Phosphoinositide 3-kinase/Akt and Nuclear Factor κB Pathways Are Involved in Tumor Necrosis Factor-related Apoptosis-inducing Ligand Resistance in Human Gastric Cancer Cells

Molecular Medicine Reports. May-Jun, 2010  |  Pubmed ID: 21472268

Human gastric cancer cells are generally believed to be less sensitive to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis, but the events responsible for this resistance are as yet unclear. In this study, we investigated the role of the phosphoinositide 3-kinase (PI3K)/Akt, nuclear factor κB (NF-κB) and extracellular signal-regulated kinase (ERK) signaling pathways in the TRAIL resistance of gastric cancer cells. TRAIL failed to induce observable apoptosis in the three cell lines. Further investigation revealed that TRAIL engagement led to the activation of PI3K/Akt as well as of NF-κB. The inhibition of PI3K/Akt by a specific inhibitor facilitated TRAIL-induced apoptosis. Blockage of TRAIL-induced NF-κB activation by transient transfection with a phosphorylation-defective mutant IκB also enhanced the sensitivity of cells towards TRAIL. Meanwhile, ERKs were highly activated in the resting cells and were not further activated by TRAIL treatment. However, the inhibition of ERK activity by PD98059 also enhanced the apoptosis-inducing ability of TRAIL. Our data demonstrated that the activation of PI3K/Akt and NF-κB by TRAIL is responsible for resistance to TRAIL in human gastric cancer cells. Blockage of survival signals significantly enhances the apoptosis induced by TRAIL.

Effects of Infrasound at 8 Hz 90 DB/130 DB on NMDAR1 Expression and Changes in Intracellular Calcium Ion Concentration in the Hippocampus of Rats

Molecular Medicine Reports. Nov-Dec, 2010  |  Pubmed ID: 21472333

In the present study, we investigated the effect of infrasound on the expression of N-methyl-D-aspartate (NMDAR)1 as well as changes in intracellular calcium ion concentration ([Ca2+]i) in the hippocampus of rats. Sprague-Dawley (SD) rats were exposed for 2 h daily to infrasound at 8 Hz 90 dB or 130 dB, and NMDAR1 expression was examined on days 1, 7, 14, 21 and 28. The expression of NMDAR1 in the rat hippocampus upon exposure to infrasound at 8 Hz 90 dB sound pressure level (SPL) showed an initial decrease on day 1, an increase on days 7 and 14, a further decrease on day 21, and a return to normal levels on day 28. The peak level was observed on day 14 in every examined subregion of the hippocampus. By contrast, exposure to infrasound at 8 Hz 130 dB SPL had opposite effects, showing an increase on day 1, a decrease on day 7, a decrease to the lowest point on days 14, another increase on day 21 and a return to normal levels on day 28. The lowest expression of NMDAR1 was found in the CA1 and CA3 regions on day 14 and in the DG region on day 7 with exposure at 130 dB. There were significant differences in [Ca2+]i concentration on days 14 and 21 with infrasonic exposure at both 8 Hz 90 dB and 130 dB, but no significant differences in [Ca2+]i concentration on days 1, 7 and 28 compared to the control group. The highest [Ca2+]i level was noted on day 14 with infrasound exposure at 8 Hz 130 dB. These changes suggest that 8 Hz 90 dB/130 dB infrasound exposure induced certain reversible changes in NMDAR1 expression and [Ca2+]i concentration in hippocampal cells, which may influence mnemonic functions related to the hippocampus.

Syphilitic Proctitis Mimicking Rectal Cancer: A Case Report

World Journal of Gastrointestinal Pathophysiology. Aug, 2010  |  Pubmed ID: 21607150

Syphilitic proctitis is a rare disease. It usually presents as proctitis, ulcer and neoplasm but lacks pathognomonic clinical symptoms. It is, therefore, difficult to diagnose and is occasionally treated inappropriately. We report the case of a 51-year-old man who had a hard, ulcerated mass, which occupied the circumference of the rectal wall and which mimicked a rectal tumor. Fortunately, positive finding from routine toluidine red unheated serum test and treponema pallidum particle agglutination tests made us reevaluate the patient and led us to suspect syphilitic proctitis. This diagnosis was finally confirmed after successful penicillin G benzathine therapy which made surgery unnecessary.

Autologous Bone Marrow Mesenchymal Stem Cell Transplantation in Liver Failure Patients Caused by Hepatitis B: Short-term and Long-term Outcomes

Hepatology (Baltimore, Md.). Sep, 2011  |  Pubmed ID: 21608000

Our study aimed to investigate the short-term efficacy and long-term prognosis of liver failure patients caused by hepatitis B after a single transplantation with autologous marrow mesenchymal stem cells (MMSCs). A total of 527 inpatients with liver failure caused by hepatitis B were recruited and received the same medical treatments, among whom 53 patients underwent a single transplantation with autologous MMSCs. A total of 105 patients matched for age, sex, and biochemical indexes, including alanine aminotransferase (ALT), albumin, total bilirubin (TBIL), prothrombin time (PT), and Model for End-Stage Liver Disease (MELD), comprised the control group. A total of 120 mL of bone marrow was obtained from each patient and then diluted and separated. Then, the MMSC suspension was slowly transfused into the liver through the proper hepatic artery. The success rate of transplantation was 100%, without serious side effects or complications. Levels of ALB, TBIL, and PT and MELD score of patients in the transplantation group were markedly improved from 2-3 weeks after transplantation, compared with those in the control group. At 192 weeks of follow-up, there were no dramatic differences in incidence of hepatocellular carcinoma (HCC) or mortality between the two groups. Additionally, there were no significant differences in the incidence of HCC or mortality between patients with and without cirrhosis in the transplantation group. Conclusion: Autologous MMSC transplantation is safe for liver failure patients caused by chronic hepatitis B. Short-term efficacy was favorable, but long-term outcomes were not markedly improved. In respect to several parameters, this method is preferable for patients with liver cirrhosis and may have potential for reducing their incidence of HCC and mortality.

A Ratiometric Fluorescent Probe for Cyanide Based on FRET

Organic & Biomolecular Chemistry. Jul, 2011  |  Pubmed ID: 21614384

On the basis of FRET from 4-(N,N-dimethylamino)benzamide to fluorescein, a new ratiometric fluorescence probe bearing a hydrazone binding unit was developed for highly selective and sensitive detection of CN(-) in aqueous solution.

Intra-amniotic Administration of Exogenous Pulmonary Surfactant for Improving in Lung Maturity of Fetal Rabbits with Intrauterine Infection Caused by Premature Rupture of Membranes

Bosnian Journal of Basic Medical Sciences / Udruženje Basičnih Mediciniskih Znanosti = Association of Basic Medical Sciences. May, 2011  |  Pubmed ID: 21619557

This study was to investigate the effect of intra-amniotic administration of pulmonary surfactant (PS) on lung maturation in conditions of experimentally induced premature rupture of membranes (PROM) and intrauterine infection of rabbits. To establish animal (rabbit) models of intrauterine infection caused by PROM, E. coli was intrauterinely injected in 24-and 26-day pregnant animals. Twenty healthy pregnancy adult Japanese white rabbits were divided into three groups: the infection group (8 rabbits), infection group with intra-amniotic PS administration (8 rabbits) and healthy controls (4 rabbits). Ultrastructure changes in the lung were observed under an electron microscope 19.5 hours after intervention. The results showed that the lung infection levels of fetal rabbits in the infection group and the infection group with PS had no significant difference. Bacillus bodies and infiltrated inflammatory cells can be occasionally seen in the alveoli, bronchial lumen, and cytoplasm.The type II alveolar epithelial cells (AT-II) were decreased in the infection group than that in control group. Lamellar bodies showed vacuolation changes and different levels of apoptosis. In the infection group with PS, the count of AT-II did not show an obvious decrease. Lamellar bodies increased, and different secretion forms appeared. Also, there was little apoptosis and no obvious collagen fiber hyperplasia in antenatal administration of PS group. We believe that once PROM has happened, intrauterine infection and inflammation stimulated a cascade reaction on the fetal lung, leading to abnormal changes in the alveolar ultrastructure. Intra-amniotic administration of PS can improve the fetal lung ultrastructure and its maturity.

[The Curative Effects of Different Drugs on Liver Cell Damage of Rats Induced by Acute Nickel Carbonyl Poisoning]

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi = Zhonghua Laodong Weisheng Zhiyebing Zazhi = Chinese Journal of Industrial Hygiene and Occupational Diseases. Feb, 2011  |  Pubmed ID: 21619836

To assess the curative effects of different drugs on liver cell damage of rats induced by acute nickel carbonyl poisoning.

[The Changes of Blood Neurotransmitter Levels in Workers Occupationally Exposed to Ethylbenzene]

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi = Zhonghua Laodong Weisheng Zhiyebing Zazhi = Chinese Journal of Industrial Hygiene and Occupational Diseases. Feb, 2011  |  Pubmed ID: 21619842

To explore the effects of occupational ethylbenzene exposure on blood neurotransmitter levels in population.

[The Neurobehavioral Effects of Population Occupationally Exposed to Ethylbenzene]

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi = Zhonghua Laodong Weisheng Zhiyebing Zazhi = Chinese Journal of Industrial Hygiene and Occupational Diseases. Feb, 2011  |  Pubmed ID: 21619843

To evaluate the influence of ethylbenzene on the neurobehavior of occupationally exposed workers.

Cloning and Characterization of a Novel CoA-ligase Gene from Penicillium Chrysogenum

Folia Microbiologica. May, 2011  |  Pubmed ID: 21625874

A novel phenylacetic acid (PAA)-induced CoA-ligase-encoding gene, designated as phlC, has been cloned from penicillin-producing fungus Penicillium chrysogenum. The open reading frame of phlC cDNA was 1671 bp and encoded a 556 amino acid residues protein with the consensus AMP binding site and a peroxisomal targeting signal 1 on its C terminus. The deduced amino acid sequence showed 37% and 38% identity with characterized P. chrysogenum Phl and PhlB protein, respectively. Functional recombinant PhlC protein was overexpressed in Escherichia coli. The purified recombinant enzyme was capable to convert PAA into its corresponding CoA ester with a specific activity of 129.5 ± 3.026 pmol/min per mg protein. Similar to Phl and PhlB, PhlC displayed broad substrate spectrum and showed higher activities to medium- and long-chain fatty acids. The catalytic properties of PhlC have been determined and compared to those of Phl and PhlB.

Toxicity Prediction of Dioxins and Dioxins-like Compounds Based on the Molecular Fragments Variable Connectivity Index

Bulletin of Environmental Contamination and Toxicology. Aug, 2011  |  Pubmed ID: 21626111

The toxicity of 95 doxins and dioxin-like compounds was investigated by quantitative structure-activity relationship (QSAR) with the molecular fragments variable connectivity index (mfVCI). For each of the four homologues, the models have good fitting (R² > 0.80) and predictive (Q²EXT > 0.80) ability. The models developed from more than one homologues are also satisfactory with R² > 0.80 and Q²EXT > 0.77. The molecular fragments weights have the ability to diagnose the contribution of the molecular fragments to the toxicity of the compounds. The mfVCI may play an important role in the development of molecular descriptors in further QSAR research.

Direct Synthesis of Aryl Ketones by Palladium-catalyzed Desulfinative Addition of Sodium Sulfinates to Nitriles

Chemistry (Weinheim an Der Bergstrasse, Germany). Jul, 2011  |  Pubmed ID: 21626598

Screening of the Common Culture Conditions Affecting Crystallinity of Bacterial Cellulose

Journal of Industrial Microbiology & Biotechnology. Dec, 2011  |  Pubmed ID: 21630052

By analyzing with X-ray diffraction and FT-IR spectroscopy, the main effective factors among common culture conditions on crystallinity index and I(α) fraction of cellulose produced by Gluconacetobacter xylinus were examined with Plackett-Burman design experiment. Varying pH value in the medium by adjusting the composition of citrate buffer or by adding HCl/NaOH solution indicates it is the content of citrate buffer rather than its function of pH buffering that gives the influence on crystallinity. Further experiment reveals that Na+ concentration of 0.174 mol/l in medium with citrate buffer added would decrease the crystallinity index significantly. Comparison of carbon sources shows that fructose leads to a higher crystallinity index than glucose, which suggests a relationship between crystallinity and production speed of bacterial cellulose affected by carbon sources. An interesting phenomenon was that a longer period of cultivation would decrease the crystallinity of bacterial cellulose. The reason is assumed to be the dense network of cellulose formed by bacterial cells that restrict the motion of themselves as the incubation period extends. Though the effect of inoculum age is still unclear, the influence on crystallinity of bacterial cellulose caused by variation of some ordinary culture conditions can be drawn out from data of this work.

Impaired Adrenergic- and Corticotropic-axis Outflow During Exercise in Chronic Obstructive Pulmonary Disease

Metabolism: Clinical and Experimental. Nov, 2011  |  Pubmed ID: 21632072

Exercise stimulates coordinated release of the sympathoadrenal hormones adrenocorticotropic hormone (ACTH), cortisol, norepinephrine (NE), and epinephrine (Epi). The study hypothesis was that chronic obstructive pulmonary disease (COPD) is marked by heightened sympathoadrenal outflow at comparable relative workloads. The location of the study was at a clinical research unit. Eight healthy men and 9 men with stable COPD (forced expiratory volume at 1 second <75% predicted) were studied. Volunteers rested (baseline) or exercised at individual submaximal (35% ± 5%) or maximal oxygen consumption. Blood was sampled every 2 minutes for 40 minutes concurrently. Two-way analysis of covariance was applied to examine group (healthy/COPD) and exercise (3 levels) effects on ACTH, cortisol, NE, and Epi release and regularity (estimable by approximate entropy). The timing of peak hormone concentrations was Epi, 14 minutes; NE, 16 minutes; ACTH, 22 minutes; and cortisol, 34 minutes in both cohorts. Type of exercise regimen influenced all 4 hormones (each P < .001), and subject group (control vs COPD) affected cortisol (P < .001) and Epi (P = .048) responses. Exercise regimen and group together controlled ACTH, cortisol, and Epi (each P < .001), but not NE, responses. In particular, endocrine responses were attenuated in COPD compared with control subjects. Approximate entropy analysis also identified loss of maximal exercise-induced ACTH-secretory regularity in COPD patients (P = .042). These outcomes demonstrate impaired rather than augmented exercise-associated sympathocorticotropic-axis outflow in patients with COPD even when outcomes are normalized to maximal oxygen consumption, suggesting that factors other than fitness are at work.

Studies of H4R Antagonists Using 3D-QSAR, Molecular Docking and Molecular Dynamics

Journal of Molecular Modeling. Jun, 2011  |  Pubmed ID: 21647664

Three-dimensional quantitative structure-activity relationship studies were performed on a series of 88 histamine receptor 4 (H4R) antagonists in an attempt to elucidate the 3D structural features required for activity. Several in silico modeling approaches, including comparative molecular field analysis (CoMFA), comparative similarity indices analysis (CoMSIA), molecular docking, and molecular dynamics (MD), were carried out. The results show that both the ligand-based CoMFA model (Q (2) = 0.548, R (ncv) (2)  = 0.870, R (pre) (2)  = 0.879, SEE = 0.410, SEP = 0.386) and the CoMSIA model (Q (2) = 0.526, R (ncv) (2) =0.866, R (pre) (2)  = 0.848, SEE = 0.416, SEP = 0.413) are acceptable, as they show good predictive capabilities. Furthermore, a combined analysis incorporating CoMFA, CoMSIA contour maps and MD results shows that (1) compounds with bulky or hydrophobic substituents at positions 4-6 in ring A (R2 substituent), positively charged or hydrogen-bonding (HB) donor groups in the R1 substituent, and hydrophilic or HB acceptor groups in ring C show enhanced biological activities, and (2) the key amino acids in the binding pocket are TRP67, LEU71, ASP94, TYR95, PHE263 and GLN266. To our best knowledge, this work is the first to report the 3D-QSAR modeling of these H4R antagonists. The conclusions of this work may lead to a better understanding of the mechanism of antagonism and aid in the design of new, more potent H4R antagonists.

Structural Models Describing Placebo Treatment Effects in Schizophrenia and Other Neuropsychiatric Disorders

Clinical Pharmacokinetics. Jul, 2011  |  Pubmed ID: 21651312

Large variation in placebo response within and among clinical trials can substantially affect conclusions about the efficacy of new medications in psychiatry. Developing a robust placebo model to describe the placebo response is important to facilitate quantification of drug effects, and eventually to guide the design of clinical trials for psychiatric treatment via a model-based simulation approach. In addition, high dropout rates are very common in the placebo arm of psychiatric clinical trials. While developing models to evaluate the effect of placebo response, the data from patients who drop out of the trial should be considered for accurate interpretation of the results. The objective of this paper is to review the various empirical and semi-mechanistic models that have been used to quantify the placebo response in schizophrenia trials. Pros and cons of each placebo model are discussed. Additionally, placebo models used in other neuropsychiatric disorders like depression, Alzheimer's disease and Parkinson's disease are also reviewed with the objective of finding those placebo models that could be useful for clinical studies of both acute and chronic schizophrenic disease conditions. Better understanding of the patterns of dropout and the factors leading to dropouts are crucial in identifying the true placebo response. We therefore also review dropout models that are used in the development of models for treatment effects and in the optimization of clinical trials by simulation approaches. The use of an appropriate modelling strategy that is capable of identifying the potential sources of variable placebo responses and dropout rates is recommended for improving the sensitivity in discriminating between the effects of active treatment and placebo.

Which is the Optimal Biologically Effective Dose of Stereotactic Body Radiotherapy for Stage I Non-small-cell Lung Cancer? A Meta-analysis

International Journal of Radiation Oncology, Biology, Physics. Nov, 2011  |  Pubmed ID: 21658853

To assess the relationship between biologically effective dose (BED) and efficacy of stereotactic body radiation therapy (SBRT) and to explore the optimal BED range for Stage I non-small-cell lung cancer (NSCLC).

Comparative Effects of Chlorpyrifos in Wild Type and Cannabinoid Cb1 Receptor Knockout Mice

Toxicology and Applied Pharmacology. Nov, 2011  |  Pubmed ID: 21672545

Endocannabinoids (eCBs) modulate neurotransmission by inhibiting the release of a variety of neurotransmitters. The cannabinoid receptor agonist WIN 55.212-2 (WIN) can modulate organophosphorus (OP) anticholinesterase toxicity in rats, presumably by inhibiting acetylcholine (ACh) release. Some OP anticholinesterases also inhibit eCB-degrading enzymes. We studied the effects of the OP insecticide chlorpyrifos (CPF) on cholinergic signs of toxicity, cholinesterase activity and ACh release in tissues from wild type (+/+) and cannabinoid CB1 receptor knockout (-/-) mice. Mice of both genotypes (n=5-6/treatment group) were challenged with CPF (300 mg/kg, 2 ml/kg in peanut oil, sc) and evaluated for functional and neurochemical changes. Both genotypes exhibited similar cholinergic signs and cholinesterase inhibition (82-95% at 48h after dosing) in cortex, cerebellum and heart. WIN reduced depolarization-induced ACh release in vitro in hippocampal slices from wild type mice, but had no effect in hippocampal slices from knockouts or in striatal slices from either genotype. Chlorpyrifos oxon (CPO, 100 μM) reduced release in hippocampal slices from both genotypes in vitro, but with a greater reduction in tissues from wild types (21% vs 12%). CPO had no significant in vitro effect on ACh release in striatum. CPF reduced ACh release in hippocampus from both genotypes ex vivo, but reduction was again significantly greater in tissues from wild types (52% vs 36%). In striatum, CPF led to a similar reduction (20-23%) in tissues from both genotypes. Thus, while CB1 deletion in mice had little influence on the expression of acute toxicity following CPF, CPF- or CPO-induced changes in ACh release appeared sensitive to modulation by CB1-mediated eCB signaling in a brain-regional manner.

C-Reactive Protein Predicts the Severity of Coronary Artery Disease Beyond Low-Density Lipoprotein Cholesterol

Angiology. Jun, 2011  |  Pubmed ID: 21676965

Prospective studies and clinical trials have shown that C-reactive protein (CRP) independently predicts the occurrence of cardiovascular events, even in individuals without hypercholesterolemia. We evaluated whether CRP can predict the severity of coronary artery stenosis in patients with lower low-density lipoprotein cholesterol (LDL-C) levels. A total of 418 patients with lower LDL-C (<3.37 mmol/L) who underwent coronary angiography were recruited. The median levels of CRP increased according to the number of stenotic vessels. Multivariable adjustment model indicated that CRP was associated with the severity of coronary artery disease (CAD) in the top to the bottom third comparison of CRP levels, yielding an odds ratio of 1.72 (95% confidence interval: 1.08-2.74); this trend was preserved after excluding the confounding effect of statin treatment. C-reactive protein may serve as a useful biomarker for improving the risk assessment and secondary prevention of CAD patients without hypercholesterolemia.

Enhanced Efficacy of Sirolimus-eluting Bioabsorbable Magnesium Alloy Stents in the Prevention of Restenosis

Journal of Endovascular Therapy : an Official Journal of the International Society of Endovascular Specialists. Jun, 2011  |  Pubmed ID: 21679083

To determine the efficacy of sirolimus-eluting bioabsorbable magnesium alloy stents (SEBMAS) in restenosis prevention.

Structural Insights into the Down-regulation of Overexpressed P185(her2/neu) Protein of Transformed Cells by the Antibody ChA21

The Journal of Biological Chemistry. Sep, 2011  |  Pubmed ID: 21680730

p185(her2/neu) belongs to the ErbB receptor tyrosine kinase family, which has been associated with human breast, ovarian, and lung cancers. Targeted therapies employing ectodomain-specific p185(her2/neu) monoclonal antibodies (mAbs) have demonstrated clinical efficacy for breast cancer. Our previous studies have shown that p185(her2/neu) mAbs are able to disable the kinase activity of homomeric and heteromeric kinase complexes and induce the conversion of the malignant to normal phenotype. We previously developed a chimeric antibody chA21 that specifically inhibits the growth of p185(her2/neu)-overexpressing cancer cells in vitro and in vivo. Herein, we report the crystal structure of the single-chain Fv of chA21 in complex with an N-terminal fragment of p185(her2/neu), which reveals that chA21 binds a region opposite to the dimerization interface, indicating that chA21 does not directly disrupt the dimerization. In contrast, the bivalent chA21 leads to internalization and down-regulation of p185(her2/neu). We propose a structure-based model in which chA21 cross-links two p185(her2/neu) molecules on separate homo- or heterodimers to form a large oligomer in the cell membrane. This model reveals a mechanism for mAbs to drive the receptors into the internalization/degradation path from the inactive hypophosphorylated tetramers formed dynamically by active dimers during a "physiologic process."

A Better Way to Do Small-for-size Liver Transplantation in Rats

Frontiers of Medicine. Mar, 2011  |  Pubmed ID: 21681683

Establishing a model for small-for-size liver transplantation is the basis for this study of partial and living donor graft liver transplantation. This study aims to explore a simpler and more effective way of establishing a 30% small-for-size liver transplantation in rats. Sprague-Dawley rats were selected as the donors and recipients. Small-for-size orthotopic liver transplantation was performed using Kamada's two-cuff method. The donor's liver was flushed via the abdominal aorta and hepatectomy was performed in situ. The animals were divided into three groups depending on the graft selected, with 40 pairs of rats in each group. In group I, the median lobe of the liver was used as graft; in group II, the right half of the median lobe and the right lobe were used as graft; and in group III, the median and right lobes were used as graft. In groups I and II, the bodyweights of donors were the same as those of recipients; however, in group III the bodyweights of donors were 100-120 g less than those of the recipients. The duration needed for transplantation, the 7-day survival rates, and the technical complication rates were compared among these three groups. The time required for hepatectomy was shorter in group III compared with groups I and II (8.8±0.7 min vs. 11.5±1.1 min and 10.1±1.0 min, P = 0.001). The cold ischemia time for the grafts, the anhepatic times, and the transplantation times for the recipients were not significantly different among the three groups. Compared with groups I and II, the incidence of bleeding, bile leakage, and inferior vena caval strictures were significantly decreased in group III (P<0.05). No significant differences between the three groups were found based on other complications after the operation (P>0.05). Group III had better 7-day survival rates and longer median survival times but the differences were not statistically significant. The method of small for donor bodyweight using the median and right lobes for grafting may be a more effective and simpler way of establishing a 30% small-for-size liver transplantation in rats, as shown by the shorter hepatectomy time and the occurrence of fewer complications after the operation.

