemia As a Mechanism of Pancreatic Cancer Metastasis

Frontiers in Bioscience : a Journal and Virtual Library. 2012  |  Pubmed ID: 22201834

As a vital step in the progression of cancer, metastasis poses the largest problem in cancer treatment and is the main cause of death of cancer patients. In pancreatic cancer, almost 80% of patients have locally deteriorated or metastatic disease and thus are not appropriate for resection at the time of diagnosis. Due to the high rate of incidence and mortality, it is crucial to study the molecular mechanisms of metastasis to clarify therapeutic targets to hinder the spread of cancer. Diabetes mellitus has long been considered a potential risk factor for pancreatic cancer. In this review, we comprehensively describe the role of hyperglycemia in governing critical steps of the metastatic process. In particular, we focus on the hyperglycemia-dependent aspects of the Epithelial-Mesenchymal Transition (EMT) and vascular dysfunction. Furthermore, we discuss how hyperglycemia-related production of reactive oxygen species (ROS) may play an important role in these two processes. A deep understanding of metastasis mechanisms will identify novel targets for therapeutic intervention.

Research Resource: The Estrogen Receptor α Cistrome Defined by DamIP

Molecular Endocrinology (Baltimore, Md.). Feb, 2012  |  Pubmed ID: 22207717

Gene expression is tightly regulated by transcription factors and cofactors that function by directly or indirectly interacting with DNA of the genome. Understanding how and where these proteins bind provides essential information to uncover genetic regulatory mechanisms. We have developed a new method to study DNA-protein interaction in vivo called DNA adenine methyltransferase (Dam)IP, which is based on fusing a protein of interest to a mutant form of Dam from Escherichia coli. We showed previously that DamIP can efficiently identify in vivo binding sites of Dam-tethered human estrogen receptor (hER)α. In current study, we present the cistrome of hERα determined by DamIP and high throughput sequencing (DamIP-seq). The DamIP-seq-defined hERα cistrome identifies many new binding regions and overlaps with those determined by chromatin immunoprecipitation (ChIP)-chip or ChIP-seq. Elements uniquely identified by DamIP-seq include a unique class of elements that show low, but persistent, hERα binding when reexamined by conventional ChIP. In contrast, DamIP-seq fails to detect some elements with very transient hERα binding. The methyl-adenine modifications introduced by Dam are stable and do not decrease over 12 d. In summary, the current study provides both an alternate view of the hERα cistrome to further understand the mechanism of hERα-mediated transcription and a new tool to explore other transcriptional factors and cofactors that is very different from conventional ChIP.

Unraveling the Molecular Mystery of Retinal Pigment Epithelium Phagocytosis

Advances in Experimental Medicine and Biology. 2012  |  Pubmed ID: 22183395

The Neural Basis of Impossible Figures: Evidence from an FMRI Study of the Two-pronged Trident

Neuroscience Letters. Feb, 2012  |  Pubmed ID: 22178858

In the present study, we used the two-pronged trident task to investigate the neural basis of impossible figures processing by using event-related functional magnetic resonance imaging (fMRI). Our fMRI results showed that there were no brain regions with significantly stronger responses to possible condition than to impossible condition. However, impossible condition showed significantly more activation in the right inferior temporal gyrus (ITG), the fusiform gyrus (FG) and the right superior parietal gyrus (SPG). The right SPG in the dorsal visual pathway might be related to spatial information processing and the right lateral occipital complex (LOC) (FG and ITG) in the ventral visual pathway (the object-selective regions) might be related to the representation of the impossible 3D structure. Therefore, our results indicated that the impossible 3D structure might be difficult to be represented by human visual system, and the impossible perception might be derived from the detecting and resolving the contradiction in the subjects' interpretations according to different perceptions triggered by 3D cues.

Selective Degeneration of Synapses in the Dorsal Cochlear Nucleus of Chinchilla Following Acoustic Trauma and Effects of Antioxidant Treatment

Hearing Research. Jan, 2012  |  Pubmed ID: 22178982

The purpose of this study was to reveal synaptic plasticity within the dorsal cochlear nucleus (DCN) as a result of noise trauma and to determine whether effective antioxidant protection to the cochlea can also impact plasticity changes in the DCN. Expression of synapse activity markers (synaptophysin and precerebellin) and ultrastructure of synapses were examined in the DCN of chinchilla 10 days after a 105 dB SPL octave-band noise (centered at 4 kHz, 6 h) exposure. One group of chinchilla was treated with a combination of antioxidants (4-hydroxy phenyl N-tert-butylnitrone, N-acetyl-l-cysteine and acetyl-l-carnitine) beginning 4 h after noise exposure. Down-regulated synaptophysin and precerebellin expression, as well as selective degeneration of nerve terminals surrounding cartwheel cells and their primary dendrites were found in the fusiform soma layer in the middle region of the DCN of the noise exposure group. Antioxidant treatment significantly reduced synaptic plasticity changes surrounding cartwheel cells. Results of this study provide further evidence of acoustic trauma-induced neural plasticity in the DCN and suggest that loss of input to cartwheel cells may be an important factor contributing to the emergence of hyperactivity in the DCN after noise exposure. Results further suggest that early antioxidant treatment for acoustic trauma not only rescues cochlear hair cells, but also has impact on central auditory structures.

Global Emission of Black Carbon from Motor Vehicles from 1960 to 2006

Environmental Science & Technology. Jan, 2012  |  Pubmed ID: 22185218

Black carbon (BC) is a key short-lived climate change forcer. Motor vehicles are important sources of BC in the environment. BC emission factors (EF(BC)), defined as BC emitted per mass of fuel consumed, are critical in the development of BC emission inventories for motor vehicles. However, measured EF(BC) for motor vehicles vary in orders of magnitude, which is one of the major sources of uncertainty in the estimation of emissions. In this study, the main factors affecting EF(BC) for motor vehicles were investigated based on 385 measured EF(BC) collected from the literature. It was found that EF(BC) for motor vehicles of a given year in a particular country can be predicted using gross domestic product per capita (GDP(c)), temperature, and the year a country's GDP(c) reached 3000 USD (Y(3000)). GDP(c) represents technical progress in terms of emission control, while Y(3000) suggest the technical transfer from developed to developing countries. For global BC emission calculations, 87 and 64% of the variation can be eliminated for diesel and gasoline vehicles by using this model. In addition to a reduction in uncertainty, the model can be used to develop a global on-road vehicle BC emission inventory with spatial and temporal resolution.

Effects of Short- and Long-term Hypercholesterolemia on Contrast-induced Acute Kidney Injury

American Journal of Nephrology. 2012  |  Pubmed ID: 22189165

Background: Whether hypercholesterolemia is a risk factor for contrast-induced acute kidney injury (CI-AKI) remains unclear. In the present study, the effects of short- and long-term dietary hypercholesterolemia on contrast media-induced nephrotoxicity were evaluated. Methods: Rats were fed either a normal rodent diet (N) or high-cholesterol diet (H). At the end of 2 and 8 weeks, 8 rats from each diet group were given a tail vein injection of either iohexol (group NC and group HC) or vehicle (group N and group H). Blood lipids, renal function and renal hemodynamics were evaluated 1 day after contrast media administration. Renal and urinary prostaglandin E(2) (PGE(2)) and thromboxane B(2) (TXB(2)) were detected by radioimmunoassay. Renal nitric oxide and malondialdehyde (MDA) were measured by the Griess reaction and thiobarbituric acid method, respectively. Results: Contrast media administration increased serum creatinine levels and induced severe renal tubular necrosis in rats fed the high-cholesterol diet for 8 weeks but not in rats fed the normal diet or high-cholesterol diet for 2 weeks. The renal and urinary PGE(2) and TXB(2) levels increased significantly in rats in group H and group HC at the end of 8 weeks. Renal nitric oxide production decreased, and MDA levels increased markedly in group HC and group H at the end of 8 weeks. Conclusions: We conclude that long-term hypercholesterolemia appeared to be a risk factor for CI-AKI, which might be associated with disorders in intrarenal prostaglandins and abnormalities in renal nitric oxide system induced by lipid peroxidation.

