Transcriptome Network Analysis Reveals Candidate Genes for Renal Cell Carcinoma

Journal of Cancer Research and Therapeutics.   |  Pubmed ID: 22531510

Renal cell carcinoma (RCC) is a kidney cancer that originates in renal parenchyma and it is the most common type of kidney cancer with approximately 80% lethal cases.

[Simulation of Multimedia Fate of Phenanthrene in the Yangtze Estuary]

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.]. Aug, 2011  |  Pubmed ID: 22619976

A Level III fugacity model is used to simulate the concentration distribution of phenanthrene in air, water, sediment and plants in the Yangtze estuary. Based on simulation results, transfer fluxes among-phase are calculated, and also, the key model parameters are determined by means of sensitivity analysis. The results indicated that the advection of air is the main source of phenanthrene in this area, while the main disappeared way from the study region is the advection of air and water. The degradation of phenanthrene in air is the most and the degradation in sediment is the least. The air is the major store of phenanthrene, where phenanthrene was found accounts for 86.36% of the total amount, however, the phenanthrene concentrations is only 0.5 x 10(-7) mol x m(-3). The phenanthrene concentrations are higher in sediment and plants which are 1.5 x 10(-6) mol x m(-3) and 4.4 x 10(-6) mol x m(-3), respectively. The distribute coefficient and the sedimentation rate of the phenanthrene control the distribution of the phenanthrene in each medium.

[Post-stroke Speech Disorder Treated with Acupuncture and Psychological Intervention Combined with Rehabilitation Training: a Randomized Controlled Trial]

Zhongguo Zhen Jiu = Chinese Acupuncture & Moxibustion. Jun, 2011  |  Pubmed ID: 21739683

To assess the clinical efficacy on post-stroke speech disorder treated with acupuncture and psychological intervention combined with rehabilitation training.

Protective Effects of Glycyrrhizic Acid by Rectal Treatment on a TNBS-induced Rat Colitis Model

The Journal of Pharmacy and Pharmacology. Mar, 2011  |  Pubmed ID: 21749393

The research compared rectal and oral treatments with glycyrrhizic acid for trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats.

The Roles of Sodium Channels in Nociception: Implications for Mechanisms of Neuropathic Pain

Pain Medicine (Malden, Mass.). Jul, 2011  |  Pubmed ID: 21752183

Animal models have provided useful insights into the development and treatment of neuropathic pain. New genetic data from both human studies and transgenic mouse models suggest that specific voltage-gated sodium channel subtypes are associated with specific types of pain and, as such, may be useful analgesic drug targets for a variety of pain types including neuropathic pain. Global voltage-gated sodium channel blockers such as lidocaine have proven efficacy in treating pain but can be limited by adverse effects when administered systemically. Selective sodium channel blockers targeting channels at the periphery (Nav1.7, Nav1.8, and Nav1.9) could potentially reduce the side effect profile. Individual isoforms of voltage-gated sodium channels have been linked to particular types of pain. Nav1.7 is a useful target for ameliorating acute mechanical pain and inflammatory pain, and strong evidence also suggests that Nav1.9 could be targeted for treating inflammatory pain. Selective blockers of Nav1.8 could also have clinical benefit for visceral pain. Although there is no association between a single sodium channel isoform and neuropathic pain, combined blockade of peripherally expressed isoforms Nav1.7, Nav1.8, and Nav1.9 may prove useful.

Gas-phase Acidity Studies of Dual Hydrogen-bonding Organic Silanols and Organocatalysts

The Journal of Organic Chemistry. Sep, 2011  |  Pubmed ID: 21770464

The fundamental properties of a series of organic monosilanols, silanediols, disiloxanediols, and known hydrogen-bonding organocatalysts have been examined in the gas phase using computational and experimental mass spectrometry methods. The organosilicon diol molecules contain dual hydrogen-bonding groups that were designed as potential hosts and hydrogen-bonding catalysts. Newly measured acidities are reported, and implications regarding solvent effects, catalysis, and molecular recognition are discussed.

Distribution of 5-hydroxymethylcytosine in Different Human Tissues

Journal of Nucleic Acids. 2011  |  Pubmed ID: 21772996

5-hydroxymethylcytosine (5-hmC) is a modified form of cytosine recently found in mammalians and is believed, like 5-methylcytosine, to also play an important role in switching genes on and off. By utilizing a newly developed 5-hmC immunoassay, we determined the abundance of 5-hmC in human tissues and compared 5-hmC states in normal colorectal tissue and cancerous colorectal tissue. Significant differences of 5-hmC content in different tissues were observed. The percentage of 5-hmC measured is high in brain, liver, kidney and colorectal tissues (0.40-0.65%), while it is relatively low in lung (0.18%) and very low in heart, breast, and placenta (0.05-0.06%). Abundance of 5-hmC in the cancerous colorectal tissues was significantly reduced (0.02-0.06%) compared to that in normal colorectal tissues (0.46-0.57%). Our results showed for the first time that 5-hmC distribution is tissue dependent in human tissues and its abundance could be changed in the diseased states such as colorectal cancer.

Dickkopf-1 Regulates Bone Formation in Young Growing Rodents and Upon Traumatic Injury

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. Nov, 2011  |  Pubmed ID: 21773994

The physiological role of Dickkopf-1 (Dkk1) during postnatal bone growth in rodents and in adult rodents was examined utilizing an antibody to Dkk1 (Dkk1-Ab) that blocked Dkk1 binding to both low density lipoprotein receptor-related protein 6 (LRP6) and Kremen2, thereby preventing the Wnt inhibitory activity of Dkk1. Treatment of growing mice and rats with Dkk1-Ab resulted in a significant increase in bone mineral density because of increased bone formation. In contrast, treatment of adult ovariectomized rats did not appreciably impact bone, an effect that was associated with decreased Dkk1 expression in the serum and bone of older rats. Finally, we showed that Dkk1 plays a prominent role in adult bone by mediating fracture healing in adult rodents. These data suggest that, whereas Dkk1 significantly regulates bone formation in younger animals, its role in older animals is limited to pathologies that lead to the induction of Dkk1 expression in bone and/or serum, such as traumatic injury.

[Advances in Research on the Prevalence and Prevention of Disabilities in China]

Zhonghua Liu Xing Bing Xue Za Zhi = Zhonghua Liuxingbingxue Zazhi. Jun, 2011  |  Pubmed ID: 21781466

[Case-control Study on Combined Therapy for Preventing Postsurgery Stiffness After Elbow Fracture]

Zhongguo Gu Shang = China Journal of Orthopaedics and Traumatology. Jun, 2011  |  Pubmed ID: 21786549

To research the efficacy,security and necessity of combined therapy for preventing postsurgery stiffness after elbow fracture.

CEP70 Protein Interacts with γ-tubulin to Localize at the Centrosome and is Critical for Mitotic Spindle Assembly

The Journal of Biological Chemistry. Sep, 2011  |  Pubmed ID: 21795687

Deregulation of the mitotic spindle has been implicated in genomic instability, an important aspect of tumorigenesis and malignant transformation. To ensure the fidelity of chromosome transmission, the mitotic spindle is assembled by exquisite mechanisms and orchestrated by centrosomes in animal cells. Centrosomal proteins especially are thought to act coordinately to ensure accurate spindle formation, but the molecular details remain to be investigated. In this study, we report the molecular characterization and functional analysis of a novel centrosomal protein, Cep70. Our data show that Cep70 localizes to the centrosome throughout the cell cycle and binds to the key centrosomal component, γ-tubulin, through the peptide fragments that contain the coiled-coil domains. Our data further reveal that the centrosomal localization pattern of Cep70 is dependent on its interaction with γ-tubulin. Strikingly, Cep70 plays a significant role in the organization of both preexisting and nascent microtubules in interphase cells. In addition, Cep70 is necessary for the organization and orientation of the bipolar spindle during mitosis. These results thus report for the first time the identification of Cep70 as an important centrosomal protein that interacts with γ-tubulin and underscore its critical role in the regulation of mitotic spindle assembly.

Cardiovascular Parameters of Computed Tomographic Pulmonary Angiography to Assess Pulmonary Vascular Resistance in Patients with Chronic Thromboembolic Pulmonary Hypertension

International Journal of Cardiology. Aug, 2011  |  Pubmed ID: 21820745

OBJECTIVES: The purpose is to identify the role of cardiovascular parameters of computed tomographic pulmonary angiography (CTPA) to assess pulmonary vascular resistance (PVR) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). BACKGROUND: The assessment of PVR is of great importance in the management of patients with CTEPH. The role of CPTA in assessment of PVR of CTEPH remains to be explored. METHODS: Clinical and radiological data of 90 patients (55 men, age 17-84years) with CTEPH were retrospectively reviewed in this study. All patients received CTPA before right-heart catheterization. Cardiovascular parameters and Pulmonary Artery Obstruction Indices including Qanadli Index and Mastora Index were evaluated on CTPA. Hemodynamic PVR was calculated with the standard formula according to data from right-heart catheterization. The correlation of cardiovascular parameters of CTPA and PVR was analyzed. RESULTS: In Cardiovascular parameters, neither Qanadli Index(r=0.134, p=0.208) nor Mastora Index (r=0.149, p=0.90) did correlate with PVR. Cobb angle(r=0.613, p=0.000), the ratio of right to left ventricular area(r=0.422, p=0.000)and the ratio of right to left ventricular transverse diameter (r=0.410, p=0.000) respectively correlated with PVR. By receiver operating characteristic curve analysis, a Cobb angle cutoff value of 67.55° had a sensitivity of 72.5% and a specificity of 84.0% to determine PVR ≥1000 (dyn.sec/cm(5)) and its Area Under Curve is (0.800±0.048). By stepwise linear regression analysis, Cobb angle was only one variable (R=0.601) shown to be independently associated with PVR, leading to the following equation: PVR=25.796×Cobb angle-585.935(F=37.929, p=0.000). CONCLUSION: The analysis of CTPA-derived cardiovascular parameters, especially the Cobb angle, is a reliable tool for estimating PVR in patients with CTEPH, but Pulmonary Artery Obstruction Indices do not correlate with PVR.

Saccharomyces As a Vaccine Against Systemic Aspergillosis: 'the Friend of Man' a Friend Again?

Journal of Medical Microbiology. Oct, 2011  |  Pubmed ID: 21825307

The mortality of clinical Aspergillus infections necessitates consideration of the utility of a vaccine. We have found that Saccharomyces species can act as a protective vaccine against a lethal systemic Aspergillus infection, and describe experiments optimizing a subcutaneous regimen with killed yeast. Three injections of 2.5 mg given a week apart, 2 weeks prior to challenge, consistently, significantly, provided survival protection and reduction of infection in organs in survivors. The protection was independent of the strain of Saccharomyces, and possibly even the species, and could be demonstrated in several inbred (including C'-deficient) and outbred mouse strains. The protective moiety(ies) appeared to reside in the cell wall and was resistant to 100 °C, but not to protease or formalin. Alum potentiated the protection. The protection was comparable or superior to that of several Aspergillus-specific preparations described in the literature. Other studies have indicated that heat-killed Saccharomyces can protect against infection with at least three other fungal genera, raising the possibility of development of a panfungal vaccine, and such a vehicle has been studied in clinical trials, without dose-limiting toxicity.

Application of a Disposable Screen-printed Electrode to Depression Diagnosis for Laboratory Rats Based on Blood Serotonin Detection

Analytical Sciences : the International Journal of the Japan Society for Analytical Chemistry. 2011  |  Pubmed ID: 21828923

No exact and digital diagnostic methods for depression have been found. In this study, we prepared a 5-HT biosensor based on screen-printed electrode and applied it to a rat depression model caused by chronic unpredictable mild stress (CUMS). During CUMS, the blood 5-HT and the depression behavior of the depressed rats and the rats treated by antidepressants were recorded. The correlation coefficient of 5-HT was 0.9966 (0 - 4 × 10(-6) M) on the sensor. Results demonstrated that 5-HT level of the depressed rats declined while the depression behavior was aggravated. Fluoxetine (20 mg/kg) and lentinan (10, 20 mg/kg) mildly elevated 5-HT level and slowly regulated the behavior. Mifepristone (20 mg/kg) and Rhizoma Coptidis water extract (10, 20, 100 mg/kg) quickly reversed 5-HT level and the depression behavior. This sensor can accurately test blood 5-HT and might be applied to rapid diagnosis for depression and evaluation of antidepressants effect.

Cycloxygenase-2 is Essential for the Survival and Proliferation of Gastric Cancer Cells

Cell Biochemistry and Biophysics. Dec, 2011  |  Pubmed ID: 21830126

Cycloxygenase-2 catalyzes the synthesis of prostaglandins from arachidonic acid and this enzyme has been implicated in the metastasis of gastric cancer. In order to examine the significance of cycloxygenase-2 (Cox-2) in the survival and proliferation of gastric cancer cells, we have stably overexpressed an antisense Cox-2 in two gastric cancer cell lines, SGC7901 and AGS, in order to reduce the expression of this protein. The sense and antisense Cox-2 expression vectors were created by cloning COX-2 cDNA, in pIRES2-EGFP plasmid. Cox-2 gene expression was monitored by RT-PCR and Western blotting and the results indicated that cells with antisense Cox-2 construct had significantly reduced Cox-2 expression in comparison to the cells that received sense-Cox-2 plasmid. Reduction of Cox-2 expression in SGC7901 and AGS gastric cancer cells led to markedly decreased proliferation. The metastatic capability of the two cell lines, as assessed by in vitro colony formation assay, is also significantly compromised by lowered Cox-2 expression. Thus, this study demonstrates that Cox-2 activity is necessary for the proliferation and metastasis of gastric cancer cells.

Human Polymerase-Associated Factor Complex (PAFc) Connects the Super Elongation Complex (SEC) to RNA Polymerase II on Chromatin

Proceedings of the National Academy of Sciences of the United States of America. Sep, 2011  |  Pubmed ID: 21873227

The Super Elongation Complex (SEC), containing transcription elongation activators/coactivators P-TEFb, ELL2, AFF4/1, ENL, and AF9, is recruited by HIV-1 Tat and mixed lineage leukemia (MLL) proteins to activate the expression of HIV-1 and MLL-target genes, respectively. In the absence of Tat and MLL, however, it is unclear how SEC is targeted to RNA polymerase (Pol) II to stimulate elongation in general. Furthermore, although ENL and AF9 can bind the H3K79 methyltransferase Dot1L, it is unclear whether these bindings are required for SEC-mediated transcription. Here, we show that the homologous ENL and AF9 exist in separate SECs with similar but nonidentical functions. ENL/AF9 contacts the scaffolding protein AFF4 that uses separate domains to recruit different subunits into SEC. ENL/AF9 also exists outside SEC when bound to Dot1L, which is found to inhibit SEC function. The YEATS domain of ENL/AF9 targets SEC to Pol II on chromatin through contacting the human Polymerase-Associated Factor complex (PAFc) complex. This finding explains the YEATS domain's dispensability for leukemogenesis when ENL/AF9 is translocated to MLL, whose interactions with PAFc and DNA likely substitute for the PAFc/chromatin-targeting function of the YEATS domain.

Secretion of Bacterial Chondroitinase ABC from Bone Marrow Stromal Cells by Glycosylation Site Mutation: a Promising Approach for Axon Regeneration

Medical Hypotheses. Nov, 2011  |  Pubmed ID: 21885201

Growth-inhibitory chondroitin sulfate proteoglycans (CSPGs) contribute a lot to failure of axon regeneration. Chondroitinase ABC (ChABC) digests glycosaminoglycan chains attached in CSPGs and can thereby promote axonal regeneration beyond a lesion site. However, CSPGs expression are up-regulated for almost 7 weeks after spinal cord injury (SCI) in vivo, so single dose of exogenous ChABC is insufficient for long distance of axon sprout and functional recovery. It is considered an ideal strategy to transfect neurons and/or glia at the injury site with a vector containing the gene encoding chondroitinase, so they can secrete ChABC themselves. Mammalian cells in the current studies, however, can not secret ChABC efficiently. It is well established that glycosylation is a common obstacle for eukaryotic cells to secret bacterial protein. ChABC is a protein heavily glycosylated structurally, and it was reported that inhibiting the glycosylation of xylosyltransferase-1 with a DNA enzyme could reduce GAG chains in the lesion of spinal cord. So presence of glycosylation sites in the bacterial sequence is supposed the barrier that preventing ChABC secretion from mammalian cells. We intend to mutate the key N-glycosylation sites of the bacterial ChABC sequence and transduce it into BMSCs by lentivirus vector. The modified BMSCs are expected to promote axon regeneration through multiple mechanisms, providing sustained ChABC and neurotrophic factors, as well as filling in the cavities formed post-trauma. The transduced BMSCs with gene mutated in key glycosylation sites in the present hypothesis provide a promising strategy to promote axon regeneration.

Increased Callus Mass and Enhanced Strength During Fracture Healing in Mice Lacking the Sclerostin Gene

Bone. Dec, 2011  |  Pubmed ID: 21890008

Humans with inherited sclerostin deficiency have high bone mass. Targeted deletion of the sclerostin gene in mice (SOST-KO) causes increases in bone formation, bone mass and bone strength. Inhibition of sclerostin by a monoclonal antibody increases bone formation and enhances fracture healing in rodent and primate models. In this study, we describe the temporal progression of femoral fracture healing in SOST-KO mice compared with wild type (WT) control mice to further characterize the role of sclerostin in fracture healing. Sixty-seven male 9-10 week-old SOST-KO (N=37) and WT (N=30) mice underwent a closed femoral fracture. Weekly radiography was used to monitor the progress of healing. Histologic sections were used to characterize callus composition, evaluate callus bridging, and quantify lamellar bone formation on days 14 and 28. Densitometry and biomechanical testing were utilized to characterize bone mass and strength at the fractured and contralateral femurs on day 45. A significant improvement in time to radiographic healing (no discernible fracture line) was observed in SOST-KO mice, which corresponded to an increase in histologic bony bridging at 14 days (38% versus 0% in WT). Both genotypes appeared to be nearly fully bridged at 28 days post-fracture. The increased bridging at 14 days was associated with 97% greater bone area and 40% lower cartilage area in the callus of SOST-KO mice as compared to WT mice. Bone formation-related endpoints were higher in SOST-KO mice at both 14 and 28 days. At 45 days post-fracture, peak load and bone mass were significantly greater in the fractured femurs of SOST-KO mice as compared to WT mice. In conclusion, fractures in mice lacking sclerostin showed accelerated bridging, greater callus maturation, and increased bone formation and strength in the callus.

Vitellogenin Mediates Phagocytosis Through Interaction with FcγR

Molecular Immunology. Oct, 2011  |  Pubmed ID: 21908048

Vitellogenin (Vg), once reported to be a female-specific protein, has been identified in both male and juvenile fishes. However, the biological significance of the production of Vg in the male and juvenile fishes is elusive. Our previous studies showed that Vg is an opsonin capable of enhancing phagocytosis, but the mechanism by which Vg mediates phagocytosis is unknown. In this study we demonstrated that Vg-opsonized phagocytosis was characterized by pseudopod extension and depended upon tyrosine kinase. In contrast, inhibition of Rho family proteins and microtubule depolymerization had little effects on Vg-opsonized phagocytosis. Besides, Vg-opsonized phagocytosis was substantially blocked by monoclonal antibodies against FcγRs but not by CR3 antibody. Moreover, theoretical prediction analysis further revealed that Vg had the potency to interact with Fcγ receptors. Finally, the expression of proinflammatory cytokine genes tnf-α and il-1β was significantly up-regulated by Vg, and this up-regulation was inhibited by selective inhibitors of FcR signaling pathways, wortmannin and piceatannol. Taken together, these results suggest that Vg plays an IgG-like role in that it activates FcγR-mediated phagocytosis, thus establishing an antibody-like function for Vg for the first time.

LyP-1-conjugated Doxorubicin-loaded Liposomes Suppress Lymphatic Metastasis by Inhibiting Lymph Node Metastases and Destroying Tumor Lymphatics

Nanotechnology. Oct, 2011  |  Pubmed ID: 21914940

Lymphatic metastasis can be greatly promoted by metastases growth and lymphangiogenesis in lymph nodes (LNs). LyP-1, a cyclic peptide, is able to specifically bind with tumor cells and tumor lymphatics in metastatic LNs. This work aimed to use LyP-1-conjugated liposomes (L-LS) loaded with doxorubicin (DOX) (L-LS/DOX) to suppress lymphatic metastasis by inhibiting both metastases and tumor lymphatics in LNs. L-LS were prepared and exhibited sizes around 90 nm and spherical morphology as characterized by transmission electron microscopy. The in vitro cellular studies showed that LyP-1 modification obviously increased liposome uptake by MDA-MB-435 tumor cells and enhanced the cytotoxicity of liposomal DOX. A popliteal and iliac LN metastases model was successfully established by subcutaneous inoculation of tumor cells to nude mice. The immunofluorescence staining analysis indicated that LyP-1 modification enabled specific binding of liposome with tumor lymphatics and enhanced the destroying effect of liposomal DOX on tumor lymphatics. The in vivo fluorescence imaging and pharmacodynamic studies showed that LyP-1 modification increased liposome uptake by metastatic LNs and that L-LS/DOX significantly decreased metastatic LN growth and LN metastasis rate. These results suggested that L-LS/DOX were an effective delivery system for suppressing lymphatic metastasis by simultaneously inhibiting LN metastases and tumor lymphatics.

[Study on Nanoparticles in Yangtze Estuary]

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.]. Jul, 2011  |  Pubmed ID: 21922810

Filtration and cross-flow ultrafiltration (CFUF) was applied for the effective separation of NPs in the Yangtze Estuary. The physiochemical properties of NP were characterized, and their relationships with environmental factors were further studied in the present study. The results show that NP size in Yangtze Estuary ranged from 69.5 to 263.5 nm with the average value of 157.3 nm and Zeta-potential values ranged from -40.1 mV to 196.0 mV. NOC concentrations ranged from 0.3 mg/L to 1.5 mg/L and the average value was 0.7 mg/L. NOC account for 5.1% to 30.5% of DOC, with an average of 16.7%. The binding capacity of metals with NP in the Yangtze River Estuary was in the order of Zn > Cu > total Cr > Co > Ni > Mn > Fe > Li > Al > B > K > Ba > Sr > Mg > Ca > Na, which reveals that terrigenous input may be the main source of NOC in the Yangtze River. The binding capacity of NP with trace metal is generally higher than the conventional metallic element. There was no significant correlation between NP size and salinity, DOC, NOC, SPM and Zeta-potential, respectively. Compared to NOC and UOC, better correlation was investigated between DOC, salinity and NP bound trace metals.

[Temporal Variation Characteristics of PGEs Concentrations in Road Dust]

Huan Jing Ke Xue= Huanjing Kexue / [bian Ji, Zhongguo Ke Xue Yuan Huan Jing Ke Xue Wei Yuan Hui "Huan Jing Ke Xue" Bian Ji Wei Yuan Hui.]. Sep, 2011  |  Pubmed ID: 22165238

In order to study temporal variation characteristics and influencing mechanism of platinum group elements (PGEs) in road dust, 24 seasonal samples and 18 inter annual samples of road dust were collected from roads in Shanghai, and were analysed by ICP-MS following aqua regia digestion. The results are as following: average concentrations of PGEs in spring, summer, autumn, winter were 10.40 (6.06-17.28) ng/g, 11.60 (5.52-20.11) ng/g, 32.91(18.53-61.05) ng/g, 32.33 (16.29-47.89) ng/g with Rh, 52.99 (27.48-100.2) ng/g, 53.77 (20.42-72.31) ng/g, 125.50 (75.41-247.8) ng/g, 132.59 (78.45-199.9) ng/g with Pd, 13.58 (7.96-30.97) ng/g, 13.24 (6.40-17.96) ng/g, 48.20 (25.07-122.9) ng/g, 53.63 (22.11-107.7) ng/g with Pt. PGEs concentrations had obvious seasonal change that were lower in spring and summer, higher in autumn and winter, and rainfall were main effect factors. The comparison of levels of PGEs between 2003 and 2007 showed that PGEs concentrations in road dust had increased over the period of 4 years with 11% - 19% of average annual growth rate because of the rapid increase in the number of vehicles in Shanghai. Meanwhile, the average PGEs ratios of road dust samples from Shanghai were inconsistent with Ely's result. These differences were contributed by the change of VECs type.

[The Effect of Serum Concentration on the Growth, Proliferation and Collagen Secretion in Mouse L929 Fibroblasts]

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi = Chinese Journal of Cellular and Molecular Immunology. Jul, 2011  |  Pubmed ID: 21722523

To observe the effect of serum concentration on the growth, proliferation and secretion of collagen I, collagen III and hydroxyproline in mouse fibroblasts L929, to optimize serum concentration for cell growth, proliferation and collagen secretion.

MiRNA-1 Targets Fibronectin1 and Suppresses the Migration and Invasion of the HEp2 Laryngeal Squamous Carcinoma Cell Line

FEBS Letters. Oct, 2011  |  Pubmed ID: 21924268

MicroRNAs (miRNAs) are an evolutionarily conserved class of endogenous, non-coding RNAs that modulate gene expression at the post-transcriptional level and are involved in tumorigenesis. In this study, we demonstrate that miR-1 suppresses the potential for growth, migration and invasion in the HEp2 cell line. Furthermore, we validate that FN1 is a direct target gene for miR-1 via fluorescent reporter assay and is negatively regulated by miR-1. Moreover, the knockdown of FN1 has the same phenotypic effects as the overexpression of miR-1. Taken together, our results provide evidence that miR-1 may play a role as a tumor suppressor gene in laryngeal carcinoma.

In Vivo RNAi Screen Reveals Neddylation Genes As Novel Regulators of Hedgehog Signaling

PloS One. 2011  |  Pubmed ID: 21931660

Hedgehog (Hh) signaling is highly conserved in all metazoan animals and plays critical roles in many developmental processes. Dysregulation of the Hh signaling cascade has been implicated in many diseases, including cancer. Although key components of the Hh pathway have been identified, significant gaps remain in our understanding of the regulation of individual Hh signaling molecules. Here, we report the identification of novel regulators of the Hh pathway, obtained from an in vivo RNA interference (RNAi) screen in Drosophila. By selectively targeting critical genes functioning in post-translational modification systems utilizing ubiquitin (Ub) and Ub-like proteins, we identify two novel genes (dUba3 and dUbc12) that negatively regulate Hh signaling activity. We provide in vivo and in vitro evidence illustrating that dUba3 and dUbc12 are essential components of the neddylation pathway; they function in an enzyme cascade to conjugate the ubiquitin-like NEDD8 modifier to Cullin proteins. Neddylation activates the Cullin-containing ubiquitin ligase complex, which in turn promotes the degradation of Cubitus interruptus (Ci), the downstream transcription factor of the Hh pathway. Our study reveals a conserved molecular mechanism of the neddylation pathway in Drosophila and sheds light on the complex post-translational regulations in Hh signaling.

Genetic Association Between ADAM10 Gene Polymorphism and Alzheimer's Disease in a Northern Han Chinese Population

Brain Research. Nov, 2011  |  Pubmed ID: 21959176

The ADAM10 gene encodes a member of a disintegrin and metalloprotease family, which, after overexpression in Alzheimer's disease (AD), prevents amyloid pathology and improves long-term potentiation and memory. A common polymorphism (rs2305421) within ADAM10 has been recently associated with the risk of developing AD in Europeans. In order to assess the involvement of the ADAM10 polymorphism in the risk of developing late-onset AD (LOAD), we analyzed the genotype and allele distributions of the ADAM10 (rs2305421) polymorphism in 788 Northern Han Chinese subjects. The results revealed no significant differences in the distributions of allele or genotype between LOAD and control groups. However, when these data were stratified by the Apolipoprotein E (ApoE) ε4 status, in the subjects with ApoE ε4, there were significant differences in the allele (P=0.037) and genotype (P=0.035). Moreover, logistic regression analysis revealed that the rs2305421 polymorphism presented strong associations with LOAD in the recessive model (OR=0.611, 95% CI=0.408-0.931, P=0.023). This study suggests that the rs2305421 polymorphism in ADAM10 gene could modify the risk for LOAD in a Northern Han Chinese population.

