Suqing Wang

Down-regulation of c-Met and Bcl2 by microRNA-206, activates apoptosis, and inhibits tumor cell proliferation, migration and colony formation.

Hsa-miRNA-206 (miR-206), highly expressed in skeletal muscle, has recently been discovered to have anticancer properties in different tissues. However, the role of miR-206 on lung cancer is still ambiguous. In this study, we investigated the role of miR-206 on the development of lung cancer. The results indicated that miR-206 expression was suppressed in lung cancer tissues and very low levels were found in non-small cell lung cancer (NSCLS) cell liness. Transient transfection of miR-206 into cultured A549 and SK-MES-1 cells led to significant decrease in cell growth, migration, invasion and colony formation, and promoted cell apoptosis. Using bioinformatics, we identified putative miR-206 binding sites within the 3′-untranslated region (3′-UTR) of the human c-Met and Bcl2 mRNA. The expression of c-Met and Bcl2 proteins were shown to be down-regulated after treated with miR-206 by subsequent Western blot and qRT-PCR analysis. Conversely, up-regulation of c-Met and Bcl2 were confirmed in tissue samples of human lung cancer, with its level inversely correlated with miR-206 expression. In addition, miR-206 also decreased the gene expression of MMP-9, CCND1 and CCND2 while increased the gene expression of p57 (Kip2) in A549 and SK-MES-1 cells. Taken together, our results demonstrated that miR-206 suppressed c-Met and Bcl2 expression in NSCLS and could function as a potent tumor suppressor in c-Met/Bcl2-over expressing tumors. Inhibition of miR-206 function could contribute to aberrant cell proliferation, migration, invasion and apoptosis, leading to NSCLS development.

Role of kruppel-like transcription factors in adipogenesis

The zinc-finger transcription factors of the kruppel-like factor family (KLF) are critical in many physiological and pathological processes including cell proliferation, differentiation, inflammation, and apoptosis. Recently, there is increasing evidence that suggests these KLFs have an important role in fat biology. This review summarizes the role of KLFs in lipid metabolism, especially in adipogenesis, and reveals the relationship networks among members of KLF family in differentiation.

Transforming growth factor β suppresses glutamate–cysteine ligase gene expression and induces oxidative stress in a lung fibrosis model

The concentration of glutathione (GSH), the most abundant intracellular free thiol and an important antioxidant, is decreased in the lung in both fibrotic diseases and experimental fibrosis models. The underlying mechanisms and biological significance of GSH depletion, however, remain unclear. Transforming growth factor β (TGF-β) is the most potent and ubiquitous profibrogenic cytokine and its expression is increased in almost all fibrotic diseases. In this study, we show that increasing TGF-β1 expression in mouse lung to a level comparable to those found in lung fibrotic diseases by intranasal instillation of AdTGF-β1(223/225), an adenovirus expressing constitutively active TGF-β1, suppressed the expression of both catalytic and modifier subunits of glutamate-cysteine ligase (GCL), the rate-limiting enzyme in de novo GSH synthesis, decreased GSH concentration, and increased protein and lipid peroxidation in mouse lung. Furthermore, we show that increasing TGF-β1 expression activated JNK and induced activating transcription factor 3, a transcriptional repressor involved in the regulation of the catalytic subunit of GCL, in mouse lung. Control virus (AdDL70-3) had no significant effect on any of these parameters, compared to saline-treated control. Concurrent with GSH depletion, TGF-β1 induced lung epithelial apoptosis and robust pulmonary fibrosis. Importantly, lung GSH levels returned to normal, whereas fibrosis persisted at least 21 days after TGF-β1 instillation. Together, the data suggest that increased TGF-β1 expression may contribute to the GSH depletion observed in pulmonary fibrosis diseases and that GSH depletion may be an early event in, rather than a consequence of, fibrosis development.

Relationship of body fat and cardiorespiratory fitness with cardiovascular risk in Chinese children.

