[Control Study for Muscle Force and Component of Body of Female Patients with Knee Osteoarthritis]

Zhongguo Gu Shang = China Journal of Orthopaedics and Traumatology. Nov, 2008  |  Pubmed ID: 19143243

To understand the information of female patients with knee osteoarthritis regarding muscle force, constitution parameter.

Biotic and Abiotic Stress Responses Through Calcium-dependent Protein Kinase (CDPK) Signaling in Wheat (Triticum Aestivum L.)

Plant Signaling & Behavior. Sep, 2008  |  Pubmed ID: 19704816

Calcium-dependent protein kinases (CDPKs) sense the calcium concentration changes in plant cells and play important roles in signaling pathways for disease resistance and various stress responses as indicated by emerging evidences. Among the 20 wheat CDPK genes studied, 10 were found to respond to drought, salinity and ABA treatments. Consistent with previous observations, one CDPK gene was shown to respond to multiple abiotic stresses in wheat suggesting that CDPKs could be converging points for multiple signaling pathways. Among the 12 wheat CDPK genes that were responsive to Blumeria graminis tritici (Bgt) infection or the treatment of hydrogen peroxide (H(2)O(2)), eight also responded to abiotic stresses, suggesting a cross-talk between biotic and abiotic stress signaling pathways. Phylogenetic analysis indicated that some of these genes were closely related to CDPKs from other species, whose functions have been partially studied, suggesting similar functions wheat CDPK genes. Combining the up-to-date knowledge of CDPK functions and our observations, a model was developed to project the possible roles of wheat CDPK genes in the signaling of biotic and abiotic stress responses.

Mitochondria-initiated Apoptosis Triggered by Oxidative Injury Play a Role in Total Parenteral Nutrition-associated Liver Dysfunction in Infant Rabbit Model

Journal of Pediatric Surgery. Sep, 2009  |  Pubmed ID: 19735813

The aim of the study was to investigate oxidative injury and apoptosis as the mechanisms underlying total parenteral nutrition (TPN)-associated liver dysfunction.

Oxidized Low-density Lipoprotein (Ox-LDL) Impacts on Erythrocyte Viscoelasticity and Its Molecular Mechanism

Journal of Biomechanics. Oct, 2009  |  Pubmed ID: 19747680

The oxidized low-density lipoprotein (Ox-LDL) plays an important role in atherosclerosis, yet it remains unclear if it damages circulating erythrocytes. In this study, erythrocyte deformability and its membrane proteins after Ox-LDL incubations are investigated by micropipette aspiration, thiol radical measurement, and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Results show that Ox-LDL incubation reduces the erythrocyte deformability, decreases free thiol radical contents in erythrocytes, and induces the cross-linking among membrane proteins. SDS-PAGE analysis reveals a high molecular weight (HMW) complex as well as new bands between spectrins and band 3 and reduced ratios between band 3 and other major membrane skeletal proteins. Analyses indicate that Ox-LDL makes erythrocytes harder to deform through a molecular mechanism by which the oxidation of free thiol radicals forms disulfide bonds among membrane skeletal proteins.

Microwave Enabled Umpulong Mechanism Based Rapid and Efficient Four- and Six-component Domino Formations of 2-(2'-azaaryl)imidazoles and Anti-1,2-diarylethylbenzamides

The Journal of Organic Chemistry. Dec, 2009  |  Pubmed ID: 19938854

Concise and efficient six-component and four-component domino approaches to anti-1,2-diarylethylbenzamides and highly substituted 2-(2'-azaaryl)imidazoles have been developed under solvent-free and microwave-irradiation conditions. The reactions showed a broad scope of substrates in which a wide range of common commercial aromatic aldehydes and heteroaryl nitriles can be used. The syntheses were finished within short periods (15-34 min) with good to excellent chemical yields and stereoselectivity that avoided tedious workup isolations. New mechanisms involving an umpolung have been proposed for these two reaction processes.

[Screening of Anti-Cry1Ac ScFv from A Phage Display Antibody Library.]

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi = Chinese Journal of Cellular and Molecular Immunology. Dec, 2009  |  Pubmed ID: 19961804

To clone human anti-Cry1Ac single-chain antibodies (scFv) from Tomlinson J phage antibody library.

[Feasibility of Packaging Screening for Cervical Cancer, Breast Cancer, and Reproductive Tract Infection in a Rural Area in China]

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae. Oct, 2009  |  Pubmed ID: 19968083

To investigate the prevalence of cervical cancer, breast cancer, and reproductive tract infection (RTI) among women living in a county of China, identify these women's recognition about these three diseases and their attitude toward the screening, and evaluate the feasibility of the packaging screening program in rural areas in China.

[Characterization of Hormone Receptor Status in 5758 Chinese Females with Breast Cancer]

Zhonghua Zhong Liu Za Zhi [Chinese Journal of Oncology]. Sep, 2009  |  Pubmed ID: 20021865

To analyze the characteristics of hormone receptor status in Chinese females with breast cancer.

Human Papillomavirus Testing for Cervical Cancer Screening: Results from a 6-year Prospective Study in Rural China

American Journal of Epidemiology. Sep, 2009  |  Pubmed ID: 19692327

Long-term follow-up evaluations of cervical screening approaches are limited in low-resource areas. This prospective study assessed the risk of future cervical intraepithelial neoplasia grade 2 or worse (CIN2+) associated with baseline human papillomavirus (HPV) and cytologic status. In rural China, 1,997 women were screened with 6 screening tests, including colposcopic evaluations, and underwent biopsies in 1999. In December 2005, 1,612 women with cervical intraepithelial neoplasia grade 1 or less at baseline were rescreened by visual inspection, liquid-based cytology, and HPV-DNA testing. All women underwent colposcopy at follow-up, with biopsies taken from women with visually apparent lesions or cytologic abnormalities. Twenty women developed incident CIN2+. The crude relative risk of CIN2+ for baseline HPV-positive women was 52 (95% confidence interval: 12.1, 222.5). The crude relative risk of CIN2+ was 167 (95% confidence interval: 21.9, 1,265) for baseline and follow-up repeatedly HPV-positive women compared with repeatedly HPV-negative women. Among 1,374 baseline HPV-negative women, 2 and no incident CIN2+ cases were detected in baseline cytologically normal and abnormal subgroups, respectively. Among 238 baseline HPV-positive women, 6 of 18 incident cases of CIN2+ developed in the cytologically normal group. This study demonstrates that a single oncogenic HPV-DNA test is more effective than cytology in predicting future CIN2+ status.

[Diagnosis and Treatment of Ovotesticular Disorders of Sex Development in Children]

Zhonghua Nan Ke Xue = National Journal of Andrology. Jul, 2009  |  Pubmed ID: 19694378

To investigate the diagnosis and treatment of ovotesticular disorders of sex development (DSD) in children.

Diversity-oriented Synthesis of Kröhnke Pyridines

Journal of Combinatorial Chemistry. Sep-Oct, 2009  |  Pubmed ID: 19694408

An efficient reagent-controlled approach for the regiospecific synthesis of new 2,2'-bipyridine derivatives in high-temperature water via microwave-assisted multicomponent reactions of aldehydes, 3-aryl-3-oxopropanenitrile, 2-acetylpyridine, and ammonium acetate is reported. Furthermore, aromatic aldehydes reacted with 1,2-diphenylethanone, resulting in structurally complex penta-arylpyridines. This chemistry provides an efficient and promising synthetic strategy to diversity-oriented construct poly arylpyridine skeleton.

A New Dynamic Device for Low-dimensional Materials Testing

The Review of Scientific Instruments. Dec, 2009  |  Pubmed ID: 20059182

As the geometrical size of low-dimensional materials decreases to micro- or nanoscale, the traditional dynamic loading system cannot be used anymore to measure the dynamic mechanical property. In this study, a new dynamic loading system was developed. A piezoelectric transducer actuator was used for displacement loading, and a mechanical lever was designed to amplify the displacement load. Finite element method simulation and validation experiments were conducted to analyze the strength and function of the mechanical lever. As an application test, a sample from an aluminum film was investigated using the system. The success of the experiment, as shown by the results, demonstrated the feasibility of the system for low-dimensional materials study.

Biorheological Properties of Reconstructed Erythrocytes and Its Function of Carrying-releasing Oxygen

Artificial Cells, Blood Substitutes, and Immobilization Biotechnology. 2009  |  Pubmed ID: 19148839

Erythrocyte shape and biomechanical properties have close relation to its physiological function. In this research the erythrocyte was reconstructed with natural structure protein and lipids based on cellular mechanics and hemorheology concepts. The biomechanical properties of the reconstructed erythrocyte were determined with the micropipette aspiration system. The shapes of reconstructed erythrocyte were obtained with electron scanning microscope. The oxygen carrying-releasing function was analyzed with the HEMOX analyzer from TCS, the experimental results indicated that the reconstructed erythrocytes were similar to the natural erythrocyte: having biconcave disc shape, good deformability and carrying-releasing oxygen function.

A Small Molecule That Binds Hedgehog and Blocks Its Signaling in Human Cells

Nature Chemical Biology. Mar, 2009  |  Pubmed ID: 19151731

Small-molecule inhibition of extracellular proteins that activate membrane receptors has proven to be extremely challenging. Diversity-oriented synthesis and small-molecule microarrays enabled the discovery of robotnikinin, a small molecule that binds the extracellular Sonic hedgehog (Shh) protein and blocks Shh signaling in cell lines, human primary keratinocytes and a synthetic model of human skin. Shh pathway activity is rescued by small-molecule agonists of Smoothened, which functions immediately downstream of the Shh receptor Patched.

Novel Inhibitors of Human Histone Deacetylase (HDAC) Identified by QSAR Modeling of Known Inhibitors, Virtual Screening, and Experimental Validation

Journal of Chemical Information and Modeling. Feb, 2009  |  Pubmed ID: 19182860

Inhibitors of histone deacetylases (HDACIs) have emerged as a new class of drugs for the treatment of human cancers and other diseases because of their effects on cell growth, differentiation, and apoptosis. In this study we have developed several quantitative structure-activity relationship (QSAR) models for 59 chemically diverse histone deacetylase class 1 (HDAC1) inhibitors. The variable selection k nearest neighbor (kNN) and support vector machines (SVM) QSAR modeling approaches using both MolconnZ and MOE chemical descriptors generated from two-dimensional rendering of compounds as chemical graphs have been employed. We have relied on a rigorous model development workflow including the division of the data set into training, test, and external sets and extensive internal and external validation. Highly predictive QSAR models were generated with leave-one-out cross-validated (LOO-CV) q2 and external R2 values as high as 0.80 and 0.87, respectively, using the kNN/MolconnZ approach and 0.93 and 0.87, respectively, using the SVM/MolconnZ approach. All validated QSAR models were employed concurrently for virtual screening (VS) of an in-house compound collection including 9.5 million molecules compiled from the ZINC7.0 database, the World Drug Index (WDI) database, the ASINEX Synergy libraries, and other commercial databases. VS resulted in 45 structurally unique consensus hits that were considered novel putative HDAC1 inhibitors. These computational hits had several novel structural features that were not present in the original data set. Four computational hits with novel scaffolds were tested experimentally, and three of them were confirmed active against HDAC1, with IC50 values for the most active compound of 1.00 microM. The fourth compound was later identified to be a selective inhibitor of HDAC6, a Class II HDAC. Moreover, two of the confirmed hits are marketed drugs, which could potentially facilitate their further development as anticancer agents. This study illustrates the power of the combined QSAR-VS method as a general approach for the effective identification of structurally novel bioactive compounds.

Identifying the Proteins to Which Small-molecule Probes and Drugs Bind in Cells

Proceedings of the National Academy of Sciences of the United States of America. Mar, 2009  |  Pubmed ID: 19255428

Most small-molecule probes and drugs alter cell circuitry by interacting with 1 or more proteins. A complete understanding of the interacting proteins and their associated protein complexes, whether the compounds are discovered by cell-based phenotypic or target-based screens, is extremely rare. Such a capability is expected to be highly illuminating--providing strong clues to the mechanisms used by small-molecules to achieve their recognized actions and suggesting potential unrecognized actions. We describe a powerful method combining quantitative proteomics (SILAC) with affinity enrichment to provide unbiased, robust and comprehensive identification of the proteins that bind to small-molecule probes and drugs. The method is scalable and general, requiring little optimization across different compound classes, and has already had a transformative effect on our studies of small-molecule probes. Here, we describe in full detail the application of the method to identify targets of kinase inhibitors and immunophilin binders.

Total Internal Reflection with Fluorescence Correlation Spectroscopy: Applications to Substrate-supported Planar Membranes

Journal of Structural Biology. Oct, 2009  |  Pubmed ID: 19269331

In this paper, the conceptual basis and experimental design of total internal reflection with fluorescence correlation spectroscopy (TIR-FCS) is described. The few applications to date of TIR-FCS to supported membranes are discussed, in addition to a variety of applications not directly involving supported membranes. Methods related, but not technically equivalent, to TIR-FCS are also summarized. Future directions for TIR-FCS are outlined.

Theoretical Analysis of Alendronate and Risedronate Effects on Canine Vertebral Remodeling and Microdamage

Journal of Biomechanics. May, 2009  |  Pubmed ID: 19285313

Bisphosphonates suppress bone remodeling activity, increase bone volume, and significantly reduce fracture risk in individuals with osteoporosis and other metabolic bone diseases. The objectives of the current study were to develop a mathematical model that simulates control and 1 year experimental results following bisphosphonate treatment (alendronate or risedronate) in the canine fourth lumbar vertebral body, validate the model by comparing simulation predictions to 3 year experimental results, and then use the model to predict potential long term effects of bisphosphonates on remodeling and microdamage accumulation. To investigate the effects of bisphosphonates on bone volume and microdamage, a mechanistic biological model was modified from previous versions to simulate remodeling in a representative volume of vertebral trabecular bone in dogs treated with various doses of alendronate or risedronate, including doses equivalent to those used for treatment of post-menopausal osteoporosis in humans. Bisphosphonates were assumed to affect remodeling by suppressing basic multicellular unit activation and reducing resorption area. Model simulation results for trabecular bone volume fraction, microdamage, and activation frequency following 1 year of bisphosphonate treatment are consistent with experimental measurements. The model predicts that trabecular bone volume initially increases rapidly with 1 year of bisphosphonate treatment, and continues to slowly rise between 1 and 3 years of treatment. The model also predicts that microdamage initially increases rapidly, 0.5-1.5-fold for alendronate or risedronate during the first year of treatment, and reaches its maximum value by 2.5 years before trending downward for all dosages. The model developed in this study suggests that increasing bone volume fraction with long term bisphosphonate treatment may sufficiently reduce strain and damage formation rate so that microdamage does not accumulate above that which is initiated in the first two years of treatment.

[Recurrent Extramammary Paget's Disease of the Penis and Scrotum: Clinical Analysis of 18 Cases]

Zhonghua Nan Ke Xue = National Journal of Andrology. Jan, 2009  |  Pubmed ID: 19288746

To investigate the causes, therapeutic methods and prognosis of recurrent extramammary Paget's disease of the penis and scrotum.

Selective Block of Tunneling Nanotube (TNT) Formation Inhibits Intercellular Organelle Transfer Between PC12 Cells

FEBS Letters. May, 2009  |  Pubmed ID: 19345217

Organelle exchange between cells via tunneling nanotubes (TNTs) is a recently described form of intercellular communication. Here, we show that the selective elimination of filopodia from PC12 cells by 350 nM cytochalasin B (CytoB) blocks TNT formation but has only a weak effect on the stability of existing TNTs. Under these conditions the intercellular organelle transfer was strongly reduced, whereas endocytosis and phagocytosis were not affected. Furthermore, the transfer of organelles significantly correlated with the presence of a TNT-bridge. Thus, our data support that in PC12 cells filopodia-like protrusions are the principal precursors of TNTs and CytoB provides a valuable tool to selectively interfere with TNT-mediated cell-to-cell communication.

Two Asymmetric Syntheses of AMG 221, an Inhibitor of 11beta-hydroxysteroid Dehydrogenase Type 1

The Journal of Organic Chemistry. May, 2009  |  Pubmed ID: 19391575

Two asymmetric syntheses of AMG 221 (2), an inhibitor of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) discovered in our laboratories, are reported. One of the syntheses utilizes chiral trimethylsilyl cyanohydrin 12 as starting material and the other utilizes its enantiomer ent-12. The displacement approach involves the conversion of 12 to 2 via a six-step sequence, occurs with net inversion of configuration, and employs amine 6 as starting material. This route features a novel approach toward chiral dialkylsubstituted alpha-mercaptoacids. The cyclization approach entails the synthesis of 2 from ent-12 in 2 steps, takes place with net retention of configuration, and uses thiourea 8 as starting material. The final step of this route exemplifies a novel synthesis of chiral C-5 dialkylsubstituted 2-aminothiazolones from chiral alpha-hydroxyacids and thioureas. Insights into the mechanism of this transformation and study of the effect of the medium on the stereochemical outcome of the reaction are presented.

Matrix Metalloproteinase-7 and ADAM-12 (a Disintegrin and Metalloproteinase-12) Define a Signaling Axis in Agonist-induced Hypertension and Cardiac Hypertrophy

Circulation. May, 2009  |  Pubmed ID: 19398663

Excessive stimulation of Gq protein-coupled receptors by cognate vasoconstrictor agonists induces a variety of cardiovascular processes, including hypertension and hypertrophy. Here, we report that matrix metalloproteinase-7 (MMP-7) and a disintegrin and metalloproteinase-12 (ADAM-12) form a novel signaling axis in these processes.

Fano-resonance-based Mach-Zehnder Optical Switch Employing Dual-bus Coupled Ring Resonator As Two-beam Interferometer

Optics Express. Apr, 2009  |  Pubmed ID: 19399151

A kind of Mach-Zehnder optical switch with a dual-bus coupled ring resonator as a two-beam interferometer is proposed and investigated. The analysis based on the transfer matrix method shows that a sharp asymmetric Fano line shape can be generated in the transmission spectra of such a configuration, which can be used to significantly reduce the phase change required for switching. Meanwhile, it can also be found that complete extinctions can be achieved in both switching states if the structural parameters are carefully chosen and the phase bias is properly set. Through tuning the phase difference between the arms of the Mach-Zehnder interferometer, complete extinction can be easily kept within a large range of the ring-bus coupling ratios in the OFF state. By properly modulating the phase change in the ring waveguide, the shift of the resonant frequency and the asymmetry of the transmission spectra can be controlled to finally enable optical switching with a high extinction ratio, even complete extinction, in the ON state. The switching functionality is verified by the finite-difference time-domain simulation.

In Vitro and in Vivo Suppression of Hepatocellular Carcinoma Growth by Midkine-antisense Oligonucleotide-loaded Nanoparticles

World Journal of Gastroenterology : WJG. Apr, 2009  |  Pubmed ID: 19399928

To synthesize antisense oligonucleotides (ASODNs) of midkine (MK), package the ASODNs with nanoparticles, and to inhibit hepatocellular carcinoma (HCC) growth using these nanoparticles.

N546 in Beta18-beta19 Loop is Important for Binding and Toxicity of the Bacillus Thuringiensis Cry1Ac Toxin

Journal of Invertebrate Pathology. Jun, 2009  |  Pubmed ID: 19416731

Our previous mutagenic analysis showed that the unique residue N546 in the apex of beta18-beta19 loop of Bacillus thuringiensis Cry1Ac toxin is important for its toxicity. In this study, trypsin digestion susceptibility, binding to BBMV and oligomer formation activity was therefore analyzed to determine the mechanism of toxicity change of these mutant toxins. The results showed that residue N546 was not involved in toxin oligomerisation and maintaining the stability of toxin, the enhanced toxicity of mutant N546A was just because of increased binding to BBMV, and reduction in toxicity of other mutants were caused by reduction in initial or irreversible binding to BBMV. This is the first report that revealed N546 in Cry1Ac domain III played an essential role in its insecticidal activity and binding to insect BBMV.

Antitumor Agents. 266. Design, Synthesis, and Biological Evaluation of Novel 2-(furan-2-yl)naphthalen-1-ol Derivatives As Potent and Selective Antibreast Cancer Agents

Journal of Medicinal Chemistry. Jun, 2009  |  Pubmed ID: 19425534

In a continuing study, we explored how the individual rings in neo-tanshinlactone (1) influence its potent and selective in vitro antibreast cancer activity. Accordingly, we discovered a novel class of antibreast cancer agents, 2-(furan-2-yl)naphthalen-1-ol derivatives, based on an active C-ring opened model compound 5. Further optimization led to 18 and 21, which showed decreased cytotoxic potency but better selectivity than neo-tanshinlactone analogue 2. Interestingly, 20 showed broad cytotoxicity against human cancer cell lines.

Elevated Serum Soluble Fas Ligand is a Promising Marker of Testicular Toxicity Induced by Epirubicin in Rats

Toxicology Letters. Apr, 2009  |  Pubmed ID: 19429229

To investigate the role of the Fas/Fas ligand (Fas/FasL) system in testicular toxicity induced by epirubicin (Epi) and to correlate the system with the serum levels of soluble Fas and Fas ligand (sFas/sFasL), epirubicin was intraperitoneally administered to male Sprague-Dawley male rats at doses of 1.2mg/kg once a week for 10 weeks, and genital organ weights and histopathology were examined. Fas and FasL expression in rat testis were examined by immunohistochemistry. Apoptosis was assessed by TUNEL assay. Expression levels of Fas and FasL were analyzed by RT-PCR and Western blotting. Serum sFas/sFasL levels were determined by ELISA. The results show that the testicular toxicity of Epi involved germ cell apoptosis. Fas and FasL protein expression levels were markedly increased in Epi-treated rat testes, as was expression of sFasL. In particular, increasing serum sFasL levels were positively correlated with elevated expression levels of FasL and sFasL in the testes of Epi-treated rats, revealing serum sFasL to be a promising marker of testicular toxicity after cytotoxic chemotherapy.

Real-time Polymerase Chain Reaction MicroRNA Detection Based on Enzymatic Stem-loop Probes Ligation

Analytical Chemistry. Jul, 2009  |  Pubmed ID: 19469541

MiRNAs (microRNAs) are a group of endogenous, small noncoding RNA with the length of 18-25 nucleotides, which have recently been demonstrated to play important roles in a wide range of biological processes. In this work, we developed a simple, sensitive, specific, and inexpensive assay through the combination of enzymatic probe ligation and real-time PCR amplification for the measurement of mature miRNAs. A couple of novel DNA probes with a stem-loop structure were implemented to reduce nonspecific ligation by at least 100-fold. The assay has several remarkable features including wide dynamic range, low total RNA input (0.02-0.2 ng), distinct anti-interference from precursor miRNAs (signal-to-noise ratio > 500), and single-base mismatch discrimination among miRNA sequences. In addition, a one-tube assay could be accomplished by designing a couple of universal probes, which makes it feasible to examine the expression of a whole family of miRNA (such as let-7) at one time. Finally, we validated the method for quantifying the expression of four mature miRNAs including miR-122, miR-1, miR-34a, and let-7a across 10 mouse tissues, where U6 snRNA could be simultaneously examined as an endogenous control. Thus, this method revealed a great potential for miRNA quantitation in ordinary laboratory studies and clinical diagnoses.

[Tadalafil for Erectile Dysfunction: Efficacy Evaluation]

Zhonghua Nan Ke Xue = National Journal of Andrology. Apr, 2009  |  Pubmed ID: 19472916

A new type of phosphodiesterase 5 inhibitor, Tadalafil, has been used clinically to treat erectile dysfunction (ED). In this review, we analyzed the recent findings from the clinical trials on tadalafil in ED treatment. All data showed that oral tadalafil was an effective and well-tolerated therapeutic for ED, with many potential pharmacological actions. All this may help to give full play to the clinical value of tadalafil.

[Clinicopathological Characteristics and Prognosis of Patients with Breast Cancer over 65 Years of Age]

Zhonghua Yi Xue Za Zhi. Jan, 2009  |  Pubmed ID: 19489267

To study clinicopathological characteristics and prognosis of elderly women with breast cancer.

[Influence of Migu Capsule and Strengthening Spleen Prescription on the Expression of Small Intestine VDR MRNA in Calf Muscle on Ovariectomy Rats]

Zhongguo Gu Shang = China Journal of Orthopaedics and Traumatology. May, 2009  |  Pubmed ID: 19522400

To observe the effect of Migu capsule and Strengthening Spleen prescriptions on the expression of vitamin D receptor on small intestine and calf muscle of the rat, while observing whether the Chinese medicine complex prescriptions of different effect such as invigorating the kidney and strengthening the spleen had selectivity to expression of the VDR mRNA.

Discovery of Geranylgeranyltransferase-I Inhibitors with Novel Scaffolds by the Means of Quantitative Structure-activity Relationship Modeling, Virtual Screening, and Experimental Validation

Journal of Medicinal Chemistry. Jul, 2009  |  Pubmed ID: 19537691

Geranylgeranylation is critical to the function of several proteins including Rho, Rap1, Rac, Cdc42, and G-protein gamma subunits. Geranylgeranyltransferase type I (GGTase-I) inhibitors (GGTIs) have therapeutic potential to treat inflammation, multiple sclerosis, atherosclerosis, and many other diseases. Following our standard workflow, we have developed and rigorously validated quantitative structure-activity relationship (QSAR) models for 48 GGTIs using variable selection k nearest neighbor (kNN), automated lazy learning (ALL), and partial least squares (PLS) methods. The QSAR models were employed for virtual screening of 9.5 million commercially available chemicals, yielding 47 diverse computational hits. Seven of these compounds with novel scaffolds and high predicted GGTase-I inhibitory activities were tested in vitro, and all were found to be bona fide and selective micromolar inhibitors. Notably, these novel hits could not be identified using traditional similarity search. These data demonstrate that rigorously developed QSAR models can serve as reliable virtual screening tools, leading to the discovery of structurally novel bioactive compounds.