Kinetic, Mechanistic, and Structural Modeling Studies of Truncated Wild-type Leucine-rich Repeat Kinase 2 and the G2019S Mutant

Biochemistry. Nov, 2011  |  Pubmed ID: 21961647

Leucine-rich repeat kinase 2 (LRRK2), a large and complex protein that possesses two enzymatic properties, kinase and GTPase, is one of the major genetic factors in Parkinson's disease (PD). Here, we characterize the kinetic and catalytic mechanisms of truncated wild-type (t-wt) LRRK2 and its most common mutant, G2019S (t-G2019S), with a structural interpretation of the kinase domain. First, the substitution of threonine with serine in the LRRKtide peptide results in a much less efficient substrate as demonstrated by a 26-fold decrease in k(cat) and a 6-fold decrease in binding affinity. The significant decrease in k(cat) is attributed to a slow chemical transfer step as evidenced by the inverse solvent kinetic isotope effect in the proton inventory and pL (pH or pD)-dependent studies. The shape of the proton inventory and pL profile clearly signals the involvement of a general base (pK(a) = 7.5) in the catalysis with a low fractionation factor in the ground state. We report for the first time that the increased kinase activity of the G2019S mutant is substrate-dependent. Homology modeling of the kinase domain (open and closed forms) and structural analysis of the docked peptide substrates suggest that electrostatic interactions play an important role in substrate recognition, which is affected by G2019S and may directly influence the kinetic properties of the enzyme. Finally, the GTPase activity of the t-G2019S mutant was characterized, and the mutation modestly decreases GTPase activity without significantly affecting GTP binding affinity.

Adaptive Cell Segmentation and Tracking for Volumetric Confocal Microscopy Images of a Developing Plant Meristem

Molecular Plant. Sep, 2011  |  Pubmed ID: 21965456

Automated segmentation and tracking of cells in actively developing tissues can provide high-throughput and quantitative spatiotemporal measurements of a range of cell behaviors; cell expansion and cell-division kinetics leading to a better understanding of the underlying dynamics of morphogenesis. Here, we have studied the problem of constructing cell lineages in time-lapse volumetric image stacks obtained using Confocal Laser Scanning Microscopy (CLSM). The novel contribution of the work lies in its ability to segment and track cells in densely packed tissue, the shoot apical meristem (SAM), through the use of a close-loop, adaptive segmentation, and tracking approach. The tracking output acts as an indicator of the quality of segmentation and, in turn, the segmentation can be improved to obtain better tracking results. We construct an optimization function that minimizes the segmentation error, which is, in turn, estimated from the tracking results. This adaptive approach significantly improves both tracking and segmentation when compared to an open loop framework in which segmentation and tracking modules operate separately.

Effects of Chinese Herbal Medicine Serum on the Apoptosis of Sinoatrial Node Cells Induced by Simulated Ischemia-reperfusion

Journal of Traditional Chinese Medicine = Chung I Tsa Chih Ying Wen Pan / Sponsored by All-China Association of Traditional Chinese Medicine, Academy of Traditional Chinese Medicine. Sep, 2011  |  Pubmed ID: 21977866

To study the effect of Chinese herbal medicine Kangxin Fumai Granule ((see text) Granule for heart diseases) serum on the primary cultured sinoatrial node (SAN) cell apoptosis induced by simulated ischemia-reperfusion (IR).

Dimethylenastron Suppresses Human Pancreatic Cancer Cell Migration and Invasion in Vitro Via Allosteric Inhibition of Mitotic Kinesin Eg5

Acta Pharmacologica Sinica. Dec, 2011  |  Pubmed ID: 21986572

The mitotic kinesin Eg5 plays a critical role in bipolar spindle assembly, and its inhibitors have shown impressive anticancer activity in preclinical studies. This study was undertaken to investigate the effect of dimethylenastron, a specific inhibitor of Eg5, on the migration and invasion of pancreatic cancer cells.

[Analysis of Influencing Factors for Curative Effect of Maxillofacial Fractures]

Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi = Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery. Sep, 2011  |  Pubmed ID: 22256740

To explore the influencing factors for curative effect of maxillofacial fractures.

Polyamidoamine-grafted Multiwalled Carbon Nanotubes for Gene Delivery: Synthesis, Transfection and Intracellular Trafficking

Bioconjugate Chemistry. Nov, 2011  |  Pubmed ID: 21995530

Functionalized multiwalled carbon nanotubes (f-MWNTs) are of great interest and designed as a novel gene delivery system. In this paper, we presented synthesis of polyamidoamine-functionalized multiwalled carbon nanotubes (PAA-g-MWNTs) and their application as a novel gene delivery system. The PAA-g-MWNTs, obtained from amide formation between PAA and chemically oxidized MWNTs, were stable in aqueous solution and much less toxic to cells than PAA and PEI 25KDa. More importantly, PAA-g-MWNTs showed comparable or even higher transfection efficiency than PAA and PEI at optimal w/w ratio. Intracellular trafficking of Cy3-labeled pGL-3 indicated that a large number of Cy3-labeled pGL-3 were attached to nucleus membrane, the majority of which was localized in nucleus after incubation with cells for 24 h. We have demonstrated that PAA modification of MWNTs facilitate higher DNA uptake and gene expression in vitro. All these facts suggest potential application of PAA-g-MWNTs as a novel gene vector with high transfection efficiency and low cytotoxicity.

[Oral Health Services Utilization and Influencing Factors in Downtown Community Residents Older Than 15 Years in Beijing]

Zhonghua Kou Qiang Yi Xue Za Zhi = Zhonghua Kouqiang Yixue Zazhi = Chinese Journal of Stomatology. Mar, 2011  |  Pubmed ID: 21575443

To investigate the utilization of oral health services and to analyze the factors associated with oral health services for the community residents.

[Simultaneous Determination of 15 Industrial Synthetic Dyes in Condiment by Solid Phase Extraction-high Performance Liquid Chromatography]

Se Pu = Chinese Journal of Chromatography / Zhongguo Hua Xue Hui. Feb, 2011  |  Pubmed ID: 21598518

A new method was established for the determination of 15 industrial synthetic dyes in condiment by solid phase extraction-high performance liquid chromatography (SPE-HPLC). The samples were extracted by methanol-water (1:1, v/v) and purified by a solid phase extraction column. Then, the chromatographic separation was achieved on a Luna C18 column by linear gradient elution. The mobile phase was 10 mmol/L ammonium acetate-acetonitrile (containing 1% acetic acid). The results showed that the 15 industrial synthetic dyes can be separated efficiently. The recoveries of the 15 industrial synthetic dyes spiked in condiment were between 84.6% and 114.2% with the relative standard deviations of 0.9% - 10.3%. The limits of detection of this method was 0.05 - 0.18 mg/kg for the 15 industrial synthetic dyes. The method is simple, sensitive, accurate, repeatable and can be used for simultaneous determination of the 15 illegally added industrial synthetic dyes.

Effects of Early Administration of a Novel Anticholinergic Drug on Acute Respiratory Distress Syndrome Induced by Sepsis

Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. Nov, 2011  |  Pubmed ID: 22037734

Acute respiratory distress syndrome (ARDS) is the inflammatory disorder of the lung most commonly caused by sepsis. It was hypothesized that treating the lung with penehyclidine hydrochloride (PHC), a new type of hyoscyamus drug, early in the development of sepsis could diminish the lung dysfunction.

Interleukin-10 is Expressed in HepG2.2.15 Cells and Regulated by STAT1 Pathway

Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban. Oct, 2011  |  Pubmed ID: 22038351

This study investigated the expression profiles of IL-10 gene in three human hepatoma cell lines including Huh7, HepG2, and HepG2 transfected with a plasmid containing hepatitis B virus (HBV) named HepG2.2.15. RT-PCR analysis demonstrated that IL-10 message RNA was absent in HepG2 and Huh7 cells, whereas it was present in HepG2.2.15 cells, which was consistent with ELISA result. Furthermore, except for lamivudine other antiviral treatments did not significantly decrease the HBV DNA level in HepG2.2.15 cells, while they had different effects on the expression of IL-10 protein, although stimulation by LPS had no significant effect. In addition, except for poly(I:C), the other treatments decreased the expression of IL-10 protein to different degrees, but had no significant effects on the expression of NF-κB and MyD88. Meanwhile, all treatments we used had effect on the expression of STAT1. In conclusion, IL-10 was expressed in HepG2.2.15 cells and STAT1 pathway might be involved in the regulation of IL-10 expression in HepG2.2.15 cells, but it was not the sole pathway, the exact mechanism warrants further study.

[Serum Carotenoid Concentrations in Some Chinese Adults from Urban, Suburban and Rural Communities]

Wei Sheng Yan Jiu = Journal of Hygiene Research. Sep, 2011  |  Pubmed ID: 22043709

The study was carried out to analyze serum carotenoids concentration of some Chinese adults by HPLC.

Bupropion Hydro-bromide Propanol Hemisolvate

Acta Crystallographica. Section E, Structure Reports Online. Oct, 2011  |  Pubmed ID: 22064727

The title compound {systematic name: N-[1-(3-chloro-phen-yl)-1-oxopropan-2-yl]-tert-butanaminium bromide propanol hemisolvate}, C(13)H(19)ClNO(+)·Br(-)·0.5C(3)H(8)O, crystallizes with two independent bupropion hydro-bromide ion pairs and a solvent 1-propanol mol-ecule in the asymmetric unit. In both mol-ecules, the expected proton transfer from HBr to the amino group of the bupropion mol-ecule is observed, and intra- and inter-molecular N-H⋯Br hydrogen-bond inter-actions are formed. These inter-actions link the mol-ecules into hydrogen-bond dimers. The side chains of the two cations have slightly different orientations. The 1-propanol solvent mol-ecule is linked to a bromide ion by an O-H⋯Br hydrogen bond.

The Biology and Dynamics of Mammalian Cortical Granules

Reproductive Biology and Endocrinology : RB&E. 2011  |  Pubmed ID: 22088197

Cortical granules are membrane bound organelles located in the cortex of unfertilized oocytes. Following fertilization, cortical granules undergo exocytosis to release their contents into the perivitelline space. This secretory process, which is calcium dependent and SNARE protein-mediated pathway, is known as the cortical reaction. After exocytosis, the released cortical granule proteins are responsible for blocking polyspermy by modifying the oocytes' extracellular matrices, such as the zona pellucida in mammals. Mammalian cortical granules range in size from 0.2 um to 0.6 um in diameter and different from most other regulatory secretory organelles in that they are not renewed once released. These granules are only synthesized in female germ cells and transform an egg upon sperm entry; therefore, this unique cellular structure has inherent interest for our understanding of the biology of fertilization. Cortical granules are long thought to be static and awaiting in the cortex of unfertilized oocytes to be stimulated undergoing exocytosis upon gamete fusion. Not till recently, the dynamic nature of cortical granules is appreciated and understood. The latest studies of mammalian cortical granules document that this organelle is not only biochemically heterogeneous, but also displays complex distribution during oocyte development. Interestingly, some cortical granules undergo exocytosis prior to fertilization; and a number of granule components function beyond the time of fertilization in regulating embryonic cleavage and preimplantation development, demonstrating their functional significance in fertilization as well as early embryonic development. The following review will present studies that investigate the biology of cortical granules and will also discuss new findings that uncover the dynamic aspect of this organelle in mammals.

Distinct White Matter Abnormalities in Different Idiopathic Generalized Epilepsy Syndromes

Epilepsia. Dec, 2011  |  Pubmed ID: 22092238

By definition idiopathic generalized epilepsy (IGE) is not associated with structural abnormalities on conventional magnetic resonance imaging (MRI). However, recent quantitative studies suggest white and gray matter alterations in IGE. The purpose of this study was to investigate whether there are white and/or gray matter structural differences between controls and two subsets of IGE, namely juvenile myoclonic epilepsy (JME) and IGE with generalized tonic-clonic seizures only (IGE-GTC).

Mdp3 is a Novel Microtubule-binding Protein That Regulates Microtubule Assembly and Stability

Cell Cycle (Georgetown, Tex.). Nov, 2011  |  Pubmed ID: 22142902

Microtubule-binding proteins are a group of molecules that associate with microtubules, regulate the structural properties of microtubules, and thereby participate in diverse microtubule-mediated cellular activities. A recent mass spectrometry-based proteomic study has identified microtubule-associated protein 7 (MAP7) domain-containing 3 (Mdp3) as a potential microtubule-binding protein. However, its subcellular localization and functional importance are not characterized. In this study, by GST-pulldown assays, we found that Mdp3 interacted with tubulin both in cells and in vitro. Immunofluorescence microscopy and microtubule cosedimentation assays revealed that Mdp3 also associated with microtubules. Serial deletion experiments showed that the two coiled coil motifs of Mdp3 were critical for its interaction with tubulin and microtubules. Cold recovery and nocodazole washout assays further demonstrated an important role for Mdp3 in regulating cellular microtubule assembly. Our data also showed that Mdp3 significantly enhanced the stability of cellular microtubules. By tubulin turbidity assay, we found that Mdp3 could promote microtubule assembly and stability in the purified system. In addition, we found that Mdp3 expression varied during the cell cycle and in primary tissues. These findings thus establish Mdp3 as a novel microtubule-binding protein that regulates microtubule assembly and stability.

AV59M KCNJ11 Gene Mutation Leading to Intermediate DEND Syndrome in a Chinese Child

Journal of Pediatric Endocrinology & Metabolism : JPEM. 2011  |  Pubmed ID: 22145471

Heterozygous activating mutations in the KCNJ11 gene can cause permanent and transient neonatal diabetes. In the present study, we sequenced the KCNJ11 gene in a Chinese boy diagnosed with permanent neonatal diabetes mellitus (PNDM) and also in his parents. A heterozygous 175G > A (V59M) mutation was identified in the patient, while no KCNJ11 gene mutations were found in his parents, indicating that this mutation is de novo. The patient with the V59M mutation successfully switched from insulin injections to oral glibenclamide; 2 years of follow-up revealed that the patient had intermediate developmental delay, epilepsy and neonatal diabetes (DEND) syndrome. This is the first patient who is reported to have iDEND syndrome due to KCNJ11 V59M mutation in China.

[Efficacy and Safety of Palonosetron Versus Tropisetron in the Prevention of Highly Emetogenic Chemotherapy-induced Acute and Delayed Vomiting in Chinese Cancer Patients]

Zhonghua Yi Xue Za Zhi. Sep, 2011  |  Pubmed ID: 22321885

To explore the efficacy and safety of palonosetron in the prevention of acute and delayed chemotherapy-induced nausea and vomiting after moderate to severe emetogenic chemotherapy.

[Relationship Between Spinal Ventricular Septal Angle by Computer Tomographic Pulmonary Angiography and Right Cardiac Functions, N-terminal Brain Natriuretic Peptide in Chronic Thromboembolic Pulmonary Hypertension]

Zhonghua Yi Xue Za Zhi. Nov, 2011  |  Pubmed ID: 22333610

To explore the relationship of spinal ventricular septal angle (SVSA) measured by computer tomographic pulmonary angiography (CTPA) and right cardiac functions, N-terminal brain natriuretic peptide (NT-proBNP) in the patients with chronic thromboembolic pulmonary hypertension (CTEPH).

[Predicting Value of Various Clinical Probability Scores for Diagnosis of Lower Limb Deep Venous Thrombosis in Chinese Patients]

Zhonghua Xin Xue Guan Bing Za Zhi. Nov, 2011  |  Pubmed ID: 22336453

To evaluate the predicting value of Wells, Kahn, St. André and Constans scores for the diagnosis of deep venous thrombosis in Chinese patients.

[Predictive Study of HBsAg in Different Stages of Neonatal Venous Blood on Failure of Blocking HBV Mother to Infant Transmission]

Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi = Zhonghua Shiyan He Linchuang Bingduxue Zazhi = Chinese Journal of Experimental and Clinical Virology. Oct, 2011  |  Pubmed ID: 22338218

In this study, we discuss the predictive value of different content of HBsAg in different stages of neotal venous blood on failure of blocking mother to infant transmission of HBV.

[Progress in Epidemiology Study on Stroke]

Zhonghua Liu Xing Bing Xue Za Zhi = Zhonghua Liuxingbingxue Zazhi. Sep, 2011  |  Pubmed ID: 22340868

[The Prevention of Denhong Injection on Contrast-induced Renal Impairment After Percutaneous Coronary Intervention]

Zhongguo Zhong Xi Yi Jie He Za Zhi Zhongguo Zhongxiyi Jiehe Zazhi = Chinese Journal of Integrated Traditional and Western Medicine / Zhongguo Zhong Xi Yi Jie He Xue Hui, Zhongguo Zhong Yi Yan Jiu Yuan Zhu Ban. Dec, 2011  |  Pubmed ID: 22384545

To investigate the prevention of Danhong Injection (DHI) on contrast-induced renal impairment after percutaneous coronary intervention (PCI).

MicroRNA-214 Suppresses Growth and Invasiveness of Cervical Cancer Cells by Targeting UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 7

The Journal of Biological Chemistry. Apr, 2012  |  Pubmed ID: 22399294

MicroRNAs are a class of small noncoding RNAs that function as key regulators of gene expression at the post-transcriptional level. In this study, we demonstrate that miR-214 is frequently down-regulated in cervical cancer, and its expression reduces the proliferation, migration, and invasiveness of cervical cancer cells, whereas inhibiting its expression results in enhanced proliferation, migration, and invasion. miR-214 binds to the 3'-UTR of UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 7 (GALNT7), thereby repressing GALNT7 expression. Furthermore, we are the first to show, using quantitative real-time PCR, that GALNT7 is frequently up-regulated in cervical cancer. The knockdown of GALNT7 markedly inhibits cervical cancer cell proliferation, migration, and invasion, whereas ectopic expression of GALNT7 significantly enhances these properties, indicating that GALNT7 might function as an oncogene in cervical cancer. The restoration of GALNT7 expression can counteract the effect of miR-214 on cell proliferation, migration, and invasiveness of cervical cancer cells. Together, these results indicate that miR-214 is a new regulator of GALNT7, and both miR-214 and GALNT7 play important roles in the pathogenesis of cervical cancer.

Protein-protein Interaction Network-based Detection of Functionally Similar Proteins Within Species

Proteins. Jul, 2012  |  Pubmed ID: 22411607

Although functionally similar proteins across species have been widely studied, functionally similar proteins within species showing low sequence similarity have not been examined in detail. Identification of these proteins is of significant importance for understanding biological functions, evolution of protein families, progression of co-evolution, and convergent evolution and others which cannot be obtained by detection of functionally similar proteins across species. Here, we explored a method of detecting functionally similar proteins within species based on graph theory. After denoting protein-protein interaction networks using graphs, we split the graphs into subgraphs using the 1-hop method. Proteins with functional similarities in a species were detected using a method of modified shortest path to compare these subgraphs and to find the eligible optimal results. Using seven protein-protein interaction networks and this method, some functionally similar proteins with low sequence similarity that cannot detected by sequence alignment were identified. By analyzing the results, we found that, sometimes, it is difficult to separate homologous from convergent evolution. Evaluation of the performance of our method by gene ontology term overlap showed that the precision of our method was excellent.

N'-(2-Hy-droxy-4-meth-oxy-benzyl-idene)-4-methyl-benzohydrazide

Acta Crystallographica. Section E, Structure Reports Online. Mar, 2012  |  Pubmed ID: 22412575

The asymmetric unit of the title compound, C(16)H(16)N(2)O(3), contains four independent mol-ecules with different conformations; the dihedral angles between the two benzene rings in the mol-ecules are 39.7 (3), 45.4 (3), 50.6 (3) and 51.6 (3)°. Intramolecular O-H⋯N hydrogen bonds are observed in the molecule. In the crystal, N-H⋯O hydrogen bonds link the mol-ecules into two crystallographically independent chains propagating in [010], and each chain is formed by two alternating independent mol-ecules. Weak C-H⋯O inter-actions also occur.

Clinical Predictors for Diagnosing Pandemic (H1N1) 2009 and Seasonal Influenza (H3N2) in Fever Clinics in Beijing, China

Biomedical and Environmental Sciences : BES. Feb, 2012  |  Pubmed ID: 22424628

Symptomatic predictors of influenza could assess risks and improve decisions about isolation and outpatient treatment. To develop such predictors, we undertook a prospective analysis of pandemic (H1N1) 2009 and seasonal influenza (H3N2) in patients attending fever clinics.

Cep70 Contributes to Angiogenesis by Modulating Microtubule Rearrangement and Stimulating Cell Polarization and Migration

Cell Cycle (Georgetown, Tex.). Apr, 2012  |  Pubmed ID: 22437770

Centrosomal proteins intricately regulate diverse microtubule-mediated cellular activities, including cell polarization and migration. However, the direct participation of these proteins in angiogenesis, which involves vascular endothelial cell migration from preexisting blood vessels, remains elusive. Here we show that the centrosomal protein Cep70 is necessary for angiogenic response in mice. This protein is also required for tube formation and capillary sprouting in vitro from vascular endothelial cells. Wound healing and transwell assays reveal that Cep70 plays a significant role in endothelial cell migration. Depletion of Cep70 results in severe defects in membrane ruffling and centrosome reorientation, indicating a requirement for this protein in cell polarization. In addition, Cep70 is critically involved in microtubule rearrangement in response to the migratory stimulus. Our data further demonstrate that Cep70 is important for Cdc42 and Rac1 activation to promote angiogenesis. These findings thus establish Cep70 as a crucial regulator of the angiogenic process and emphasize the significance of microtubule rearrangement and cell polarization and migration in angiogenesis.

Massilia Namucuonensis Sp. Nov., Isolated from a Soil Sample

International Journal of Systematic and Evolutionary Microbiology. Mar, 2012  |  Pubmed ID: 22447703

A Gram-staining-negative, rod-shaped and non-spore-forming bacterium, designated strain 333-1-0411(T), was isolated from a soil sample collected from Namucuo, Tibet Autonomous Region, China and characterized in a taxonomic study using a polyphasic approach. The major fatty acid components of strain 333-1-0411(T) were summed feature 3 (C(16 : 1)ω7c and/or C(16 : 1)ω6c) and C(16 : 0); its major polar lipids were phosphatidylethanolamine, diphosphatidylglycerol and phosphatidylglycerol. Q-8 was the dominant ubiquinone, and the G+C content of the genomic DNA was 66.7 mol%. A phylogenetic tree based on 16S rRNA gene sequences showed that strain 333-1-0411(T) fell within the evolutionary radiation encompassed by the genus Massilia. The 16S rRNA gene sequence similarities between strain 333-1-0411(T) and recognized species of the genus Massilia ranged from 95.4 % to 97.2 %, and the most closely related strains were Massilia flava Y9(T) (97.2 %) and Massilia albidiflava 45(T) (97.0 %). However, the DNA-DNA relatedness values between strain 333-1-0411(T) and M. flava Y9(T) and M. albidiflava 45(T) were 20.2 % and 27.2 %, respectively. Based on the phenotypic, chemotaxonomic and phylogenetic properties, strain 333-1-0411(T) is considered to represent a novel species of the genus Massilia, for which the name Massilia namucuonensis sp. nov. is proposed. The type strain is 333-1-0411(T) ( = CGMCC 1.11014(T) = DSM 25159(T)).

Biomedical Applications of Graphene

Theranostics. 2012  |  Pubmed ID: 22448195

Graphene exhibits unique 2-D structure and exceptional phyiscal and chemical properties that lead to many potential applications. Among various applications, biomedical applications of graphene have attracted ever-increasing interests over the last three years. In this review, we present an overview of current advances in applications of graphene in biomedicine with focus on drug delivery, cancer therapy and biological imaging, together with a brief discussion on the challenges and perspectives for future research in this field.

MiR-20a Promotes Migration and Invasion by Regulating TNKS2 in Human Cervical Cancer Cells

FEBS Letters. Mar, 2012  |  Pubmed ID: 22449978

miR-20a is an important member of the miR-17-92 cluster, and its real function in cervical cancer cells is unknown. Our study demonstrated that miR-20a was upregulated in cervical cancer tissues. Overexpression of miR-20a in cervical cancer-derived cell lines, HeLa and C-33A, enhanced long-term cellular proliferation, migration and invasion, whereas inhibition of miR-20a suppressed those functions. We also confirmed that oncogenic TNKS2 is directly upregulated by miR-20a. Furthermore, suppression of TNKS2 expression could inhibit colony formation, migration and invasion of cervical cancer cells. Therefore, we concluded that miR-20a can promote migration and invasion of cervical cancer cells through the upregulation of TNKS2.

Inhibition of Sclerostin by Systemic Treatment with Sclerostin Antibody Enhances Healing of Proximal Tibial Defects in Ovariectomized Rats

Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society. Mar, 2012  |  Pubmed ID: 22457198

Recent studies suggest a possible role for inhibitors of sclerostin such as sclerostin antibody (Scl-Ab) as an anabolic treatment for osteoporosis. Since Scl-Ab has also been shown to potentiate bone repair, we examined the effect of Scl-Ab treatment in a metaphyseal defect repair model in ovariectomized (OVX) rats. Four weeks after OVX or sham surgery, 3 mm circular defects were created bilaterally in the proximal tibia of all rats. After defect surgery, Saline or 25 mg/kg Scl-Ab was administered twice weekly for 3 weeks. Of note, healing was advanced in the 1-week post-defect surgery in OVX controls over Sham controls, with increases in bone volume and fluorochrome labeling observed. However, by week 2, OVX controls fell significantly behind in the repair response compared with Sham controls. Scl-Ab treatment significantly increased bone volume in the defect in OVX rats over the 3-week time course as examined by either microCT or histology. Significant increases in bone formation via fluorochrome labeling of the new bone were observed with Scl-Ab treatment, while osteoclast parameters were not different. With its powerful anabolic potential, bone-specific activity, and potential for low dosing frequency, Scl-Ab treatment could provide enhanced bone repair, particularly in situations of compromised bone repair such as osteoporotic bone.

Effect of Peripheral Administration of Cholecystokinin on Food Intake in Apolipoprotein AIV Knockout Mice

American Journal of Physiology. Gastrointestinal and Liver Physiology. Jun, 2012  |  Pubmed ID: 22461023

Apolipoprotein AIV (apo AIV) and cholecystokinin (CCK) are satiation factors secreted by the small intestine in response to lipid meals. Apo AIV and CCK-8 has an additive effect to suppress food intake relative to apo AIV or CCK-8 alone. In this study, we determined whether CCK-8 (1, 3, or 5 μg/kg ip) reduces food intake in fasted apo AIV knockout (KO) mice as effectively as in fasted wild-type (WT) mice. Food intake was monitored by the DietMax food system. Apo AIV KO mice had significantly reduced 30-min food intake following all doses of CCK-8, whereas WT mice had reduced food intake only at doses of 3 μg/kg and above. Post hoc analysis revealed that the reduction of 10-min and 30-min food intake elicited by each dose of CCK-8 was significantly larger in the apo AIV KO mice than in the WT mice. Peripheral CCK 1 receptor (CCK1R) gene expression (mRNA) in the duodenum and gallbladder of the fasted apo AIV KO mice was comparable to that in WT mice. In contrast, CCK1R mRNA in nodose ganglia of the apo AIV KO mice was upregulated relative to WT animals. Similarly, upregulated CCK1R gene expression was found in the brain stem of apo AIV KO mice by in situ hybridization. Although it is possible that the increased satiating potency of CCK in apo AIV KO mice is mediated by upregulation of CCK 1R in the nodose ganglia and nucleus tractus solitarius, additional experiments are required to confirm such a mechanism.

