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  • 1
    Publication Date: 2015-01-16
    Description: We present MethHC ( http://MethHC.mbc.nctu.edu.tw ), a database comprising a systematic integration of a large collection of DNA methylation data and mRNA/microRNA expression profiles in human cancer. DNA methylation is an important epigenetic regulator of gene transcription, and genes with high levels of DNA methylation in their promoter regions are transcriptionally silent. Increasing numbers of DNA methylation and mRNA/microRNA expression profiles are being published in different public repositories. These data can help researchers to identify epigenetic patterns that are important for carcinogenesis. MethHC integrates data such as DNA methylation, mRNA expression, DNA methylation of microRNA gene and microRNA expression to identify correlations between DNA methylation and mRNA/microRNA expression from TCGA (The Cancer Genome Atlas), which includes 18 human cancers in more than 6000 samples, 6548 microarrays and 12 567 RNA sequencing data.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 2
    Publication Date: 2015-04-08
    Description: It is not known whether exposure to air pollutants causes systemic oxidative stress in children. We investigated the association between exposure to air pollution and biomarkers of oxidative stress in relation to a governmental air quality intervention implemented during the 2008 Beijing Olympic Games. We studied 36 schoolchildren during 5 time periods before and during the Olympic Games in Beijing (June 2007–September 2008). The oxidative stress biomarkers 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and malondialdehyde were measured in urine samples collected daily during each period. Generalized estimating equations were used to examine the relationship between repeated biomarker measurements and ambient air pollutant levels. During the Olympic intervention period, substantial reductions in air pollution (–19% to –72%), urinary 8-oxodG concentrations (–37.4%; 95% confidence interval: –53.5, –15.7), and urinary malondialdehyde concentrations (–25.3%; 95% confidence interval: –34.3, –15.1) were found. Malondialdehyde and 8-oxodG were significantly associated with concentrations of black carbon, fine particulate matter with an aerodynamic with diameter less than 2.5 μm, sulfur dioxide, nitrogen dioxide, and carbon monoxide. Biomarker changes per each interquartile-range increase in pollutants were largest at lag 0 or lag 1. In a 2-pollutant model, the most robust associations were for black carbon. These findings suggest that exposure to black carbon leads to systemic oxidative stress in children.
    Print ISSN: 0002-9262
    Electronic ISSN: 1476-6256
    Topics: Medicine
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  • 3
    Publication Date: 2015-08-21
    Description: Background Patients with advanced breast cancer positive for human epidermal growth factor receptor 2 (HER2) are at high risk for brain metastasis (BM). The prevalence and significance of expression of HER2 and its truncated form p95HER2 (p95) in BM is unknown. Methods Seventy-five pairs of formalin-fixed paraffin-embedded samples from matched primary breast cancers (PBCs) and BM were assayed for quantitative p95 and HER2-total (H2T) protein expression using the p95 VeraTag and HERmark assays, respectively. Results There was a net increase in p95 and H2T expression in BM relative to the matched PBC (median 1.5-fold, P = .0007 and 2.1-fold, P 〈 .0001, respectively). Cases with H2T-positive tumors were more likely to have the largest (≥5-fold) increase in p95 (odds ratio = 6.3, P = .018). P95 positivity in PBC correlated with progression-free survival (hazard ratio [HR] = 2.2, P = .013), trended with shorter time to BM (HR = 1.8, P = .070), and correlated with overall survival (HR = 2.1, P = .042). P95 positivity in BM correlated with time to BM (HR = 2.0, P = .016) but did not correlate with overall survival from the time of BM diagnosis (HR = 1.2, P = .61). Conclusions This is the first study of quantitative p95 and HER2 expression in matched PBC and BM. BM of breast cancer shows significant increases in expression of both biomarkers compared with matched PBC. These data provide a rationale for future correlative studies on p95 and HER2 levels in BM.