Transcriptional Down-regulation of Brca1 and E-cadherin by CtBP1 in Breast Cancer

Molecular Carcinogenesis. Jun, 2011  |  Pubmed ID: 21681822

Carboxyl-terminal binding protein 1 (CtBP1) is a transcriptional co-repressor with oncogenic potential. Immunohistochemistry staining using human breast cancer tissue arrays revealed that 92% of invasive ductal breast cancer cases have CtBP1-positive staining compared to 4% CtBP1-positive in normal breast tissue. To explore the functional impact of CtBP1 in breast cancer, we examined CtBP1's transcriptional regulation of known tumor suppressors, breast cancer susceptibility gene 1 (Brca1), and E-cadherin. We found CtBP1 was recruited to the promoter regions of Brca1 and E-cadherin genes in breast cancer cells. Concomitantly, Brca1 loss was detected in 57% and E-cadherin loss was detected in 76% of human invasive ductal breast cancers, and correlated with CtBP1 nuclear staining in these lesions. Importantly, siRNA knock down of CtBP1 restored Brca1 and E-cadherin expression in breast cancer cell lines, implying CtBP1 down-regulates Brca1 and E-cadherin genes in human breast cancer. This study provides evidence that although genetic loss of Brca1 and E-cadherin are infrequent in breast cancer, they are down-regulated at the transcriptional level by CtBP1 expression. Thus, CtBP1 activation could be a potential biomarker for breast cancer development. © 2011 Wiley-Liss, Inc.

Integrated Transcriptional and Proteomic Analysis with in Vitro Biochemical Assay Reveal the Important Role of CYP3A46 in T-2 Toxin Hydroxylation in Porcine Primary Hepatocytes

Molecular & Cellular Proteomics : MCP. Sep, 2011  |  Pubmed ID: 21685020

Both T-2 toxin and its metabolites are highly potent mycotoxins that can cause severe human and animal diseases upon exposure. Understanding the toxic mechanism and biotransformation process of T-2 toxin at a cellular level is essential for the development of counter-measures. We investigated the effect of T-2 toxin in porcine primary hepatocytes using porcine genome array and two-dimensional difference gel electrophoresis with matrix-assisted laser desorption/ionization tandem time of flight mass spectrometry. Integrated transcriptional and proteomic analysis demonstrated that T-2 toxin adversely affected porcine hepatocytes by initiating lipid metabolism disorder, oxidative stress response, and apoptosis. In addition, xenobiotic metabolism genes, including cytochrome P450 3As (CYP3A46 and CYP3A39), carboxylesterase 1Cs (CES1C4 and CES1C5), and epoxide hydrolase (EPHX1), increased in T-2 toxin treatment cells. Using HepG2 cells to over-express the recombinant xenobiotic metabolism genes above and rapid resolution liquid chromatography/tandem mass spectrometry to detect metabolites of T-2 toxin, we determined that porcine CYP3A46 mainly catalyzed T-2 to form 3'-hydroxy-T-2, which was further confirmed by purified CYP3A46 protein. However, recombinant porcine CES1C5 and EPHX1 did not enhance hydrolysis and de-epoxidation of T-2 implying that other esterases and epoxide hydrolases may play dominant roles in those reactions.

A Wulff-type Boronate for Boronate Affinity Capture of Cis-diol Compounds at Medium Acidic PH Condition

Chemical Communications (Cambridge, England). Jul, 2011  |  Pubmed ID: 21687891

A new Wulff-type boronate was designed and synthesized. Upon immobilization on a polymeric monolith and acidified as boronic acid, the ligand exhibited specific boronate affinity to cis-diol compounds at medium acidic pH condition.

A Cross-sectional Study of the Microeconomic Impact of Cardiovascular Disease Hospitalization in Four Low- and Middle-income Countries

PloS One. 2011  |  Pubmed ID: 21695127

To estimate individual and household economic impact of cardiovascular disease (CVD) in selected low- and middle-income countries (LMIC).

Ultrasensitive DNA Detection Based on Au Nanoparticles and Isothermal Circular Double-assisted Electrochemiluminescence Signal Amplification

Chemical Communications (Cambridge, England). Aug, 2011  |  Pubmed ID: 21695310

We report here an ultrasensitive DNA detection approach which combines Au NPs enhanced electrochemiluminescence (ECL) of the CdS nanocrystal (NC) film with isothermal circular amplification reaction of polymerase and nicking endonuclease (NEase). By the double-signal amplification, this approach could sensitively respond down to 5 aM DNA.

Drug Release Behaviors of a PH Sensitive Semi-interpenetrating Polymer Network Hydrogel Composed of Poly(vinyl Alcohol) and Star Poly[2-(dimethylamino)ethyl Methacrylate]

International Journal of Pharmaceutics. Sep, 2011  |  Pubmed ID: 21704139

A series of pH sensitive semi-interpenetrating polymer network (semi-IPN) structural hydrogels composed of poly(vinyl alcohol) (PVA) and 21-arm star poly[2-(dimethylamino)ethyl methacrylate] (star PDMAEMA) with different molecular weight were prepared. Riboflavin was used as a model drug to evaluate the drug loading capacities and drug release behaviors of the semi-IPN structural hydrogels. The molecular weight of the star PDMAEMA polymers was calculated by GPC, and the formation of semi-IPN structure was confirmed by FTIR and SEM. It was found that the molecular weight of star PDMAEMA has significant effect on the structure, swelling ratio and drug release behaviors of the semi-IPN hydrogel at different pH conditions. The results suggested that the PVA/star PDMAEMA-50,000 hydrogel exhibited highest swelling ratio and drug loading capacity. The pH-sensitive semi-IPN hydrogel based on star PDMAEMA could be a promising drug delivery system due to the controllable porous structure.

[Mobile Phone Based Wireless Microscopy Imaging Technology]

Zhongguo Yi Liao Qi Xie Za Zhi = Chinese Journal of Medical Instrumentation. Mar, 2011  |  Pubmed ID: 21706785

This article proposes a new device named "Wireless Cellscope" that combining mobile phone and optical microscope together. The established wireless microscope platform consists of mobile phone, network monitor, miniaturized microscope or high resolution microscope etc. A series of conceptual experiments were performed on microscopic observation of ordinary objects and mice tumor tissue slices. It was demonstrated that, the new method could acquire microscopy images via a wireless way, which is spatially independent. With small size and low cost, the device thus developed has rather wide applicability in non-disturbing investigation of cell/tissue culture and long distance observation of dangerous biological sample etc.

[VOCs Analyzing and Odor Indicator Selecting in Ambient Air of Landfill Area]

Huan Jing Ke Xue= Huanjing Kexue / [bian Ji, Zhongguo Ke Xue Yuan Huan Jing Ke Xue Wei Yuan Hui "Huan Jing Ke Xue" Bian Ji Wei Yuan Hui.]. Apr, 2011  |  Pubmed ID: 21717729

The odor pollution of landfill is one of seriously pollutions in city ambient area. Main pollution points in the landfill area have been detected by preliminary research. For a particular purpose to recover the materials changing in odor dispersion process and to find out odor indication material, GC-MS method was used to detect materials in the different site at down wind direction. Then, similarity coefficient of VOCs (volatile organic compounds) composition between every two site were calculated and compared to look for changing regular of odor pollution in diffusion process. The odor pollution indictor material has be found in the materials that appeared in down wind direction of operation area and compared its' olfaction threshold. The results show that: there have 19 types of common materials in the landfill area, including monoaromatics, alkanes and halogenated compounds; Materials in the air of operation area site has marked influence on down windward direction air of landfill, and m-xlyene has been selected as odor pollution indictor of landfill air by this research.

Protective Autophagy Antagonizes Oxaliplatin-induced Apoptosis in Gastric Cancer Cells

Chinese Journal of Cancer. Jul, 2011  |  Pubmed ID: 21718595

Oxaliplatin-based chemotherapy is used for treating gastric cancer. Autophagy has been extensively implicated in cancer cells; however, its function is not fully understood. Our study aimed to determine if oxaliplatin induce autophagy in gastric cancer MGC803 cells and to assess the effect of autophagy on apoptosis induced by oxaliplatin. MGC803 cells were cultured with oxaliplatin. Cell proliferation was measured using MTT assay, and apoptosis was determined by flow cytometry. Protein expression was detected by Western blot. Autophagy was observed using fluorescent microscopy. Our results showed that the rate of apoptosis was 9.73% and 16.36% when MGC803 cells were treated with 5 and 20 μg/mL oxaliplatin for 24 h, respectively. In addition, caspase activation and poly ADP-ribose polymerase (PARP) cleavage were detected. Furthermore, when MGC803 cells were treated with oxaliplatin for 24 h, an accumulation of punctate LC3 and an increase of LC3-II protein were also detected, indicating the activation of autophagy. Phosphorylation of Akt and mTOR were inhibited by oxaliplatin. Compared to oxaliplatin alone, the combination of autophagy inhibitor chlorochine and oxaliplatin significantly enhanced the inhibition of cell proliferation and the induction of cell apoptosis. In conclusion, oxaliplatin-induced protective autophagy partially prevents apoptosis in gastric cancer MGC803 cells. The combination of autophagy inhibitor and oxaliplatin may be a new therapeutic option for gastric cancer.

Lithium, an Anti-psychotic Drug, Greatly Enhances the Generation of Induced Pluripotent Stem Cells

Cell Research. Oct, 2011  |  Pubmed ID: 21727907

Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by defined factors. The low efficiency of reprogramming and genomic integration of oncogenes and viral vectors limited the potential application of iPSCs. Here we report that Lithium (Li), a drug used to treat mood disorders, greatly enhances iPSC generation from both mouse embryonic fibroblast and human umbilical vein endothelial cells. Li facilitates iPSC generation with one (Oct4) or two factors (OS or OK). The effect of Li on promoting reprogramming only partially depends on its major target GSK3β. Unlike other GSK3β inhibitors, Li not only increases the expression of Nanog, but also enhances the transcriptional activity of Nanog. We also found that Li exerts its effect by promoting epigenetic modifications via downregulation of LSD1, a H3K4-specific histone demethylase. Knocking down LSD1 partially mimics Li's effect in enhancing reprogramming. Our results not only provide a straightforward method to improve the iPSC generation efficiency, but also identified a histone demethylase as a critical modulator for somatic cell reprogramming.

Dietary Factors Associated with Hypertension

Nature Reviews. Cardiology. Aug, 2011  |  Pubmed ID: 21727918

Hypertension is one of the major risk factors for cardiovascular disease, with an impact on global health. Multiple studies have suggested that various dietary factors are associated with blood pressure (BP) and hypertension. The purpose of this Review is to provide up-to-date knowledge on the impact of dietary factors on BP and hypertension, to compare types and recommended intakes of dietary factors in hypertension management and prevention guidelines from different countries and organizations, and to outline global population-based healthy-diet strategies for hypertension control. Of the 27 dietary factors we evaluated on the basis of specified review criteria, 17 have been proposed to have protective effects against hypertension, six were proposed to be risk factors for hypertension, and the association between BP and the remaining factors was considered inconclusive. Excessive sodium intake is a causal risk factor for hypertension, whereas a diet rich in fruit, vegetables, and low-fat dairy products, and low in sodium and saturated fat has been recommended to prevent and reduce hypertension on the basis of strong evidence. Notable differences exist in the recommended types and intakes of dietary factors among available hypertension management and prevention guidelines. Available evidence supports the vigorous implementation of dietary strategies against hypertension through population-based, national action plans.

A Study on the Thermochemotherapy Effect of Nanosized As2O3/MZF Thermosensitive Magnetoliposomes on Experimental Hepatoma in Vitro and in Vivo

Nanotechnology. Aug, 2011  |  Pubmed ID: 21730756

In this paper, we describe the synthesis and characterization of a nanosized, thermosensitive magnetoliposome encapsulating magnetic nanoparticles (MZFs) and antitumor drugs (As(2)O(3)). The nanoliposomes were spherical and mostly single volume, with an average diameter of 128.2 nm. Differential scanning calorimetry (DSC) showed a liposome phase transition temperature of 42.71 °C. After that, we studied the liposomes' anti-hepatoma effect in vitro and in vivo. The antitumor effect of the nanoliposomes on human hepatoma cells, SMMC-7721, and changes in expression of apoptosis-related proteins were examined in vitro. The results show that As(2)O(3)/MZF thermosensitive magnetoliposomes combined with hyperthermia had a great impact on the Bax/Bcl-2 ratio, which increased to 1.914 and exhibited a rapid response to induce apoptosis of tumor cells. An in situ rabbit liver tumor model was established and used to evaluate the antitumor effect of combined hyperthermia and chemotherapy following transcatheter arterial embolization with As(2)O(3)/MZF thermosensitive magnetoliposomes. The results demonstrated a strong anti-hepatoma effect, with a tumor volume inhibition rate of up to 85.22%. Thus, As(2)O(3)/MZF thermosensitive magnetoliposomes may play a great role in the treatment of hepatocarcinoma.

[Expression of Tumor Necrosis Factor in Placenta Tissue of Pregnant Rats with Chronic Peridontitis]

Zhonghua Kou Qiang Yi Xue Za Zhi = Zhonghua Kouqiang Yixue Zazhi = Chinese Journal of Stomatology. May, 2011  |  Pubmed ID: 21733379

To examine the expression of tumor necrosis factor in placenta of pregnant rats with chronic periodontitis.

Isocratic Method for Affinity Enrichment of Covalently-linked Peptides in Cyanogen Bromide Cleavage of Proteins

Proteomics. Jul, 2011  |  Pubmed ID: 21751378

The low resolution three-dimensional structure of a protein can be inferred from existing disulfide bridges or experimentally introduced chemical crosslinks. The general procedure involves enzymatic digestion of a protein followed by mass spectrometry-based identification of covalently-linked peptides, native disulfide-linked peptides and chemically cross-linked peptides. To facilitate unambiguous identification of these peptides, an isocratic purification method was developed for selective enrichment of covalently-linked cyanogen bromide (CNBr) fragments. This method capitalizes on the ability of homoserine lactone moieties at the C-termini of CNBr cleavage products for selective conjugation of primary-amine containing affinity tag. The availability of two C-termini within covalently-linked peptides allows for the conjugation of two affinity tags, whereas the other peptides have only one affinity tag at the C-terminus, which enables selective enrichment of covalently-linked peptides by utilization of affinity tag with moderate dissociation constant. Here we demonstrate successful implementation of this method with tetrahistidine as the affinity tag for enrichment of covalently-linked CNBr fragments of test peptides and proteins.

9-[(2-Chloro-benz-yl)amino]-5-(3,4,5-trimeth-oxy-phen-yl)-5,5a,8a,9-tetra-hydro-furo[3',4':6,7]naphtho-[2,3-d][1,3]dioxol-6(8H)-one

Acta Crystallographica. Section E, Structure Reports Online. Jun, 2011  |  Pubmed ID: 21754859

In the title compound, C(29)H(28)ClNO(7), the tetra-hydro-furan ring and the six-membered ring fused to it both display envelope conformations. The dihedral angles between the plane of the benzene ring of the benzo[d][1,3]dioxole system and the planes of the other two benzene rings are 80.59 (3) and 63.60 (2)°.

9-{[4-(Dimethyl-amino)-benz-yl]amino}-5-(3,4,5-trimeth-oxy-phen-yl)-5,5a,8a,9-tetra-hydro-furo[3',4':6,7]naphtho-[2,3-d][1,3]dioxol-6(8H)-one

Acta Crystallographica. Section E, Structure Reports Online. Jun, 2011  |  Pubmed ID: 21754898

In the title compound, C(31)H(34)N(2)O(7), the fused tetra-hydro-furan and six-membered rings each display an envelope conformation. The dihedral angles between the benzene ring of the benzo[d][1,3]dioxole and the other two benzene rings are 89.68 (3) and 63.38 (2)°. In the crystal, weak inter-molecular C-H⋯O hydrogen bonds link the mol-ecules.

Weak Anion Exchange Chromatographic Profiling of Glycoprotein Isoforms on a Polymer Monolithic Capillary

Journal of Chromatography. A. Sep, 2011  |  Pubmed ID: 21925666

High resolution separation of intact glycoproteins, which is essential for many aspects such as finger-print profiling, represents a great challenge because one glycoprotein can exhibit many isoforms with close physicochemical properties. Monolithic columns are important separation media for the separation of intact proteins due to its significant advantages such as easy preparation, high column efficiency and high permeability. However, there are few reports on high resolution profiling of intact glycoproteins. Herein, we presented a polymeric weak anion exchange (WAX) monolithic capillary for high resolution separation of glycoprotein isoforms. A base monolith was first prepared through ring-opening polymerization between tris(2,3-epoxypropyl)isocyanurate and tri(2-aminoethyl), and then modified through reacting with ammonia aqueous solution to convert the unreacted epoxide moieties into primary amino groups. The prepared monolithic capillary was characterized in terms of morphology, pore size, hydrophilicity and reproducibility. The obtained WAX monolithic capillary exhibited desired through-pores and mesopore size, stable skeleton and hydrophilic nature. The performance of the capillary was evaluated using several typical glycoproteins such as α(1)-acid glycoprotein (AGP) as mode analytes. Effects of the experimental parameters on the glycoform resolution were investigated. Under the optimized separation conditions, the tested glycoproteins were all resolved into distinct glycoforms. A comparative investigation with capillary zone electrophoresis (CZE) revealed that this WAX column provided better selectivity as more isoforms were observed, although the resolution of some glycoprotein isoforms decreased.

Haploidentical Hematopoietic Stem Cell Transplantation in Hematologic Malignancies with G-CSF Mobilized Bone Marrow Plus Peripheral Blood Stem Cells Grafts Without T Cell Depletion: a Single Center Report of 29 Cases

Leukemia & Lymphoma. Dec, 2011  |  Pubmed ID: 21929286

Haploidentical Hematopoietic stem cell transplantation (Haplo-HSCT) has provided an alternative option since virtually all patients have an immediately available donor. Here, we report the results of Haplo-HSCT with granulocyte-colony-stimulating factor (G-CSF) mobilized bone marrow grafts plus peripheral blood stem cells as the grafts without T-cell depletion. Twenty-nine patients with the mean age of 27.27 years (ranging from 15 to 51 years) were enrolled in this study, and 10 cases were in high risk status. The patients received myeloablative preconditioning with or without total body irradiation and acute graft-versus-host disease (GVHD) prophylaxis consisting of basiliximab, cyclosporine A, methotrexate, mycophenolate mofetil and a rabbit anti-thymocyte globulin. All the patients attained successful neutrophil and platelet recovery. The mean times for neutrophil and platelet recovery were 17.1 and 20.9 days, respectively. During the follow-up at a median time of 30.69 months (ranging from 3 to 76 months), nine patients developed aGVHD grade II-IV, including two developed grade III-IV GVHD after donor lymphocyte infusion. The incidence of cGVHD was 48.3%. 13 patients died within the first two years after transplantation, and the total disease-free survival rate longer than 2 years was 55.2%. These results suggest that G-CSF-primed bone marrow plus peripheral blood stem cell grafts are an appropriate stem cell source for Haplo-HSCT and large scale investigations are needed to confirm this protocol.

Conversion of Molecular Information by Luminescent Nanointerface Self-assembled from Amphiphilic Tb(III) Complexes

Journal of the American Chemical Society. Nov, 2011  |  Pubmed ID: 21932810

A novel amphiphilic Tb(3+) complex (TbL(+)) having anionic bis(pyridine) arms and a hydrophobic alkyl chain is developed. It spontaneously self-assembles in water and gives stable vesicles that show sensitized luminescence of Tb(3+) ions at neutral pH. This TbL(+) complex is designed to show coordinative unsaturation, i.e., water molecules occupy some of the first coordination spheres and are replaceable upon binding of phosphate ions. These features render TbL(+) self-assembling receptor molecules which show increase in the luminescence intensity upon binding of nucleotides. Upon addition of adenosine triphosphate (ATP), significant amplification of luminescent intensity was observed. On the other hand, ADP showed moderately increased luminescence and almost no enhancement was observed for AMP. Very interestingly, the increase in luminescence intensity observed for ATP and ADP showed sigmoidal dependence on the concentration of added nucleotides. It indicates positive cooperative binding of these nucleotides to TbL(+) complexes preorganized on the vesicle surface. Self-assembly of amphiphilic Tb(3+) receptor complexes provides nanointerfaces which selectively convert and amplify molecular information of high energy phosphates linked by phosphoanhydride bonds into luminescence intensity changes.

CD4+CD38+HLA-DR+ Cells: a Predictor of Viral Set Point in Chinese Men with Primary HIV Infection Who Have Sex with Men

Japanese Journal of Infectious Diseases. 2011  |  Pubmed ID: 21937825

Twenty-three Chinese men with primary HIV infection (PHI) who have sex with men, and 17 asymptomatic HIV-infected patients participated in this study. The effect of different initial activation parameters on viral set points and the immunologic progression of subjects with PHI were determined. We found that the proportions of CD38+DR+ and CD38-DR+ T cells were lower while those of CD38+DR- and CD38-DR- T cells were higher in patients with PHI than in the asymptomatic HIV-infected patients. The initial proportion of CD4+CD38+DR+ T cells emerged as a statistically significant predictor (P < 0.05) of viral set points by multivariate least squares regression. In addition, individuals with a higher initial proportion of CD4+CD38+DR+ cells were more likely to have CD4+ T cell counts decrease to ≤ 350 cells/µl (P = 0.015), as determined by Kaplan-Meier curve analysis. We concluded that the initial CD4+CD38+DR+ T cell level in PHI patients is an important prognostic parameter of viral set points and is therefore related to disease progression.

Microbial Fuel Cell Based Biosensor for in Situ Monitoring of Anaerobic Digestion Process

Bioresource Technology. Nov, 2011  |  Pubmed ID: 21945210

A wall-jet microbial fuel cell (MFC) was developed for the monitoring of anaerobic digestion (AD). This biofilm based MFC biosensor had a character of being portable, short hydraulic retention time (HRT) for sample flow through and convenient for continuous operation. The MFC was installed in the recirculation loop of an upflow anaerobic fixed-bed (UAFB) reactor in bench-scale where pH of the fermentation broth and biogas flow were monitored in real time. External disturbances to the AD were added on purpose by changing feedstock concentration, as well as process configuration. MFC signals had good correlations with online measurements (i.e. pH, gas flow rate) and offline analysis (i.e. COD) over 6-month operation. These results suggest that the MFC signal can reflect the dynamic variation of AD and can potentially be a valuable tool for monitoring and control of bioprocess.

A Prophylactic Effect of an Oligodeoxynucleotide Containing a Cytidine-guanosine Motif Against Japanese Cedar Pollen-induced T-helper Type 2 Allergic Response

The Journal of Asthma : Official Journal of the Association for the Care of Asthma. Nov, 2011  |  Pubmed ID: 21967528

Over 10% of entire population in Japan suffer from allergic diseases induced by Japanese cedar pollen (JCP) every spring. In terms of preventive medicine, it has become a matter of urgency to establish successful prophylactic and therapeutic strategies for controlling the disorders. The effect of an oligodeoxynucleotide containing a cytidine-guanosine motif (CpG ODN) on the regulation of immune responses induced by JCP was investigated in this study.

Heat Shock Protein 10 (Hsp10) in Immune-related Diseases: One Coin, Two Sides

International Journal of Biochemistry and Molecular Biology. 2011  |  Pubmed ID: 21969171

Heat shock protein 10 (Hsp10) in eukaryotes, originally identified as a mitochondrial chaperone, now is also known to be present in cytosol, cell surface, extracellular space and peripheral blood. Functionally besides participating in mitochondrial protein folding in association with Hsp60, Hsp10 appears to be related to pregnancy, cancer and autoimmune inhibition. Hsp10 can be released to peripheral blood at very early time point of pregnancy and given another name called early pregnancy factor (EPF), which seems to play a critical role in developing a pregnant niche. In malignant disorders, Hsp10 is usually abnormally expressed in the cytosol of malignant cells and further released to extracellular space, resulting in tumor-promoting effect from various aspects. Furthermore, distinct from other heat shock protein members, whose soluble form is recognized as danger signal by immune cells and triggers immune responses, Hsp10 after release, however, is designed to be an inhibitory signal by limiting immune response. This review discusses how Hsp10 participates in various physiological and pathological processes from basic protein molecule folding to pregnancy, cancer and autoimmune diseases, and emphasizes how important the location is for the function exertion of a molecule.

Interdonation Intervals and Patterns of Return Among Blood Donors in Brazil

Transfusion. Oct, 2011  |  Pubmed ID: 21981543

BACKGROUND: In Brazil, most donations come from repeat donors, but there are little data on return behavior of donors. STUDY DESIGN AND METHODS: Donors who made at least one whole blood donation in 2007 were followed for 2 years using a large multicenter research database. Donation frequency, interdonation intervals, and their association with donor demographics, status, and type of donation were examined among three large blood centers in Brazil, two in the southeast and one in the northeast. RESULTS: In 2007, of 306,770 allogeneic donations, 38.9% came from 95,127 first-time donors and 61.1% from 149,664 repeat donors. Through December 31, 2009, a total of 28.1% of first-time donors and 56.5% of repeat donors had donated again. Overall, the median interdonation interval was approximately 6 months. Among men it was 182 and 171 days for first-time and repeat donors, and among women, 212 and 200 days. Predictors of return behavior among first-time donors were male sex (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.13-1.20), community donation (OR, 2.26; 95% CI, 2.20-2.33), and age 24 years or less (OR, 0.62-0.89 for donors ≥25 years). Among repeat donors predictors were male sex (OR, 1.35; 95% CI, 1.32-1.39), age 35 years or more (OR, 1.08-1.18 vs. ≤24 years), and community donation (OR, 2.39; 95% CI, 2.33-2.44). Differences in return by geographic region were evident with higher return rates in the northeast of Brazil. CONCLUSION: These data highlight the need to develop improved communication strategies for first-time and replacement donors to convert them into repeat community donors.