[Significance of Three Imaging Examinations Performed Before Decompression Surgery for Traumatic Optic Nerve Injury]

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi = Chinese Journal of Otorhinolaryngology Head and Neck Surgery. Feb, 2009  |  Pubmed ID: 19558894

[A Review of Health Economic Evaluation on Cervical Cancer Screening by Visual Inspection with Acetic Acid]

Zhonghua Liu Xing Bing Xue Za Zhi = Zhonghua Liuxingbingxue Zazhi. Jan, 2009  |  Pubmed ID: 19565857

Maintenance of Adrenergic Vascular Tone by MMP Transactivation of the EGFR Requires PI3K and Mitochondrial ATP Synthesis

Cardiovascular Research. Dec, 2009  |  Pubmed ID: 19578070

G-protein-coupled receptors (GPCRs) modulate vascular tone, at least in part, via matrix metalloproteinase (MMP) transactivation of the epidermal growth factor receptor (EGFR). We previously have identified novel signalling pathways downstream of the EGFR suggestive of mitogen-activated protein kinase and mitochondrial redox control of vascular tone. In the present study, we examined whether MMP modulation of vascular tone involves phosphoinositide 3-kinase (PI3K) and mitochondrial ATP synthesis.

Tumor Necrosis Factor-alpha-converting Enzyme is a Key Regulator of Agonist-induced Cardiac Hypertrophy and Fibrosis

Hypertension. Sep, 2009  |  Pubmed ID: 19581512

Cardiac remodeling is associated with hypertrophy and fibrosis processes, which may depend on the activity of matrix metalloproteinases (MMPs) and "a disintegrin and metalloproteinases" (ADAMs). We investigated whether ADAM-17 (tumor necrosis factor-alpha-converting enzyme [TACE]) plays a role in agonist-induced cardiac remodeling and the relationships established among TACE, MMP-2, and ADAM-12. We targeted TACE in rodent models of spontaneous and agonist-induced hypertension using RNA interference combined with quantitative RT-PCR, activity determinations, and functional studies. Treatment of spontaneously hypertensive rats with previously validated TACE small-interfering RNA for 28 days resulted in systemic knockdown of TACE expression. TACE knockdown effectively stopped the development of cardiac hypertrophy. Mice receiving angiotensin II (1.4 mg/kg per day for 12 days) exhibited cardiac hypertrophy, as well as fibrosis, which was associated with elevated myocardial expression of molecular markers of hypertrophy (alpha-skeletal actin, beta-myosin heavy chain, and brain natriuretic peptide) and fibrosis (collagen types I and III and fibronectin), as well as MMP-2 and ADAM-12. Treatment with TACE small-interfering RNA (but not with PBS or luciferase small-interfering RNA) inhibited TACE expression, thus preventing angiotensin II-induced cardiac hypertrophy and fibrosis. Moreover, knockdown of TACE inhibited angiotensin II-induced overexpression of markers of myocardial hypertrophy and fibrosis, as well as ADAM-12 and MMP-2. These findings provide the first in vivo evidence that agonist-induced cardiac hypertrophy and fibrosis processes are signaled through TACE, which acts through novel pathways involving transcriptional regulation of ADAM-12 and MMP-2. Targeting TACE has potential therapeutic importance for modulating agonist-induced cardiac remodeling.

[Research Progress in Estimating Parameters of Blood Substitute Function]

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi = Journal of Biomedical Engineering = Shengwu Yixue Gongchengxue Zazhi. Jun, 2009  |  Pubmed ID: 19634692

The shortage of healthy blood resource and the problem of virus infection have urged the study of blood substitute. The technologies of modified hemoglobin, perfluorocarbons and Hb-vesicles have been developing quickly, and some of which have already been formed into large-scale preparation and production. However, there is no completed evaluation system for the blood substitute at present, and it is still hard to estimate the function of blood substitute completely. This article takes the evaluation of the blood substitute as a key point, discusses the evaluation parameters of blood substitute, and presents the physical and chemical property, the availability and safety as well as the preservation condition of the blood substitute. The data concerned are based on the studies in China and abroad and referred to the latest progress all over the world.

Activating Mutations of the TRPML1 Channel Revealed by Proline-scanning Mutagenesis

The Journal of Biological Chemistry. Nov, 2009  |  Pubmed ID: 19638346

The mucolipin TRP (TRPML) proteins are a family of endolysosomal cation channels with genetically established importance in humans and rodent. Mutations of human TRPML1 cause type IV mucolipidosis, a devastating pediatric neurodegenerative disease. Our recent electrophysiological studies revealed that, although a TRPML1-mediated current can only be recorded in late endosome and lysosome (LEL) using the lysosome patch clamp technique, a proline substitution in TRPML1 (TRPML1(V432P)) results in a large whole cell current. Thus, it remains unknown whether the large TRPML1(V432P)-mediated current results from an increased surface expression (trafficking), elevated channel activity (gating), or both. Here we performed systemic Pro substitutions in a region previously implicated in the gating of various 6 transmembrane cation channels. We found that several Pro substitutions displayed gain-of-function (GOF) constitutive activities at both the plasma membrane (PM) and endolysosomal membranes. Although wild-type TRPML1 and non-GOF Pro substitutions localized exclusively in LEL and were barely detectable in the PM, the GOF mutations with high constitutive activities were not restricted to LEL compartments, and most significantly, exhibited significant surface expression. Because lysosomal exocytosis is Ca(2+)-dependent, constitutive Ca(2+) permeability due to Pro substitutions may have resulted in stimulus-independent intralysosomal Ca(2+) release, hence the surface expression and whole cell current of TRPML1. Indeed, surface staining of lysosome-associated membrane protein-1 (Lamp-1) was dramatically increased in cells expressing GOF TRPML1 channels. We conclude that TRPML1 is an inwardly rectifying, proton-impermeable, Ca(2+) and Fe(2+)/Mn(2+) dually permeable cation channel that may be gated by unidentified cellular mechanisms through a conformational change in the cytoplasmic face of the transmembrane 5 (TM5). Furthermore, activation of TRPML1 in LEL may lead to the appearance of TRPML1 proteins at the PM.

A Case Report of Severe Aspergillus Flavus Penile Infection

Asian Journal of Andrology. Sep, 2009  |  Pubmed ID: 19684607

Factors Associated with Serum Retinol, Alpha-tocopherol, Carotenoids, and Selenium in Hispanics with Problems of HIV, Chronic Hepatitis C, and Drug Use

Journal of Public Health Policy. Sep, 2009  |  Pubmed ID: 19806070

The effects of hepatitis and drug use on nutritional problems in HIV infection have rarely been examined despite the importance of drug use in the global HIV pandemic. We examined the effects of HIV, hepatitis C, and drug use on serum micronutrients in 300 US Hispanic adults. Chronic hepatitis C infection was associated with lower serum retinol (-8.2 microg/dl, P < 0.0001), alpha-tocopherol (-0.10 ln microg/dl, P = 0.024), and carotenoids (-19.8 microg/dl, P < 0.0001). HIV infection was associated with lower selenium (-6.1 microg/l, P = 0.028). Elevated triglycerides in HIV infection were associated with higher serum retinol and alpha-tocopherol. Drug use was not independently associated with micronutrient alterations. We conclude that hepatitis C is an important determinant of low serum micronutrients, and should be considered in any nutritional assessment of HIV infected populations. As the safety of micronutrient supplementation is not established, policy for appropriate HIV clinical care should distinguish between populations with and without hepatitis coinfection.

MEPE/OF45 Protects Cells from DNA Damage Induced Killing Via Stabilizing CHK1

Nucleic Acids Research. Dec, 2009  |  Pubmed ID: 19808933

Matrix extracellular phosphoglycoprotein/osteoblast factor 45 (MEPE/OF45) was cloned in 2000 with functions related to bone metabolism. We identified MEPE/OF45 for the first time as a new co-factor of CHK1 in mammalian cells to protect cells from DNA damage induced killing. We demonstrate here that MEPE/OF45 directly interacts with CHK1. Knocking down MEPE/OF45 decreases CHK1 levels and sensitizes the cells to DNA damage inducers such as ionizing radiation (IR) or camptothicin (CPT)-induced killing. Over-expressing wild-type MEPE/OF45, but not the mutant MEPE/OF45 (depleted the key domain to interact with CHK1) increases CHK1 levels in the cells and increases the resistance of the cells to IR or CPT. MEPE/OF45, interacting with CHK1, increases CHK1 half-life and decreases CHK1 degradation through the ubiquitine-mediated pathway. In addition, the interaction of MEPE/OF45 with CHK1 decreases CHK1 levels in the ubiquitin E3 ligases (Cul1 and Cul4A) complex, which suggests that MEPE/OF45 competes with the ubiquitin E3 ligases binding to CHK1 and thus decreases CHK1 from ubiquitin-mediated proteolysis. These findings reveal an important role of MEPE/OF45 in protecting cells from DNA damage induced killing through stabilizing CHK1, which would provide MEPE/OF45 as a new target for sensitizing tumor cells to radiotherapy or chemotherapy.

Syntheses of Aminoalcohol-derived Macrocycles Leading to a Small-molecule Binder to and Inhibitor of Sonic Hedgehog

Bioorganic & Medicinal Chemistry Letters. Nov, 2009  |  Pubmed ID: 19819139

We report the synthesis and biological activity of a library of aminoalcohol-derived macrocycles from which robotnikinin, a binder to and inhibitor of Sonic Hedgehog, was derived. Using an asymmetric alkylation to set a key stereocenter and an RCM reaction to close the macrocycle, we were able to synthesize compounds for testing. High-throughput screening via small-molecule microarray (SMM) technology led to the discovery of a compound capable of binding ShhN. Follow-up chemistry led to a library of macrocycles with enhanced biological activity relative to the original hit compounds. Differences in ring size and stereochemistry, leading to alterations in the mode of binding, may account for differences in the degree of biological activity. These compounds are the first ones reported that inhibit Shh signaling at the ShhN level.

Dynamic Changes in Phenolic Compounds and Antioxidant Activity in Oats (Avena Nuda L.) During Steeping and Germination

Journal of Agricultural and Food Chemistry. Nov, 2009  |  Pubmed ID: 19827789

Samples from naked oat were steeped and germinated under controlled conditions in an incubator. Changes of phenolic compounds and antioxidant activity were investigated in oats during steeping and germination. Results revealed that phenolic compounds and antioxidant activity of oats varied with the difference in steeping and germination stages. Compared with raw grains, short-term steeping treatment did not show significant effects (p > 0.05) on phenolic content. Germination can significantly result in the decrease in bound phenolic and the increase in free and total phenolics. Main phenolic acids and avenanthramides were isolated and quantified by HPLC analysis. During steeping, phenolic acids decreased (p < 0.05); avenanthramide N-(3',4'-dihydroxy)-(E)-cinnamoyl-5-hydroxyanthranilic acid first decreased and then increased (p < 0.05), while avenanthramides N-(4'-hydroxy)-(E)-cinnamoyl-5-hydroxyanthranilic acid and N-(4'-hydroxy-3'-methoxy)-(E)-cinnamoyl-5-hydroxyanthranilic acid did not change significantly (p > 0.05). During germination, gallic and caffeic acids first increased (p < 0.05) and then decreased, whereas p-coumaric and ferulic acids and avenanthramides increased (p < 0.05). Nevertheless, avenanthramides did not change significantly (p > 0.05) during the last stage of germination. Oat extracts exhibited increasing high antioxidant activity with the steeping and germination going on, which may explain that antioxidant activity correlated (p < 0.01) significantly with the content of phenolic compounds.

Catanionic Surfactant Vesicles for Electrostatic Molecular Sequestration and Separation

Physical Chemistry Chemical Physics : PCCP. Nov, 2009  |  Pubmed ID: 19830312

Mixtures of oppositely charged surfactants, commonly called catanionic mixtures, are one of the most interesting and promising areas of colloidal chemistry. In this paper we review our previous work and report new results on electrostatic adsorption of organic solutes and DNA to the exterior surfaces of catanionic, unilamellar vesicles which form spontaneously in mixtures of sodium dodecylbenzenesulfonate (SDBS) and cetyltrimethylammonium tosylate (CTAT). Our group, along with others, has shown that organic ions and polyelectrolytes will bind to the exterior surface of oppositely charged catanionic vesicles through interactions with unpaired ionic surfactants present in the vesicle bilayer. The electrostatic sequestration of organic ions with catanionic vesicles is extremely efficient with excellent long-term stability and can be used to perform separations on mixtures of charged organic solutes. Using regular solution theory extended to vesicle-forming surfactant mixtures, we can understand how the composition of the bilayer changes with surfactant dilution, and we study this effect using fluorescence correlation spectroscopy (FCS). We employ FCS to make sensitive measurements of bilayer adsorption and compare the adsorption of a small molecular probe with that of a single-stranded, dye-labeled DNA molecule. From these FCS studies, adsorption isotherms can be obtained that report on the relative binding strengths of the two systems. The results show that DNA binds much more strongly to the exterior surface of positively charged catanionic vesicles, and can even stabilize vesicles at very low surfactant concentrations near the critical aggregation concentration (cac).

Fms-like Tyrosine Kinase 3 Ligand Regulates Migratory Pattern and Antigen Uptake of Lung Dendritic Cell Subsets in a Murine Model of Allergic Airway Inflammation

Journal of Immunology (Baltimore, Md. : 1950). Dec, 2009  |  Pubmed ID: 19917684

Fms-like tyrosine kinase 3 ligand (Flt3L) reverses the features of allergic airway inflammation and increases a Th2-suppressive regulatory lung CD11c(high)CD11b(low) dendritic cell (DC) subset in a mouse model. We examined the migratory pattern and Ag uptake efficiency of lung DC subsets in the therapeutic effect of Flt3L. Lung CD11c(high)CD11b(low) and CD11c(low)CD11b(high) DCs from PBS-treated, OVA-sensitized, and Flt3L-treated/OVA-sensitized BALB/c mice were sorted using MACS and FACS for phenotype analysis. Lymphatic chemokine expression in thoracic lymph nodes was determined by immunohistochemistry. Migration of two lung DC subsets to lymphatic chemokines was examined in vitro using a Transwell chemotaxis assay. Labeled Ag was intranasally delivered into mouse lung to track the migration and Ag uptake of lung DCs. The in vitro cytokine secretion of mediastinal lymph node cells was determined using ELISA. CD11c(low)CD11b(high) DCs have higher expression of CCR5, CCR6, and CCR7, but lower expression of CCR2 than CD11c(high)CD11b(low) DCs. CD11c(low)CD11b(high) DCs in Flt3L-treated/OVA-sensitized mice demonstrated a less mature phenotype, inefficiency in Ag uptake, and impaired migration in vitro to lymphatic chemokine than those in OVA-sensitized mice. Administration of Flt3L decreased the expression of CCR5 and CCR7 in CD11c(low)CD11b(high) DCs in OVA-sensitized mice. Fewer Ag-carrying cells were detected in the lungs and lymph nodes in Flt3L-treated/OVA-sensitized mice than OVA-sensitized mice with a greater decrease in CD11c(low)CD11b(high) DCs. Mediastinal lymph node cells from Flt3L-treated mice secreted higher levels of Th1 cytokines and IL-10 than OVA-sensitized mice in vitro. In conclusion, Flt3L-generated lung immunogenic CD11c(low)CD11b(high) DCs have a less mature phenotype, impaired Ag uptake, and impaired migration to draining lymph nodes.

Computational Studies of Ammonia Channel Function in Glutamine 5'-phosphoribosylpyrophosphate Amidotransferase

Biochemistry. Dec, 2009  |  Pubmed ID: 19921932

Glutamine 5'-phosphoribosylpyrophosphate amidotransferase (GPATase) catalyzes the synthesis of 5'-phosphoribosylamine in a reaction that involves the translocation of ammonia along an intramolecular tunnel linking the two active sites of the enzyme. We now report a locally enhanced sampling (LES) strategy for modeling ammonia transfer between the active sites of Escherichia coli GPATase in its active conformation. Our calculations demonstrate that the ammonia channel in GPATase is best regarded as a "pipe" through which ammonia travels in the absence of an external "driving" potential. This combined LES/PMF computational approach, which offers a straightforward alternative to steered molecular dynamics simulations in studies of substrate channeling, also provides new insights into the molecular basis of the reduced ammonia transfer efficiency exhibited by the L415A GPATase mutant.

Metformin Inhibits Nuclear Factor KappaB Activation and Decreases Serum High-sensitivity C-reactive Protein Level in Experimental Atherogenesis of Rabbits

Heart and Vessels. Nov, 2009  |  Pubmed ID: 20108078

Previous studies demonstrated that metformin has obvious antiatherogenic properties, but the exact mechanism remains unclear. Therefore, we established an atherosclerotic rabbit model in order to investigate the potential effects of metformin on transcription factor nuclear factor kappaB (NF-kappaB) and serum high-sensitivity C-reactive protein (hs-CRP) level, which had been regarded as proatherogenic factors. New Zealand rabbits were randomly divided into three groups: a control group (n = 8), an atherosclerotic group (AS group, n = 8), and a metformin treatment group (Met group, n = 8). The experimental atherosclerotic rabbit model was successfully established at the end of the 8th week. From the 9th week, rabbits in the Met group were administered with 150 mg/kg metformin daily by gavage. Blood samples were collected at days 0 and 8, and at 16 weeks to detect the level of blood lipid and serum glucose. At the end of the experiment, blood samples were withdrawn for determining serum hs-CRP. Aortic samples were harvested for histomorphometric analysis. Immunohistochemistry and Western blotting were used to detect the expression of NF-kappaB subunit p65 in nuclear extracts and phosphorylation of inhibitor of nuclear factor kappaB (IkappaB) in cytoplasmic extracts. An experimental atherosclerotic rabbit model was successfully established. The expression of nuclear NF-kappaB subunit p65 and cytoplasmic phosphorylation of IkappaB protein in the vessel wall was enhanced (P < 0.01, respectively) in the AS group, and serum hs-CRP level was significantly increased in the AS group compared with the control group (3.90 +/- 0.25 mg/l versus 1.36 +/- 0.14 mg/l, P < 0.01). Treatment with metformin significantly attenuated the progression of aortic atherosclerosis. In the Met group, there was a marked reduction in nuclear NF-kappaB subunit p65 and cytoplasmic phosphorylation of IkappaB protein expression (P < 0.01). Serum hs-CRP concentration was also significantly decreased (3.20 +/- 0.20 mg/l versus 3.90 +/- 0.25 mg/l, P < 0.05). Metformin inhibits the phosphorylation of IkappaB and the activation of NF-kappaB in the vessel wall of experimental atherogenesis of rabbits, as well as decreasing the serum level of hs-CRP, thus suggesting that metformin has vascular anti-inflammatory properties, which may be one of its antiatherogenic mechanisms.

[Extract Human DNA from Maggot Crop Contents by Phenol-chloroform Method Coupled with Paramagnetic Particle Method]

Fa Yi Xue Za Zhi. Dec, 2009  |  Pubmed ID: 20225616

To establish an effective phenol-chloroform method coupled with paramagnetic particle method for human DNA extraction from maggot crop contents in STR genotyping.

Low Bandgap Polymers by Copolymerization of Thiophene with Benzothiadiazole

Macromolecular Rapid Communications. Jan, 2009  |  Pubmed ID: 21706537

Three low bandgap copolymers of thiophene and benzothiadiazole with electron-donating and electron-withdrawing substituents, P1, P2, and P3, have been synthesized by Pd-catalyzed Stille-coupling. Electronic energy levels of the polymers are estimated by cyclic voltammetry. The polymer films show a broad absorption band in the wavelength range from 300 to 750 nm. Among the polymers, the polymer that contains the 5,6-dinitrobenzothiadiazole unit, P3, possesses the smallest bandgap of 1.55 eV calculated from its absorption band-edge at ≈800 nm. With the increase of the electron-withdrawing ability of the substituents on the benzothiadiazole unit, the energy bandgap of the polymers decreased in the order P1 > P2 > P3. The results indicate that stronger electron-withdrawing substituents on the acceptor unit can effectively decrease the bandgap of the polymers.

Giant Cell Arteritis: a Rare Disease in Asians

Journal of Clinical Rheumatology : Practical Reports on Rheumatic & Musculoskeletal Diseases. Feb, 2009  |  Pubmed ID: 19131766

TRP Channels of Intracellular Membranes

Journal of Neurochemistry. Apr, 2010  |  Pubmed ID: 20132470

Ion channels are classically understood to regulate the flux of ions across the plasma membrane in response to a variety of environmental and intracellular cues. Ion channels serve a number of functions in intracellular membranes as well. These channels may be temporarily localized to intracellular membranes as a function of their biosynthetic or secretory pathways, i.e., en route to their destination location. Intracellular membrane ion channels may also be located in the endocytic pathways, either being recycled back to the plasma membrane or targeted to the lysosome for degradation. Several channels do participate in intracellular signal transduction; the most well known example is the inositol 1,4,5-trisphosphate receptor (IP(3)R) in the endoplasmic reticulum. Some organellar intracellular membrane channels are required for the ionic homeostasis of their residing organelles. Several newly-discovered intracellular membrane Ca(2+) channels actually play active roles in membrane trafficking. Transient receptor potential (TRP) proteins are a superfamily (28 members in mammal) of Ca(2+)-permeable channels with diverse tissue distribution, subcellular localization, and physiological functions. Almost all mammalian TRP channels studied thus far, like their ancestor yeast TRP channel (TRPY1) that localizes to the vacuole compartment, are also (in addition to their plasma membrane localization) found to be localized to intracellular membranes. Accumulated evidence suggests that intracellularly-localized TRP channels actively participate in regulating membrane traffic, signal transduction, and vesicular ion homeostasis. This review aims to provide a summary of these recent works. The discussion will also be extended to the basic membrane and electrical properties of the TRP-residing compartments.

QDs-DNA Nanosensor for the Detection of Hepatitis B Virus DNA and the Single-base Mutants

Biosensors & Bioelectronics. Apr, 2010  |  Pubmed ID: 20138498

We report here a quantum dots-DNA (QDs-DNA) nanosensor based on fluorescence resonance energy transfer (FRET) for the detection of the target DNA and single mismatch in hepatitis B virus (HBV) gene. The proposed one-pot DNA detection method is simple, rapid and efficient due to the elimination of the washing and separation steps. In this study, the water-soluble CdSe/ZnS QDs were prepared by replacing the trioctylphosphine oxide (TOPO) on the surface of QDs with 3-mercaptopropionic acid (MPA). Subsequently, oligonucleotides were attached to the QDs surface to form functional QDs-DNA conjugates. Along with the addition of DNA targets and Cy5-modified signal DNAs into the QDs-DNA conjugates, sandwiched hybrids were formed. The resulting assembly brings the Cy5 fluorophore, the acceptor, and the QDs, the donor, into proximity, leading to fluorescence emission from the acceptor by means of FRET on illumination of the donor. In order to efficiently detect single-base mutants in HBV gene, oligonucleotide ligation assay was employed. If there existed a single-base mismatch, which could be recognized by the ligase, the detection probe was not ligated and no Cy5 emission was produced due to the lack of FRET. The feasibility of the proposed method was also demonstrated in the detection of synthetic 30-mer oliginucleotide targets derived from the HBV with a sensitivity of 4.0nM by using a multilabel counter. The method enables a simple and efficient detection that could be potentially used for high throughput and multiplex detections of target DNA and the mutants.

Effects of Trabecular Type and Orientation on Microdamage Susceptibility in Trabecular Bone

Bone. May, 2010  |  Pubmed ID: 20149908

Trabecular architecture becomes more rod-like and anisotropic in osteoporotic and aging trabecular bone. In order to address the effects of trabecular type and orientation on trabecular bone damage mechanics, microstructural finite element modeling was used to identify the yielded tissue in ten bovine tibial trabecular bone samples compressed to 1.2% on-axis apparent strain. The yielded tissue was mapped onto individual trabeculae identified by an Individual Trabeculae Segmentation (ITS) technique, and the distribution of the predicted yielding among trabecular types and orientations was compared to the experimentally measured microdamage. Although most of the predicted yielded tissue was found in longitudinal plates (73+/-11%), the measured microcrack density was positively correlated with the proportion of the yielded tissue in longitudinal rods (R(2)=0.52, p=0.02), but not in rods of other directions or plates. The overall fraction of rods and the fractions of rods along the longitudinal and transverse axes were also correlated with the measured microcrack density. In contrast, diffuse damage area did not correlate with any of these quantities. These results agree with the findings that both in vitro and in vivo microcrack densities are correlated with Structure Model Index (SMI), and are also consistent with decreased energy to failure in more rod-like trabecular bone. Together the results suggest that bending or buckling deformations of rod-like trabeculae may make trabecular structures more susceptible to microdamage formation. Moreover, while simple strain-based tissue yield criteria may account for macroscopic yielding, they may not be suitable for identifying damage.