A High-affinity Monoclonal Antibody Against the FLAG Tag Useful for G-protein-coupled Receptor Study

Analytical Biochemistry. Jun, 2012  |  Pubmed ID: 22465329

The FLAG sequence (DYKDDDDK) is an artificial sequence widely used to detect, quantify, and purify proteins expressed as FLAG-fusion proteins. Several highly specific monoclonal antibodies for FLAG are commercially available; however, they are not always sensitive enough to detect proteins expressed at low levels and can give rise to unacceptable levels of background signal when used for immunostaining in vitro and in vivo. The current study reports the successful establishment of hybridoma cells that produce an extremely high-affinity antibody to FLAG, namely 2H8 Ab. 2H8 Ab stained FLAG-tagged G-protein-coupled receptors more strongly than commercially available antibodies in both flow cytometry and immunostaining experiments with no background staining. 2H8 was sensitive enough to detect FLAG-tagged G-protein-coupled receptors and soluble proteins in crude preparations, which could not be achieved using commercially available antibodies. Only 10 ng of 2H8 Ab was required to immunoprecipitate FLAG-tagged G-protein-coupled receptors from cell lysates. Of note, 2H8 stained FLAG-tagged BLT2, a low-affinity leukotriene B4 receptor, expressed in vivo in the small intestine of mice under control of the villin promoter. Thus, 2H8 Ab is a promising tool for analyzing various FLAG-fusion proteins, particularly G-protein-coupled receptors, both in vitro and in vivo.

The Ubiquitin Ligase Siah1 Controls ELL2 Stability and Formation of Super Elongation Complexes to Modulate Gene Transcription

Molecular Cell. May, 2012  |  Pubmed ID: 22483617

Super elongation complexes (SECs) contain two different transcription elongation factors, P-TEFb and ELL1/2, linked by the scaffolding protein AFF4 or AFF1. They stimulate the expression of both normal and disease-related genes, especially those of HIV or those involved in leukemogenesis. Among all SEC subunits, ELL2 is stoichiometrically limiting and uniquely regulated at the level of protein stability. Here we identify the RING domain protein Siah1, but not the homologous Siah2, as the E3 ubiquitin ligase for ELL2 polyubiquitination and proteasomal degradation. Siah1 cannot access and ubiquitinate ELL2 bound to AFF4, although, at high concentrations, it also degrades AFF4/1 to destroy SECs. Prostratin and HMBA, two well-studied activators of HIV transcription and latency, enhance ELL2 accumulation and SECs formation largely through decreasing Siah1 expression and ELL2 polyubiquitination. Given its importance in formation of SECs, the Siah1 ubiquitination pathway provides a fresh avenue for developing strategies to control disease-related transcription.

PIWIL4 Regulates Cervical Cancer Cell Line Growth and is Involved in Down-regulating the Expression of P14ARF and P53

FEBS Letters. May, 2012  |  Pubmed ID: 22483988

Recently, PIWIL4 has been identified as a functional protein involved in tumorigenesis. Cervical cancer is the second most prevalent form of cancer worldwide. The relationship between PIWIL4 and cervical cancer is still unknown. Here, we found that PIWIL4 is up-regulated in human cervical cancer tissues in comparison to adjacent normal tissues, and it promotes cell growth and proliferation by inhibiting apoptosis through the p14ARF/p53 pathway. PIWIL4 can also promote the invasion of cervical cancer cells. These results suggest that PIWIL4 might play an oncogenic role in cervical cancer and be useful as a new therapeutic target in the future.

Efficient Synthesis and Sulfonation of Ordered Mesoporous Carbon Materials

Journal of Colloid and Interface Science. Jul, 2012  |  Pubmed ID: 22487231

Ordered mesoporous carbons (OMCs) with hexagonal structure were efficiently synthesized via cooperative self-assembly of phenol/formaldehyde resol and surfactant F127 under acidic aqueous conditions. Induced by HCl, a gel phase mainly containing phenol/formaldehyde resol and F127 was obtained within several hours. X-ray diffraction (XRD), transmission electron microscope (TEM) and nitrogen adsorption isotherms indicated that the synthesized samples possess 2-D hexagonal mesostructure. The influence of the synthesis conditions, including acid concentration and mass ratio of resol to F127, was investigated. When the acid concentration was fixed in the range of 0.6-2.0 M and the mass ratio of resol to F127 in the range of 3.5-4.0, highly ordered mesoporous carbon could be synthesized. The synthesized OMCs could be easily sulfonated in concentrated sulfuric acid at elevated temperature. The results indicate that the mesostructural stability and the content of the surface sulfonic acid (SO(3)H) groups depend mainly on the pyrolysis temperature of the OMCs and the sulfonation temperature, suggesting that the combination of pyrolysis and sulfonation temperature is essential for developing OMCs with high densities of SO(3)H groups.

Hierarchical TiO2 Nanospheres with Dominant {001} Facets: Facile Synthesis, Growth Mechanism, and Photocatalytic Activity

Chemistry (Weinheim an Der Bergstrasse, Germany). Jun, 2012  |  Pubmed ID: 22499525

Hierarchical TiO(2) nanospheres with controlled surface morphologies and dominant {001} facets were directly synthesized from Ti powder by a facile, one-pot, hydrothermal method. The obtained hierarchical TiO(2) nanospheres have a uniform size of 400-500 nm and remarkable 78 % fraction of {001} facets. The influence of the reaction temperature, amount of HF, and reaction time on the morphology and the exposed facets was systematically studied. A possible growth mechanism speculates that Ti powder first dissolves in HF solution, and then flowerlike TiO(2) nanostructures are formed by assembly of TiO(2) nanocrystals. Because of the high concentration of HF in the early stage, these TiO(2) nanostructures were etched, and hollow structures formed on the surface. After the F(-) ions were effectively absorbed on the crystal surfaces, {001} facets appear and grow steadily. At the same time, the {101} facets also grow and meet the {101} facets from adjacent truncated tetragonal pyramids, causing coalescence of these facets and formation of nanospheres with dominant {001} facets. With further extension of the reaction time, single-crystal {001} facets of hierarchical TiO(2) nanospheres are dissolved and TiO(2) nanospheres with dominant {101} facets are obtained. The photocatalytic activities of the hierarchical TiO(2) nanospheres were evaluated and found to be closely related to the exposed {001} facets. Owing to the special hierarchical architecture and high percentage of exposed {001} facets, the TiO(2) nanospheres exhibit much enhanced photocatalytic efficiency (almost fourfold) compared to P25 TiO(2) as a benchmark material. This study provides new insight into crystal-facet engineering of anatase TiO(2) nanostructures with high percentage of {001} facets as well as opportunities for controllable synthesis of 3D hierarchical nanostructures.

In Vitro Antioxidant Effects and Cytotoxicity of Polysaccharides Extracted from Laminaria Japonica

International Journal of Biological Macromolecules. Jun, 2012  |  Pubmed ID: 22521618

A water-soluble crude polysaccharide (WPS) was obtained from Laminaria japonica by hot water extraction. Three major polysaccharide fractions (WPS-1, WPS-2 and WPS-3) were purified from WPS by anion-exchange chromatography. Monosaccharide components analysis indicated that galactose was the predominant monosaccharide in WPS and WPS-3, accounting for 56.25% and 54.11%, respectively. And fucose was the predominant monosaccharide in WPS-1 and WPS-2, accounting for 46.91% and 45.1%, respectively. Antioxidant activity tests revealed that WPS-2 showed significant function of scavenging hydroxyl free radical and WPS-1 exhibited the highest inhibitory effects on superoxide radical. Cytotoxicity of all polysaccharide fractions was evaluated by MTT assay and Hoechst 33258 staining. Results showed that WPS-1 and WPS-2 significantly inhibited the growth of A375 cells and low anti-proliferative effects of WPS-2 on vascular smooth muscle cells (VSMCs) were observed. These results suggested that the polysaccharide fraction of WPS-2 might be explored as a potential safe antioxidant and antitumor agent.

2-[(5-Chloro-2-oxidobenzyl-idene)aza-nium-yl]-2-methyl-propane-1,3-diol

Acta Crystallographica. Section E, Structure Reports Online. Feb, 2012  |  Pubmed ID: 22346933

The title compound, C(11)H(14)ClNO(3), was prepared by the condensation of equimolar quanti-ties of 5-chloro-salicyl-aldehyde and 2-amino-2-methyl-propane-1,3-diol in methanol. In the crystal, it exists in the zwitterionic form, with nominal proton transfer from the phenol group to the imine N atom. This results in the formation of an intra-molecular N-H⋯O hydrogen bond, which generates an S(6) ring. Inter-molecular O-H⋯O hydrogen bonds arise from the hy-droxy groups, forming (001) sheets.

[Periodontal Health Status Assessed by Community Periodontal Index and Related Factors in Adult Population of Beijing Urban Community]

Beijing Da Xue Xue Bao. Yi Xue Ban = Journal of Peking University. Health Sciences. Feb, 2012  |  Pubmed ID: 22353916

To investigate the periodontal health conditions by using community periodontal index (CPI) and analyze the effects of related risk factors.

[Clinical Analysis of Permanent Neonatal Diabetes Mellitus in 10 Cases]

Zhongguo Dang Dai Er Ke Za Zhi = Chinese Journal of Contemporary Pediatrics. Feb, 2012  |  Pubmed ID: 22357476

Fig Trees at the Northern Limit of Their Range: the Distributions of Cryptic Pollinators Indicate Multiple Glacial Refugia

Molecular Ecology. Apr, 2012  |  Pubmed ID: 22335780

Climatic oscillations during the last few million years had well-documented effects on the distributions and genomes of temperate plants and animals, but much less is known of their impacts on tropical and subtropical species. In contrast to Europe and North America, ice-sheets did not cover most of China during glacial periods, and the effects of glacial cycles were less dramatic. Fig trees are a predominantly tropical group pollinated by host-specific fig wasps. We employed partial mitochondrial COI (918 bp) and nuclear ITS2 (462 bp) gene sequences to investigate the genetic structure and demographic histories of the wasps that pollinate the subtropical Ficus pumila var. pumila in Southeastern China. Deep genetic divergence in both mitochondrial (7.2-11.6%) and nuclear genes (1.6-2.9%) indicates that three pollinator species are present and that they diverged about 4.72 and 6.00 Myr bp. This predates the Quaternary ice ages, but corresponds with the formation of the Taiwan Strait and uplifting of the Wuyi-Xianxia Mountains. The three pollinators have largely allopatric distribution patterns in China and display different postglacial demographic histories. Wiebesia spp. 1 and 2 occupy, respectively, the northern and southern regions of the mainland host range. Their populations both underwent significant postglacial spatial expansions, but at different times and at different rates. Wiebesia sp. 3 is largely restricted to northern islands and shows less evidence of recent population expansion. Their mainly allopatric distributions and different demographic histories are consistent with host plant postglacial expansion from three distinct refugia and suggest one mechanism whereby fig trees gain multiple pollinators.

Genotypic Variants at 2q33 and Risk of Esophageal Squamous Cell Carcinoma in China: A Meta-analysis of Genome-wide Association Studies

Human Molecular Genetics. Feb, 2012  |  Pubmed ID: 22323360

Genome-wide association studies have identified susceptibility loci for esophageal squamous cell carcinoma. We conducted a meta-analysis of all single nucleotide polymorphisms (SNPs) that showed nominally significant p-values in two previously published genome-wide scans that included a total of 2961 esophageal squamous cell carcinoma cases and 3400 controls. The meta-analysis revealed five SNPs at 2q33 with P < 5 x 10(-8) and the strongest signal was rs13016963, with a combined odds ratio (95% confidence interval) of 1.29 (1.19-1.40) and P = 7.63 x 10(-10). An imputation analysis of 4304 SNPs at 2q33 suggested a single association signal and the strongest imputed SNP associations were similar to those from the genotyped SNPs. We conducted an ancestral recombination graph analysis with 53 SNPs to identify one or more haplotypes that harbor the variants directly responsible for the detected association signal. This showed that the five SNPs exist in a single haplotype along with 45 imputed SNPs in strong linkage disequilibrium and the strongest candidate was rs10201587, one of the genotyped SNPs. Our meta-analysis found genome-wide significant SNPs at 2q33 that map to the CASP8/ALS2CR12/TRAK2 gene region. Variants in CASP8 have been extensively studied across a spectrum of cancers with mixed results. The locus we identified appears to be distinct from the widely studied rs3834129 and rs1045485 SNPs in CASP8. Future studies of esophageal and other cancers should focus on comprehensive sequencing of this 2q33 locus and functional analysis of rs13016963 and rs10201587and other strongly correlated variants.

MicroRNA-182 Targets CAMP-responsive Element-binding Protein 1 and Suppresses Cell Growth in Human Gastric Adenocarcinoma

The FEBS Journal. Apr, 2012  |  Pubmed ID: 22325466

MicroRNAs (miRNAs) constitute a class of noncoding RNAs that post-transcriptionally regulate gene expression. Recent evidence indicates that many miRNAs function as oncogenes or tumor suppressors by negatively regulating their target genes. In our previous study, using miRNA microarray analysis, we found that miRNA-182 (miR-182) was significantly downregulated in human gastric adenocarcinoma tissue samples. Here, we confirmed the downregulation of miR-182 in a larger sample of gastric tissue samples. Overexpression of miR-182 suppressed the proliferation and colony formation of gastric cancer cells. An oncogene, encoding cAMP-responsive element binding protein 1 (CREB1), serves as a direct target gene of miR-182. A fluorescent reporter assay confirmed that miR-182 binds specifically to the predicted site of the CREB1 mRNA 3'-UTR. When miR-182 was overexpressed in gastric cancer cell lines, both the mRNA and protein levels of CREB1 were depressed. Furthermore, CREB1 was present at a high level in human gastric adenocarcinoma tissues, and this was inversely correlated with miR-182 expression. Ectopic expression of CREB1 overcame the suppressive phenotypes of gastric cancer cells caused by miR-182. These results indicate that miR-182 targets the CREB1 gene and suppresses gastric adenocarcinoma cell growth, suggesting that miR-182 shows tumor-suppressive activity in human gastric cancer.

Technetium-99m-labelled HL91 and Technetium-99m-labelled MIBI SPECT Imaging for the Detection of Ischaemic Viable Myocardium: a Preliminary Study

Clinical Physiology and Functional Imaging. Jan, 2012  |  Pubmed ID: 22152075

The assessment of myocardial viability has become an important aspect of the diagnostic and prognostic work-up of patients with coronary artery disease. Technetium-99m labelled sestamibi ((99m)Tc-MIBI) myocardial perfusion imaging may underestimate the viability of ischaemic myocardium. Technetium-99m labelled 4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime ((99m)Tc-HL91) is a hypoxia-avid agent which can identify acutely ischaemic viable myocardium in a canine model using a standard gamma camera. The aim of this study was to evaluate uptake character of ischaemic viable myocardium and diagnostic performance of single-photon emission computed tomography (SPECT) imaging by (99m)Tc-HL91 and (99m)Tc-MIBI in detecting ischaemic viable myocardium in coronary heart disease.

De Novo Sequencing and a Comprehensive Analysis of Purple Sweet Potato (Impomoea Batatas L.) Transcriptome

Planta. Jul, 2012  |  Pubmed ID: 22270559

High-throughput RNA sequencing was performed for comprehensively analyzing the transcriptome of the purple sweet potato. A total of 58,800 unigenes were obtained and ranged from 200 nt to 10,380 nt with an average length of 476 nt. The average expression of one unigene was 34 reads per kb per million reads (RPKM) with a maximum expression of 1,935 RPKM. At least 40,280 (68.5%) unigenes were identified to be protein-coding genes, in which 11,978 and 5,184 genes were homologous to Arabidopsis and rice proteins, respectively. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis showed that 19,707 (33.5%) unigenes were classified to 1,807 terms of GO including molecular functions, biological processes, and cellular components and 9,970 (17.0%) unigenes were enriched to 11,119 KEGG pathways. We found that at least 3,553 genes may be involved in the biosynthesis pathways of starch, alkaloids, anthocyanin pigments, and vitamins. Additionally, 851 potential simple sequence repeats (SSRs) were identified in all unigenes. Transcriptome sequencing on tuberous roots of the sweet potato yielded substantial transcriptional sequences and potentially useful SSR markers which provide an important data source for sweet potato research. Comparison of two RNA-sequence datasets from the purple and the yellow sweet potato showed that UDP-glucose-flavonoid 3-O-glucosyltransferase was one of the key enzymes in the pathway of anthocyanin biosynthesis and that anthocyanin-3-glucoside might be one of the major components for anthocyanin pigments in the purple sweet potato. This study contributes to the molecular mechanisms of sweet potato development and metabolism and therefore that increases the potential utilization of the sweet potato in food nutrition and pharmacy.

Poly(amidoamine)s with Pendant Primary Amines and Flexible Backbone for Enhanced Nonviral Gene Delivery: Transfection and Intracellular Trafficking

Journal of Biomedical Materials Research. Part A. Apr, 2012  |  Pubmed ID: 22275314

We synthesized poly(amidoamine)s with pendant primary amines and flexible backbone (polymers 1-3) by Michael polyaddition of N-tert-butyloxycarbonyl (N-Boc) protected diamine to 1,6-Bis(acrylamido)hexane, followed by the deprotection of N-Boc under acidic conditions. The physicochemical properties of polymers 1-3, including buffer capacity, DNA-binding capacity, cytotoxicity, particle sizes, and zeta potentials of polycation/DNA complexes, were explored. All the three polymers possess high buffer capacity and excellent DNA-binding capacity. In vitro MTT assay revealed that these synthesized poly(amidoamine)s were less cytotoxic than commercial branched PEI (25 kDa). These poly(amidoamine)s with pendant primary amines and flexible backbone were evaluated as in vitro nonviral gene delivery vectors for 293T and COS-7 cells. All the three polymers exhibited high transfection efficiencies, which were even higher than branched PEI (25 kDa) at optimized conditions. Further evidences from confocal laser scanning microscope (CLSM) demonstrated that the high transfection efficiencies of polymers 1-3 were due to the efficient uptake and intracellular trafficking of plasmid DNA in the cells during the transfection.

Impact of Condom Use and Standardized Sexually Transmitted Disease Treatment on HIV Prevention Among Men Who Have Sex with Men in Hunan Province: Using the Asian Epidemic Model

AIDS Research and Human Retroviruses. Mar, 2012  |  Pubmed ID: 22280149

We evaluated the HIV/AIDS epidemic among men who have sex with men (MSM) in Hunan Province using the Asian Epidemic Model (AEM) and explored the impact of both condom use and standardized STD treatment on HIV prevention programs. The AEM was used to estimate HIV infection under four different scenarios: (1) condom use among MSM maintained at the 2005 level, (2) condom use among MSM improved since 2005, (3) the sexually transmitted infection (STI) prevalence rate among MSM maintained at the 2008 level, and (4) the STI prevalence rate among MSM improved since 2008. Compared with the rate of condom use at the 2005 level among MSM, if the rate of condom use had continuously improved, the number of new infections would have been reduced by 79.1% and the number of people living with HIV and AIDS would decrease by more than 8600 by 2020 and the cumulative number of new infections would have been reduced by 63.6% since 2006 while the number of new HIV infections among females would decline from 2015 with a drop of over 35% by 2020. When compared with the projection based on an unchanged rate of STI infection, the number of new HIV infections would decrease by 49.4% by 2020, and the decreased number of people living with HIV and AIDS would be more than 4000. The total number of 5200 newly infected HIV cases could be reduced from 2006 to 2020 and the number of newly infected HIV cases among the general female population would be reduced by 15.4%. With both the increased rate of condom use and standardized STD treatment for the MSM population in Hunan Province, the spread of HIV infection in both MSM and the general female population would decrease.

Asian Medicine: Call for More Safety Data

Nature. Feb, 2012  |  Pubmed ID: 22297960

An Iminosugar N-pentafluorobenzyl-1-deoxynojirimycin As a Novel Potential Immunosuppressant for the Treatment of Th2-related Diseases

Bioorganic & Medicinal Chemistry Letters. Jan, 2012  |  Pubmed ID: 22101135

Increased levels of Th2 cytokine interleukin-4 (IL-4) have been reported to be involved in the pathogenesis of the parasite Schistosoma japonicum (S. japonicum) infection or detected in the serum of the causative agent of acquired immunodeficiency syndrome (AIDS) patients. This correlates with a worsened outcome of AIDS. The inhibition of a Th2 type response might aid in the treatment of these Th2-related diseases. Previously, we found that N-pentafluorobenzyl-1-deoxynojirimycin (5F-DNM), a new derivative of 1-deoxynojirimycin (DNM) (an inhibitor of the glycoprotein processing enzymes, glucosidase I and II), had specific inhibition effects on human CD4(+) T cells. In this study, we further found that 5F-DNM not only markedly inhibited in vitro IL-4 production from human PBMCs, CD4(+) T cells and mouse splenocytes but also strongly inhibited the production of IL-4 in splenocytes from a mouse model of S. japonicum infection. The numbers of S. japonicum worms were significantly decreased in vivo upon the treatment of mice with 5F-DNM. We demonstrated the mechanism of 5F-DNM effects on CD4(+) T cells acts via the inhibition of the IL-4/JAK1/STAT6 signaling pathway. Moreover, 5F-DNM was found to induce CD4 internalization (transfer from the cellular surface to the cytoplasm) in CD4(+) T cells and had no significant effects on the overall expression levels of CD4. These findings indicate that 5F-DNM might be used as a potential candidate for the treatment of S. japonicum parasitic infection, AIDS and other Th2-related diseases.

Ezetimibe: Its Novel Effects on the Prevention and the Treatment of Cholesterol Gallstones and Nonalcoholic Fatty Liver Disease

Journal of Lipids. 2012  |  Pubmed ID: 22132342

The cholesterol absorption inhibitor ezetimibe can significantly reduce plasma cholesterol concentrations by inhibiting the Niemann-Pick C1-like 1 protein (NPC1L1), an intestinal sterol influx transporter that can actively facilitate the uptake of cholesterol for intestinal absorption. Unexpectedly, ezetimibe treatment also induces a complete resistance to cholesterol gallstone formation and nonalcoholic fatty liver disease (NAFLD) in addition to preventing hypercholesterolemia in mice on a Western diet. Because chylomicrons are the vehicles with which the enterocytes transport cholesterol and fatty acids into the body, ezetimibe could prevent these two most prevalent hepatobiliary diseases possibly through the regulation of chylomicron-derived cholesterol and fatty acid metabolism in the liver. It is highly likely that there is an intestinal and hepatic cross-talk through the chylomicron pathway. Therefore, understanding the molecular mechanisms whereby cholesterol and fatty acids are absorbed from the intestine could offer an efficacious novel approach to the prevention and the treatment of cholesterol gallstones and NAFLD.

Protein Isoaspartate Methyltransferase-mediated 18O-labeling of Isoaspartic Acid for Mass Spectrometry Analysis

Analytical Chemistry. Jan, 2012  |  Pubmed ID: 22132761

Arising from spontaneous aspartic acid (Asp) isomerization or asparagine (Asn) deamidation, isoaspartic acid (isoAsp, isoD, or beta-Asp) is a ubiquitous nonenzymatic modification of proteins and peptides. Because there is no mass difference between isoaspartyl and aspartyl species, sensitive and specific detection of isoAsp, particularly in complex samples, remains challenging. Here we report a novel assay for Asp isomerization by isotopic labeling with (18)O via a two-step process: the isoAsp peptide is first specifically methylated by protein isoaspartate methyltransferase (PIMT, EC 2.1.1.77) to the corresponding methyl ester, which is subsequently hydrolyzed in (18)O-water to regenerate isoAsp. The specific replacement of (16)O with (18)O at isoAsp leads to a mass shift of 2 Da, which can be automatically and unambiguously recognized using standard mass spectrometry, such as collision-induced dissociation (CID), and data analysis algorithms. Detection and site identification of several isoAsp peptides in a monoclonal antibody and the β-delta sleep-inducing peptide (DSIP) are demonstrated.

Immunogenicity of Lactobacillus-expressing VP2 and VP3 of the Infectious Pancreatic Necrosis Virus (IPNV) in Rainbow Trout

Fish & Shellfish Immunology. Jan, 2012  |  Pubmed ID: 22138084

Infectious pancreatic necrosis virus (IPNV) infects salmonid fish with high mortality and causes serious economic losses to salmonid aquaculture. Lactobacillus strains have a number of properties that make them attractive candidates as delivery vehicles for the presentation to the mucosa of compounds with pharmaceutical interest, in particular vaccines. Here, Lactobacilli/Escherichia coli shuttle vector pPG1 (surface-displayed) or pPG2 (secretory) with the capsid VP2 gene inserted was transformed into Lactobacillus casei to yield two recombinant strains: Lc:PG1-VP2 and Lc:PG2-VP2, respectively. Rainbow trout immunized respectively with Lc:PG1-VP2, Lc:PG2-VP2, Lc:PG1-VP3 and Lc:PG2-VP3 elicited anti-IPNV immune responses (serum IgM) via oral route. Statistical results of serum IgM titer with neutralizing activity showed that immunogenicity of Lc:PG2-VP2 was more powerful than that of Lc:PG1-VP2 (P < 0.001), Lc:PG1-VP3 (P < 0.001) and Lc:PG2-VP3 (P < 0.001), which was confirmed by viral loads reduction analyzed by real-time RT-PCR in orally immunized rainbow trout after virus challenge. Comparing with negative control, rainbow trout orally dosed with Lc:PG2-VP2 resulted in ∼46-fold reduction in virus load on days 10 post viral challenge as well as Lc:PG1-VP2(∼20-fold), Lc:PG2-VP3(∼6-fold) and Lc:PG1-VP3(∼3-fold). Taken together, Lc:PG2-VP2 exhibited a more appropriate candidate as live bacteria vaccine against IPNV infection in rainbow trout.

Intracellular Pathways and Nuclear Localization Signal Peptide-mediated Gene Transfection by Cationic Polymeric Nanovectors

Biomaterials. Feb, 2012  |  Pubmed ID: 22071097

Polyethylenimine (PEI) - based polymers are promising cationic nanovectors. A good understanding of the mechanism by which cationic polymers/DNA complexes are internalized and delivered to nuclei helps to identify which transport steps may be manipulated in order to improve the transfection efficiency. In this work, cell internalization and trafficking of PEI-CyD (PC) composed of β-cyclodextrin (β-CyD) and polyethylenimine (PEI, Mw 600) are studied. The results show that the PC transfected DNA is internalized by binding membrane-associated proteoglycans. The endocytic pathway of the PC particles is caveolae- and clathrin-dependent with both pathways converging to the lysosome. The intracellular fate of the PC provides visual evidence that it can escape from the lysosome. Lysosomal inhibition with chloroquine has no effect on PC mediated transfection implying that blocking the lysosomal traffic does not improve transfection. To improve the nuclear delivery of PC transfected DNA, nuclear localization signal (NLS) peptides are chosen to conjugate and combine with the PC. Compared to PC/pDNA, PC-NLS/pDNA, and PC/pDNA/NLS can effectively improve gene transfection in dividing and non-dividing cells.