Anticoagulant, Anti-aggregation and Antithrombotic Effects of a Novel Hexapeptide

The Journal of Pharmacy and Pharmacology. Nov, 2011  |  Pubmed ID: 21988426

Hexapeptide is a novel synthetic oligopeptide with a structure similar to that of eptifibatide. This study was designed to investigate the anticoagulant, anti-aggregation, disaggregation and anti-thrombogenesis effects of hexapeptide.

Nanostructure Control of Graphene-composited TiO2 by a One-step Solvothermal Approach for High Performance Dye-sensitized Solar Cells

Nanoscale. Nov, 2011  |  Pubmed ID: 22006266

We present a one-step solvothermal approach to prepare uniform graphene-TiO(2) nanocomposites with delicately controlled TiO(2) nanostructures, including ultra-small 2 nm nanoparticles, 12 nm nanoparticles and nanorods. Using three composites as photoanode materials, the effect of nanostructure of graphene-composited TiO(2) on the performance of dye-sensitized solar cells was investigated, and results showed that the ultra-small 2 nm TiO(2)-graphene composite based photoanode exhibited the highest power conversion efficiency of 7.25%.

[Comparative Study of Wild and Cultivated Astragali Radix in Daqingshan District in Wuchuan of Neimenggu]

Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica. Jun, 2011  |  Pubmed ID: 22007536

To make a comparative study on wild and cultivated Astragali Radix in Wuchuan, Neimenggu where is one of the geo-authentic producing areas of Astragalus membranaceus var. mongholicus.

The TGF-{beta}1/Smad/CTGF Pathway and Corpus Cavernosum Fibrous-Muscular Alterations in Rats with Streptozotocin-Induced Diabetes

Journal of Andrology. Oct, 2011  |  Pubmed ID: 22016353

Diabetes-associated erectile dysfunction is associated with increased extracellular matrix deposition and reduced smooth muscle content in the corpus cavernosum. The mechanisms of these processes are not well understood. In this study we investigated fibro-muscular changes in the corpus cavernosum of rats with streptozotocin-induced diabetes and determine the mechanisms underlying pathological changes in penile structure and function. Forty 8-week-old Sprague-Dawley rats were randomly distributed into control and diabetic groups. Diabetes was induced by a one-time intraperitoneal injection of streptozotocin (60 mg/kg). Twelve weeks later, erectile function was measured by cavernous nerve electrostimulation with real time intracorporal pressure assessment. The penis was harvested for the histological examination (Masson's trichrome stain, picrosirius red stain, Hart's elastin stain, TUNEL, and immunohistochemistry) and Western blot. Diabetes significantly attenuated erectile response to cavernous nerve electrostimulation. Diabetic animals exhibited a decreased smooth muscle/collagen ratio in the corpus cavernosum. The ratio of collagen I to II fibers was significantly lower in the corpora of diabetic rats compared to controls. Cavernous elastic fibers were fragmented in diabetic rats. There was up-regulation of the TGF-β1/Smad/CTGF signaling pathway in diabetic rats. Phospho-Smad2 expression was higher in smooth muscle cells and fibroblasts of diabetic rats, as was the apoptotic index. The up-regulation of the TGF-β1/Smad/CTGF signaling pathway might play an important role in diabetes-induced Fibrous-Muscular structural changes and deterioration of erectile function.

[Cloning of Blakeslea Trispora CarRA Gene by PCR-driven Overlap Extension and Construction of an Activity Detection System]

Sheng Wu Gong Cheng Xue Bao = Chinese Journal of Biotechnology. Jul, 2011  |  Pubmed ID: 22016982

Blakeslea trispora CarRA has both lycopene cyclase and phytoene synthase activity. In order to analyze the double functional activity of CarRA proteins and to detect the active sites of lycopene cyclase, we constructed two detection systems in Escherichia coli by color complementary. Through PCR-driven overlap extension we got carRA gene cDNA, then constructed prokaryotes expression vector pET28a-carRA. pET28a-carRA with plasmid pAC-LYC carrying crtl/crtB/crtE gene clusters were co-transformed to BL21(DE3) to validate lycopene cyclase activity. We constructed the plasmid pAC-LYC delta (crtB) carrying crtl/crtE gene clusters, then co-transtormed them with pET28a-carRA to BL21(DE3) to validate phytoene synthase activity. Based on color complementary, and HPLC analysis of metabolites, we confirmed that the CarRA protein activity detection system was reliable. Our study provides a screening model for specific mutation of lycopene cyclase without affecting phytoene synthase activity.

[Study on the Chemical Constituents of Rumex Patientia]

Zhong Yao Cai = Zhongyaocai = Journal of Chinese Medicinal Materials. Jun, 2011  |  Pubmed ID: 22017004

OBJECTIVE : To study the chemical constituents of roots of Rumex patientia.

Functionalized Carbon Nanotubes for Anticancer Drug Delivery

Expert Review of Medical Devices. Sep, 2011  |  Pubmed ID: 22026621

In vitro and in vivo results reflect that functionalized carbon nanotubes (f-CNTs) are promising for the development of unique delivery systems of anticancer drugs. Functionalization of CNTs and drug loading are realized by covalent attachment and/or physical approaches. Poly(ethylene glycol) is the most adopted species for functionalization, which can increase the dispersity in aqueous solution and biocompatibility of CNTs. Several types of anticancer drugs, such as paclitaxel and doxorubicin, are loaded onto f-CNTs and their treatment efficacy has been demonstrated in vitro and in vivo. However, f-CNTs of well-controlled structures, such as uniform length and well-defined chemistry, which are not available so far, are important to solve the current controversy over the mechanisms of cell uptake of f-CNTs, and are a prerequisite to investigate whether f-CNTs can be platform materials for anticancer drug delivery with improved efficacy.

Mobile Phone-enabled Control of Medical Care and Handicapped Assistance

Expert Review of Medical Devices. Nov, 2011  |  Pubmed ID: 22029471

Mobile phones are now playing an ever more crucial role in people's daily lives. They are serving not only as a way of talking and delivering messages, but also for exchanging various information. Nevertheless, the functional limit of the phone is still far from being reached. Among the many promising applications, using mobile phones as an actuating element to control data or devices is useful in quite a few emerging medical care and handicapped assistance settings owing to its wireless communication feature. In this article, selected progresses of mobile phone-enabled controlling have been summarized, with more focus on evaluating its emerging roles in medical care. Several typical applications in the area are illustrated and some potential technical challenges and key issues worthy of pursuit are outlined. The intent of the article is to provide an elementary knowledge for people with different backgrounds, such as electrical or biomedical engineers, as well as people who are working on interdisciplinary areas. It is expected that medical care at any time and anywhere will be possible via the actuation platform provided by the mobile phone and mobile medicine will be pushed forward to a new height in the coming years.

TBX3 Over-expression Causes Mammary Gland Hyperplasia and Increases Mammary Stem-like Cells in an Inducible Transgenic Mouse Model

BMC Developmental Biology. 2011  |  Pubmed ID: 22039763

The T-box transcription factor TBX3 is necessary for early embryonic development and for the normal development of the mammary gland. Homozygous mutations, in mice, are embryonic lethal while heterozygous mutations result in perturbed mammary gland development. In humans, mutations that result in the haploinsufficiency of TBX3 causes Ulnar Mammary Syndrome (UMS) characterized by mammary gland hypoplasia as well as other congenital defects. In addition to its role in mammary gland development, various studies have also supported a role for Tbx3 in breast cancer development. TBX3 is over-expressed in various breast cancer cell lines as well as cancer tissue and has been found to contribute to breast cancer cell migration. Previous studies have suggested that TBX3 contributes to cancer development by its ability to bypass senescence by repressing the expression of p14(ARF)-tumor suppressor. Although many studies have shown that a dysregulation of TBX3 expression may contribute to cancer progression, no direct evidence shows TBX3 causes breast cancer.

Evidence for Inter- and Intra-clade Recombinations in Rabies Virus

Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases. Dec, 2011  |  Pubmed ID: 22041506

Homologous recombination is considered rare in negative-strand RNA viruses and has not been reported for rabies virus. In this study, full-length genomes of 44 rabies virus strains were analyzed for potential homologous recombination events. Phylogenetic analysis classified these strains into three clades. By applying six different recombination detection methods, one inter-clade and one intra-clade potential recombination events were identified with high confidence values. Software-predicted recombination break points of the two events were all located within the polymerase gene. This report presents the first evidence suggesting the possibility of homologous recombination in rabies virus, which could provide valuable insights for understanding the diversity and evolution of rabies virus as well as other negative-strand RNA viruses.

Ratiometric Fluorescence Detection of Cyanide Based on a Hybrid Coumarin-hemicyanine Dye: the Large Emission Shift and the High Selectivity

Chemical Communications (Cambridge, England). Dec, 2011  |  Pubmed ID: 22045110

A new ratiometric fluorescent cyanide probe was developed based on the nucleophilic attack of CN(-) toward the indolium group of a hybrid coumarin-hemicyanine dye, by which high selectivity as well as large emission shift could be achieved.

The Gold (III) Porphyrin Complex, Gold-2a, Suppresses WNT1 Expression in Breast Cancer Cells by Enhancing the Promoter Association of YY1

American Journal of Translational Research. 2011  |  Pubmed ID: 22046489

The gold (III) porphyrin complex, gold-2a, elicits anti-tumor activity by targeting the Wnt/β-catenin signaling pathway [Chow KH et al, Cancer Research 2010;70(1):329-37]. Here, the molecular mechanisms underlying the inhibitory effects of this compound on WNT1 gene expression were elucidated further. A response element to gold-2a was identified located within the -1290 to -1112 nt region of the WNT1 promoter, containing a binding site for the transcription regulator Yin Yang 1 (YY1). Gold-2a promoted the association of YY1 and suppressor of zeste 12 (Suz12; a component of the polycomb repressor complex 2) with the WNT1 promoter. Under normal culture conditions, the intracellular translocalization of YY1 was synchronized with cell cycle progression and WNT1 expression. Gold-2a promoted the nuclear accumulation and abolished the nuclear exportation of YY1, resulting in a persistent inhibition of WNT1 expression and a cell cycle arrest at G1/S phase. A dimorphic role of YY1 in regulating cell proliferation and division was revealed. Thus, the present study extends the understanding of the anti-tumor mechanism of gold-2a to the epigenetic level, which involves the modulation of the dynamic interactions between YY1 and a specific region of the WNT1 promoter.

Endothelial Nitric Oxide Synthase Gene Polymorphisms (G894T, 4b/a and T-786C) and Preeclampsia: Meta-Analysis of 18 Case-Control Studies

DNA and Cell Biology. Nov, 2011  |  Pubmed ID: 22054068

Studies investigating the association between endothelial nitric oxide synthase (eNOS) gene polymorphisms and preeclampsia reported contradictory or nonconclusive results. We performed a meta-analysis of 18 genetic association studies that examined the relationship between preeclampsia and the G894T, 4a/b and T-786C polymorphisms of the eNOS gene. Subgroup analysis by ethnicity and potential sources of heterogeneity and bias were explored. The MEDLINE, EMBASE, and Google Scholar databases were searched to access the relevant genetic association studies up to June 2011. For the allelic analysis of the G894T variant, all studies showed no significant association. For the genotypic analysis, the combined studies of the G allele showed negative significance (odds ratio [OR]=0.56; 95% confidence interval [CI]: 0.33-0.97), all the studies showed positively significance when the T allele was combined (OR=1.17; 95% CI: 1.01-1.36), and results were also positively significant in non-Asian populations (OR=1.20; 95% CI: 1.02-1.43). For the allelic analysis of the 4b/a variant, all studies showed no significant association, but results were negatively significant in non-Asian populations (OR=0.67; 95% CI: 0.46-0.98). For the genotype analysis, combined studies of the b allele showed negative significance (OR=0.55; 95% CI: 0.36-0.84). Moreover, non-Asian studies showed negatively significant results (OR=0.45; 95% CI: 0.28-0.72). For the analysis of the T-786C variant, none of the studies showed significant results. The synthesis of available evidence supports the fact that intron 4a allele, homozygosity for the 894T and intron 4a of eNOS are positively associated with preeclampsia. Large, multiethnic confirmatory, and well-designed studies are needed to determine the relation between preeclampsia and polymorphisms of the eNOS gene.

Nuclear and Chloroplast SSR Markers in Paeonia Delavayi (Paeoniaceae) and Cross-species Amplification in P. Ludlowii

American Journal of Botany. Dec, 2011  |  Pubmed ID: 22074777

• Premise of the study: Microsatellite primers were developed for Paeonia delavayi and P. ludlowii (Paeoniaceae) to study their population genetics and phytogeography. • Methods and Results: Nine polymorphic nuclear microsatellite loci were isolated from an enriched library of P. delavayi and primers were designed. The number of alleles per locus ranged from two to 16; the observed and expected heterozygosities ranged from 0.014 to 0.687 and 0.042 to 0.875, respectively. Six polymorphic chloroplast microsatellite loci were identified in P. delavayi and primers were provided. The number of alleles per locus ranged from two to six and the polymorphic information content ranged from 0.08 to 0.716. Both nuclear and chloroplast primers were successfully applicable to P. ludlowii. • Conclusions: The markers developed here will facilitate analyses of genetic diversity, population genetic structure, phytogeographical patterns, and conservation for P. delavayi and P. ludlowii.

An Embryonic Stem Cell-based System for Rapid Analysis of Transcriptional Enhancers

Genesis (New York, N.Y. : 2000). Nov, 2011  |  Pubmed ID: 22083581

With the growing use of genome-wide screens for cis-regulatory elements, there is a pressing need for platforms that enable fast and cost-effective experimental validation of identified hits in relevant developmental and tissue contexts. Here, we describe a murine embryonic stem cell (ESC)-based system that facilitates rapid analysis of putative transcriptional enhancers. Candidate enhancers are targeted with high efficiency to a defined genomic locus via recombinase-mediated cassette exchange. Targeted ESCs are subsequently differentiated in vitro into desired cell types, where enhancer activity is monitored by reporter gene expression. As a proof of principle, we analyzed a previously characterized, Sonic hedgehog (Shh)-dependent, V3 interneuron progenitor (pV3)-specific enhancer for the Nkx2.2 gene, and observed highly specific enhancer activity. Given the broad potential of ESCs to generate a spectrum of cell types, this system can serve as an effective platform for the characterization of gene regulatory networks controlling cell fate specification and cell function. genesis 1-8, 2012. © 2012 Wiley Periodicals, Inc.

[Cisplatin Enhances TRAIL-induced Apoptosis in Gastric Cancer Cells Through Clustering Death Receptor 4 into Lipid Rafts]

Zhonghua Zhong Liu Za Zhi [Chinese Journal of Oncology]. Jul, 2011  |  Pubmed ID: 22093622

Gastric cancer cells are insensitive to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). To sensitize gastric cancer cells to TRAIL, we treated gastric cancer MGC803 cells with TRAIL and cisplatin.

Probiotics for Treating Persistent Diarrhea in Children

The American Journal of Nursing. Dec, 2011  |  Pubmed ID: 22112890

Modeling the Basal Dynamics of P53 System

PloS One. 2011  |  Pubmed ID: 22114721

The tumor suppressor p53 has become one of most investigated genes. Once activated by stress, p53 leads to cellular responses such as cell cycle arrest and apoptosis.

Biocompatibility of Fe₃O₄@Au Composite Magnetic Nanoparticles in Vitro and in Vivo

International Journal of Nanomedicine. 2011  |  Pubmed ID: 22131827

This research was conducted to assess the biocompatibility of the core-shell Fe(3)O(4)@ Au composite magnetic nanoparticles (MNPs), which have potential application in tumor hyperthermia.

Immunohistochemical Expressions of Fatty Acid Synthase and Phosphorylated C-Met in Thyroid Carcinomas of Follicular Origin

International Journal of Clinical and Experimental Pathology. 2011  |  Pubmed ID: 22135723

Thyroid carcinoma is the most common endocrine malignancy and the first cause of death among endocrine cancers. Fatty acid synthase (FASN) and c-Met are overexpressed in many types of human cancers. Recent studies have suggested a functional interaction between FASN and c-Met. However, their roles in thyroid carcinomas have not been fully investigated. In this study, we evaluated the expressions of FASN and phosphorylated (p)-c-Met by using immunohistochemistry in thyroid carcinomas of follicular origin, from 32 patients. The adjacent non-neoplastic thyroid tissue was also evaluated for comparison. Immunoreactive intensity and extensiveness were semi-quantified. The overexpression of FASN was observed in a subset of papillary thyroid carcinomas (PTC) including the classical type and tall cell, follicular, trabecular/insular and diffuse sclerosing variants, a subset of follicular thyroid carcinomas (FTC), and the PTC and FTC components in anaplastic thyroid carcinomas (ATC). No overexpression was observed in the ATCs per se and the columnar cell, solid, and cribriform variants of PTCs. All Hürthle cell variant FTCs and non-neoplastic Hürthle cells demonstrated positive staining for FASN while the non-neoplastic follicular cells without Hürthle cell change were negative. An association in overexpression between FASN and p-c-Met was observed in the majority of carcinomas as well as in the non-neoplastic Hürthle cells. In conclusion, overexpressions of FASN and p-c-Met were observed in a subset of thyroid carcinomas of follicular origin, which may be of values for targeted therapy and predicting prognosis while the positive immunostaining for these immunomarkers may be nonspecific for Hürthle cell thyroid carcinomas.

Elevated Expression of PEG10 in Human Placentas from Preeclamptic Pregnancies

Acta Histochemica. Dec, 2011  |  Pubmed ID: 22137777

The aim of this study was to determine qualitative and quantitative changes in paternally expressed gene 10 (PEG10) expression in preeclamptic placentas. Placental tissues were obtained immediately after delivery from women with normal pregnancies (n=20) and patients with preeclampsia (n=20). Quantitative real-time RT-PCR, Western blot analysis and immunohistochemistry were used to determine PEG10 gene expression and localization in placental tissues. Compared with the normal group, PEG10 was highly expressed at both mRNA and protein levels in preeclampsia (P<0.05). In immunohistochemical staining, PEG10 was present in the syncytiotrophoblast, cytotrophoblast, endothelial cell and stroma of all placentas. Notably, the intensity of PEG10 expression in the syncytiotrophoblast, cytotrophoblast and stem villi was much higher in preeclampsia than in normal. In conclusion, elevated expression of PEG10 is likely to be involved in the pathophysiology of preeclampsia. Further studies are needed to elucidate the precise role of PEG10 in preeclampsia.

Minimalist and Universal Peptidomimetics

Chemical Society Reviews. Aug, 2011  |  Pubmed ID: 21483946

Many "new generation" peptidomimetics are designed to present amino acid side chains only; they do not have structural features that resemble peptide main chains. These types of molecules have frequently been presented in the literature as mimics of specific secondary structures. However, many "side-chain only" peptidomimetics do not rest in single conformational states, but exist in a limited number of freely interconverting forms. These different conformations may resemble different secondary structures, so referring to them as, for instance, turn- or helical-mimics understates the ways they could adapt to various binding situations. Sets of scaffolds that can be used to mimic aspects of nearly every secondary structure, i.e. universal peptidomimetics, can be constructed. These may assume a privileged place in library design, particularly in high throughput screening for pharmacological probes for which binding conformations, or even the target itself, is unknown at the time the library is designed (critical review, 101 references).

Oleanane-type Triterpene Saponins and Cassaine-type Diterpenoids from Erythrophleum Fordii

Planta Medica. Sep, 2011  |  Pubmed ID: 21484673

Phytochemical investigation of the EtOH extract of the leaves of Erythrophleum fordii led to the isolation of two oleanane-type triterpene saponins (1-2) and five cassaine-type diterpenoids (4-8) along with one known methyl 3 β-hydroxy-erythrosuamate (3). Their structures were established by extensive NMR, as well as ESI-MS analyses and acid hydrolysis. Biological evaluation of compounds 3- 8 against five human cancer cell lines revealed that compounds 5-7 exhibited potent cytotoxic activity with IC₅₀ values ranging from 1.51 to 8.68 µM.

Mechanism of Immune Hyporesponsiveness Induced by Recipient- Derived Immature Dendritic Cells in Liver Transplantation Rat

Chinese Medical Sciences Journal = Chung-kuo I Hsüeh K'o Hsüeh Tsa Chih / Chinese Academy of Medical Sciences. Mar, 2011  |  Pubmed ID: 21496420

To investigate the mechanism of immune hyporesponsiveness induced by donor-antigen- unloaded recipient-derived immature dendritic cell (imDC) of liver grafts in rats.

Inhibition of B16 Murine Melanoma Metastasis and Enhancement of Immunity by Fever-range Whole Body Hyperthermia

International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group. 2011  |  Pubmed ID: 21501029

Whole body hyperthermia (WBH) has been regarded as a promising alternative therapy to cure late stage cancer with metastasis. As the final biological and therapeutic effects are dependent on the specific protocol, the potential of using a microwave-based WBH approach for metastasis inhibition is established and its typical results are discussed.

CT-guided Single High-dose Percutaneous Acetic Acid Injection for Small Hepatocellular Carcinoma: A Long-term Follow-up Study

European Journal of Radiology. Apr, 2011  |  Pubmed ID: 21511422

OBJECTIVE: To evaluate the long-term outcome of CT-guided single high-dose percutaneous acetic acid injection (PAI) for the treatment of small hepatocellular carcinoma (SHCC). MATERIALS AND METHODS: Sixty-eight consecutive patients (37 men and 31 women; age 52±16 years) with SHCC have undergone CT-guided single high-dose PAI therapy since December 2000. Complications of high-dose PAI were recorded. Tumour survival and recurrence rates were assessed. RESULTS: All PAI therapies were successful and no severe complications developed. The average follow-up period was 46±18 months. The overall survival rates at 1, 2, 3, 4 and 5 years were 93%, 82%, 68%, 59% and 51%, respectively. The cumulative local recurrence rates for the main tumour at 1, 2, 3, 4 and 5 years were 18%, 22%, 25%, 28% and 28%, respectively. The cumulative new tumour recurrence rates at 1, 2, 3, 4 and 5 years were 24%, 40%, 43%, 60% and 62%, respectively. CONCLUSION: CT-guided single high-dose PAI is safe and effective for the treatment of SHCC after long-term follow-up.

[Association Between High Sensitivity C-reactive Protein Levels in Serum and the 5-year-accumulative-risk of Diabetes.]

Zhonghua Liu Xing Bing Xue Za Zhi = Zhonghua Liuxingbingxue Zazhi. Jan, 2011  |  Pubmed ID: 21518530

OBJECTIVE: To analyze the association between hs-CRP (high-sensitivity C-reactive protein) levels in serum and the 5-year-accumulative-risk of diabetes in a general population. METHODS: Participants were from the cohort of Peking University residential community in the Chinese Multi-provincial Cohort Study (CMCS). Two surveys on cardiovascular risk factors and the measurements of serum hs-CRP levels were conducted in 2002 and 2007, respectively. Individuals with incomplete information and those having infectious diseases at baseline were excluded. A total of 1045 participants aged 45 to 74 years and free of diabetes at baseline were included in this analysis. RESULTS: The age-standardized 5-year accumulative incidence rate of diabetes was 8.8% (male: 9.8%, female: 8.2%) and increased significantly with the level of hs-CRP in both women and men (P < 0.01). After adjustment for age, hypertension, low-density liproprotein cholesterol, and high-density liproprotein cholesterol, triglycerides, fasting glucose, smoking status and central obesity, people with hs-CRP ≥ 3 mg/L had a 3.30 times higher risk of developing diabetes in men and 2.58 times for women when compared to those with hs-CRP < 1 mg/L. The areas under the receiver operating characteristic curves of baseline hs-CRP level in predicting the incidence of diabetes were 0.619 (95%CI: 0.536 - 0.701) in men and 0.667 (95%CI: 0.585 - 0.749) in women. CONCLUSION: Serum hs-CRP levels could predict the incidence of diabetes, indicating that inflammation might have great importance in the onset of diabetes.

N-Cyclo-hexyl-2-(5-meth-oxy-1H-indol-3-yl)-2-oxoacetamide

Acta Crystallographica. Section E, Structure Reports Online. 2011  |  Pubmed ID: 21522980

In the title compound, C(17)H(20)N(2)O(3), the cyclo-hexane ring adopts a chair conformation. In the crystal, inter-molecular N-H⋯O hydrogen bonds link the mol-ecules into layers parallel to the ac plane.