Efficient and Rapid Generation of Induced Pluripotent Stem Cells Using an Alternative Culture Medium

Cell Research. Mar, 2010  |  Pubmed ID: 20157334

Molecular Cloning of a Novel Nuclear Factor, TDRP1, in Spermatogenic Cells of Testis and Its Relationship with Spermatogenesis

Biochemical and Biophysical Research Communications. Mar, 2010  |  Pubmed ID: 20170638

We reported the identification of a novel gene termed TDRP (encoding testis development-related protein) that might be involved in spermatogenesis. The human TDRP gene had two distinct transcripts, TDRP1 and TDRP2, which encoded proteins of 183 aa and 198 aa respectively. Tdrp mRNA was predominantly expressed in testis tissue. We generated rabbit polyclonal antibodies specific against human TDRP1. Immunohistochemistry analysis showed TDRP1 was expressed in spermatogenic cells, especially with high expression in spermatocytes. We provided evidence that TDRP1 distributed in both cytoplasm and nuclei of spermatogenic cells. Expression patterns of Tdrp1 mRNA and its protein were investigated in the rat testis tissues of different developmental stages. Both Tdrp1 mRNA and its protein were barely detected in the testis of neonatal rats, increased remarkably at 3weeks postpartum, and peaked at 2months postpartum. We also investigated TDRP1 expressions in testis tissues of azoospermic men with defective spermatogenesis. Western blot analysis showed that TDRP1 expressions were significantly lower in the testis tissues of azoospermic men compared with normal controls. These current data demonstrated that as a nuclear factor, TDRP1 might play an important role in spermatogenesis.

Gold(I)-catalyzed Tandem Cyclization Approach to Tetracyclic Indolines

Organic Letters. Apr, 2010  |  Pubmed ID: 20196563

Two highly stereoselective cationic gold(I)-catalyzed tandem cyclization reactions of alkynylindoles are described. These reactions demonstrated a novel and general strategy to rapidly construct highly functionalized polycyclic indolines. This approach was successfully employed for a formal synthesis of the akuammiline alkaloid minfiensine.

Surface Structural Transformation and the Phase Transition Kinetics of Brookite TiO₂

Chemistry, an Asian Journal. Oct, 2010  |  Pubmed ID: 20718075

PI(3,5)P(2) Controls Membrane Trafficking by Direct Activation of Mucolipin Ca(2+) Release Channels in the Endolysosome

Nature Communications. 2010  |  Pubmed ID: 20802798

Membrane fusion and fission events in intracellular trafficking are controlled by both intraluminal Ca(2+) release and phosphoinositide (PIP) signalling. However, the molecular identities of the Ca(2+) release channels and the target proteins of PIPs are elusive. In this paper, by direct patch-clamping of the endolysosomal membrane, we report that PI(3,5)P(2), an endolysosome-specific PIP, binds and activates endolysosome-localized mucolipin transient receptor potential (TRPML) channels with specificity and potency. Both PI(3,5)P(2)-deficient cells and cells that lack TRPML1 exhibited enlarged endolysosomes/vacuoles and trafficking defects in the late endocytic pathway. We find that the enlarged vacuole phenotype observed in PI(3,5)P(2)-deficient mouse fibroblasts is suppressed by overexpression of TRPML1. Notably, this PI(3,5)P(2)-dependent regulation of TRPML1 is evolutionarily conserved. In budding yeast, hyperosmotic stress induces Ca(2+) release from the vacuole. In this study, we show that this release requires both PI(3,5)P(2) production and a yeast functional TRPML homologue. We propose that TRPMLs regulate membrane trafficking by transducing information regarding PI(3,5)P(2) levels into changes in juxtaorganellar Ca(2+), thereby triggering membrane fusion/fission events.

Animal Cells Connected by Nanotubes Can Be Electrically Coupled Through Interposed Gap-junction Channels

Proceedings of the National Academy of Sciences of the United States of America. Oct, 2010  |  Pubmed ID: 20855598

Tunneling nanotubes (TNTs) are recently discovered conduits for a previously unrecognized form of cell-to-cell communication. These nanoscale, F-actin-containing membrane tubes connect cells over long distances and facilitate the intercellular exchange of small molecules and organelles. Using optical membrane-potential measurements combined with mechanical stimulation and whole-cell patch-clamp recording, we demonstrate that TNTs mediate the bidirectional spread of electrical signals between TNT-connected normal rat kidney cells over distances of 10 to 70 μm. Similar results were obtained for other cell types, suggesting that electrical coupling via TNTs may be a widespread characteristic of animal cells. Strength of electrical coupling depended on the length and number of TNT connections. Several lines of evidence implicate a role for gap junctions in this long-distance electrical coupling: punctate connexin 43 immunoreactivity was frequently detected at one end of TNTs, and electrical coupling was voltage-sensitive and inhibited by meclofenamic acid, a gap-junction blocker. Cell types lacking gap junctions did not show TNT-dependent electrical coupling, which suggests that TNT-mediated electrical signals are transmitted through gap junctions at a membrane interface between the TNT and one cell of the connected pair. Measurements of the fluorescent calcium indicator X-rhod-1 revealed that TNT-mediated depolarization elicited threshold-dependent, transient calcium signals in HEK293 cells. These signals were inhibited by the voltage-gated Ca(2+) channel blocker mibefradil, suggesting they were generated via influx of calcium through low voltage-gated Ca(2+) channels. Taken together, our data suggest a unique role for TNTs, whereby electrical synchronization between distant cells leads to activation of downstream target signaling.

Analysis of Isoform Specific ERK Signaling on the Effects of Interleukin-1β on COX-2 Expression and PGE2 Production in Human Chondrocytes

Biochemical and Biophysical Research Communications. Nov, 2010  |  Pubmed ID: 20883667

The MAPK/ERK pathway is involved in IL-1β-induced cyclooxygenase (COX-2) expression and prostaglandin E2 (PGE2) production; two factors that play important roles in OA pathogenesis. In the present study, we find that IL-1β induced COX-2 expression and PGE2 production in human chondrocytes via a process that required the activation of the MAPK/ERK pathway. To evaluate the respective roles and relationship of ERK1 and ERK2 on IL-1β induced COX-2 expression and PGE2 production, small interfering RNA was used to knockdown ERK1, ERK2 or both in human chondrocytes. COX-2 expression and PGE2 production were significantly suppressed to a similar degree by the silencing of ERK1 or ERK2 alone. Moreover, the combined knockdown displayed a synergistic effect. Simultaneously, Western blotting indicated that the knockdown of ERK1 or ERK2 down regulated phospho-ERK1 and ERK1 or phospho-ERK2 and ERK2 levels, respectively. No significant compensatory mechanism through the upregulation of the other phospho-ERK and ERK isoform was observed. The combined silencing suppressed both phospho-ERK1/2 and ERK1/2. In conclusion, each ERK isoform similarly influenced IL-1β-mediated COX-2 expression and PGE2 production in human chondrocytes, and ERK1 and ERK2 displayed synergistic effects. Although, inhibition of both ERK1 and ERK2 would be a more effective, each ERK isoform may sufficiently regulate these effects in human chondrocytes. ERK1 or ERK2 may be potential therapeutic target for the inflammatory process of OA.

Quantitative Techniques for Assessing and Controlling the Dispersion and Biological Effects of Multiwalled Carbon Nanotubes in Mammalian Tissue Culture Cells

ACS Nano. Dec, 2010  |  Pubmed ID: 21067152

In vivo studies have demonstrated that the state of dispersion of carbon nanotubes (CNTs) plays an important role in generating adverse pulmonary effects. However, little has been done to develop reproducible and quantifiable dispersion techniques to conduct mechanistic studies in vitro. This study was to evaluate the dispersion of multiwalled carbon nanotubes (MWCNTs) in tissue culture media, with particular emphasis on understanding the forces that govern agglomeration and how to modify these forces. Quantitative techniques such as hydrophobicity index, suspension stability index, attachment efficiency, and dynamic light scattering were used to assess the effects of agglomeration and dispersion of as-prepared (AP), purified (PD), or carboxylated (COOH) MWCNTs on bronchial epithelial and fibroblast cell lines. We found that hydrophobicity is the major factor determining AP- and PD-MWCNT agglomeration in tissue culture media but that the ionic strength is the main factor determining COOH-MWCNT suspendability. Bovine serum albumin (BSA) was an effective dispersant for MWCNTs, providing steric and electrosteric hindrances that are capable of overcoming hydrophobic attachment and the electrostatic screening of double layer formation in ionic media. Thus, BSA was capable of stabilizing all tube versions. Dipalmitoylphosphatidylcholine (DPPC) provided additional stability for AP-MWCNTs in epithelial growth medium (BEGM). While the dispersion state did not affect cytotoxicity, improved dispersion of AP- and PD-MWCNTs increased TGF-β1 production in epithelial cells and fibroblast proliferation. In summary, we demonstrate how quantitative techniques can be used to assess the agglomeration state of MWCNTs when conducting mechanistic studies on the effects of dispersion on tissue culture cells.

Transgenic Barley with Overexpressed PTrx Increases Aluminum Resistance in Roots During Germination

Journal of Zhejiang University. Science. B. Nov, 2010  |  Pubmed ID: 21043055

A transgenic barley line (LSY-11-1-1) with overexpressed Phalaris coerulescens thioredoxin gene (PTrx) was employed to measure the growth, protein oxidation, cell viability, and antioxidase activity in barley roots during germination on the presence of 2 mmol/L AlCl(3) on filter paper. The results show that (1) compared with the non-transgenic barley, LSY-11-1-1 had enhanced root growth, although both were seriously inhibited after AlCl(3) treatment; (2) the degree of protein oxidation and loss of cell viability in roots of LSY-11-1-1 were much less than those in roots of non-transgenic barley, as reflected by lower contents of protein carbonyl and Evans blue uptakes in LSY-11-1-1; (3) activities of catalase (CAT), glutathione peroxidase (GPX), ascorbate peroxidase (APX), and glutathione reductase (GR) in LSY-11-1-1 root tips were generally higher than those in non-transgenic barley root tips, although these antioxidase activities gave a rise to different degrees in both LSY-11-1-1 and non-transgenic barley under aluminum stress. These results indicate that overexpressing PTrx could efficiently protect barley roots from oxidative injury by increasing antioxidase activity, thereby quenching ROS caused by AlCl(3) during germination. These properties raise the possibility that transgenic barley with overexpressed PTrx may be used to reduce the aluminum toxicity in acid soils.

Synthesis of Spherical Polyelectrolyte Brushes by Thermo-controlled Emulsion Polymerization

Macromolecular Rapid Communications. Jul, 2010  |  Pubmed ID: 21567523

A novel method of thermo-controlled emulsion polymerization has been employed to synthesize spherical polyelectrolyte brushes that consist of a solid polystyrene core and a poly (acrylic acid) (PAA) shell covalently attached on the core surface densely by one end. The growth of brushes from the core surface was monitored by dynamic light scattering (DLS). The particle size of PS core latex showed a narrow size distribution when observed by scanning electron microscopy (SEM). The brush size changed significantly upon changing pH value and ionic strength, and displayed similar behavior to brushes prepared by photo-emulsion polymerization. The grafting density of the PAA brush, which was determined by cutting off the PAA chains using alkali hydrolysis, confirmed the formation of PAA brushes.

3-(2-Amino-eth-yl)-2-[4-(trifluoro-meth-oxy)anilino]quinazolin-4(3H)-one

Acta Crystallographica. Section E, Structure Reports Online. 2010  |  Pubmed ID: 21588052

In the title compound, C(17)H(15)F(3)N(4)O(2), the dihedral angle between the trifluoro-meth-oxy-substituted benzene ring and the pyrimidinone ring is 45.1 (5)°, while that between the fused benzene ring and the pyrimidinone ring is 0.67 (1)°. Part of one of the benzene rings and its trifluoro-meth-oxy substituent are disordered over two positions of approximately equal occupancy (0.51:0.49). Inter-molecular N-H⋯O and N-H⋯N hydrogen bonds contribute to the stability of the crystal structure. A weak intra-molecular C-H⋯F contact is also found. In addition, π-π stacking inter-actions, with centroid-centroid distances in the range 3.673 (6)-3.780 (8) Å, and weak C-H⋯π inter-actions are also observed.

2-[2-(2-Anilino-4-oxo-3,4-dihydro-quinazolin-3-yl)phen-oxy]-3-phenyl-quinazolin-4(3H)-one Methanol Hemisolvate

Acta Crystallographica. Section E, Structure Reports Online. 2010  |  Pubmed ID: 21588376

In the title compound, C(34)H(23)N(5)O(3)·0.5CH(3)OH, each pyrimid-in-one heterocycle and its adjacent benzene ring are almost coplanar, making dihedral angles of 0.69 (13) and 1.87 (13)°. The lower pyrimidinone ring makes a dihedral angle of 40.41 (15)° with the -NH- bonded phenyl ring. O-H⋯O hydrogen bonds and weak C-H⋯π inter-actions are observed in the crystal structure. The methanol solvent molecule is disordered over two positions of equal occupancy.

Variants in the Fat Mass and Obesity Associated (FTO) Gene Are Associated with Obesity and C-reactive Protein Levels in Chinese Han Populations

Clinical and Investigative Medicine. Médecine Clinique Et Experimentale. 2010  |  Pubmed ID: 21134343

Various genetic variants of the fat mass and obesity associated gene (FTO) have been linked to obesity in populations of Europeans. Low-grade inflammation is a key feature of obesity, characterized by elevated plasma levels of C-reactive protein (CRP). In the present study, we have investigated whether the FTO-risk variant is associated with obesity and CRP in the Chinese population.

[Case Control Study on the Association Between Abnormality Curvature of Cervical Spine and Pathogenesy of Cervical Spondylosis]

Zhongguo Gu Shang = China Journal of Orthopaedics and Traumatology. Oct, 2010  |  Pubmed ID: 21137284

To explore the relationship between the abnormality curvature of cervical spine and pathogenesy of cervical spondylosis, in order to provide a new way in diagnosis of cervical spondylosis.

Growth Characteristics of Nanocrystalline Silicon Films Fabricated by Using Chlorinated Precursors at Low Temperatures

Journal of Nanoscience and Nanotechnology. Nov, 2010  |  Pubmed ID: 21137990

We employed plasma enhanced chemical vapor deposition technique to fabricate nanocrystalline Si films at a low temperature of 250 degrees C by using SiCl4 and H2 as source gases. The evolution of microstructure of the films with deposition periods shows that nanocrystalline Si can be directly grown on amorphous substrate at the initial growth process, which is in contrast to the growth behavior observed in the SiH4/H2 system. Furthermore, it is interesting to find that the area density of nanocrystalline Si as well as grain size can be controlled by modulating the concentration of SiCl4. By decreasing the SiCl4 concentration, the area density of nanocrystalline Si can be enhanced up to 10(11) cm(-2), while the grain size is shown to decrease down to 10 nm. It is suggested that Cl plays an important role in the low-temperature growth of nanocrystalline Si.

[The Comparative Study of Lymph Node Dissection by Video-assisted Thoracoscopic Surgery (VATS) and Conventional Lateral Incision Surgery]

Zhongguo Fei Ai Za Zhi = Chinese Journal of Lung Cancer. Dec, 2010  |  Pubmed ID: 21159251

although widely adopted, there is lack of comparative data for patients undergoing lymph node dissection in radical surgery of lung cancer by video-assisted thoracoscopic surgery (VATS) vs conventional lateral incision surgery. The aim of this study is to compare the effects of lymph node dissection in radical surgery of lung cancer by VATS.

[Relationship of Body Mass Index with Cancer Detection in Prostate Biopsy]

Zhonghua Yi Xue Za Zhi. Nov, 2010  |  Pubmed ID: 21162790

To investigate the relationship of body mass index with cancer detection on prostate biopsy.

A Non-oxidative Electrochemical Approach to Online Measurements of Dopamine Release Through Laccase-catalyzed Oxidation and Intramolecular Cyclization of Dopamine

Biosensors & Bioelectronics. Feb, 2010  |  Pubmed ID: 19926273

A new electrochemical approach to selective online measurements of dopamine (DA) release in the cerebral microdialysate is demonstrated with a non-oxidative mechanism based on the distinct reaction properties of DA and the excellent biocatalytic activity of laccase. To make the successful transition of the distinct sequential reaction properties of DA from a conceptual determination protocol to a practical online analytical system, laccase enzyme is immobilized onto magnetite nanoparticles and the nanoparticles are confined into a fused-silica capillary through an external magnetic field to fabricate a magnetic microreactor. The microreactor is placed in the upstream of the thin-layer electrochemical flow cell to efficiently catalyze the oxidation of DA into its quinonoid form and thereby initialize the sequential reactions including deprotonation, intramolecular cyclization, disproportionation and/or oxidation to finally give 5,6-dihydroxyindoline quinone. The electrochemical reduction of the produced 5,6-dihydroxyindoline quinone at bare glassy carbon electrode is used as the readout for the DA measurement. The laccase-immobilized microreactor is also found to catalyze the oxidation of ascorbic acid (AA) and 3,4-dihydroxyphenylacetic acid (DOPAC) into electroinactive species and, as such, to eliminate the great interference from both species. Moreover, the successful transition of the mechanism for DA detection from the conventional oxidative electrochemical approach to the non-oxidative one substantially enables the measurements virtually interference-free from physiological levels of uric acid, 5-hydroxytryptamine, norepinephrine, and epinephrine. The current response is linear with DA concentration within a concentration range from 1 to 20 microM with a sensitivity of 3.97 nA/microM. The detection limit, based on a signal-to-noise ratio of 3, is calculated to be 0.3 microM. The high selectivity and the good linearity as well as the high stability of the online method make it very potential for continuous monitoring of cerebral DA release in physiological and pathological processes.

Effects of Fish CYP Inducers on Difloxacin N-demethylation in Kidney Cell of Chinese Idle (Ctenopharyngodon Idellus)

Fish Physiology and Biochemistry. Sep, 2010  |  Pubmed ID: 19685219

A drug-drug interaction occurs when the effect of one drug is altered by the presence of another drug which is generally associated with the induction of cytochrome P450s (CYPs) activity. Thus, unexpected treatment failures often happen resulting from inappropriate coadministration in fisheries. However, little information is available about CYP induction in fish. The reaction of difloxacin (DIF) biotransformation to sarafloxacin (SAR) belongs to N-demethylation catalyzed mainly by CYP(s). In order to supply useful information on CYP induction, the present study assessed the effects of fish-specific CYP inducers on DIF N-demethylation and enzyme kinetics in kidney cell of Chinese idle (CIK; grass carp (Ctenopharyngodon idellus)) by RP-HPLC. Results demonstrated that the amounts of SAR formation and enzymatic parameters Clint and Vmax were significantly increased due to beta-naphthoflavone (BNF) pretreatment. Therefore, we suggest that CYP1A may be involved in DIF N-demethylation in CIK. This study provides instructive information to ensure treatment success via avoiding CYP induction in fisheries.

The Single Transoral Approach for Os Odontoideum with Irreducible Atlantoaxial Dislocation

European Spine Journal : Official Publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. Jul, 2010  |  Pubmed ID: 19597851

We report a 52-year-old female patient with a 2-year history of local neck pain, decreased cervical spine rotation, progressive numbness and weakness of both arms. Preoperative, dynamic X-rays, computed tomography, three-dimensional computed tomography demonstrated a displaced Os odontoideum with irreducible Subluxation of C1/2. We used a single transoral approach release, reduction using an assistance of skull traction, bone fusion and stabilization in the treatment of Os odontoideum with irreducible alantoaxial dislocation. Postoperative, the patient was free of all symptoms and X-rays taken showed a stable fusion of C1/2 at 6th postoperative month. This technique in the treatment of Os odontoideum with irreducible alantoaxial dislocation is atraumatic and effective. And preoperative dynamic X-rays, computed tomography, three-dimensional computed tomography and MRI scans provided an invaluable aid to select this operative procedure.

A De Novo Mutation of STK11 Gene in a Chinese Patient with Peutz-Jeghers Syndrome

Digestive Diseases and Sciences. Apr, 2010  |  Pubmed ID: 19507030

Peutz-Jeghers syndrome (PJS) is an autosomal-dominant inherited disorder characterized by mucocutaneous pigmentation, hamartomatous polyposis of the gastrointestinal tract, and an increased risk for the development of both gastrointestinal and extraintestinal malignancies. Germline mutation of the STK11 gene, which encodes a serine-threonine kinase, is responsible for PJS. We collected blood samples from a Chinese PJS family consisting of a total of four individuals (one male and three females) including one PJS patient. The whole coding region of STK11 was amplified by polymerase chain reaction and products analyzed by direct sequencing. Molecular analysis of the STK11 gene in this case of PJS revealed a substitution of thymine 217 for adenine (C.217T > A) in exon 1, resulting in a change of codon 73 from cysteine to serine (C73S). The point mutation was not found in normal individuals in this PJS family or in 100 control individuals. The results presented here enlarge the spectrum of mutations of the STK11 gene by identifying a de novo mutation in a PJS patient and further support the hypothesis that STK11 mutations are disease-causing mutations for PJS.

Bifidobacterium Adolescentis Supplementation Ameliorates Parenteral Nutrition-induced Liver Injury in Infant Rabbits

Digestive Diseases and Sciences. Oct, 2010  |  Pubmed ID: 20094783

Parenteral nutrition (PN)-induced liver injury is associated with gut atrophy, and probiotics have demonstrated the ability to stabilize the intestinal microecosystem and offer protection against bacterial translocation from the gut to the liver. Therefore, we hypothesized that enteral Bifidobacterium supplements could alleviate PN-associated liver injury.

Evaluation of Nonsyndromic Multiple Supernumerary Teeth Using Three-dimensional Computerized Tomography: a Case Report and Literature Review

The Journal of Contemporary Dental Practice. 2010  |  Pubmed ID: 20098970

The aims of this report are to present a case of nonsyndromic multiple supernumerary teeth and a discussion of the value of three-dimensional computerized tomography (3D CT) for precise radiographic imaging of the anomaly.

Vibrational Signature of Double-end-linked Molecules at Au Nanojunctions Probed by Surface-enhanced Raman Spectroscopy

Chemistry (Weinheim an Der Bergstrasse, Germany). Feb, 2010  |  Pubmed ID: 20029918

Surgical Complications in Kidney Transplantation in Nonhuman Primates

Microsurgery. May, 2010  |  Pubmed ID: 20049911

Surgical complications are important causes of graft loss in the nonhuman primate kidney transplantation model. We reviewed the incidence and intervention methods in 182 kidney transplantations performed in our lab recently 2 years in Cynomolgus monkeys. There were six renal artery thromboses (3.3%), eight urine leakages (4.4%), and five ureteral stenoses (2.7%). All renal artery thrombosis cases were found within 3 days after surgery. Urine leakage appeared from the 5th to 12th day after surgery and all cases were caused by ureter rupture. Reexploration was performed in five cases to reanastomose ureter with stent. Four cases reached long-term survival. The rest one died of graft rejection. Ureteral stenoses were found in long-term survival cases. Ureter reanastomoses with stent were performed in two cases. The postoperative renal functions of these two monkeys recovered to normal and they survived until study termination. From this large number of study, our experience indicated that kidney transplantation in the nonhuman primate is a safe procedure with low complications. Reexploration is recommended for salvage of the graft with urine leakage and ureteral stenosis.

Characterizations and Anti-tumor Activities of Three Acidic Polysaccharides from Angelica Sinensis (Oliv.) Diels

International Journal of Biological Macromolecules. Jan, 2010  |  Pubmed ID: 19941888

In this study, three acidic polysaccharides (APS-3a, APS-3b and APS-3c) were obtained from Angelica sinensis (Oliv.) Diels. They displayed different structural features and anti-tumor activities. APS-3b and APS-3c significantly inhibited the growth of S180 tumors and increased the life spans of S180 tumor-bearing mice, whereas APS-3a had no significant effect. Further experiments showed that APS-3b and APS-3c could cause a concentration-dependent proliferation of the splenocytes, up-regulate IFN-gamma, IL-2 and IL-6 mRNA expressions in splenocytes and stimulate the productions of NO and TNF-alpha in peritoneal macrophages. Taken together, the three acidic polysaccharides displayed different anti-tumor activities which were associated with their different structural characteristics.

Morphological Assessment of Basic Multicellular Unit Resorption Parameters in Dogs Shows Additional Mechanisms of Bisphosphonate Effects on Bone

Calcified Tissue International. Jan, 2010  |  Pubmed ID: 19953232

Bisphosphonates (BPs) slow bone loss by reducing initiation of new basic multicellular units (BMUs). Whether or not BPs simply prevent osteoclasts from initiating new BMUs that resorb bone or also reduce the amount of bone they resorb at the BMU level is not clear. The goal of this study was to determine the effects of BPs on three morphological parameters of individual BMUs, resorption depth (Rs.De), area (Rs.Ar), and width (Rs.Wi). After 1 year of treatment with vehicle (VEH), alendronate (ALN; 0.10, 0.20, or 1.00 mg/kg/day), or risedronate (RIS; 0.05, 0.10, or 0.50 mg/kg/day), resorption cavity morphology was assessed in vertebral trabecular bone of beagle dogs by histology. Animals treated with ALN or RIS at the doses representing those used to treat postmenopausal osteoporosis (0.20 and 0.10 mg/kg/day, respectively) had significantly lower Rs.Ar (-27%) and Rs.Wi (-17%), with no difference in Rs.De, compared to VEH-treated controls. Low doses of ALN and RIS did not affect any parameters, whereas higher doses resulted in similar changes to those of the clinical dose. There were no significant differences in the resorption cavity measures between RIS and ALN at any of the dose equivalents. These results highlight the importance of examining parameters beyond erosion depth for assessment of resorption parameters. Furthermore, these results suggest that in addition to the well-known effects of BPs on reducing the number of active BMUs, these drugs also reduce the activity of osteoclasts at the individual BMU level at doses at and above those used clinically for the treatment of postmenopausal osteoporosis.