    Print ISSN: 1522-8517
    Electronic ISSN: 1523-5866
    Topics: Medicine
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  • 4
    Publication Date: 2015-07-26
    Description: : Allostery allows for the fine-tuning of protein function. Targeting allosteric sites is gaining increasing recognition as a novel strategy in drug design. The key challenge in the discovery of allosteric sites has strongly motivated the development of computational methods and thus high-quality, publicly accessible standard data have become indispensable. Here, we report benchmarking data for experimentally determined allosteric sites through a complex process, including a ‘Core set’ with 235 unique allosteric sites and a ‘Core-Diversity set’ with 147 structurally diverse allosteric sites. These benchmarking sets can be exploited to develop efficient computational methods to predict unknown allosteric sites in proteins and reveal unique allosteric ligand–protein interactions to guide allosteric drug design. Availability and implementation: The benchmarking sets are freely available at http://mdl.shsmu.edu.cn/asbench . Contact: jian.zhang@sjtu.edu.cn Supplementary information: Supplementary data are available at Bioinformatics online
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 5
    Publication Date: 2015-07-10
    Description: BACKGROUND The objective of this study was to investigate the genetic association of 4 candidate variants with blood pressure and test the modifying effects of environmental factors including age, sex, and body mass index (BMI). METHODS We used a linear mixed-effects model to test for variant main effects and variant interactions with age, sex, and BMI on systolic (SBP) and diastolic (DBP) blood pressure in 7,319 Chinese adults from the China Health and Nutrition Survey (CHNS). We attempted to replicate our significant interaction findings in 1,996 Chinese men from the Fangchenggang Area Male Health and Examination Survey (FAMHES). RESULTS Two variants (rs11105378 near ATP2B1 and rs1458038 near FGF5 ) were significantly associated ( P 〈 0.00625 = 0.05/8) with both SBP and DBP in CHNS. Variant rs1378942 near CSK was nominally associated with SBP ( P = 0.01). The signal at rs1458038 exhibited a genotype-by-BMI interaction affecting blood pressure ( P interaction = 0.0018 for SBP; P interaction = 0.049 for DBP), with the strongest variant effects in those with the highest BMI. In FAMHES, rs1458038 also showed stronger effects on SBP and DBP among men with the highest BMI. CONCLUSIONS Our findings suggest high BMI increases the effect of the blood pressure-increasing allele at rs1458038 near FGF5 , further highlighting the importance of obesity prevention in reducing hypertension risk.
    Print ISSN: 0895-7061
    Electronic ISSN: 1879-1905
    Topics: Medicine
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  • 6
    Publication Date: 2015-07-24
    Description: Aims We aimed to evaluate the changes in water-use efficiency (WUE) in native tree species in forests of subtropical China, and determine how coexisting species would be responding to increases in atmospheric carbon dioxide (CO 2 ) concentrations and nitrogen (N) deposition. Methods We used model forest ecosystems in open-top chambers to study the effects of elevated CO 2 ( ca . 700 µmol mol –1 ) alone and together with N addition (NH 4 NO 3 applied at 100kg N ha –1 year –1 ) on WUE of four native tree species ( Schima superba , Ormosia pinnata , Castanopsis hystrix and Acmena acuminatissima ) from 2006 to 2010. Important findings Our result indicated that all species increased their WUE when they were exposed to elevated CO 2 . Although higher WUE was shown in faster-growing species ( S. superba and O. pinnata ) than that of slower-growing species ( C. hystrix and Acmena acuminatissima ), the increased extent of WUE induced by elevated CO 2 was higher in the slower-growing species than that of the faster-growing species ( P 〈 0.01). The N treatment decreased WUE of S. superba, while the effects on other species were not significant. The interactions between elevated CO 2 and N addition increased intrinsic WUE of S. superba significantly ( P 〈 0.001), however, it did not affect WUE of the other tree species significantly. We conclude that the responses of native tree species to elevated CO 2 and N addition are different in subtropical China. The species-specific effects of elevated CO 2 and N addition on WUE would have important implications on species composition in China’s subtropics in response to global change.
    Print ISSN: 1752-993X
    Electronic ISSN: 1752-9921
    Topics: Biology
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  • 7
    Publication Date: 2015-06-26
    Description: We aimed to evaluate the value of the contrast volume to creatinine clearance (V/CrCl) ratio for predicting contrast-induced nephropathy (CIN) and to determine a safe V/CrCl cut-off value to avoid CIN in patients with chronic total occlusions (CTOs) undergoing cardiac catheterization. We prospectively enrolled 728 consecutive patients with CTOs undergoing cardiac catheterization. Receiver-operator characteristic (ROC) curves were used to identify the optimal sensitivity for the observed range of V/CrCl. The predictive value of V/CrCl for CIN was assessed using multivariate logistic regression. Twenty-one patients (2.88%) developed CIN. There was a significant association between a higher V/CrCl ratio and CIN risk ( P 〈 0.001). ROC curve analysis indicated that a V/CrCl ratio of 2.76 was a fair discriminator for CIN (C-statistic = 0.77). After adjusting for other known CIN predictors, V/CrCl ratio 〉2.76 remained significantly associated with CIN (OR = 5.22; 95% CI = 1.65–16.53, P = 0.005) or worse long-term outcomes [death: hazard ratio (HR) = 2.72, 95% CI = 1.32–5.60, P = 0.007; major adverse clinical events: HR = 1.46, 95% CI = 1.03–2.06, P = 0.034]. A V/CrCl ratio 〉2.76 was a predictor of CIN and was independently associated with poor long-term outcomes from our data.