Dimeric Prenylated C6-C3 Compounds from the Stem Bark of Illicium Oligandrum

Journal of Natural Products. May, 2011  |  Pubmed ID: 21524101

Three new dimeric prenylated C6-C3 compounds, namely, illicidiones A (1), B (2), and C (3), were isolated from the stem bark of Illicium oligandrum. The structure and absolute configuration of these compounds were determined by extensive spectroscopic and chemical analyses, including NMR, modified Mosher method, and single-crystal X-ray study. Compounds 1-3 exhibited weak anti-inflammatory activities.

Z Intensity-weighted Position Self-respiratory Gating Method for Free-breathing 3D Cardiac CINE Imaging

Magnetic Resonance Imaging. Jul, 2011  |  Pubmed ID: 21524873

A free-breathing 3D cine steady-state free precession (SSFP) technique was developed using the z intensity-weighted position (ZIP) which is the center of mass of a projection along the slice direction as a respiratory gating signal. The ZIP signal was continuously acquired using a slice encoded k-space center sampling in every TR. The performance of this gating method was compared with a method using the k-space center signal (KC) and with conventional 2D breath-hold cine SSFP in healthy subjects by measuring image quality and left ventricular function. The preliminary data obtained here demonstrated that the ZIP gating method provided superior respiratory motion artifact suppression when compared to the KC gating and provided left ventricular ejection fractions, and end-diastolic and end-systolic volumes similar to those obtained with the breath-hold 2D cine SSFP acquisition.

Association of Angiotensin-converting Enzyme Gene Insertion/deletion Polymorphism with High-altitude Pulmonary Oedema: a Meta-analysis

Journal of the Renin-angiotensin-aldosterone System : JRAAS. Dec, 2011  |  Pubmed ID: 21525147

High-altitude pulmonary oedema (HAPE) is a non-cardiogenic hydrostatic oedema involving a genetic component. Considering the low incidence of HAPE, sample sizes in current reports are relatively limited. We aimed to assess the association between the angiotensin-converting enzyme (ACE) I/D polymorphism and HAPE via a meta-analysis of published and unpublished data.

[Effect of PCP on the Living Cell Content and Distribution in Biofilms]

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.]. Feb, 2011  |  Pubmed ID: 21528571

The phospholipids method for the determination of the living cell content in the biofilm was established to study the wastewater biofilm. With the micro-slicing technology, the biofilm was divided into 150 microm-layer for the phospholipids analysis. Results showed the phospholipids were approximately normal distribution along the biofilm depth without no addition of pentachlorophenol (PCP). The absolute values were between (1 246.2 +/- 217.4) microg/L and (527.2 +/- 95.3) microg/L with the maximum occurring at the depth of (0.60 +/- 0.15) microm, indicating the highest concentrations of the living cell in the biofilm. With the PCP concentrations of 5 microg/L, 10 microg/L and 20 microg/L and the exposure times of 2 h, 6 h and 24 h, respectively, the results of the orthogonal experiments showed the value of phospholipids decreased greatly along the biofilm depth only with the exception of 5 microg/L PCP concentration and 2 h exposure time, with a concentration decline by up to 70% especially close to the peak of phospholipids distribution. Results proved that PCP has an adversely influence on the living cells, and the influence can be enhanced with the increase of PCP amount and the exposure time.

Microwave-assisted, Divergent Solution-phase Synthesis of 1,3,6-trisubstituted Pyrazolo[3,4-d]pyrimidines

ACS Combinatorial Science. Jul, 2011  |  Pubmed ID: 21528879

A concise and highly divergent synthetic route has been developed to rapidly access 1,3,6-trisubstituted pyrazolopyrimidines. The synthesis features a microwave assisted one-pot N1-alkylation/Suzuki-Miyaura reaction as the key step. The sequence of the synthetic scheme can be varied to selectively modify the N1, C3, or C6 position at a late synthetic stage, thereby providing a highly efficient approach to explore the structure-activity relationships of pyrazolopyrimidine derivatives. The scope of these reactions has also been explored.

Identification and Molecular Characterization of Two Novel Mutations in COL1A2 in Two Chinese Families with Osteogenesis Imperfecta

Journal of Genetics and Genomics = Yi Chuan Xue Bao. Apr, 2011  |  Pubmed ID: 21530898

Osteogenesis imperfecta (OI, also known as brittle bone disease) is caused mostly by mutations in two type I collagen genes, COL1A1 and COL1A2 encoding the pro-α1 (I) and pro-α2 (I) chains of type I collagen, respectively. Two Chinese families with autosomal dominant OI were identified and characterized. Linkage analysis revealed linkage of both families to COL1A2 on chromosome 7q21.3-q22.1. Mutational analysis was carried out using direct DNA sequence analysis. Two novel missense mutations, c.3350A>G and c.3305G>C, were identified in exon 49 of COL1A2 in the two families, respectively. The c.3305G>C mutation resulted in substitution of a glycine residue (G) by an alanine residue (A) at codon 1102 (p.G1102A), which was found to be mutated into serine (S), argine (R), aspartic acid (D), or valine (V) in other families. The c.3350A>G variant may be a de novo mutation resulting in p.Y1117C. Both mutations co-segregated with OI in respective families, and were not found in 100 normal controls. The G1102 and Y1117 residues were evolutionarily highly conserved from zebrafish to humans. Mutational analysis did not identify any mutation in the COX-2 gene (a modifier gene of OI). This study identifies two novel mutations p.G1102A and p.Y1117C that cause OI, significantly expands the spectrum of COL1A2 mutations causing OI, and has a significant implication in prenatal diagnosis of OI.

Activation of AMPK by Berberine Promotes Adiponectin Multimerization in 3T3-L1 Adipocytes

FEBS Letters. Jun, 2011  |  Pubmed ID: 21536037

Adiponectin is assembled into trimer (LMW), hexamer (MMW) and high-molecular-weight (HMW) multimer in adipocytes. The HMW adiponectin is more metabolically active and closely associated with peripheral insulin sensitivity. In this study, we reported that berberine, an isoquinoline alkaloid with insulin-sensitizing effect, inhibits the expression of adiponectin, but promotes the assembly of HMW adiponectin and increases the ratio of HMW to total adiponectin. Berberine activates AMPK. Knockdown of AMPKα1 abolishes the effect of berberine. Activation of AMPK by AICAR also increases the level of HMW adiponectin. Our study suggested that activation of AMPK by berberine promotes adiponectin multimerization.

Differentiation of Neural Stem Cells Influences Their Chemotactic Responses to Vascular Endothelial Growth Factor

Journal of Neuroscience Research. Aug, 2011  |  Pubmed ID: 21538456

Although much effort has been devoted to the delineation of factors involved in the migration of neural stem/progenitor cells (NSCs), the relationship between the chemotactic response and the differentiation status of these cells remains elusive. In the present study, we found that NSCs in varying differentiation states possess different chemotactic responses to vascular endothelial growth factor (VEGF): first, the number of chemotaxing NSCs and the optimal concentrations of VEGF that induced the peak migration vary greatly; second, time-lapse video analysis shows that NSCs at certain differentiation states migrate more efficiently toward VEGF, although the migration speed remains unchanged irrespective of cell states; third, the phosphorylation status of Akt, ERK1/2, SAPK/JNK, and p38MAPK is closely related to the differentiation levels of NSCs subjected to VEGF; and, finally, although inhibition of ERK1/2 signaling significantly attenuates VEGF-stimulated transfilter migration of both undifferentiated and differentiating NSCs, NSCs show normal chemotactic response after treatment with inhibitors of SAPK/JNK or p38MAPK. Meanwhile, interference with PI3K/Akt signaling prevents only NSCs of 12 hr differentiation, but not NSCs of 1 day or 3 days differentiation, from migrating in response to VEGF. Moreover, blocking of PI3K/Akt or MAPK signaling impairs the migration efficiency and/or speed, the extent of which depends on the cell differentiation status. Collectively, these results demonstrate that differentiation of NSCs influences their chemotactic responses to VEGF: NSCs in varying differentiation states have different migratory capacities, thereby shedding light on optimization of the therapeutic potential of NSCs to be employed for neural regeneration after injury.

Studies of New Fused Benzazepine As Selective Dopamine D3 Receptor Antagonists Using 3D-QSAR, Molecular Docking and Molecular Dynamics

International Journal of Molecular Sciences. 2011  |  Pubmed ID: 21541053

In recent years, great interest has been paid to the development of compounds with high selectivity for central dopamine (DA) D3 receptors, an interesting therapeutic target in the treatment of different neurological disorders. In the present work, based on a dataset of 110 collected benzazepine (BAZ) DA D3 antagonists with diverse kinds of structures, a variety of in silico modeling approaches, including comparative molecular field analysis (CoMFA), comparative similarity indices analysis (CoMSIA), homology modeling, molecular docking and molecular dynamics (MD) were carried out to reveal the requisite 3D structural features for activity. Our results show that both the receptor-based (Q(2) = 0.603, R(2) (ncv) = 0.829, R(2) (pre) = 0.690, SEE = 0.316, SEP = 0.406) and ligand-based 3D-QSAR models (Q(2) = 0.506, R(2) (ncv) =0.838, R(2) (pre) = 0.794, SEE = 0.316, SEP = 0.296) are reliable with proper predictive capacity. In addition, a combined analysis between the CoMFA, CoMSIA contour maps and MD results with a homology DA receptor model shows that: (1) ring-A, position-2 and R(3) substituent in ring-D are crucial in the design of antagonists with higher activity; (2) more bulky R(1) substituents (at position-2 of ring-A) of antagonists may well fit in the binding pocket; (3) hydrophobicity represented by MlogP is important for building satisfactory QSAR models; (4) key amino acids of the binding pocket are CYS101, ILE105, LEU106, VAL151, PHE175, PHE184, PRO254 and ALA251. To our best knowledge, this work is the first report on 3D-QSAR modeling of the new fused BAZs as DA D3 antagonists. These results might provide information for a better understanding of the mechanism of antagonism and thus be helpful in designing new potent DA D3 antagonists.

Clinical Analysis of the Treatment of Spinocerebellar Ataxia and Multiple System Atrophy-cerebellar Type with Umbilical Cord Mesenchymal Stromal Cells

Cytotherapy. Sep, 2011  |  Pubmed ID: 21545234

The aims of this study were to observe the safety and effectiveness of umbilical cord mesenchymal stromal cells (UC-MSC) in the treatment of spinocerebellar ataxia (SCA) and multiple system atrophy-cerebellar type (MSA-C).

Asthma-associated Polymorphisms in 17q21 Influence Cord Blood ORMDL3 and GSDMA Gene Expression and IL-17 Secretion

The Journal of Allergy and Clinical Immunology. Jun, 2011  |  Pubmed ID: 21546069

In a genome-wide association study, genetic variants on chromosome 17q21 were strongly associated with childhood asthma and orosomucoid 1-like 3 (ORMDL3) gene expression. Regulation of the 17q21 locus and its immunologic relevance early in life have not been well characterized.

Different Associations of Apolipoprotein E Polymorphism with Metabolic Syndrome by Sex in an Elderly Chinese Population

Metabolism: Clinical and Experimental. Oct, 2011  |  Pubmed ID: 21550086

The metabolic syndrome (MetS) is characterized by a cluster of metabolic disorders including abnormal lipid and lipoprotein metabolism. Apolipoprotein E (ApoE) is involved in the regulation of the metabolism of cholesterol, lipoproteins, and triglycerides. The common ApoE polymorphism has been found to be associated with cardiovascular disease and diabetes. This study evaluated the ApoE genetic polymorphism and its relation to MetS defined by the modified National Cholesterol Education Program and International Diabetes Federation criteria in a population-based cross-sectional survey of an elderly Chinese population in Beijing, China. Genotypes of 937 men and 1385 women were included in the study. All participants were measured for blood pressure, anthropometric measurements, and fasting concentrations of glucose, triglycerides, cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. We applied a logistic regression model to derive adjusted odds ratios (ORs) and their 95% confidence intervals. In this Chinese population, the ɛ2, ɛ3, and ɛ4 allele frequencies were 8.3%, 83.4%, and 8.3% for men and 8.7%, 82.9%, and 8.4% for women, respectively. In men, concentrations of fasting triglycerides were higher among the APOE2 and E4 subjects; and a lower level of high-density lipoprotein cholesterol was observed in the APOE4 group. There were approximately linear associations of low-density lipoprotein cholesterol levels with APOE genotype groups in both men and women. We observed that the ɛ4 allele was associated with a significantly increased OR of MetS defined by the modified National Cholesterol Education Program criteria in men (OR, 1.75; 95% confidence interval, 1.17-2.63). In summary, our data show that common polymorphism of ApoE gene is associated with the presence of MetS in an elderly Chinese population.

[Study on Mobile Phone Based Wireless ECG Monitoring Technology System Typical Demonstration Applications]

Zhongguo Yi Liao Qi Xie Za Zhi = Chinese Journal of Medical Instrumentation. Jan, 2011  |  Pubmed ID: 21553529

Based on the mobile phone platform with wireless real-time ECG monitoring system developed in our lab, this article is dedicated to evaluate its practical value in people test. A series of new conceptual experiments were designed and performed. Particularly, ECG characteristics under different age, gender, health and motion conditions are evaluated. Effects of living habits such as drinking wine, coffee including various psychological conditions such as excitation, anxiety etc. to the ECG response are investigated. The human ECG under different time in a day such as morning, afternoon and late-night was evaluated. These conceptual experiments, which are hard to conduct otherwise using conventional devices, demonstrate the pervasive merits of the new system for fundamental study of heart disease as well as daily healthcare.

Conjoint Analysis of Patient Preferences on Medicare Medication Therapy Management

Journal of the American Pharmacists Association : JAPhA. May-Jun, 2011  |  Pubmed ID: 21555290

To identify attributes of medication therapy management (MTM) valued by Medicare beneficiaries and to determine patient preferences and willingness to pay for MTM attributes.

Evidence for Association Between Disrupted-in-Schizophrenia 1 (DISC1) Gene Polymorphisms and Autism in Chinese Han Population: a Family-based Association Study

Behavioral and Brain Functions : BBF. 2011  |  Pubmed ID: 21569632

Disrupted-in-Schizophrenia 1 (DISC1) gene is one of the most promising candidate genes for major mental disorders. In a previous study, a Finnish group demonstrated that DISC1 polymorphisms were associated with autism and Asperger syndrome. However, the results were not replicated in Korean population. To determine whether DISC1 is associated with autism in Chinese Han population, we performed a family-based association study between DISC1 polymorphisms and autism.

The Controversial Links Among Calorie Restriction, SIRT1, and Resveratrol

Free Radical Biology & Medicine. Jul, 2011  |  Pubmed ID: 21569839

It has been widely known that slow metabolism induced by calorie restriction (CR) can extend the life span of model organisms though the underlying mechanism remains poorly understood. Accumulated evidence suggests that SIRT1 may be actively involved in CR-induced signaling pathways. As a putative activator of SIRT1, resveratrol, known for the French paradox, can partially mimic the physiological effects of CR. While the deacetylase activity of SIRT1 is important for the beneficial effects of resveratrol, resveratrol-induced SIRT1 activation has recently been challenged by the observations that resveratrol could not induce SIRT1-mediated deacetylation of native substrates in vitro. To resolve the discrepancy of resveratrol-induced activation of SIRT1 deacetylase activity between the in vitro and in vivo assays, a model of indirect SIRT1 activation by resveratrol is proposed. In this review, we will discuss the emerging roles of SIRT1 and resveratrol in CR and focus on debate over the links between SIRT1 and resveratrol.

A Biosensor Prepared by Co-entrapment of a Glucose Oxidase and a Carbon Nanotube Within an Electrochemically Deposited Redox Polymer Multilayer

Bioelectrochemistry (Amsterdam, Netherlands). Jun, 2011  |  Pubmed ID: 21570925

A glucose biosensor based on a nanocomposite made by layer-by-layer electrodeposition of the redox polymer into a multilayer containing glucose oxidase (GOx) and single-walled carbon nanotubes (SWCNT) on a screen-printed carbon electrode (SPCE) surface was developed. The objectives of the electrodeposition of redox polymer are to stabilize further the multilayer using a coordinative cross-linked redox polymer and to wire the GOx. The electrochemistry of the layer-by-layer assembly of the GOx/SWCNT/redox polymer nanocomposite was followed by cyclic voltammetry. The resultant biosensor provided stable and reproducible electrocatalytic responses to glucose, and the electrocatalytic current for glucose oxidation was enhanced with an increase in the number of layers. The biosensor displayed a linear range from 0.5 to 6.0mM, a sensitivity of 16.4μA/(mMcm(2)), and a response time of about 5s. It shows no response to 0.05mM of ascorbic acid, 0.32mM of uric acid and 0.20mM of acetaminophen using a Nafion membrane covering the nanocomposite-modified electrode surface.

A Study of Cycling Induced Degradation Mechanisms in Si Nanocrystal Memory Devices

Nanotechnology. Jun, 2011  |  Pubmed ID: 21572215

The endurance of Si nanocrystal memory devices under Fowler-Nordheim program and erase (P/E) cycling is investigated. Both threshold voltage (V(th)) and subthreshold swing (SS) degradation are observed when using a high program or erase voltage. The change of SS is found to be proportional to the shift of V(th), indicating that the generation of interface traps plays a dominant role. The charge pumping and the mid-gap voltage methods have been used to analyze endurance degradation both qualitatively and quantitatively. It is concluded that high erase voltage causes severe threshold voltage degradation by generating more interface traps and trapped oxide charges.

[Characteristics of Human Metapneumovirus Respiratory Tract Infection in Children and the Relationship Between the Infection and Meteorological Conditions]

Zhonghua Er Ke Za Zhi. Chinese Journal of Pediatrics. Mar, 2011  |  Pubmed ID: 21575373

To study the epidemiology of human metapneumovirus (hMPV) infection in children and its relations with meteorological conditions in Suzhou.

[Predicting Clinical Chemo-sensitivity of Primary Ovarian Cancer Using Adenosine Triphosphate-tumor Chemosensitivity Assay Combined with Detection of Drug Resistance Genes]

Zhonghua Fu Chan Ke Za Zhi. Mar, 2011  |  Pubmed ID: 21575453

To predict clinical chemotherapy sensitivity of primary ovarian cancer by jointing adenosine triphosphate (ATP)-tumor chemo-sensitivity assay (TCA) method in vitro and detection of drug resistance genes, provide reference for clinical treatment.

Characterization of 2-(2,6-dichloro-benzyl)-thiazolo[5,4-d]pyrimidin-7-yl]-(4-trifluoromethyl-phenyl)-amine (JNJ-39729209) As a Novel TRPV1 Antagonist

European Journal of Pharmacology. Aug, 2011  |  Pubmed ID: 21575625

As an integrator of multiple nociceptive and/or inflammatory stimuli, TRPV1 is an attractive therapeutic target for the treatment of various painful disorders. Several TRPV1 antagonists have been advanced into clinical trials and the initial observations suggest that TRPV1 antagonism may be associated with mild hyperthermia and thermal insensitivity in man. However, no clinical efficacy studies have been described to date, making an assessment of risk:benefit impossible. Furthermore, it is not clear whether these early observations are representative of all TRPV1 antagonists and whether additional clinical studies with novel TRPV1 antagonists are required in order to understand optimal compound characteristics. In the present study we describe 2-(2,6-dichloro-benzyl)-thiazolo[5,4-d]pyrimidin-7-yl]-(4-trifluoromethyl-phenyl)-amine (JNJ-39729309) as a novel, TRPV1 antagonist. JNJ-39729209 displaced tritiated resiniferotoxin binding to TRPV1 and prevented TRPV1 activation by capsaicin, protons and heat. In-vivo, JNJ-39729209 blocked capsaicin-induced hypotension, induced a mild hyperthermia and inhibited capsaicin-induced hypothermia in a dose dependent manner. JNJ-39729209 showed significant efficacy against carrageenan- and CFA-evoked thermal hyperalgesia and exhibited significant anti-tussive activity in a guinea-pig model of capsaicin-induced cough. In pharmacokinetic studies, JNJ-39729209 was found to have low clearance, a moderate volume of distribution, good oral bioavailability and was brain penetrant. On the basis of these findings, JNJ-39729209 represents a structurally novel TRPV1 antagonist with potential for clinical development. The advancement of JNJ-39729209 into human clinical trials could be useful in further understanding the analgesic potential of TRPV1 antagonists.

β-Elemene-induced Autophagy Protects Human Gastric Cancer Cells from Undergoing Apoptosis

BMC Cancer. 2011  |  Pubmed ID: 21595977

β-Elemene, a compound found in an herb used in traditional Chinese medicine, has shown promising anti-cancer effects against a broad spectrum of tumors. The mechanism by which β-elemene kills cells remains unclear. The aim of the present study is to investigate the anti-tumor effect of β-elemene on human gastric cancer cells and the molecular mechanism involved.

Iridoid Glycosides and Glycosidic Constituents from Eriophyton Wallichii Benth

Phytochemistry. Oct, 2011  |  Pubmed ID: 21601897

C₉-iridoid glycosides, wallichiisides A-C, and four dimers, wallichiisides D-G, together with 13 known glycosidic compounds, were isolated from whole plants of Eriophyton wallichii Benth. Their structures were elucidated by spectroscopic methods and comparison with literature values. Four of these compounds showed moderate DPPH free radical scavenging activity.

Depressed Hippocampal MEK/ERK Phosphorylation Correlates with Impaired Cognitive and Synaptic Function in Zinc-deficient Rats

Nutritional Neuroscience. Mar, 2011  |  Pubmed ID: 21605499

An experiment was performed to observe changes of mitogen-activated protein kinase ERK (MEK)/extracellular signal-regulated kinase (ERK) signaling pathways in the hippocampus of zinc-deficient (ZD) rats and the correlation with cognitive dysfunction. Forty-four male weanling Wistar rats were randomly assigned to ZD (n = 22) and control (pair-fed, n = 22) groups. After a 4-week treatment, Y-maze was used to test the spatial memory of the rats. The long-term potentiation (LTP) in rat hippocampal dentate gyrus was observed simultaneously. pMEK, pERK1/2, and pCREB protein levels were examined by Western blot assays. The results demonstrated that the latency period in Y-maze was significantly shorter for the ZD rats. LTP amplitude in the ZD group decreased significantly compared with the control group. pMEK, pERK1/2, and pCREB protein expression of hippocampus in the ZD group decreased significantly. The results implicated a possibility that zinc deficiency-induced cognitive and synaptic impairment may be relevant to the MEK/ERK signaling pathway.

[Histologic Classification of Nasopharyngeal Carcinoma]

Zhonghua Bing Li Xue Za Zhi Chinese Journal of Pathology. May, 2011  |  Pubmed ID: 21756838

Local-global Interaction and the Emergence of Scale-free Networks with Community Structures

Artificial Life. 2011  |  Pubmed ID: 21762023

Understanding complex networks in the real world is a nontrivial task. In the study of community structures we normally encounter several examples of these networks, which makes any statistical inferencing a challenging endeavor. Researchers resort to computer-generated networks that resemble networks encountered in the real world as a means to generate many networks with different sizes, while maintaining the real-world characteristics of interest. The generation of networks that resemble the real world turns out in itself to be a complex search problem. We present a new rewiring algorithm for the generation of networks with unique characteristics that combine the scale-free effects and community structures encountered in the real world. The algorithm is inspired by social interactions in the real world, whereby people tend to connect locally while occasionally they connect globally. This local-global coupling turns out to be a powerful characteristics that is required for our proposed rewiring algorithm to generate networks with community structures, power law distributions both in degree and in community size, positive assortative mixing by degree, and the rich-club phenomenon.

Comparison of Immature and Mature Bone Marrow-derived Dendritic Cells by Atomic Force Microscopy

Nanoscale Research Letters. 2011  |  Pubmed ID: 21762525

ABSTRACT: A comparative study of immature and mature bone marrow-derived dendritic cells (BMDCs) was first performed through an atomic force microscope (AFM) to clarify differences of their nanostructure and adhesion force. AFM images revealed that the immature BMDCs treated by granulocyte macrophage-colony stimulating factor plus IL-4 mainly appeared round with smooth surface, whereas the mature BMDCs induced by lipopolysaccharide displayed an irregular shape with numerous pseudopodia or lamellapodia and ruffles on the cell membrane besides becoming larger, flatter, and longer. AFM quantitative analysis further showed that the surface roughness of the mature BMDCs greatly increased and that the adhesion force of them was fourfold more than that of the immature BMDCs. The nano-features of the mature BMDCs were supported by a high level of IL-12 produced from the mature BMDCs and high expression of MHC-II on the surface of them. These findings provide a new insight into the nanostructure of the immature and mature BMDCs.

[Association Between Risk Factors of Cardiovascular Diseases and Osteoporosis in Postmenopausal Chinese Women]

Zhonghua Liu Xing Bing Xue Za Zhi = Zhonghua Liuxingbingxue Zazhi. Jun, 2011  |  Pubmed ID: 21781470

To assess the relationship between cardiovascular risk factors and osteoporosis.