Efficient Inhibition of the Formation of Joint Adhesions by ERK2 Small Interfering RNAs

Biochemical and Biophysical Research Communications. Jan, 2010  |  Pubmed ID: 19958750

Transforming growth factor-beta1 and fibroblast growth factor-2 play very important roles in fibroblast proliferation and collagen expression. These processes lead to the formation of joint adhesions through the SMAD and MAPK pathways, in which extracellular signal-regulated kinase (ERK)2 is considered to be crucial. Based on these theories, we examined the effects of a lentivirus-mediated small interfering RNA (siRNA) targeting ERK2 on the suppression of joint adhesion formation in vivo. The effects were assessed in vivo from different aspects including the adhesion score, histology and joint contracture angle. We found that the adhesions in the ERK2 siRNA group became soft and weak, and were easily stretched. Accordingly, the flexion contracture angles in the ERK2 siRNA group were also reduced (P<0.05 compared with the control group). The animals appeared healthy, with no signs of impaired wound healing. In conclusion, local delivery of a lentivirus-mediated siRNA targeting ERK2 can ameliorate joint adhesion formation effectively and safely.

Silencing of Tachyzoite Enolase 2 Alters Nuclear Targeting of Bradyzoite Enolase 1 in Toxoplasma Gondii

Microbes and Infection / Institut Pasteur. Jan, 2010  |  Pubmed ID: 19770069

In Toxoplasma gondii, an intracellular parasite of the phylum Apicomplexa, two isoforms of enolase (ENO1 and ENO2) are expressed in stage-specific manner. ENO2 is expressed only in rapidly growing tachyzoites, while ENO1 is in slowly growing bradyzoites. Interestingly, the localization of ENO1 and ENO2 in the nuclear compartment has suggested possible roles of the proteins in gene regulation and/or cell cycle. To understand the physiological role of ENO2 in T. gondii, the expression of ENO2 was silenced using a homologous gene silencing procedure. The introduction or expression of ENO2 dsRNA successfully silenced the expression of ENO2 at the levels of transcripts and proteins. While there was no change in the growth rate of both tachyzoites and bradyzoites, a subtle phenotypic change was observed in the localization of the ENO1 gene product in the bradyzoite stage.

Prestin Forms Oligomer with Four Mechanically Independent Subunits

Brain Research. May, 2010  |  Pubmed ID: 20347723

Prestin is the motor protein of cochlear outer hair cells (OHCs) with the unique capability of performing direct, rapid, and reciprocal electromechanical conversion. Prestin consists of 744 amino acids with a molecular mass of approximately 81.4 kDa. The predicted membrane topology and molecular mass of a single prestin molecule appear inadequate to account for the size of intramembrane particles (IMPs) expressed in the OHC membrane. Although recent biochemical evidence suggests that prestin forms homo-oligomers, most likely as a tetramer, the oligomeric structure of prestin in OHCs remains unclear. We obtained the charge density of prestin in the gerbil OHCs by measuring their nonlinear capacitance (NLC). The average charge density (22,608 microm(-2) measured was four times the average IMP density (5686 microm(-2) reported in the freeze-fracture study. This suggests that each IMP contains four prestin molecules, based on the general notion that each prestin transfers a single elementary charge. We subsequently compared the voltage dependency and the values of slope factor of NLC and somatic motility simultaneously measured from the same OHCs to determine whether NLC and motility are fully coupled and how prestin subunits function within the tetramer. We showed that the voltage dependency and slope factors of NLC and motility were not statistically different, suggesting that NLC and motility are fully coupled. The fact that the slope factor is the same between NLC and motility suggests that each prestin monomer in the tetramer is in parallel, each interacting independently with cytoplasmic or other partners to facilitate the mechanical response.

A Series of Alpha-heterocyclic Carboxaldehyde Thiosemicarbazones Inhibit Topoisomerase IIalpha Catalytic Activity

Journal of Medicinal Chemistry. Apr, 2010  |  Pubmed ID: 20353152

A series of novel thiosemicarbazone derivatives bearing condensed heterocyclic carboxaldehyde moieties were designed and synthesized. Among them, TSC24 exhibited broad antiproliferative activity in a panel of human tumor cells and suppressed tumor growth in mice. The mechanism research revealed that TSC24 was not only an iron chelator but also a topoisomerase IIalpha catalytic inhibitor. Its inhibition on topoisomerase IIalpha was due to direct interaction with the ATPase domain of topoisomerase IIalpha which led to the block of ATP hydrolysis. Molecular docking predicted that TSC24 might bind at the ATP binding site, which was confirmed by the competitive inhibition assay. These results about the mechanisms involved in the anticancer activities of thiosemicarbazones will aid in the rational design of novel topoisomerase II-targeted drugs and will provide insights into the discovery and development of novel cancer therapeutics based on the dual activity to chelate iron and to inhibit the catalytic activity of topoisomerase IIalpha.

Nuclear Translocation of Nuclear Factor Kappa B in First Trimester Deciduas and Chorionic Villi in Early Spontaneous Miscarriage Women

International Journal of Molecular Sciences. 2010  |  Pubmed ID: 20386652

The nuclear factor kappa B is widely expressed in the distinct subpopulations of chorionic villi and deciduas of first-trimester pregnancies. We examined the cellular distribution and expression of nuclear factor kappa B in the human first-trimester chorionic villi and deciduas of women with early spontaneous miscarriage and viable pregnancy by confocal laser scanning microscope and immunohistochemistry. There is a greater nuclear translocation of nuclear factor kappa B is restricted to villous stromal cells, decidual stromal cells, glandular epithelial cells and vessel endothelial cells in early spontaneous miscarriage than in viable pregnancies. Collectively these observations suggest that over-activation of nuclear factor kappa B has a relationship with early spontaneous miscarriages.

[The Effects of Occupational Soluble Chromate Exposure on Immunological Function of T-cell]

Zhonghua Yu Fang Yi Xue Za Zhi [Chinese Journal of Preventive Medicine]. Jan, 2010  |  Pubmed ID: 20388357

To investigate the early changes of some immunological function of T-cell in chromate workers.

Involvement of Microsomal Triglyceride Transfer Protein in Nonalcoholic Steatohepatitis in Novel Spontaneous Mouse Model

Journal of Hepatology. Jun, 2010  |  Pubmed ID: 20392512

Nonalcoholic fatty liver disease (NAFLD) is currently recognized as a global health issue and encompasses a wide spectrum of entities, ranging from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH). The lack of a spontaneous animal model of NASH, however, has hampered basic research in this field.

[Eighteen Cases of Plerosising Intra-orbital Wall Blow-out Fracture with the Nasal Septal Cartilage Under the Endoscopic Transnasal]

Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi = Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery. Mar, 2010  |  Pubmed ID: 20464988

To investigate the surgical method of plerosising intra-orbital wall blow-out fracture through ethmoid sinuses under trans-nasal endoscopy with the graft of nasal septal cartilage.

[Research Progress of Blood Substitutes for the Treatment of Hemorrhagic Shock]

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi = Journal of Biomedical Engineering = Shengwu Yixue Gongchengxue Zazhi. Apr, 2010  |  Pubmed ID: 20481338

Hemorrhagic shock is a medical complication caused by the reduction of circulation blood in body. The routine treatment of hemorrhagic shock is to infuse blood or substitute. However, the duration of blood storage is short,the procedures for matching of blood are necessary, and there is the risk of spreading some hematogenous diseases. All these have limited the use of blood-transfusion in the emergent situations such as disaster and war. Thus, the research of blood substitutes is promoted. Considering the scarcity of domestic research report on the use of blood substitutes for the treatment of hemorrhagic shock, we present an overview in this paper.

[Incomplete Palate Cleft Patient with Mirror-image Dextrocardia and Situs Inversus Viscerums: Report of One Case]

Shanghai Kou Qiang Yi Xue = Shanghai Journal of Stomatology. Apr, 2010  |  Pubmed ID: 20485994

Cleft palate is one of the most common congenital defects, occurring alone or in combination with other malformations. Cleft palate with mirror-image dextrocardia and situs inversus viscerums is rare. This paper presented a case of incomplete cleft palate patient with mirror-image dextrocardia and situs inversus viscerums. The patient had a family history of cleft palate and had no family history of congenital heart disease. He was found to have congenital heart disease during preoperative assessment. Without intracardiac malformation, the patient was routinely operated under general anesthesia. The patient had an uneventful postoperative course and was discharged 8 days after operation. Further investigation is needed whether multiple defects in this patient are independent diseases or a part of possible recessive syndrome.

Pt-Ru/CeO2/carbon Nanotube Nanocomposites: an Efficient Electrocatalyst for Direct Methanol Fuel Cells

Langmuir : the ACS Journal of Surfaces and Colloids. Jul, 2010  |  Pubmed ID: 20486650

Pt-Ru/CeO(2)/multiwalled carbon nanotube (MWNT) electrocatalysts were prepared using a rapid sonication-facilitated deposition method and were characterized by X-ray diffraction (XRD), X-ray photoemission spectroscopy (XPS), transmission electron microscopy (TEM), energy-dispersive spectroscopy (EDS), and voltammetry. Morphological characterization by TEM revealed that CeO(2) nanoparticles (NPs) were in intimate contact with Pt-Ru NPs, and both were highly dispersed on the exteriors of nanotubes with a small size and a very narrow size distribution. Compared with the Pt-Ru/MWNT and Pt/MWNT electrocatalysts, the as-prepared Pt-Ru/CeO(2)/MWNT exhibited a significantly improved electrochemically active surface area (ECSA) and a remarkably enhanced activity toward methanol oxidation. The effects of the Pt-Ru loading and the Pt-to-Ru molar ratio on the electrocatalytic activity of Pt-Ru/CeO(2)/MWNT for methanol oxidation were investigated. We found that a maximum activity toward methanol oxidation reached at the 10 wt % of Pt-Ru loading and 1:1 of Pt-to-Ru ratio. Moreover, the role of CeO(2) in the catalysts for the enhancement of methanol oxidation was discussed in terms of both bifunctional mechanism and electronic effects.

Chemical Genetics Identifies Small-molecule Modulators of Neuritogenesis Involving Neuregulin-1/ErbB4 Signaling

ACS Chemical Neuroscience. Jan, 2010  |  Pubmed ID: 20495671

Genetic findings have suggested that neuregulin-1 (Nrg1) and its receptor v-erb-a erythroblastic leukemia viral oncogene homolog 4 (ErbB4) may play a role in neuropsychiatric diseases. However, the downstream signaling events and relevant phenotypic consequences of altered Nrg1 signaling in the nervous system remain poorly understood. To identify small molecules for probing Nrg1-ErbB4 signaling, a PC12-cell model was developed and used to perform a live-cell, image-based screen of the effects of small molecules on Nrg1-induced neuritogenesis. By comparing the resulting phenotypic data to that of a similar screening performed with nerve growth factor (NGF), this multidimensional screen identified compounds that directly inhibit Nrg1-ErbB4 signaling, such as the 4-anilino-quinazoline Iressa (gefitinib), as well as compounds that potentiate Nrg1-ErbB4 signaling, such as the indolocarbazole K-252a. These findings provide new insights into the regulation of Nrg1-ErbB4 signaling events and demonstrate the feasibility of using such a multidimensional, chemical-genetic approach for discovering probes of pathways implicated in neuropsychiatric diseases.

Identification of P27/KIP1 Expression Level As a Candidate Biomarker of Response to Rapalogs Therapy in Human Cancer

Journal of Molecular Medicine (Berlin, Germany). Sep, 2010  |  Pubmed ID: 20508912

Rapamycin analogs temsirolimus and everolimus have been approved for the treatment of advanced renal cancer and are being tested in a wide spectrum of human tumors. However, objective response rates with rapalogs in clinical trials were modest and variable. Identification of biomarkers capable of predicting response to rapalogs is of increasing interest. We analyzed pairwise Pearson correlation coefficients (r) between rapalogs activity and gene expression profile for each NCI-60 cell line. p27 showed the highest positive correlation among 9,706 gene probes tested. At cellular levels, breast cancer MCF-7, T47D, and BT-474 cells, expressing high levels of p27, were sensitive to rapalogs, whereas the cells expressed low levels of p27, such as MDA-MB-231, MDA-MB-468, and MDA-MB-435 cells, exhibited resistance to rapalogs. Mechanistic study indicated that this correlation is likely determined by the basal level of p27 regardless of the phosphorylation or redistribution of p27 upon rapalogs treatment, which may provide a putative threshold to block G1/S transition. Consistently, down-regulation of p27 by siRNA conferred MCF-7 and BT-474 cells insensitive to rapalogs. Moreover, a significant positive correlation between p27 gene expression and rapamycin anti-tumor activity was also observed in mice bearing different human cancer cell xenografts. In conclusion, p27 expression level is positively correlated with the anticancer activity of rapalogs in vitro and in vivo. We propose p27 expression level may be also a candidate predictive biomarker for patient selection for rapalogs-based therapy, which requires clinical validation in a series of patients treated with rapalogs.

WJD008, a Dual Phosphatidylinositol 3-kinase (PI3K)/mammalian Target of Rapamycin Inhibitor, Prevents PI3K Signaling and Inhibits the Proliferation of Transformed Cells with Oncogenic PI3K Mutant

The Journal of Pharmacology and Experimental Therapeutics. Sep, 2010  |  Pubmed ID: 20522531

The phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt)-mammalian target of rapamycin (mTOR) signaling pathway is often constitutively activated in various human cancers, providing validated targets for cancer therapy. Among a series of 5-cyano-6-morpholino-4-substituted-pyrimidine analogs designed and synthesized based on PI3K target, 4-(2-(dimethylamino)vinyl)-2-(3-hydroxyphenyl)-6-morpholinopyrimidine-5-carbonitrile (WJD008) was selected for further pharmacological characterization because of its potent activity against PI3K signaling. WJD008 inhibited kinase activity of PI3Kalpha and mTOR with less activity against PIKK family members. In cellular settings, WJD008 abrogated insulin-like growth factor-I-activated PI3K-Akt-mTOR signaling cascade and blocked the membrane translocation of a pleckstrin homology domain containing enhanced green fluorescent protein-general receptor for phosphoinositides, isoform 1-pleckstrin homology fusion protein, suggesting down-regulation of phosphatidylinositol (3,4,5)-trisphosphate output induced by WJD008 resulted in inactivation of PI3K pathway. Consequently, WJD008 arrested cells in G(1) phase without induction of apoptosis. Furthermore, WJD008 reversed the hyperactivation of the PI3K pathway caused by the oncogenic mutation of p110alpha H1047R and suppressed the proliferation and clonogenesis of transformed RK3E cells harboring this mutant. WJD008 was superior to the pan-PI3K inhibitor wortmannin against proliferation of a panel of cancer cells independently of their status of PI3K pathway or tissue originations. In summary, WJD008 is a potent dual PI3K/mTOR modulator with antiproliferative and anticlonogenic activity in tumor cells and transformed cells with PIK3CA mutant, which provides new clues for the design and development of this chemical scaffold as an anticancer drug.

Intermittent High Glucose Enhances Cell Proliferation and VEGF Expression in Retinal Endothelial Cells: the Role of Mitochondrial Reactive Oxygen Species

Molecular and Cellular Biochemistry. Oct, 2010  |  Pubmed ID: 20524146

Proliferation of human retinal endothelial cells (HRECs) is an important event in the development of diabetic retinopathy. Glucose fluctuations are strong predictor of diabetic vascular complications. In this study we have investigated the effect of intermittent high glucose on proliferation and expression of vascular endothelial growth factor (VEGF) in HRECs. The possible involvement of mitochondrial reactive oxygen species (ROS) was assessed. HRECs were incubated for 72 h in media containing different glucose concentrations: 5, 25, 5 mmol/l alternating with 25 mmol/l glucose, with or without Mn(III)tetrakis(4-benzoic acid) porphyrin chloride (MnTBAP) and thenoyltri-fluoroacetone (TTFA). The cell proliferation, VEGF expression, mitochondrial ROS, nitrotyrosine and 8-hydroxydeoxyguanosine (8-OHdG) were measured. In cultured HRECs, treatment with constant or intermittent high glucose significantly increased [(3)H]thymidine incorporation in a time-dependent manner. Treatment with constant high glucose for 48 h resulted in significant increases in [(3)H]thymidine incorporation, mRNA and protein levels of VEGF compared with HRECs treated with the normal glucose, which were markedly enhanced in cells exposed to intermittent high glucose. The levels of mitochondrial ROS, nitrotyrosine and 8-OhdG were significantly elevated under both intermittent and constant high glucose conditions, the effect being greater under intermittent high glucose. In addition, the antioxidants MnTBAP or TTFA can effectively prevent cell proliferation and overexpression of VEGF, as well as overproduction of mitochondrial ROS, nitrotyrosine and 8-OhdG in HRECs induced by constant or intermittent high glucose. Intermittent high glucose enhances cell proliferation and overexpression of VEGF through reactive oxygen species (ROS) overproduction at the mitochondrial transport chain level in HRECs, indicating that glycemic variability have important pathological effects on the development of diabetic retinopathy dependent of mitochondrial ROS.

PHF8 is a Histone H3K9me2 Demethylase Regulating RRNA Synthesis

Cell Research. Jul, 2010  |  Pubmed ID: 20531378

Dimethylation of histone H3 lysine 9 (H3K9me2) is an important epigenetic mark associated with transcription repression. Here, we identified PHF8, a JmjC-domain-containing protein, as a histone demethylase specific for this repressing mark. Recombinant full-length wild type protein could remove methylation from H3K9me2, but mutation of a conserved histidine to alanine H247A abolished the demethylase activity. Overexpressed exogenous PHF8 was colocalized with B23 staining. Endogenous PHF8 was also colocalized with B23 and fibrillarin, two well-established nucleolus proteins, suggesting that PHF8 is localized in the nucleolus and may regulate rRNA transcription. Indeed, PHF8 bound to the promoter region of the rDNA gene. Knockdown of PHF8 reduced the expression of rRNA, and overexpression of the gene resulted in upregulation of rRNA transcript. Concomitantly, H3K9me2 level was elevated in the promoter region of the rDNA gene in PHF8 knockdown cells and reduced significantly when the wild type but not the catalytically inactive H247A mutant PHF8 was overexpressed. Thus, our study identified a histone demethylase for H3K9me2 that regulates rRNA transcription.

Dispersion and Stability Optimization of TiO2 Nanoparticles in Cell Culture Media

Environmental Science & Technology. Oct, 2010  |  Pubmed ID: 20536146

Accurate evaluation of engineered nanomaterial toxicity requires not only comprehensive physical-chemical characterization of nanomaterials as produced, but also thorough understanding of nanomaterial properties and behavior under conditions similar to those used for in vitro and in vivo toxicity studies. In this investigation, TiO(2) nanoparticles were selected as a model nanoparticle and bovine serum albumin (BSA) was selected as a model protein for studying the effect of protein-nanoparticle interaction on TiO(2) nanoparticle dispersion in six different mammalian, bacteria, and yeast cell culture media. Great improvement in TiO(2) dispersion was observed upon the addition of BSA, even though the degree of dispersion varied from medium to medium and phosphate concentration in the cell culture media was one of the key factors governing nanoparticle dispersion. Fetal bovine serum (FBS) was an effective dispersing agent for TiO(2) nanoparticles in all six media due to synergistic effects of its multiple protein components, successfully reproduced using a simple "FBS mimic" protein cocktail containing similar concentrations of BSA, γ-globulin, and apo-transferrin.

An IL-2 Paradox: Blocking CD25 on T Cells Induces IL-2-driven Activation of CD56(bright) NK Cells

Journal of Immunology (Baltimore, Md. : 1950). Jul, 2010  |  Pubmed ID: 20543101

Daclizumab (Dac), an Ab against the IL-2R alpha-chain, inhibits brain inflammation in patients with multiple sclerosis, while expanding CD56(bright) immunoregulatory NK cells in vivo. We hypothesized that this unexpected expansion is paradoxically IL-2 driven; caused by the increased availability of T cell-derived IL-2 for NK cell signaling. To this end, we performed ex vivo functional analyses of CD56(bright) NK cells and T cells from patients in clinical trials with Dac. We developed in vitro models to investigate mechanisms for ex vivo observations. We observed that Dac treatment caused decreased numbers and proliferation of FoxP3(+) T regulatory cells (Tregs), a model T cell population known to be dependent on IL-2 for proliferation and survival. As anticipated, Dac therapy inhibited IL-2 signaling in all T cells; however, we also observed functional adaptation of T cells to low IL-2 signal in vivo, characterized by the concomitant enhancement of IL-7 signaling on all T cells and parallel increase of CD127 expression by Tregs. In contrast, IL-2 signaling on CD56(bright) NK cells was not inhibited by Dac and their in vivo proliferation and cytotoxicity actually increased. Mechanistic studies indicated that the activation of CD56(bright) NK cells was likely IL-2 driven, as low doses of IL-2, but not IL-15, mimicked this activation in vitro. Our study provides insight into the role that IL-2 and CD25 play in functional regulation of two important immunoregulatory cell populations in humans: FoxP3(+) Tregs and CD56(bright) NK cells.

Viable Fertile Mice Generated from Fully Pluripotent IPS Cells Derived from Adult Somatic Cells

Stem Cell Reviews. Sep, 2010  |  Pubmed ID: 20549390

Previous studies demonstrated that induced pluripotent stem (iPS) cells could produce viable mice through tetraploid complementation, which was thought to be the most stringent test for pluripotency. However, these highly pluripotent iPS cells were previously reported to be generated from fibroblasts of embryonic origin. Achieving fully pluripotent iPS cells from multiple cell types, especially easily accessible adult tissues, will lead to a much greater clinical impact. We successfully generated high-pluripotency iPS cells from adult tail tip fibroblasts (TTF) that resulted in viable, full-term, fertile TTF-iPS animals with no obvious teratoma formation or other developmental abnormalities. Comparison of iPS cells from embryonic origin (MEF), progenitor cells (neural stem cells) or differentiated somatic cells (TTF) reveals that fully pluripotent developmental potential can be reached by each cell type, although with different induction efficiencies. This work provides the means for studying the mechanisms and regulation of direct reprogramming, and has encouraging implications for future clinical applications and therapeutic interventions.

Type and Orientation of Yielded Trabeculae During Overloading of Trabecular Bone Along Orthogonal Directions

Journal of Biomechanics. Sep, 2010  |  Pubmed ID: 20554282

Trabecular architecture plays a major role in bone mechanics. Osteoporosis leads to a transition from a plate-like to a more rod-like trabecular morphology, which may contribute to fracture risk beyond that predicted by changes in density. In this study, microstructural finite element analysis results were analyzed using individual trabeculae segmentation (ITS) to identify the type and orientation of trabeculae where tissue yielded during compressive overloads in two orthogonal directions. For both apparent loading conditions, most of the yielded tissue was found in longitudinally oriented plates. However, the primary loading mode of yielded trabeculae was axial compression with superposed bending for on-axis loading in contrast to bending for transverse loading. For either loading direction, most plate-like trabeculae yielded in the same loading mode, regardless of their orientation. In contrast, rods oriented parallel to the loading axis yielded in compression, while rods oblique or perpendicular to the loading axis yielded in combined bending and tension. The predominance of tissue yielding in plates during both on-axis and transverse overloading explains why on-axis overloading is detrimental to the off-axis mechanical properties. At the same time, a large fraction of the tissue in rod-like trabeculae parallel to the loading direction yielded in both on-axis and transverse loading. Hence, rods may be more likely to be damaged and potentially resorbed by damage mediated remodeling.

[Study on the Method of Construct the Three-dimensional Finite Element Model of Cervical Vertebrae Semidislocation]

Zhongguo Gu Shang = China Journal of Orthopaedics and Traumatology. May, 2010  |  Pubmed ID: 20575294

Cervical vertebra semidislocation was one of major pathological aspects of cervical spondylosis, and it was also the target of manipulation to treat cervical spondylosis. The aim of this study was to combine the technology of three dimensional finite element analysis to investigate the method to construct the cervical vertebra semidislocation model.

New Insights into Glutamate Ototoxicity in Cochlear Hair Cells and Spiral Ganglion Neurons

Acta Oto-laryngologica. Dec, 2010  |  Pubmed ID: 20632907

Excess glutamate (Glu) exposure (20 mM) in the cochlear perilymph affects the physiological function of outer hair cells (OHCs) within a 2 h period and induces apoptosis in the modiolus spiral ganglion neurons (SGNs) in an apoptosis-inducing factor (AIF)-dependent manner.

[Intravital Observation Technology of Dorsal Microcirculatory Chamber and Its Application]

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi = Journal of Biomedical Engineering = Shengwu Yixue Gongchengxue Zazhi. Jun, 2010  |  Pubmed ID: 20649045

Observation of microcirculation plays an important role on the basic research and clinical diagnosis. However, an observation as such on the anesthetized patient will cause stress reaction, thus it will affect normal physiological state and interfere experimental results. At present, a method adopting dorsal microcirculatory chamber (DMC) to do in vivo observation in an unanesthetized state can eliminate the influence of anesthesia. Based on the research reports and practical applications of this method abroad, we summarize, in here, the configuration, function, observation techniques; the application of DMC; and the research states of microcirculation observation.

Prime-boost Vaccinations Using Recombinant Flavivirus Replicon and Vaccinia Virus Vaccines: an ELISPOT Analysis

Immunology and Cell Biology. Mar, 2011  |  Pubmed ID: 20680025

Recombinant Kunjin replicon virus-like particle (VLP), vaccinia virus (rVV) and DNA vaccines were tested in a large series of prime-boost vaccinations using interferon (IFN)γ ELISPOT assays that reflected effector (E), effector memory (EM) and central memory (CM) responses. All vaccine constructs encoded the murine polytope immunogen and responses to four CD8 T-cell epitopes (TYQRTRALV, SYIPSAEKI, YPHFMPTNL and RPQASGVYM) were measured. VLP/rVV out performed (by 14- to 20-fold) DNA/rVV for induction of CM responses, whereas EM responses were only marginally increased. DNA/VLP induced more EM, but not CM responses, than VLP alone, illustrating that DNA priming is not universally beneficial. rVV/VLP gave comparable results to VLP/rVV combinations, although the former induced approximately threefold more E responses, illustrating the utility of poxvirus priming in this setting. Although higher doses of VLP and rVV increased responses after single immunizations, such dose increases provided only marginal benefit in heterologous prime-boost settings. Triple combinations also provided no benefit over two vaccinations. DNA vaccination was associated with broad CM, but not EM responses, and the breadth of EM and E responses was significantly improved by increasing viral vector dose. VLP/rVV, rather than DNA priming, induced T cells with consistently high IFNγ secretion profiles across all ELISPOT measures. Vector-specific CD8 T-cell responses generally correlated well with immunogen-specific responses, although, as expected, single use of each vector reduced the relative levels of vector-specific responses. These experiments illustrate the utility of replicons in heterologous prime-boost vaccinations, and illustrate the diversity of data that can be obtained from ELISPOT analyses.