Preliminary Strategic Environmental Assessment of the Great Western Development Strategy: Safeguarding Ecological Security for a New Western China

Environmental Management. Feb, 2012  |  Pubmed ID: 22190169

The Great Western Development Strategy (GWDS) is a long term national campaign aimed at boosting development of the western area of China and narrowing the economic gap between the western and the eastern parts of China. The Strategic Environmental Assessment (SEA) procedure was employed to assess the environmental challenges brought about by the western development plans. These plans include five key developmental domains (KDDs): water resource exploitation and use, land utilization, energy generation, tourism development, and ecological restoration and conservation. A combination of methods involving matrix assessment, incorporation of expert judgment and trend analysis was employed to analyze and predict the environmental impacts upon eight selected environmental indicators: water resource availability, soil erosion, soil salinization, forest destruction, land desertification, biological diversity, water quality and air quality. Based on the overall results of the assessment, countermeasures for environmental challenges that emerged were raised as key recommendations to ensure ecological security during the implementation of the GWDS. This paper is intended to introduce a consensus-based process for evaluating the complex, long term pressures on the ecological security of large areas, such as western China, that focuses on the use of combined methods applied at the strategic level.

The Ecology, Genetic Diversity, and Phylogeny of Huaiyangshan Virus in China

Journal of Virology. Mar, 2012  |  Pubmed ID: 22190717

Surveys were carried out to better understand the tick vector ecology and genetic diversity of Huaiyangshan virus (HYSV) in both regions of endemicity and regions of nonendemicity. Haemaphysalis longicornis ticks were dominant in regions of endemicity, while Rhipicephalus microplus is more abundant in regions of nonendemicity. HYSV RNA was found in human and both tick species, with greater prevalence in H. longicornis and lesser prevalence in R. microplus. Phylogenetic analyses indicate that HYSV is a novel species of the genus Phlebovirus.

A Potentially Common Peptide Target in Secreted Heat Shock Protein-90α for Hypoxia-inducible Factor-1α-positive Tumors

Molecular Biology of the Cell. Feb, 2012  |  Pubmed ID: 22190738

Deregulated accumulation of hypoxia-inducible factor-1α (HIF-1α) is a hallmark of many solid tumors. Directly targeting HIF-1α for therapeutics is challenging. Our finding that HIF-1α regulates secretion of heat shock protein-90α (Hsp90α) for cell migration raises the exciting possibility that targeting the secreted Hsp90α from HIF-1α-positive tumors has a better clinical outlook. Using the HIF-1α-positive and metastatic breast cancer cells MDA-MB-231, we show that down-regulation of the deregulated HIF-1α blocks Hsp90α secretion and invasion of the cells. Reintroducing an active, but not an inactive, HIF-1α into endogenous HIF-1α-depleted cells rescues both Hsp90α secretion and invasion. Inhibition of Hsp90α secretion, neutralization of secreted Hsp90α action, or removal of the cell surface LRP-1 receptor for secreted Hsp90α reduces the tumor cell invasion in vitro and lung colonization and tumor formation in nude mice. Furthermore, we localized the tumor-promoting effect to a 115-amino acid region in secreted Hsp90α called F-5. Supplementation with F-5 is sufficient to bypass the blockade of HIF-1α depletion and resumes invasion by the tumor cells under serum-free conditions. Because normal cells do not secrete Hsp90α in the absence of stress, drugs that target F-5 should be more effective and less toxic in treatment of HIF-1α-positive tumors in humans.

Structural Modification of Ginsenoside Rh(2) by Fatty Acid Esterification and Its Detoxification Property in Antitumor

Bioorganic & Medicinal Chemistry Letters. Jan, 2012  |  Pubmed ID: 22196118

Ginsenoside Rh(2), one of the most important ginsenosides with anticancer properties in red ginseng, has been developed as principal antitumor ingredient for clinical use. However, the cytotoxicity test in human hepatocyte cell line QSG-7701 (IC(50) 37.3μM) indicated that Rh(2) might show strong cytotoxic side-effect on the normal liver cells. For blunting the toxicity, Rh(2) was structurally modified by reacting with octanoyl chloride to give a dioctanoyl ester of Rh(2) (D-Rh(2)) in the present study. MTT assay in QSG-7701 cell line in vitro showed that the cytotoxicity of D-Rh(2) on human hepatocyte cells (IC(50) 80.5μM) was significantly lower than that of Rh(2). While antitumor xenograft assay in mice bearing H22 liver cancer cells in vivo showed that the antitumor activity of D-Rh(2) retained to be strong as that of Rh(2). According to previous pharmacokinetic studies, the fatty acid esterification of Rh(2) might be of detoxification reaction to cells. Additionally, D-Rh(2) showed significant enhancement on increasing thymus index at the dose of 10mg/kg compared with vehicle treated control group. Thus, D-Rh(2) might indirectly affect tumor growth by stimulating lymphocytes to become cytotoxic to tumor cells. Finally, our findings suggested that D-Rh(2), the fatty acid ester of Rh(2), might attenuate the side-effect by detoxification to human normal cell and could be a more potential candidate for developing as an antitumor drug.

Linear Sweep Voltammetric Studies on the Complex of Alizarin Red S with Aloe Polysaccharide and Determination of Aloe Polysaccharide

Carbohydrate Research. Feb, 2012  |  Pubmed ID: 22196364

A new electrochemical method for the determination of aloe polysaccharide based on its interaction with alizarin red s was established on a pretreated glassy carbon electrode in pH 3.5 Britton-Robinson buffer solution by linear sweep voltammetry in this work. The decrease of the second order derivative linear sweep voltammetric reductive peak current of alizarin red s is in proportion to aloe polysaccharide concentration due to the formation of a complex between them in the range from 0.032 to 0.448μmolL(-1), and the detection limit is 0.0051μmolL(-1) (3σ). The binding ratio and the binding constant of the complex were calculated as 1:1 and 2.75×10(4), respectively. Different kinds of complex samples of aloe polysaccharide were detected satisfactorily by this method.

Ginsenoside Re Attenuates Diabetes-associated Cognitive Deficits in Rats

Pharmacology, Biochemistry, and Behavior. Mar, 2012  |  Pubmed ID: 22197711

This study was designed to investigate the effect of ginsenoside Re (Re) on cognitive functions, oxidative stress and inflammation in streptozotocin-induced diabetic rats.

Microfluidic Study of Fast Gas-liquid Reactions

Journal of the American Chemical Society. Feb, 2012  |  Pubmed ID: 22176612

We present a new concept for studies of the kinetics of fast gas-liquid reactions. The strategy relies on the microfluidic generation of highly monodisperse gas bubbles in the liquid reaction medium and subsequent analysis of time-dependent changes in bubble dimensions. Using reactions of CO(2) with secondary amines as an exemplary system, we demonstrate that the method enables rapid determination of reaction rate constant and conversion, and comparison of various binding agents. The proposed approach addresses two challenges in studies of gas-liquid reactions: a mass-transfer limitation and a poorly defined gas-liquid interface. The proposed strategy offers new possibilities in studies of the fundamental aspects of rapid multiphase reactions, and can be combined with throughput optimization of reaction conditions.

Ectopic Expression of a Wheat MYB Transcription Factor Gene, TaMYB73, Improves Salinity Stress Tolerance in Arabidopsis Thaliana

Journal of Experimental Botany. Feb, 2012  |  Pubmed ID: 22140235

MYB transcription factors (TFs) play pivotal roles in the abiotic stress response in plants, but their characteristics and functions in wheat (Triticum aestivum L.) have not been fully investigated. A novel wheat MYB TF gene, TaMYB73, is reported here based on the observation that its targeting probe showed the highest salinity-inducibility level among all probes annotated as MYB TFs in the cDNA microarray. TaMYB73 is a R2R3 type MYB protein with transactivation activity, and binds with types I, II, and IIG MYB binding motifs. The gene was induced by NaCl, dehydration, and several phytohormones, as well as some stress-, ABA-, and GA-responsive cis-elements present in its promoter region. Its over-expression in Arabidopsis enhanced the tolerance to NaCl as well as to LiCl and KCl, whereas it had no contribution to mannitol tolerance. The over-expression lines had superior germination ability under NaCl and ABA treatments. The expression of many stress signalling genes such as AtCBF3 and AtABF3, as well as downstream responsive genes such as AtRD29A and AtRD29B, was improved in these over-expression lines, and TaMYB73 can bind with promoter sequences of AtCBF3 and AtABF3. Taken together, it is suggested that TaMYB73, a novel MYB transcription factor gene, participates in salinity tolerance based on improved ionic resistance partly via the regulation of stress-responsive genes.

Self Assembly of Janus Ellipsoids

Langmuir : the ACS Journal of Surfaces and Colloids. Jan, 2012  |  Pubmed ID: 22171980

We propose a primitive model of Janus ellipsoids that represents particles with an ellipsoidal core and two semisurfaces coded with dissimilar properties, for example, hydrophobicity and hydrophilicity, respectively. We investigate the effects of the aspect ratio on the self-assembly morphology and aggregation processes using Monte Carlo simulations. We also discuss certain differences between our results and those of earlier results for Janus spheres. In particular, we find that the size and structure of the aggregate can be controlled by the aspect ratio.