Interaction of a Wolbachia WSP-like Protein with a Nuclear-encoded Protein of Brugia Malayi

International Journal for Parasitology. Aug, 2011  |  Pubmed ID: 21782817

The Brugia malayi endosymbiont Wolbachia has recently been shown to be essential for its host's survival and development. However, relatively little is known about Wolbachia proteins that interact with the filarial host and which might be important in maintaining the obligate symbiotic relationship. The Wolbachia surface proteins (WSPs) are members of the outer membrane protein family and we hypothesise that they might be involved in the Wolbachia-Brugia symbiotic relationship. Notably, immunolocalisation studies of two WSP members, WSP-0432 and WSP-0284 in B. malayi female adult worms showed that the corresponding proteins are not only present on the surface of Wolbachia but also in the host tissues, with WSP-0284 more abundant in the cuticle, hypodermis and the nuclei within the embryos. These results confirmed that WSPs might be secreted by Wolbachia into the worm's tissue. Our present studies focus on the potential involvement of WSP-0284 in the symbiotic relationship of Wolbachia with its filarial host. We show that WSP-0284 binds specifically to B. malayi crude protein extracts. Furthermore, a fragment of the hypothetical B. malayi protein (Bm1_46455) was found to bind WSP-0284 by panning of a B. malayi cDNA library. The interaction of WSP-0284 and this protein was further confirmed by ELISA and pull-down assays. Localisation by immunoelectron microscopy within Wolbachia cells as well as in the worm's tissues, cuticle and nuclei within embryos established that both proteins are present in similar locations within the parasite and the bacteria. Identifying such specific interactions between B. malayi and Wolbachia proteins should lead to a better understanding of the molecular basis of the filarial nematode and Wolbachia symbiosis.

Differences in Bio-incompatibility Among Four Biocompatible Dialyzer Membranes Using in Maintenance Hemodialysis Patients

Renal Failure. 2011  |  Pubmed ID: 21787159

Following the introduction of modified cellulosic and then synthetic membrane dialyzers, it was realized that the dialyzer bio-incompatibility depends on the membrane composition. We designed a prospective, randomized, cohort study of 6 months to determine several parameters of biocompatibility in maintenance hemodialysis (MHD) patients treated with four different membrane dialyzers.

PEG-detachable and Acid-labile Cross-linked Micelles Based on Orthoester Linked Graft Copolymer for Paclitaxel Release

Nanotechnology. Aug, 2011  |  Pubmed ID: 21788685

Polyethylene glycol detachable graft copolymer, mPEG-g-p(NAS-co-BMA), was synthesized by grafting 2-(ω-methoxy)PEGyl-1,3-dioxan-5-ylamine onto poly(N-(acryloyloxy)succinimide-co-butyl methacrylate). Pseudo in situ cross-linking of the mPEG-g-p(NAS-co-BMA) was performed in dimethylformamide phosphate buffer (v/v = 1/1) by an acid-labile diamine cross-linker bearing two symmetrical cyclic orthoesters. The cross-linked (CL) micelles with different contents of mPEG segments represented different morphologies. The CL micelles containing approximately one mPEG segment exhibited 'echini' morphology whereas the CL micelle with approximately three mPEG segments formed nanowires. The hydrolysis rate of the CL micelles is highly pH-dependent and much more rapid at mild acid than physiological conditions. Hydrolyzates of the CL micelles formed vesicles because new amphiphilic copolymers were formed. Paclitaxel (PTX) was successfully loaded into the CL micelles and a controlled and pH-dependent release behavior was observed. No obvious cytotoxicity was found for the CL micelles at concentration as high as 800  mg l( - 1).

[Relatively Specific Effect of Electroacupuncture of Different Acupoints on Hypothalamic Monoamine Neurotransmitters in Myocardial Ischemia Rats]

Zhen Ci Yan Jiu = Acupuncture Research / [Zhongguo Yi Xue Ke Xue Yuan Yi Xue Qing Bao Yan Jiu Suo Bian Ji]. Jun, 2011  |  Pubmed ID: 21793386

To observe the effect of electroacupuncture (EA) of "Shenmen" (HT 7), "Neiguan" (PC 6), etc. on monoamine neurotransmitter contents of hypothalamic paraventricular nucleus (PVN) region in myocardial ischemia (MI) rats, so as to analyze the substantial basis of efficacy specificity of acupoints in improving MI.

A Rare Perforated Gastrointestinal Stromal Tumor in the Jejunum: a Case Report

The Turkish Journal of Gastroenterology : the Official Journal of Turkish Society of Gastroenterology. 2011  |  Pubmed ID: 21796562

We herein report a 45-year-old Chinese male with a perforated jejunal gastrointestinal stromal tumor causing acute diffuse peritonitis and incomplete intestinal obstruction. At urgent laparotomy, a perforated tumor was found in the jejunum about 40 cm from the Treitz's ligament, and the upper small intestine was twisted 1080°. The clinical symptom of this case is extremely rare, and has not been reported in the literature previously.

Genotoxicity in Vinyl Chloride-exposed Workers and Its Implication for Occupational Exposure Limit

American Journal of Industrial Medicine. Oct, 2011  |  Pubmed ID: 21796658

Vinyl chloride monomer (VCM) is a colorless gas under room temperature and has been mostly used to produce polyvinyl chloride (PVC) since the 1970s. It is classified by the International Agency of Research on Cancer (IARC) as a known human carcinogen (Group 1). In this study, genetic damage in VCM workers was evaluated in relation to their occupational cumulative exposure to VCM.

Alteration of Inhibitory and Activating Natural Killer Cell Receptor Expression on T Cells in Human Immunodeficiency Virus-infected Chinese

Microbiology and Immunology. Oct, 2011  |  Pubmed ID: 21806677

T cell expression of NKRs can trigger or inhibit cell-mediated cytotoxicity. However, few studies on T lymphocyte NKR expression in HIV infection exist. Here, we examined the expression patterns of NKG2D, NKG2A, and KIR3DL1 on CD8⁺ and CD3⁺CD8⁻ cells by multicolor flow cytometry in groups of patients with HIV, AIDS or HAART-treated AIDS, as well as HIV-negative normal controls. Individual analysis of KIR3DL1 on CD3⁺ CD8⁺ or CD3⁺CD8⁻ cells revealed no significant differences among any of the groups (P > 0.05). In contrast, the percentage of NKG2A⁺NKG2D⁻CD8⁺ T cells was higher in the AIDS group than in the HIV-negative normal control group (P < 0.01). Meanwhile, the prevalence of NKG2D⁺ NKG2A⁻ CD8⁺ T cells was lower in the AIDS group than in HIV-negative normal controls (P < 0.001). Similar results were also observed for the percentage of NKG2A⁺ NKG2D⁻ on CD3⁺ CD8⁻ cells. However, in contrast to CD8⁺ T cells, the frequencies of NKG2D⁺ NKG2A⁻ on CD3⁺CD8⁻ cells were higher in AIDS and HIV patients than in HIV-negative normal controls (P < 0.01, P < 0.05, respectively). The percentage of NKG2A⁺NKG2⁻CD8⁺ T cells was negatively correlated with CD4⁺T cell counts (r=-0.499, P < 0.01), while the percentage of NKG2D⁺NKG2A⁻CD8⁺ T cells was positively correlated with CD4⁺ T cell counts (r= 0.494, P < 0.01). The percentage of NKG2D⁺NKG2A⁻CD3⁺CD8⁻ T cells was also positively correlated with viral load (r= 0.527, P < 0.01) and negatively correlated with CD4⁺ T cell counts (r=-0.397, P < 0.05). Finally, HAART treatment reversed the changes in NKR expression caused by HIV infection. These results indicate that the expression of NKRs on T cells may be correlated with HIV disease progression.

Alteration of Inhibitory and Activating NK Cell Receptor Expression on NK Cells in HIV-infected Chinese

Cellular Immunology. 2011  |  Pubmed ID: 21813117

Natural killer (NK) cell function, based on the expression of activating and inhibitory natural killer receptors (NKRs), may become abnormal during human immunodeficiency virus (HIV) infection. In this study, we investigated changes in receptor expression with individual and combinational analysis on NK cell subsets in HIV-infected Chinese. The results showed that natural killer group 2 member D (NKG2D) expression on total NK cells decreased significantly in HIV infection, while the expressions of natural killer group 2 member A (NKG2A) and killer cell immunoglobulin-like receptor, three domains, long cytoplasmic tail 1 (KIR3DL1) on total NK cells were not significantly different between any of the groups including HIV-positive treatment-naïve group, AIDS treatment-naïve group, HAART-treatment AIDS group and HIV-negative control group. Individual analysis of NKG2A(+) and KIR3DL1(+) cells revealed no significant differences in expression in any NK cell subsets between any of the groups, but the combinational analysis of NKG2D(-)NKG2A(+), and NKG2D(-)KIR3DL1(+) on the NK CD56(dim) cell subset in the AIDS group were increased compared to the HIV-negative control group. On the contrary, NKG2D(-)NKG2A(+) expression on the CD56(bright) subset decreased in the AIDS group compared to the control group. Highly active antiretroviral therapy (HAART) treatment almost completely restored the levels of these receptor expressions. The results indicate that the distinct alteration of activating and inhibitory NKR expression on NK cells and its subsets occurred during HIV progression. Moreover, the imbalanced change of activating and inhibitory NKRs on NK cells and its subsets may explain the impaired NK cell immunity in HIV infected individuals.

Motif Difficulty (MD): A Predictive Measure of Problem Difficulty for Evolutionary Algorithms Using Network Motifs

Evolutionary Computation. Aug, 2011  |  Pubmed ID: 21815769

Abstract One of the major challenges in the field of evolutionary algorithms (EAs) is to characterise which kinds of problems are easy and which are not. Researchers have been attracted to predict the behaviour of EAs in different domains. We introduce fitness landscape networks (FLNs) that are formed using operators satisfying specific conditions and define a new predictive measure that we call motif difficulty (MD) for comparison-based EAs. Because it is impractical to exhaustively search the whole network, we propose a sampling technique for calculating an approximate MD measure. Extensive experiments on binary search spaces are conducted to show both the advantages and limitations of MD. Multidimensional knapsack problems (MKPs) are also used to validate the performance of approximate MD on FLNs with different topologies. The effect of two representations, namely binary and permutation, on the difficulty of MKPs is analysed.

Synthesis of 4β-triazole-podophyllotoxin Derivatives by Azide-alkyne Cycloaddition and Biological Evaluation As Potential Antitumor Agents

European Journal of Medicinal Chemistry. Sep, 2011  |  Pubmed ID: 21821321

A representative synthetic process of derivatizing the natural product podophyllotoxin utilizing the copper-catalyzed azide-alkyne cycloaddition (CuAAC) is described including molecular design, reaction optimization and X-ray structure confirmation. Evaluation of cytotoxicity against human cancer cell lines (Hela, K562 and K562/A02) using MTT assay proves that these triazole derivatives have good antitumor activities. High activities toward the drug resistant K562/A02 cell line reveal promising future for these derivatives. The rarely prepared 1,5-disubstituted triazole isomers, which would be omitted by the "click chemistry", were found to have superior cytotoxicities to that of the 1,4-disubstituted isomers.

Morphoproteomics Demonstrates Activation of Mammalian Target of Rapamycin Pathway in Papillary Thyroid Carcinomas with Nuclear Translocation of MTOR in Aggressive Histological Variants

Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc. Dec, 2011  |  Pubmed ID: 21822208

We used morphoproteomics to investigate mammalian target of rapamycin (MTOR) signaling pathway in papillary thyroid carcinomas and correlated the results with clinicopathological parameters. Archival paraffin-embedded tissue of papillary thyroid carcinomas was obtained from 30 patients, including 15 classical type and 8 follicular, 4 tall-cell, 1 columnar-cell, 1 diffuse sclerosing and 1 cribriform variants. Immunohistochemical stains were performed for three phosphorylated (p) protein analytes: p-MTOR (Ser2448), p-Akt (Ser473) and p-p70S6K (Thr389). Chromogenic signals and subcellular compartmentalization (nuclear, cytoplasmic and plasmalemmal) were evaluated. Clinicopathological parameters were reviewed. Immunoreactivities for p-MTOR, p-Akt and p-p70S6K were observed in all papillary thyroid carcinomas. In addition to an expression of p-MTOR in cytoplasmic location, nuclear translocation of p-MTOR with variable loss of plasmalemmal expression, and with concomitant nuclear expression of p-Akt, was also identified in all tall-cell, columnar-cell and diffuse sclerosing variants of papillary thyroid carcinoma. There were no significant differences in the clinicopathological parameters, including tumor size, extrathyroidal extension, angioinvasion and nodal metastases between the groups with and without nuclear expression of p-MTOR (P>0.05). The expressions of p-MTOR in cytoplasmic and/or plasmalemmal locations with the concomitant immunoreactivity for p-p70S6K in all papillary thyroid carcinomas indicate the activation of MTOR complex 1 pathway. The nuclear translocation of p-MTOR evidences the activation of MTOR complex 2 and is identified only in the known aggressive histological variants of papillary thyroid carcinoma, including tall-cell, columnar-cell and diffuse sclerosing variants. Thus, these results suggest the constitutive activation of MTOR signaling pathway in papillary thyroid carcinomas and provide a new insight of biogenetic basis for the aggressive histological variants of papillary thyroid carcinoma. The pattern of expression of p-MTOR in papillary thyroid carcinomas may serve as a diagnostic/prognostic marker and a potential therapeutic target.

Optimal Codon Identities in Bacteria: Implications from the Conflicting Results of Two Different Methods

PloS One. 2011  |  Pubmed ID: 21829489

A correlation method was recently adopted to identify selection-favored 'optimal' codons from 675 bacterial genomes. Surprisingly, the identities of these optimal codons were found to track the bacterial GC content, leading to a conclusion that selection would generally shape the codon usages to the same direction as the overall mutation does. Raising several concerns, here we report a thorough comparative study on 203 well-selected bacterial species, which strongly suggest that the previous conclusion is likely an illusion. Firstly, the previous study did not preclude species that are suffering weak or no selection pressures on their codon usages. For these species, as showed in this study, the optimal codon identities are prone to be incorrect and follow GC content. Secondly, the previous study only adopted the correlation method, without considering another method to test the reliability of inferred optimal codons. Actually by definition, optimal codons can also be identified by simply comparing codon usages between high- and low-expression genes. After using both methods to identify optimal codons for the selected species, we obtained highly conflicting results, suggesting at least one method is misleading. Further we found a critical problem of correlation method at the step of calculating gene bias level. Due to a failure of accurately defining the background mutation, the problem would result in wrong optimal codon identities. In other words, partial mutational effects on codon choices were mistakenly regarded as selective influences, leading to incorrect and biased optimal codon identities. Finally, considering the translational dynamics, optimal codons identified by comparison method can be well-explained by tRNA compositions, whereas optimal codons identified by correlation method can not be. For all above reasons, we conclude that real optimal codons actually do not track the genomic GC content, and correlation method is misleading in identifying optimal codons and better be avoided.

Multimodal Characterization of Compositional, Structural and Functional Features of Human Atherosclerotic Plaques

Biomedical Optics Express. Aug, 2011  |  Pubmed ID: 21833365

Detection of atherosclerotic plaque vulnerability has critical clinical implications for avoiding sudden death in patients with high risk of plaque rupture. We report on multimodality imaging of ex-vivo human carotid plaque samples using a system that integrates fluorescence lifetime imaging (FLIM), ultrasonic backscatter microscopy (UBM), and photoacoustic imaging (PAI). Biochemical composition is differentiated with a high temporal resolution and sensitivity at the surface of the plaque by the FLIM subsystem. 3D microanatomy of the whole plaque is reconstructed by the UBM. Functional imaging associated with optical absorption contrast is evaluated from the PAI component. Simultaneous recordings of the optical, ultrasonic, and photoacoustic data present a wealth of complementary information concerning the plaque composition, structure, and function that are related to plaque vulnerability. This approach is expected to improve our ability to study atherosclerotic plaques. The multimodal system presented here can be translated into a catheter based intraluminal system for future clinical studies.

Reducing Plasma Membrane Sphingomyelin Increases Insulin Sensitivity

Molecular and Cellular Biology. Oct, 2011  |  Pubmed ID: 21844222

It has been shown that inhibition of de novo sphingolipid synthesis increases insulin sensitivity. For further exploration of the mechanism involved, we utilized two models: heterozygous serine palmitoyltransferase (SPT) subunit 2 (Sptlc2) gene knockout mice and sphingomyelin synthase 2 (Sms2) gene knockout mice. SPT is the key enzyme in sphingolipid biosynthesis, and Sptlc2 is one of its subunits. Homozygous Sptlc2-deficient mice are embryonic lethal. However, heterozygous Sptlc2-deficient mice that were viable and without major developmental defects demonstrated decreased ceramide and sphingomyelin levels in the cell plasma membranes, as well as heightened sensitivity to insulin. Moreover, these mutant mice were protected from high-fat diet-induced obesity and insulin resistance. SMS is the last enzyme for sphingomyelin biosynthesis, and SMS2 is one of its isoforms. Sms2 deficiency increased cell membrane ceramide but decreased SM levels. Sms2 deficiency also increased insulin sensitivity and ameliorated high-fat diet-induced obesity. We have concluded that Sptlc2 heterozygous deficiency- or Sms2 deficiency-mediated reduction of SM in the plasma membranes leads to an improvement in tissue and whole-body insulin sensitivity.

Quantitative PK-PD Model-based Translational Pharmacology of a Novel Kappa Opioid Receptor Antagonist Between Rats and Humans

The AAPS Journal. Dec, 2011  |  Pubmed ID: 21847689

Pharmacokinetic-pharmacodynamic (PK-PD) modeling greatly enables quantitative implementation of the "learn and confirm" paradigm across different stages of drug discovery and development. This work describes the successful prospective application of this concept in the discovery and early development of a novel κ-opioid receptor (KOR) antagonist, PF-04455242, where PK-PD understanding from preclinical biomarker responses enabled successful prediction of the clinical response in a proof of mechanism study. Preclinical data obtained in rats included time course measures of the KOR antagonist (PF-04455242), a KOR agonist (spiradoline), and a KOR-mediated biomarker response (prolactin secretion) in plasma. Clinical data included time course measures of PF-04455242 and prolactin in 24 healthy volunteers following a spiradoline challenge and single oral doses of PF-04455242 (18 and 30 mg). In both species, PF-04455242 successfully reversed spiradoline-induced prolactin response. A competitive antagonism model was developed and implemented within NONMEM to describe the effect of PF-04455242 on spiradoline-induced prolactin elevation in rats and humans. The PK-PD model-based estimate of K(i) for PF-04455242 in rats was 414 ng/mL. Accounting for species differences in unbound fraction, in vitro K(i) and brain penetration provided a predicted human K(i) of 44.4 ng/mL. This prediction was in good agreement with that estimated via the application of the proposed PK-PD model to the clinical data (i.e., 39.2 ng/mL). These results illustrate the utility of the proposed PK-PD model in supporting the quantitative translation of preclinical studies into an accurate clinical expectation. As such, the proposed PK-PD model is useful for supporting the design, selection, and early development of novel KOR antagonists.

A Causal Analysis of Intra-abdominal Hemorrhage After Reduced-size Liver Transplantation in Rat

Cell Biochemistry and Biophysics. Dec, 2011  |  Pubmed ID: 21858590

In this study, we analyzed causes of abdominal hemorrhage after reduced-size liver transplantation in rat. Healthy SD rats (weight range of 260-280 g) underwent liver transplantation, the donors were female and the recipients were male rats. The recipients were, on average, by <10 g heavier than the donors. All operations on donor rats were performed by the same person using unaided eyesight. Operations on recipient rats were performed by two persons using unaided eyesight. About 270 rats received reduced-size liver transplantation of which 44 died because of intra-abdominal hemorrhages. The distribution of abdominal hemorrhage sites was as follows: 28 cases with anastomotic hemorrhages of the inferior vena cava of the superior liver, 9 cases with subcapsular hemorrhage, 9 cases with tied hemorrhages from the left lateral lobe, 7 cases with hemorrhages from the papillary lobe, 7 hemorrhages from the triangular lobe, 5 hemorrhages of the right suprarenal vein and lumbar veins, 4 hemorrhages caused by mechanical injury, 4 cuff hemorrhages of the portal vein and the inferior vein cava of the inferior liver, 8 anastomotic hemorrhages of the inferior vena cava of the superior liver and the tied hemorrhage of the left outboard lobe, and 5 hemorrhages of the two tied points of the reduced-size liver. Ten hemorrhages were stopped by suture or/and ligature, and 6 were stopped by washing with or soaking in hot water. Results of this study will be helpful to raise success rates of reduced-size liver transplantation.

The Measurement of Differential EXAFS Modulated by High Pressure

Journal of Synchrotron Radiation. Sep, 2011  |  Pubmed ID: 21862852

Differential EXAFS (DiffEXAFS) is able to detect subtle atomic perturbations in the local area of the absorbing atom. Here a new method of performing DiffEXAFS experiments under the modulation of high pressure has been developed. Periodic pressure was achieved in the gasket with the help of a dynamic diamond anvil cell, and the measurements were conducted in common energy-scanning mode. This technique has been utilized on ZnSe at 4.8 GPa. The present results have demonstrated a good agreement with the equation of state of ZnSe, and revealed sensitivity to atomic displacements of one order higher in magnitude than that of conventional EXAFS.

[Spatiotemporal Analysis of Event-related Potentials During Mind Wandering]

Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University. Aug, 2011  |  Pubmed ID: 21868316

To investigate the neural mechanism of mind wandering.

Demonstration of Motionless Knudsen Pump Based Micro-gas Chromatography Featuring Micro-fabricated Columns and On-column Detectors

Lab on a Chip. Oct, 2011  |  Pubmed ID: 21869988

This paper reports the investigation of a micro-gas chromatography (μGC) system that utilizes an array of miniaturized motionless Knudsen pumps (KPs) as well as microfabricated separation columns and optical detectors. A prototype system was built to achieve a flow rate of 1 mL min(-1) and 0.26 mL min(-1) for helium and dry air, respectively, when they were used as carrier gas. This system was then employed to evaluate GC performance compromises and demonstrate the ability to separate and detect gas mixtures containing analytes of different volatilities and polarities. Furthermore, the use of pressure programming of the KP array was demonstrated to significantly shorten the analysis time while maintaining a high detection resolution. Using this method, we obtained a high resolution detection of 5 alkanes of different volatilities within 5 min. Finally, we successfully detected gas mixtures of various polarities using a tandem-column μGC configuration by installing two on-column optical detectors to obtain complementary chromatograms.

Enantioselective Endocrine-disrupting Effects of Bifenthrin on Hormone Synthesis in Rat Ovarian Cells

Toxicology. Nov, 2011  |  Pubmed ID: 21871944

Bifenthrin (BF), a broad-spectrum and widely used synthetic pyrethroid, is a typical chiral pesticide. More attention is being paid to the health risk assessment of the enantioselective toxicity of BF isomers. In this study, we used rat ovarian granulosa cells as in vitro model to investigate effects of BF enantiomers on the biosynthesis of two hormones, progesterone and prostaglandin E2 (PGE2), which are critical for mammalian reproduction. We showed that 1S-cis-BF, but not 1R-cis-BF significantly decreased the secretion of progesterone and PGE2 in granulosa cells. 1S-isomer of BF reduced the expression of genes P450scc, StAR, PBR and DBI, as well as COX-2, which are involved in regulating the rate-limiting steps of progesterone or PGE2 biosynthesis. The transcriptional activation of StAR and COX-2 promoter were disrupted by 1S-cis-BF. Furthermore, activity of protein kinase C (PKC), an important signaling mediator of progesterone and PGE2 synthesis, was differentially inhibited by 1S-cis-BF. The data of molecular docking revealed that one hydrogen bond was formed between 1S-cis-BF and PKC protein. In conclusion, we firstly reported in this study the enantioselective disrupting effects of BF isomers on progesterone and PGE2 synthesis via PKC pathway in rat ovarian cells. Our findings suggest that the enantioselective toxicity of chiral pesticides should be considered for evaluating mammalian reproductive health, a toxicologic endpoint of great concern in health risk assessment.