High-throughput Purification Platform in Support of Drug Discovery

ACS Combinatorial Science. Jan, 2012  |  Pubmed ID: 22032344

The application of parallel synthesis is an efficient approach to explore the chemical space and to rapidly develop meaningful structure activity relationship (SAR) data for drug discovery programs. However, the effectiveness of the parallel synthesis requires a high throughput purification workflow that can process a large number of crude samples within a meaningful time frame. This paper describes a high throughput purification platform that has been adopted at Merck's Rahway research site. The platform includes the evaluation of crude samples, mass-directed HPLC purification, fraction analysis, compound registration, final compound purity assessment and assay distribution. Assisting with the sample tracking and the data management is the internally designed laboratory information management system, Light Automation Framework (LAF). Using this process and the tools described herein, the group has successfully achieved purities of 95% or greater for 90% of samples.

Are People Willing to Buy Natural Disaster Insurance in China? Risk Awareness, Insurance Acceptance, and Willingness to Pay

Risk Analysis : an Official Publication of the Society for Risk Analysis. Mar, 2012  |  Pubmed ID: 22443206

After the Wenchuan earthquake (magnitude 7.9, May 12, 2008), intensive debates on how China should establish a natural disaster insurance system were initiated among researchers, policymakers, and insurance professionals. Our focus was the social aspects of disaster insurance, explored in China through a nationwide survey. Our questionnaires investigated people's risk awareness, insurance acceptance, their opinions on governmental measures for disaster management, and their willingness to pay for disaster house insurance. We analyzed the results at both regional and individual scales. We found that the integrated hazard index and respondents' experience of insurance (considered objective factors), and their opinions on the importance of insurance and government responsibility (considered subjective factors) showed strong correlation with the regional overall acceptance of disaster insurance. An individual's decision to participate highly depended on his/her experience of both insurance and disaster and his/her opinion on the importance of insurance as a coping mechanism. Respondents from poverty-stricken or less-developed counties were not necessarily more reluctant to accept natural disaster insurance, though they exhibited relatively lower ability to afford insurance. In general, respondents had correct perceptions of natural disasters in their areas; however, people from regions with a greater multihazard threat showed less willingness to accept disaster insurance because they tended to expect the government to undertake to cover losses and considered insurance to be less important. People's willingness to pay for an assumed disaster house insurance was also investigated and analyzed. We consequently discuss the policy implications for developing a disaster insurance system in China.

PAHs in Indoor Dust Samples in Shanghai's Universities: Levels, Sources and Human Exposure

Environmental Geochemistry and Health. Apr, 2012  |  Pubmed ID: 22527117

Given the significant amount of time people spend indoors, the occurrence of polycyclic aromatic hydrocarbons (PAHs) in indoor dust and their potential risks are of great concern. In the present study, ten dust samples from lecture theatres and twelve samples from dining halls were collected from university campuses in Shanghai to investigate the PAH levels, possible sources and human exposure. The total concentrations of 18 PAHs ranged from 9.84 to 21.44 μg/g for dust samples from lecture theatres, and 9.63-44.13 μg/g for samples from dining halls. Total PAH concentrations in indoor dust samples showed a better correlation to black carbon compared to total organic carbon contents. PAHs in dining halls samples showed a similar distribution pattern with that of commercial kitchen air, which indicated that cooking activities could contribute most of the PAHs found in dining halls. Principal component analysis revealed both petrogenic and pyrogenic sources. The potential health risk for PAHs was assessed in terms of BaP equivalent carcinogenic power and estimated daily intake (EDI). Relatively high EDI values compared to other studies suggested that PAHs posed a potential threat to human health in indoor environments at Shanghai's universities.

Microtubule-binding Protein CLIP-170 is a Mediator of Paclitaxel Sensitivity

The Journal of Pathology. Mar, 2012  |  Pubmed ID: 21989536

CLIP-170 is a microtubule-binding protein and participates in diverse microtubule-associated cellular activities by regulating microtubule dynamics. Here we provide evidence that CLIP-170 is a mediator of the sensitivity of the anti-microtubule drug paclitaxel in breast cancer. In vitro cell proliferation assays reveal that CLIP-170 expression in breast cancer cell lines correlates with their sensitivity to paclitaxel. In addition, CLIP-170 expression in clinical samples of breast cancer correlates with the pathological response of tumours to paclitaxel-containing chemotherapy. Mitotic index and caspase-3 activity analyses reveal that CLIP-170 increases the abilities of paclitaxel to block cell cycle progression at mitosis and to induce apoptosis in breast cancer cells. By microtubule sedimentation assay and binding affinity analysis, we further find that CLIP-170 promotes paclitaxel binding to microtubules. In vitro tubulin polymerization assay shows that CLIP-170 enhances the activity of paclitaxel to promote microtubule assembly. These results demonstrate that CLIP-170 mediates paclitaxel sensitivity in breast cancer via a microtubule-dependent mechanism.

Recombinant Human Endostatin Endostar Inhibits Tumor Growth and Metastasis in a Mouse Xenograft Model of Colon Cancer

Pathology Oncology Research : POR. Apr, 2012  |  Pubmed ID: 21938482

To investigate the effects of recombinant human endostatin Endostar on metastasis and angiogenesis and lymphangiogenesis of colorectal cancer cells in a mouse xenograft model. Colon cancer cells SW620 were injected subcutaneously into the left hind flank of nude mice to establish mouse xenograft models. The mice were treated with normal saline or Endostar subcutaneously every other day. The growth and lymph node metastasis of tumor cells, angiogenesis and lymphangiogenesis in tumor tissue were detected. Apoptosis and cell cycle distribution were studied by flow cytometry. The expression of VEGF-A, -C, or -D in SW620 cells was determined by immunoblotting assays. Endostar inhibited tumor growth and the rate of lymph node metastasis (P < 0.01). The density of blood vessels in or around the tumor area was 12.27 ± 1.21 and 22.25 ± 2.69 per field in Endostar-treated mice and controls (P < 0.05), respectively. Endostar also decreased the density of lymphatic vessels in tumor tissues (7.84 ± 0.81 vs. 13.83 ± 1.08, P < 0.05). Endostar suppresses angiogenesis and lymphangiogenesis in the lymph nodes with metastases, simultaneously. The expression of VEGF-A, -C and -D in SW620 cells treated with Endostar was substantially lower than that of controls. Endostar inhibited growth and lymph node metastasis of colon cancer cells by inhibiting angiogenesis and lymphangiogenesis in a mouse xenograft model of colon cancer.

Development of a High-throughput Screen Targeting Caspase-8-mediated Cleavage of the Amyloid Precursor Protein

Analytical Biochemistry. Feb, 2012  |  Pubmed ID: 22178911

Caspases, effectors of apoptosis, are key mediators of neuronal death in several neurodegenerative diseases. Caspase-8 and caspase-6 have been implicated in the pathogenesis of amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, and Alzheimer's disease (AD). ß-Amyloid precursor protein (APP) is cleaved at Asp664 in its intracellular domain by caspase-8. We and other laboratories recently showed that obliteration of the caspase cleavage site on APP alleviates functional AD-like deficits in a mouse model. Therefore, caspase cleavage of APP constitutes a potential novel target for therapeutic intervention. To identify chemical inhibitors of caspase-8 cleavage, we screened a subset of the chemical library at the Harvard NeuroDiscovery Center's Laboratory for Drug Discovery in Neurodegeneration. We show that caspase-8, but not caspase-1, -3, or -9, cleaves a biotinylated peptide derived from APP at Asp664, and we report the development of a sensitive high-throughput assay for caspase-8 cleavage of APP and the use of that assay for the identification of specific small molecule "hit" compounds that potently inhibit Asp664 cleavage of APP. Furthermore, we demonstrate that one of these compounds (LDN-0021835) inhibits the cleavage of APP at Asp664 in cell-based assays.

Dragon's Blood Inhibits Chronic Inflammatory and Neuropathic Pain Responses by Blocking the Synthesis and Release of Substance P in Rats

Journal of Pharmacological Sciences. 2012  |  Pubmed ID: 22198006

As a traditional Chinese medicine, dragon's blood (DB) is widely used in treating various pains for thousands of years due to its potent anti-inflammatory and analgesic effects. In the present study, we observed that intragastric administration of DB at dosages of 0.14, 0.56, and 1.12 g/kg potently inhibited paw edema, hyperalgesia, cyclooxygenase-2 (COX-2) protein expression, or preprotachykinin-A mRNA expression in carrageenan-inflamed or sciatic nerve-injured (chronic constriction injury) rats, respectively. A short-term (15 s or 10 min) pre-exposure of cultured rat dorsal root ganglion (DRG) neurons to DB (0.3, 3, and 30 µg/ml) or its component cochinchinenin B (CB; 0.1, 1, and 10 µM) blocked capsaicin-evoked increases in both the intracellular calcium ion concentration and the substance P release. Moreover, a long-term (180 min) exposure of cultured rat DRG neurons to DB or CB significantly attenuated bradykinin-induced substance P release. These findings indicate that DB exerts anti-inflammatory and analgesic effects by blocking the synthesis and release of substance P through inhibition of COX-2 protein induction and intracellular calcium ion concentration. Therefore, DB may serve as a promising potent therapeutic agent for treatment of chronic pain, and its effective component CB might partly contribute to anti-inflammatory and analgesic effects.

Hybrid Cu(x)O/TiO₂ Nanocomposites As Risk-reduction Materials in Indoor Environments

ACS Nano. Feb, 2012  |  Pubmed ID: 22208891

Photocatalytic TiO(2) powders impart ultraviolet light-induced self-cleaning and antibacterial functions when coated on outdoor building materials. For indoor applications, however, TiO(2) must be modified for visible-light and dark sensitivity. Here we report that the grafting of nanometer-sized Cu(x)O clusters onto TiO(2) generates an excellent risk-reduction material in indoor environments. X-ray absorption near-edge structure using synchrotron radiation and high-resolution transmission electron microscopic analyses revealed that Cu(x)O clusters were composed of Cu(I) and Cu(II) valence states. The Cu(II) species in the Cu(x)O clusters endow TiO(2) with efficient visible-light photooxidation of volatile organic compounds, whereas the Cu(I) species impart antimicrobial properties under dark conditions. By controlling the balance between Cu(I) and Cu(II) in Cu(x)O, efficient decomposition and antipathogenic activity were achieved in the hybrid Cu(x)O/TiO(2) nanocomposites.

Histone Deacetylase Activity is Required for Skin Langerhans Cell Maturation and Phagocytosis

Journal of Dermatological Science. Feb, 2012  |  Pubmed ID: 22222421

Prediction and Characterization of Protein-protein Interaction Networks in Swine

Proteome Science. 2012  |  Pubmed ID: 22230699

Studying the large-scale protein-protein interaction (PPI) network is important in understanding biological processes. The current research presents the first PPI map of swine, which aims to give new insights into understanding their biological processes.

Expression of Infectious Pancreatic Necrosis Virus (IPNV) VP2-VP3 Fusion Protein in Lactobacillus Casei and Immunogenicity in Rainbow Trouts

Vaccine. Feb, 2012  |  Pubmed ID: 22234263

Infectious pancreatic necrosis virus (IPNV) infects wild and cultured salmonids, causing high mortality in juvenile trouts and salmons. IPNV VP2-VP3 fusion gene was constructed by splicing overlap extension (SOE) PCR and inserted into Lactobacillus/Escherichia coli shuttle vectors (pPG1and pPG2) followed by transformation of Lactobacillus casei competent cell to yield two recombinant strains: Lc:PG1-VP2-VP3 (surface-displayed) and Lc:PG2-VP2-VP3 (secretory). Subsequently, juvenile rainbow trouts were inoculated with the recombinant strains via orogastric route. Our results demonstrated that Lactobacillus-derived VP2-VP3 fusion protein could induce production of serum IgM specific for IPNV with neutralizing activity in rainbow trouts. Statistical analyses of IgM levels showed that immunogenicity of Lc:PG1-VP2-VP3 was more powerful than that of Lc:PG2-VP2-VP3 (P<0.001) in rainbow trouts. This result has been confirmed by viral loads reduction analyzed by real-time RT-PCR in orogastrically immunized rainbow trouts after virus challenging. Comparing to trouts received Lactobacillus (control), rainbow trouts orogastrically dosed with Lc:PG1-VP2-VP3 resulted in ∼10-fold reduction in viral loads on day 10 post-virus challenging, and ∼4-fold did by Lc:PG2-VP2-VP3. Taken together, Lc:PG1-VP2-VP3 functions as novel mucosal vaccine against IPNV infection in rainbow trouts, which most likely come true.

Detection of Bacterial Diversity in Rat's Periodontitis Model Under Imitational Altitude Hypoxia Environment

Archives of Oral Biology. Jan, 2012  |  Pubmed ID: 21840496

Oral epidemiologic investigations in China western territory have showed that the immigrants in the plateau have a higher morbidity with periodontitis. To find the possible relationship between the pathogenesis of periodontitis and altitude hypoxia, we designed a periodontitis rat model via housed in low pressure oxygen chamber and investigated the bacterial diversity in the gingival crevicular fluid (GCF).

[Community Structure and Spatial Distribution of Anaerobic Ammonium Oxidation Bacteria in the Sediments of Chongming Eastern Tidal Flat in Summer]

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.]. Mar, 2012  |  Pubmed ID: 22624399

The objectives of this study were to identify whether there were Anaerobic Ammonium Oxidation (ANAMMOX) bacteria in the surface sediments of Chongming eastern tidal flat in the Yangtze estuary and the feature of their community structure and spatial distribution. Based on the total DNA extracted from the surface sediments of Chongming eastern tidal flat, ANAMMOX-specific 16S rDNA fragments were amplified. PCR products were cloned and sequenced, and an ANAMMOX-specific 16S rDNA gene library was established. Phylogenetic tree was constructed using MEGA5 after the sequences were checked in the GenBank database. Phylogenetic analysis indicated that the clone sequences CM-L-7 and CM-L-18 had 98% identities with ANAMMOX bacteria Candidatus 'Scalindua sp.'. CM-L-13 had 94% identities with Candidatus 'Scalindua wagneri'. CM-M-6 had 94% identities with Candidatus 'Kuenenia sp.'. CM-M-22 had 95% identities with Anaerobic ammonium-oxidizing planctomycete JMK-1. CM-H-15 had 94% identities with Candidatus 'Kuenenia stuttgartiensis'. The results indicated that there were ANAMMOX bacteria in the surface sediments of Chongming eastern tidal flat, but the ANAMMOX species were diverse in different tidal flats: Candidatus 'Scalindua' was the predominant group in the low tidal flat, while Candidatus 'Kuenenia' was the major population in the high tidal flat and the middle tidal flat. In comparison with the high and low tidal flats, the community structure of ANAMMOX bacteria in the middle tidal flat was the most complicated. A portion of the sequences related to uncultivated bacteria outside the known ANAMMOX cluster, probably indicated that there were potential ANAMMOX bacteria in the sediments of Chongming eastern tidal flat.

Sectional Anatomy Aid for Improvement of Decompression Surgery Approach to Vertical Segment of Facial Nerve

The Journal of Craniofacial Surgery. May, 2012  |  Pubmed ID: 22627402

The aim of this study was to find a surgical approach to a vertical segment of the facial nerve (VFN) with a relatively wide visual field and small lesion by studying the location and structure of VFN with cross-sectional anatomy. High-resolution spiral computed tomographic multiplane reformation was used to reform images that were parallel to the Frankfort horizontal plane. To locate the VFN, we measured the distances as follows: from the VFN to the paries posterior bony external acoustic meatus on 5 typical multiplane reformation images, to the promontorium tympani and the root of the tympanic ring on 2 typical images. The mean distances from the VFN to the paries posterior bony external acoustic meatus are as follows: 4.47 mm on images showing the top of the external acoustic meatus, 4.20 mm on images with the best view of the window niche, 3.35 mm on images that show the widest external acoustic meatus, 4.22 mm on images with the inferior margin of the sulcus tympanicus, and 5.49 mm on images that show the bottom of the external acoustic meatus. The VFN is approximately 4.20 mm lateral to the promontorium tympani on images with the best view of the window niche and 4.12 mm lateral to the root of the tympanic ring on images with the inferior margin of the sulcus tympanicus. The other results indicate that the area and depth of the surgical wound from the improved approach would be much smaller than that from the typical approach. The surgical approach to the horizontal segment of the facial nerve through the external acoustic meatus and the tympanic cavity could be improved by grinding off the external acoustic meatus to show the VFN. The VFN can be found by taking the promontorium tympani and tympanic ring as references. This improvement is of high potential to expand the visual field to the facial nerve, remarkably without significant injury to the patients compared with the typical approach through the mastoid process.

Internal Carotid Artery in the Operative Plane of Endoscopic Endonasal Transsphenoidal Surgery

The Journal of Craniofacial Surgery. May, 2012  |  Pubmed ID: 22627403

The objective of this study was to measure the related parameters of intercarotid artery (ICA) in the operative plane of endonasal transsphenoidal approach for hypophyseal surgeries. Nine parameters of the ICA were examined in the computed tomographic angiographic (CTA) scan of 101 patients. The shortest distance between the middle point of the nasal columella and the projective point of the ICA (D(3)) was 85.50 (5.79) mm. The shortest distance between the anterior wall of the sphenoid sinus and the projective point of the ICA (D(4)) was 16.93 (3.50) mm. The distance between the bilateral projective points of the ICA (D(5)) was 21.60 (3.45) mm. The shortest distance from the anterior wall of the sphenoid sinus to the line between the bilateral projective points of the ICA (D(6)) was 12.1 (3.91) mm. The shortest distance between the middle point of nasal columella and the anterior wall of the sphenoid sinus (D(7)) was 72.67 (5.99) mm. The width of the angle between the bilateral ICA projective point from the middle point of the nasal columella (A(1)) was 14.9 (2.32) degrees. The width of the angle between the bilateral ICA projective points from the anterior-most point of sphenoid sinus (A(2)) was 85.49 (18.12) degrees. Clinically, it is relatively safe to work within the distances and angles measured in this research, and these results may provide information for clinical surgery of pituitary tumor.

The Effect of Fetal and Early Postnatal Iron Deficiency on Iron Metabolism in Adult Rats

Biological Trace Element Research. May, 2012  |  Pubmed ID: 22628058

Undernutrition during pregnancy and/or lactation plays an important role on the overall health of offspring later in life. Using a rodent model, the present study was conducted to examine the effect of fetal and early postnatal iron deficiency on iron metabolism in adult animals. Rats were treated with three stages of low or normal iron diets from gestation until the end of the study. During the first stage (4 weeks prior to 3 weeks after pregnancy, total 7 weeks), two groups of adult females (dams) were fed with either a low-iron (7.4 mg iron/kg, group LD) or control-iron (274 mg/kg, group CD) diet. During the second stage (from 3 to 13 weeks of age, total 10 weeks), all pups from stage 1 (both the LD and CD groups) were placed on a control-iron diet for 10 weeks (groups LD-CD and CD-CD, respectively). During the third stage (from 13 to 29 weeks of age, total 16 weeks), both LD-CD and CD-CD groups from stage 2 were fed with a low-iron (named LD-CD-LD and CD-CD-LD groups, respectively). We found that the live birth rate of the offspring of the LD dams (84.7 %) was significantly lower than that of the CD dams (95.4 %). During stage 2, the mean body weight of the LD-CD male or LD-CD female rats exceeded the CD-CD male rats (p < 0.05). Compared with the CD-CD-LD rats, the LD-CD-LD rats had significantly increased total iron binding capacity, and higher levels of transferrin, serum erythropoietin (EPO), renal EPO mRNA, duodenal divalent metal transporter-1, and renal transferrin receptors. These findings indicate that rats with an early-life experience of iron deficiency (during pregnancy and the nursing period) can develop stronger iron absorption capabilities in adulthood.

MicroRNA-10a Targets CHL1 and Promotes Cell Growth, Migration and Invasion in Human Cervical Cancer Cells

Cancer Letters. May, 2012  |  Pubmed ID: 22634495

MicroRNAs (miRNAs) play an important role in cancer initiation, progression and metastasis by regulating their target genes. Here, we found microRNA-10a (miR-10a) is upregulated in human cervical cancer and promotes the colony formation activity, migration and invasion of HeLa and C33A cells. Subsequently, CHL1 is confirmed as a target of miR-10a and is negatively regulated by miR-10a at mRNA and protein levels. Furthermore, knockdown of CHL1 expression results in increased colony formation activity, migration and invasion. Finally, overexpression of CHL1 lacked the 3'UTR abolished the effects of miR-10a. Our results may provide a strategy for blocking tumor metastasis.

Mechanism of Cellular Uptake of Graphene Oxide Studied by Surface-enhanced Raman Spectroscopy

Small (Weinheim an Der Bergstrasse, Germany). May, 2012  |  Pubmed ID: 22641430

The last few years have witnessed rapid development of biological and medical applications of graphene oxide (GO), such as drug/gene delivery, biosensing, and bioimaging. However, little is known about the cellular uptake mechanism and pathway of GO. In this work, surface-enhanced Raman scattering (SERS) spectroscopy is employed to investigate the cellular internalization of GO loaded with Au nanoparticles (NPs) by Ca Ski cells. The presence of Au NPs on the surface of GO enables detection of enhanced intrinsic Raman signals of GO inside the cell. The SERS results reveal that GO is distributed inhomogeneously inside the cell. Furthermore, internalization of Au-GO into Ca Ski cells is mainly via clathrin-mediated endocytosis, and is an energy-dependent process.

Regenerative Responses in Slow- and Fast-twitch Muscles Following Moderate Contusion Spinal Cord Injury and Locomotor Training

European Journal of Applied Physiology. May, 2012  |  Pubmed ID: 22644570

The aim of this study was to use the rat moderate spinal cord contusion model to investigate the effects of incomplete spinal cord injury (SCI) on the muscle regeneration process, comparing regeneration of slow-twitch plantarflexor soleus muscle and fast-twitch dorsiflexor tibialis anterior (TA) muscle. Additionally, we wanted to examine the effect of a week of locomotor training following incomplete SCI on the muscle regeneration process in these muscles and also determine if a week of similar locomotor training is sufficient to initiate muscle regeneration in control, non-injured rats. Thirty-two, adult, female, Sprague-Dawley rats were chosen for the study. Moderate, midthoracic contusion SCIs were produced using a NYU (New York University) impactor in all rats except controls. Animals were randomly assigned to treadmill training or untrained groups. Rats in the treadmill training group were manually treadmill trained starting at 1 week after SCI, for 10 bouts (2 sessions of 20 min of actual stepping) over 5 days and control rats in the training group received similar training. Our results indicate that a muscle regenerative response was initiated only in the slow-twitch soleus muscle in the initial 2 weeks following SCI, the addition of 1 week of locomotor treadmill training led to a significant increase in soleus regenerative process. No significant regenerative process was observed in the fast-twitch TA. Increased muscle regeneration in soleus is suggested by our findings of increased expression of (1) insulin-like growth factor-1, involved in the activation of satellite cells; (2) Pax7, a marker of satellite cell activation; (3) myogenin, a muscle regulatory protein; and (4) embryonic myosin, an indicator of new muscle fiber formation. Locomotor training in control, non-injured animals did not induce similar changes towards the regenerative process.

Distribution of Nd3+ Ions in Oxyfluoride Glass Ceramics

Nanoscale Research Letters. May, 2012  |  Pubmed ID: 22647385

It has been an open question whether Nd3+ ions are incorporated into the crystalline phase in oxyfluoride glass ceramics or not. Moreover, relative research has indicated that spectra characters display minor differences between before and after heat treatment in oxyfluoride glass compared to similar Er3+-, Yb3+-, Tm3+-, Eu3+-, etc.-doped materials. Here, we have studied the distribution of Nd3+ ions in oxyfluoride glass ceramics by X-ray diffraction quantitative analysis and found that almost none of the Nd3+ ions can be incorporated into the crystalline phase. In order to confirm the rationality of the process, the conventional mathematical calculation and energy-dispersive spectrometry line scanning are employed, which show good consistency. The distribution of Nd3+ ions in oxyfluoride glass ceramics reported here is significant for further optical investigations and applications of rare-earth doped oxyfluoride glass ceramics.

[Molecularly-imprinted Solid Phase Extraction Coupled with High Performance Liquid Chromatography for the Determination of Ractopamine in Feed Samples]

Se Pu = Chinese Journal of Chromatography / Zhongguo Hua Xue Hui. Jan, 2012  |  Pubmed ID: 22667092

Molecularly imprinted polymers (MIPs) with high selectivity to ractopamine (RAC) were prepared by using RAC as template, acrylamide (AM) as monomer, and ethylene glycol dimethacrylate (EGDMA) as cross-linker. The effects of four porogens (methanol, acetonitrile, acetone, and chloroform-methanol) with triethylamine (30:1, v/v) on the recognition capability of MIPs to RAC and the morphological characteristics of the polymers were investigated. Orthogonal test was used to optimize the preparation of MIPs, and the optimal compositions were as follows: 1.0 mmol RAC, 4.0 mmol AM, 20.0 mmol EGDMA, 6.0 mL acetonitrile-triethylamine (30:1, v/v), and 50.0 mg azobisisobutyronitrile. A high performance liquid chromatographic method based on molecularly-imprinted solid-phase extraction (MISPE) was developed for the determination of ractopamine in feed samples. The limit of detection (LOD, S/N = 3) of ractopamine was 0.1 mg/kg. The linear range was 0.50-100 mg/L (r = 0.999 4). Mean recoveries of RAC spiked in 3 kinds of feed samples at 1.0, 10 and 100 mg/kg were above 80% with the relative standard deviations of less than 10%. The clean-up efficiency of MISPE was ideal for feed samples. The method is more sensitive and reproduciable than the standard analytical method for the determination of RAC in feed matrices.

Adult Cerebrospinal Fluid Does Not Support Neurogenesis from Fetal Rat Neural Stem Cells

Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. Jun, 2012  |  Pubmed ID: 22673817

The purpose was to study the effect of human cerebrospinal fluid (CSF) on differentiation of rat neural stem cells (NSCs), and thus explore the feasibility of transplanting stem cells via lumbar puncture clinically. Rat NSCs derived from fetal brain were divided into two groups, and cultured in DMEM/F12 supplemented with 10 % FBS and human CSF, respectively. Cellular growth was observed with an inverted microscope, and immunostaining was used to analyze differentiation of NSCs in both groups. Cells of fetal brain showed shapes of spindle or star with minor sprouts at fifth day post-culture, and stained with nestin. NSCs in the control group differentiated into neurons, with positive staining to NSE, when cultured further in DMEM/F12 supplemented with 10 % FBS. While NSCs in the experiment group, cultured in CSF, differentiated into astroglia on eighth day, with positive immunostaining to GFAP. The new neurons dissolved rapidly when they were cultured in CSF. Human CSF cannot promote NSCs to differentiation toward neuron, nor support newborn neurons survival. It seems an inappropriate approach to transplant stem cells through CSF.

Rap1 and Its Regulatory Proteins: the Tumor Suppressor, Oncogene, Tumor Suppressor Gene Axis in Head and Neck Cancer

Small GTPases. Jul, 2012  |  Pubmed ID: 22684501

Squamous cell carcinoma of the head and neck (SCCHN) is the sixth most common cancer, globally. Previously, we showed that Rap1GAP is a tumor suppressor gene that inhibits tumor growth, but promotes invasion in SCCHN. In this work, we discuss the role of Rap1 and Rap1GAP in SCCHN progression in the context of a microRNA-oncogene-tumor suppressor gene axis, and investigate the role of Rap1GAP in EZH2-mediated invasion. Loss of expression of microRNA-101 in SCCHN leads to upregulation of EZH2, a histone methyltransferase. Overexpression of EZH2 silences Rap1GAP via methylation, thereby promoting activation of its target, Rap1. This microRNA-controlled activation of Rap1, via EZH2-mediated silencing of Rap1GAP, is a novel mechanism of Rap1 regulation. In two independent SCCHN cell lines, downregulation of EZH2 inhibits proliferation and invasion. In both cell lines, stable knockdown of EZH2 (shEZH2) recovers Rap1GAP expression and inhibits proliferation. However, siRNA-mediated knockdown of Rap1GAP in these cells rescues proliferation but not invasion. Thus, EZH2 promotes proliferation and invasion via Rap1GAP-dependent and -independent mechanisms, respectively. Although the studies presented here are in the context of SCCHN, our results may have broader implications, given that Rap1GAP acts as a tumor suppressor in pancreatic cancer, thyroid cancer, and melanoma.