Baculovirus As a PRRSV and PCV2 Bivalent Vaccine Vector: Baculovirus Virions Displaying Simultaneously GP5 Glycoprotein of PRRSV and Capsid Protein of PCV2

Journal of Virological Methods. Feb, 2012  |  Pubmed ID: 22172969

The GP5 glycoprotein of PRRSV is the main target for inducing neutralizing antibodies and protective immunity in the natural host. The capsid (Cap) protein is the major immunogenic protein and associated with the production of PCV2-specific neutralizing antibodies. In the present study, one genetic recombinant baculovirus BacSC-Dual-GP5-Cap was constructed. This virus displays simultaneously histidine-tagged GP5 and Cap proteins with the baculovirus glycoprotein gp64 TM and CTD on the virion surface as well as the surface of the virus-infected cells. After infection, the GP5 and Cap proteins were expressed and anchored simultaneously on the plasma membrane of Sf-9 cells, as revealed by Western blot and confocal microscopy. This report demonstrated first that both GP5 and Cap proteins were displayed successfully on the viral surface, revealed by immunogold electron microscopy. Vaccination of swine with recombinant baculovirus BacSC-Dual-GP5-Cap elicited significantly higher GP5 and Cap ELISA antibody titers in swine than the control groups. Virus neutralization test also showed that serum from the BacSC-Dual-GP5-Cap treated swine had significant levels of virus neutralization titers. Lymphocyte proliferation responses could be induced in swine immunized with BacSC-Dual-GP5-Cap than the control groups. These findings demonstrate that the BacSC-Dual-GP5-Cap bivalent subunit vaccine can be a potential vaccine against PRRSV and PCV2 infections.

Sensitivity Analysis of Bi-layered Ceramic Dental Restorations

Dental Materials : Official Publication of the Academy of Dental Materials. Feb, 2012  |  Pubmed ID: 22169069

The reliability and longevity of ceramic prostheses have become a major concern. The existing studies have focused on some critical issues from clinical perspectives, but more researches are needed to address fundamental sciences and fabrication issues to ensure the longevity and durability of ceramic prostheses. The aim of this paper was to explore how "sensitive" the thermal and mechanical responses, in terms of changes in temperature and thermal residual stress of the bi-layered ceramic systems and crown models will be with respect to the perturbation of the design variables chosen (e.g. layer thickness and heat transfer coefficient) in a quantitative way.

Hydrogen-rich Saline Prevents Neointima Formation After Carotid Balloon Injury by Suppressing ROS and the TNF-α/NF-κB Pathway

Atherosclerosis. Feb, 2012  |  Pubmed ID: 22153150

Reactive oxygen species (ROS) play a pivotal role in neointima hyperplasia after balloon injury. Molecular hydrogen has emerged as a novel antioxidant and has been proven effective in treating many diseases.

Preparation of Nanocrystalline Cellulose Via Ultrasound and Its Reinforcement Capability for Poly(vinyl Alcohol) Composites

Ultrasonics Sonochemistry. May, 2012  |  Pubmed ID: 22153226

Rod-shaped nanocrystalline cellulose (NCC) was prepared from microcrystalline cellulose (MCC) using the purely physical method of high-intensity ultrasonication. Scanning electron microscopy, transmission electron microscopy, and X-ray diffraction was used for the characterization of the morphology and crystal structure of the material. The thermal properties were investigated using thermogravimetric analysis. The reinforcement capabilities of the obtained NCC were investigated by adding it to poly(vinyl alcohol) (PVA) via the solution casting method. The results revealed that the prepared NCC had a rod-shaped structure, with diameters between 10 and 20 nm and lengths between 50 and 250 nm. X-ray diffraction results indicated that the NCC had the cellulose I crystal structure similar to that of MCC. The crystallinity of the NCC decreased with increasing ultrasonication time. The ultrasonic effect was non-selective, which means it can remove amorphous cellulose and crystalline cellulose. Because of the nanoscale size and large number of free-end chains, the NCC degraded at a slightly lower temperature, which resulted in increased char residue (9.6-16.1%), compared with that of the MCC (6.2%). The storage modulus of the nanocomposite films were significantly improved compared with that of pure PVA films. The modulus of PVA with 8 wt.% NCC was 2.40× larger than that of pure PVA.

Discovery of Potent and Selective Matrix Metalloprotease 12 Inhibitors for the Potential Treatment of Chronic Obstructive Pulmonary Disease (COPD)

Bioorganic & Medicinal Chemistry Letters. Jan, 2012  |  Pubmed ID: 22153340

Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease associated with irreversible progressive airflow limitation. Matrix metalloproteinase-12 (MMP-12) has been characterized to be one of the major proteolytic enzymes to induce airway remodeling, destruction of elastin and the aberrant remodeling of damaged alveoli in COPD and asthma. The goal of this project is to develop and identify an orally potent and selective small molecule inhibitor of MMP-12 for treatment of COPD and asthma. Syntheses and structure-activity relationship (SAR) studies of a series of dibenzofuran (DBF) sulfonamides as MMP-12 inhibitors are described. Potent inhibitors of MMP-12 with excellent selectivity against other MMPs were identified. Compound 26 (MMP118), which exhibits excellent oral efficacy in the MMP-12 induced ear-swelling inflammation and lung inflammation mouse models, had been successfully advanced into Development Track status.

RRBSMAP: a Fast, Accurate and User-friendly Alignment Tool for Reduced Representation Bisulfite Sequencing

Bioinformatics (Oxford, England). Feb, 2012  |  Pubmed ID: 22155871

Reduced representation bisulfite sequencing (RRBS) is a powerful yet cost-efficient method for studying DNA methylation on a genomic scale. RRBS involves restriction-enzyme digestion, bisulfite conversion and size selection, resulting in DNA sequencing data that require special bioinformatic handling. Here, we describe RRBSMAP, a short-read alignment tool that is designed for handling RRBS data in a user-friendly and scalable way. RRBSMAP uses wildcard alignment, and avoids the need for any preprocessing or post-processing steps. We benchmarked RRBSMAP against a well-validated MAQ-based pipeline for RRBS read alignment and observed similar accuracy but much improved runtime performance, easier handling and better scaling to large sample sets. In summary, RRBSMAP removes bioinformatic hurdles and reduces the computational burden of large-scale epigenome association studies performed with RRBS.

Adult Rhabdomyoma of the Tongue in a Child

Pathology. Jan, 2012  |  Pubmed ID: 22157693

Ligand-guided Pathway Selection in Nickel-catalyzed Couplings of Enals and Alkynes

Chemical Communications (Cambridge, England). Jan, 2012  |  Pubmed ID: 22159624

Nickel-catalyzed couplings of enals and alkynes utilizing triethylborane as the reducing agent illustrate a significant dependence on ligand structure. Simple variation of monodentate phosphines allows selective access to alkylative couplings or reductive cycloadditions, while further variation of reaction conditions provides clean access to reductive couplings and redox-neutral couplings.

Sialylation of Lipooligosaccharides Is Dispensable for the Virulence of Haemophilus Ducreyi in Humans

Infection and Immunity. Feb, 2012  |  Pubmed ID: 22144477

Sialylated glycoconjugates on the surfaces of mammalian cells play important roles in intercellular communication and self-recognition. The sialic acid preferentially expressed in human tissues is N-acetylneuraminic acid (Neu5Ac). In a process called molecular mimicry, many bacterial pathogens decorate their cell surface glycolipids with Neu5Ac. Incorporation of Neu5Ac into bacterial glycolipids promotes bacterial interactions with host cell receptors called Siglecs. These interactions affect bacterial adherence, resistance to serum killing and phagocytosis, and innate immune responses. Haemophilus ducreyi, the etiologic agent of chancroid, expresses lipooligosaccharides (LOS) that are highly sialylated. However, an H. ducreyi sialyltransferase (lst) mutant, whose LOS contain reduced levels of Neu5Ac, is fully virulent in human volunteers. Recently, a second sialyltransferase gene (Hd0053) was discovered in H. ducreyi, raising the possibility that Hd0053 compensated for the loss of lst during human infection. CMP-Neu5Ac is the obligate nucleotide sugar donor for all bacterial sialyltransferases; LOS derived from an H. ducreyi CMP-Neu5Ac synthetase (neuA) mutant has no detectable Neu5Ac. Here, we compared an H. ducreyi neuA mutant to its wild-type parent in several models of pathogenesis. In human inoculation experiments, the neuA mutant formed papules and pustules at rates that were no different than those of its parent. When grown in media with and without Neu5Ac supplementation, the neuA mutant and its parent had similar phenotypes in bactericidal, macrophage uptake, and dendritic cell activation assays. Although we cannot preclude a contribution of LOS sialylation to ulcerative disease, these data strongly suggest that sialylation of LOS is dispensable for H. ducreyi pathogenesis in humans.