Renal Impairment Caused by Chronic Occupational Chromate Exposure

International Archives of Occupational and Environmental Health. Apr, 2011  |  Pubmed ID: 20717692

To determine the nephritic toxicity of chromate after chronic occupational exposure.

Measuring Surface Binding Thermodynamics and Kinetics by Using Total Internal Reflection with Fluorescence Correlation Spectroscopy: Practical Considerations

The Journal of Physical Chemistry. B. Jan, 2011  |  Pubmed ID: 21166379

The combination of total internal reflection illumination and fluorescence correlation spectroscopy (TIR-FCS) is an emerging method useful for, among a number of things, measuring the thermodynamic and kinetic parameters describing the reversible association of fluorescently labeled ligands in solution with immobilized, nonfluorescent surface binding sites. However, there are many parameters (both instrumental and intrinsic to the interaction of interest) that determine the nature of the acquired fluorescence fluctuation autocorrelation functions. In this work, we define criteria necessary for successful measurements and then systematically explore the parameter space to define conditions that meet the criteria. The work is intended to serve as a guide for experimental design, in other words, to provide a methodology to identify experimental conditions that will yield reliable values of the thermodynamic and kinetic parameters for a given interaction.

Molecular Imaging of Vulnerable Plaques in Rabbits Using Contrast-enhanced Ultrasound Targeting to Vascular Endothelial Growth Factor Receptor-2

Journal of Clinical Ultrasound : JCU. Feb, 2011  |  Pubmed ID: 21213333

Increased neovascularization has been identified as a feature of atherosclerotic plaque vulnerability and can be traced by microbubble ultrasound contrast agents (UCA). We investigated the relationship between retention of a vascular endothelial growth factor receptor 2 (VEGFR-2) targeted UCA and VEGFR-2 expression in a vulnerable plaque model in rabbits.

A Photoprotection Strategy for Microsecond-resolution Single-molecule Fluorescence Spectroscopy

Nature Methods. Feb, 2011  |  Pubmed ID: 21217750

Time resolution of current single-molecule fluorescence techniques is limited to milliseconds because of dye blinking and bleaching. Here we introduce a photoprotection strategy that affords microsecond resolution by combining efficient triplet quenching by oxygen and Trolox with minimized bleaching via the oxygen radical scavenger cysteamine. Using this approach we resolved the single-molecule microsecond conformational fluctuations of two proteins: the two-state folder α-spectrin SH3 domain and the ultrafast downhill folder BBL.

Diversity-oriented Synthesis of Spiro-substituted 1,3-thiazine Library Via a One-pot, Two-step, Three-component Reaction

ACS Combinatorial Science. Jan, 2011  |  Pubmed ID: 21247130

A sequential one-pot, two-step, three-component reaction for efficient synthesis of spiro-substituted 1,3-thiazine library has been developed. The syntheses were achieved by reacting cyanoacetamide with isothiocyanate derivatives to give rise to 2-cyano-3-mercaptoacrylamides, which are trapped in situ by various cycloketones through cyclization, providing multifunctionalized spiro-substituted 1,3-thiazine analogues. This procedure features short reaction time, generally good to excellent yields, easily available starting materials, and operational simplicity. This chemistry provides an efficient and promising synthetic strategy to diversity-oriented construction of the 1,3-thiazine skeleton.

Decreased Dissolution of ZnO by Iron Doping Yields Nanoparticles with Reduced Toxicity in the Rodent Lung and Zebrafish Embryos

ACS Nano. Feb, 2011  |  Pubmed ID: 21250651

We have recently shown that the dissolution of ZnO nanoparticles and Zn(2+) shedding leads to a series of sublethal and lethal toxicological responses at the cellular level that can be alleviated by iron doping. Iron doping changes the particle matrix and slows the rate of particle dissolution. To determine whether iron doping of ZnO also leads to lesser toxic effects in vivo, toxicity studies were performed in rodent and zebrafish models. First, we synthesized a fresh batch of ZnO nanoparticles doped with 1-10 wt % of Fe. These particles were extensively characterized to confirm their doping status, reduced rate of dissolution in an exposure medium, and reduced toxicity in a cellular screen. Subsequent studies compared the effects of undoped to doped particles in the rat lung, mouse lung, and the zebrafish embryo. The zebrafish studies looked at embryo hatching and mortality rates as well as the generation of morphological defects, while the endpoints in the rodent lung included an assessment of inflammatory cell infiltrates, LDH release, and cytokine levels in the bronchoalveolar lavage fluid. Iron doping, similar to the effect of the metal chelator, DTPA, interfered in the inhibitory effects of Zn(2+) on zebrafish hatching. In the oropharyngeal aspiration model in the mouse, iron doping was associated with decreased polymorphonuclear cell counts and IL-6 mRNA production. Doped particles also elicited decreased heme oxygenase 1 expression in the murine lung. In the intratracheal instillation studies in the rat, Fe doping was associated with decreased polymorphonuclear cell counts, LDH, and albumin levels. All considered, the above data show that Fe doping is a possible safe design strategy for preventing ZnO toxicity in animals and the environment.

Effect of Donor JNK Signal Transduction Inhibition on Transplant Outcome in Brain Dead Rat Model

Inflammation. Jan, 2011  |  Pubmed ID: 21274743

Renal grafts from brain-dead donors compared to living donors have a significantly shortened survival time due to heightened renal immunogenicity. The influence of pretreatment with a JNK signal transduction inhibitor on ischemia-reperfusion injury was examined in a renal transplant model using donors from a standardized rat model of brain death. Donors were treated immediately after induction of brain death with a JNK signal transduction inhibitor or saline. Kidney grafts from experimental group and control groups (saline-treated brain dead or living donor grafts) were examined serially up to 7 days post transplantation by morphology, immmunohistology, and real-time PCR. JNK inhibition reduced the intensity of ischemia-reperfusion injury and acute rejection compared to saline treated donors. Likewise, cellular infiltration, mRNA transcription of some representative proinflammatory mediators and MHC-II molecules in the grafts were diminished in the JNK-inhibited donors compared to saline controls. Lewis rats transplanted with kidneys from JNK inhibited, brain-dead BN donors survived significantly longer than rats transplanted with saline treated brain-dead donors. The JNK inhibitor pretreatment of brain dead rats improved donor kidney quality, and improved graft survival.

Sex Difference in QTc Prolongation in Chronic Institutionalized Patients with Schizophrenia on Long-term Treatment with Typical and Atypical Antipsychotics

Psychopharmacology. Jul, 2011  |  Pubmed ID: 21301815

The rate-corrected electrocardiographic QT (QTc) interval may significantly increase in patients with schizophrenia taking antipsychotics. The objective of this naturalistic study was to assess the prevalence of prolonged QTc interval in a large population of inpatients with chronic schizophrenia and to explore QTc relationship with demographic variables and prescribed treatments.

Effects and Relationship of ERK1 and ERK2 in Interleukin-1β-induced Alterations in MMP3, MMP13, Type II Collagen and Aggrecan Expression in Human Chondrocytes

International Journal of Molecular Medicine. Apr, 2011  |  Pubmed ID: 21305249

Interleukin (IL)-1β plays an important role in the pathogenesis of osteoarthritis and catabolic processes in articular cartilage. Growing evidence suggests that ERK1/2 activation is involved in IL-1β-mediated matrix metalloproteinase (MMP) 3, MMP13, type II collagen and aggrecan expression in chondrocytes. To investigate the respective effects and the relationship of ERK1 and ERK2, knockdown of ERK1 and/or ERK2 was performed in human chondrocytes using specific small interfering RNAs (siRNAs), and the cells were treated with IL-1β (10 ng/ml) for 24 h. Uninfected chondrocytes treated with IL-1β (10 ng/ml) were used as a positive control. Other cells cultured without IL-1β or siRNA treatment were used as a negative control. The mRNA levels of MMP3, MMP13, type II collagen and aggrecan were evaluated by quantitative real-time PCR. The protein levels of MMP3 and MMP13 in the culture medium were examined by ELISA. The protein levels of type II collagen, aggrecan, ERK1/2 and phospho-ERK1/2 were evaluated by western blotting. The results indicate that IL-1β enhances MMP3 and MMP13 expression and inhibits type II collagen and aggrecan expression. Activation of the MAPK/ERK pathway was observed. Knockdown of ERK1 or ERK2 significantly reversed these effects to similar degree. Combined knockdown of ERK1 and ERK2 displayed synergistic effects. ERK1 and phospho-ERK1 or ERK2 and phospho-ERK2 were inhibited by knockdown of ERK1 or ERK2, respectively. No compensatory effect by up-regulation of the opposite isoform was observed. The combined knockdown suppressed ERK1/2 and phospho-ERK1/2. The data suggest that although inhibition of both ERK1 and ERK2 is more effective, inhibition of either ERK isoform may be sufficient and could be used for novel therapies or as drug targets for pharmacological intervention in cartilage breakdown in osteoarthritis.

[Clinical Application of Completed Video-assisted Thoracic Surgery Lobectomy (with 186 Cases Report)]

Zhong Nan Da Xue Xue Bao. Yi Xue Ban = Journal of Central South University. Medical Sciences. Jan, 2011  |  Pubmed ID: 21311144

To evaluate the postsurgery effects of completed video-assisted thoracic surgery (VATS) lobectomy and the indication for non-small cell lung cancer cases (NSCLC).

Use of a High-throughput Screening Approach Coupled with in Vivo Zebrafish Embryo Screening to Develop Hazard Ranking for Engineered Nanomaterials

ACS Nano. Mar, 2011  |  Pubmed ID: 21323332

Because of concerns about the safety of a growing number of engineered nanomaterials (ENM), it is necessary to develop high-throughput screening and in silico data transformation tools that can speed up in vitro hazard ranking. Here, we report the use of a multiparametric, automated screening assay that incorporates sublethal and lethal cellular injury responses to perform high-throughput analysis of a batch of commercial metal/metal oxide nanoparticles (NP) with the inclusion of a quantum dot (QD1). The responses chosen for tracking cellular injury through automated epifluorescence microscopy included ROS production, intracellular calcium flux, mitochondrial depolarization, and plasma membrane permeability. The z-score transformed high volume data set was used to construct heat maps for in vitro hazard ranking as well as showing the similarity patterns of NPs and response parameters through the use of self-organizing maps (SOM). Among the materials analyzed, QD1 and nano-ZnO showed the most prominent lethality, while Pt, Ag, SiO2, Al2O3, and Au triggered sublethal effects but without cytotoxicity. In order to compare the in vitro with the in vivo response outcomes in zebrafish embryos, NPs were used to assess their impact on mortality rate, hatching rate, cardiac rate, and morphological defects. While QDs, ZnO, and Ag induced morphological abnormalities or interfered in embryo hatching, Pt and Ag exerted inhibitory effects on cardiac rate. Ag toxicity in zebrafish differed from the in vitro results, which is congruent with this material's designation as extremely dangerous in the environment. Interestingly, while toxicity in the initially selected QD formulation was due to a solvent (toluene), supplementary testing of additional QDs selections yielded in vitro hazard profiling that reflect the release of chalcogenides. In conclusion, the use of a high-throughput screening, in silico data handling and zebrafish testing may constitute a paradigm for rapid and integrated ENM toxicological screening.

Polymorphisms of GSTP1 is Associated with Differences of Chemotherapy Response and Toxicity in Breast Cancer

Chinese Medical Journal. Jan, 2011  |  Pubmed ID: 21362365

Although chemotherapy is one of the most important treatments of breast cancer, it is limited by significant inter-individual variations in response and toxicity. The metabolism of epirubicin (EPI) and cyclophosphamide (CTX) is mainly mediated by cytochrome P450s (CYPs) and glutathione S-transferases (GSTs). It has been well-known that the activities of these enzymes are polymorphic in population due to their genetic polymorphisms. The aim of this research was to examine the effects of genetic polymorphisms in CYP3A, GSTP1 and MDR1 genes on treatment response and side-effects of breast cancer patients receiving EPI/CTX chemotherapy.

Differential Expression of Syndecan-1 Mediates Cationic Nanoparticle Toxicity in Undifferentiated Versus Differentiated Normal Human Bronchial Epithelial Cells

ACS Nano. Apr, 2011  |  Pubmed ID: 21366263

Most in vitro toxicity studies on engineered nanomaterials (ENMs) use transformed rather than primary cells for logistical reasons. However, primary cells may provide a more appropriate connection to in vivo toxicity because these cells maintain their phenotypic fidelity and are also capable of differentiating into lineages that may be differently affected by potentially hazardous ENMs. Few studies to date have focused on the role of cellular differentiation in determining ENM toxicity. We compared the response of undifferentiated and differentiated primary human bronchial epithelial (NHBE) cells to cationic mesoporous silica nanoparticles (MSNPs) that are coated with polyethyleneimine (PEI) since this polymer is known to exert differential cytotoxicity depending on its molecular weight and cationic density. The attachment of cationic PEI polymers to the MSNP surface was used to assess these materials' toxicological potential in undifferentiated and differentiated human bronchial epithelial cells, using a multiparametric assay that screens for an integrated set of sublethal and lethal response outcomes. MSNPs coated with high molecular weight (10 and 25 kD) polymers were more toxic in differentiated cells than particles coated with shorter length polymers. The increased susceptibility of the differentiated cells is in agreement with more abundant expression of a proteoglycan, syndecan-1, which contains copious heparin sulfate side chains. Pretreatment with heparinase to remove the negatively charged sulfates decreased MSNP-PEI binding to the cell surface and lowered the cytotoxic potential of the cationic particles. These data demonstrate the importance of studying cellular differentiation as an important variable in the response of primary cells to toxic ENM properties.

Highly Enantioselective Hydrogenation of Styrenes Directed by 2'-hydroxyl Groups

Organic Letters. Apr, 2011  |  Pubmed ID: 21384895

A new synthetic strategy that turns styrene-type olefins into excellent substrates for Rh-catalyzed asymmetric hydrogenation by installing a 2'-hydroxyl substituent is described. This methodology accommodates trisubstituted olefinic substrates in various E/Z mixtures, leading to valuable benzylic chiral compounds including (R)-tolterodine. It is also demonstrated that the 2'-hydroxyl groups could be readily removed in high yield without loss of ee from the products. Thus, this technology represents an attractive alternative to the Ir(P-N) catalyst system for the asymmetric hydrogenation of unfunctionalized olefins.

[Surgical Correction of Penoscrotal Transposition with Hypospadias: Experience with 83 Cases]

Zhonghua Nan Ke Xue = National Journal of Andrology. Feb, 2011  |  Pubmed ID: 21404712

To investigate the techniques of surgical correction of penoscrotal transposition with hypospadias.

Multiple Cavernous Hemangiomas of the Orbit

Yan Ke Xue Bao = Eye Science / "Yan Ke Xue Bao" Bian Ji Bu. Mar, 2011  |  Pubmed ID: 21425496

Cavernous hemangioma of the orbit is often unilateral and solitary. Multiple cavernous hemangiomas of the orbit are extremely rare. The authors reported four patients who had more than two cavernous hemangiomas in one orbit.

Selective Gold(I)-catalyzed Formation of Tetracyclic Indolines: a Single Transition Structure and Bifurcations Lead to Multiple Products

The Journal of Organic Chemistry. May, 2011  |  Pubmed ID: 21428454

Several alkynylindoles undergo gold(I)-catalyzed cyclization reactions to form a single isomer in each case. Density functional theory shows why this reaction is favored over the many possible regio- and stereoisomeric reaction pathways. This transformation involves a two-step no-intermediate mechanism with surface bifurcations leading to two or three products. Such bifurcations could explain reactivity in many gold(I)-catalyzed enyne cyclization reactions.

[Study on the Effect of Vertebrae Semi-dislocation on the Stress Distribution in Facet Joint and Interuertebral Disc of Patients with Cervical Syndrome Based on the Three Dimensional Finite Element Model]

Zhongguo Gu Shang = China Journal of Orthopaedics and Traumatology. Feb, 2011  |  Pubmed ID: 21442800

To study the effect of vertebrae semi-dislocation on the stress distribution in facet joint and interuertebral disc of patients with cervical syndrome using three dimensional finite element model.

Multistimuli Responsive Supramolecular Vesicles Based on the Recognition of P-Sulfonatocalixarene and Its Controllable Release of Doxorubicin

ACS Nano. Apr, 2011  |  Pubmed ID: 21443257

We report the novel construction of nanosupramolecular binary vesicles based on host-guest complex formation between p-sulfonatocalix[4]arene and asymmetric viologen, which was identified by UV-vis and fluorescence spectroscopy, dynamic laser scattering, transmission electron microscopy, scanning electron microscopy, and surface tension experiments. The critical aggregation concentration of asymmetric viologen decreases pronouncedly by a factor of ca. 1000 owing to the complexation of p-sulfonatocalix[4]arene. Furthermore, we have demonstrated that the resulting vesicles can respond to multiple external stimuli, including temperature, host-guest inclusion, and redox. Methods of warming and inclusion of cyclodextrins were then employed to disrupt the vesicle architecture to release hydrophilic doxorubicin from the interior of the vesicle. Finally, cell experiments were performed to evaluate the cellular toxicity of the supramolecular binary vesicle and the anticancer efficiency of doxorubicin-loaded vesicle.

Direct Detection of Structurally Resolved Dynamics in a Multiconformation Receptor-ligand Complex

Journal of the American Chemical Society. Apr, 2011  |  Pubmed ID: 21469679

Structure-based drug design relies on static protein structures despite significant evidence for the need to include protein dynamics as a serious consideration. In practice, dynamic motions are neglected because they are not understood well enough to model, a situation resulting from a lack of explicit experimental examples of dynamic receptor-ligand complexes. Here, we report high-resolution details of pronounced ~1 ms time scale motions of a receptor-small molecule complex using a combination of NMR and X-ray crystallography. Large conformational dynamics in Escherichia coli dihydrofolate reductase are driven by internal switching motions of the drug-like, nanomolar-affinity inhibitor. Carr-Purcell-Meiboom-Gill relaxation dispersion experiments and NOEs revealed the crystal structure to contain critical elements of the high energy protein-ligand conformation. The availability of accurate, structurally resolved dynamics in a protein-ligand complex should serve as a valuable benchmark for modeling dynamics in other receptor-ligand complexes and prediction of binding affinities.

Preattentive Processing Abnormalities in Chronic Pain: Neurophysiological Evidence from Mismatch Negativity

Pain Medicine (Malden, Mass.). May, 2011  |  Pubmed ID: 21481165

To investigate the characteristics of mismatch negativity (MMN) in chronic pain patients and the effect of chronic pain on MMN morphology in order to supply the neurophysiological evidence on preattentive processing abnormalities in chronic pain patients.

Electrohydrodynamic Deposition of Polymeric Droplets Under Low-frequency Pulsation

Langmuir : the ACS Journal of Surfaces and Colloids. May, 2011  |  Pubmed ID: 21506585

Circularly shaped polymeric droplets with diameter of about 20 μm have been intermittently ejected and deposited in an orderly manner on a collector from a syringe needle by means of near-field, electrohydrodynamic reactions using pulsating voltages at around 2.25 kV. The needle has an inner diameter of 100 μm and was placed 1 mm above a silicon conductor substrate to have location control for droplet depositions. Under low-frequency operation of less than 100 Hz, the deposition frequency of droplets, f(dep), has been observed to be equal to the frequency of the applied driving voltage divided by an integer, N, as small as 1. Furthermore, the diameter of the deposited droplets has been found to be linearly dependent on (Q/f(dep))(1/3), where Q is the polymer solution supply rate at around 30 nL/s. These experimentally observed droplet ejection rules under low-frequency pulsation provide useful design guidelines for controllable deposition of polymer droplets in various potential applications, including electrohydrodynamic printing.

A Simple Approach for Local Contact Angle Determination on a Heterogeneous Surface

Langmuir : the ACS Journal of Surfaces and Colloids. May, 2011  |  Pubmed ID: 21510655

We report a simple approach for measuring the local contact angle of liquids on a heterogeneous surface consisting of intersected hydrophobic and hydrophilic patch arrays, specifically by employing confocal microscopy and the addition of a very low concentration of Rhodamine-B (RB) (2 × 10(-7) mol/L). Interestingly, RB at that concentration was found to be aggregated at the air-liquid and solid (hydrophobic patch only)-liquid interfaces, which helps us to distinguish the liquid and solid interfaces as well as hydrophobic and hydrophilic patches by their corresponding fluorescent intensities. From the measured local contact angles, the line tension can be easily derived and the value is found to be (-2.06-1.53) × 10(-6) J/m.

New Multicomponent Cyclization: Domino Synthesis of Pentasubstituted Pyridines Under Solvent-free Conditions

Organic & Biomolecular Chemistry. Jun, 2011  |  Pubmed ID: 21523293

An efficient methodology for the synthesis of highly functionalized pyridine derivatives starting from readily available common reactants has been developed under microwave irradiation and solvent-free conditions. The new domino reaction enables successful assembly of five new σ bonds including two C-N bonds in a one-pot operation. A new mechanism has been proposed, which involves a novel reaction and sequence consisting of deprotonation-imine formation-anionic carbonyl addition.

Pairing Phosphoinositides with Calcium Ions in Endolysosomal Dynamics: Phosphoinositides Control the Direction and Specificity of Membrane Trafficking by Regulating the Activity of Calcium Channels in the Endolysosomes

BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology. Jun, 2011  |  Pubmed ID: 21538413

The direction and specificity of endolysosomal membrane trafficking is tightly regulated by various cytosolic and membrane-bound factors, including soluble NSF attachment protein receptors (SNAREs), Rab GTPases, and phosphoinositides. Another trafficking regulatory factor is juxta-organellar Ca(2+) , which is hypothesized to be released from the lumen of endolysosomes and to be present at higher concentrations near fusion/fission sites. The recent identification and characterization of several Ca(2+) channel proteins from endolysosomal membranes has provided a unique opportunity to examine the roles of Ca(2+) and Ca(2+) channels in the membrane trafficking of endolysosomes. SNAREs, Rab GTPases, and phosphoinositides have been reported to regulate plasma membrane ion channels, thereby suggesting that these trafficking regulators may also modulate endolysosomal dynamics by controlling Ca(2+) flux across endolysosomal membranes. In this paper, we discuss the roles of phosphoinositides, Ca(2+) , and potential interactions between endolysosomal Ca(2+) channels and phosphoinositides in endolysosomal dynamics.

Revealing the Molecular Structure of Single-molecule Junctions in Different Conductance States by Fishing-mode Tip-enhanced Raman Spectroscopy

Nature Communications. 2011  |  Pubmed ID: 21556059

The conductance of single-molecule junctions may be governed by the structure of the molecule in the gap or by the way it bonds with the leads, and the information contained in a Raman spectrum is ideal for examining both. Here we demonstrate that molecule-to-surface bonding may be characterized during electron transport by 'fishing-mode' tip-enhanced Raman spectroscopy (FM-TERS). This technique allows mutually verifiable single-molecule conductance and Raman signals with single-molecule contributions to be acquired simultaneously at room temperature. Density functional theory calculations reveal that the most significant spectral change seen for a gold-4,4'-bipyridine-gold junction results from the deformation of the pyridine ring in contact with the drain electrode at high voltage, and these calculations suggest that a stronger bonding interaction between the molecule and the drain may account for the nonlinear dependence of conductance on bias voltage. FM-TERS will lead to a better understanding of electron-transport processes in molecular junctions.

Aspect Ratio Determines the Quantity of Mesoporous Silica Nanoparticle Uptake by a Small GTPase-dependent Macropinocytosis Mechanism

ACS Nano. Jun, 2011  |  Pubmed ID: 21563770

Although the aspect ratio (AR) of engineered nanomaterials (ENMs) is one of the key physicochemical parameters that could determine biological outcome, not much is understood about how AR contributes to shaping biological outcome. By using a mesoporous silica nanoparticle (MSNP) library that has been constructed to cover a range of different lengths, we could demonstrate that the AR of rod-shaped particles determines the rate and abundance of MSNP uptake by a macropinocytosis process in HeLa and A549 cancer cell lines. MSNPs with an AR of 2.1-2.5 were taken up in larger quantities compared to shorter or longer length rods by a process that is sensitive to amiloride, cytochalasin D, azide, and 4 °C inhibition. The rods with intermediary AR also induced the maximal number of filopodia, actin polymerization, and activation of small GTP-binding proteins (e.g., Rac1, CDC42) that involve assembly of the actin cytoskeleton and filopodia formation. When assessing the role of AR in the delivery of paclitaxel or camptothecin, the rods with AR 2.1-2.5 were clearly more efficient for drug delivery and generation of cytotoxic killing in HeLa cells. All considered, our data suggest an active sensoring mechanism by which HeLa and A549 cells are capable of detecting AR differences in MSNP to the extent that accelerated macropinocytosis can be used to achieve more efficient drug delivery.