    Print ISSN: 1520-765X
    Electronic ISSN: 1554-2815
    Topics: Medicine
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  • 8
    Publication Date: 2015-06-18
    Description: Background: Associations between anthropometry and head and neck cancer (HNC) risk are inconsistent. We aimed to evaluate these associations while minimizing biases found in previous studies. Methods: We pooled data from 1 941 300 participants, including 3760 cases, in 20 cohort studies and used multivariable-adjusted Cox proportional hazard regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of anthropometric measures with HNC risk overall and stratified by smoking status. Results: Greater waist circumference (per 5 cm: HR = 1.04, 95% CI 1.03–1.05, P -value for trend = 〈0.0001) and waist-to-hip ratio (per 0.1 unit: HR = 1.07, 95% CI 1.05–1.09, P -value for trend = 〈0.0001), adjusted for body mass index (BMI), were associated with higher risk and did not vary by smoking status ( P -value for heterogeneity = 0.85 and 0.44, respectively). Associations with BMI ( P -value for interaction = 〈0.0001) varied by smoking status. Larger BMI was associated with higher HNC risk in never smokers (per 5 kg/m 2 : HR = 1.15, 95% CI 1.06–1.24, P -value for trend = 0.0006), but not in former smokers (per 5 kg/m 2 : HR = 0.99, 95% CI 0.93–1.06, P -value for trend = 0.79) or current smokers (per 5 kg/m 2 : HR = 0.76, 95% CI 0.71–0.82, P -value for trend = 〈0.0001). Larger hip circumference was not associated with a higher HNC risk. Greater height (per 5 cm) was associated with higher risk of HNC in never and former smokers, but not in current smokers. Conclusions: Waist circumference and waist-to-hip ratio were associated positively with HNC risk regardless of smoking status, whereas a positive association with BMI was only found in never smokers.
    Print ISSN: 0300-5771
    Electronic ISSN: 1464-3685
    Topics: Medicine
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  • 9
    Publication Date: 2015-12-11
    Description: Concerns about high caffeine intake and coffee as a vehicle for added fat and sugar have raised questions about the net impact of coffee on health. Although inverse associations have been observed for overall mortality, data for cause-specific mortality are sparse. Additionally, few studies have considered exclusively decaffeinated coffee intake or use of coffee additives. Coffee intake was assessed at baseline by self-report in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Hazard ratios were estimated using Cox proportional hazards models. Among 90,317 US adults without cancer at study baseline (1998–2001) or history of cardiovascular disease at study enrollment (1993–2001), 8,718 deaths occurred during 805,644 person-years of follow-up from 1998 through 2009. Following adjustment for smoking and other potential confounders, coffee drinkers, as compared with nondrinkers, had lower hazard ratios for overall mortality (〈1 cup/day: hazard ratio (HR) = 0.99 (95% confidence interval (CI): 0.92, 1.07); 1 cup/day: HR = 0.94 (95% CI: 0.87, 1.02); 2–3 cups/day: HR = 0.82 (95% CI: 0.77, 0.88); 4–5 cups/day: HR = 0.79 (95% CI: 0.72, 0.86); ≥6 cups/day: HR = 0.84 (95% CI: 0.75, 0.95)). Similar findings were observed for decaffeinated coffee and coffee additives. Inverse associations were observed for deaths from heart disease, chronic respiratory diseases, diabetes, pneumonia and influenza, and intentional self-harm, but not cancer. Coffee may reduce mortality risk by favorably affecting inflammation, lung function, insulin sensitivity, and depression.
    Print ISSN: 0002-9262
    Electronic ISSN: 1476-6256
    Topics: Medicine
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  • 10
    Publication Date: 2015-12-02
    Description: G-quadruplex (G4) is a promising target for anti-cancer treatment. In this paper, we provide the first evidence supporting the presence of G4 in the mitochondrial DNA (mtDNA) of live cells. The molecular engineering of a fluorescent G4 ligand, 3,6-bis(1-methyl-4-vinylpyridinium) carbazole diiodide (BMVC), can change its major cellular localization from the nucleus to the mitochondria in cancer cells, while remaining primarily in the cytoplasm of normal cells. A number of BMVC derivatives with sufficient mitochondrial uptake can induce cancer cell death without damaging normal cells. Fluorescence studies of these anti-cancer agents in live cells and in isolated mitochondria from HeLa cells have demonstrated that their major target is mtDNA. In this study, we use fluorescence lifetime imaging microscopy to verify the existence of mtDNA G4s in live cells. Bioactivity studies indicate that interactions between these anti-cancer agents and mtDNA G4 can suppress mitochondrial gene expression. This work underlines the importance of fluorescence in the monitoring of drug-target interactions in cells and illustrates the emerging development of drugs in which mtDNA G4 is the primary target.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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