Hemorrhagic Fever Caused by a Novel Bunyavirus in China: Pathogenesis and Correlates of Fatal Outcome

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. Feb, 2012  |  Pubmed ID: 22144540

Background. Hemorrhagic fever-like illness caused by a novel Bunyavirus, Huaiyangshan virus (HYSV, also known as Severe Fever with Thrombocytopenia virus [SFTSV] and Fever, Thrombocytopenia and Leukopenia Syndrome [FTLS]), has recently been described in China. Methods. Patients with laboratory-confirmed HYSV infection who were admitted to Union Hospital or Zhongnan Hospital between April 2010 and October 2010 were included in this study. Clinical and routine laboratory data were collected and blood, throat swab, urine, or feces were obtained when possible. Viral RNA was quantified by real-time reverse-transcriptase polymerase chain reaction. Blood levels of a range of cytokines, chemokines, and acute phase proteins were assayed. Results. A total of 49 patients with hemorrhagic fever caused by HYSV were included; 8 (16.3%) patients died. A fatal outcome was associated with high viral RNA load in blood at admission, as well as higher serum liver transaminase levels, more pronounced coagulation disturbances (activated partial thromboplastin time, thrombin time), and higher levels of acute phase proteins (phospholipase A, fibrinogen, hepcidin), cytokines (interleukin [IL]-6, IL-10, interferon-γ), and chemokines (IL-8, monocyte chemotactic protein 1, macrophage inflammatory protein 1b). The levels of these host parameters correlated with viral RNA levels. Blood viral RNA levels gradually declined over 3-4 weeks after illness onset, accompanied by resolution of symptoms and laboratory abnormalities. Viral RNA was also detectable in throat, urine, and fecal specimens of a substantial proportion of patients, including all fatal cases assayed. Conclusions. Viral replication and host immune responses play an important role in determining the severity and clinical outcome in patients with infection by HYSV.

Stereoselective Separation and Determination of Triadimefon and Triadimenol in Wheat, Straw, and Soil by Liquid Chromatography-tandem Mass Spectrometry

Journal of Separation Science. Jan, 2012  |  Pubmed ID: 22102610

A sensitive and rapid analytical method was developed for simultaneous determination of triadimefon (TF) and triadimenol (TN) stereoisomers in wheat, straw, and soil by liquid chromatography coupled with triple quadrupole mass spectrometry (LC-MS/MS). The direct enantioseparation of TF and TN was performed on a Lux cellulose-1 column packed with cellulose-tris-(3,5-dimethylphenylcarbamate). The effects of mobile-phase composition on the separation were investigated and stereoisomeric elution orders were confirmed with a polarimeter detector. The pesticides were extracted from samples with acetonitrile and cleaned up by solid-phase extraction or activated carbon. Based on the developed stereoselective LC-MS/MS method, for TF and TN stereoisomers, good linearities were obtained over the concentration range of 0.003-4 mg/L; recoveries were 84.2-102.7% in wheat, 84.0-104.0% in straw, and 85.2-106.8% in soil at spiked concentrations of 0.007-2.0 mg/kg; intra-day and inter-day assay precisions were below 12.2%. Limits of detection (LODs) and limits of quantification (LOQs) in wheat, straw, and soil were 0.001-0.005 mg/kg and 0.007-0.02 mg/kg, respectively. Finally, the method was successfully applied to detect TF and TN stereoisomers in wheat, straw, and soil samples from residual trials in farm.

Loss of the Methyl Lysine Effector Protein PHF20 Impacts the Expression of Genes Regulated by the Lysine Acetyltransferase MOF

The Journal of Biological Chemistry. Jan, 2012  |  Pubmed ID: 22072714

In epigenetic signaling pathways, histone tails are heavily modified, resulting in the recruitment of effector molecules that can influence transcription. One such molecule, plant homeodomain finger protein 20 (PHF20), uses a Tudor domain to read dimethyl lysine residues and is a known component of the MOF (male absent on the first) histone acetyltransferase protein complex, suggesting it plays a role in the cross-talk between lysine methylation and histone acetylation. We sought to investigate the biological role of PHF20 by generating a knockout mouse. Without PHF20, mice die shortly after birth and display a wide variety of phenotypes within the skeletal and hematopoietic systems. Mechanistically, PHF20 is not required for maintaining the global H4K16 acetylation levels or locus specific histone acetylation but instead works downstream in transcriptional regulation of MOF target genes.

Human Cytochrome P450scc (CYP11A1) Catalyzes Epoxide Formation with Ergosterol

Drug Metabolism and Disposition: the Biological Fate of Chemicals. Mar, 2012  |  Pubmed ID: 22106170

Cytochrome P450scc (P450scc) catalyzes the cleavage of the side chain of both cholesterol and the vitamin D(3) precursor, 7-dehydrocholesterol. The aim of this study was to test the ability of human P450scc to metabolize ergosterol, the vitamin D(2) precursor, and define the structure of the major products. P450scc incorporated into the bilayer of phospholipid vesicles converted ergosterol to two major and four minor products with a k(cat) of 53 mol · min(-1) · mol P450scc(-1) and a K(m) of 0.18 mol ergosterol/mol phospholipid, similar to the values observed for cholesterol metabolism. The reaction of ergosterol with P450scc was scaled up to make enough of the two major products for structural analysis. From mass spectrometry, NMR, and comparison of the NMR data to that for similar molecules, we determined the structures of the two major products as 20-hydroxy-22,23-epoxy-22,23-dihydroergosterol and 22-keto-23-hydroxy-22,23-dihydroergosterol. Molecular modeling and nuclear Overhauser effect (or enhancement) spectroscopy spectra analysis helped to establish the configurations at C20, C22, and C23 and determine the final structures of major products as 22R,23S-epoxyergosta-5,7-diene-3β,20α-diol and 3β,23S-dihydroxyergosta-5,7-dien-22-one. It is likely that the formation of the second product is through a 22,23-epoxy (oxirane) intermediate followed by C22 hydroxylation with the formation of strained 22-hydroxy-22,23-epoxide (oxiranol), which is immediately transformed to the more stable α-hydroxyketone. Molecular modeling of ergosterol into the P450scc crystal structure positioned the ergosterol side chain consistent with formation of the above products. Thus, we have shown that P450scc efficiently catalyzes epoxide formation with ergosterol giving rise to novel epoxy, hydroxy, and keto derivatives, without causing cleavage of the side chain.

Evaluation of Driver Fatigue on Two Channels of EEG Data

Neuroscience Letters. Jan, 2012  |  Pubmed ID: 22116020

Electroencephalogram (EEG) data is an effective indicator to evaluate driver fatigue. The 16 channels of EEG data are collected and transformed into three bands (θ, α, and β) in the current paper. First, 12 types of energy parameters are computed based on the EEG data. Then, Grey Relational Analysis (GRA) is introduced to identify the optimal indicator of driver fatigue, after which, the number of significant electrodes is reduced using Kernel Principle Component Analysis (KPCA). Finally, the evaluation model for driver fatigue is established with the regression equation based on the EEG data from two significant electrodes (Fp1 and O1). The experimental results verify that the model is effective in evaluating driver fatigue.

Anti-tumor Activity of Paclitaxel Through Dual-targeting Carrier of Cyclic RGD and Transferrin Conjugated Hyperbranched Copolymer Nanoparticles

Biomaterials. Feb, 2012  |  Pubmed ID: 22118775

Targeted delivery strategies are becoming increasingly important. Herein, a novel hyperbranched amphiphilic poly[(amine-ester)-co-(D,L-lactide)]/1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine copolymer (HPAE-co-PLA/DPPE) with RGD peptide (cRGDfK) and transferrin (Tf) on the periphery was synthesized and used to prepare paclitaxel-loaded nanoparticles (NPs) for dual-targeting chemotherapy. These NPs show satisfactory size distribution, high encapsulated efficiency and a pH-dependent release profile. The intrinsic fluorescence of the hyperbranched copolymer renders the detection and tracking of NPs in vitro and in vivo conveniently. In vitro cytotoxicity studies proved that the presence of cRGDfK enhanced the cytotoxic efficiency by 10 folds in α(ν)β(3) integrin over-expressed human umbilical vein endothelial cells, while Tf improved cytotoxicity by 2 folds in Tf receptor over-expressed human cervical carcinoma cells. The drug-loaded NPs can be efficiently transported into the vascular endothelial cells and the target tumor cells. These results indicate that the cRGDfK and Tf decorated HPAE-co-PLA/DPPE could deliver chemotherapies specifically inside the cell via receptor-mediated endocytosis with greater efficacy. Therefore, such a fluorescent nanocarrier prepared from non-cytotoxic and biodegradable polymers is promising for drug delivery in tumor therapy.