[Voxel-based Morphometry on Grey Matter Concentration of the Brain in First-episode, Antipsychotic-naive Major Depressive Disorder]

Zhong Nan Da Xue Xue Bao. Yi Xue Ban = Journal of Central South University. Medical Sciences. Apr, 2011  |  Pubmed ID: 21566281

To examine the structural differences in regional gray matter density between a sample of major depressive disorder (MDD) and healthy controls, using the magnetic resonance imaging (MRI) to find the base of pathophysiologic mechanism in depression development.

The Role of Adiponectin (ADIPOQ) Gene Polymorphisms in the Susceptibility and Prognosis of Non-small Cell Lung Cancer

Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire. Jun, 2011  |  Pubmed ID: 21619462

To study the role of the adiponectin (ADIPOQ) gene single-nucleotide polymorphism (SNP) in the susceptibility and prognosis for non-small cell lung cancer (NSCLC), we recruited 344 patients with NSCLC, of which 141 had undergone surgical resection and post-surgery follow up. For controls, there were 264 healthy volunteers for the control group, matched in age and sex with the NSCLC patients. Genotyping of SNPs in the ADIPOQ gene, namely, rs266729 (11365C>G); rs822395 (4034A>C); rs822396 (3964A>G); rs2241766 (+45T>G) were performed. Of all SNPs in the ADIPOQ gene, only the TT genotype and T allele frequency of the rs2241766 were more prevalent in NSCLC subjects than in controls. The TT genotype of rs2241766 was significantly associated with susceptibility to NSCLC before and after adjustment for age, sex, body mass index, and smoking status. In the survival analyses of subjects receiving surgical resection, only the SNPs of rs2241766 were significantly related to overall survival of NSCLC. Our results suggest that the SNP rs2241766 of the ADIPOQ gene may determine both susceptibility to NSCLC, and the prognosis for those who underwent surgical treatment.

Catalytic Asymmetric Synthesis of a Tertiary Benzylic Carbon Center Via Phenol-directed Alkene Hydrogenation

The Journal of Organic Chemistry. Jul, 2011  |  Pubmed ID: 21630712

An expeditious synthetic approach to chiral phenol 1, a key building block in the preparation of a series of drug candidates, is reported. The strategy includes a cost-effective and readily scalable route to cyclopentanone 3 from isobutyronitrile (10). The sterically hindered and enolizable ketone 3 was subsequently employed in a challenging Grignard addition mediated by LaCl(3)·2LiCl. A novel preparation of the lanthanide reagent required for this transformation is described. To complete the process, a highly enantioselective hydrogenation step afforded the target (1). The importance of the phenol group to the success of this asymmetric transformation is discussed.

Follow-up Results of Children with Melamine Induced Urolithiasis: a Prospective Observational Cohort Study

World Journal of Pediatrics : WJP. Aug, 2011  |  Pubmed ID: 21633859

Melamine-contaminated milk powder was the cause of the 2008 outbreak of urolithiasis in young children and infants in China, but the prognosis of these children remains unknown. We hypothesized that urolithiasis induced by melamine-contaminated milk powder may be associated with secondary renal injury.

Estimation of Cancer Cases and Deaths Attributable to Infection in China

Cancer Causes & Control : CCC. Aug, 2011  |  Pubmed ID: 21667067

The burden of cancer attributable to infection in China has not been systematically quantified in detail.

Expression of Nuclear Factor -κBp65 in Mononuclear Cells in Kawasaki Disease and Its Relation to Coronary Artery Lesions

Indian Journal of Pediatrics. Nov, 2011  |  Pubmed ID: 21688043

To assess the association of nuclear factor-kappa B (NF-κB) and complications of Kawasaki disease (KD) in Chinese children.

A Selective Inhibitor and Probe of the Cellular Functions of Jumonji C Domain-containing Histone Demethylases

Journal of the American Chemical Society. Jun, 2011  |  Pubmed ID: 21585201

Histone methylations are important chromatin marks that regulate gene expression, genomic stability, DNA repair, and genomic imprinting. Histone demethylases are the most recent family of histone-modifying enzymes discovered. Here, we report the characterization of a small-molecule inhibitor of Jumonji C domain-containing histone demethylases. The inhibitor derives from a structure-based design and preferentially inhibits the subfamily of trimethyl lysine demethylases. Its methyl ester prodrug, methylstat, selectively inhibits Jumonji C domain-containing his-tone demethylases in cells and may be a useful small-molecule probe of chromatin and its role in epigenetics.

Altered White Matter Integrity in First-episode, Treatment-naive Young Adults with Major Depressive Disorder: a Tract-based Spatial Statistics Study

Brain Research. Jan, 2011  |  Pubmed ID: 21047498

Because most previous diffusion tensor imaging (DTI) studies have focused on late-life depression, this study examined the possible changes in brain white matter (WM) in first-episode, treatment-naive young adults with major depressive disorder (MDD). DTI was performed in 25 (10 males and 15 females) first-episode, treatment-naive young adult patients with MDD and 25 healthy controls matched for age, gender, and education. A whole-brain statistical comparison method called tract-based spatial statistics (TBSS) was used to analyze the data. Compared with healthy controls, patients with MDD showed decreased fractional anisotropy (FA) values in three WM tracts: the left anterior limb of the internal capsule, the right parahippocampal gyrus, and the left posterior cingulate cortex. Further analysis revealed that FA values in the left anterior limb of the internal capsule were negatively correlated with the severity of depressive symptoms. No regions showed higher FA in MDD patients than in controls. The present results support the hypothesis that altered WM integrity, especially in the cortical-subcortical neural circuit, may contribute to the pathophysiology of MDD. Furthermore, these findings provide novel evidence that microstructural abnormalities in WM may occur early in the course of depression.

Graphene As a Spacer to Layer-by-layer Assemble Electrochemically Functionalized Nanostructures for Molecular Bioelectronic Devices

Langmuir : the ACS Journal of Surfaces and Colloids. Sep, 2011  |  Pubmed ID: 21793577

This study demonstrates the capability of graphene as a spacer to form electrochemically functionalized multilayered nanostructures onto electrodes in a controllable manner through layer-by-layer (LBL) chemistry. Methylene green (MG) and positively charged methylimidazolium-functionalized multiwalled carbon nanotubes (MWNTs) were used as examples of electroactive species and electrochemically useful components for the assembly, respectively. By using graphene as the spacer, the multilayered nanostructures of graphene/MG and graphene/MWNT could be readily formed onto electrodes with the LBL method on the basis of the electrostatic and/or π-π interaction(s) between graphene and the electrochemically useful components. Scanning electron microscopy (SEM), ultraviolet-visible spectroscopy (UV-vis), and cyclic voltammetry (CV) were used to characterize the assembly processes, and the results revealed that nanostructure assembly was uniform and effective with graphene as the spacer. Electrochemical studies demonstrate that the assembled nanostructures possess excellent electrochemical properties and electrocatalytic activity toward the oxidation of NADH and could thus be used as electronic transducers for bioelectronic devices. This potential was further demonstrated by using an alcohol dehydrogenase-based electrochemical biosensor and glucose dehydrogenase-based glucose/O(2) biofuel cell as typical examples. This study offers a simple route to the controllable formation of graphene-based electrochemically functionalized nanostructures that can be used for the development of molecular bioelectronic devices such as biosensors and biofuel cells.

Predictive Performance of Prostate Cancer Risk in Chinese Men Using 33 Reported Prostate Cancer Risk-associated SNPs

The Prostate. Jul, 2011  |  Pubmed ID: 21796652

BACKGROUND: Genome-wide association studies (GWAS) have identified more than 30 single nucleotide polymorphisms (SNPs) that were reproducibly associated with prostate cancer (PCa) risk in populations of European descent. In aggregate, these variants have shown potential to predict risk for PCa in European men. However, their utility for PCa risk prediction in Chinese men is unknown. METHODS: We selected 33 PCa risk-related SNPs that were originally identified in populations of European descent. Genetic scores were estimated for subjects in a Chinese case-control study (1,108 cases and 1,525 controls) based on these SNPs. To assess the performance of the genetic score on its ability to predict risk for PCa, we calculated area under the curve (AUC) of the receiver operating characteristic (ROC) in combination with 10-fold cross-validation. RESULTS: The genetic score was significantly higher for cases than controls (P = 5.91 × 10(-20) ), and was significantly associated with risk of PCa in a dose-dependent manner (P for trend: 4.78 × 10(-18) ). The AUC of the genetic score was 0.604 for risk prediction of PCa in Chinese men. When ORs derived from this Chinese study population were used to calculate genetic score, the AUCs were 0.631 for all 33 SNPs and 0.617 when using only the 11 significant SNPs. CONCLUSION: Our results indicate that genetic variants related to PCa risk may be useful for risk prediction in Chinese men. Prospective studies are warranted to further evaluate these findings. Prostate © 2011 Wiley-Liss, Inc.

AAK1 Identified As an Inhibitor of Neuregulin-1/ErbB4-dependent Neurotrophic Factor Signaling Using Integrative Chemical Genomics and Proteomics

Chemistry & Biology. Jul, 2011  |  Pubmed ID: 21802010

Target identification remains challenging for the field of chemical biology. We describe an integrative chemical genomic and proteomic approach combining the use of differentially active analogs of small molecule probes with stable isotope labeling by amino acids in cell culture-mediated affinity enrichment, followed by subsequent testing of candidate targets using RNA interference-mediated gene silencing. We applied this approach to characterizing the natural product K252a and its ability to potentiate neuregulin-1 (Nrg1)/ErbB4 (v-erb-a erythroblastic leukemia viral oncogene homolog 4)-dependent neurotrophic factor signaling and neuritogenesis. We show that AAK1 (adaptor-associated kinase 1) is a relevant target of K252a, and that the loss of AAK1 alters ErbB4 trafficking and expression levels, providing evidence for a previously unrecognized role for AAK1 in Nrg1-mediated neurotrophic factor signaling. Similar strategies should lead to the discovery of novel targets for therapeutic development.

Identification of Changes in Wheat (Triticum Aestivum L.) Seeds Proteome in Response to Anti-trx S Gene

PloS One. 2011  |  Pubmed ID: 21811579

Thioredoxin h (trx h) is closely related to germination of cereal seeds. The cDNA sequences of the thioredoxin s (trx s) gene from Phalaris coerulescens and the thioredoxin h (trx h) gene from wheat are highly homologous, and their expression products have similar biological functions. Transgenic wheat had been formed after the antisense trx s was transferred into wheat, and it had been certified that the expression of trx h decreased in transgenic wheat, and transgenic wheat has high resistance to pre-harvest sprouting.

[Adherent Culture of CD133+ Cells in Glioblastomas and Expression of ADLH1]

Sichuan Da Xue Xue Bao. Yi Xue Ban = Journal of Sichuan University. Medical Science Edition. May, 2011  |  Pubmed ID: 21827011

To investigate the influence of adherent culture on the acquisition of CD133+ cells in glioblastomas and the expressions of acetaldehyde dehydrogenase 1 (ALDH1) in the undifferentiated and differentiated cells.

High Content Screening in Zebrafish Speeds Up Hazard Ranking of Transition Metal Oxide Nanoparticles

ACS Nano. Sep, 2011  |  Pubmed ID: 21851096

Zebrafish is an aquatic organism that can be used for high content safety screening of engineered nanomaterials (ENMs). We demonstrate, for the first time, the use of high content bright-field and fluorescence-based imaging to compare the toxicological effect of transition metal oxide (CuO, ZnO, NiO, and Co(3)O(4)) nanoparticles in zebrafish embryos and larvae. High content bright-field imaging demonstrated potent and dose-dependent hatching interference in the embryos, with the exception of Co(3)O(4) which was relatively inert. We propose that the hatching interference was due to the shedding of Cu and Ni ions, compromising the activity of the hatching enzyme, ZHE1, similar to what we previously proposed for Zn(2+). This hypothesis is based on the presence of metal-sensitive histidines in the catalytic center of this enzyme. Co-introduction of a metal ion chelator, diethylene triamine pentaacetic acid (DTPA), reversed the hatching interference of Cu, Zn, and Ni. While neither the embryos nor larvae demonstrated morphological abnormalities, high content fluorescence-based imaging demonstrated that CuO, ZnO, and NiO could induce increased expression of the heat shock protein 70:enhanced green fluorescence protein (hsp70:eGFP) in transgenic zebrafish larvae. Induction of this response by CuO required a higher nanoparticle dose than the amount leading to hatching interference. This response was also DTPA-sensitive. We demonstrate that high content imaging of embryo development, morphological abnormalities, and HSP70 expression can be used for hazard ranking and determining the dose-response relationships leading to ENM effects on the development of the zebrafish embryo.

In Vitro Kinetics of Oxygen Transport in Erythrocyte Suspension or Unmodified Hemoglobin Solution from Human and Other Animals

Canadian Journal of Physiology and Pharmacology. Sep, 2011  |  Pubmed ID: 21851162

Oxygen transport behavior in erythrocyte suspension or in hemoglobin solution was studied as a potential therapeutic model for the clinical treatment of blood loss, and this can also provide physiological data with which to evaluate blood substitutes. In the present project, we examined the in vitro kinetics of hemoglobin binding to and releasing oxygen, to provide detailed oxygen-flux measurements for unmodified hemoglobin solutions and erythrocyte suspensions in human, as well as other vertebrates. An in vitro method was used, based on a widely used artificial system, with the oxygen saturation level being detected in real time. Results from this study indicated that the kinetic curves of human erythrocyte suspensions and hemoglobin solutions were either S-shaped or hyperbolic, respectively. Based on these curves, the significance of T(50) emerged in our investigation, where T(50) is defined as the time needed for 50% hemoglobin to be saturated with oxygen, and reflects the efficiency with which hemoglobin carries oxygen. This parameter may be used to diagnose blood diseases, and could be a standard for evaluating blood substitutes. In this study, we also compared the T(50) of 4 species of vertebrates, and found that it shows a distinct efficiency of oxygen binding related to species, and potentially reveals the evolutionary function of hemoglobin and its possible adaptation to the environment.

Identification of Forensically Important Sarcophagid Flies (Diptera: Sarcophagidae) in China, Based on COI and 16S RDNA Gene Sequences

Journal of Forensic Sciences. Nov, 2011  |  Pubmed ID: 21854377

Insects attracted to cadavers may provide important indications of the postmortem interval (PMI). However, use of the flesh flies (Diptera: Sarcophagidae) for PMI estimation is limited as the species are often not morphologically distinct, especially as immatures. In this study, 23 forensically important flesh flies were collected from 13 locations in 10 Chinese provinces. Then, a 278-bp segment of the cytochrome oxidase subunits one (COI) gene and a 289-bp segment of the 16S rDNA gene of all specimens were successfully sequenced. Phylogenetic analysis of the sequenced segments showed that all sarcophagid specimens were properly assigned into four species (Boerttcherisca peregrina [Robineau-Desvoidy, 1830], Helicophagella melanura [Meigen, 1826], Parasarcophaga albiceps [Meigen, 1826], and Parasarcophaga dux [Thompson, 1869]) with relatively strong supporting values, thus indicating that the COI and 16S rDNA regions are suitable for identification of sarcophagid species. The difference between intraspecific threshold and interspecific divergence confirmed the potential of the two regions for sarcophagid species identification.

[Treatment of Thoracolumbar Burst Fracture with Subtotal Vertebrectomy, Decompression and Strut Grafting Through Posterolateral Approach]

Zhongguo Gu Shang = China Journal of Orthopaedics and Traumatology. Jul, 2011  |  Pubmed ID: 21870392

To explore the clinical effect of subtotal vertebrectomy, decompression and strut grafting in treating thoracolumbar burst fractures through posterolateral approach via posterior midline incision.

[Experimental Study on the Mechanism of Icariin Improving Human Osteoblasts Proliferation and the Expression of OPG Protein]

Zhongguo Gu Shang = China Journal of Orthopaedics and Traumatology. Jul, 2011  |  Pubmed ID: 21870401

To establish the human osteoblasts culture system in vitro, observe the effects of icariin on human osteoblasts proliferation and expression of OPG protein, and to explore the mechanism of promoting bone formation about human osteoblast in icariin.

Amygdala Hyperactivation and Prefrontal Hypoactivation in Subjects with Cognitive Vulnerability to Depression

Biological Psychology. Dec, 2011  |  Pubmed ID: 21878364

The hopelessness theory (HT) of depression is a diathesis-stress theory which construes cognitive vulnerability (CV) to depression. Neuroimaging studies examining depression have implicated the amygdala as an important potential locus of dysfunction in the processing of salient threatening stimuli. However, little is known about neural activation in the brain of subjects with CV to depression. Medication-free major depressive disorder (MDD) subjects (N=29), never depressed subjects with CV (N=26), and demographically matched never depressed healthy control (HC) subjects (N=31) were scanned using functional magnetic resonance imaging (fMRI) while performing an emotional matching task. The MDD subjects showed elevated left amygdala responses and reduced left dorsolateral prefrontal cortex (dlPFC) activation levels relative to HC subjects. Similarly, CV subjects had greater activity in the amygdala bilaterally and lesser activation in the dlPFC bilaterally, relative to HC subjects. The present findings raise the possibility that cognitive vulnerability to depression might be characterized by hypoactivation of the prefrontal cortex and hyperactivation of the amygdala in response to emotional stimuli; our observations might provide a potential interpretation to explain the abnormalities in neural networks mediating cognitive modulation of emotions in individuals with cognitive vulnerability to depression.

Extraordinary Enhancement of Raman Scattering from Pyridine on Single Crystal Au and Pt Electrodes by Shell-isolated Au Nanoparticles

Journal of the American Chemical Society. Oct, 2011  |  Pubmed ID: 21899270

We used shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) to systematically study the adsorption of pyridine on low-index Au(hkl) and Pt(hkl) single crystal electrodes. Our gold-core silica-shell nanoparticles (Au@SiO(2) NPs) boost the intensity of Raman scattering from molecules adsorbed on atomically flat surfaces. The average enhancement factor reaches 10(6) for Au(110) and 10(5) for Pt(110), which is comparable to or even greater than that obtained for bare gold NPs (a widely adopted SERS substrate). 3D-FDTD simulations reveal that this large enhancement is due to the transfer of the "hotspots" from NP-NP gaps to NP-surface gaps. We also found that the SHINERS intensity strongly depends on the surface crystallographic orientation, with differences up to a factor of 30. Periodic DFT calculations and theoretical analysis of dielectric functions indicate that this facet-dependence is predominantly governed by the dielectric property of the surface. The results presented in this work may open up new approaches for the characterization of adsorbates and reaction pathways on a wide range of smooth surfaces.

MMP-2 Mediates Angiotensin II-induced Hypertension Under the Transcriptional Control of MMP-7 and TACE

Hypertension. Jan, 2011  |  Pubmed ID: 21079048

Development of cardiovascular disease induced by excessive Gq protein-coupled receptor agonist stimulation depends on signaling networks involving multiple matrix metalloproteinases (MMPs) and metalloproteinase disintegrins (ADAMs). Here, we hypothesized that MMP-2, being a major gelatinase in cardiac and vascular tissue, was likely to play a key role in cardiovascular homeostasis. We targeted MMP-2 using complementary and overlapping approaches involving pharmacological inhibition and RNA interference in mice treated with angiotensin II (1.4 mg/kg per day) for 12 days. We studied the development of hypertension (by tail cuff plethysmography), cardiac hypertrophy (by M-mode echocardiography, cardiomyocyte cross-sectional area, and quantitative real-time polymerase chain reaction (qRT-PCR) analysis of hypertrophy marker genes), and fibrosis (by picrosirius red collagen staining and qRT-PCR analysis of fibrosis marker genes) in mice receiving angiotensin II. We found that angiotensin II infusion upregulated MMP-2 concurrent with the development of hypertension, hypertrophy, and fibrosis. This upregulation of MMP-2 depended on MMP-7 and TACE (tumor necrosis factor-α convertase, ADAM-17). RNA interference targeting MMP-7 and TACE attenuated the angiotensin II-induced upregulation of MMP-2 and prevented the development of hypertension, as well as development of cardiac hypertrophy and fibrosis. In contrast, pharmacological inhibition and RNA interference of MMP-2 attenuated angiotensin II-induced hypertension, without influencing development of cardiac hypertrophy or fibrosis. Downstream of MMP-7 and TACE, MMP-2 mediated angiotensin II-induced hypertension, but did not mediate cardiac hypertrophy or fibrosis. This suggests a functional specialization of MMP-2 in agonist-induced cardiovascular disease development that has potential implications for the design of metalloproteinase-based therapeutic strategies.

Damage Initiation Sites in Osteoporotic and Normal Human Cancellous Bone

Bone. Mar, 2011  |  Pubmed ID: 21081188

Using a finite element (FE) method called biomechanical stereology, Wang et al. previously reported increased microcrack formation and propagation in bone samples from patients with a history of osteoporotic fracture as compared to normal subjects. In this study, we re-analyzed the data from Wang's report to determine the microscopic differences between bone tissue from osteoporotic patients and normal subjects that caused these different patterns of bone tissue damage between the groups. The morphological features examined were the number of "voids" (or osteocyte lacunae) visible and the distance of the lacunae from the initiation of the microcracks. We found that bone samples from patients with a history of osteoporotic fracture contained significantly more lacunae than normal control specimens. We also found a significant correlation (r² = 0.483, p = 0.001) between the number of lacunae visible in the image and the number of microcracks formed. These results help to explain the differences in total microcrack number between the osteoporotic and normal subjects reported in our previous work.

Different Reaction Patterns of Dopamine Content to Prenatal Exposure to Chlorpyrifos in Different Periods

Journal of Applied Toxicology : JAT. May, 2011  |  Pubmed ID: 21089160

Developmental exposure to chlorpyrifos (CPF) induces abnormalities in neurotransmission. In the present study, we evaluated the dopamine reaction patterns in brain regions after CPF exposure during different prenatal periods. Animals were exposed on gestational days (GD) 7.5-11.5 or 13-17 and assessed at GD17, and at postnatal days (PN) 14 and 60. CPF exposure during GD7.5-11.5 elicited a decrease in dopamine content at each measurement stages, with more changes in the hippocampus than in the cerebral cortex. In contrast, CPF exposure in GD13-17 elicited a decrease in dopamine content at PN14 and PN60, with more changes in the cerebral cortex than in the hippocampus. These results suggest that the two key brain regions involved in learning and memory, the cerebral cortex and hippocampus, react differently to CPF exposure in different prenatal periods. The abnormalities did not recover long after cessation of CPF exposure and deficiencies persisted into pre-puberty and adulthood.

Time Course of Affective Processing Bias in Major Depression: An ERP Study

Neuroscience Letters. Jan, 2011  |  Pubmed ID: 21036200

The current study investigated the time course of the affective processing bias in major depressive disorder (MDD) in a visual three-stimulus semantic oddball task using event-related potentials (ERPs). MDD patients showed decreased P1 latency over right posterior regions to negative relative to positive target stimuli, reflecting a very early onset of the negativity bias in emotional perception. Compared to controls, MDD patients showed enlarged anterior P2 amplitude to positive target stimuli, reflecting an affective bias in the early attentional stages of processing. In addition, MDD patients showed relatively high N2 and reduced P3 amplitudes to negative compared with positive target stimuli, as well as marginally reduced N2 amplitude to positive target stimuli compared with controls. This suggests that the negativity bias also occurs during later strategic evaluation stages. Therefore, the present study extended previous findings by demonstrating that the affective processing bias in MDD begins in the early stages of perceptual processing and continues at later cognitive stages.

Effects of a Novel Ultrasound Contrast Agent with Long Persistence on Right Ventricular Pressure: Comparison with SonoVue

Ultrasonics. Feb, 2011  |  Pubmed ID: 20825961

This work investigated the effect of infusion of a self-made ultrasound contrast agent with long persistence (named ZHIFUXIAN) on rat right ventricular pressure and made a preliminary evaluation on the relative safety of the novel microbubbles. Normal saline, SonoVue and ZHIFUXIAN were injected through caudal vein at the total volume of 0.5ml for each injection. The right ventricular systolic pressure (RVSP) and end-diastolic pressure (RVEDP) were monitored and the changes of the pressure were compared with baseline readings. RVSP increased when saline, SonoVue or ZHIFUXIAN were injected, the greatest change being after SonoVue (about 2mmHg), but there was no statistical significance compared with baseline (P>0.05). There was no significant difference in RVSP between saline, SonoVue and ZHIFUXIAN at any time point. Also, there was no significant difference in RVEDP between groups at each time point and between different time points in each group. The results indicate that the self-made microbubbles effect on right ventricular hemodynamics is equivalent to that of normal saline at the same volume needed for effective enhanced imaging, demonstrating that it does not produce changes in right ventricular blood pressure under the study conditions. Pathological examination also showed it had no obvious influence on lung, liver and kidney.

Discrimination Between Pathological and Normal Voices Using GMM-SVM Approach

Journal of Voice : Official Journal of the Voice Foundation. Jan, 2011  |  Pubmed ID: 20137892

Acoustic features of vocal tract function are used widely in the study of pathological voices detection. Classification of normal and pathological voices by acoustic parameters is a useful way to diagnose voice diseases. In this aspect, mel-frequency cepstral coefficients are proved to be effective with traditional classifiers such as Gaussian Mixture Model (GMM). However, the accuracy of the classification method can be further improved. In this article, a Gaussian mixture model supervector kernel-support vector machine (GMM-SVM) classifier is compared with GMM classifier for the detection of voice pathology. We found that a sustain vowel phonation can be classified as normal or pathological with an accuracy of 96.1%. Voice recordings are selected from the Kay database to carry out the experiments. Experimental results show that equal error rates decrease from 8.0% for GMM to 4.6% for GMM-SVM.