Inhibition of HBV Replication by VPS4B and Its Dominant Negative Mutant VPS4B-K180Q in Vivo

Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban. Jun, 2012  |  Pubmed ID: 22684550

This study examined the anti-hepatitis B virus (HBV) effect of wild-type (WT) vacuolar protein sorting 4B (VPS4B) and its dominant negative (DN) mutant VPS4B-K180Q in vivo in order to further explore the relationship between HBV and the host cellular factor VPS4. VPS4B gene was amplified from Huh7 cells by RT-PCR and cloned into the eukaryotic expression vector pXF3H. Then, the VPS4B plasmid and the VPS4B-K180Q mutation plasmid were constructed by using the overlap extension PCR site-directed mutagenesis technique. VPS4B and HBV vectors were co-delivered into mice by the hydrodynamic tail-vein injection to establish HBV vector-based models. Quantities of HBsAg and HBeAg in the mouse sera were determined by ElectroChemiLuminescence (ECL). HBV DNA in sera was measured by real-time quantitative PCR. Southern blot analysis was used to assay the intracellular HBV nuclear capsid-related DNA, real-time quantitative PCR to detect the HBV-related mRNA and immunohistochemical staining to observe the HBcAg expression in the mouse liver tissues. Our results showed that VPS4B and its mutant VPS4B-K180Q could decrease the levels of serum HBsAg, HBeAg and HBV-DNA. In addition, the HBV DNA replication and the mRNA level of HBV in the liver tissues of treated mice could be suppressed by VPS4B and VPS4B-K180Q. It was also found that VPS4B and VPS4B-K180Q had an ability to inhibit core antigen expression in the infected mouse liver. Furthermore, the anti-HBV effect of mutant VPS4B-K180Q was more potent than that of wild-type VPS4B. Taken together, it was concluded that VPS4B and its DN mutant VPS4B-K180Q have anti-HBV effect in vivo, which helps develop molecular therapeutic strategies for HBV infection.

Saccharomyces As a Vaccine Against Systemic Candidiasis

Immunological Investigations. Jun, 2012  |  Pubmed ID: 22686468

We have shown heat-killed Saccharomyces (HKY) is a protective vaccine against aspergillosis and coccidioidomycosis. To test the hypothesis that the efficacy of HKY- induced protection may be due to the cross-reactive antigens in the cell walls of the different fungi, we studied the effect of HKY against systemic candidiasis. Male CD-1 mice were given different regimens of HKY subcutaneously prior to intravenous challenge with Candida albicans. Compared to PBS controls, the administration of HKY (6 × 10(7)) 3, 4 or 6 times prolonged survival (all P < 0.05) and reduced fungal load in the kidney (all P < 0.05). An HKY dose of 1.2 × 10(8) given 4 times prolonged survival (P = 0.02), but showed dose-limiting toxicity. HKY given by an oral route, or by a subcutaneous route with alum as an adjuvant, did not improve survival. Overall, we found that HKY protects mice from infection by Candida albicans in a dose-and regimen-dependent manner. To understand the protection induced by HKY against different fungal species, additional studies of epitope mapping are warranted.

Insulin Increases Central Apolipoprotein E Levels As Revealed by an Improved Technique for Collection of Cerebrospinal Fluid from Rats

Journal of Neuroscience Methods. Jun, 2012  |  Pubmed ID: 22691999

Cerebrospinal fluid (CSF) provides an invaluable analytical window to the central nervous system (CNS) because it reflects the dynamically changing complement of CNS constituents. We describe an improved method for sampling CSF in rats that is easy to perform. It has a 96% success rate of CSF collection and consistently yields large volumes (150-200 μl) of CSF. The blood contamination rate is also low (6%) as determined by both visual inspection and the lack of molecular detection of apolipoprotein B, a plasma-derived protein, which is absent in the CNS. This improved method of CSF sampling can have broad applicability in physiological and pharmacological evaluation for diverse CNS targets. We used this technique to provide proof of principle by examining the effect of intraperitoneal insulin on the level of apolipoprotein E (apoE) in the CSF. Insulin (0.5 and 1 U/kg) led to a significant increase of insulin in both plasma and CSF at 2 h after intraperitoneal administration and decreased blood glucose for at least 2h. ApoE concentrations in CSF, but not in plasma, were also significantly increased, and its time-course was inversely correlated with the alterations in blood glucose over 2 h. These results provide a pharmacological validation of the novel CSF sampling and validation procedure for sampling rat CSF.

[Application of EARS in Early-warning of Influenza Pandemic in Beijing]

Beijing Da Xue Xue Bao. Yi Xue Ban = Journal of Peking University. Health Sciences. Jun, 2012  |  Pubmed ID: 22692313

To illustrate the efficiency of cumulative sum (CUSUM) in pre-warning of the influenza peak in Beijing.

Paenibacillus Typhae Sp. Nov., Isolated from Roots of Typha Angustifolia L

International Journal of Systematic and Evolutionary Microbiology. Jun, 2012  |  Pubmed ID: 22707528

A Gram-staining-positive, facultatively anaerobic and rod-shaped bacterium, designated strain xj7T, was isolated from roots of Typha angustifolia L. growing in Beijing Cuihu Wetland, China. The isolate was identified as a member of the genus Paenibacillus based on the phenotypic characteristics and phylogenetic inference. The novel strain was spore-forming, motile, catalase-positive and oxidase-negative. Optimal growth of strain xj7T occurred at 28-30 °C and pH 7.0-7.5. Diphosphatidylglycerol was the most abundant polar lipid in comparison to phosphatidylglycerol, phosphatidylethanolamine, one unknown phospholipid and three unknown aminophospholipids. The diamino acid found in the cell-wall peptidoglycan was meso-diaminopimelic acid. The predominant isoprenoid quinone was MK-7. The major fatty acid components were anteiso-C15: 0 (56.1 %), iso-C16:0 (9.1 %), C16:0 (8.0 %), iso-C14:0 (6.3 %) and iso-C15:0 (5.1 %). The G+C content of genomic DNA was 47.9 mol%. Phylogenetic analysis based on the 16S rRNA gene sequence showed that strain xj7T fell within the evolutionary radiation encompassed by the genus Paenibacillus, its closest neighbours were Paenibacillus borealis KK19T (97.5 %) and Paenibacillus durus DSM 1735T (97.1%). However, the DNA-DNA relatedness values between strain xj7T and P. borealis KK19T, and that between strain xj7T and P. durus DSM 1735T, were both 35 %. Based on their phenotypic, chemotaxonomic and phylogenetic properties, strain xj7T is considered to represent a novel species of the genus Paenibacillus, for which the name Paenibacillus typhae sp. nov. is proposed. The type strain is xj7T (= CGMCC 1.11012T = DSM 25190T).

A Facile One-step Hydrothermal Synthesis of Rhombohedral CuFeO2 Crystals with Antivirus Property

Chemical Communications (Cambridge, England). Jul, 2012  |  Pubmed ID: 22711005

The rhombohedral-like CuFeO(2) crystals are synthesized via a facile hydrothermal route by using propionaldehyde as a reducing agent. The obtained CuFeO(2) crystals show promising efficiency in the inactivation of bacteriophage Qβ.

Characterization of RNA Damage Under Oxidative Stress in Escherichia Coli

Biological Chemistry. Feb, 2012  |  Pubmed ID: 22718628

We have examined the level of 8-hydroxyguanosine (8-oxo-G), an oxidized form of guanosine, in RNA in Escherichia coli under normal and oxidative stress conditions. The level of 8-oxo-G in RNA rises rapidly and remains high for hours in response to hydrogen peroxide (H₂O₂) challenge in a dose-dependent manner. H₂O₂ induced elevation of 8-oxo-G content is much higher in RNA than that of 8-hydroxydeoxyguanosine (8-oxo-dG) in DNA. Under normal conditions, the 8-oxo-G level is low in RNA isolated from the ribosome and it is nearly three times higher in non-ribosomal RNAs. In contrast, 8-oxo-G generated by a short exposure to H₂O₂ is almost equally distributed in various RNA species, suggesting that although ribosomal RNAs are normally less oxidized, they are not protected against exogenous H₂O₂. Interestingly, highly folded RNA is not protected from oxidation because 8-oxo-G generated by H₂O₂ treatment in vitro increases to approximately the same levels in tRNA and rRNA in both native and denatured forms. Lastly, increased RNA oxidation is closely associated with cell death by oxidative stress. Our data suggests that RNA is a primary target for reactive oxygen species and RNA oxidation is part of the paradox that cells have to deal with under oxidative stress.

MiR-17-5p Targets TP53INP1 and Regulates Cell Proliferation and Apoptosis of Cervical Cancer Cells

IUBMB Life. Jun, 2012  |  Pubmed ID: 22730212

MicroRNAs are a class of small endogenous noncoding RNAs that function as post-transcriptional regulators. Tumor protein p53-induced nuclear protein 1 (TP53INP1) is a p53 target gene and is a major player in the stress response. Here, we identified TP53INP1 as a target of miR-17-5p. miR-17-5p suppressed cell growth and promoted apoptosis of cervical cancer cells, whereas the effects of TP53INP1 were opposite, and ectopic expression of TP53INP1 counteracted the suppression of cell growth caused by miR-17-5p. The same correlations between miR-17-5p and TP53INP1 were observed in cervical cancer tissues. Together, these results indicated that miR-17-5p functions as a tumor suppressor in cervical cancer cells by targeting TP53INP1.

A PROPOSED APPROACH TO INFORMED CONSENT FOR BIOBANKS IN CHINA

Bioethics. Jul, 2012  |  Pubmed ID: 22762502

Biobanks are potential goldmines for genomics research. They have become increasingly common as a means to determine the relationship between lifestyle, environmental exposures and predisposition to genetic disease. More and more countries are developing massive national scale biobanks, including Iceland, the UK and Estonia. Now several large-scale regional and national biobanks are planned in China, such as Shanghai Biobank, which is defined as a key-element in Shanghai's twelfth five-year Development Plan of Science and Technology. It is imperative that the authors who are in charge of the ethical aspect of Shanghai Biobank discuss the ethical aspects of these biobanks up front. Currently there is a great deal of heterogeneity in the approaches to informed consent taken by different countries. In the article, after briefly introducing the biobanks in China, we focus on the three most common approaches: classical informed consent, tiered consent, and one-time general (or blanket) consent, and propose a version of the latter for China, based on compelling arguments.

[Clinical Application of Cone Beam CT in the Treatment of Jaw Bone Cyst]

Hua Xi Kou Qiang Yi Xue Za Zhi = Huaxi Kouqiang Yixue Zazhi = West China Journal of Stomatology. Jun, 2012  |  Pubmed ID: 22768763

To evaluate the value of cone beam CT (CBCT) in the treatment of jaw bone cyst.

The Correlation Between the CLEC16A Gene and Genetic Susceptibility to Type 1 Diabetes in Chinese Children

International Journal of Endocrinology. 2012  |  Pubmed ID: 22778732

Objective. The CLEC16A gene is related to the genetic susceptibility to T1DM with racial variability. This study investigated the association between CLEC16A gene polymorphisms and T1DM in Chinese children. Methods. 131 Chinese children with T1DM were selected for study, and 121 healthy adult blood donors were selected as normal controls. PCR and mass spectrometry was used to study the distributions of 17 CLEC16A alleles in patients and controls. The relationship between CLEC16A gene polymorphisms and T1DM was studied. Results. The distributions of two polymorphisms (rs12921922, rs12931878) of CLEC16A in T1DM and healthy controls were significantly different, while the distributions of other CLEC16A polymorphisms show no significant differences. The alleles of rs12921922 are C and T. The frequency of the T allele was significantly increased in patients versus healthy controls. The alleles of rs12931878 are A and C. The frequencies of the A allele are significantly increased in T1DM patients versus healthy controls. Conclusion. Two polymorphisms in the CLEC16A gene correlate with increased susceptibility to T1DM in Chinese children, revealing that it was another new gene that correlates with susceptibility to T1DM in multiple populations.

[Lateral Closing Wedge Osteotomy for Treatment of Traumatic Cubitus Varus Deformity in Children]

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi = Zhongguo Xiufu Chongjian Waike Zazhi = Chinese Journal of Reparative and Reconstructive Surgery. Jun, 2012  |  Pubmed ID: 22792757

To investigate the effectiveness of lateral closing wedge osteotomy for treatment of traumatic cubitus varus deformity in children.

Measurement of Jugular Foramen to the Adjacent Structures with Thin-section Computed Tomographic Image

The Journal of Craniofacial Surgery. Jul, 2012  |  Pubmed ID: 22801120

This study aimed to measure the bilateral internal aperture of the jugular foramen to internal acoustic pore, bilateral external aperture of the jugular foramen to occipital condyle, and atlas transverse process, so as to provide imaging evidence for different ways of clinical operation and smoothen the operation by protecting important nerves and blood vessels in this area. We scan 120 volunteers' skulls on computed tomography who had no skull base lesions. High-resolution spiral computed tomography multiplane reformation is used to rebuild the three-dimensional reconstruction of the brain. The difference of our study from others is that we select some specific sections to make the measurement more accurately.

Epidemiological Characteristics of Japanese Encephalitis in Guizhou Province, China, 1971-2009

Biomedical and Environmental Sciences : BES. Jun, 2012  |  Pubmed ID: 22840580

The aim of the study was to establish the contemporary epidemiological characteristics of Japanese encephalitis (JE) in Guizhou Province.

Rotavirus Capsid Surface Protein VP4-coated Fe(3)O(4) Nanoparticles As a Theranostic Platform for Cellular Imaging and Drug Delivery

Biomaterials. Nov, 2012  |  Pubmed ID: 22841921

The development of a theranostic nanoplatform based on rotavirus structural protein VP4-coated Fe(3)O(4) nanoparticles (NPs) for dual modality magnetic resonance/fluorescence cellular imaging and drug delivery is reported. VP4 protein was obtained from Escherichia coli approach, and then chemically conjugated to Fe(3)O(4) NPs premodified with meso-2,3-dimercaptosuccinnic acid (DMSA) in the presence of 1-ethyl-3-(3-dimethyaminopropyl) carbodiimide (EDC). Next, the VP4-coated Fe(3)O(4) NPs were loaded with doxorubicin (DOX), a typical anticancer drug, via formation of amide bond through the EDC approach. Prussian blue staining analysis reveals that the VP4-coated Fe(3)O(4) NPs can be internalized efficiently by MA104 and HepG2 cells, thereby significantly improving cellular MRI sensitivity, compared with dextran- and BSA-coated Fe(3)O(4) NPs. In addition, DOX loaded on the VP4-coated Fe(3)O(4) NPs exhibits significant cytotoxicity to the cancer cells (HepG2). The current work provides a general approach toward the rational design and synthesis of a versatile theranostic nanoplatform based on functional protein-coated magnetic NPs with good biocompatibility, biodegradability, and capability of simultaneously performing multimodality imaging and therapy for optimal clinical outcomes.

Evaluation of the Uptake Function of Liver in Rats with Obstructive Jaundice Before and After Relief from Obstruction by Superparamagnetic Iron Oxide-enhanced Magnetic Resonance Imaging

Oncology Letters. Aug, 2012  |  Pubmed ID: 22844357

The aim of this study was to investigate the changes in the uptake function of the liver in rats with obstructive jaundice prior to and following relief from obstructive jaundice, and to investigate whether superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) could be used to assess liver uptake function. In total, 40 male Sprague Dawley rats were randomly assigned into four groups: Obstructive jaundice, internal drainage, external drainage and sham surgery. The common bile ducts in the obstructive jaundice group were ligated. Internal drainage (ID) and external drainage (ED) groups were ligated, followed by internal drainage or external drainage, respectively. The T2 and T2* values of the liver parenchyma were measured. Liver sections were stained with Perls' Prussian blue, and hematoxylin and eosin. The number of SPIO-nanoparticle clusters was counted manually using a microscope. Total bilirubin of the blood was measured. Results showed that the T2 and T2* values and total bilirubin of the obstructive jaundice group were significantly higher compared to the other three groups. The number of SPIO-nanoparticle clusters in the obstructive jaundice group was significantly lower compared to the other three groups. In conclusion, obstructive jaundice suppresses liver uptake function in rats, which may be reversed by internal and external biliary drainage. However, no significant difference was found between the therapeutic effect of ID and ED on liver uptake function. Thus, SPIO-enhanced MRI may be used to evaluate the uptake function of the liver.

[Application of Visualization on Emerging Infectious Disease Based on CiteSpace II]

Zhonghua Liu Xing Bing Xue Za Zhi = Zhonghua Liuxingbingxue Zazhi. Jun, 2012  |  Pubmed ID: 22883276

Validation of Polo-like Kinase 1 As a Therapeutic Target in Pancreatic Cancer Cells

Cancer Biology & Therapy. Oct, 2012  |  Pubmed ID: 22892842

Polo-like kinase 1 (PLK1) is a serine/threonine protein kinase and plays a critical role in mitosis. PLK1 has also been regarded as a valuable target for cancer treatment, and several PLK1 inhibitors are currently undergoing clinical investigations. In this study, our data show that the expression level of PLK1 is upregulated in human pancreatic cancer cells. Molecular modeling studies indicate that DMTC inhibits PLK1 activity through competitive displacement of ATP from its binding pocket. Our data further show that DMTC suppresses the proliferation of pancreatic cancer cells and induces the formation of multinucleated cells, ultimately resulting in apoptosis. In addition, combination index analysis demonstrates that DMTC acts synergistically with the chemotherapeutic drug gemcitabine in inhibiting the proliferation of pancreatic cancer cells. These results thus suggest a potential of using PLK1 inhibitors for the treatment of pancreatic cancer.

Bis[μ-bis-(diphenyl-phosphan-yl)methane-κ(2)P:P']bis-[(isoquinoline-κN)silver(I)] Bis-(trifluoro-methane-sulfonate)-isoquinoline (1/1)

Acta Crystallographica. Section E, Structure Reports Online. Aug, 2012  |  Pubmed ID: 22904705

The title complex, [Ag(2)(C(25)H(22)P(2))(2)(C(9)H(7)N)(2)](CF(3)SO(3))(2)·C(9)H(7)N, was prepared by the reaction of silver(I) trifluoro-methane-sulfonate with isoquinoline and bis-(diphenyl-phosphan-yl)methane (dppm). The dinuclear mol-ecule is located about a center of inversion and the Ag(I) atom is coordinated by two dppm P atoms and one isoquinoline N atom, forming an eight-membered metalla ring. In addition, in the asymmetric unit, there is a half-mol-ecule of isoquinoline located about a center of inversion. Since this mol-ecule does not possess this symmetry, for one position in the ring there is superposition of both a C atom of a C-H group and the isoquinoline N atom. In the structure, the Ag-P distances [2.4296 (9) and 2.4368 (9) Å] agree with the corresponding distances in related structures, while the Ag-N bond length [2.489 (3) Å] is slightly longer than that in related structures. On the other hand, the P-Ag-P angle [156.44 (3)°] is much larger than the corresponding angles in related structures. The trifluoro-methane-sulfonate anions do not coordinate to Ag(I) atoms. As is usually found for these anions, the -CF(3) group is disordered over two orientations [occupancies = 0.57 (12) and 0.43 (12)].

Novel Heterozygous Mutation C.662_663insG Compound with IVS7-2A>G Mutation in SLC26A4 Gene in a Chinese Family with Pendred Syndrome

International Journal of Pediatric Otorhinolaryngology. Nov, 2012  |  Pubmed ID: 22906308

Pendred syndrome is one of the most common hereditary determined diseases in patients with syndromic sensorineural hearing impairment. Mutations in the SLC26A4 gene are a major cause of Pendred syndrome. However, Pendred syndrome is quite rare in China. This investigation aims to identify genetic cause of a Chinese family with Pendred syndrome.

Opposing Roles for Complement Component C5a in Tumor Progression and the Tumor Microenvironment

Journal of Immunology (Baltimore, Md. : 1950). Sep, 2012  |  Pubmed ID: 22914051

Promoting complement (C) activation may enhance immunological mechanisms of anti-tumor Abs for tumor destruction. However, C activation components, such as C5a, trigger inflammation, which can promote tumor growth. We addressed the role of C5a on tumor growth by transfecting both human carcinoma and murine lymphoma with mouse C5a. In vitro growth kinetics of C5a, control vector, or parental cells revealed no significant differences. Tumor-bearing mice with C5a-transfected xenografted tumor cells had significantly less tumor burden as compared with control vector tumors. NK cells and macrophages infiltrated C5a-expressing tumors with significantly greater frequency, whereas vascular endothelial growth factor, arginase, and TNF-α production were significantly less. Tumor-bearing mice with high C5a-producing syngeneic lymphoma cells had significantly accelerated tumor progression with more Gr-1+CD11b+ myeloid cells in the spleen and overall decreased CD4+ and CD8+ T cells in the tumor, tumor-draining lymph nodes, and the spleen. In contrast, tumor-bearing mice with low C5a-producing lymphoma cells had a significantly reduced tumor burden with increased IFN-γ-producing CD4+ and CD8+ T cells in the spleen and tumor-draining lymph nodes. These studies suggest concentration of local C5a within the tumor microenvironment is critical in determining its role in tumor progression.

Novel Evidence Demonstrates That Epithelial-mesenchymal Transition Contributes to Nephrolithiasis-induced Renal Fibrosis

The Journal of Surgical Research. Aug, 2012  |  Pubmed ID: 22920554

PURPOSE: To investigate fibrotic lesions in renal tissues obtained from patients with large calculi, and to selectively evaluate the expression and clinical significance of Twist and E-cadherin in nephrolithiasis patients. METHODS: We recruited 50 patients with kidney stone and 32 matched healthy controls. We determined plasma creatinine (Cr) and corrected Cr clearance (CCr). For the 50 patients, we detected daily urine protein excretion. At the end of percutaneous nephroscopic lithotomy, we performed puncture biopsy to acquire kidney tissue. We obtained normal control kidney tissues from non-nephrolithiasis patients who received a surgical biopsy during open surgery. We determined the expression of Twist and E-cadherin by immunohistochemical staining and scored it with clinical parameters. In addition, we analyzed the degree of expression of Twist and its correlation with long-term renal survival. RESULTS: Overall, the renal function of patients significantly decreased, as indicated by Cr and reduced CCr compared with healthy controls. Activated Twist was strongly expressed in tubular epithelial cells from kidneys of nephrolithiasis patients, whereas we found little positive staining of Twist in normal kidneys. Meanwhile, the expression of E-cadherin was significantly suppressed in kidneys of nephrolithiasis patients. Twist expression was inversely correlated with E-cadherin expression; using multivariate analysis, data showed that the factors influencing renal survival in patients were CCr (relative ratio, 4.39; 95% confidence interval, 1.34-14.38; P = 0.013) and the extent of Twist expression (relative ratio, 3.45; 95% confidence interval, 1.10-10.68; P = 0.033). CONCLUSIONS: Our data suggest that the possible novel EMT marker molecule Twist and Twist staining might be a valuable index predicting renal fibrosis progression in human nephrolithiasis.

Current Understanding of LRRK2 in Parkinson's Disease: Biochemical and Structural Features and Inhibitor Design

Future Medicinal Chemistry. Sep, 2012  |  Pubmed ID: 22924508

Since leucine-rich repeat kinase 2 (LRRK2) was linked to Parkinson's disease in 2004, kinase activity of LRRK2 has been believed to play a critical role in the pathogenesis of Parkinson's disease. As a result, identification of LRRK2 inhibitors has been a focus for drug discovery. However, most LRRK2 mutations do not simply increase kinase activity. In this review we summarize the potential mechanisms that regulate the kinase activity of LRRK2. We outline some currently available kinase inhibitors, including the identification of a DFG-out (type-II) inhibitor. Finally, we discuss the relationship of LRRK2 with tau and α-synuclein. The fact that all three proteins are autophapgy-related provides a future strategy for the identification of LRRK2 physiological substrate(s).

Apolipoprotein E Does Not Cross the Blood-cerebrospinal Fluid Barrier, As Revealed by an Improved Technique for Sampling CSF from Mice

American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. Nov, 2012  |  Pubmed ID: 22933021

Apolipoprotein E (apoE) is a 34-kDa glycoprotein that is important in lipoprotein metabolism both peripherally and centrally. Because it is primarily produced in the liver, apoE observed in the brain or cerebrospinal fluid (CSF) could have originated in the periphery; i.e., circulating apoE may cross the blood-brain barrier (BBB) and/or enter CSF and be taken up by brain cells. To determine whether this occurs, a second-generation adenovirus encoding human apoE3 was administered intravenously (iv) to C57BL/6J mice, and the detection of human apoE3 in the CSF was used as a surrogate measure of central availability of this protein utilizing an improved method for sampling CSF from mice. This improved technique collects mouse CSF samples with a 92% success rate and consistently yields relatively large volumes of CSF with a very low rate of blood contamination, as determined by molecular assessment of apolipoprotein B, a plasma-derived protein that is absent in the central nervous system. Through this improved method, we demonstrated that in mice receiving the administered apoE3 adenovirus, human apoE3 was expressed at high levels in the liver, leading to high levels of human apoE3 in mouse plasma. In contrast, human apoE3 levels in the CSF, as assessed by a sensitive ELISA, were essentially undetectable in human apoE3 adenovirus-treated mice, and comparable to levels in LacZ adenovirus-treated control mice. These data indicate that apoE in the CSF cannot be derived from the plasma pool and, therefore, must be synthesized locally in the brain.

Improvement of Vitreoscilla Hemoglobin Function by Bacillus Licheformis Glutamate-specific Endopeptidase Treatment

Protein Expression and Purification. Nov, 2012  |  Pubmed ID: 22963793

Vitreoscilla hemoglobin (VHb) was widely used in metabolic engineering to improve oxygen utilization in the low oxygen environment. It is sometimes necessary to remove affinity tags because they may impede functions of target proteins. Here we report an efficient method employing Glutamate-specific endopeptidase from Bacillus licheformis (GSE-BL) to perform the cleavage between VHb and His-tag. The optimal length of GSE-BL treatment was 15min. Results of SDS-PAGE and western blot demonstrated that the His-tag of VHb-His(6) was nearly completely removed, the purity of VHb was enhanced from 74% to 99.5%, and the yield of tagless VHb from VHb-His(6) was 92.2%. Results of CO difference spectrum suggested that tagless VHb was more prone to bind to CO compared with VHb-His(6). It was observed that tagless VHb displayed higher catalase activity than VHb-His(6). The enhancement of welan gum yield was more significant by addition of tagless VHb compared with addition of VHb-His(6). This method can be utilized to mass-produce tagless VHb, thus widening the application of VHb in various industries.