Effects of Fenton Treatment on the Properties of Effluent Organic Matter and Their Relationships with the Degradation of Pharmaceuticals and Personal Care Products

Water Research. Feb, 2012  |  Pubmed ID: 22118906

This study examined effects of Fenton oxidation on trace level pharmaceuticals and personal care products (PPCPs) commonly occurring in wastewater. The tested PPCPs included acetaminophen, atenolol, atrazine, carbamazepine, metoprolol, dilantin, DEET, diclofenac, pentoxifylline, oxybenzone, caffeine, fluoxetine, gemfibrozil, ibuprofen, iopromide, naproxen, propranolol, sulfamethoxazole, bisphenol-A and trimethoprim. Transformations of effluent organic matter (EfOM) caused by Fenton oxidation were also quantified. All tested PPCPs, except atrazine and iopromide, were completely removed by Fenton treatment carried out using a 20mg/L Fe (II) concentration and a 2.5 H(2)O(2)/Fe (II) molar ratio. Up to 30% on the total carbon concentration was removed during Fenton treatment which was accompanied by the oxidation of EfOM molecules and formation of oxidation products such as oxalic, formic and acetic acids and, less prominently, formaldehyde, acetaldehyde, propionaldehyde and glycolaldehyde. The absorbance of EfOM treated with Fenton reagent at varying Fe (II) concentration and contact time underwent a consistent decrease. The relative decrease of EfOM absorbance was strongly and unambiguously correlated with the removal of all tested PPCPs.

New Sesquiterpenoids from the Dried Flower Buds of Tussilago Farfara and Their Inhibition on NO Production in LPS-induced RAW264.7 Cells

Fitoterapia. Mar, 2012  |  Pubmed ID: 22120501

Three new sesquiterpenoids, 1α-(3″-ethyl-cis-crotonoyloxy)-8-angeloyloxy-3β,4β-epoxy-bisabola-7(14),10-diene (1), 7β-angeloyloxy-14-hydroxy-notonipetranone (2) and 1α-hydroxy-7β-(4-methylsenecioyloxy)-oplopa-3(14)Z,8(10)-dien-2-one (3) were isolated from ethanolic extract of the dried flower buds of Tussilago farfara L., along with nine known sesquiterpenoids (4-12). All of these compounds were evaluated for their effect on the inhibition of nitric oxide (NO) production induced by lipopolysaccharide in macrophage cell line RAW 264.7 and exhibited inhibitory activity on NO production in a dose-dependent manner. 7β-(4-Methylsenecioyloxy)-oplopa-3(14)E,8(10)-dien-2-one (8) was proved to be the best among these tested sesquiterpenoids with an IC(50) value of 10.80μM.

Bifunctional Peptides That Precisely Biomineralize Au Clusters and Specifically Stain Cell Nuclei

Chemical Communications (Cambridge, England). Jan, 2012  |  Pubmed ID: 22134202

A bifunctional peptide containing a domain that targets cell nuclei and a domain with the ability to biomineralize and capture Au clusters is presented. The peptide-Au clusters exhibit red emission (λ(em) = 677 nm) and specifically stain the nuclei of three cell lines.

MicroRNA Signature in Thyroid Fine Needle Aspiration Cytology Applied to "atypia of Undetermined Significance" Cases

Thyroid : Official Journal of the American Thyroid Association. Jan, 2012  |  Pubmed ID: 22136206

MicroRNA (miR) expression signatures are proposed to be able to differentiate thyroid cancer from benign thyroid lesions. We selected eight miRs (miR-146b, -221, -187, -197, -346, -30d, -138, and -302c) to examine the potential use of miRs to supplement diagnostic cytology in cases designated as "atypia of undetermined significance."

Up-regulation of NDRG2 Through Nuclear Factor-kappa B is Required for Leydig Cell Apoptosis in Both Human and Murine Infertile Testes

Biochimica Et Biophysica Acta. Feb, 2012  |  Pubmed ID: 22138128

Many pro-apoptotic factors, such as nuclear factor-kappa B (NF-κB) and Fas, play crucial roles in the process of Leydig cell apoptosis, ultimately leading to male sterility, such as in Sertoli cell only syndrome (SCO) and hypospermatogenesis. However, the molecular mechanism of such apoptosis is unclear. Recent reports on N-myc downstream-regulated gene 2 (ndrg2) have suggested that it is involved in cellular differentiation, development, and apoptosis. The unique expression of NDRG2 in SCO and hypospermatogenic testis suggests its pivotal role in those diseases. In this study, we analyzed NDRG2 expression profiles in the testes of normal spermatogenesis patients, hypospermatogenesis patients, and SCO patients, as well as in vivo and in vitro models, which were Sprague-Dawley rats and the Leydig cell line TM3 treated with the Leydig cell-specific toxicant ethane-dimethanesulfonate (EDS). Our data confirm that NDRG2 is normally exclusively located in the cytoplasm of Leydig cells and is up-regulated and translocates into the nucleus under apoptotic stimulations in human and murine testis. Meanwhile, transcription factor NF-κB was activated by EDS administration, bound to the ndrg2 promoter, and further increased in expression, effects that were abolished by NF-κB inhibitor Pyrrolidine dithiocarbamate (PDTC). Furthermore, siRNA knock-down of ndrg2 led to increased proliferative or decreased apoptotic TM3 cells, while over-expression of ndrg2 had the reverse effect. This study reveals that ndrg2 is a novel gene that participates in Leydig cell apoptosis, with essential functions in testicular cells, and suggests its possible role in apoptotic Leydig cells and male fertility.

Development of a Label-free and Innovative Approach Based on Surface Plasmon Resonance Biosensor for On-site Detection of Infectious Bursal Disease Virus (IBDV)

Biosensors & Bioelectronics. Jan, 2012  |  Pubmed ID: 22138467

An innovative, specific and label-free detection approach based on optical surface plasmon resonance (SPR) was developed and employed in the development of a rapid and quantitative bioanalyzer for detecting infectious bursal disease virus (IBDV) in the field. A unique bioanalyzer based on this approach was established which consists of a micro-flow cell, a temperature regulator, an integrated biosensor, an optical platform, an electronic control unit incorporated into a photoelectric conversion device, and a universal serial bus (USB) interface circuit board. The procedure for detecting IBDV was systematically described, and experimentally validated. The self-assembly technology was used to make the IBDmAb adhere to the surface of the sensor chip by a bifunctional cross-linker. By this approach there exhibited a linear relationship between the IBDV concentrations and the corresponding responses in the range of dilution factors from 100 to 1600 with R(2) 0.97982. We were able to detect 400-fold diluted IBDV using this biochip repeatedly with a calculated relative standard deviation (RSD) of 3.6%. We also showed that the detection limit of the SPR biosensor biochip was around 1/18 of the detection limit of the IBDV diagnostic strip. Satisfactory recoveries were obtained from the recovery test. The approach presented here was shown to have great potential to be used in the IBDV epidemic regions and hence help to promote the effective implementation of sound control strategies against IBDV.

Dnmt3a is Essential for Hematopoietic Stem Cell Differentiation

Nature Genetics. Jan, 2012  |  Pubmed ID: 22138693

Loss of the de novo DNA methyltransferases Dnmt3a and Dnmt3b in embryonic stem cells obstructs differentiation; however, the role of these enzymes in somatic stem cells is largely unknown. Using conditional ablation, we show that Dnmt3a loss progressively impairs hematopoietic stem cell (HSC) differentiation over serial transplantation, while simultaneously expanding HSC numbers in the bone marrow. Dnmt3a-null HSCs show both increased and decreased methylation at distinct loci, including substantial CpG island hypermethylation. Dnmt3a-null HSCs upregulate HSC multipotency genes and downregulate differentiation factors, and their progeny exhibit global hypomethylation and incomplete repression of HSC-specific genes. These data establish Dnmt3a as a critical participant in the epigenetic silencing of HSC regulatory genes, thereby enabling efficient differentiation.