Interplay Between MDM2, MDMX, Pirh2 and COP1: the Negative Regulators of P53

Molecular Biology Reports. Jan, 2011  |  Pubmed ID: 20333547

MDM2, Pirh2 and COP1 are important E3 ubiquitin ligases, which directly interact with p53 and target p53 for proteasome-mediated degradation. MDMX, the MDM2 homologous protein, inhibits p53-mediated transcription activity. The interplay between MDM2, MDMX, Pirh2 and COP1 has not been reported, except the interaction between MDM2 and MDMX. Here, we reported that there were interactions between these four proteins independently of p53. The protein levels of MDM2, MDMX, Pirh2 and COP1 changed when any two of them were co-transfected. Our data also showed that the integrity of MDM2 RING finger domain was crucial for its ability to elevate the protein levels of COP1 and Pirh2. Any two of these four proteins could inhibit p53-mediated transcriptional activity synergistically. Furthermore, COP1 inhibited MDM2 self-ubiquitination and interfered with MDMX ubiquitination by MDM2. Our results suggest that MDM2, MDMX, Pirh2 and COP1 might inhibit p53 activity synergistically in vivo.

Salient Latent Constructs Underlying Smoking Initiation and Continuous Use by Student-Smokers of Huazhong University of Science and Technology, China

Asia-Pacific Journal of Public Health / Asia-Pacific Academic Consortium for Public Health. Dec, 2011  |  Pubmed ID: 22186389

The factor analysis model was used to parsimoniously reduce the number of variables that influence smoking among students to salient factors that cut across continents, race, and sociocultural settings among university students in China. Stratified random sampling and snowball techniques were employed to obtain the sample. A Likert-type questionnaire was used to collect data. The results revealed that of the 39 variables identified to influence smoking, 34 were retained and regrouped in terms of common features they share into 13 salient factors that accounted for 58% of variances in the original variables. The predominant hidden construct was influence by association. The other 12 factors were labeled and ordered as follows: emotional needs, family history, addiction, peer pressure, lack of full realization of the consequences of their action as regards the expense of smoking, social needs, advertisement, psychological needs, self-image, environmental factors, ineffective policies, and underestimation of health risks. Irrespective of regional demarcations, factors that influence smoking initiation and continuous use are same.

Prediction of New Clinical Vertebral Fractures in Elderly Men Using Finite Element Analysis of CT Scans

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. Dec, 2011  |  Pubmed ID: 22190331

Vertebral strength, as estimated by finite element analysis of computed tomography (CT) scans, has not yet been compared against areal bone mineral density (BMD) by dual energy x-ray absorptiometry (DXA) for prospectively assessing the risk of new clinical vertebral fractures. To do so, we conducted a case-cohort analysis of 306 men aged 65 yrs and older, which included 63 men who developed new clinically-identified vertebral fractures and 243 men who did not, all observed over an average of 6.5 years. Non-linear finite element analysis was performed on the baseline CT scans, blinded to fracture status, to estimate L1 vertebral compressive strength and a load-to-strength ratio. Volumetric BMD by quantitative CT and areal BMD by DXA were also evaluated. We found that, for the risk of new clinical vertebral fracture, the age-adjusted hazard ratio per standard deviation change for areal BMD (3.2; 95% CI: 2.0-5.2) was significantly lower (p < 0.005) than for strength (7.2; 3.6-14.1), numerically lower than for volumetric BMD (5.7; 3.1-10.3), and similar for the load-to-strength ratio (3.0; 2.1-4.3). After also adjusting for race, BMI, clinical center, and areal BMD, all these hazard ratios remained highly statistically significant, particularly those for strength (8.5; 3.6-20.1) and volumetric BMD (9.4; 4.1-21.6). The area-under-the-curve for areal BMD (AUC = 0.76) was significantly lower than for strength (AUC = 0.83, p = 0.02), volumetric BMD (AUC = 0.82, p = 0.05), and the load-to-strength ratio (AUC = 0.82, p = 0.05). We conclude that, compared to areal BMD by DXA, vertebral compressive strength and volumetric BMD consistently improved vertebral fracture risk assessment in this cohort of elderly men. © 2011 American Society for Bone and Mineral Research.

Single-molecule Colocalization Studies Shed Light on the Idea of Fully Emitting Versus Dark Single Quantum Dots

Small (Weinheim an Der Bergstrasse, Germany). Jul, 2011  |  Pubmed ID: 21710484

In this report the correlation between the solution photoluminescence (PL) quantum yield and the fluorescence emission of individual semiconductor quantum dots (QDs) is investigated. This is done by taking advantage of previously reported enhancement in the macroscopic quantum yield of water-soluble QDs capped with dihydrolipoic acid (DHLA) when self-assembled with polyhistidine-appended proteins, and by using fluorescence coincidence analysis (FCA) to detect the presence of "bright" and "dark" single QDs in solution. This allows for changes in the fraction of the two QD species to be tracked as the PL yield of the solution is progressively altered. The results clearly indicate that in a dispersion of luminescent nanocrystals, "bright" (intermittently emitting) single QDs coexist with "permanently dark" (non-emitting) QDs. Furthermore, the increase in the fraction of emitting QDs accompanies the increase in the PL quantum yield of the solution. These findings support the idea that a dispersion of QDs consists of two optically distinct populations of nanocrystals--one is "bright" while the other is "dark;" and that the relative fraction of these two populations defines the overall PL yield.

[Contents and Biodegradation of Soluble Organic Carbon in Different Plant Residues from the Loess Plateau]

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.]. Apr, 2011  |  Pubmed ID: 21717760

Soluble organic carbon (SOC) in plant residues extracted by water or different extractants is an active component, and has important roles in carbon and nitrogen biogeochemical process in soil ecosystem. Reestablishing the vegetation on the Loess Plateau is changing the types and amounts of the plant residues into soil ecosystem. Therefore, our objective was to evaluate the contents and biodegradation of SOC of residues of different species from this region. Six species of plant residues were sampled from Shenmu, North of the Loess Plateau, and the contents of SOC in two sizes residues (2 mm and 1 cm length) was extracted with two extractants (distilled water and 0.01 mol x L(-1) CaCl2). And a 7-day incubation experiment (25 degrees C) was conducted to compare the biodegradability of SOC of the different plant residues. The contents of SOC in the different plant species ranged from 4.21 g x kg(-1) to 76.25 g x kg(-1), and the rates of SOC to total carbon (SOC/TC) of the plant residues were in range of 0.99% and 19.84%. The order about the average content of SOC and SOC/TC of the different plant species was trees > shrubs > grasses. After 7-day of incubation, rates of biodegradation of SOC in different plant residues ranged from 34. 7% to 75. 1% (averaged 56.3%). The proportion of complex structure SOC increased significantly in solution at the end of incubation, indicated the rapid biodegradation of labile composition in the residues.

Systematic Confirmation Study of Reported Prostate Cancer Risk-associated Single Nucleotide Polymorphisms in Chinese Men

Cancer Science. Oct, 2011  |  Pubmed ID: 21756274

More than 30 prostate cancer (PCa) risk-associated loci have been identified in populations of European descent by genome-wide association studies. We hypothesized that a subset of these loci might be associated with PCa risk in Chinese men. To test this hypothesis, 33 single nucleotide polymorphisms (SNP), one each from the 33 independent PCa risk-associated loci reported in populations of European descent, were investigated for their associations with PCa risk in a case-control study of Chinese men (1108 cases and 1525 controls). We found that 11 of the 33 SNP were significantly associated with PCa risk in Chinese men (P < 0.05). The reported risk alleles were associated with increased risk for PCa, with allelic odds ratios ranging from 1.12 to 1.44. The most significant locus was located on 8q24 region 2 (rs16901979, P = 5.14 × 10(-9)) with a genome-wide significance (P < (-8) ), and three loci reached the Bonferroni correction significance level (P < 1.52 × 10(-3)), including 8q24 region 1 (rs1447295, P = 7.04 × 10(-6)), 8q24 region 5 (rs10086908, P = 9.24 × 10(-4)) and 8p21 (rs1512268, P = 9.39 × 10(-4)). Our results suggest that a subset of the PCa risk-associated SNP discovered by genome-wide association studies among men of European descent is also associated with PCa risk in Chinese men. This finding provides evidence of ethnic differences and similarity in genetic susceptibility to PCa. Genome-wide association studies in Chinese men are needed to identify Chinese-specific PCa risk-associated SNP.

NF-kB Activity-dependent P-selectin Involved in Ox-LDL-induced Foam Cell Formation in U937 Cell

Biochemical and Biophysical Research Communications. Aug, 2011  |  Pubmed ID: 21763287

Oxidized low-density lipoprotein (ox-LDL) plays a critical role in regulation of atherosclerosis. However, little is known about the role of Nuclear factor kB (NF-kB) activity-dependent P-selectin in ox-LDL-induced foam cell formation during atherosclerosis. In this study, we first investigated ox-LDL induced foam cell formation in the human U937 promonocytic cell line in a dose- and time-dependent manner. Treatment of U937 cells with ox-LDL increased lipid accumulation as well as intracellular cholesterol content. Next, a comparative analysis of gene expression profiling using cDNA microarray and Real-time-PCR indicated that ox-LDL exposure induced, in three treated groups, an extremely marked increase in the mRNA level of P-selectin. Protein levels of P-selectin and its upstream regulators IkBa and NF-kB showed that NF-kB pathway is involved in the ox-LDL-induced foam cell formation. Finally, overexpression of NF-kB significantly accelerated, whereas, inhibition of NF-kB with siRNA remarkably attenuated ox-LDL-induced macrophage-derived foam cell formation. It was concluded that the activity of NF-kB is augmented during macrophage-derived foam cell formation. Activation of NF-kB increased, whereas, inhibition of NF-kB decreased ox-LDL-induced P-selectin expression and lipid accumulation in macrophages, suggesting ox-LDL induced expression of P-selectin through degradation of IkBa and activation of NF-kB in the regulation of foam cell formation.

[Bioremediation of Petroleum Hydrocarbon-contaminated Soils by Cold-adapted Microorganisms: Research Advance]

Ying Yong Sheng Tai Xue Bao = The Journal of Applied Ecology / Zhongguo Sheng Tai Xue Xue Hui, Zhongguo Ke Xue Yuan Shenyang Ying Yong Sheng Tai Yan Jiu Suo Zhu Ban. Apr, 2011  |  Pubmed ID: 21774336

Cold-adapted microorganisms such as psychrotrophs and psychrophiles widely exist in the soils of sub-Arctic, Arctic, Antarctic, alpine, and high mountains, being the important microbial resources for the biodegradation of petroleum hydrocarbons at low temperature. Using the unique advantage of cold-adapted microorganisms to the bioremediation of petroleum hydrocarbon-contaminated soils in low temperature region has become a research hotspot. This paper summarized the category and cold-adaptation mechanisms of the microorganisms able to degrade petroleum hydrocarbon at low temperature, biodegradation characteristics and mechanisms of different petroleum fractions under the action of cold-adapted microorganisms, bio-stimulation techniques for improving biodegradation efficiency, e. g., inoculating petroleum-degrading microorganisms and adding nutrients or bio-surfactants, and the present status of applying molecular biotechnology in this research field, aimed to provide references to the development of bioremediation techniques for petroleum hydrocarbon-contaminated soils.

[Protection of Hyperoxia-induced Lung Injury by Granulocyte-macrophage Colony-stimulating Factor Via RAGE-NF-κB Signaling Pathway in Newborn Rats]

Zhonghua Yi Xue Za Zhi. Aug, 2011  |  Pubmed ID: 22093994

To explore the effects of granulocyte-macrophage colony-stimulating factor (GMCSF) on hyperoxia exposure lung injury in newborn rats and elucidate its protective mechanism of operating via the signaling pathway of advanced glycation end products (RAGE)-NF-κB.

Long-distance Electrical Coupling Via Tunneling Nanotubes

Biochimica Et Biophysica Acta. Sep, 2011  |  Pubmed ID: 21930113

Tunneling nanotubes (TNTs) are nanoscaled, F-actin containing membrane tubes that connect cells over several cell diameters. They facilitate the intercellular exchange of diverse components ranging from small molecules to organelles and pathogens. In conjunction with recent findings that TNT-like structures exist in tissue, they are expected to have important implications in cell-to-cell communication. In this review we will focus on a new function of TNTs, namely the transfer of electrical signals between remote cells. This electrical coupling is not only determined by the biophysical properties of the TNT, but depends on the presence of connexons interposed at the membrane interface between TNT and the connected cell. Specific features of this coupling are compared to conventional gap junction communication. Finally, we will discuss possible down-stream signaling pathways of this electrical coupling in the recipient cells and will discuss putative effects of different physiological activities. This article is part of a Special Issue entitled: The communicating junctions: Composition, structure and functions.

Impaired Thymic Export and Apoptosis Contribute to Regulatory T-cell Defects in Patients with Chronic Heart Failure

PloS One. 2011  |  Pubmed ID: 21935395

Animal studies suggest that regulatory T (T(reg)) cells play a beneficial role in ventricular remodeling and our previous data have demonstrated defects of T(reg) cells in patients with chronic heart failure (CHF). However, the mechanisms behind T(reg-)cell defects remained unknown. We here sought to elucidate the mechanism of T(reg-)cell defects in CHF patients.

[Application of Colonic Interposition in the Digestive Tract Reconstruction After Esophagectomy]

Zhonghua Wei Chang Wai Ke Za Zhi = Chinese Journal of Gastrointestinal Surgery. Sep, 2011  |  Pubmed ID: 21948535

To evaluate the safety of colonic interposition after esophagectomy.

Mechanical Property and Tissue Mineral Density Differences Among Severely Suppressed Bone Turnover (SSBT) Patients, Osteoporotic Patients, and Normal Subjects

Bone. Dec, 2011  |  Pubmed ID: 21958843

Pathogenesis of atypical fractures in patients on long term bisphosphonate therapy is poorly understood, and the type, the manner in which they occur and the fracture sites are quite different from the usual osteoporotic fractures. We hypothesized that the tissue-level mechanical properties and mean degree of mineralization of the iliac bone would differ among 1) patients with atypical fractures and severely suppressed bone turnover (SSBT) associated with long-term bisphosphonate therapy, 2) age-matched, treatment-naïve osteoporotic patients with vertebral fracture, 3) age-matched normals and 4) young normals. Large differences in tissue-level mechanical properties and/or mineralization among these groups could help explain the underlying mechanism(s) for the occurrence of typical osteoporotic and the atypical femoral shaft fractures. Elastic modulus, contact hardness, plastic deformation resistance, and tissue mineral densities of cortical and trabecular bone regions of 55 iliac bone biopsies--12 SSBT patients (SSBT; aged 49-77), 11 age-matched untreated osteoporotic patients with vertebral fracture (Osteoporotic), 12 age-matched subjects without bone fracture (Age-Matched Normal), and 20 younger subjects without bone fracture (Young Normal)--were measured using nanoindentation and quantitative backscattered electron microscopy. For cortical bone nanoindentation properties, only plastic deformation resistance was different among the groups (p<0.05), with greater resistance to plastic deformation in the SSBT group compared to all other groups. For trabecular bone, all nanoindentation properties and mineral density of the trabecular bone were different among the groups (p<0.05). The SSBT group had greater plastic deformation resistance and harder trabecular bone compared to the other three groups, stiffer bone compared to the Osteoporotic and Young Normal groups, and a trend of higher mineral density compared to the Age-Matched Normal and Osteoporotic groups. Lower heterogeneity of modulus and contact hardness for cortical bone of the SSBT and trabecular bone of the Osteoporotic fracture groups, respectively, compared to the non-fractured groups, may contribute to fracture susceptibility due to lowered ability to prevent crack propagation. We tentatively conclude that, in addition to extremely low bone formation rate, atypical fractures in SSBT and/or long-term bisphosphonate treatment may be associated with greater mean plastic deformation resistance properties and less heterogeneous elastic properties of the bone.

[Hereditary Tendency of Varicocele]

Zhonghua Nan Ke Xue = National Journal of Andrology. Sep, 2011  |  Pubmed ID: 21961249

To investigate the hereditary tendency of varicocele.

Anti-DR5 Monoclonal Antibody-mediated DTIC-loaded Nanoparticles Combining Chemotherapy and Immunotherapy for Malignant Melanoma: Target Formulation Development and in Vitro Anticancer Activity

International Journal of Nanomedicine. 2011  |  Pubmed ID: 21976975

The increased incidence of malignant melanoma in recent decades, along with its high mortality rate and pronounced resistance to therapy pose an enormous challenge. Novel therapeutic strategies, such as immunotherapy and targeted therapy, are urgently needed for melanoma. In this study, a new active targeting drug delivery system was constructed to combine chemotherapy and active specific immunotherapy.

Second-generation Aptamer-conjugated PSMA-targeted Delivery System for Prostate Cancer Therapy

International Journal of Nanomedicine. 2011  |  Pubmed ID: 21980237

miR-15a and miR-16-1 have been identified as tumor suppressor genes in prostate cancer, but their safe and effective delivery to target cells is key to the successful use of this therapeutic strategy. RNA aptamer A10 has been used as a ligand, targeting prostate cancer cells that express prostate-specific membrane antigen (PSMA). Compared with A10, the binding of the second-generation RNA aptamer, A10-3.2, to PSMA is more efficient.

[Dynamic CT Cisternography in the Diagnosis and Treatment of Intracranial Arachnoid Cysts]

Sichuan Da Xue Xue Bao. Yi Xue Ban = Journal of Sichuan University. Medical Science Edition. Sep, 2011  |  Pubmed ID: 22007506

To investigate the communication between intracranial arachnoid cysts and subarachnoid space using CT cisternography (CTC) and consecutive CT scans.

Gray Matter Volume Abnormalities in Individuals with Cognitive Vulnerability to Depression: A Voxel-based Morphometry Study

Journal of Affective Disorders. Nov, 2011  |  Pubmed ID: 22129771

BACKGROUND: The hopelessness theory of depression posits that individuals with negative cognitive styles are at an increased risk for depression following negative life events. In neuroimaging studies, brain gray matter volume abnormalities correlate with the presence of depressive disorders. However, it is unknown whether changes in gray matter volume also appear in healthy individuals with cognitive vulnerability to depression (CVD). METHODS: 30 subjects diagnosed with CVD, 33 first-episode patients with major depressive disorder (MDD), and 32 healthy controls were examined using voxel-based morphometry following magnetic resonance imaging (MRI). RESULTS: We found significant volumetric differences between three groups in the left precentral gyrus, right fusiform gyrus and the right thalamus. In these regions, compared to controls, CVD subjects showed reduced gray matter volumes in the left precentral gyrus and right fusiform gyrus. MDD patients demonstrated reduced gray matter volume in the left precentral gyrus and increased gray matter volume in the right thalamus. Additionally, CVD individuals had significantly smaller right fusiform gyrus and right thalamus than MDD patients. The weakest-link scores on CSQ were negatively correlated with gray matter volumes in the left precentral gyrus. CONCLUSIONS: Reductions in brain gray matter volume exist widely in individuals with CVD. In addition, there exist similar abnormalities in gray matter volume in both CVD subjects and MDD patients. Reductions of gray matter volume in the left precentral gyrus might be correlated to the negative cognitive styles, as well as an increased risk for depression.

Iatrogenic False Aneurysm Caused by Surgery of a Traumatic Intracranial False Aneurysm

Neurology India. Sep-Oct, 2011  |  Pubmed ID: 22019664

A superficial temporal artery (STA) false aneurysm caused by surgery of a traumatic intracranial false aneurysm is reported. A 28-year-old man underwent craniotomy for aneurysm clipping 20 days after traumatic head injury. At surgery the aneurysm was a false aneurysm due to its avulsion from the parent artery without a real neck. A "clip wrapping" technique was used to repair the deficit on the parent artery. On postoperative Day 25, repeat digital subtraction angiogram (DSA) revealed a new right STA aneurysm, which was not apparent in the preoperative DSA. We feel that this aneurysm might have probably resulted from the iatrogenic injury to the STA during the initial surgery as the location of aneurysm was at the initial craniotomy site. The pathophysiology, etiology, surgical treatment and preventive measures of false aneurysms have been discussed.

Dispersal State of Multiwalled Carbon Nanotubes Elicits Profibrogenic Cellular Responses That Correlate with Fibrogenesis Biomarkers and Fibrosis in the Murine Lung

ACS Nano. Dec, 2011  |  Pubmed ID: 22047207

We developed a dispersal method for multiwalled carbon nanotubes (MWCNTs) that allows quantitative assessment of dispersion on profibrogenic responses in tissue culture cells and in mouse lung. We demonstrate that the dispersal of as-prepared (AP), purified (PD), and carboxylated (COOH) MWCNTs by bovine serum albumin (BSA) and dipalmitoylphosphatidylcholine (DPPC) influences TGF-β1, PDGF-AA, and IL-1β production in vitro and in vivo. These biomarkers were chosen based on their synergy in promoting fibrogenesis and cellular communication in the epithelial-mesenchymal cell trophic unit in the lung. The effect of dispersal was most noticeable in AP- and PD-MWCNTs, which are more hydrophobic and unstable in aqueous buffers than hydrophilic COOH-MWCNTs. Well-dispersed AP- and PD-MWCNTs were readily taken up by BEAS-2B, THP-1 cells, and alveolar macrophages (AM) and induced more prominent TGF-β1 and IL-1β production in vitro and TGF-β1, IL-1β, and PDGF-AA production in vivo than nondispersed tubes. Moreover, there was good agreement between the profibrogenic responses in vitro and in vivo as well as the ability of dispersed tubes to generate granulomatous inflammation and fibrosis in airways. Tube dispersal also elicited more robust IL-1β production in THP-1 cells. While COOH-MWCNTs were poorly taken up in BEAS-2B and induced little TGF-β1 production, they were bioprocessed by AM and induced less prominent collagen deposition at sites of nongranulomatous inflammation in the alveolar region. Taken together, these results indicate that the dispersal state of MWCNTs affects profibrogenic cellular responses that correlate with the extent of pulmonary fibrosis and are of potential use to predict pulmonary toxicity.

Evidence of a Dissociation Pattern in Resting-State Default Mode Network Connectivity in First-Episode, Treatment-Naive Major Depression Patients

Biological Psychiatry. Dec, 2011  |  Pubmed ID: 22177602

BACKGROUND: Imaging studies have shown that major depressive disorder (MDD) is associated with altered activity patterns of the default mode network (DMN). However, the neural correlates of the resting-state DMN and MDD-related pathopsychological characteristics, such as depressive rumination and overgeneral autobiographical memory (OGM) phenomena, still remain unclear. METHODS: Using independent component analysis, we analyzed resting-state functional magnetic resonance imaging data obtained from 35 first-episode, treatment-naive young adults with MDD and from 35 matched healthy control subjects. RESULTS: Patients with MDD exhibited higher levels of rumination and OGM than did the control subjects. We observed increased functional connectivity in the anterior medial cortex regions (especially the medial prefrontal cortex and anterior cingulate cortex) and decreased functional connectivity in the posterior medial cortex regions (especially the posterior cingulate cortex/precuneus) in MDD patients compared with control subjects. In the depressed group, the increased functional connectivity in the anterior medial cortex correlated positively with rumination score, while the decreased functional connectivity in the posterior medial cortex correlated negatively with OGM score. CONCLUSIONS: We report dissociation between anterior and posterior functional connectivity in resting-state DMNs of first-episode, treatment-naive young adults with MDD. Increased functional connectivity in anterior medial regions of the resting-state DMN was associated with rumination, whereas decreased functional connectivity in posterior medial regions was associated with OGM. These results provide new evidence for the importance of the DMN in the pathophysiology of MDD and suggest that abnormal DMN activity may be an MDD trait.

CD4+CD25+Foxp3+ Regulatory T Cells Protect Endothelial Function Impaired by Oxidized Low Density Lipoprotein Via the KLF-2 Transcription Factor

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology. 2011  |  Pubmed ID: 22178876

To investigate the regulation of CD4(+)CD25(+) Regulatory T cells (Tregs) on pro-inflammatory adhesion molecules, Krüppel-Like Factor-2 (KLF-2) and its downstream transcriptional targets in human umbilical vein endothelial cells (HUVECs) impaired by ox-LDL and the mechanisms of it.

Optic-microwave Mixing Velocimeter for Superhigh Velocity Measurement

The Review of Scientific Instruments. Dec, 2011  |  Pubmed ID: 22225206

The phenomenon that a light beam reflected off a moving object experiences a Doppler shift in its frequency underlies practical interferometric techniques for remote velocity measurements, such as velocity interferometer system for any reflector (VISAR), displacement interferometer system for any reflector (DISAR), and photonic Doppler velocimetry (PDV). While VISAR velocimeters are often bewildered by the fringe loss upon high-acceleration dynamic process diagnosis, the optic-fiber velocimeters such as DISAR and PDV, on the other hand, are puzzled by high velocity measurement over 10 km/s, due to the demand for the high bandwidth digitizer. Here, we describe a new optic-microwave mixing velocimeter (OMV) for super-high velocity measurements. By using currently available commercial microwave products, we have constructed a simple, compact, and reliable OMV device, and have successfully obtained, with a digitizer of bandwidth 6 GH only, the precise velocity history of an aluminum flyer plate being accelerated up to 11.2 km/s in a three stage gas-gun experiment.

