Vascular Endothelial Growth Factor and Ischemic Heart Disease Risk: A Mendelian Randomization Study

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The effect of statins on testosterone in men and women, a systematic review and meta-analysis of randomized controlled trials

published_or_final_versio

Birth weight and risk of ischemic heart disease: A Mendelian randomization study

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EZH2-Mediated H3K27me3 Is Involved in Epigenetic Repression of Deleted in Liver Cancer 1 in Human Cancers

Enhancer of zeste homolog 2 (EZH2), the histone methyltransferase of the Polycomb Repressive complex 2 catalyzing histone H3 lysine 27 tri-methylation (H3K27me3), is frequently up-regulated in human cancers. In this study, we identified the tumor suppressor Deleted in liver cancer 1 (DLC1) as a target of repression by EZH2-mediated H3K27me3. DLC1 is a GTPase-activating protein for Rho family proteins. Inactivation of DLC1 results in hyper-activated Rho/ROCK signaling and is implicated in actin cytoskeleton reorganization to promote cancer metastasis. By chromatin immunoprecipitation assay, we demonstrated that H3K27me3 was significantly enriched at the DLC1 promoter region of a DLC1-nonexpressing HCC cell line, MHCC97L. Depletion of EZH2 in MHCC97L by shRNA reduced H3K27me3 level at DLC1 promoter and induced DLC1 gene re-expression. Conversely, transient overexpression of GFP-EZH2 in DLC1-expressing Huh7 cells reduced DLC1 mRNA level with a concomitant enrichment of EZH2 on DLC1 promoter. An inverse relation between EZH2 and DLC1 expression was observed in the liver, lung, breast, prostate, and ovarian cancer tissues. Treating cancer cells with the EZH2 small molecular inhibitor, 3-Deazaneplanocin A (DZNep), restored DLC1 expression in different cancer cell lines, indicating that EZH2-mediated H3K27me3 epigenetic regulation of DLC1 was a common mechanism in human cancers. Importantly, we found that DZNep treatment inhibited HCC cell migration through disrupting actin cytoskeleton network, suggesting the therapeutic potential of DZNep in targeting cancer metastasis. Taken together, our study has shed mechanistic insight into EZH2-H3K27me3 epigenetic repression of DLC1 and advocated the significant pro-metastatic role of EZH2 via repressing tumor and metastasis suppressors.published_or_final_versio

Liver Enzymes and Risk of Ischemic Heart Disease and Type 2 Diabetes Mellitus: A Mendelian Randomization Study

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A propos d’un cas de grossesse abdominale très prolongée

Un cas de grossesse abdominale prolongée d'environ 18 mois avec mort foetale, vécu à l'hôpital général de référence de Mulongo dans la provincedu Katanga, en République Démocratique du Congo, est rapporté dans ce papier. Ce cas clinique d'évolution étonnante permet de faire la revue dela littérature, de rappeler l'importance d'un bon suivi clinique et  échographique de la grossesse et de s'interroger sur le niveau d'éducation de la femme ainsi que la qualité des soins prénataux en milieu rural congolais

Systematic differences among never, occasional and moderate alcohol users in southern China, and its use in alcohol research: a cross-sectional study

postprin

Systematic differences among never, occasional and moderate alcohol users in southern China, and its use in alcohol research: a cross-sectional study

postprin

Alcohol use and gamma-glutamyltransferase using a mendelian randomization design in the Guangzhou Biobank Cohort Study

published_or_final_versio

Evaluation of moderate alcohol use and cognitive function among men using a mendelian randomization design in the guangzhou biobank cohort study

Observational studies usually show that moderate alcohol use is associated with better cognitive function. Such studies are vulnerable to residual confounding arising from systematic differences between moderate alcohol users and others. A Mendelian randomization study carried out in a suitable population, such as southern Chinese men, in which alcohol use is low to moderate and is influenced by genotype, offers an alternative and superior approach for clarifying the causal effect of moderate alcohol use on cognitive function. The authors used aldehyde dehydrogenase 2 (ALDH2) genotype (AA, GA, or GG) as an instrumental variable in 2-stage least squares analysis to obtain unbiased estimates of the relation of alcohol consumption (measured in alcohol units (10 g ethanol) per day) with cognitive function, assessed from delayed 10-word recall score (n = 4,707) and Mini-Mental State Examination (MMSE) score (n = 2,284), among men from the Guangzhou Biobank Cohort Study (2003-2008). ALHD2 genotype was strongly associated with alcohol consumption, with an F statistic of 71.0 in 2-stage least squares analysis. Alcohol consumption was not associated with delayed 10-word recall score (-0.03 words per alcohol unit, 95% confidence interval:-0.18, 0.13) or MMSE score (0.06 points per alcohol unit, 95% confidence interval:-0.22, 0.34). Moderate alcohol use is unlikely to be cognitively protective. © The Author 2012. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved.postprin