Total Saponins from Rhizoma Anemarrhenae Ameliorate Diabetes-associated Cognitive Decline in Rats: Involvement of Amyloid-beta Decrease in Brain

Journal of Ethnopharmacology. Jan, 2012  |  Pubmed ID: 22101084

As a well-known Chinese Materia Medica Rhizoma Anemarrhenae has multiple pharmacological activities including antipyretic, anti-inflammatory, anti-diabetic actions, etc. This study was designed to investigate effects of total saponins from Rhizoma Anemarrhenae (TS) on diabetes-associated cognitive decline in rats and influence on amyloid-beta (Aβ) levels in brain and inflammation.

UNC-33 (CRMP) and Ankyrin Organize Microtubules and Localize Kinesin to Polarize Axon-dendrite Sorting

Nature Neuroscience. Jan, 2012  |  Pubmed ID: 22101643

The polarized distribution of neuronal proteins to axons and dendrites relies on microtubule-binding proteins such as CRMP, directed motors such as the kinesin UNC-104 (Kif1A) and diffusion barriers such as ankyrin. The causative relationships among these molecules are unknown. We show here that Caenorhabditis elegans CRMP (UNC-33) acts early in neuronal development, together with ankyrin (UNC-44), to organize microtubule asymmetry and axon-dendrite sorting. In unc-33 and unc-44 mutants, axonal proteins were mislocalized to dendrites and vice versa, suggesting bidirectional failures of axon-dendrite identity. unc-44 directed UNC-33 localization to axons, where it was enriched in a region that resembled the axon initial segment. unc-33 and unc-44 were both required to establish the asymmetric dynamics of axonal and dendritic microtubules; in their absence, microtubules were disorganized, the axonal kinesin UNC-104 invaded dendrites, and inappropriate UNC-104 activity randomized axonal protein sorting. We suggest that UNC-44 and UNC-33 direct polarized sorting through their global effects on neuronal microtubule organization.

Direct Reprogramming of Sertoli Cells into Multipotent Neural Stem Cells by Defined Factors

Cell Research. Jan, 2012  |  Pubmed ID: 22064700

Multipotent neural stem/progenitor cells hold great promise for cell therapy. The reprogramming of fibroblasts to induced pluripotent stem cells as well as mature neurons suggests a possibility to convert a terminally differentiated somatic cell into a multipotent state without first establishing pluripotency. Here, we demonstrate that Sertoli cells derived from mesoderm can be directly converted into a multipotent state that possesses neural stem/progenitor cell properties. The induced neural stem/progenitor cells (iNSCs) express multiple NSC-specific markers, exhibit a global gene-expression profile similar to normal NSCs, and are capable of self-renewal and differentiating into glia and electrophysiologically functional neurons. iNSC-derived neurons stain positive for tyrosine hydroxylase (TH), γ-aminobutyric acid, and choline acetyltransferase. In addition, iNSCs can survive and generate synapses following transplantation into the dentate gyrus. Generation of iNSCs may have important implications for disease modeling and regenerative medicine.

FungiDB: an Integrated Functional Genomics Database for Fungi

Nucleic Acids Research. Jan, 2012  |  Pubmed ID: 22064857

FungiDB (http://FungiDB.org) is a functional genomic resource for pan-fungal genomes that was developed in partnership with the Eukaryotic Pathogen Bioinformatic resource center (http://EuPathDB.org). FungiDB uses the same infrastructure and user interface as EuPathDB, which allows for sophisticated and integrated searches to be performed using an intuitive graphical system. The current release of FungiDB contains genome sequence and annotation from 18 species spanning several fungal classes, including the Ascomycota classes, Eurotiomycetes, Sordariomycetes, Saccharomycetes and the Basidiomycota orders, Pucciniomycetes and Tremellomycetes, and the basal 'Zygomycete' lineage Mucormycotina. Additionally, FungiDB contains cell cycle microarray data, hyphal growth RNA-sequence data and yeast two hybrid interaction data. The underlying genomic sequence and annotation combined with functional data, additional data from the FungiDB standard analysis pipeline and the ability to leverage orthology provides a powerful resource for in silico experimentation.

Lysosomal Exocytosis in Schwann Cells Contributes to Axon Remyelination

Glia. Feb, 2012  |  Pubmed ID: 22042600

Myelin biogenesis is a complex process involving coordinated exocytosis, endocytosis, mRNA transport, and cytoskeletal dynamics. Although abnormalities of myelin are common in lysosomal storage diseases, our understanding of the role of lysosomes in the formation and maintenance of myelin is still limited. Here, we show that late endosomes/lysosomes in Schwann cells contain abundant myelin protein P0, which accounts for over half the total protein of compact myelin in the peripheral nervous system and exhibit Ca(2+) -dependent exocytosis in response to various stimuli. Downregulation of Rab27a, a small GTPase required for the trafficking of the secretory lysosomes to the plasma membrane, largely blocked lysosomal exocytosis in Schwann cells and reduced the remyelination of regenerated sciatic nerve. These findings highlight a novel role for lysosomes in Schwann cells and suggest that the regulated lysosome exocytosis in Schwann cells may have important physiological and pathological significance in the peripheral nervous system.

Cyclic Bisdesmosides from Actinostemma Lobatum MAXIM (Cucurbitaceae) and Their in Vitro Cytotoxicity

Fitoterapia. Jan, 2012  |  Pubmed ID: 22056664

Two new cyclic bisdesmosides elucidated as lobatoside L (1) and lobatoside M (2) and four known cyclic bisdesmosides (3-6) were isolated from Actinostemma lobatum MAXIM (Cucurbitaceae). Their structures were determined on the basis of spectroscopic analyses including IR, HR-FAB-MS, TOCSY, 1D- and 2D-NMR experiments and chemical reactions. The inhibitory effects of the six compounds on human cancer cell growth (including esophageal squamous carcinoma cell line ECA109, lung cancer cell line A549 and gastric cancer cell line MGC-803) were determined using the MTT assay. The results revealed that the six compounds exhibited cytotoxicity against all the cell lines tested, and compounds 1, 3 and 5 showed significant activities in a dose dependent manner against all the cell lines, especially for compound 1 and 5, the IC(50) values for ECA-109 cells were 8.25 μM and 3.71 μM. The results demonstrated that compounds 1 and 5's activities are 2- and 4-fold that of cisplatin.

Hypoglycemic Effect of Protopanaxadiol-type Ginsenosides and Compound K on Type 2 Diabetes Mice Induced by High-fat Diet Combining with Streptozotocin Via Suppression of Hepatic Gluconeogenesis

Fitoterapia. Jan, 2012  |  Pubmed ID: 22056666

Compound K (CK) is a final intestinal metabolite of protopanaxadiol-type ginsenosides (PDG) from Panax ginseng. Although anti-diabetic activity of CK have been reported with genetic mouse models (db/db mice) in recent years, the therapeutic usefulness of CK and PDG in type 2 diabetes, a more prevalent form of diabetes, remains unclear. In the present investigation, we developed a mouse of non-insulin-dependent diabetes mellitus that closely simulated the metabolic abnormalities of the human disease. For this purpose, type 2 diabetes was induced in male ICR mice by combining of streptozotocin. The male ICR mice fed with HFD for 4 weeks received 100mg/kg of STZ injected intraperitoneally. After 4 weeks, mice with fasting (12h) blood glucose levels (FBG) above 7.8 mmol/L were divided into 3 groups (n=12) and treated with vehicle (diabetes model, DM), 300 mg/kg/day of PDG and 30 mg/kg/day of CK for 4 weeks while continuing on the high-fat diet. Hypoglycemic effects of CK and PDG were consistently demonstrated by FBG levels, and insulin-sensitizing effects were seen during oral glucose tolerance testing (OGTT). Moreover, the mechanism of hypoglycemic effect in type 2 diabetic mice was examined. Gluconeogenic genes, Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose-6-phosphatase (G6Pase), were decreased in two treatment groups with CK showing greater effects. These findings demonstrated the hypoglycemic and insulin-sensitizing capabilities of CK on type 2 diabetes induced by HFD/STZ via down-regulation of PEPCK and G6Pase expression in liver.

Effectiveness of Statins on Total Cholesterol and Cardiovascular Disease and All-cause Mortality in Osteoarthritis and Rheumatoid Arthritis

The Journal of Rheumatology. Jan, 2012  |  Pubmed ID: 22045835

There is increasing prevalence of hypercholesterolemia among patients with osteoarthritis (OA) and rheumatoid arthritis (RA). We examined the effectiveness of statins on total cholesterol (TC), cardiovascular (CV) morbidity, and mortality in patients with OA or RA.