[Study of Biological Characteristics of the IVpi-189 Virus Derived from Persistent Influenza A Virus-infected Cell Line]

Bing Du Xue Bao = Chinese Journal of Virology / [bian Ji, Bing Du Xue Bao Bian Ji Wei Yuan Hui]. Jul, 2011  |  Pubmed ID: 21874900

To investigate biological characteristics of the IVpi-189 progeny virus derived from the culture of influenza A virus as a live-attenuated vaccine candidate. Persistent infection of a cultured cell line with influenza A virus (MDCK-IVpi) was established by incubating continuously influenza virus-infected cells at a lower temperature. The infectious progeny virus derived from MDCK-IVpi cells at the 189rd subculture was designated as the IVpi-189 strain of influenza virus. The cytopathic effect induced by IVpi-189 virus was observed under different temperature conditions. The production of infectious progeny virus was examined at 38 and 32 degrees C by plaque titration of cell-associated and released virus. IVpi-189 virus showed cytopathic effect as strong as that of IVwt in infected cell line of MDCK at 32 degrees C. However, when culture temperature was raised to 38 degrees C, the cytopathic effect induced by IVpi-189 virus was delayed and less pronounced. Virus growth in IVpi-189 virus-infected cells at 38 degrees C was significantly reduced as compared with that of IVwt virus, although both viruses yielded nearly equivalent high titers of cell-associated and released virus at 32 degrees C. The reasons of the decreased proliferative ability of IVpi-189 virus at high culture temperature were unrelated with virus inactivation or the release of progeny virus, but associated with the decreased replication of infectious progeny virus in the infected cells. IVpi-189 virus derived from MDCK cells infected persistently with influenza A virus showed biological characteristics as a potential live-attenuated vaccine candidate.

Histopathological Classification of Nasopharyngeal Carcinoma

Asian Pacific Journal of Cancer Prevention : APJCP. 2011  |  Pubmed ID: 21875256

This article reviews all related research and reports on nasopharyngeal cancer (NPC) histopathological classifications worldwide. Despite continuous advance of Chinese and international NPC histopathological classification research, it was difficult to unify previous with current China classifications, and the China with World Health Organization (WHO) classifications. For example, non-keratinizing and undifferentiated carcinoma of the WHO NPC classification does not coincide with poorly-differentiated squamous cell carcinoma of the previous China classification. In addition, the incidence rates of different NPC pathological types show obvious regional discrepancies. It suggested that for facilitating Chinese and international NPC research and exchange, NPC histopathological classifications worldwide should be effectively unified.

Determination for Enterobacter Cloacae Based on a Europium Ternary Complex Labeled DNA Probe

Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy. Nov, 2011  |  Pubmed ID: 21880541

The fast detection and accurate diagnosis of the prevalent pathogenic bacteria is very important for the treatment of disease. Nowadays, fluorescence techniques are important tools for diagnosis. A two-probe tandem DNA hybridization assay was designed for the detection of Enterobacter cloacae based on time-resolved fluorescence. In this work, the authors synthesized a novel europium ternary complex Eu(TTA)(3)(5-NH(2)-phen) with intense luminescence, high fluorescence quantum yield and long lifetime before. We developed a method based on this europium complex for the specific detection of original extracted DNA from E. cloacae. In the hybridization assay format, the reporter probe was labeled with Eu(TTA)(3)(5-NH(2)-phen) on the 5'-terminus, and the capture probe capture probe was covalent immobilized on the surface of the glutaraldehyde treated glass slides. The original extracted DNA of samples was directly used without any DNA purification and amplification. The detection was conducted by monitoring the fluorescence intensity from the glass surface after DNA hybridization. The detection limit of the DNA was 5×10(-10) mol L(-1). The results of the present work proved that this new approach was easy to operate with high sensitivity and specificity. It could be conducted as a powerful tool for the detection of pathogen microorganisms in the environment.

Study of the Relationship Between Genetics and Geography in Determining the Quality of Astragali Radix

Biological & Pharmaceutical Bulletin. 2011  |  Pubmed ID: 21881225

Astragali Radix (AR), prepared from the roots of Astragalus membranaceus (FISCH. ex LINK) BUNGE or its variey, A. membranaceus (FISCH. ex LINK) BUNGE var. mongholicus (BUNGE) HSIAO., is one of the most used and valuable traditional Chinese medicines (TCMs). Historically, Hunyuan, Shanxi Province in China is the geo-authentic producing area of AR and crude AR from here called "geo-authentic." According to tradition, geo-authentic TCMs define both authenticity and quality. However, no scientific investigation has ever determined whether the superior quality of Hunyuan AR is due to the genetic characteristics or to the local environment. In our study, seeds of 30 AR samples representing the two varieties from different regions were cultivated in Hunyuan under the same conditions. A method, using ultra-performance liquid chromatography coupled with photodiode array detector and evaporative light scattering detectors, was developed to evaluate the quality through a simultaneous determination of four major isoflavonoids and four major saponins. The two AR varieties were successfully distinguished by principal component analysis while samples of the same species with different seeds origins could not be distinguished. A genetic study demonstrated that the internal transcribed spacer sequences of the nuclear ribosomal DNA in A. membranaceus var. mongholicus samples from different geographical regions were highly conservative. These results indicate that the content of active components in AR depends on the interaction of genotype and environment. At the varietal level, genetic properties appear to be more important for pharmaceutical quality than environmental factors, while on the intraspecific level environmental factors might be more important than genetic properties.

No Association of Polymorphisms in the CDK5, NDEL1, and LIS1 with Autism in Chinese Han Population

Psychiatry Research. Dec, 2011  |  Pubmed ID: 21890215

Autism is a pervasive neurodevelopmental disorder. CDK5 (cyclin-dependent kinase 5) and its interacting molecules are involved in neurodevelopment. We performed a family-based association analysis between CDK5, NDEL1, and LIS1 polymorphisms and autism in a Chinese Han population. Our study did not detect a significant association. It indicated that common genetic variations in these genes might not play a role in the genetic predisposition to autism.

Demographics of Apheresis Platelet Donors in Five Blood Centers in China

Transfusion. Sep, 2011  |  Pubmed ID: 21895674

BACKGROUND: Blood component donations by apheresis has become more common in modern blood transfusion practices. However, apheresis donation still remains less common in China. This study describes the demographic profile and transfusion-transmissible infection (TTI) prevalence among donors making apheresis platelet (AP) donations compared to those making whole blood (WB) donations and the differences among five geographically diverse blood centers in China. STUDY DESIGN AND METHODS: This is a descriptive study using data from all successful donations at the five blood centers in 2008 and 2009. Donor demographic and TTI screening reactive rates were collected for WB and AP donations and blood centers. Logistic regression was used to identify independent factors associated with AP donations. RESULTS: From January 1, 2008, to December 31, 2009, there were 512,594 WB and 26,199 AP donations at five blood centers. AP donations accounted for 4.9% of all donations. AP donations have lower reactive rate than WB donations for hepatitis B virus surface antigen, hepatitis C virus antibodies, human immunodeficiency virus antibodies, and syphilis screening testing. Males, donors older than 25 years old, non-Han donors, and donors with below high school educational level were more likely to make AP donations. The characteristics of AP donations differed among the five Chinese blood centers. CONCLUSION: Our analysis suggests that the characteristics of AP donations in China are different from WB donations and differ among the five Chinese blood centers. Some of the differences are likely due to different recruitment policies. Further studies should be conducted to understand what motivates Chinese blood donors to participate as AP donors.

Preliminary Study of Whole-body Diffusion-weighted Imaging in Detecting Pulmonary Metastatic Lesions from Clear Cell Renal Cell Carcinoma: Comparison with CT

Acta Radiologica (Stockholm, Sweden : 1987). Nov, 2011  |  Pubmed ID: 21903870

Whole-body diffusion-weighted imaging (DWI) has been widely used in detecting malignant metastases, including pulmonary metastases.

Nitroolefin-based Coumarin As a Colorimetric and Fluorescent Dual Probe for Biothiols

Chemical Communications (Cambridge, England). Oct, 2011  |  Pubmed ID: 21909533

A coumarin-based thiol probe featuring the 1,4-addition reaction of thiols to nitroolefin was reported. The molecular probe exhibited higher selectivity toward biothiols (Cys, Hcy and GSH) than other amino acids.

Increased Susceptibility of ST2-deficient Mice to Polymicrobial Sepsis is Associated with an Impaired Bactericidal Function

Journal of Immunology (Baltimore, Md. : 1950). Oct, 2011  |  Pubmed ID: 21911606

ST2, a member of the Toll/IL-1R superfamily, negatively regulates both TLR2 and TLR4 signaling. In this study, we report that ST2-deficient mice were more susceptible to polymicrobial sepsis than their wild-type littermates, with increased production of proinflammatory cytokines. Bacterial clearance from the circulation and visceral organs following polymicrobial infection was markedly impaired in ST2-deficient mice. This was associated with substantially reduced uptake, phagocytosis, and intracellular killing of both Gram-positive and Gram-negative bacteria by ST2-deficient phagocytes. Consistent with a reduced antimicrobial response, phagocytes lacking ST2 displayed a defect in bactericidal activity in response to bacterial challenges with severely impaired phagosome maturation and NOX2 function. Thus, ST2-deficient mice exhibit an increased susceptibility to polymicrobial infection with impaired bacterial clearance, which is associated with defects in phagosome maturation and NOX2-derived production of reactive oxygen species characterized in ST2-deficient phagocytes.

[Effect of Continuous Renal Replacement Therapy Started at Different Time on Patients with Multiple Organ Dysfunction Syndrome]

Zhonghua Yi Xue Za Zhi. Jun, 2011  |  Pubmed ID: 21914312

To explore the effects of continuous renal replacement therapy (CRRT) on serum cytokines and prognosis in multiple organ dysfunction syndrome (MODS) patients based on different therapeutic opportunities.

Molecular Evolution of Adh and LEAFY and the Phylogenetic Utility of Their Introns in Pyrus (Rosaceae)

BMC Evolutionary Biology. 2011  |  Pubmed ID: 21917170

The genus Pyrus belongs to the tribe Pyreae (the former subfamily Maloideae) of the family Rosaceae, and includes one of the most important commercial fruit crops, pear. The phylogeny of Pyrus has not been definitively reconstructed. In our previous efforts, the internal transcribed spacer region (ITS) revealed a poorly resolved phylogeny due to non-concerted evolution of nrDNA arrays. Therefore, introns of low copy nuclear genes (LCNG) are explored here for improved resolution. However, paralogs and lineage sorting are still two challenges for applying LCNGs in phylogenetic studies, and at least two independent nuclear loci should be compared. In this work the second intron of LEAFY and the alcohol dehydrogenase gene (Adh) were selected to investigate their molecular evolution and phylogenetic utility.

Highly Sensitive Electrochemiluminescence Detection of Single-nucleotide Polymorphisms Based on Isothermal Cycle-assisted Triple-stem Probe with Dual-nanoparticle Label

Analytical Chemistry. Nov, 2011  |  Pubmed ID: 21923133

We report here a new electrochemiluminescence (ECL) approach for detection of single nucleotide polymorphisms (SNPs) based on isothermal cycle-assisted triple-stem probe labeled with Au nanoparticles (NPs) and CdTe NPs. The system is composed of a CdS nanocrystals (NCs) film on glassy carbon electrode (GCE) as ECL emitter attached a double-stem DNA probe labeled with Au NPs. Then, the third stem labeled with CdTe NPs hybridizes with the double-stem DNA to form a triple-stem probe with the two labels near the CdS NCs film. A dual-quenched ECL of CdS NCs film is achieved due to energy transfer (ET) from CdS NCs to Au NPs and CdTe NPs, which makes the sensor exhibit relatively low background. Once the one base mutant DNA (mDNA) sequence as target of SNPs analysis displaces the third stem and hybridizes with the double-stem probe, forcing Au NPs away from the CdS NCs film, an ECL enhancement by the ECL-induced surface plasmon resonance of Au NPs is observed. Furthermore, after an isothermal cycle induced by primer, polymerase, and nicking endonuclease (NEase), a further enhancement of ECL is obtained. Taking advantages of the isothermal circular amplification system and the triple-stem probe architecture which enables turning its high selectivity toward specific target sequences, the reported biosensor shows excellent discrimination capabilities of SNPs with high selectivity and low detection limit (35 aM).

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

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

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

[Congenital Syphillis Presenting Congenital Nephrotic Syndrome in Two Children and Related Data Review]

Beijing Da Xue Xue Bao. Yi Xue Ban = Journal of Peking University. Health Sciences. Dec, 2011  |  Pubmed ID: 22178846

To study the clinical features of congenital syphillis presenting congenital nephrotic syndrome(CNS) in children.

Erratum To: Epidemiological Characteristics of Adult SCIWORA in Tianjin, China: a Preliminary Study

European Spine Journal : Official Publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. Dec, 2011  |  Pubmed ID: 22183891

Comprehensive Analysis of Tandem Amino Acid Repeats from Ten Angiosperm Genomes

BMC Genomics. Dec, 2011  |  Pubmed ID: 22195734

ABSTRACT: BACKGROUND: The presence of tandem amino acid repeats (AARs) is one of the signatures of eukaryotic proteins. AARs were thought to be frequently involved in bio-molecular interactions. Comprehensive studies that primarily focused on metazoan AARs have suggested that AARs are evolving rapidly and are highly variable among species. However, there is still controversy over causal factors of this inter-species variation. In this work, we attempted to investigate this topic mainly by comparing AARs in orthologous proteins from ten angiosperm genomes. RESULTS: Angiosperm AAR content is positively correlated with the GC content of the protein coding sequence. However, based on observations from fungal AARs and insect AARs, we argue that the applicability of this kind of correlation is limited by AAR residue composition and species' life history traits. Angiosperm AARs also tend to be fast evolving and structurally disordered, supporting the results of comprehensive analyses of metazoans. The functions of conserved long AARs are summarized. Finally, we propose that the rapid mRNA decay rate, alternative splicing and tissue specificity are regulatory processes that are associated with angiosperm proteins harboring AARs. CONCLUSIONS: Our investigation suggests that GC content is a predictor of AAR content in the protein coding sequence under certain conditions. Although angiosperm AARs lack conservation and 3D structure, a fraction of the proteins that contain AARs may be functionally important and are under extensive regulation in plant cells.

A Poised Chromatin Platform for TGF-β Access to Master Regulators

Cell. Dec, 2011  |  Pubmed ID: 22196728

Specific chromatin marks keep master regulators of differentiation silent yet poised for activation by extracellular signals. We report that nodal TGF-β signals use the poised histone mark H3K9me3 to trigger differentiation of mammalian embryonic stem cells. Nodal receptors induce the formation of companion Smad4-Smad2/3 and TRIM33-Smad2/3 complexes. The PHD-Bromo cassette of TRIM33 facilitates binding of TRIM33-Smad2/3 to H3K9me3 and H3K18ac on the promoters of mesendoderm regulators Gsc and Mixl1. The crystal structure of this cassette, bound to histone H3 peptides, illustrates that PHD recognizes K9me3, and Bromo binds an adjacent K18ac. The interaction between TRIM33-Smad2/3 and H3K9me3 displaces the chromatin-compacting factor HP1γ, making nodal response elements accessible to Smad4-Smad2/3 for Pol II recruitment. In turn, Smad4 increases K18 acetylation to augment TRIM33-Smad2/3 binding. Thus, nodal effectors use the H3K9me3 mark as a platform to switch master regulators of stem cell differentiation from the poised to the active state.

Cytotoxic Cardenolides from the Stems of Periploca Forrestii

Steroids. Dec, 2011  |  Pubmed ID: 22212302

Six new cardenolides, periforosides D-E (1-2), periforgenin C (3) and periforosides F-H (4-6), as well as 10 previously identified cardenolides (7-16) were isolated from the ethanol extract of the stems of Periploca forrestii. The structures of the new compounds were determined using extensive spectroscopic analyses including HRESI-MS, 1D and 2D NMR data. Evaluation of the cytotoxic activity of all the isolated compounds in five different human cancer cell lines indicated that compounds 2-6, 8, 9 and 12-16 have potent activity.

On-line Preconcentration of Sodium Dodecyl Sulfate-protein Complexes Using Electrokinetic Supercharging Method with a Prefilled Water Plug in Capillary Sieving Electrophoresis

Se Pu = Chinese Journal of Chromatography / Zhongguo Hua Xue Hui. Sep, 2011  |  Pubmed ID: 22233073

An electrokinetic supercharging (EKS) method with a prefilled water plug at the head column of capillary was developed for on-line preconcentration of sodium dodecyl sulfate (SDS)-protein complexes in capillary sieving electrophoresis (CSE). Conventional EKS is a combination of electrokinetic injection with transient isotachophoresis (tr-ITP). The capillary is first filled with background electrolyte, then an appropriate amount of a leading electrolyte is filled and electro-injection is carried out for certain duration. After that, terminating electrolyte is filled, and tr-ITP is subsequently initiated, followed by capillary electrophoresis (CE) separation. In this work, the performance of EKS was evaluated by integrating multiple sub-methods step by step, and a water plug containing polymer was introduced before electrokinetic injection in order to further improve the concentration effect. The positive effects of the sub-methods were verified, including molecular sieving effect of polymer, field enhanced sample injection (FESI) with and without a water plug, and transient isotachophoretic electrophoresis-based FESI. It was observed that analyte discrimination usually encountered in conventional electrokinetic injection was eliminated due to the similar charge to mass ratios of SDS-protein complexes. Based on these results, a hybrid on-line preconcentration method, EKS with injecting a water plug containing polymer before sample electrokinetic injection, was proposed and used to indiscriminately preconcentrate SDS-protein complexes, which provided a sensitivity enhancement factor of more than 1000. It was very suitable for the analysis of low-abundance proteins, providing the information of their molecular mass.

[Study on Mobile Phone Enabled Wireless Detection of Saliva Glucose]

Zhongguo Yi Liao Qi Xie Za Zhi = Chinese Journal of Medical Instrumentation. Sep, 2011  |  Pubmed ID: 22242375

In this study, based on the correlation between the blood and saliva glucose, we proposed and developed a new conceptual method of using mobile phone to measure wirelessly the glucose concentration in saliva. According to the experiments on simulated saliva, the new system could draw, display, store and carry out calculation on the correlation curves between saliva glucose and electrical parameters. This demonstrates the feasibility and bright future of the new technique.

[Simultaneous Determination of Ibuprofen and Arginine in Ibuprofen Injection Using Ultra Performance Liquid Chromatography]

Se Pu = Chinese Journal of Chromatography / Zhongguo Hua Xue Hui. Oct, 2011  |  Pubmed ID: 22268358

An ultra performance liquid chromatography-photodiode array detector (UPLC-PDA) method was developed for the determination of ibuprofen and the solubilizer arginine in ibuprofen injection. 2,4-Dinitroflurobenzene (DNFB) was used as the precolumn derivatization reagent. The separation of ibuprofen and arginine derivative was performed on a BEH C18 column (50 mm x 2. 1 mm, 1.7 microm) with the mobile phase consisting of acetonitrile-0. 05 mol/L potassium dihydrogen phosphate (pH 2. 5) in a gradient elution mode at a flow rate of 0.4 mL/min. Ultraviolet absorption detection wavelengths were set at 357 nm for arginine derivative and 220 nm for ibuprofen. The column temperature was set at 30 degrees C. Good linearities were obtained in the ranges of 2.0 - 100.5 mg/L for ibuprofen and 1.7 - 84.5 mg/L for arginine, both with the correlation coefficients (r) of 0. 999 7. The spiked recoveries were 99. 8% and 99. 6% with the relative standard deviations (RSDs) of 0. 37% and 0. 25% for ibuprofen and arginine, respectively. Their respective limits of quantification (LOQs) (S/N = 10) were 0. 1 ng and 0. 2 ng, and the limits of detection (LODs) (S/N= 3) were 0.03 ng and 0.05 ng. The results demonstrated that the proposed method is simple, accurate, reproducible and suitable for the quality control of ibuprofen injection.

Malignant Fibrous Histiocytoma of the Spleen Accompanying with Hepatic Cyst: Report of a Case and Review of the Literature

Journal of Research in Medical Sciences : the Official Journal of Isfahan University of Medical Sciences. Jul, 2011  |  Pubmed ID: 22279467

Primary malignant fibrous histiocytoma (MFH) of the spleen is extremely rare. Since the first description of primary splenic MFH reported by Govoni et al in 1982, to the best of our knowledge, only 13 cases of MFH of the spleen have been reported in the English language literature in Medline. We herein report a rare case of primary splenic MFH accompanying with hepatic cyst in a 48-year-old Chinese female who treated successfully by laparoscopic splenectomy and fenestration, which has not yet been reported in the literature. Compared with the 13 previously cases of MFH of the spleen, our case is the first case accompanied with other disease, and also the first case treated successfully by laparoscopic splenectomy. A literature review of MFH of the spleen previously reported in the English language literature in Medline is also provided.

Solid Pseudopapillary Tumor of the Pancreas in a Pregnant Woman

Acta Gastro-enterologica Belgica. Dec, 2011  |  Pubmed ID: 22319967

Solid pseudopapillary tumor (SPT) of the pancreas is a rare neoplasm of low malignant potential that mostly affects young women in the second or third decade of life. The number of such patients reported in the literature has increased in recent years, while SPT in pregnancy is extremely rare. To the best of our knowledge, only one case of SPT in pregnancy has been reported in the English-language literature. We herein report a case of asymptomatic SPT in a 26-year-old Chinese female in the 14th week of pregnancy, and present our experience of the surgical management of SPT in pregnancy.

A Functional Polymorphism in the Epidermal Growth Factor Gene Is Associated with Risk for Glioma in a Chinese Population

Genetic Testing and Molecular Biomarkers. Nov, 2011  |  Pubmed ID: 22106858

Epidermal growth factor (EGF) plays a key role in survival of neural and glial precursor cells. A single nucleotide polymorphism of the EGF gene +61G/A in the 5'-untranslated region has been reported to be associated with susceptibility to glioma. The purpose of this study was to investigate the potential association between EGF +61G/A and brain glioma in a Chinese population. A case-control study involving 180 patients with glioma and 360 controls was done. Polymerase chain reaction restriction fragment-length polymorphism assay was used to analyze the EGF +61G/A genotypes. Patients with glioma had a significantly higher frequency of AA genotype (odds ratio, 2.25; 95% confidence interval, 1.20, 4.21; p=0.01] than controls. When stratified by histologic features and World Health Organization grade of glioma, distribution of each genotype did not significantly differ. Our data suggested that the EGF +61G AA genotype was associated with a higher glioma risk in a Chinese population. This finding is in contrast with previous studies that reported G allele as a risk factor for glioma in white patients.

[Trend of Changes on Incidence and Pathological Proportions of Nasopharyngeal Carcinoma in Zhongshan City, Guangdong Province, During 1970 - 2007]

Zhonghua Liu Xing Bing Xue Za Zhi = Zhonghua Liuxingbingxue Zazhi. Nov, 2011  |  Pubmed ID: 22336551

To understand the nasopharyngeal carcinoma (NPC) incidence and pathological changes in Zhongshan city, during 1970 - 2007.

Genetic Analysis of Hantaviruses and Their Rodent Hosts in Central-south China

Virus Research. Feb, 2012  |  Pubmed ID: 22108583

Hantaan virus (HTNV) and Seoul virus (SEOV) are two major zoonotic pathogens of hemorrhagic fever with renal syndrome (HFRS) in Asia. Hubei province, which is located in the central-south China, had been one of the most severe epidemic areas of HFRS. To investigate phylogenetic relationships, genetic diversity and geographic distribution of HTNV and SEOV in their reservoir hosts, a total of 687 rodents were trapped in this area between 2000 and 2009. Sequences of partial S- and M-segments of hantaviruses and mitochondrial D-loop gene from 30 positive samples were determined. Our data indicated that SEOV and HTNV were co-circulating in Hubei. Phylogenetic analysis based on partial S- and M-segment sequences revealed two and three previously undefined lineages of SEOV, and a novel genetic lineage of HTNV, respectively. Four inter-lineage reassortment SEOVs carried by Rattus norvegicus and Apodemus agrarius were observed. It suggests that SEOV may cause spillover infections to A. agrarius naturally. The abundance of the phylogenetic lineages of SEOV suggested that central-south China was a radiation center for SEOVs.

The Increasing Prevalence of Serologic Markers for Syphilis Among Chinese Blood Donors in 2008 Through 2010 During a Syphilis Epidemic

Transfusion. Feb, 2012  |  Pubmed ID: 22321121

BACKGROUND: In China, the growing syphilis epidemic parallels the spread of human immunodeficiency virus (HIV) in the general population. This study evaluated the prevalence and incidence of serologic markers for syphilis among donors at five Chinese blood centers. STUDY DESIGN AND METHODS: We examined whole blood and apheresis donations collected from January 2008 through December 2010. Postdonation testing of syphilis was conducted using two different Treponema pallidum antibody enzyme-linked immunosorbent assay kits. The prevalence of serologic markers for syphilis (%), and the rate of coinfection with HIV-1/2, hepatitis B virus (HBV), and hepatitis C virus (HCV) were calculated. A multivariable logistic regression analysis was conducted examining donor characteristics associated with positive syphilis serology. Seroconversion rate and syphilis incidence were estimated. RESULTS: Of 801,511 donations, 60% were from first-time donors and 40% were from repeat donors. There was a significant increase in syphilis serologic markers among first-time donors with 0.41, 0.45, and 0.57% positivity over 3 years (p < 0.001). Approximately 2.8, 0.8, and 0.5% of HIV-1/2-, HBV-, and HCV-positive donations also tested reactive for syphilis. Logistic regression results suggest that first-time donors were nine times more likely to be syphilis positive than repeat donors. Higher syphilis positivity was associated with donors older than 25 years and with less education. Estimated incidence among repeat donations was 33 (95% confidence interval, 29-39) per 100,000 person-years. CONCLUSION: The increase in syphilis serologic prevalence reflected the syphilis epidemic in the general population. Without screening, most of these syphilis-positive donations would get into the blood supply. Thus, during a syphilis epidemic, continued syphilis screening of blood donations may be important to maintain blood safety and public health.