Puncture of Foramen Ovale Cranium in Computed Tomography Three-dimensional Reconstruction

The Journal of Craniofacial Surgery. Sep, 2012  |  Pubmed ID: 22976635

ABSTRACT: The study aimed to provide the anatomic data for puncture of foramen ovale cranium in oral cavity. We scan 100 volunteers' skull on computed tomography who have no lesion of skull base, of which the images were for three-dimensional reconstruction. The following observations and measurements were carried out: the shape, size of foramen ovale cranium, and the angle and length of puncture line. The results we got are the following: foramen ovale cranium appears as oval, kidney shape, round, pear shape, and strip shape. Foramen ovale diameter is 8.20 ± 1.54 mm, and width is 4.08 ± 0.73 mm for men and 4.23 ± 0.79 mm for female. The distance from the center of foramen ovale to the maxillary second molar is 51.65 mm for male and 48.77 mm for female. The puncture line is from the center of foramen ovale to the maxillary second molar. The angle of the puncture line with the vertical plane, which is through the midpoint of supraorbital margin and the infraorbital margin, is 40.27 degrees for men and 37.31 degrees for women. The angle of the puncture line with the horizontal plane is 49.37 degrees for men and 52.26 degrees for women. The angle of the puncture line with the sagittal plane is 3.78 degrees. All data between the left and right sides have no statistically significant difference (P > 0.05), but the diameter, the length of the puncture, and the angle of puncture line with the horizontal and vertical have significant differences on sex (P < 0.01). The anatomic character of the foramen ovale cranium has important value on the accuracy of puncture for the treatment of trigeminal neuralgia.

MicroRNA-181b Targets CAMP Responsive Element Binding Protein 1 in Gastric Adenocarcinomas

IUBMB Life. Jul, 2012  |  Pubmed ID: 22539488

MicroRNAs are a class of small endogenous non-coding RNAs that function as post-transcriptional regulators. In our previous study, we found that miR-181b was significantly downregulated in human gastric adenocarcinoma tissue samples compared to the adjacent normal gastric tissues. In this study, we confirm the down-regulation of miR-181b in human gastric cancer cell lines versus the gastric epithelial cells. Overexpression of miR-181b suppressed the proliferation and colony formation rate of gastric cancer cells. miR-181b downregulated the expression of cAMP responsive element binding protein 1 (CREB1) by binding its 3' untranslated region. Overexpression of CREB1 counteracted the suppression of growth in gastric cancer cells caused by ectopic expression of miR-181b. These results indicate that miR-181b may function as a tumor suppressor in gastric adenocarcinoma cells through negative regulation of CREB1.

[Analysis of Larval Excretory-secretory Antigen and Its Immunodiagnosis of Angiostrongyliasis Cantonensis Infection]

Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University. Apr, 2012  |  Pubmed ID: 22543125

To analyze the diagnostic value of larval excretory-secretory antigen in Angiostrongylus cantonensis (LESA) infection.

Protective Effects of Rosuvastatin in Experimental Renal Failure Rats Via Improved Endothelial Function

Biological Research for Nursing. Apr, 2012  |  Pubmed ID: 22544519

Rosuvastatin is a statin (3-hydroxy-3-methylglutaryl coenzyme-A [HMG-CoA] reductase inhibitor) that also serves as an endothelial dysfunction salvager in many disease models. Endothelial dysfunction is assumed to play a pivotal role in the process of chronic renal failure. The authors tested rosuvastatin on a rat model of renal failure with hypertension. Renal failure was induced by 5/6 nephrectomy (Nx). Fisher rats were divided into four groups: sham (n = 10), sham + rosuvastatin (n = 10), Nx (n = 9), and Nx + rosuvastatin (n =10). After 4 weeks, the authors determined renal function, lipid profile, and urine albumin excretion, investigated small renal arteries for endothelium function in response to acetylcholine by perfused juxtamedullary nephron technique, and detected intrarenal inflammatory cytokine expression by real-time reverse transcription polymerase chain reaction. 5/6 Nx significantly increased blood urea nitrogen, serum creatinine, and systolic/diastolic blood pressure, and severe albuminuria developed. The deterioration of renal function, hypertension, and albuminuria were almost normalized by rosuvastatin therapy; in addition, rosuvastatin prevented intrarenal inflammatory cytokine expression and the impaired response to acetylcholine of the renal endothelium. Microscopically, rosuvastatin significantly inhibited the development of progressing renal fibrosis, preserved glomerular structure and tubular integrity, and significantly reduced the degree of tubular atrophy and interstitial fibrosis. In conclusion, HMG-CoA reductase inhibitor rosuvastatin can ameliorate markers of endothelium dysfunction and offers a significant protective effect against the development of renal failure caused by 5/6 Nx in rats. Rosuvastatin might, therefore, represent a novel therapeutic agent for chronic kidney disease.

Regulation of Vascular Endothelial Cell Polarization and Migration by Hsp70/Hsp90-organizing Protein

PloS One. 2012  |  Pubmed ID: 22558459

Hsp70/Hsp90-organizing protein (HOP) is a member of the co-chaperone family, which directly binds to chaperones to regulate their activities. The participation of HOP in cell motility and endothelial cell functions remains largely unknown. In this study, we demonstrate that HOP is critically involved in endothelial cell migration and angiogenesis. Tube formation and capillary sprouting experiments reveal that depletion of HOP expression significantly inhibits vessel formation from endothelial cells. Wound healing and transwell migration assays show that HOP is important for endothelial cell migration. By examination of centrosome reorientation and membrane ruffle dynamics, we find that HOP plays a crucial role in the establishment of cell polarity in response to migratory stimulus. Furthermore, our data show that HOP interacts with tubulin and colocalizes with microtubules in endothelial cells. These findings indicate HOP as a novel regulator of angiogenesis that functions through promoting vascular endothelial cell polarization and migration.

Comment on "The Study of Urban Metabolism and Its Applications to Urban Planning and Design" by Kennedy Et Al. (2011)

Environmental Pollution (Barking, Essex : 1987). Aug, 2012  |  Pubmed ID: 22560710

MicroRNA-19a and -19b Regulate Cervical Carcinoma Cell Proliferation and Invasion by Targeting CUL5

Cancer Letters. Sep, 2012  |  Pubmed ID: 22561557

MicroRNAs (miRNAs) play a key role in the regulation of gene expression. In this study, we demonstrate that microRNA-19a and -19b (miR-19a/b) are highly expressed in human cervical cancer cells and are involved in maintaining the malignant phenotypes of HeLa and C33A cells. Up-regulation of miR-19a and miR-19b promoted cell growth and invasion, whereas knockdown of miR-19a and miR-19b yielded the reverse phenotype. CUL5 was identified as a novel target gene of both miR-19a and miR-19b. CUL5 ectopic over-expression without its 3' untranslated region (UTR) abolished the effect of miR-19a/b on HeLa and C33A cell proliferation and invasion. These results indicated that miR-19a/b directly and negatively regulate CUL5 expression in cervical cancer cells, highlighting the importance of miR-19a and miR-19b and their target genes in tumorigenesis.

A Septal Angle Measured on Computed Tomographic Pulmonary Angiography Can Noninvasively Estimate Pulmonary Vascular Resistance in Patients with Chronic Thromboembolic Pulmonary Hypertension

Journal of Thoracic Imaging. May, 2012  |  Pubmed ID: 22562020

To explore the correlation between a septal angle measured on computed tomographic pulmonary angiography (CTPA) and pulmonary vascular resistance (PVR) determined by right heart catheterization in patients with chronic thromboembolic pulmonary hypertension (CTEPH).

Computational Tools for Quantitative Analysis of Cell Growth Patterns and Morphogenesis in Actively Developing Plant Stem Cell Niches

Methods in Molecular Biology (Clifton, N.J.). 2012  |  Pubmed ID: 22576099

Pattern formation in developmental fields involves precise spatial arrangement of different cell types in a dynamic landscape wherein cells exhibit a variety of behaviors, such as cell division, cell expansion, and cell migration [Reddy (Curr Opin Plant Biol 11:88-931, 2008) and Meyerowitz (Cell 88:299-3082, 2007)]. The information is exchanged between multiple cell layers through cell-cell communication processes to regulate gene expression and cell behaviors in specifying distinct cell types. Therefore, a quantitative and dynamic understanding of the spatial and temporal organization of gene expression and cell behavioral patterns within multilayered and actively growing developmental fields is crucial to model the process of development. The quantification of spatiotemporal dynamics of cell behaviors requires computational tools in image analysis, statistical modeling, pattern recognition, machine learning, and dynamical system identification. Here, we give a brief account of recently developed methods in analyzing both local and global growth patterns in Arabidopsis shoot apical meristems. The computational toolkit can be used to gain new insights into causal relationships among cell growth, cell division, changes in gene expression patterns, and organ development by analyzing various mutants that affect these processes. This may allow us to develop function space models that capture variations in several growth parameters both at local/single-cell level and at global/organ level. In the long run, this may enable clustering of molecular pathways that mediate distinct cell behaviors.

Toxic Effect of Using Twenty Percent Alcohol on Corneal Epithelial Tight Junctions During LASEK

Molecular Medicine Reports. Jul, 2012  |  Pubmed ID: 22576735

The aim of this study was to determine the effect of using 20% alcohol on corneal epithelial tight junctions during laser epithelial keratomileusis (LASEK). Sixty Sprague-Dawley rats were randomly divided into two equal groups. The central area of the rat corneas in one group were demarcated with a 3-mm trephine, treated with 20% alcohol for 45 sec and washed with sterile balanced salt solution. The epithelium was removed by an epithelial microhoe used in LASEK. In the other group, the rat corneal epithelium in the central area was mechanically scraped. The experimental animals were sacrificed at 24, 48, 72, 96 and 120 h after surgery. The levels of the tight junction proteins, claudin-1 and ZO-1, were determined by immunofluorescence and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analyses. We found that at approximately 48 h after surgery, the wounded corneas were replaced by corneals with regenerated epithelium. Immunofluorescence analysis demonstrated that the expressions of claudin-1 and ZO-1 in the corneal epithelium of the alcohol-treated group were weaker compared to the mechanical group at the 24 and 48 h time-points. Semi-quantitative RT-PCR analysis showed that the mRNA levels of claudin-1 and ZO-1 in the central cornea after alcohol treatment were lower compared to those in the mechanical group from 24 to 48 h, with no significant difference after 72 h. Thus, we conclude that the treatment with 20% alcohol during LASEK results in damage to the corneal epitheleal tight junctions and prolongs normal recovery time.

Distribution of PAHs in Tissues of Wetland Plants and the Surrounding Sediments in the Chongming Wetland, Shanghai, China

Chemosphere. May, 2012  |  Pubmed ID: 22578517

Polycyclic aromatic hydrocarbons (PAHs) concentrations were determined in sediments and three types of wetland plants collected from the intertidal flats in the Chongming wetland. The concentration of total PAHs in sediments ranged from 38.7 to 136.2 ngg(-1). Surface sediment concentrations were higher in regions with plant cover than in bare regions. Rhizome-layer sediments (56.8-102.4 ngg(-1)) contained less PAHs than surface sediments (0-5 cm). Concentrations of PAHs in plant tissues ranged from 51.9 to 181.2 ngg(-1), with highest concentrations in the leaves of Scirpus. Most of the PAHs in the leaves and other plant tissues were low molecular weight compounds (LMW, 2-4 rings), and a similar distribution pattern of PAHs in different types of plants was also observed. Source analysis indicated that plants and sediments both came from pyrogenic sources, but plants had additional petroleum contamination. The low ratio of benzo[a]anthracene over chrysene suggests that the wetland PAHs came mainly from long-distance atmospheric transportation. Significant bioaccumulation of PAHs from the sediments into plants was not observed for high molecular weight PAHs (HMW, 5-6 rings) in Chongming wetland. The small RCFs (root concentration factor from sediments) for HMW PAHs and large RCFs for LMW PAHs suggested that roots accumulated LMW PAHs selectively from sediments in Chongming wetland.

Development of a Loop-mediated Isothermal Amplification Assay for Rapid Detection of Bovine Parvovirus

Journal of Virological Methods. May, 2012  |  Pubmed ID: 22584269

A loop-mediated isothermal amplification (LAMP) assay was developed for detection of bovine parvovirus (BPV) DNA. Four primers were designed to recognize six distinct regions on the target DNA based on a highly conserved sequence in the VP2 region of the BPV genome. The optimized LAMP reaction conditions were 8mM Mg(2+), 1.2mM betaine, and an incubation at 63°C for 45min. After amplification the products were detected either by observing a ladder pattern following gel electrophoresis, observation of turbidity, or a color change with the addition of SYBR Green I to the reaction tube. The detection limit of the LAMP assay was 9 copies of BPV-DNA and was 100 times more sensitive than conventional PCR. A ladder pattern of bands after gel electrophoresis was observed for only BPV isolates and showed that the BPV LAMP assay was highly specific without any cross-reactivity with other related viruses. The LAMP assay was evaluated further using 59 field samples and the results were comparable to conventional PCR. The LAMP assay is a simple, rapid and economic detection method; it can provide a useful technique suitable for detection of BPV infection in both field conditions and laboratory settings.

Vaccination with Mannan Protects Mice Against Systemic Aspergillosis

Medical Mycology : Official Publication of the International Society for Human and Animal Mycology. May, 2012  |  Pubmed ID: 22587733

Invasive aspergillosis is a major cause of mortality in immunocompromised patients and therapeutic options are often limited, thus a vaccine would be desirable. We presently studied acid-stable cell-wall mannan (α-1, 6-linked backbone highly branched with α-1, 2; α-1, 3; and β-1, 2-linked manno-oligomers) derived from C. albicans, with or without conjugation to bovine serum albumin (BSA), as a vaccine against systemic aspergillosis. Mice were vaccinated subcutaneously with mannan or mannan-BSA conjugate weekly 3 times, ending 2 weeks prior to infection with A. fumigatus conidia. Results showed that the protection induced by mannan is dose-dependent; 12 mg unconjugated mannan alone or > 0.3 mg mannan-BSA consistently enhanced survival (P < 0.05). Fungal burdens in brains and kidneys were reduced after > 0.3 mg of mannan-BSA (all P < 0.05). Mannan-induced protection was improved about 40-fold by conjugation of BSA to mannan. Mannan-BSA (500 kDa) was more protective than 40 kDa mannan-BSA. Mannan is a candidate for a cross-protective conjugate fungal vaccine.

Pressure-assisted Low-loss Fusion Splicing Between Photonic Crystal Fiber and Single-mode Fiber

Optics Express. Oct, 2012  |  Pubmed ID: 23187209

We demonstrate low-loss splicing between a photonic crystal fiber (PCF) and a single-mode fiber (SMF) with a conventional electric-arc fusion splicer, where nitrogen gas (N₂) with a proper pressure is pumped into the air holes of the PCF to control the air-hole collapse ratio so as to optimize the mode-field match at the joint. The method is applicable to both solid-core and hollow-core PCFs. With this method, we achieve a splice loss (measured at 1550 nm) of ~0.40 dB for a solid-core PCF and ~1.05 dB for a hollow-core PCF. The method could find wide applications in the fabrication of PCF-based devices.

Isolation and Characterization of Polymorphic Microsatellites in Iris Ensata (Iridaceae)

American Journal of Botany. Dec, 2012  |  Pubmed ID: 23196402

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MiR-490-3p Modulates Cell Growth and Epithelial to Mesenchymal Transition of Hepatocellular Carcinoma Cells by Targeting Endoplasmic Reticulum-Golgi Intermediate Compartment Protein 3*(ERGIC3)

The Journal of Biological Chemistry. Dec, 2012  |  Pubmed ID: 23212913

MicroRNAs (miRNAs) are considered to be regulators of various biological processes in cancers, including the epithelial to mesenchymal transition (EMT), which is a key factor in cancer metastasis. In this study, we aimed to clarify the potential roles of miR-490-3p in hepatocellular carcinoma (HCC) cells. Using real time quantitative RT-PCR, we discovered that miR-490-3p was upregulated in HCC tissues and cells compared to the adjacent non-tumor tissues and normal cells. We also found that overexpression of miR-490-3p led to an increase in cell proliferation, migration and invasion abilities and that it contributed to EMT. The inhibition of miR-490-3p had the opposite effect on the cells. We identified endoplasmic reticulum-Golgi intermediate compartment protein 3 (ERGIC3) as a direct target gene for miR-490-3p. Unlike most miRNA-mRNA interactions, miR-490-3p increased ERGIC3 mRNA and protein levels as well as the intensity of expression of the EGFP reporter gene controlled by the 3'UTR of ERGIC3 mRNA. The upregulation by miR-490-3p also required the participation of Ago2. The inhibition of miR-490-3p reduced the expression of ERGIC3. Overexpression of ERGIC3 led to the same effects on HCC cells as miR-490-3p overexpression. Importantly, silencing ERGIC3 reversed the cellular responses mediated by miR-490-3p overexpression. In conclusion, our study indicated for the first time that miR-490-3p functioned like an oncogene in HCC cells and that the inhibition of miR-490-3p might provide an potential treatment approach for HCC patients.

[Distribution Characteristics and Potential Risk of Pcbs in Surface Water from Three Tributaries of Yangtze River in Different Periods]

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.]. Aug, 2012  |  Pubmed ID: 23213875

Eighty-one surface water samples were collected from 3 tributaries of the Yangtze River in different periods. Contents of 28 PCB congeners in surface water samples were measured using Varian CP3800/300 GC-MS/MS technique. PCB8, 18, and 28 are the most predominant PCB congeners in the samples from tributaries. The measured level of PCBs in the samples from the Tuo river, downstream of Ouchi River and Songlihongdao tributary were 1.96-2.59 ng x L(-1), 1.84-2.54 ng x L(-1) and 1.52-2.38 ng x L(-1). The average concentrations of PCBs in the samples were lower than USEPA criterion continuous concentration (14 ng x L(-1)), which were also in the same order of magnitude of those reported with lower levels in European and American countries. The estimated cumulative cancer risk for the local residents who drink water from tributaries were 0.15 x 10(-7)-0.26 x 10(-7), which shows that cancer risk are negligible due to PCBs contamination in these samples.

[Procalcitonin As a Predictor of Trauma Severity and Post-traumatic Sepsis in Children]

Sichuan Da Xue Xue Bao. Yi Xue Ban = Journal of Sichuan University. Medical Science Edition. Sep, 2012  |  Pubmed ID: 23230744

To determine the association of procalcitonin (PCT) with trauma severity and post traumatic sepsis in children.

Delocalization Error of Density-functional Approximations: a Distinct Manifestation in Hydrogen Molecular Chains

The Journal of Chemical Physics. Dec, 2012  |  Pubmed ID: 23231216

Delocalization error is one of the major sources of inaccuracy for mainstream density functional approximations and it is responsible for many of the most glaring failures. Quantitative identification of delocalization error in chemical species and analysis of its influence on calculated thermodynamic properties have remained scarce. In this work we demonstrate unambiguously the effect of delocalization error on a series of hydrogen molecular chains and elucidate the underlying relationship between the error magnitude and system geometry. This work stresses the necessity of minimizing delocalization error associated with density functional approximations.

[Distributions of Matrix-bound Phosphine in Surface Sediments of the Yangtze Estuary]

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, 2012  |  Pubmed ID: 23233971

Concentrations of matrix-bound phosphine (MBP) in the surface sediments of the Yangtze Estuary were investigated in the present study using gas chromatography coupled with a pulsed flame photometric detector (GC-PFPD), and the potential environmental factors were discussed. It was shown that the MBP concentrations were relatively higher in May than in November, with the ranges of 139-426 ng x kg(-1) and 111-192 ng x kg(-1), respectively. Also, there was the significant spatial difference in MBP concentrations at the study area. In addition, it was observed that MBP was significantly related to TP, IP, OP, pH, and activities of APA in the surface sediments. However, no significant correlations were found between MBP, organic carbon and salinity.

Safety of Lamivudine Treatment for Chronic Hepatitis B in Early Pregnancy

World Journal of Gastroenterology : WJG. Dec, 2012  |  Pubmed ID: 23236240

To evaluate the safety of lamivudine (LAM) treatment for chronic hepatitis B in early pregnancy.

In Vitro Assessment of Macleaya Cordata Crude Extract Bioactivity and Anticancer Properties in Normal and Cancerous Human Lung Cells

Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Fur Toxikologische Pathologie. Dec, 2012  |  Pubmed ID: 23238228

The purpose of this study is to assess the bioactivity and anticancer properties of Macleaya cordata crude extract in vitro using normal fetal lung fibroblast MRC5 and adenocarcinomic epithelial cell A549 as model systems,. Treatment of extract induced cell detachment, rounding, and irregularity in shape, in both normal and adenocarcinomic human lung cells, in accompanied of significant reduction in cell proliferation. The data indicated that necrosis appeared to be involved in compromising cell growth in both types of lung cells since membrane permeability and cell granularity were elevated. Although apoptosis was evident, the responses were differential in normal and diseased lung cells. Viability of treated MRC5 cells was reduced in a dose-dependent manner, demonstrating that the normal lung cells are sensitive to the extract. Surprisingly, A549 viability was slightly elevated in response to extract exposure at low concentration, implying that cells survived were metabolically active; the viability was reduced accordingly to treatment at higher concentrations. The present findings demonstrate that the crude extract of M. cordata contains agents affecting the functioning of normal and diseased lung cells in vitro. The observed cytotoxic effects against adenocarcinomic lung cells validate the potential of using M. cordata as herbal intervention in combined with conventional chemotherapy for lung cancer treatment.

Apolipoprotein AIV Requires Cholecystokinin and Vagal Nerves to Suppress Food Intake

Endocrinology. Dec, 2012  |  Pubmed ID: 23027805

Apolipoprotein AIV (apo AIV) and cholecystokinin (CCK) are gastrointestinal satiation signals that are stimulated by fat consumption. Previous studies have demonstrated that peripheral apo AIV cannot cross the blood-brain barrier. In the present study, we hypothesized that peripheral apo AIV uses a CCK-dependent system and intact vagal nerves to relay its satiation signal to the hindbrain. To test this hypothesis, CCK-knockout (CCK-KO) mice and Long-Evan rats that had undergone subdiaphragmatic vagal deafferentation (SDA) were used. Intraperitoneal administration of apo AIV at 100 or 200 μg/kg suppressed food intake of wild-type (WT) mice at 30, 60, and 90 min. In contrast, the same dose did not reduce food intake in the CCK-KO mice. Blockade of the CCK 1 receptor by lorglumide, a CCK 1 receptor antagonist, attenuated apo AIV-induced satiation. Apo AIV at 100 μg/kg reduced food intake in SHAM rats but not in SDA rats. Furthermore, apo AIV elicited an increase in c-Fos-positive cells in the nucleus of the solitary tract (NTS), area postrema, dorsal motor nucleus of the vagus, and adjacent areas of WT mice but elicited only an attenuated increase in these same regions in CCK-KO mice. Apo AIV-induced c-Fos positive cells in the NTS and area postrema of WT mice were reduced by lorglumide. Lastly, apo AIV increased c-Fos positive cells in the NTS of SHAM rats but not in SDA rats. These observations imply that peripheral apo AIV requires an intact CCK system and vagal afferents to activate neurons in the hindbrain to reduce food intake.

Targeted Expression of MiR-34a Using the T-VISA System Suppresses Breast Cancer Cell Growth and Invasion

Molecular Therapy : the Journal of the American Society of Gene Therapy. Dec, 2012  |  Pubmed ID: 23032974

Recurrence and metastasis result in a poor prognosis for breast cancer patients. Recent studies have demonstrated that microRNAs (miRNAs) play vital roles in the development and metastasis of breast cancer. In this study, we investigated the therapeutic potential of miR-34a in breast cancer. We found that miR-34a is downregulated in breast cancer cell lines and tissues, compared with normal cell lines and the adjacent nontumor tissues, respectively. To explore the therapeutic potential of miR-34a, we designed a targeted miR-34a expression plasmid (T-VISA-miR-34a) using the T-VISA system, and evaluated its antitumor effects, efficacy, mechanism of action, and systemic toxicity. T-VISA-miR-34a induced robust, persistent expression of miR-34a, and dramatically suppressed breast cancer cell growth, migration, and invasion in vitro by downregulating the protein expression levels of the miR-34a target genes E2F3, CD44, and SIRT1. In an orthotopic mouse model of breast cancer, intravenous injection of T-VISA-miR-34a:liposomal complex nanoparticles significantly inhibited tumor growth, prolonged survival, and did not induce systemic toxicity. In conclusion, T-VISA-miR-34a lead to robust, specific overexpression of miR-34a in breast cancer cells and induced potent antitumor effects in vitro and in vivo. T-VISA-miR-34a may provide a potentially useful, specific, and safe-targeted therapeutic approach for breast cancer.

[Different Expression of TNF-alpha in Brain and Peripheral Organs After Cerebral Contusion of Rats]

Fa Yi Xue Za Zhi. Aug, 2012  |  Pubmed ID: 23033663

To compare the expression of tumor necrosis factor-alpha (TNF-alpha) between brain and peripheral organs after cerebral contusion in order to provide the scientific theoretical basis for forensic pathological diagnosis and wound age estimation.

Effects of Different Anesthetics on Oscillations in the Rat Olfactory Bulb

Journal of the American Association for Laboratory Animal Science : JAALAS. 2012  |  Pubmed ID: 23043811

Different types of oscillations in the olfactory bulb (OB), including θ (1 to 4 and 5 to 12 Hz), β (13 to 30 Hz), and γ oscillations (31 to 64 and 65 to 90 Hz), are important in olfactory information processing and olfactory-related functions and have been investigated extensively in recent decades. The awake and anesthetized states, 2 different brain conditions, are used widely in electrophysiologic studies of OB. Chloral hydrate, pentobarbital, and urethane are commonly used anesthetics in these studies. However, the influence of these anesthetics on the oscillations has not been reported. In the present study, we recorded the local field potential (LFP) in the OB of rats that were freely moving or anesthetized with these agents. Chloral hydrate and pentobarbital had similar effects: they slightly affected the power of θ oscillations; significantly increased the power of β oscillations; significantly decreased the power of γ oscillations, and showed similar recovery of γ oscillations. Urethane had very different effects: it significantly increased oscillations at 1 to 4 Hz but decreased those at 5 to 12 Hz, decreased β and γ oscillations, and showed no overt recovery in γ oscillations. These results provide experimental evidence of different effects of various anesthetics on OB oscillations and suggest that the choice of anesthetic should consider the experimental application.

[Expressions of OB-R, IRF-1 and GR-β in Airway Smooth Muscle Cells of Obese Rats with Asthma]

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi = Chinese Journal of Cellular and Molecular Immunology. Oct, 2012  |  Pubmed ID: 23046934

To explore the relationship between obesity and difficult-to-treat asthma by observing the expressions of leptin receptor (OB-R), interferon regulatory factor-1 (IRF-1) and glucocorticoid receptor-β (GR-β) in airway smooth muscle cells (ASMCs) of obese rats with asthma.

The Symptoms Get Worse After Pregnancy in Sheehan's Syndrome: A Case Report

Case Reports in Medicine. 2012  |  Pubmed ID: 23049563

Sheehan's syndrome, which is pituitary necrosis after severe postpartum hemorrhage and hypovolemia, may cause hypopituitarism immediately or several years later, depending on the degree of tissue destruction. We report an unusual case, in which a 55-year-old woman with Sheehan's syndrome got worse symptoms after spontaneous labor. In 1998, she had severe postpartum hemorrhage and pituitary necrosis during the third delivery, thus it was diagnosed as Sheehan's syndrome by clinical manifestations, laboratory tests, and magnetic resonance imaging. She was treated by replacement therapy including hydrocortisone and levothyroxine sodium. However, she had the fourth spontaneous pregnancy in 2000 and got worse symptoms after delivery. We carefully concluded that pregnancy provided no evidence against the diagnosis of Sheehan's syndrome because pregnancy might improve hypopituitarism by stimulating the pituitary remnant to undergo hyperplasia and irritating the placenta to secrete hormone. However, pregnancy might aggravate the symptoms by inducing autoimmunity as well. All in all, early diagnosis and adequate medical treatment are important to provide a good prognosis of Sheehan's syndrome.