Magnetic Susceptibility Anisotropy of Human Brain in Vivo and Its Molecular Underpinnings

NeuroImage. Feb, 2012  |  Pubmed ID: 22036681

Frequency shift of gradient-echo MRI provides valuable information for assessing brain tissues. Recent studies suggest that the frequency and susceptibility contrast depend on white matter fiber orientation. However, the molecular underpinning of the orientation dependence is unclear. In this study, we investigated the orientation dependence of susceptibility of human brain in vivo and mouse brains ex vivo. The source of susceptibility anisotropy in white matter is likely to be myelin as evidenced by the loss of anisotropy in the dysmyelinating shiverer mouse brain. A biophysical model is developed to investigate the effect of the molecular susceptibility anisotropy of myelin components, especially myelin lipids, on the bulk anisotropy observed by MRI. This model provides a consistent interpretation of the orientation dependence of macroscopic magnetic susceptibility in normal mouse brain ex vivo and human brain in vivo and the microscopic origin of anisotropic susceptibility. It is predicted by the theoretical model and illustrated by the experimental data that the magnetic susceptibility of the white matter is least diamagnetic along the fiber direction. This relationship allows an efficient extraction of fiber orientation using susceptibility tensor imaging. These results suggest that anisotropy on the molecular level can be observed on the macroscopic level when the molecules are aligned in a highly ordered manner. Similar to the utilization of magnetic susceptibility anisotropy in elucidating molecular structures, imaging magnetic susceptibility anisotropy may also provide a useful tool for elucidating the microstructure of ordered biological tissues.

Diamine Oxidase As a Marker for Diagnosis of Superior Mesenteric Arterial Occlusion

Hepato-gastroenterology. Jan-Feb, 2012  |  Pubmed ID: 22024144

Background/Aims: We investigated changes in serum diamine oxidase (DAO) activity during superior mesenteric arterial occlusion. We aimed to evaluate its value in the early diagnosis of superior mesenteric arterial occlusion. Methodology: Seventy mature male Sprague-Dawley rats were used in the study. These were divided into 7 groups of 10 rats each: 10min, 15min, 30min, 45min, 60min and 90min superior mesenteric arterial occlusion (SMA-O) groups, and a sham group. Blood samples were taken at the indicated time points for measuring serum DAO activity. Simultaneously, the small-intestinal segments were assessed histologically and graded according to Chiu's score. Results: In the 15min group, SMA-O resulted in a rapid increase in DAO activity. Serum DAO activity and the mucosal injury score fitted well with the cubic model (r2=0.985, p<0.01). There was a positive correlation between ischemic duration and small-intestinal mucosal injury (r=0.909, p<0.01). Taking DAO=29.81U/L as a early diagnostic standard for superior mesenteric arterial occlusion, the sensitivity, accuracy and specificity were 94.34% (50/53), 95.71% (67/70), 100% (17/17), respectively. Conclusions: Serum DAO activity is a sensitive predictor of small-intestinal injury. Our finding suggests that measurement of serum DAO levels might provide a marker for early diagnosis of superior mesenteric arterial occlusion.

Antiepidermal Growth Factor Receptor Monoclonal Antibody Improves Survival Outcomes in the Treatment of Patients with Metastatic Colorectal Cancer

Anti-cancer Drugs. Feb, 2012  |  Pubmed ID: 21955998

The aim of this study was to determine whether or not the addition of anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody (mAb) to standard chemotherapy or best supportive care (BSC), compared with chemotherapy or BSC alone, can improve overall survival (OS) and progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC), and evaluate the influence of KRAS mutant status on the efficacy of anti-EGFR mAb. Medline, Embase, the Cochrane controlled trials register, and the Science Citation Index were searched. Nine trials were identified, covering a total of 7941 patients. The treatment of mCRC with a combination of anti-EGFR mAb and chemotherapy or BSC, as compared with chemotherapy or BSC alone, improved the OS [hazard ratio (HR), 0.90 (0.84-0.96); P=0.002]. The benefit of anti-EGFR mAb in patients with KRAS wild-type tumors was apparent in relation to a marginal trend toward improved OS [HR, 0.84 (0.70-1.01); P=0.06], and significantly improved PFS [HR, 0.64 (0.51-0.81); P<0.001]. No benefit for the addition of anti-EGFR mAb was detected for any efficacy end-point in patients with KRAS mutant tumors. The summary HRs (anti-EGFR mAb vs control) were 0.98 (0.88-1.08) (P=0.71) for OS and 1.08 (0.94-1.25) (P=0.27) for PFS, respectively. In conclusion, this analysis provides confirmation that, compared with chemotherapy or BSC alone, anti-EGFR mAb with chemotherapy or BSC reduces the risk of progression and death of mCRC and that this benefit is seen only in patients with wild-type KRAS tumors.

A Comparative Mechanical and Bone Remodelling Study of All-ceramic Posterior Inlay and Onlay Fixed Partial Dentures

Journal of Dentistry. Jan, 2012  |  Pubmed ID: 22019798

Comparative studies of bone remodelling and mechanical stresses between inlay and onlay fixed partial dentures (FPD) are rather limited. The purpose of this paper was to evaluate the biological consequence in posterior mandibular bone and the mechanical responses in these two different prosthetic configurations.

Early Use of Noninvasive Positive Pressure Ventilation for Acute Lung Injury: A Multicenter Randomized Controlled Trial*

Critical Care Medicine. Feb, 2012  |  Pubmed ID: 22020236

OBJECTIVE:: Noninvasive positive pressure ventilation is beneficial for patients with acute respiratory failure. However, its possible benefit for patients with acute lung injury (200 mm Hg < PaO2/FIO2 ≤300 mm Hg) remains unclear. Our aim was to assess the safety and efficacy of noninvasive positive pressure ventilation for patients with acute lung injury and compare this with high-concentration oxygen therapy. DESIGN:: A multicentered randomized controlled trial. SETTING:: Ten multipurpose intensive care units. PATIENTS:: Forty patients who fulfilled the criteria for acute lung injury were included in this study. INTERVENTIONS:: Patients were randomly allocated to receive either noninvasive positive pressure ventilation (noninvasive positive pressure ventilation group) or high-concentration oxygen therapy through a Venturi mask (control group). MEASUREMENTS AND MAIN RESULTS:: Twenty-one patients were assigned to the noninvasive positive pressure ventilation group and 19 were in the control group. At study entry, the patients' characteristics in the two groups were similar. Noninvasive positive pressure ventilation application decreased the respiratory rate and improved PaO2/FIO2 with time. The proportion of patients requiring intubation and the actual number of intubations in the noninvasive positive pressure ventilation group were significantly less than in the control group (one of 21 vs. seven of 19; p = .02, and one of 21 vs. four of 19; p = .04, respectively). Noninvasive positive pressure ventilation showed a trend for reducing inhospital mortality (one of 21 vs. five of 19; p = .09). The total number of organ failures in the noninvasive positive pressure ventilation group was significantly lower than in the control group (three vs. 14; p < .001). CONCLUSIONS:: Noninvasive positive pressure ventilation is safe for selected patients with acute lung injury. However, a larger randomized trial with need for intubation and mortality as the outcomes of interest is required.

Increased MiR-146a in Gastric Cancer Directly Targets SMAD4 and is Involved in Modulating Cell Proliferation and Apoptosis

Oncology Reports. Feb, 2012  |  Pubmed ID: 22020746

MicroRNAs (miRNAs) have emerged as important gene regulators and are recognized as oncogenes or tumor suppressor genes in carcinogenesis. Gastric cancer is one of the most common malignant diseases worldwide. Our previous studies have revealed that miR-146a is upregulated in gastric epithelial cells infected with Helicobacter pylori (H. pylori) and in mucosal tissues from H. pylori-positive patients. However, the role of miR-146a in gastric cancer is largely unknown. In the current study, we showed that miR-146a was upregulated in 20 gastric cancer tissues compared with matched non-tumor adjacent tissues by quantitative RT-PCR. Furthermore, ectopic expression of miR-146a could improve cell proliferation in vitro by using Cell Counting kit 8 (CCK-8). We also found that miR-146a inhibited apoptosis of gastric cancer cells by flow cytometry (FCM) and Caspase-Glo® 3/7 assay. Using target prediction algorithms, luciferase reporter assay and Western blot assay, SMAD family member 4 (SMAD4) was identified as a target gene of miR-146a in gastric cancer. Moreover, an inverse correlation was observed between the expression of SMAD4 mRNA and miR-146a in gastric cancer tissues (R=-0.731, P=0.039, Pearson's correlation). Taken together, our results provide important evidence that miR-146a can directly target SMAD4, and suggest that miR-146a may play a role in the development of gastric cancer by modulating cell proliferation and apoptosis. miR-146a could serve as a potential biomarker and therapeutic target against gastric cancer.