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.

Production of the Monoclonal Antibody Against Sudan 2 for Immunoassay of Sudan Dyes in Egg

Analytical Biochemistry. Feb, 2012  |  Pubmed ID: 22327048

Many methods have been reported to determine the residues of Sudan dyes in food samples. Among the reported methods, enzyme linked immunosorbent assay (ELISA) was a usually used practical screen tool. In this study, a novel hapten of Sudan 2 was synthesized by coupling 4-amino-3-methylbenzoic acid to β-naphthol, and the monoclonal antibody against Sudan 2 was produced. The obtained antibody can recognize Sudan 1, 2, 3, 4, Sudan red G and Para red simultaneously. After evaluation of different coating antigens, a heterologous indirect competitive ELISA was then developed to determine the six Sudan dyes in egg. The crossreactivities for the six analytes were in a range of 63%-100% and the limits of detection were in a range of 0.2-0.5 ng/g depending on the compound. Intra- and inter-assay recoveries from the standards fortified blank egg were in a range of 71.7%-97.6% with coefficients of variation lower than 17.1%.

Phenolic Compounds and Antioxidant Activities of Liriope Muscari

Molecules (Basel, Switzerland). 2012  |  Pubmed ID: 22328078

Five phenolic compounds, namely N-trans-coumaroyltyramine (1), N-trans-feruloyltyramine (2), N-trans-feruloyloctopamine (3), 5,7-dihydroxy-8-methoxyflavone (4) and (3S)3,5,4'-trihydroxy-7-methoxy-6-methylhomoisoflavanone (5), were isolated from the fibrous roots of Liriope muscari (Liliaceae). Compounds 2-5 were isolated for the first time from the Liriope genus. Their in vitro antioxidant activities were assessed by the DPPH and ABTS scavenging methods with microplate assays. The structure-activity relationships of compounds 1-3 are discussed.

Sex Differences in Anterior Cingulate Cortex Activation During Impulse Inhibition and Behavioral Correlates

Psychiatry Research. Jan, 2012  |  Pubmed ID: 22285718

Poor impulse inhibition is associated with behavioral problems including aggression and violence as well as clinical diagnoses such as attention deficit hyperactivity disorder (ADHD) and substance abuse, all of which are more prevalent in men than in women. Studies have found that fronto-parietal and fronto-striatal-thalamic networks are critical for successful impulse inhibition. However, few studies have investigated neural differences in these networks between men and women. In this study, we use a well established behavioral task, the parametric Go/noGo task, to explore the relationships between brain regional activity during impulse control and impulsivity trait measures, as well as sex differences in these relationships. We found that males showed heightened activation of the rostral anterior cingulate, which correlated with ratings related to impulsivity. We also found that the activation/deactivation in males and females correlates with personality ratings in a sex-specific manner.

A Novel Method for Fast and Robust Estimation of Fluorescence Decay Dynamics Using Constrained Least-squares Deconvolution with Laguerre Expansion

Physics in Medicine and Biology. Feb, 2012  |  Pubmed ID: 22290334

We report a novel method for estimating fluorescence impulse response function (fIRF) from noise-corrupted time-domain fluorescence measurements of biological tissue. This method is based on the use of high-order Laguerre basis functions and a constrained least-squares approach that addresses the problem of overfitting due to increased model complexity. The new method was extensively evaluated on fluorescence data from simulation, fluorescent standard dyes, ex vivo tissue samples of atherosclerotic plaques and in vivo oral carcinoma. Current results demonstrate that this method allows for rapid and accurate deconvolution of multiple channel fluorescence decays without adaptively adjusting the Laguerre scale parameter. The appropriate choice of the scale parameter is essential for accurate estimation of the fIRF. The method described here is anticipated to play an important role in the development of computational techniques for real-time analysis of time-resolved fluorescence data from biological tissues and to support the advancement of fluorescence lifetime instrumentation for biomedical diagnostics by providing a means for on-line robust analysis of fluorescence decay.

Risk Factors for Autistic Regression: Results of an Ambispective Cohort Study

Journal of Child Neurology. Jan, 2012  |  Pubmed ID: 22290858

A subgroup of children diagnosed with autism experience developmental regression featured by a loss of previously acquired abilities. The pathogeny of autistic regression is unknown, although many risk factors likely exist. To better characterize autistic regression and investigate the association between autistic regression and potential influencing factors in Chinese autistic children, we conducted an ambispective study with a cohort of 170 autistic subjects. Analyses by multiple logistic regression showed significant correlations between autistic regression and febrile seizures (OR = 3.53, 95% CI = 1.17-10.65, P = .025), as well as with a family history of neuropsychiatric disorders (OR = 3.62, 95% CI = 1.35-9.71, P = .011). This study suggests that febrile seizures and family history of neuropsychiatric disorders are correlated with autistic regression.

The Magnetic Assembly of Polymer Colloids in a Ferrofluid and Its Display Applications

Nanoscale. Feb, 2012  |  Pubmed ID: 22297654

Nonmagnetic polymer colloids have been assembled into colloidal photonic crystals in a ferrofluid by applying an external magnetic field based on the dipole-dipole interactions of "magnetic holes". The photonic crystal disassembles immediately when the magnetic field is removed. The mechanism of assembly can be explained by two simultaneous processes: phase separation and colloidal assembly. In this work, increasing the size of the building blocks still produces colorful photonic crystals due to their 2nd order diffraction. With a larger building block, the magnetic response between the polymer colloids is greatly enhanced so that an instant and reversible assembly/disassembly can be realized in a much weaker magnetic field and lower ferrofluid concentration. Based on these investigations, a magnetically controlled photonic display unit has been fabricated, which works in a weak magnetic field, has stable reflection signals and possesses fast and reversible on/off switching of reflections.

Cytotoxic Angucycline Class Glycosides from the Deep Sea Actinomycete Streptomyces Lusitanus SCSIO LR32

Journal of Natural Products. Feb, 2012  |  Pubmed ID: 22304344

Five new C-glycoside angucyclines, named grincamycins B-F (1-5), and a known angucycline antibiotic, grincamycin (6), were isolated from Streptomyces lusitanus SCSIO LR32, an actinomycete of deep sea origin. The structures of these compounds were elucidated on the basis of extensive spectroscopic analyses, including MS and 1D and 2D NMR experiments. All compounds except grincamycin F (5) exhibited in vitro cytotoxicities against the human cancer cell lines HepG2, SW-1990, HeLa, NCI-H460, and MCF-7 and the mouse melanoma cell line B16, with IC(50) values ranging from 1.1 to 31 μM.

"One-stop-shop" Cardiac MRI at 3.0T for the Detection of Coronary Artery Disease

International Journal of Cardiology. Feb, 2012  |  Pubmed ID: 22305773

Event-related Potentials Reveal Early Activation of Body Part Representations in Action Concept Comprehension

Neuroscience Letters. Jan, 2012  |  Pubmed ID: 22306088

With tasks involving action concept comprehension, many fMRI studies have reported brain activations in sensori-motor regions specific to effectors of the referent action. There is relatively less evidence whether such activations reflect early semantic access or late conceptual re-processing. Here we recorded event-related potentials when participants recognized noun-verb pairs. For Congruent pairs, the verb was the one most commonly associated with the noun (e.g., football-kick). Compared with a control condition, verbs in Congruent pairs showed priming effects in the time windows of 100-150ms and 210-260ms. Such activation seems to be specific to body part but not other aspects of the action as similar priming effect was also found when the noun and verb involved different actions though sharing the same body part (e.g., football-jump), documenting for the first time the early activation of body part representations in action concept comprehension.

Icariin Ameliorates Streptozotocin-induced Diabetic Retinopathy in Vitro and in Vivo

International Journal of Molecular Sciences. 2012  |  Pubmed ID: 22312291

This study investigated the effect of Icariin (ICA) supplementation on diabetic retinopathy (DR) in a streptozotocin-induced diabetic rat model system. Fifty Sprague Dawley rats were randomly distributed into a control group and a streptozotocin-induced diabetes group. Diabetic rats were randomly divided into two groups; one group received ICA 5 mg/kg/day for 12 weeks by oral gavage; the other group received saline gavage as a placebo. Retinal morphological changes, endothelial markers (RECA), collagen IV (Col-IV), vascular endothelial growth factor (VEGF), and neuropathic changes (Thy-1 and Brn3a expression) of the retinal ganglion cells (RGCs) were investigated. The effects of ICA at various concentrations (0, 10(1), 10(2), 10(3) nmol/mL) on neurite growth were investigated also in retinal ganglion cells (RGC) cultured from both diabetic and normal animals. Numerous pathological changes (deceased expression of RECA, VEGF, Thy-1, and Brn3a as well as decreased Collagen IV and Müller cell content) were noted in the retinal vessels of diabetic rats; these changes were attenuated in diabetic animals that received ICA. ICA enhanced neurite growth in RGC from both normal rats and diabetic rats in a dose dependent fashion. ICA may be useful in the treatment of diabetic retinopathy. Further investigations are indicated.

Primary Small Cell Carcinoma of the Lesser Omentum

The Kaohsiung Journal of Medical Sciences. Feb, 2012  |  Pubmed ID: 22313540

Although pulmonary small cell carcinoma (SCC) is seen frequently, SCC that originates from the extrapulmonary organs is extremely rare. We herein report a case of a SCC located in the lesser omentum. A 61-year-old male was admitted to our department due to intermittent epigastralgia for 2 months. Ultrasonography (US) revealed an irregular hypoechoic mass measuring about 58 mm × 50 mm × 45 mm under the left lobe of the liver. Magnetic resonance imaging (MRI) was performed to verify the irregular mass with T1- and T2- weighted images between the left lobe of liver and the stomach. At laparotomy, the well-circumscribed neoplasm was found in the lesser omentum, and the fundus of the neoplasm was located in the root of left gastric artery. Intraoperative microscopic evaluation of frozen sections revealed malignancy of the lesser omentum. Resection of the neoplasm was performed, and the combined resection of the vagal nerve was also performed for the partial adhesion. Pyloroplasty was performed for avoiding delayed gastric emptying caused by combined resection of vagal nerve. The lymph nodes dissection at lesser curvature and right cardia was also performed with a negative result. Based on the histological findings, the final diagnosis of primary lesser omental SCC was confirmed. The pathologic staging showed locoregional disease.

Impact of Diabetes, High Triglycerides and Low HDL Cholesterol on Risk for Ischemic Cardiovascular Disease Varies by LDL Cholesterol Level: A 15-year Follow-up of the Chinese Multi-provincial Cohort Study

Diabetes Research and Clinical Practice. Jan, 2012  |  Pubmed ID: 22244364

AIMS: A large proportion of ischemic cardiovascular disease occur in people without hypercholesterolemia. We aimed to investigate whether risk factors other than low-density lipoprotein cholesterol (LDL-C) have different impacts on cardiovascular risk in people with low verses high LDL-C levels. METHODS: A total of 30,378 participants (35-64 years) were followed for 15 years in the Chinese Multi-provincial Cohort Study. Associations of coronary heart disease (CHD) and ischemic stroke with risk factors other than LDL-C were assessed in participants with low (<130mg/dL) and high (≥130mg/dL) LDL-C levels. RESULTS: During the follow-up, 65.5% of CHD and 70.2% of ischemic stroke events occurred in participants with low LDL-C. High triglycerides predicted CHD (HR=1.74, 95% CI 1.25-2.42, P=0.001), and low HDL-C predicted ischemic stroke (HR=1.54, 95% CI 1.18-2.03, P=0.002) only in participants with low LDL-C. Diabetes predicted CHD in participants with high LDL-C (HR=2.38, 95% CI 1.31-4.34, P=0.005), but not in those with low LDL-C. Older age, male, hypertension, central obesity, and smoking had similar effects on the risk in both groups. CONCLUSIONS: Triglycerides and low HDL-C should be addressed in the management of dyslipidemia in people with low LDL-C. When LDL-C is high, tighter management of glycemia and LDL-C is warranted.

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

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

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

Rapid, Sensitive, and Multiplexed On-chip Optical Sensors for Micro-gas Chromatography

Lab on a Chip. Feb, 2012  |  Pubmed ID: 22245960

We developed and characterized a rapid, sensitive and integrated optical vapor sensor array for micro-gas chromatography (μGC) applications. The sensor is based on the Fabry-Pérot (FP) interferometer formed by a micrometre-thin vapor-sensitive polymer layer coated on a silicon wafer. The thickness and the refractive index of the polymer vary in response to the vapor analyte, resulting in a change in the reflected intensity of the laser impinged on the sensor. In our study, four different polymers were coated on four wells pre-etched on a silicon wafer to form a spatially separated sensor array. A CMOS imager was employed to simultaneously monitor the polymers' response, thus enabling multiplexed detection of a vapor analyte passing through the GC column. A sub-second detection time was demonstrated. In addition, a sub-picogram detection limit was achieved, representing orders of magnitude improvement over the on-chip vapor sensors previously reported.

Thromboembolic Events During the Perioperative Period in Patients Undergoing Permanent Pacemaker Implantation

Clinical Cardiology. Feb, 2012  |  Pubmed ID: 22262234

Thromboembolism (TE) is one of the most serious complications after pacemaker implantation. It has been demonstrated that several patient characteristics and different pacing modes are related to an increased risk of TE events during long-term follow-up.

Myocardial Perfusion Magnetic Resonance Imaging Using Sliding-Window Conjugate-Gradient Highly Constrained Back-Projection Reconstruction for Detection of Coronary Artery Disease

The American Journal of Cardiology. Jan, 2012  |  Pubmed ID: 22264595

Myocardial perfusion magnetic resonance imaging (MRI) with sliding-window conjugate-gradient highly constrained back-projection reconstruction (SW-CG-HYPR) allows whole left ventricular coverage, improved temporal and spatial resolution and signal/noise ratio, and reduced cardiac motion-related image artifacts. The accuracy of this technique for detecting coronary artery disease (CAD) has not been determined in a large number of patients. We prospectively evaluated the diagnostic performance of myocardial perfusion MRI with SW-CG-HYPR in patients with suspected CAD. A total of 50 consecutive patients who were scheduled for coronary angiography with suspected CAD underwent myocardial perfusion MRI with SW-CG-HYPR at 3.0 T. The perfusion defects were interpreted qualitatively by 2 blinded observers and were correlated with x-ray angiographic stenoses ≥50%. The prevalence of CAD was 56%. In the per-patient analysis, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of SW-CG-HYPR was 96% (95% confidence interval 82% to 100%), 82% (95% confidence interval 60% to 95%), 87% (95% confidence interval 70% to 96%), 95% (95% confidence interval 74% to100%), and 90% (95% confidence interval 82% to 98%), respectively. In the per-vessel analysis, the corresponding values were 98% (95% confidence interval 91% to 100%), 89% (95% confidence interval 80% to 94%), 86% (95% confidence interval 76% to 93%), 99% (95% confidence interval 93% to 100%), and 93% (95% confidence interval 89% to 97%), respectively. In conclusion, myocardial perfusion MRI using SW-CG-HYPR allows whole left ventricular coverage and high resolution and has high diagnostic accuracy in patients with suspected CAD.

Molecular Characterization and Immunolocalization of a Protein Disulfide Isomerase from Angiostrongylus Cantonensis

Parasitology Research. Jan, 2012  |  Pubmed ID: 22218922

Protein disulfide isomerases (PDIs), belonging to the thioredoxin superfamily, are oxidoreductases that catalyze the formation, reduction, and isomerization of disulfide bonds among cysteine residues of proteins. In this study, we report the cloning and characterization of a cDNA encoding a protein disulfide isomerase (AcPDI) from a cDNA library of fourth-stage larvae of Angiostrongylus cantonensis. The deduced amino acid sequence contains two thioredoxin domains and exhibits high identity to the homologues from other species. Quantitative real-time PCR (qRT-PCR) was performed at the third-stage larvae, fourth-stage larvae, and adult stage of A. cantonensis, and the results revealed that the AcPDI mRNA, while expressed at all three stages, is expressed at a significantly higher level in female adult worms. Results of immunohistochemical studies indicated that the AcPDI expression was specifically localized in the tegument and uterus wall of female adult worms. Biochemical analysis showed that recombinant AcPDI was biologically active in vitro and exhibited the typical biochemical functions of PDIs: oxidase/isomerase and reductase activities. Collectively, these results implied that AcPDI may be a female-enriched protein and associated with the reproductive development of A. cantonensis. In addition, considering its biochemical properties, AcPDI may be involved in the formation of the cuticle of A. cantonensis.

A Naphthalimide-based Glyoxal Hydrazone for Selective Fluorescence Turn-on Sensing of Cys and Hcy

Organic Letters. Jan, 2012  |  Pubmed ID: 22220759

A fluorescent turn-on probe for Cys/Hcy based on inhibiting the C═N isomerization quenching process by an intramolecular hydrogen bond was reported. The probe exhibited higher selectivity toward Cys/Hcy over other amino acids as well as thiol-containing compounds.

Urinary Metabonomics Study on Biochemical Changes in an Experimental Model of Chronic Renal Failure by Adenine Based on UPLC Q-TOF/MS

Clinica Chimica Acta; International Journal of Clinical Chemistry. Mar, 2012  |  Pubmed ID: 22227165

Chronic renal failure (CRF) is a serious clinical symptom, occurring as the end result of all kinds of chronic kidney disease and its pathophysiological mechanism is not yet well understood. We investigated the metabolic profiling of urine samples from CRF model rats to find potential disease biomarkers and research pathology of CRF.

ERK and P38 MAPK Signaling Pathways Are Involved in Ochratoxin A-induced G2 Phase Arrest in Human Gastric Epithelium Cells

Toxicology Letters. Mar, 2012  |  Pubmed ID: 22230261

Ochratoxin A (OTA) is a ubiquitous mycotoxin with potential nephrotoxic, hepatotoxic, and immunotoxic effects. Recent work from our laboratory found that OTA evoked G2 phase arrest in GES-1 cells in vitro by modulating the key factors Cdc25C, Cdc2 and cyclinB1, which were critical to the G2/M phase transmission, suggested that OTA-induced G2 arrest mediate at least in part OTA toxicity effect. However, the molecular mechanism of this effect is currently unclear. In the present study, we showed that treatment of GES-1 cells with OTA could induce the activation of MAPK family members ERK and p38. ERK inhibitor PD98059 and p38 inhibitor SB203580 significantly reversed the depression of Cdc25C/p-Cdc25C, Cdc2/p-Cdc2, cyclinB1 as well as the cyclinB1-Cdc2 complex, thereby, abolished the delay in G2 phase. In addition, silencing ERK and p38 expression with siRNA significantly inhibited OTA-induced G2 arrest in GES-1 cells as well. Collectively, these data suggest that the ERK and p38 MAPK signaling pathways play important roles in the regulation of OTA-induced G2 arrest in GES-1 cells.

Natural Products As Kinase Inhibitors

Natural Product Reports. Feb, 2012  |  Pubmed ID: 22231144

Covering: up to 2011Natural products have been widely used to dissect the basic mechanisms of fundamental life science and as clinical therapeutics. Recently, there has been significant interest in discovering new chemical pharmacophores in natural products to fulfil the vast demand for novel kinase inhibitors and address critical unmet medical needs with respect to signal transduction pathways. In this review, we summarize the history of several different classes of natural product-derived kinase inhibitors, discuss their kinome-wide target profiles and examine their structural binding modes based on available 3D X-ray structures. In particular, their origin, target activity, selectivity, scope and potential therapeutic development are highlighted against the backdrop of medicinal chemistry.

Albumin and C-reactive Protein Levels Predict Short-term Mortality, Which May Not Be Associated with PEG

Gastrointestinal Endoscopy. Jan, 2012  |  Pubmed ID: 22196825

βPix Plays a Dual Role in Cerebral Vascular Stability and Angiogenesis, and Interacts with Integrin α(v)β(8)

Developmental Biology. Mar, 2012  |  Pubmed ID: 22206757

The growth of new blood vessels by angiogenesis and their stabilization by the recruitment of perivascular mural cells are thought to be two sequential, yet independent events. Here we identify molecular links between both processes through the βPix and integrin α(v)β(8) proteins. Bubblehead (bbh) mutants with a genetic mutation in βPix show defective vascular stabilization. βPix is a guanine nucleotide exchange factor and scaffold protein that binds many proteins including Git1, which bridges βPix to integrins at focal adhesions. Here we show that the ability of βPix to stabilize vessels requires Git1 binding residues. Knockdown of Git1 leads to a hemorrhage phenotype similar to loss of integrin α(v), integrin β(8) or βPix, suggesting that vascular stabilization through βPix involves interactions with integrins. Furthermore, double loss of function of βPix and integrin α(v) shows enhanced hemorrhage rates. Not only is vascular stability impaired in these embryos, but we also uncover a novel role of both βPix and integrin α(v)β(8) in cerebral angiogenesis. Downregulation of either βPix or integrin α(v)β(8) results in fewer and morphologically abnormal cerebral arteries penetrating the hindbrain. We show that this is coupled with a significant reduction in endothelial cell proliferation in bbh mutants or integrin α(v)β(8) morphants. These data suggest that a complex involving βPix, GIT1 and integrin α(v)β(8) may regulate vascular stability, cerebral angiogenesis and endothelial cell proliferation in the developing embryo.

Alternative Splicing of Apoptosis-related Genes in Imatinib-treated K562 Cells Identified by Exon Array Analysis

International Journal of Molecular Medicine. Apr, 2012  |  Pubmed ID: 22211240

Imatinib is the therapeutic standard for newly diagnosed patients with chronic myeloid leukemia (CML). In these patients, imatinib has been shown to induce an apoptotic response specifically in cells expressing the oncogenic fusion protein BCR-ABL. Previous studies in our lab revealed that imatinib-induced apoptosis in K562 cells involves a shift in production of Bcl-x splice isoforms towards the pro-apoptotic Bcl-xs splice variant. Here, we report the findings from our subsequent study to identify other apoptosis-related genes that are differentially spliced in response to imatinib treatment. Gene expression profiling of imatinib-treated K562 cells was performed by the Affymetrix GeneChip® Human Exon 1.0 ST array, and differences in exon-level expression and alternative splicing were analyzed using the easyExon software. Detailed analysis by reverse transcription-PCR (RT-PCR) and sequencing of key genes confirmed the experimental results of the exon array. Our results suggest that imatinib treatment of K562 cells causes a transcriptional shift towards alternative splicing in a large number of apoptotic genes. The present study provides insight into the molecular character of apoptotic leukemia cells and may help to improve the mechanism of imatinib therapy in patients with CML.

Site-specific Ubiquitination is Required for Relieving the Transcription Factor Miz1-mediated Suppression on TNF-α-induced JNK Activation and Inflammation

Proceedings of the National Academy of Sciences of the United States of America. Jan, 2012  |  Pubmed ID: 22184250

The transcription factor zinc-finger protein Miz1 represses TNF-α-induced JNK activation and the repression is relieved upon TNF-α stimulation. However, the underlying mechanism is incompletely understood. Here we report that Miz1 interferes with the ubiquitin conjugating enzyme (E2) Ubc13 for binding to the RING domain of TNF-receptor associated factor 2 (TRAF2), thereby inhibiting the ubiquitin ligase (E3) activity of TRAF2 and suppressing TNF-α-induced JNK activation. Upon TNF-α stimulation, Miz1 rapidly undergoes K48-linked polyubiquitination at Lys388 and Lys472 residues and subsequent proteasomal degradation in a TRAF2-dependent manner. Replacement of Lysine 388 and Lysine 472 by arginines generates a nondegradable Miz1 mutant, which significantly suppresses TNF-α-induced JNK1 activation and inflammation. Thus, our results reveal a molecular mechanism by which the repression of TNF-α-induced JNK activation by Miz1 is de-repressed by its own site-specific ubiquitination and degradation, which may account for the temporal control of TNF-α-JNK signaling.