Molecular Characterization of Differentially Expressed TXNIP Gene and Its Association with Porcine Carcass Traits

Molecular Biology Reports. Dec, 2012  |  Pubmed ID: 23053948

Thioredoxin interacting protein (TXNIP), which plays a regulatory role in lipid metabolism and immune regulation, is down-regulated expressed in F(1) hybrids Landrace × Yorkshire skeletal muscle. Here we described the molecular characterization of porcine TXNIP gene. The full-length cDNA contains a coding sequence of 1,176 bp nucleotides with untranslated regions of 263 bp at 5'-end and 441 bp at 3'-end, respectively. The predicted molecular mass and isoelectric point of porcine TXNIP is 43.81 kDa and 7.385, respectively. The deduced 391 amino acids exhibit high identity with other mammalian TXNIP. The TXNIP gene contains eight coding exons and seven non coding introns, spans approximately 3,348 bp. The expression of porcine TXNIP mRNA is almost absent in Landrace × Yorkshire and lower level in 6-month-old pigs during skeletal muscle development. Other stages and breeds were high level expressed. Statistical analysis showed the TXNIP gene polymorphism (c.575-4T>C) was different between F(1) hybrids and their parents, was highly associated with dressing percentage (DP) and thorax-waist fat thickness (TFT) in the Yorkshire × Meishan F(2) population. The possible role of TXNIP was discussed.

Effects of Pyrolysis Temperature, Time and Leaf Litter and Powder Coal Ash Addition on Sludge-derived Adsorbents for Nitrogen Oxide

Bioresource Technology. Dec, 2012  |  Pubmed ID: 23063747

The objective of this research was to seek a cost effective solution to prepare adsorbents for nitrogen oxide from surplus sludge. Leaf litter and powder coal ash were used as cheap and easily available additives. An adsorbent for nitrogen oxide was prepared by pyrolysis of dried sludge mixed with zinc chloride. Under optimum pyrolysis conditions of 375°C for 90 min and a zinc chloride content of 30%, the surface area of the adsorbent with leaf litter was 514.41 m(2)/g, the surface area of the adsorbent with powder coal ash was 432.34 m(2)/g, respectively, corresponding to an increase of 90.70% and 60.27% when compared to the adsorbent without the additives. The saturated adsorption quantity of the adsorbent with leaf litter reached 271 mg/g at 20°C. The results indicated that the sludge-derived adsorbent was quite promising for nitrogen oxide removal.

Effect of FAK, DLC-1 Gene Expression on OVCAR-3 Proliferation

Molecular Biology Reports. Dec, 2012  |  Pubmed ID: 23079702

The study investigates the effect of FAK, DLC-1 on OVCAR-3 proliferation. FAK gene siRNA vector recombinant plasmid was constructed using RNA interference technique. FAK gene-transfected OVCAR-3 cells, OVCAR-3 cells with DLC-1 gene expression, and OVCAR-3 cells with simultaneous expression of DLC-1 and FAK genes were obtained using gene transfection technology. In addition, siRNA control group and blank control were also given. Effect of FAK, DLC-1 gene expression on OVCAR-3 proliferation was examined by FCM and Cell Counting Kit-8 (CCK-8) methods. Results showed that DLC-1 gene high expression and FAK gene silencing, single silencing FAK gene, and single DLC-1 gene high expression in OVCAR-3 cells may decrease S and G2/M phase proportion of the cell cycle. Moreover, DLC-1 gene high expression and FAK gene silencing in OVCAR-3 cells can display the most significant effect. This confirmed that DLC-1 gene high expression and FAK gene silencing may significantly inhibit the OVCAR-3 cells proliferation. CCK-8 analysis showed that silence FAK gene expression or/and increasing DLC-1 gene expression may decrease OVCAR-3 growth rate. Moreover, simultaneous silence the expression of FAK gene and high expression of DLC-1 gene can display the most significant effect on OVCAR-3 growth. It can be concluded that downregulation of FAK gene expression or/and upregulation of DLC-1 gene expression can all inhibit the OVCAR-3 growth. Moreover, DLC-1 gene expression and FAK gene silencing can display the most marked inhibitory effect on the OVCAR-3 growth.

Association of CYP3A Polymorphisms with the Pharmacokinetics of Cyclosporine A in Early Post-renal Transplant Recipients in China

Acta Pharmacologica Sinica. Dec, 2012  |  Pubmed ID: 23085740

To evaluate retrospectively the association of cytochrome P450 3A (CYP3A) and ATP-binding cassette sub-family B member 1 (ABCB1) gene polymorphisms with the pharmacokinetics of cyclosporine A (CsA) in Chinese renal transplant patients.

High Level of Circulating Endothelial Progenitor Cells Positively Correlates with Serum Vascular Endothelial Growth Factor in Patients with Renal Cell Carcinoma

The Journal of Urology. Dec, 2012  |  Pubmed ID: 23088990

Although accumulated evidence indicates that circulating endothelial progenitor cells contribute to tumor neovascularization, to our knowledge the level of these cells and its correlation with serum vascular endothelial growth factor in patients with renal cell carcinoma have not been studied. We measured this level and investigated its clinical significance in patients with renal cell carcinoma.

In Vitro Assessment of Reproductive Toxicity of Cigarette Smoke and Deleterious Consequences of Maternal Exposure to Its Constituents

Biological Research. 2012  |  Pubmed ID: 23096353

Cigarette smoke is known to be a serious health risk factor and considered reproductively toxic. In the current study, we investigated whether constituents of cigarette smoke, pyrazine, 2-ethylpyridine, and 3-ethylpyridine, adversely affect reproductive functioning such as oocyte maturation and sperm capacitation. Our findings indicated that three smoke components were involved in retardation of oocyte maturation in a dose-dependent manner and the lowest-observed-adverse-effect level (LOAEL) was determined to be 10(-10)M. However, individual smoke components administrated at the LOAEL did not attenuate oocyte maturation, demonstrating that all three toxicants were equally required for the observed growth impairment. When exposed to all three components at 10(-10)M during in vitro capacitation, murine sperm lost forward progression and were unable to show adequate hyperactivation, which is indicative of the incompletion of the capacitation process. Only sperm administrated with 3-ethylpyridine alone showed significant reduction in capacitation status, suggesting the chemical is the one responsible for disrupting sperm capacitation. Taken together, this is the first report that documents the effect of cigarette smoke components on oocyte maturation and sperm capacitation. The present findings demonstrate the adverse effects of smoke constituents of mammalian reproduction and the differences in sensitivity to smoke components between male and female gametes. Since both processes take place in the female reproductive system, our data provide new insights into deleterious consequences of maternal exposure to cigarette smoke.

Microwave-assisted Synthesis and in Vitro Antibacterial Activity of Novel Steroidal Thiosemicarbazone Derivatives

Bioorganic & Medicinal Chemistry Letters. Dec, 2012  |  Pubmed ID: 23102890

Herein, we reported the synthesis of 16 novel steroidal thiosemicarbazone derivatives via the condensation of steroidal ketones and substituted thiosemicarbazides under solvent-free conditions using microwave irradiation. The yields obtained are in the range of 84-96% using microwave method and 46-62% using conventional method. All the synthesized compounds (7a-p) have been characterized by (1)H NMR, ESI-MS, IR and elemental analyses. All the series compounds (7a-p) were evaluated for their antibacterial activity against and the results were compared with the standard drug Amoxicillin. Some of the compounds from the series like 7c, 7o and 7p were equipotent with Amoxicillin against Pseudomonas aeruginosa. Also compound 7h was better than Amoxicillin against Staphylococcus aureus and Bacillus subtilis.

PEGylated Graphene Oxide-mediated Protein Delivery for Cell Function Regulation

ACS Applied Materials & Interfaces. Nov, 2012  |  Pubmed ID: 23106794

Delivery of proteins into cells may alter cellular functions as various proteins are involved in cellular signaling by activating or deactivating the corresponding pathways and, therefore, can be used in cancer therapy. In this study, we have demonstrated for the first time that PEGylated graphene oxide (GO) can be exploited as a nanovector for efficient delivery of proteins into cells. In this approach, GO was functionalized with amine-terminated 6-armed polyethylene glycol (PEG) molecules, thereby providing GO with proper physiological stability and biocompatibility. Proteins were then loaded onto PEG-grafted GO (GO-PEG) with high payload via noncovalent interactions. GO-PEG could deliver proteins to cytoplasm efficiently, protecting them from enzymatic hydrolysis. The protein delivered by GO-PEG reserves its biological activity that regulates the cell fate. As a result, delivery of ribonuclease A (RNase A) led to cell death and transport of protein kinase A (PKA) induced cell growth. Taken together, this work demonstrated the feasibility of PEGlyated GO as a promising protein delivery vector with high biocompatibility, high payload capacity and, more importantly, capabilities of protecting proteins from enzymatic hydrolysis and retaining their biological functions.

Diversity, Abundance, and Activity of Ammonia-oxidizing Bacteria and Archaea in Chongming Eastern Intertidal Sediments

Applied Microbiology and Biotechnology. Oct, 2012  |  Pubmed ID: 23108528

Ammonia oxidation plays a pivotal role in the cycling and removal of nitrogen in aquatic sediments. Certain bacterial groups and a novel group of archaea, which is affiliated with the novel phylum Thaumarchaeota, can perform this initial nitrification step. We examined the diversity and abundance of ammonia-oxidizing β-Proteobacteria (β-AOB) and ammonia-oxidizing archaea (AOA) in the sediments of Chongming eastern tidal flat using the ammonia monooxygenase-α subunit (amoA) gene as functional markers. Clone library analysis showed that AOA had a higher diversity of amoA gene than β-AOB. The β-Proteobacterial amoA community composition correlated significantly with water soluble salts in the sediments, whereas the archaeal amoA community composition was correlated more with nitrate concentrations. Quantitative PCR (qPCR) results indicated that the abundance of β-AOB amoA gene (9.11 × 10(4)-6.47 × 10(5) copies g(-1) sediment) was always greater than that of AOA amoA gene (7.98 × 10(3)-3.51 × 10(5) copies g(-1) sediment) in all the samples analyzed in this study. The β-Proteobacterial amoA gene abundance was closely related to organic carbon, while no significant correlations were observed between archaeal amoA gene abundance and the environmental factors. Potential nitrification rates were significantly greater in summer than in winter and correlated strongly with the abundance of amoA genes. Additionally, a greater contribution of single amoA gene to potential nitrification occurred in summer (1.03-5.39 pmol N copy(-1) day(-1)) compared with winter (0.16-0.38 pmol N copy(-1) day(-1)), suggesting a higher activity of ammonia-oxidizing prokaryotes in warm seasons.

In-line Fiber Optic Interferometric Sensors in Single-mode Fibers

Sensors (Basel, Switzerland). 2012  |  Pubmed ID: 23112608

In-line fiber optic interferometers have attracted intensive attention for their potential sensing applications in refractive index, temperature, pressure and strain measurement, etc. Typical in-line fiber-optic interferometers are of two types: Fabry-Perot interferometers and core-cladding-mode interferometers. It's known that the in-line fiber optic interferometers based on single-mode fibers can exhibit compact structures, easy fabrication and low cost. In this paper, we review two kinds of typical in-line fiber optic interferometers formed in single-mode fibers fabricated with different post-processing techniques. Also, some recently reported specific technologies for fabricating such fiber optic interferometers are presented.

[Logistic Regression Analysis of Platelet Transfusion Effects in Cases of Cancer Patients]

Zhonghua Yi Xue Za Zhi. Sep, 2012  |  Pubmed ID: 23158668

To explore the influencing factors of platelet transfusion effects in cancer patients.

Sclerostin Antibody Increases Bone Volume and Enhances Implant Fixation in a Rat Model

The Journal of Bone and Joint Surgery. American Volume. Sep, 2012  |  Pubmed ID: 22992878

Previous studies have demonstrated that sclerostin blockade is anabolic for bone. This study examined whether systemic administration of sclerostin antibody would increase implant fixation and peri-implant bone volume in a rat model.

MicroRNA-10a is Involved in the Metastatic Process by Regulating Eph Tyrosine Kinase Receptor A4-Mediated Epithelial-mesenchymal Transition and Adhesion in Hepatoma Cells*

Hepatology (Baltimore, Md.). Sep, 2012  |  Pubmed ID: 22996586

MicroRNAs (miRNAs) have been reported to be associated with the development of cancers. However, the function of miRNAs in human hepatocellular carcinoma (HCC) remains largely undefined. Here we found that overexpression of miR-10a promoted the migration and invasion of QGY-7703 and HepG2 cells in vitro but suppressed metastasis in vivo. Cell adhesion assays showed that miR-10a suppressed HCC cell-matrix adhesion, which could explain the results of the in vivo animal experiments. The Eph tyrosine kinase receptor, EphA4, was identified as the direct and functional target gene of miR-10a. Knockdown of EphA4 phenocopied the effect of miR-10a and ectopic expression of EphA4 restored the effect of miR-10a on migration, invasion, and adhesion in HCC cells. We further demonstrated that miR-10a and EphA4 regulated the epithelial-mesenchymal transition process and the β1-integrin pathway to affect cell invasion and adhesion. Conclusion: Our findings highlight the importance of miR-10a in regulating the metastatic properties of HCC by directly targeting EphA4 and may provide new insights into the pathogenesis of HCC. (HEPATOLOGY 2012).

[Long-range Transport Potential of Typical Organic Pollutants in Nanjing]

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.]. Jul, 2012  |  Pubmed ID: 23002609

In this study, the long-range transport potentials (LRTP) of typical organic pollutants including p,p'-DDT, gamma-HCH, BaP and HCB in air and water of Nanjing were estimated using the TaPL3 model. The research results showed that the characteristic travel distances (CTD) of BaP and p,p'-DDT through air were relatively low, 198 km and 255 km, respectively, indicating relatively low LRTP and difficulty in pollution dispersion. In contrast, gamma-HCH and HCB tended to transport over longer distances through water and air, with CTD values of 91 558 km and 19 056 km in water and 1 858 km and 21 104 km in air, respectively, indicating that the dispersion of pollution in air and water of the studied area was relatively easy. Furthermore, the stickiness of gamma-HCH and HCB in water was negative, and the values were -2.1 and -54.86, respectively, indicating that gamma-HCH and HCB tended to remain in the atmosphere. The mass fractions in air after they passed air and achieved the steady state were 0.551% and 2.2%, respectively, whereas the mass fractions in air after they passed water and achieved the steady state were 0. 149% and 1.05% , respectively, which were higher than those of p,p'-DDT and BaP.

Overexpression of FoxM1 is Associated with Tumor Progression in Patients with Clear Cell Renal Cell Carcinoma

Journal of Translational Medicine. 2012  |  Pubmed ID: 23006512

Fork head box M1 (FoxM1) is a proliferation-associated transcription factor essential for cell cycle progression. Numerous studies have documented that FoxM1 has multiple functions in tumorigenesis and its elevated levels are frequently associated with cancer progression. The present study was conducted to investigate the expression of FoxM1 and its prognostic significance in clear cell renal cell carcinoma (ccRCC). Meanwhile, the function of FoxM1 in human ccRCC was further investigated in cell culture models.

HEXIM1 Controls Satellite Cell Expansion After Injury to Regulate Skeletal Muscle Regeneration

The Journal of Clinical Investigation. Nov, 2012  |  Pubmed ID: 23023707

The native capacity of adult skeletal muscles to regenerate is vital to the recovery from physical injuries and dystrophic diseases. Currently, the development of therapeutic interventions has been hindered by the complex regulatory network underlying the process of muscle regeneration. Using a mouse model of skeletal muscle regeneration after injury, we identified hexamethylene bisacetamide inducible 1 (HEXIM1, also referred to as CLP-1), the inhibitory component of the positive transcription elongation factor b (P-TEFb) complex, as a pivotal regulator of skeletal muscle regeneration. Hexim1-haplodeficient muscles exhibited greater mass and preserved function compared with those of WT muscles after injury, as a result of enhanced expansion of satellite cells. Transplanted Hexim1-haplodeficient satellite cells expanded and improved muscle regeneration more effectively than WT satellite cells. Conversely, HEXIM1 overexpression restrained satellite cell proliferation and impeded muscle regeneration. Mechanistically, dissociation of HEXIM1 from P-TEFb and subsequent activation of P-TEFb are required for satellite cell proliferation and the prevention of early myogenic differentiation. These findings suggest a crucial role for the HEXIM1/P-TEFb pathway in the regulation of satellite cell–mediated muscle regeneration and identify HEXIM1 as a potential therapeutic target for degenerative muscular diseases.

Upregulation of Protein Phosphatase 2A and NR3A-Pleiotropic Effect of Simvastatin on Ischemic Stroke Rats

PloS One. 2012  |  Pubmed ID: 23251573

Ca(2+) influxes are regulated by the functional state of N-methyl-D-aspartate receptors (NMDARs). Dephosphorylation of NMDARs subunits decreases Ca(2+) influxes. NR3, a novel subunit of NMDARs, also decreases Ca(2+) influxes by forming new NMDARs with NR1 and NR2. It is meaningful to uncover whether protein phosphatase 2A (PP2A) and NR3A play a role in the protective effect of Simvastatin on ischemic stroke. In the present study, the Sprague-Dawley rats were pretreated with Simvastatin for 7 days before middle cerebral artery occlusion was performed to mimic ischemic stroke. The results showed that Simvastatin decreased brain ischemic infarct area significantly while increasing the expression levels of PP2A and NR3A, thus dephosphorylating the serine sites of NR1 (ser896 and ser897) along with increased enzymatic activities of PP2A. The protein levels of NR3A decreased as the enzymatic activities of PP2A were inhibited by okadaic acid. The results indicated that Simvastatin could protect the cerebrum from ischemic injury through a signaling mechanism involving elevated levels of PP2A and NR3A, and that PP2A might involve in the regulatory mechanism of NR3A expression.

[Study on HPLC Fingerprint Chromatograms of Cell Wall-broken Decoction Pieces of Notoginseng]

Zhong Yao Cai = Zhongyaocai = Journal of Chinese Medicinal Materials. Jul, 2012  |  Pubmed ID: 23252266

To establish the HPLC fingerprint chromatograms of crude Notoginseng, cell wall-broken powder and cell wall-broken decoction pieces of Notoginseng and provide evidence for quality control of cell wall-broken decoction pieces of Notoginseng.

Epigallocatechin Gallate Attenuates Interstitial Cystitis In Human Bladder Urothelium Cells by Modulating Purinergic Receptors

The Journal of Surgical Research. Dec, 2012  |  Pubmed ID: 23260235

BACKGROUND: Epigallocatechin gallate (EGCG) has exhibited antitumor properties against bladder cancer. However, its effects in interstitial cystitis (IC) have not been investigated. METHODS: Here, we performed repeated cystoscopy and re-biopsy of bladder mucosa before and after intravesical irrigation of EGCG in eight patients diagnosed with IC based on clinical and histopathologic assessments. Six normal bladder tissue samples were obtained from age-, race-, and sex-matched asymptomatic control subjects. IC symptom index was used to compare the therapeutic effect in IC patients. Patient-derived bladder epithelial cells were cultured and cell stretch experiments and ATP assays were performed. The expression of purinergic receptors X(1), X(2), and X(3,) and Y(1), Y(2), and Y(11), in biopsied samples was detected by Western blotting and real-time polymerase chain reaction, respectively. Moreover, the expression of inducible NO synthase, phosphorylated Akt, and phosphorylated NF-κB was also assessed. RESULTS: All EGCG-treated patients demonstrated different extents of remission of symptoms. We found a significant upregulation in P2X(1), P2X(2), and P2X(3) receptor proteins and P2Y(1), P2Y(2), and P2Y(11) receptor transcripts in IC patients. However, EGCG therapy attenuated the expression of all purinergic receptors. In addition, EGCG demonstrated prominent antioxidative and antiinflammatory effects via inhibition of the upregulation of iNOS and phosphorylated NF-κB. Furthermore, the stretch-activated release of ATP in cultured bladder urothelial cells was greater in cells derived from IC patients, compared with those from the control patients, but EGCG, at all concentrations tested, effectively abolished the increase in ATP release from stretched IC patient-derived cells. CONCLUSIONS: Our study suggests that inhibition of the expression of purinergic receptors and ATP release in urothelial cells by EGCG supports further development of EGCG as a novel therapeutic option for IC.

Induction of Gene Expression in Bacteria at Optimal Growth Temperatures

Applied Microbiology and Biotechnology. Dec, 2012  |  Pubmed ID: 23271670

Traditional temperature-sensitive systems use either heat shock (40-42 °C) or cold shock (15-23 °C) to induce gene expression at temperatures that are not the optimal temperature for host cell growth (37 °C). This impacts the overall productivity and yield by disturbing cell growth and cellular metabolism. Here, we have developed a new system which controls gene expression in Escherichia coli at more permissive temperatures. The temperature-sensitive cI857-P (L) system and the classic lacI-P ( lacO ) system were connected in series to control the gene of interest. When the culture temperature was lowered, the thermolabile cI857 repressor was activated and blocked the expression of lacI from P (L). Subsequently, the decrease of LacI derepressed the expression of gene of interest from P ( lacO ). Using a green fluorescent protein marker, we demonstrated that (1) gene expression was tightly regulated at 42 °C and strongly induced by lowering temperature to 25-37 °C; (2) different levels of gene expression can be induced by varying culture temperature; and (3) gene expression after induction was sustained until the end of the log phase. We then applied this system in the biosynthesis of acetoin and demonstrated that high yield and production could be achieved using temperature induction. The ability to express proteins at optimal growth temperatures without chemical inducers is advantageous for large-scale and industrial fermentations.

A Targeted In Vivo RNAi Screen Reveals Deubiquitinases As New Regulators of Notch Signaling

G3 (Bethesda, Md.). Dec, 2012  |  Pubmed ID: 23275879

Notch signaling is highly conserved in all metazoan animals and plays critical roles in cell fate specification, cell proliferation, apoptosis, and stem cell maintenance. Although core components of the Notch signaling cascade have been identified, many gaps in the understanding of the Notch signaling pathway remain to be filled. One form of posttranslational regulation, which is controlled by the ubiquitin-proteasome system, is known to modulate Notch signaling. The ubiquitination pathway is a highly coordinated process in which the ubiquitin moiety is either conjugated to or removed from target proteins by opposing E3 ubiquitin ligases and deubiquitinases (DUBs). Several E3 ubiquitin ligases have been implicated in ubiquitin conjugation to the receptors and the ligands of the Notch signaling cascade. In contrast, little is known about a direct role of DUBs in Notch signaling in vivo. Here, we report an in vivo RNA interference screen in Drosophila melanogaster targeting all 45 DUBs that we annotated in the fly genome. We show that at least four DUBs function specifically in the formation of the fly wing margin and/or the specification of the scutellar sensory organ precursors, two processes that are strictly dependent on the balanced Notch signaling activity. Furthermore, we provide genetic evidence suggesting that these DUBs are necessary to positively modulate Notch signaling activity. Our study reveals a conserved molecular mechanism by which protein deubiquitination process contributes to the complex posttranslational regulation of Notch signaling in vivo.

[Anatomic Distribution of Embolus at CT Pulmonary Angiography in Patients Suspected Acute Pulmonary Embolism]

Zhonghua Jie He He Hu Xi Za Zhi = Zhonghua Jiehe He Huxi Zazhi = Chinese Journal of Tuberculosis and Respiratory Diseases. Nov, 2012  |  Pubmed ID: 23290039

To summarize and analyse the morphology and distribution of embolus in patients suspected acute pulmonary embolism.

The Treatment Effect of Diazoxide on 44 Patients with Congenital Hyperinsulinism

Journal of Pediatric Endocrinology & Metabolism : JPEM. 2012  |  Pubmed ID: 23329758

Abstract Objective: To study the treatment effect and safety of diazoxide on patients with congenital hyperinsulinism (CHI). Research design and methods: A total of 44 patients who have been hospitalized to our hospital and used diazoxide as a trial after diagnosis of CHI were chosen as research subjects. The clinical data of the patients were analyzed, and the treatment effects and safety of diazoxide on CHI were evaluated. Results: In the 44 patients studied, the blood glucoses of 36 cases recovered to normal level after using diazoxide, indicating that the 36 patients respond to the treatment of diazoxide. Eight cases still showed severe hypoglycemia after using diazoxide for 10 days, which indicated that the eight patients were unresponsive to diazoxide treatment. Eighteen patients suffered the side effect of fluid retention, and 12 patients suffered transient gastrointestinal reactions. Conclusion: Diazoxide is a first-line treatment of CHI with high safety. Most of the patients with CHI were responsive to diazoxide treatment. Diazoxide should be used as a trial immediately after CHI diagnosis was made.

[Research on the Treatment of Wastewater Containing PVA by Ozonation-activated Sludge Process]

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.]. Nov, 2012  |  Pubmed ID: 23323416

The wastewater containing polyvinyl alcohol (PVA) was characterized with poor biodegradability, and was difficult to remove. In order to find an economically reasonable and practical technology, the research on the removal efficiency of different concentration wastewater containing PVA by ozonation-activated sludge process was studied, and the result was compared with the traditional activated sludge process. The results showed that the ozonation-activated sludge process was not suitable for treating influent with COD below 500 mg x L(-1) and the wastewater PVA concentration was 10-30 mg x L(-1). When the influent COD was between 500-800 mg x L(-1) and the PVA concentration was 15-60 mg x L(-1), the system had advantages on dealing with this kind of wastewater, and the average removal efficiency of COD and PVA were 92.8% and 57.4%, which were better than the traditional activated sludge process 4.1% and 15.2% respectively. In addition, the effluent concentrations of COD could keep between 30-60 mg x L(-1). When the influent COD was 1 000-1 200 mg x L(-1) and the PVA concentration was 20-70 mg x L(-1), the average removal efficiencies of COD and PVA were 90.9% and 45.3%, which were better than the traditional activated sludge process 12.8% and 12.1% respectively, but the effluent should to be further treated. Compared with the traditional activated sludge process, ozonation-activated sludge process had high treatment efficiency, stable running effect, and effectively in dealing with industrial wastewater containing PVA.

Suppression of KCNQ/M (Kv7) Potassium Channels in Dorsal Root Ganglion Neurons Contributes to the Development of Bone Cancer Pain in a Rat Model

Pain. Dec, 2012  |  Pubmed ID: 23352759

Bone cancer pain has a strong impact on the quality of life of patients, but is difficult to treat. Better understanding of the pathogenic mechanisms underlying bone cancer pain will likely lead to the development of more effective treatments. In the present study, we investigated whether inhibition of KCNQ/M channels contributed to the hyperexcitability of primary sensory neurons and to the pathogenesis of bone cancer pain. By using a rat model of bone cancer pain based on intratibial injection of MRMT-1 tumour cells, we documented a prominent decrease in expression of KCNQ2 and KCNQ3 proteins and a reduction of M-current density in small-sized dorsal root ganglia (DRG) neurons, which were associated with enhanced excitability of these DRG neurons and the hyperalgesic behaviours in bone cancer rats. Coincidently, we found that inhibition of KCNQ/M channels with XE-991 caused a robust increase in the excitability of small-sized DRG neurons and produced an obvious mechanical allodynia in normal rats. On the contrary, activation of the KCNQ/M channels with retigabine not only inhibited the hyperexcitability of these small DRG neurons, but also alleviated mechanical allodynia and thermal hyperalgesia in bone cancer rats, and all of these effects of retigabine could be blocked by KCNQ/M-channel antagonist XE-991. These results suggest that repression of KCNQ/M channels leads to the hyperexcitability of primary sensory neurons, which in turn causes bone cancer pain. Thus, suppression of KCNQ/M channels in primary DRG neurons plays a crucial role in the development of bone cancer pain.