Correlation of TWIST2 Up-regulation and Epithelial-mesenchymal Transition During Tumorigenesis and Progression of Cervical Carcinoma

Gynecologic Oncology. Jan, 2012  |  Pubmed ID: 22018873

Globally, cervical cancer is the second most common cancer among women, and determining potential targets involved in tumor progression is necessary. This study investigated the clinic-pathological significance of twist homolog 2 (TWIST2), a basic helix-loop-helix transcription factor, and correlated TWIST2 and E-cadherin expression in cervical cancer.

Synthesis of Silver Nanoparticles by Solar Irradiation of Cell-free Bacillus Amyloliquefaciens Extracts and AgNO3

Bioresource Technology. Jan, 2012  |  Pubmed ID: 22019398

Silver nanoparticles (AgNPs) were obtained by solar irradiation of cell-free extracts of Bacillusamyloliquefaciens and AgNO3. Light intensity, extract concentration, and NaCl addition influenced the synthesis of AgNPs. Under optimized conditions (solar intensity 70,000 lx, extract concentration 3 mg/mL, and NaCl content 2 mM), 98.23±0.06% of the Ag+ (1 mM) was reduced to AgNPs within 80 min, and the ζ-potential of AgNPs reached -70.84±0.66 mV. TEM (Transmission electron microscopy) and XRD (X-ray diffraction) analysis confirmed that circular and triangular crystalline AgNPs with mean diameter of 14.6 nm were synthesized. Since heat-inactivated extracts also mediated the formation of AgNPs, enzymatic reactions are likely not involved in AgNPs formation. A high absolute ζ-potential value of the AgNPs, possibly caused by interaction with proteins likely explains the high stability of AgNPs suspensions. AgNPs showed antimicrobial activity against Bacillussubtilis and Escherichiacoli in liquid and solid medium.

Clerodane Diterpenoids from Tinospora Sagittata (Oliv.) Gagnep

Planta Medica. Jan, 2012  |  Pubmed ID: 21969117

Three new clerodane diterpene glycosides, tinospinosides A (1), B (2), and C (3) were isolated from the roots of Tinospora sagittata (Oliv.) Gagnep. Their structures were determined to be (2 S,4a R,6a R,9 R,10a S,10b S)-2-(3-furanyl)-9-( β-D-glucopyranosyloxy)-1,4,4a,5,6,6a,9,10,10a,10b-decahydro-6a,10b-dimethyl-4-oxo-2H-naphtho[2,1-c]pyran-7-carboxylic acid methyl ester (1), (2 S,4a S,6a R,9 R,10a R,10b S)-2-(3-furanyl)-9-( β-D-glucopyranosyloxy)-1,4,4a,5,6,6a,9,10,10a,10b-decahydro-4a-hydroxyl-6a,10b-dimethyl-4-oxo-2H-naphtho[2,1-c]pyran-7-carboxylic acid methyl ester (2) and (2 S,4a R,6a R,9 R,10a R,10b S)-2-(3-furanyl)-9-( β-D-glucopyranosyloxy)-1,4,4a,5,6,6a,9,10,10a,10b-decahydro-4a-hydroxyl-6a,10b-dimethyl-4-oxo-2H-naphtho[2,1-c]pyran-7-carboxylic acid methyl ester (3), by various spectroscopic analyses, chemical reactions, and computer-assisted calculations. The inhibitory activities of NO production by these compounds and their chemical derivatives in lipopolysaccharide and TNF γ-activated macrophage-like cell line J774.1 were tested. Tinospin A, 12- EPI-tinospin A, tinospinoside B, and tinospinoside C showed inhibitory activities of NO production with the IC₅₀ values of 162, 182, 290, and 218 µM, respectively.

EGFR-specific PEGylated Immunoliposomes for Active SiRNA Delivery in Hepatocellular Carcinoma

Biomaterials. Jan, 2012  |  Pubmed ID: 21963149

The development of immunoliposomes for systemic siRNA (small interfering RNA) delivery is highly desired. We reported previously the development of targeted LPD (liposome-polycation-DNA complex) conjugated with anti-EGFR (epidermal growth factor receptor) Fab' (TLPD-FCC) for siRNA delivery, which showed superior gene silencing activity in EGFR-overexpressing breast cancers. However, TLPD-FCC did not achieve satisfactory gene silencing activity in EGFR-overexpressing hepatocellular carcinoma (HCC). In this study, some modifications including increased antibody conjugation efficiency and reduced PEGylation degree were made to TLPD-FCC to increase gene silencing activity in HCC. The resultant optimized liposomes denoted as TLPD-FP75 efficiently bound and delivered to EGFR-overexpressing HCC, resulting in enhanced gene silencing activity compared to untargeted LPD (NTLPD-FP75). Tissue distribution in vivo revealed that the accumulation of TLPD-FP75 was higher than NTLPD-FP75 in orthotopic HCC model of mice. The promoted uptake of TLPD-FP75 in HCC cells was confirmed by confocal microscopy. To investigate the in vivo gene silencing activity, we administered TLPD-FP75 by intravenous injections into mice bearing orthotopic HCC. The results showed TLPD-FP75 potently suppressed luciferase expression, while little silencing was observed in NTLPD-FP75. TLPD-FP75 was demonstrated to possess potent gene silencing activity in HCC and will potentially increase the feasibility of HCC gene therapy.

Vascular Smooth Muscle Cell-derived Adiponectin: A Paracrine Regulator of Contractile Phenotype

Journal of Molecular and Cellular Cardiology. Feb, 2012  |  Pubmed ID: 21952104

Adiponectin is a cardioprotective adipokine derived predominantly from visceral fat. We recently demonstrated that exogenous adiponectin induces vascular smooth muscle cell (VSMC) differentiation via repression of mTORC1 and FoxO4. Here we report for the first time that VSMC express and secrete adiponectin, which acts in an autocrine and paracrine manner to regulate VSMC contractile phenotype. Adiponectin was found to be expressed in human coronary artery and mouse aortic VSMC. Importantly, siRNA knock-down of endogenous adiponectin in VSMC significantly reduced the expression of VSMC contractile proteins. Contractile protein deficiency was also observed in primary VSMC isolated from Adiponectin(-/-) mice. This deficiency could be rescued by culturing Adiponectin(-/-) VSMC in conditioned media from wild type (WT) VSMC. Moreover, the paracrine effect of VSMC-derived adiponectin was confirmed as adiponectin neutralizing antibody blocked the rescue. Overexpressed adiponectin also exerted paracrine effects on neighboring untransfected VSMC, which was also blocked by adiponectin neutralizing antibody. Interestingly, adiponectin expression was inducible by the PPARγ agonist rosiglitazone. Our data support an important role for VSMC-derived adiponectin in maintaining VSMC contractile phenotype, contributing to critical cardioprotective functions in the vascular wall. This article is part of a Special Issue entitled "Local Signaling in Myocytes".

Improving Immobilization of Lipase Onto Magnetic Microspheres with Moderate Hydrophobicity/hydrophilicity

Colloids and Surfaces. B, Biointerfaces. Jan, 2012  |  Pubmed ID: 21955507

Magnetic microspheres with carboxyl groups were prepared by copolymerization of vinyl acetate (VAC), acrylamide (AM), and acrylic acid (AA) in the presence of oleic acid-coated Fe(3)O(4) nanoparticles. Scanning electron microscope (SEM) photo showed that the average diameter of magnetic microspheres was about 400 nm. Also, FTIR spectra analysis indicated that monomers were successfully enfolded on the microspheres' surface. They were used as support to immobilize lipase via physical adsorption and covalent binding. To investigate the effect of the microsphere surface properties on lipase immobilization, a series of microspheres with different hydrophobic/hydrophilic surface characteristics were prepared by adjusting molar percentages of different monomers. The results showed that microspheres with different hydrophobicities/hydrophilicities had different immobilized ratios and different activity recovery. Compared with microspheres having hydrophilic characteristics, that with hydrophobic characteristics had a much higher lipase binding efficiency. However, this study further demonstrated that moderate hydrophobicity/hydrophilicity of microsphere surface was very important for elevating activity recovery. When AM (hydrophilic monomer) held 14.3% of total amount of monomers, the activity recovery was the highest (reaching 87%, 418 U/g support). Possible reasons for these observations were discussed and a supposed mechanism was speculated.