Morphology Enabled Dipole Inversion for Quantitative Susceptibility Mapping Using Structural Consistency Between the Magnitude Image and the Susceptibility Map

NeuroImage. Feb, 2012  |  Pubmed ID: 21925276

The magnetic susceptibility of tissue can be determined in gradient echo MRI by deconvolving the local magnetic field with the magnetic field generated by a unit dipole. This Quantitative Susceptibility Mapping (QSM) problem is unfortunately ill-posed. By transforming the problem to the Fourier domain, the susceptibility appears to be undersampled only at points where the dipole kernel is zero, suggesting that a modest amount of additional information may be sufficient for uniquely resolving susceptibility. A Morphology Enabled Dipole Inversion (MEDI) approach is developed that exploits the structural consistency between the susceptibility map and the magnitude image reconstructed from the same gradient echo MRI. Specifically, voxels that are part of edges in the susceptibility map but not in the edges of the magnitude image are considered to be sparse. In this approach an L1 norm minimization is used to express this sparsity property. Numerical simulations and phantom experiments are performed to demonstrate the superiority of this L1 minimization approach over the previous L2 minimization method. Preliminary brain imaging results in healthy subjects and in patients with intracerebral hemorrhages illustrate that QSM is feasible in practice.

Phytochrome B Control of Total Leaf Area and Stomatal Density Affects Drought Tolerance in Rice

Plant Molecular Biology. Feb, 2012  |  Pubmed ID: 22138855

We report that phytochrome B (phyB) mutants exhibit improved drought tolerance compared to wild type (WT) rice (Oryza sativa L. cv. Nipponbare). To understand the underlying mechanism by which phyB regulates drought tolerance, we analyzed root growth and water loss from the leaves of phyB mutants. The root system showed no significant difference between the phyB mutants and WT, suggesting that improved drought tolerance has little relation to root growth. However, phyB mutants exhibited reduced total leaf area per plant, which was probably due to a reduction in the total number of cells per leaf caused by enhanced expression of Orysa;KRP1 and Orysa;KRP4 (encoding inhibitors of cyclin-dependent kinase complex activity) in the phyB mutants. In addition, the developed leaves of phyB mutants displayed larger epidermal cells than WT leaves, resulting in reduced stomatal density. phyB deficiency promoted the expression of both putative ERECTA family genes and EXPANSIN family genes involved in cell expansion in leaves, thus causing greater epidermal cell expansion in the phyB mutants. Reduced stomatal density resulted in reduced transpiration per unit leaf area in the phyB mutants. Considering all these findings, we propose that phyB deficiency causes both reduced total leaf area and reduced transpiration per unit leaf area, which explains the reduced water loss and improved drought tolerance of phyB mutants.

Transmyocardial Drilling Revascularization Combined with Heparinized BFGF-incorporating Stent Activates Resident Cardiac Stem Cells Via SDF-1/CXCR4 Axis

Experimental Cell Research. Feb, 2012  |  Pubmed ID: 22146760

To investigate whether transmyocardial drilling revascularization combined with heparinized basic fibroblast growth factor (bFGF)-incorporating degradable stent implantation (TMDRSI) can promote myocardial regeneration after acute myocardial infarction (AMI).

β-Elemene Induces Apoptosis As Well As Protective Autophagy in Human Non-small-cell Lung Cancer A549 Cells

The Journal of Pharmacy and Pharmacology. Jan, 2012  |  Pubmed ID: 22150682

β-Elemene, a novel traditional Chinese medicine, has been shown to be effective against a wide range of tumours. In this study, the antitumour effect of β-elemene on human non-small-cell lung cancer (NSCLC) A549 cells and the mechanism involved have been investigated.

A New Approach for the Determination of Oligosaccharide Structures

Carbohydrate Research. Jan, 2012  |  Pubmed ID: 22153709

A new method for the determination of oligosaccharide chains, known as the D60 one-dimensional TOCSY method is introduced in this paper. The results show that the use of this method enables a more effective coherent long-range magnetic relay transfer compared with that of existing DIPSI-2 and MMDY methods. Further, the method is easy to use and is not sensitive to the error of the pulse width. Without complex z-filtering steps, the high-quality sub-spectrum of pure absorption can be quickly obtained, which facilitates sub-spectroscopy detection for the existence of weak spin-coupling sugar components in the saccharide ring. Glycosides are taken as examples to discuss the characteristics of this method and its application in the determination of oligosaccharides in spectrum peak height.

Cloning and Characterization of the Polyether Salinomycin Biosynthesis Gene Cluster of Streptomyces Albus XM211

Applied and Environmental Microbiology. Feb, 2012  |  Pubmed ID: 22156425

Salinomycin is widely used in animal husbandry as a food additive due to its antibacterial and anticoccidial activities. However, its biosynthesis had only been studied by feeding experiments with isotope-labeled precursors. A strategy with degenerate primers based on the polyether-specific epoxidase sequences was successfully developed to clone the salinomycin gene cluster. Using this strategy, a putative epoxidase gene, slnC, was cloned from the salinomycin producer Streptomyces albus XM211. The targeted replacement of slnC and subsequent trans-complementation proved its involvement in salinomycin biosynthesis. A 127-kb DNA region containing slnC was sequenced, including genes for polyketide assembly and release, oxidative cyclization, modification, export, and regulation. In order to gain insight into the salinomycin biosynthesis mechanism, 13 gene replacements and deletions were conducted. Including slnC, 7 genes were identified as essential for salinomycin biosynthesis and putatively responsible for polyketide chain release, oxidative cyclization, modification, and regulation. Moreover, 6 genes were found to be relevant to salinomycin biosynthesis and possibly involved in precursor supply, removal of aberrant extender units, and regulation. Sequence analysis and a series of gene replacements suggest a proposed pathway for the biosynthesis of salinomycin. The information presented here expands the understanding of polyether biosynthesis mechanisms and paves the way for targeted engineering of salinomycin activity and productivity.

Imaging Protein Synthesis in Cells and Tissues with an Alkyne Analog of Puromycin

Proceedings of the National Academy of Sciences of the United States of America. Jan, 2012  |  Pubmed ID: 22160674

Synthesis of many proteins is tightly controlled at the level of translation, and plays an essential role in fundamental processes such as cell growth and proliferation, signaling, differentiation, or death. Methods that allow imaging and identification of nascent proteins are critical for dissecting regulation of translation, both spatially and temporally, particularly in whole organisms. We introduce a simple and robust chemical method to image and affinity-purify nascent proteins in cells and in animals, based on an alkyne analog of puromycin, O-propargyl-puromycin (OP-puro). OP-puro forms covalent conjugates with nascent polypeptide chains, which are rapidly turned over by the proteasome and can be visualized or captured by copper(I)-catalyzed azide-alkyne cycloaddition. Unlike methionine analogs, OP-puro does not require methionine-free conditions and, uniquely, can be used to label and assay nascent proteins in whole organisms. This strategy should have broad applicability for imaging protein synthesis and for identifying proteins synthesized under various physiological and pathological conditions in vivo.

Mequindox Induced Cellular DNA Damage Via Generation of Reactive Oxygen Species

Mutation Research. Jan, 2012  |  Pubmed ID: 22094289

Mequindox, a quinoxaline-N-dioxide derivative that possesses antibacterial properties, has been widely used as a feed additive in the stockbreeding industry in China. While recent pharmacological studies have uncovered potential hazardous effects of mequindox, exactly how mequindox induces pathological changes and the cellular responses associated with its consumption remain largely unexplored. In this study, we investigated the cellular responses associated with mequindox treatment. We report here that mequindox inhibits cell proliferation by arresting cells at the G2/M phase of the cell cycle. Interestingly, this mequindox-associated deleterious effect on cell proliferation was observed in human, pig as well as chicken cells, suggesting that mequindox acts on evolutionarily conserved target(s). To further understand the mequindox-host interaction and the mechanism underlying mequindox-induced cell cycle arrest, we measured the cellular content of DNA damage, which is known to perturb cell proliferation and compromise cell survival. Accordingly, using γ-H2AX as a surrogate marker for DNA damage, we found that mequindox treatment induced cellular DNA damage, which paralleled the chemical-induced elevation of reactive oxygen species (ROS) levels. Importantly, expression of the antioxidant enzyme catalase partially alleviated these mequindox-associated effects. Taken together, our results suggest that mequindox cytotoxicity is attributable, in part, to its role as a potent inducer of DNA damage via ROS.

Proteasome Inhibitor Bortezomib (PS-341) Enhances RANKL-induced MDA-MB-231 Breast Cancer Cell Migration

Molecular Medicine Reports. Feb, 2012  |  Pubmed ID: 22101248

The receptor activator of nuclear factor κB ligand/receptor activator of nuclear factor κB (RANKL/RANK) pathway is crucial for the migration of RANK-expressing cancer cells. The ubiquitin-proteasome protein degradation pathway plays a significant role in tumor metastasis. However, the relationship between these two pathways in tumor cell migration is unclear. In the present study, we explored the effect of the proteasome inhibitor bortezomib (PS-341) on RANKL-induced MDA-MB-231 breast cancer cell migration. Transwell migration assay showed that RANKL-induced MDA-MB-231 cell migration was significantly blocked by the decoy receptor osteoprotegerin (OPG), and was also inhibited by the PI3-K inhibitor LY294002. Western blotting results showed that Akt was rapidly activated by soluble RANKL treatment. PS-341 significantly enhanced RANKL-induced MDA-MB-231 cell migration. Further study showed that the enhancement of migration by PS-341 involved upregulation of activated Akt and RANK. Our results for the first time support the theory that PS-341 treatment may be unsuitable for RANK-positive breast cancer patients.

Guided Migration of Neural Stem Cells Derived from Human Embryonic Stem Cells by an Electric Field

Stem Cells (Dayton, Ohio). Feb, 2012  |  Pubmed ID: 22076946

Small direct current (DC) electric fields (EFs) guide neurite growth and migration of rodent neural stem cells (NSCs). However, this could be species dependent. Therefore, it is critical to investigate how human NSCs (hNSCs) respond to EF before any possible clinical attempt. Aiming to characterize the EF-stimulated and guided migration of hNSCs, we derived hNSCs from a well-established human embryonic stem cell line H9. Small applied DC EFs, as low as 16 mV/mm, induced significant directional migration toward the cathode. Reversal of the field polarity reversed migration of hNSCs. The galvanotactic/electrotactic response was both time and voltage dependent. The migration directedness and distance to the cathode increased with the increase of field strength. (Rho-kinase) inhibitor Y27632 is used to enhance viability of stem cells and has previously been reported to inhibit EF-guided directional migration in induced pluripotent stem cells and neurons. However, its presence did not significantly affect the directionality of hNSC migration in an EF. Cytokine receptor [C-X-C chemokine receptor type 4 (CXCR4)] is important for chemotaxis of NSCs in the brain. The blockage of CXCR4 did not affect the electrotaxis of hNSCs. We conclude that hNSCs respond to a small EF by directional migration. Applied EFs could potentially be further exploited to guide hNSCs to injured sites in the central nervous system to improve the outcome of various diseases. STEM CELLS 2012; 30:349-355.

Receptor Activator for Nuclear Factor κ B Expression Predicts Poor Prognosis in Breast Cancer Patients with Bone Metastasis but Not in Patients with Visceral Metastasis

Journal of Clinical Pathology. Jan, 2012  |  Pubmed ID: 22049226

It was recently reported that receptor activator for nuclear factor κ B ligand (RANKL)/receptor activator for nuclear factor κ B (RANK) pathway is critical for RANK-expressing cancer cells to home to bone and associates with disease progression of cancer. The present study was aimed to evaluate the effect of RANK on prognosis in breast cancer patients with bone metastasis and patients with visceral metastasis.

Two-photon Excited Fluorescence Lifetime Measurements Through a Double-clad Photonic Crystal Fiber for Tissue Micro-endoscopy

Journal of Biophotonics. Jan, 2012  |  Pubmed ID: 22045513

This paper presents an endoscopic configuration for measurements of tissue autofluorescence using two-photon excitation and time-correlated single photon counting detection through a double-clad photonic crystal fiber (DC-PCF) without pre-chirping of laser pulses. The instrument performance was evaluated by measurements of fluorescent standard dyes, biological fluorophores (collagen and elastin), and tissue specimens (muscle, cartilage, tendon). Current results demonstrate the ability of this system to accurately retrieve the fluorescence decay profile and lifetime of these samples. This simple setup, which offers larger penetration depth than one-photon-based techniques, may be combined with morphology-yielding techniques such as photoacoustic and ultrasound imaging.

Epidemiological Characteristics of Adult SCIWORA in Tianjin, China: a Preliminary Study

European Spine Journal : Official Publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. Jan, 2012  |  Pubmed ID: 22037845

The epidemiology of spinal cord injury without radiographic abnormality (SCIWORA) is less frequently reported in adults as compared with children. The annual incidence of SCIWORA was approximately 5.74% per million in Tianjin from 2004 to 2008. Importantly, the epidemiological characteristics of adult SCIWORA may be different from that in children. The aim of this study was to evaluate the radiological-clinical data of patients with adult SCIWORA, and to relatively analyze the epidemiological features.

Mutation P.Leu354Pro in EDA Causes Severe Hypohidrotic Ectodermal Dysplasia in a Chinese Family

Gene. Jan, 2012  |  Pubmed ID: 22008666

X-linked recessive hypohidrotic ectodermal dysplasia (XLHED) is characterized by the defective morphogenesis of teeth, hair, and eccrine sweat glands. It is associated with mutations in the EDA gene. Up to now, more than 100 mutations in the EDA gene have been reported to cause XLHED. The product of EDA gene is a trimeric type II transmembrane protein that belongs to the tumor necrosis factor (TNF) family of ligands. In this study, we identified a Chinese family with XLHED. Direct DNA sequencing of the whole coding region of EDA revealed a novel missense mutation, p.Leu354Pro in a patient affected with XLHED. This mutation was not found in either unaffected male individuals of the family or 168 normal controls. The substitution of Leu354 with Pro was found to be located in the TNF-like domain of EDA and may influence the epithelial signaling pathway required for the normal ectodermal development through altering the topology of EDA. Our finding broadens the spectrum of EDA mutations and may help to understand the molecular basis of XLHED and aid genetic counseling.

Nondestructive Evaluation of Tissue Engineered Articular Cartilage Using Time-Resolved Fluorescence Spectroscopy and Ultrasound Backscatter Microscopy

Tissue Engineering. Part C, Methods. Jan, 2012  |  Pubmed ID: 22010819

The goal of this study is to evaluate the ability of a bimodal technique integrating time-resolved fluorescence spectroscopy (TRFS) and ultrasound backscatter microscopy (UBM) for nondestructive detection of changes in the biochemical, structural, and mechanical properties of self-assembled engineered articular cartilage constructs. The cartilage constructs were treated with three chemical agents (collagenase, chondroitinase-ABC, and ribose) to induce changes in biochemical content (collagen and glycosaminoglycan [GAG]) of matured constructs (4 weeks); and to subsequently alter the mechanical properties of the construct. The biochemical changes were evaluated using TRFS. The microstructure and the thickness of the engineered cartilage samples were characterized by UBM. The optical and ultrasound results were validated against those acquired via conventional techniques including collagen and GAG quantification and measurement of construct stiffness. Current results demonstrated that a set of optical parameters (e.g., average fluorescence lifetime and decay constants) showed significant correlation (p<0.05) with biochemical and mechanical data. The high-resolution ultrasound images provided complementary cross-section information of the cartilage samples morphology. Therefore, the technique was capable of nondestructively evaluating the composition of extracellular matrix and the microstructure of engineered tissue, demonstrating great potential as an alternative to traditional destructive assays.

In Vivo Toxicological Evaluation of Anisomycin

Toxicology Letters. Jan, 2012  |  Pubmed ID: 22004851

Anisomycin is a pyrrolidine antibiotic isolated from Streptomyces griseolus. Recent studies have shown that Anisomycin as a novel immunosuppressive agent is superior to Cyclosporine A (J. Immunother. 31, 858-870, 2008). In order to make toxicological evaluation of Anisomycin, acute and four-week continuously intravenous toxicity studies were performed in mice. IC(50) value tested on peripheral lymphocytes was 25.44 ng/ml. The calculated LD(50) for Anisomycin was 119.64 mg/kg. The mice were intravenously injected through mouse tail vein with a total dose of 5, 15, 30 and 60 mg/kg/mice of Anisomycin every other day for 4 weeks. Just in the high-dose mice, death of three mice happened and body weight of the mice was significantly decreased. Statistically significant changes in organ index included increases in ratios of the spleen, liver, lung and brain to the body weight, and decrease in ratio of the thymus to the body weight. Changes in clinical biochemistry parameters included increases in the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, and decreases in the glucose (GLU) activity. The distinct inflammation appeared in the lung, liver and kidney, and the number and size of megakaryocytes in the spleen were significantly increased. Anisomycin did not induce formation of the peripheral blood micronucleus, but increased the number of micronucleated polychromatic erythrocytes in bone marrow and sperm aberrations. However, the above aberrant changes occurred only in the mice treated with the high-dose Anisomycin. These results indicate that although Anisomycin has no significant side effects at effectively therapeutic doses, its over-dosage may lead to toxicity, particularly pulmo-, nephro- and hepato-toxicity.

Infrasound Increases Intracellular Calcium Concentration and Induces Apoptosis in Hippocampi of Adult Rats

Molecular Medicine Reports. Jan, 2012  |  Pubmed ID: 21946944

In the present study, we determined the effect of infrasonic exposure on apoptosis and intracellular free Ca²⁺ ([Ca²⁺]i) levels in the hippocampus of adult rats. Adult rats were randomly divided into the control and infrasound exposure groups. For infrasound treatment, animals received infrasonic exposure at 90 (8 Hz) or 130 dB (8 Hz) for 2 h per day. Hippocampi were dissected, and isolated hippocampal neurons were cultured. The [Ca²⁺]i levels in hippocampal neurons from adult rat brains were determined by Fluo-3/AM staining with a confocal microscope system on days 1, 7, 14, 21 and 28 following infrasonic exposure. Apoptosis was evaluated by Annexin V-FITC and propidium iodide double staining. Positive cells were sorted and analyzed by flow cytometry. Elevated [Ca²⁺]i levels were observed on days 14 and 21 after rats received daily treatment with 90 or 130 dB sound pressure level (SPL) infrasonic exposure (p<0.01 vs. control). The highest levels of [Ca²⁺]i were detected in the 130 dB SPL infrasonic exposure group. Meanwhile, apoptosis in hippocampal neurons was found to increase on day 7 following 90 dB SPL infrasound exposure, and significantly increased on day 14. Upon 130 dB infrasound treatment, apoptosis was first observed on day 14, whereas the number of apoptotic cells gradually decreased thereafter. Additionally, a marked correlation between cell apoptosis and [Ca²⁺]i levels was found on day 14 and 21 following daily treatment with 90 and 130 dB SPL, respectively. These results demonstrate that a period of infrasonic exposure induced apoptosis and upregulated [Ca²⁺]i levels in hippocampal neurons, suggesting that infrasound may cause damage to the central nervous system (CNS) through the Ca²⁺‑mediated apoptotic pathway in hippocampal neurons.

Expanding the Action of Duplex RNAs into the Nucleus: Redirecting Alternative Splicing

Nucleic Acids Research. Feb, 2012  |  Pubmed ID: 21948593

Double-stranded RNAs are powerful agents for silencing gene expression in the cytoplasm of mammalian cells. The potential for duplex RNAs to control expression in the nucleus has received less attention. Here, we investigate the ability of small RNAs to redirect splicing. We identify RNAs targeting an aberrant splice site that restore splicing and production of functional protein. RNAs can target sequences within exons or introns and affect the inclusion of exons within SMN2 and dystrophin, genes responsible for spinal muscular atrophy and Duchenne muscular dystrophy, respectively. Duplex RNAs recruit argonaute 2 (AGO2) to pre-mRNA transcripts and altered splicing requires AGO2 expression. AGO2 promotes transcript cleavage in the cytoplasm, but recruitment of AGO2 to pre-mRNAs does not reduce transcript levels, exposing a difference between cytoplasmic and nuclear pathways. Involvement of AGO2 in splicing, a classical nuclear process, reinforces the conclusion from studies of RNA-mediated transcriptional silencing that RNAi pathways can be adapted to function in the mammalian nucleus. These data provide a new strategy for controlling splicing and expand the reach of small RNAs within the nucleus of mammalian cells.

Maternal Control of Seed Oil Content in Brassica Napus: the Role of Silique Wall Photosynthesis

The Plant Journal : for Cell and Molecular Biology. Feb, 2012  |  Pubmed ID: 21954986

Seed oil content is an important agronomic trait in rapeseed. However, our understanding of the regulatory processes controlling oil accumulation is still limited. Using two rapeseed lines (zy036 and 51070) with contrasting oil content, we found that maternal genotype greatly affects seed oil content. Genetic and physiological evidence indicated that difference in the local and tissue-specific photosynthetic activity in the silique wall (a maternal tissue) was responsible for the different seed oil contents. This effect was mimicked by in planta manipulation of silique wall photosynthesis. Furthermore, the starch content and expression of the important lipid synthesis regulatory gene WRINKLED1 in developing seeds were linked with silique wall photosynthetic activity. 454 pyrosequencing was performed to explore the possible molecular mechanism for the difference in silique wall photosynthesis between zy036 and 51070. Interestingly, the results suggested that photosynthesis-related genes were over-represented in both total silique wall expressed genes and genes that were differentially expressed between genotypes. A potential regulatory mechanism for elevated photosynthesis in the zy036 silique wall is proposed on the basis of knowledge from Arabidopsis. Differentially expressed ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco)-related genes were used for further investigations. Oil content correlated closely with BnRBCS1A expression levels and Rubisco activities in the silique wall, but not in the leaf. Taken together, our results highlight an important role of silique wall photosynthesis in the regulation of seed oil content in terms of maternal effects.

Exogenous Plant MIR168a Specifically Targets Mammalian LDLRAP1: Evidence of Cross-kingdom Regulation by MicroRNA

Cell Research. Jan, 2012  |  Pubmed ID: 21931358

Our previous studies have demonstrated that stable microRNAs (miRNAs) in mammalian serum and plasma are actively secreted from tissues and cells and can serve as a novel class of biomarkers for diseases, and act as signaling molecules in intercellular communication. Here, we report the surprising finding that exogenous plant miRNAs are present in the sera and tissues of various animals and that these exogenous plant miRNAs are primarily acquired orally, through food intake. MIR168a is abundant in rice and is one of the most highly enriched exogenous plant miRNAs in the sera of Chinese subjects. Functional studies in vitro and in vivo demonstrated that MIR168a could bind to the human/mouse low-density lipoprotein receptor adapter protein 1 (LDLRAP1) mRNA, inhibit LDLRAP1 expression in liver, and consequently decrease LDL removal from mouse plasma. These findings demonstrate that exogenous plant miRNAs in food can regulate the expression of target genes in mammals.

Number of Recent Sexual Partners Among Blood Donors in Brazil: Associations with Donor Demographics, Donation Characteristics, and Infectious Disease Markers

Transfusion. Jan, 2012  |  Pubmed ID: 21756264

Brazilian blood centers ask candidate blood donors about the number of sexual partners in the past 12 months. Candidates who report a number over the limit are deferred. We studied the implications of this practice on blood safety.

Association of Self-reported Snoring with Carotid Artery Intima-media Thickness and Plaque

Journal of Sleep Research. Feb, 2012  |  Pubmed ID: 21752134

Previous studies have suggested that self-reported snoring is associated with atherosclerotic vascular diseases. However, the role of self-reported snoring as an independent risk factor for subclinical atherosclerosis has not been well established. This study aimed to evaluate whether and to what extent self-reported snoring is associated with subclinical carotid atherosclerosis after adjusting for traditional cardiovascular risk factors. Carotid intima-media thickness and plaque were investigated with ultrasonography in 1245 urban Chinese aged 50-79 years between September 2007 and November 2007. Information on self-reported snoring and measurements of traditional cardiovascular risk factors was also collected. A total of 1050 participants were involved in the final analysis. The prevalence of self-reported snoring habitually (snoring frequency ≥5 days per week) was 31.5, and 64.3% of the participants in this population had a history of snoring. The mean values of the maximum intima-media thickness of bifurcation and common carotid arteries in snorers were significantly higher than in non-snorers (1.08 ± 0.14 mm versus 1.04 ± 0.14 mm, P < 0.001, in carotid bifurcation; 1.03 ± 0.15 mm versus 1.00 ± 0.15 mm, P = 0.002, in common carotid artery). After adjustment for traditional cardiovascular risk factors, logistic regression analysis showed that the odds ratio of self-reported snoring habitually for increased intima-media thickness and carotid bifurcation plaque was 1.71 [95% confidence interval (CI): 1.22-2.39; P = 0.002] and 3.63 (95% CI: 2.57-5.12; P < 0.001), respectively. In conclusion, the current study suggested that self-reported snoring is associated significantly with carotid bifurcation intima-media thickness and the presence of plaque, independent of traditional cardiovascular risk factors.

Mutation Analysis of PAX6 in a Chinese Family and a Patient with a Presumed Sporadic Case of Congenital Aniridia

Ophthalmic Research. 2012  |  Pubmed ID: 21691140

Mutations in the PAX6 are the major cause of congenital aniridia. The objective of this study was to analyze genetic mutations in PAX6 in Chinese patients with congenital aniridia.