MicroRNA 21-mediated Suppression of Sprouty1 by Pokemon Affects Liver Cancer Cell Growth and Proliferation

Journal of Cellular Biochemistry. Jan, 2013  |  Pubmed ID: 23355454

Transcriptional repressor Pokemon is a critical factor in embryogenesis, development, cell proliferation, differentiation and oncogenesis, thus behaving as an oncogene. Oncomine database suggests a potential correlation between the expressions of Pokemon and Sprouty1. This study investigated the regulatory role of Pokemon in Sprouty1 expression and the effect on liver cancer cell growth and proliferation, revealing a novel miR-21-mediated regulatory circuit. In normal (HL-7702) and cancer (QGY-7703) liver cell lines, Sprouty1 expression is inversely correlated with Pokemon levels. Targeted expression or siRNA-mediated silencing showed that Pokemon is a repressor of Sprouty1 expression at both mRNA and protein levels, but Pokemon cannot affect the promoter activity of Sprouty1. Sprouty1 is a target of miR-21 and interestingly, we found that miR-21 is up-regulated by Pokemon in liver cancer cells. Luciferase reporter assays showed that Pokemon up-regulated miR-21 transcription in a dose-dependent manner, and ChIP assay exhibited a direct binding of Pokemon to the miR-21 promoter at -747--399 bp. Site-directed mutagenesis of the GC boxes at -684--679 bp and -652--647 bp of miR-21 promoter abolished the regulatory activity by Pokemon. Furthermore, we found that the modulation of Pokemon and miR-21 expression affected the growth and proliferation of liver cancer cells QGY-7703. In summary, our findings demonstrate that Pokemon suppresses Sprouty1 expression through a miR-21-mediated mechanism, affecting the growth and proliferation of liver cancer cells. This study recognized miR-21 and Sprouty1 as novel targets of the Pokemon regulatory network. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.

MCM2 Expression Levels Predict Diagnosis and Prognosis in Gastric Cardiac Cancer

Histology and Histopathology. Jan, 2013  |  Pubmed ID: 23329420

Background: Gastric Cardiac Cancer (GCC) has high incidence and poor prognosis requiring early screening of high-risk populations. Minichromosome maintenance (MCM) proteins are used as diagnostic-biomarkers in many cancers but not validated for GCC. We evaluate MCM protein 2 (MCM2), comparing it with the validated markers Ki67 and PCNA. Methods: GCC and corresponding cardiac precancerous samples were immunostained with Ki67, MCM2 and PCNA antibodies. Results: 90% of dysplasia samples expressed MCM2, whereas Ki67 and PCNA were expressed in 67% and 80% respectively. The sensitivity and negative predictive values of MCM2 were also superior at 90% and 87%, respectively. Ki67 and PCNA expression was correlated with MCM2, but their expressions seldom reached surface layers, whereas MCM2 manifested mostly in easily accessible superficial layers. Labeling indices (LI) of Ki67 and PCNA were also lower. Significant associations between LI (MCM2), LI (PCNA), and TNM-stages, lymph node metastases and GCC grade were found (P⟨0.05). Increased protein expressions were associated with reduced overall and disease-free survival (P⟨0.05). Although Ki67 and PCNA were significant prognostic factors, there was no significant improvement in multivariate statistical analyses, in contrast to LI (MCM2) findings. Conclusions: MCM2 is a sensitive, specific and efficient biomarker of GCC having potential use in clinic.

Simultaneous Determination of Steroidal and Phenolic Endocrine Disrupting Chemicals in Fish by Ultra-high-performance Liquid Chromatography-mass Spectrometry/mass Spectrometry

Journal of Chromatography. A. Jan, 2013  |  Pubmed ID: 23336947

A sensitive and reliable analytical method based on pressurized liquid extraction (PLE) and ultra-high-performance liquid chromatography equipped with tandem mass spectrometry (UHPLC-MS/MS) has been developed for simultaneously determining the steroidal and phenolic endocrine disrupting chemicals (EDCs) in fish. The most effective extraction of the target EDCs is achieved by using PLE with on-line purification and the parameters have been optimized as follows: extraction solvent - methanol-acetonitrile (1:1, v/v), on-line purification material - 5g alumina (5% water), extraction - 3 cycles, static extraction time - 5min and extraction temperature - 60°C. Compared to the Oasis hydrophilic-lipophilic balance (HLB) solid phase extraction (SPE), freezing-lipid filtration combined with n-hexane defatting clean-up obtains much better recoveries of the target compounds and provide cleaner extracts. The matrix effect (ME) is generally eliminated by using an internal standard method. At spiking levels of 5, 50, and 100ng/g, the mean recoveries vary from 71.2% to 108% for the target EDCs with a relative standard deviation (RSD) less than 16%. The method limit of detection (LOD) and limit of quantitation (LOQ) are 0.04-0.08ng/gdw and 0.07-0.27ng/gdw, respectively. The established method has been successfully applied to fish samples from the local market to determine the target EDCs.

Reversal of Diet-Induced Obesity Increases Insulin Transport into Cerebrospinal Fluid and Restores Sensitivity to the Anorexic Action of Central Insulin in Male Rats

Endocrinology. Jan, 2013  |  Pubmed ID: 23337529

Diet-induced obesity (DIO) reduces the ability of centrally administered insulin to reduce feeding behavior and also reduces the transport of insulin from the periphery to the central nervous system (CNS). The current study was designed to determine whether reversal of high-fat DIO restores the anorexic efficacy of central insulin and whether this is accompanied by restoration of the compromised insulin transport. Adult male Long-Evans rats were initially maintained on either a low-fat chow diet (LFD) or a high-fat diet (HFD). After 22 weeks, half of the animals on the HFD were changed to the LFD, whereas the other half continued on the HFD for an additional 8 weeks, such that there were 3 groups: 1) a LFD control group (Con; n = 18), 2) a HFD-fed, DIO group (n = 17), and 3) a HFD to LFD, DIO-reversal group (DIO-rev; n = 18). The DIO reversal resulted in a significant reduction of body weight and epididymal fat weight relative to the DIO group. Acute central insulin administration (8 mU) reduced food intake and caused weight loss in Con and DIO-rev but not DIO rats. Fasting cerebrospinal fluid insulin was higher in DIO than Con animals. However, after a peripheral bolus injection of insulin, cerebrospinal fluid insulin increased in Con and DIO-rev rats but not in the DIO group. These data provide support for previous reports that DIO inhibits both the central effects of insulin and insulin's transport to the CNS. Importantly, DIO-rev restored sensitivity to the effects of central insulin on food intake and insulin transport into the CNS.

MiR-214 Reduces Cell Survival and Enhances Cisplatin-induced Cytotoxicity Via Down-regulation of Bcl2l2 in Cervical Cancer Cells

FEBS Letters. Jan, 2013  |  Pubmed ID: 23337879

MiR-214 has been shown to inhibit cell growth, migration and invasion. Here we demonstrate that ectopic expression of miR-214 reduces cell survival, induces apoptosis and enhances sensitivity to cisplatin through directly inhibiting Bcl2l2 expression in cervical cancer HeLa and C-33A cells. Further analysis reveals that apoptosis induced by miR-214 is correlated with increased expression of Bax, caspase-9, caspase-8 and caspase-3. Moreover, we show that miR-214 is regulated by DNA methylation and histone deacetylation. Taken together, these data suggest that miR-214 might be a candidate target for the development of novel therapeutic strategies to treat cervical cancer.

Inactivation or Loss of TTP Promotes Invasion in Head and Neck Cancer Via Transcript Stabilization and Secretion of MMP9, MMP2 and IL-6

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. Jan, 2013  |  Pubmed ID: 23349315

PURPOSE: Invasion is the critical step in progression of a pre-cancerous lesion to squamous cell carcinoma of the head and neck (SCCHN). Invasion is regulated by multiple pro-inflammatory mediators. Tristetraprolin (TTP) is an mRNA degrading protein that regulates multiple pro-inflammatory mediators. TTP may serve as an excellent treatment target. Rap1 is a ras-like oncoprotein that induces critical signaling pathways. In this study, the role of rap1 in TTP-mediated invasion was investigated. EXPERIMENTAL DESIGN: Using complementary approaches we modulated TTP and altered expression of IL-6 and MMP2/9, which were quantified by ELISA and zymogram. Invasion was evaluated in vitro using the Oral-Cancer-Equivalent (OCE) 3D model and in vivo in the chick chorioallantoic membrane (CAM). The role of rap1 and p38 were established using knockdown strategies. RESULTS: Downregulation of TTP significantly increased invasion via secretion of MMP9/2 and IL-6. In the novel OCE and CAM invasion models of SCCHN, cells with downregulated TTP destroyed the basement membrane to invade the underlying connective tissue. Rap1 induces p38 mitogen activated protein kinase (p38)-mediated inactivation of TTP. Inactive TTP enhances transcript stability via binding to the 3'-UTR. High IL-6 and MMP9 are prognostic for poor clinical outcomes in SCCHN patients. CONCLUSIONS: Targeting the rap1-p38-TTP cascade is an attractive novel treatment strategy in SCCHN to concurrently suppress multiple mediators of invasion.

The Complete Mitochondrial Genome of the Hybrid of Ctenopharyngodon Idella (♀) × Squaliobarbus Curriculus (♂)

Mitochondrial DNA. Jan, 2013  |  Pubmed ID: 23350616

The complete mitochondrial genome sequence of the hybrid of Ctenopharyngodon idella (♀) × Squaliobarbus curriculus (♂) was determined using PCR-based method. The total length of the mitogenome is 16,609 bp. It contains the typical structure as that of most other vertebrates, including 2 ribosomal RNA genes, 13 protein-coding genes, 22 transfer RNA genes, and 1 non-coding control region (D-loop region). The overall composition of the mitogenome was estimated to be 31.86% for A, 26.08% for T, 26.38% for C, and 15.68% for G, respectively, indicating that an A+T (57.94%)-rich feature occurs in the hybrid mitogenome. Both the termination-associated sequence and three conserved sequence blocks (CSB1, CSB2, and CSB3) were also detected in the D-loop region.

Mitochondrial DNA Sequence of the Hybrid of Squaliobarbus Curriculus (♀) × Ctenopharyngodon Idella (♂)

Mitochondrial DNA. Jan, 2013  |  Pubmed ID: 23350634

In this work, we reported the complete mitochondrial DNA sequence of the hybrid of Squaliobarbus curriculus (♀) × Ctenopharyngodon idella (♂), which was obtained by artificial hybridization. The total length of the mitochondrial genome is 16,616 bp, with the base composition of 31.15% A, 25.02% T, 27.66% C, and 16.17% G. It contains 2 ribosomal RNA genes, 13 protein-coding genes, 22 transfer RNA genes, and a major non-coding control region (D-loop region). The arrangement of these genes is the same as that found in the teleosts. All the protein initiation codons are ATG, except for COX1 that begins with GTG. The complete mitogenome of the hybrid of S. curriculus (♀) × C. idella (♂) provides an important data set for the study in genetic mechanism.

Efficacy of Theophylline Plus Salmeterol/fluticasone Propionate Combination Therapy in Patients with Asthma

Respiratory Medicine. Jan, 2013  |  Pubmed ID: 23290154

OBJECTIVE: To compare the efficacy of theophylline plus salmeterol/fluticasone propionate combination product (SFC) with SFC plus placebo in asthmatic patients. METHODS: In this randomized, stratified, parallel-group study, 325 patients were randomized to receive either 200 mg theophylline plus 50/250 μg SFC or placebo tablet plus 50/250 μg SFC twice daily for 24 weeks. Outcome variables included the level of asthma control (assessed by the Asthma Control Test) and the number of patients experiencing ≥1 exacerbations during the 24-week treatment period. Testing of lung function as well as measurement of the levels of inflammatory markers in induced sputum was performed. RESULTS: There were significantly fewer patients with ≥1 asthma exacerbation in the theophylline plus SFC group (29.6%) when compared with the SFC plus placebo group (46.9%) (p = 0.004). Theophylline plus SFC improved the FEF(25-75%) value, which indicates enhanced small airway function, to a greater extent than SFC plus placebo (66.9 ± 18.8% and 57.4 ± 17.6%, respectively; p < 0.001). A significant decrease in eosinophil count and concentration of eosinophil cationic protein in induced sputum was also seen in the theophylline plus SFC group when compared with the SFC plus placebo group (4.1 ± 2.2% and 6.3 ± 2.7%, 63.6 ± 39.5 μg/L and 89.4 ± 45.6 μg/L, respectively; all p < 0.01). CONCLUSION: The combination of theophylline plus SFC may provide greater protection against asthma exacerbations, and its administration is accompanied by significant improvements in small airway function and airway inflammation.

Overexpression of IGF-1 Attenuates Skeletal Muscle Damage and Accelerates Muscle Regeneration and Functional Recovery After Disuse

Experimental Physiology. Jan, 2013  |  Pubmed ID: 23291913

Skeletal muscle is a highly dynamic tissue that responds to endogenous and external stimuli, including alterations in mechanical loading and growth factors. In particular, the antigravity soleus muscle experiences significant muscle atrophy during disuse and extensive muscle damage upon reloading. Since insulin-like growth factor-1 (IGF-1) has been implicated as a central regulator of muscle repair and modulation of muscle size, we examined the effect of viral mediated overexpression of IGF-1 on the soleus muscle following hindlimb cast immobilization and upon reloading. Recombinant IGF-1 cDNA virus was injected into one of the posterior hindlimbs of the mice, while the contralateral limb was injected with saline (control). At 20 weeks of age, both hindlimbs were immobilized for two weeks to induce muscle atrophy in the soleus and ankle plantar flexor muscle group. Subsequently, the mice were allowed to reambulate and muscle damage and recovery was monitored over a period of 2 to 21 days. The primary finding of this study was that IGF-1 overexpression attenuated reloading-induced muscle damage in the soleus muscle, and accelerated muscle regeneration and force recovery. Muscle T2 assessed by MRI, a nonspecific marker of muscle damage, was significantly lower in IGF-1 injected, compared to contralateral soleus muscles at 2 and 5 days reambulation (P<0.05). The reduced prevalence of muscle damage in IGF-1 injected soleus muscles was confirmed on histology, with a lower fraction area of abnormal muscle tissue in IGF-I injected muscles at 2 days reambulation (33.2±3.3%vs 54.1±3.6%, P<0.05). Evidence of the effect of IGF-1 on muscle regeneration included timely increases in the number of central nuclei (21% at 5 days reambulation), paired-box transcription factor 7 (36% at 5 days), embryonic myosin (37% at 10 days), and elevated MyoD mRNA (7-fold at 2 days) in IGF-1 injected limbs (P<0.05). These findings demonstrate a potential role of IGF-1 in protecting unloaded skeletal muscles from damage and accelerating muscle repair and regeneration.

Sensitive Determination of DNA Based on the Interaction Between Prulifloxacin-terbium(III) Complex and DNA

Luminescence : the Journal of Biological and Chemical Luminescence. Jan, 2013  |  Pubmed ID: 23297144

A simple spectrofluorimetric method is described for the determination of DNA, based on its enhancement of the fluorescence intensity of prulifloxacin (PUFX)-Tb(3+) . The luminescence intensity of the PUFX-Tb(3+) complex increased up to 10-fold after adding DNA. The excitation and emission wavelengths were 345 and 545 nm, respectively. Under optimum conditions, variations in the fluorescence intensity showed a good linear relationship with the concentration of hsDNA in the range of 3.0 × 10(-9) to 1.0 × 10(-6)  g/mL, with a correlation coefficient (R) of 0.997, and the detection limit was 2.1 × 10(-9)  g/mL. The method was successfully applied to the determination of DNA in synthetic samples, and recoveries were in the range 97.3-102.0%. The mechanism of fluorescence enhancement of the PUFX-Tb(3+) complex by DNA is also discussed. The mechanism may involve formation of a ternary complex mainly by intercalation binding together with weak electrostatic interaction, which will increase the energy transition from ligand to Tb(3+) , increasing the rigidity of the complex, and decreasing the radiationless energy loss through O-H vibration of the H(2) O molecule in the PUFX-Tb(3+) complex. Compared with the previous DNA probes, the proposed method is not only more robust and friendly to the environment, but also of relatively higher sensitivity. Copyright © 2012 John Wiley & Sons, Ltd. Copyright © 2013 John Wiley & Sons, Ltd.

Clinical Effect of Catgut Implantation at Acupoints for Allergic Rhinitis: Study Protocol for a Randomized Controlled Trial

Trials. Jan, 2013  |  Pubmed ID: 23302264

ABSTRACT: BACKGROUND: Catgut implantation at acupoints has been used in China to treatment allergic rhinitis (AR) for a long time. However, its efficacy and safety in the treatment of AR is controversial due to the poor quality of the clinical trial of this therapy. This study aims to identify whether catgut implantation at acupoints is indeed an effective and safe treatment for patients with persistent or intermittent allergic rhinitis (PER or IAR) by comparing with sham catgut implantation treatment.Methods and design: This study compares real versus sham catgut implantation at acupoints in 242 patients with a history of PER or IAR and with a positive skin prick test (SPT). The trial will be conducted in the Teaching Hospital of Chengdu University of Traditional Chinese Medicine. In the study, patients will be randomly assigned by computer-generated randomization list into two groups and assessed prior to treatment. Then, they will receive two sessions of treatments (once per 2 weeks) for 4 consecutive weeks and have a follow-up phase of 12 weeks. The administration of catgut implantation (or sham-control) at acupoints follows the guidelines for clinical research on acupuncture (WHO Regional Publication, Western Pacific Series No.15, 1995), and is performed double-blindly by a well-trained physician in acupuncture. The main outcome measures include the primary and secondary indicators. Primary indicators are subjective symptoms scores evaluated by visual analogue scales (VAS) and Rhinoconjunctivitis Quality of Life Questionnaires (RQLQ). The secondary indicators are the results of laboratory examinations, such as serum allergen-specific IgE, nasal inflammatory cells counts (mast cells, eosinophils, and T cells) and nitric oxide concentration in nasal excretion. The use of anti-allergic medication will also be recorded as one of the secondary indicators. Furthermore, adverse events will be recorded and analyzed. If any participants withdraw from the trial, intention-to-treat analysis (ITT) and per-protocol (PP) analysis will be performed. DISCUSSION: The important features of this trial include the randomization procedures, large sample, and a standardized protocol of catgut implantation at acupoints. This trial will be the first study with a high evidence level in China in order to assess the efficacy and safety of catgut implantation at acupoints in treatment of AR following a randomized, double-blind sham-controlled method.Trial registration: Chinese Clinical Trial Registry: ChiCTR-TRC-12002191.

Antibiotics in the Surface Water of the Yangtze Estuary: Occurrence, Distribution and Risk Assessment

Environmental Pollution (Barking, Essex : 1987). Jan, 2013  |  Pubmed ID: 23313734

The occurrence and distribution of five groups of antibiotics were investigated in the surface water of Yangtze Estuary over four seasons. Of the 20 antibiotics, only sulfamerazine was not detected at all sampling sites, indicating widespread occurrence of antibiotic residues in the study area. Detection frequencies and concentrations of antibiotics were generally higher in January, indicating that low flow conditions and low temperature might enhance the persistence of antibiotics in water. Antibiotic levels varied with location, with the highest concentrations being observed around river discharge and sewage outfall. Furthermore, a positive correlation between total antibiotic and DOC concentrations revealed the significant role played by DOC. Risk assessment based on single compound exposure showed that sulfapyridine and sulfamethoxazole could cause medium risk to daphnid in the Yangtze Estuary.

Solution-based Synthesis of Pyrite Films with Enhanced Photocurrent Generation

Chemical Communications (Cambridge, England). Feb, 2013  |  Pubmed ID: 23287968

A direct and scalable approach for the synthesis of iron sulfide (FeS(2)) films on flexible iron (Fe) foil in aqueous solution has been developed.

CIP2A is a Predictor of Survival and a Novel Therapeutic Target in Bladder Urothelial Cell Carcinoma

Medical Oncology (Northwood, London, England). Mar, 2013  |  Pubmed ID: 23275123

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified human oncoprotein that stabilizes the c-MYC protein. Herein, we aimed to investigate its expression pattern, clinical significance, and biological function in urothelial cell carcinoma (UCC) of the bladder. CIP2A expression was examined in 20 fresh bladder UCC tissues and paired adjacent normal bladder tissues by RT-PCR and Western blot. Immunohistochemistry for CIP2A was performed on additional 117 bladder UCC tissues. The clinical significance of CIP2A expression was analyzed. CIP2A downregulation was performed in bladder UCC cell line T24 with high abundance of CIP2A, and the effects of CIP2A silencing on cell proliferation, migration, invasion in vitro, and tumor growth in vivo were evaluated. We found that CIP2A expression was upregulated in bladder UCC tissues relative to adjacent normal bladder tissues. Clinicopathological analysis showed that CIP2A expression was significantly associated with tumor stage (P = 0.004), histological grade (P = 0.007), and lymph node status (P = 0.001). The Kaplan-Meier survival curves revealed that CIP2A expression was associated with poor prognosis in bladder UCC patients (log-rank value = 14.704, P < 0.001). CIP2A expression was an independent prognostic marker of overall patient survival in a multivariate analysis (P = 0.015). Knockdown of the CIP2A expression reduced cell proliferation, anchorage-independent growth, migration, invasion, and tumor growth in xenograft model mice. Our findings suggest that CIP2A is an independent predictor of poor prognosis of bladder UCC patients, and inhibition of its expression might be of therapeutic significance.

PARP-2 Knockdown Protects Cardiomyocytes from Hypertrophy Via Activation of SIRT1

Biochemical and Biophysical Research Communications. Jan, 2013  |  Pubmed ID: 23261455

Poly(ADP-ribosyl)ation catalyzed by the poly(ADP-ribose) polymerases (PARPs) is an immediate post-translational modification of proteins with a homopolymeric chain of repeating ADP-ribose units. It is involved in various cellular processes, such as cell survival and death, transcription, DNA repair and cell division. Inhibitors of PARPs have been documented to be useful in different pathological conditions. Recently, activation of PARP-1, the founding member of PARP family, has been revealed to participate in the development and progression of cardiac hypertrophy and heart failure. However, the roles of other PARPs in cardiovascular system remain to be clarified. PARP-2 shares 69% similarity with PARP-1 in catalytic domains, but their functions do not fully overlap. In this study, we show the first evidence that PARP-2 is involved in cardiac hypertrophy. The mRNA and protein levels of PARP-2 were significantly increased in AngII-stimulated rat cardiomyocytes as well as in hearts of rats submitted to pressure overload. PARP-2 knockdown protected cardiomyocytes from hypertrophy, which may be attributed to activation of SIRT1. These findings shed new light on the understanding of PARP-2-related cardiomyopathy, and suggest the potential application of PARP-2 inhibitors in cardiac hypertrophy.

DNA Damage Response in Peritumoral Regions of Oesophageal Cancer Microenvironment

Carcinogenesis. Jan, 2013  |  Pubmed ID: 23027622

Oesophageal cancer is a highly aggressive disease, ranking among the 10 most common cancers in the world. Oesophageal cancer patients often suffer from multi-origin tumours, and therefore, it is important to improve our understanding of the complex biology, which underpins microenvironmental interactions in this disease. Extensive evidence indicates that the interaction of tumours with their microenvironment may play a crucial role in tumour initiation and progression. In this study, we analysed DNA damage response (DDR), immune cell invasion and cancer progression in 47 patients with oesophageal cancer from three different regions (tumour tissue, tumour-proximal non-malignant tissue and distant non-malignant tissue). Accumulated DDR (positive staining for γH2AX and phospho-ATM) was evident within tumour tissue and significantly increased in non-malignant tissue surrounding the tumour cells although activation of p53 by phosphorylation at serine 15 was observed only in tumour tissue. The level of DDR detected in cancer microenvironment depended largely on the distance from the tumour, as stronger DDR was observed in tumour-proximal areas compared with that in tumour-distant tissue. Induction of DDR in non-malignant tissues correlated with increased invasion of lymphocytes and macrophages and with precancerous progression. Our results support that DDR is induced in oesophageal cancer surrounding non-malignant epithelial cells, via activation of an inflammatory process, which in turn contributes to the progression of precancerous lesions. These findings provide novel pathological evidence for inflammation and DDR in influencing non-metastatic progression of cancer in its microenvironment.

Human Long-term Culture Initiating Cell Assay

Methods in Molecular Biology (Clifton, N.J.). 2013  |  Pubmed ID: 23179836

The long-term culture initiating cell (LTC-IC) assay, founded on the bone marrow long-term culture (LTC) system, measures primitive hematopoietic stem cells (termed LTC-IC) based on their capacity to produce myeloid progeny for at least 5 weeks. Adaptations of the LTC system including the use of stromal cell lines, application of limiting dilution analysis, and estimation of average hematopoietic progenitor output per LTC-IC under defined conditions have made it possible to accurately determine LTC-IC content in minimally separated and highly purified cell populations from human hematopoietic tissue sources such as bone marrow, peripheral blood, cord blood, fetal liver as well as cord blood and mobilized peripheral blood. Methodologies for measuring human LTC-IC using bulk cultures, limiting dilution analysis, and single cell cultures are described.

Potent Retro-Inverso D-Peptide for Simultaneous Targeting of Angiogenic Blood Vasculature and Tumor Cells

Bioconjugate Chemistry. Jan, 2013  |  Pubmed ID: 23241015

The application of tumor targeting ligands for the treatment of cancer holds the promise of enhanced efficacy and reduced toxicity. L-SP5 ((L)(SVSVGMKPSPRP)) is a peptide that recognizes tumor neovasculature but not normal blood vessels (Lee et al., Cancer Res.2007, 67, 10958-65). The current report presents the design and application of D-SP5 ((D)(PRPSPKMGVSVS)), a novel retro-inverso analogue of L-SP5. Peptides D-SP5 and parental L-SP5 are shown to compete for the same target sites of a yet unknown cellular target and possess a dual-targeting bioactivity for both activated endothelial cells (HUVEC) and several tumor cell lines. Cellular uptake experiments showed superior in vitro targeting abilities of D-SP5 compared with L-SP5, such as enhanced internalization into stimulated HUVEC or KB, U87, and SGC tumor cells. A radioligand receptor binding assay revealed a higher cell affinity of D-SP5 in all tested cell lines, with K(d) values for D-SP5 about 2-fold lower than for L-SP5. An up to 3-fold higher maximum binding capacity (B(max)) to cells of D-SP5 was noted. Fluorescein-labeled D-SP5 upon intravenous administration displayed strong association with tumor endothelium. D-SP5-conjugated PEG-DSPE micelles displayed enhanced tumor homing (evidenced by near-infrared in vivo imaging). When loaded with doxorubicin, D-SP5 micelles could markedly suppress tumor growth with higher efficacy than L-SP5 micelles both in vitro and in vivo in KB tumor xenografts. In summary, the data demonstrate that D-SP5 displays higher binding affinities toward tumor endothelium as well as tumor cells and enhanced tumor targeting capability in vitro and in vivo.

Oral Squamous Carcinoma Cells Secrete RANKL Directly Supporting Osteolytic Bone Loss

Oral Oncology. Feb, 2013  |  Pubmed ID: 22989723

Local invasion of bone is a frequent complication of oral squamous cell carcinoma (OSCC). Development of these osteolytic lesions is mediated by osteoclasts. Receptor activation of NF-κB ligand (RANKL) signaling, counteracted by osteoprotegerin (OPG), regulates osteoclastogenesis. Previous studies in rodent models have demonstrated that inhibition of RANKL decreases tumor growth and lesions within bone. However, the contributory role of OSCC cells to this disease process has yet to be defined.