[Effects of Harmful Algal Bloom on Bio-optical Properties of Coastal Water]

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.]. Oct, 2011  |  Pubmed ID: 22279892

Effects of harmful algal bloom (HAB) on bio-optical properties of coastal waters were studied. Bio-optical data were collected from 11 stations in the Dalian Bay, for an analysis of variable characteristics of biological factors, reflectance and absorption spectra as responses to HAB. The results indicated that, (1) the HAB which occurred in the Dalian Bay was caused by picophytoplankton. (2) Remote sensing reflectance showed an obvious difference with the normal waters: the strong absorption of the high concentration chlorophyll-a leaded to two reflection dips near 440 and 632 nm bands, a much larger fluorescence peak height around the red band accompanied by a "red shift", a sharp peak of oxygen response at 760 nm, and an enhanced reflection peak of suspended matter in the near-infrared band. (3) In addition, effects of HAB on absorption coefficient spectrum mainly reflected in the numerical size and much stronger absorption of ocean color constituents than the normal waters had been found, the a(ph) (440), a(ph) (675), a(d) (440) and a(g) (440) increased to 13.4, 14.5, 5.0 and 3.8 times of the values of normal waters, respectively. Variation features of bio-optical elements were examined and identified when HAB occurred in the Dalian Bay, which provides a way to monitor HAB by satellite remote sensing.

The Formation and Stability of DC-SIGN Microdomains Require Its Extracellular Moiety

Traffic (Copenhagen, Denmark). Jan, 2012  |  Pubmed ID: 22292921

DC-SIGN (Dendritic cell-specific ICAM-3-grabbing non-integrin) is a Ca(2+) -dependent transmembrane lectin that binds a large variety of pathogens and facilitates their uptake for subsequent antigen presentation. This receptor is present in cell surface microdomains, but factors involved in microdomain formation and their exceptional stability are not clear. To determine which domain/motif of DC-SIGN facilitates its presence in microdomains, we studied mutations at key locations including truncation of the cytoplasmic tail, and ectodomain mutations that resulted in removal of the N-linked glycosylation site, the tandem repeats and the carbohydrate recognition domain (CRD) as well as modification of the calcium sites in the CRD required for carbohydrate binding. Confocal imaging and FRAP measurements showed that the cytoplasmic domain and N-linked glycosylation site do not affect the ability of DC-SIGN to form stable microdomains. However, truncation of the CRD results in complete loss of visible microdomains and subsequent lateral diffusion of the mutants. Apart from cell adhesions, membrane domains are thought to be localized primarily via the cytoskeleton. By contrast, we propose that interactions between the CRD of DC-SIGN and the extracellular matrix and/or cis interactions with transmembrane scaffolding protein(s) play an essential role in organizing these microdomains.

Inhibition of Tumor Cell Growth, Proliferation and Migration by X-387, a Novel Active-site Inhibitor of MTOR

Biochemical Pharmacology. Jan, 2012  |  Pubmed ID: 22305748

The mammalian target of rapamycin (mTOR), is deregulated in about 50% of human malignancies and exists in two complexes: mTORC1 and mTORC2. Rapalogs partially inhibit mTORC1 through allosteric binding to mTORC1 and their efficacy is modest as a cancer therapy. A few mTOR kinase inhibitors that inhibit both mTORC1 and mTORC2 have been reported to possess potent anticancer activities. Herein, we designed and synthesized a series of pyrazolopyrimidine derivatives targeting mTOR kinase domain and X-387 was identified as a promising lead. X-387 selectively inhibited mTOR in an ATP-competitive manner while sparing a panel of kinases from the PIKK family. X-387 blocked mTORC1 and mTORC2-mediacted signaling pathway in cell lines with activated mTOR signaling and in rapamycin-resistant cells. Specifically, X-387 inhibited phosphorylation of AKT at T308, which is thought to be a target of PDK1 but not mTOR. Such activity was not due to inhibition of PI3K since X-387 did not inhibit translocation of AKT to the cell membrane. X-387 induced autophagy as observed for other mTOR inhibitors, while induced autophagy is pro-survival since concurrent inhibition of autophagy by 3-MA reinforced the antiproliferative activity of mTOR inhibitors. X-387 also inhibited cell motility, which is associated with decrease in activity of small GTPases such as RhoA, Rac1 and Cdc42. Taken together, X-387 is a promising compound lead targeting mTOR and with a wide spectrum anticancer activity among tumor cell lines. The data also underscores the complexity of the mTOR signaling pathways which are far from being understood.

Analysis of Miniature Single- and Double-notch Bending Specimens for Estimating the Fracture Toughness of Cortical Bone

Journal of Biomedical Materials Research. Part A. Feb, 2012  |  Pubmed ID: 22323431

Studies of the fracture behavior of cortical bone have determined multiple toughening mechanisms that are active during propagation of a crack. Common methods for measuring bone fracture toughness use single-notched specimens often in four-point (SN4PB) or three-point bending (SN3PB). A double-notch four-point bending (DN4PB) specimen is useful to study prefailure damage at the crack tip. Total failure occurs at one notch and only partial failure at the other allowing study of prefailure damage in the unbroken notch. There is no widely known method for calculating the fracture toughness of bone using a DN4PB specimen. A method for calculating the fracture toughness of cortical bone using a DN4PB is developed here and compared with results for a common SN3PB specimen. The new double-notch method permits using a single specimen to measure apparent fracture toughness and to study both pre- and postfailure microdamage in the bone matrix. When and how to use the new and the established test specimens for understanding bone mechanics is discussed. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012.

Inhibition of Chemokine (C-X-C Motif) Ligand 12/chemokine (C-X-C Motif) Receptor 4 Axis (CXCL12/CXCR4)-mediated Cell Migration by Targeting Mammalian Target of Rapamycin (mTOR) Pathway in Human Gastric Carcinoma Cells

The Journal of Biological Chemistry. Feb, 2012  |  Pubmed ID: 22337890

CXCL12/CXCR4 plays an important role in metastasis of gastric carcinoma. Rapamycin has been reported to inhibit migration of gastric cancer cells. However, the role of mTOR pathway in CXCL12/CXCR4-mediated cell migration and the potential of drugs targeting PI3K/mTOR pathway remains unelucidated. We found that CXCL12 activated PI3K/Akt/mTOR pathway in MKN-45 cells. Stimulating CHO-K1 cells expressing pEGFP-C1-Grp1-PH fusion protein with CXCL12 resulted in generation of PIP3, which provided direct evidence of activating PI3K by CXCL12. Down-regulation of p110β by siRNA but not p110α blocked phosphorylation of Akt and S6K1 induced by CXCL12. Consistently, p110β-specific inhibitor blocked CXCL12-activated PI3K/Akt/mTOR pathway. Moreover, CXCR4 immunoprecipitated by anti-p110β antibody increased after CXCL12-stimulation and Gi protein inhibitor pertussis toxin abrogated CXCL12-induced activation of PI3K. Further studies demonstrated that inhibitors targeting PI3K/mTOR pathway significantly blocked the chemotactic responses of MKN-45 cells triggered by CXCL12, which might be primarily attributed to inhibition of mTORC1 and related to prevention of F-actin reorganization as well as down-regulation of active Rho A, Rac1 and Cdc42. Furthermore, rapamycin inhibited the secretion of CXCL12 and the expression of CXCR4, which might form a positive feedback loop to further abolish upstream signaling leading to cell migration. Finally, we found cells expressing high levels of CXCL12 were sensitive to rapamycin in its activity inhibiting migration as well as proliferation. In summary, we found that mTOR pathway played an important role in CXCL12/CXCR4-mediated cell migration and proposed that drugs targeting mTOR pathway may be used for the therapy of metastatic gastric cancer expressing high levels of CXCL12.

Study on the Chaperone Properties of Conserved GTPases

Protein & Cell. Jan, 2012  |  Pubmed ID: 22246579

As a large family of hydrolases, GTPases are widespread in cells and play the very important biological function of hydrolyzing GTP into GDP and inorganic phosphate through binding with it. GTPases are involved in cell cycle regulation, protein synthesis, and protein transportation. Chaperones can facilitate the folding or refolding of nascent peptides and denatured proteins to their native states. However, chaperones do not occur in the native structures in which they can perform their normal biological functions. In the current study, the chaperone activity of the conserved GTPases of Escherichia coli is tested by the chemical denaturation and chaperone-assisted renaturation of citrate synthase and α-glucosidase. The effects of ribosomes and nucleotides on the chaperone activity are also examined. Our data indicate that these conserved GTPases have chaperone properties, and may be ancestral protein folding factors that have appeared before dedicated chaperones.

Single-stage Anterior Debridement and Fusion with Autografting and Internal Fixation for Pyogenic Lumbar Spondylodiscitis

Archives of Orthopaedic and Trauma Surgery. Jan, 2012  |  Pubmed ID: 22252851

INTRODUCTION: Patients with pyogenic lumbar spondylodiscitis can be successfully treated by non-operative methods. However, the typical operation for this condition includes debridement of the infected site, bone grafting and internal fixation to stabilize the spine. Single-stage anterior debridement and fusion with autografting and internal fixation of one spinal segment were performed on nine patients with pyogenic lumbar spondylodiscitis. This operative procedure is rarely documented for pyogenic lumbar spondylodiscitis. AIM: To evaluate the safety and effectiveness of single-stage anterior debridement, autografting and internal fixation of one spinal segment for pyogenic lumbar spondylodiscitis. RESULTS: At the final follow-up, seven out of the nine patients were pain free. Two patients had mild, intermittent back pain (Visual Analogue Scale rating of 1-2), which represented an improvement from their preoperative pain. All nine patients had no clinical, laboratory or radiological evidence of recurrence of infection. Moreover, all the patients showed solid bony fusion. CONCLUSION: Based on the limited population studied, it suggested that this technique may be a safe and effective operative procedure for appropriate pyogenic lumbar spondylodiscitis in patients.

Do Crystal Structures Obviate the Need for Theoretical Models of GPCRs for Structure Based Virtual Screening

Proteins. Jan, 2012  |  Pubmed ID: 22275072

Recent highly expected structural characterizations of agonist-bound and antagonist-bound beta-2 adrenoreceptor (β2AR) by X-ray crystallography have been widely regarded as critical advances to enable more effective structure-based discovery of GPCRs ligands. It appears that this very important development may have undermined many previous efforts to develop 3D theoretical models of GPCRs. To address this question directly we have compared several historical β2AR models versus the inactive state and nanobody-stabilized active state of β2AR crystal structures in terms of their structural similarity and effectiveness of use in virtual screening for β2AR specific agonists and antagonists. Theoretical models, incluing both homology and de novo types, were collected from five different groups who have published extensively in the field of GPCRs modeling; all models were built before X-ray structures became available. In general, β2AR theoretical models differ significantly from the crystal structure in terms of TMH definition and the global packing. Nevertheless, surprisingly, several models afforded hit rates resulting from virtual screening of large chemical library enriched by known β2AR ligands that exceeded those using X-ray structures; the hit rates were particularly higher for agonists. Furthemore, the screening performance of models is associated with local structural quality such as the RMSDs for binding pocket residues and the ability to capture accurately most if not all critical protein/ligand interactions. These results suggest that carefully built models of GPCRs could capture critical chemical and structural features of the binding pocket thus may be even more useful for practical structure-based drug discovery than X-ray structures. Proteins 2012. © 2012 Wiley-Liss, Inc.

Exploring One-state Downhill Protein Folding in Single Molecules

Proceedings of the National Academy of Sciences of the United States of America. Jan, 2012  |  Pubmed ID: 22184219

A one-state downhill protein folding process is barrierless at all conditions, resulting in gradual melting of native structure that permits resolving folding mechanisms step-by-step at atomic resolution. Experimental studies of one-state downhill folding have typically focused on the thermal denaturation of proteins that fold near the speed limit (ca. 10(6) s(-1)) at their unfolding temperature, thus being several orders of magnitude too fast for current single-molecule methods, such as single-molecule FRET. An important open question is whether one-state downhill folding kinetics can be slowed down to make them accessible to single-molecule approaches without turning the protein into a conventional activated folder. Here we address this question on the small helical protein BBL, a paradigm of one-state downhill thermal (un)folding. We decreased 200-fold the BBL folding-unfolding rate by combining chemical denaturation and low temperature, and carried out free-diffusion single-molecule FRET experiments with 50-μs resolution and maximal photoprotection using a recently developed Trolox-cysteamine cocktail. These experiments revealed a single conformational ensemble at all denaturing conditions. The chemical unfolding of BBL was then manifested by the gradual change of this unique ensemble, which shifts from high to low FRET efficiency and becomes broader at increasing denaturant. Furthermore, using detailed quantitative analysis, we could rule out the possibility that the BBL single-molecule data are produced by partly overlapping folded and unfolded peaks. Thus, our results demonstrate the one-state downhill folding regime at the single-molecule level and highlight that this folding scenario is not necessarily associated with ultrafast kinetics.

Sensitive and Selective Voltammetric Measurement of Hg2+ by Rational Covalent Functionalization of Graphene Oxide with Cysteamine

The Analyst. Jan, 2012  |  Pubmed ID: 22059229

We report here a new voltammetric method for the sensitive and selective determination of Hg(2+) based on rational covalent functionalization of graphene oxide with cysteamine to form cysteamine-functionalized graphene through nucleophilic ring-opening reaction between the epoxy of graphene oxide and the amino group of cysteamine in KOH solution.

Discovery and Bioactivity of 4-(2-arylpyrido[3',2':3,4]pyrrolo[1,2-f][1,2,4]triazin-4-yl) Morpholine Derivatives As Novel PI3K Inhibitors

Bioorganic & Medicinal Chemistry Letters. Jan, 2012  |  Pubmed ID: 22130133

PI3K is a promising therapeutic target for cancer. With PI-103 as the lead compound, we designed and synthesized 4-(2-arylpyrido[3',2':3,4]pyrrolo[1,2-f][1,2,4]triazin-4-yl)morpholine derivatives. 9, 10a, 10d, 10e had the IC(50) against PI3Kα comparable with PI-103. All of the compounds showed selectivity over 15 tested protein kinases and anti-proliferative activity at micromolar concentration against several cancer cell lines.

Detection of Enterovirus 71 Using Reverse Transcription Loop-mediated Isothermal Amplification (RT-LAMP)

Journal of Virological Methods. Feb, 2012  |  Pubmed ID: 22155579

Reverse transcription loop-mediated isothermal amplification (RT-LAMP), which is a visual assay for nucleic acids, is performed in a single step using one tube at 65 °C for 1.5 h. In this study, RT-LAMP was established as a method for the detection of enterovirus 71 (EV71). The detection limit of the assay was approximately 10 copies, and no cross-reactivity was noted with Coxsackievirus A16, echovirus, human rotavirus (HRV) or norovirus. This assay, which offers greater sensitivity at a lower cost compared with the conventional reverse transcription polymerase chain reaction (RT-PCR), was validated using 252 clinical specimens that had been confirmed by laboratory diagnosis using RT-PCR. Both methods produced the same results with 52 positive samples. The RT-LAMP-based assay does not require specialised equipment, and therefore, it can be performed conveniently during an outbreak or under field conditions. In brief, the RT-LAMP-based assay provided a simple, rapid and efficient method for the detection of EV71 nucleic acid under field conditions.

Calixarene-induced Aggregation of Perylene Bisimides

Organic & Biomolecular Chemistry. Jan, 2012  |  Pubmed ID: 22160001

The complex-induced aggregation of perylene bisimides by p-sulfonatocalix[n]arenes was studied, where the aggregation stability, aggregation distance, as well as the degree of order of aggregation were all improved.

Cheminformatics Meets Molecular Mechanics: a Combined Application of Knowledge-based Pose Scoring and Physical Force Field-based Hit Scoring Functions Improves the Accuracy of Structure-based Virtual Screening

Journal of Chemical Information and Modeling. Jan, 2012  |  Pubmed ID: 22017385

Poor performance of scoring functions is a well-known bottleneck in structure-based virtual screening (VS), which is most frequently manifested in the scoring functions' inability to discriminate between true ligands vs known nonbinders (therefore designated as binding decoys). This deficiency leads to a large number of false positive hits resulting from VS. We have hypothesized that filtering out or penalizing docking poses recognized as non-native (i.e., pose decoys) should improve the performance of VS in terms of improved identification of true binders. Using several concepts from the field of cheminformatics, we have developed a novel approach to identifying pose decoys from an ensemble of poses generated by computational docking procedures. We demonstrate that the use of target-specific pose (scoring) filter in combination with a physical force field-based scoring function (MedusaScore) leads to significant improvement of hit rates in VS studies for 12 of the 13 benchmark sets from the clustered version of the Database of Useful Decoys (DUD). This new hybrid scoring function outperforms several conventional structure-based scoring functions, including XSCORE::HMSCORE, ChemScore, PLP, and Chemgauss3, in 6 out of 13 data sets at early stage of VS (up 1% decoys of the screening database). We compare our hybrid method with several novel VS methods that were recently reported to have good performances on the same DUD data sets. We find that the retrieved ligands using our method are chemically more diverse in comparison with two ligand-based methods (FieldScreen and FLAP::LBX). We also compare our method with FLAP::RBLB, a high-performance VS method that also utilizes both the receptor and the cognate ligand structures. Interestingly, we find that the top ligands retrieved using our method are highly complementary to those retrieved using FLAP::RBLB, hinting effective directions for best VS applications. We suggest that this integrative VS approach combining cheminformatics and molecular mechanics methodologies may be applied to a broad variety of protein targets to improve the outcome of structure-based drug discovery studies.

Olfactory Deficits Induce Neurofilament Hyperphosphorylation

Neuroscience Letters. Jan, 2012  |  Pubmed ID: 22094386

Olfactory dysfunction, including structural abnormalities of the olfactory epithelium, the olfactory bulb and the central olfactory cortices is recognized as an early feature of Alzheimer disease (AD), the most prevalent neurodegenerative disease in aged population characterized by intracellular neurofibrillary tangles (NFTs). How olfactory deficits are linked with AD-like neuropathological changes is still unknown. Here, by using two anosmia animal models, bilateral olfactory bulbectomy (OBX) rats and Cnga2(-/Y) mice, which lack intact olfactory CNG channels, we found the immunoreactivity of phosphorylated neurofilament (NF) are highly increased in the neurites at both the hippocampus and the cortex. As hyperphosphorylated NF is one of the main components of NFTs, our study strongly suggested the underlying correlation of olfactory deficits with AD-like pathological impairments.

Replication and Cumulative Effects of GWAS-identified Genetic Variations for Prostate Cancer in Asians: a Case-control Study in the ChinaPCa Consortium

Carcinogenesis. Feb, 2012  |  Pubmed ID: 22114074

A recent genome-wide association study has identified five new genetic variants for prostate cancer susceptibility in a Japanese population, but it is unknown whether these newly identified variants are associated with prostate cancer risk in other populations, including Chinese men. We genotyped these five variants in a case-control study of 1524 patients diagnosed with prostate cancer and 2169 control subjects from the Chinese Consortium for Prostate Cancer Genetics (ChinaPCa). We found that three of the five genetic variants were associated with prostate cancer risk (P = 4.33 × 10(-8) for rs12653946 at 5p15, 4.43 × 10(-5) for rs339331 at 6q22 and 8.42 × 10(-4) for rs9600079 at 13q22, respectively). A cumulative effect was observed in a dose-dependent manner with increasing numbers of risk variant alleles (P(trend) = 2.58 × 10(-13)), and men with 5-6 risk alleles had a 2-fold higher risk of prostate cancer than men with 0-2 risk alleles (odds ratio = 2.26, 95% confidence interval = 1.78-2.87). Furthermore, rs339331 T allele was significantly associated with RFX6 and GPRC6A higher messenger RNA expression, compared with the C allele. However, none of the variants was associated with clinical stage, Gleason score or family history. These results provide further evidence that the risk loci identified in Japanese men also contribute to prostate cancer susceptibility in Chinese men.

The Effect of Programmed Cryopreservation on Immunogenicity of Bladder Mucosa in New Zealand Rabbits

Cryobiology. Feb, 2012  |  Pubmed ID: 22127304

A significant reduction in immunogenicity has been observed in some frozen-thawed tissues after cryopreservation. The objective of this study was to evaluate the effects of programmed cryopreservation on immunogenicity of rabbit bladder mucosa and on the extent of immunological rejection caused by the allograft. This study would provide theoretical support for the application of allogenic frozen-thawed bladder mucosa in the treatment of urethral stricture. Forty-two adult male New Zealand rabbits were used in this study. The immunogenicity was detected by mixed lymphocyte reaction using the allograft of bladder mucosa (fresh and frozen-thawed) and spleen lymphocytes. Twelve urethral stricture models were established in New Zealand rabbits for substitution urethroplasty using the allograft of bladder mucosa, which were divided into fresh and frozen-thawed group. Two weeks after operation, lymphocyte proliferation was detected in both blood and spleen of recipient rabbits. At the same time, immunohistochemical staining of urethral allograft was performed and the expression of CD3, CD4 and CD8 were observed. The mRNA of bladder mucosa (fresh and frozen-thawed) was extracted and the expressions of RLA-I, RLA-II and RLA-III gene were detected by real-time PCR. By mixed lymphocyte reaction, we found that allogenic lymphocyte proliferation stimulated by frozen-thawed bladder epithelial cells was significantly weaker than that of the fresh cells. The blood and spleen lymphocytes from fresh bladder mucosa group showed significantly higher proliferation rate than frozen-thawed group. Compared with the fresh group, the expression of CD3+ and CD8+ T cells infiltrated in the operation locus of bladder mucosa urethroplasty was significantly decreased in the frozen-thawed group. However, the expressions of RLA genes did not change significantly after the freeze-thaw procedure. This study demonstrates for the first time that a programmed freeze-thaw procedure of rabbit bladder mucosa could reduce its immunogenicity in allogenic bladder mucosa urethroplasty and thus restrict the extent of immunological rejection, therefore, provides theoretical support for the application of frozen-thawed bladder mucosa in the treatment of urethral stricture.

Molecular Characterization and Expression Pattern of an Odorant Receptor from the Myiasis-causing Blowfly, Lucilia Sericata (Diptera: Calliphoridae)

Parasitology Research. Feb, 2012  |  Pubmed ID: 21789580

The blowfly Lucilia sericata (Diptera: Calliphoridae) is a facultative ectoparasite that causes myiasis in both man and animals, leading to serious human health problems and economic losses in the livestock industry. Like other insects, olfaction of this species plays an important role in host location and is presumably mediated by a seven transmembrane receptor family. Here, we isolate and characterize LserOR1, which is the first candidate member of the odorant receptor gene family from L. sericata. LserOR1 displayed high amino acid conservation with previously identified Or83b orthologs from different insect species. The transcripts of LserOR1 were detected in the major olfactory organs including the antennae and maxillary palps, as well as in traditionally non-olfactory tissues such as the legs and female ovipositors. In developmental studies, a quantitative real-time PCR assay was developed and validated for determining the relative expression levels of LserOR1 during several stages. In contrast to its extremely high expression in the adult stage, LserOR1 expression was at the lowest level during the egg stage, and then increased to a peak through the first two larval stages before declining in the third-instar stage. These results suggest that a broadly expressed LserOR1 receptor is likely to be essential for olfactory sensory processes throughout the lifetime of L. sericata. The present study provides the information that may aid in the development of novel blowfly repellents using olfactory proteins as molecular targets.

Effect of Celecoxib on Proliferation, Collagen Expression, ERK1/2 and SMAD2/3 Phosphorylation in NIH/3T3 Fibroblasts

European Journal of Pharmacology. Mar, 2012  |  Pubmed ID: 22209876

In the present study, the effects of celecoxib on proliferation, collagen expression, ERK1/2 and SMAD2/3 phosphorylation in NIH/3T3 fibroblasts were investigated. NIH/3T3 fibroblasts stimulated with fibroblast growth factor-2 (FGF-2) or transforming growth factor-β1 (TGF-β1) were examined in the presence of celecoxib. Proliferation was assessed by MTT assays; ERK1/2 expression and SMAD2/3 expression were assessed by quantitative RT-PCR and western blotting; ERK1/2 phosphorylation and SMAD2/3 phosphorylation were assessed by western blot analysis. The results indicated that celecoxib could suppress cell proliferation stimulated by FGF-2 (IC(50) FGF+group, 75±1.9μmol/l) and TGF-β1 (IC(50) TGF+group, 48±1.4μmol/l), by inhibiting ERK1/2 phosphorylation but not ERK1/2 expression. Celecoxib also suppressed collagen expression (0.35-fold COL3 and 0.43-fold COL1 at 320μmol/l celecoxib relative to the untreated control after stimulation with TGF-β1 for 3h, P<0.01), by inhibiting SMAD2/3 phosphorylation but not SMAD2/3 expression. The suppression of NIH/3T3 fibroblast proliferation and collagen expression upon stimulation by FGF-2 and TGF-β1 is likely a result of the inhibition of ERK1/2 and SMAD2/3 phosphorylation by celecoxib.

Dobutamine Stress Echocardiography Assessment of Myocardial Contusion Due to Blunt Impact in Dogs

Cell Biochemistry and Biophysics. Jan, 2012  |  Pubmed ID: 21910029

We sought to investigate the role of two-dimensional stress echocardiography in the early assessment of myocardial contusion. For this purpose, 12 dogs, weighing 11.36 ± 1.50 kg, were selected and the myocardial contusion was experimentally induced. Two-dimensional dobutamine stress echocardiography (DSE) was used to detect abnormal myocardial motions segments at time phases of baseline and 0.5, 2, 4, and 8 h post-wounding. Finally, the above results were compared with pathological findings. The data show that after the dogs were induced to have severe myocardial contusion, 122 segments were found with abnormal myocardial wall motions at 0.5 h post-wounding, 133 segments at 2 h post-wounding, and 142 segments, each, at 4 h and 8 h post-wounding. The wall motion score (WMS) and wall motion score index (WMSI) increased (P < 0.001) as compared with the pre-impaction values. Considering the left ventricular axis view as the standard section, in the 60 segments examined by echocardiography, 54 segments were found to have wall motion abnormalities. Comparing with the results of pathological TTC staining, the sensitivity and specificity were found to be 100 and 66.6%, respectively. It was, therefore, concluded that two-dimensional DSE was a valuable technique in the early diagnosis of myocardial contusion due to its better sensitivity and specificity.