Backgrounds/Objectives Cardiorespiratory fitness (CRF) and body fat play an important role in elevated risk for cardiovascular disease (CVD). However, the combined effects of CRF and obesity on metabolic health in Chinese children are unclear. The purpose of this study was to investigate the independent and combined associations between body fat, CRF, and CVD risk in Chinese schoolchildren. Methods The study subjects comprised 676 schoolchildren (392 boys and 284 girls, aged 9.6±0.7 yrs old) in Wuhan, China. Their body mass index (BMI), waist circumference (WC), CRF, blood pressure (BP), lipids, glucose, and pubertal status were assessed. Children were categorized into different groups based on their BMI, WC, and CRF using Chinese obesity cut-off points and CRF sex-specific median points. Metabolic Risk Score (MRS) was computed based on the standardized scores of BP, lipids, and glucose. Results Multiple linear regression models showed that, in the separate models, body fat was positively associated with MRS while CRF was inversely associated with MRS (p<0.001). However, when assessed simultaneously, only body fat had a significant association with MRS (p<0.001). In general, low-fit children had a lower MRS compared to their counterparts, and a significant difference between the two extreme groups was observed (low CRF and high fat vs. high CRF and low fat, p<0.001). Conclusions These findings suggest that both body fat and CRF should be considered when interpreting CVD risk in Chinese children, while body fat may be correlated with CVD risk more than CRF.

Association Between Alcohol Consumption and Risk of Cardiovascular Disease and All-Cause Mortality in Patients With Hypertension: A Meta-Analysis of Prospective Cohort Studies

OBJECTIVE To conduct a meta-analysis summarizing the risk of cardiovascular disease (CVD) and all-cause mortality (ACM) in relation to alcohol consumption in patients with hypertension, focusing on clarifying dose-response associations. PATIENTS AND METHODS PubMed and EMBASE were searched for eligible prospective cohort studies from December 3, 1949, through January 18, 2014. The semi-parameter method and dose-response analysis were used. RESULTS Nine studies (11 cohorts) were included in the meta-analysis. Compared with the lowest alcohol level (abstainers/occasional drinkers), the pooled relative risk (RR) was 0.72 (95% CI, 0.68-0.77) for the third highest category (median, 10 g/d), 0.81 (95% CI, 0.71-0.93) for the second highest category (median, 20 g/d), and 0.60 (95% CI, 0.54-0.67) for the highest category (median, 30 g/d). A J-shaped relationship between alcohol use and ACM was observed, and the nadir (RR, 0.82; 95% CI, 0.76-0.88) was found to be at a dose of 8 to 10 g of alcohol consumption per day. CONCLUSION Findings of this meta-analysis suggest that low-to-moderate alcohol consumption was inversely significantly associated with the risk of CVD and ACM in patients with hypertension.

C‐reactive protein plays a marginal role in cognitive decline: a systematic review and meta‐analysis

The objective of the study was to investigate the association between peripheral levels of C‐reactive protein (CRP) and cognitive decline that is defined by 2–5 years of cognitive change in general cognitive function or specific cognitive domain.

Cytochrome P450 1B1: An Unexpected Modulator of Liver Fatty Acid Homeostasis

Cytochrome P450 1b1 (Cyp1b1) expression is absent in mouse hepatocytes, but present in liver endothelia and activated stellate cells. Increased expression during adipogenesis suggests a role of Cyp1b1 metabolism in fatty acid homeostasis. Wild-type C57BL/6j (WT) and Cyp1b1-null (Cyp1b1-ko) mice were provided low or high fat diets (LFD and HFD, respectively). Cyp1b1-deletion suppressed HFD-induced obesity, improved glucose tolerance and prevented liver steatosis. Suppression of lipid droplets in sinusoidal hepatocytes, concomitant with enhanced glycogen granules, was a consistent feature of Cyp1b1-ko mice. Cyp1b1 deletion altered the in vivo expression of 560 liver genes, including suppression of PPARγ, stearoyl CoA desaturase 1 (Scd1) and many genes stimulated by PPARα, each consistent with this switch in energy storage mechanism. Ligand activation of PPARα in Cyp1b1-ko mice by WY-14643 was, nevertheless, effective. Seventeen gene changes in Cyp1b1-ko mice correspond to mouse transgenic expression that attenuated diet-induced diabetes. The absence of Cyp1b1 in mouse hepatocytes indicates participation in energy homeostasis through extra-hepatocyte signaling. Extensive sexual dimorphism in hepatic gene expression suggests a developmental impact of estrogen metabolism by Cyp1b1. Suppression of Scd1 and increased leptin turnover support enhanced leptin participation from the hypothalamus. Cyp1b1-mediated effects on vascular cells may underlie these changes.

Presence of enteroviruses in recreational water in Wuhan, China

Contaminated recreational waters pose a public health concern, as the potential for waterborne diseases exists in water contaminated with human fecal waste. Worldwide, bacterial indicators such as Escherichia coli, enterococci, and total and fecal coliform are used as indicators of water quality. However, enteric viruses also present a public health concern and their presence cannot always be determined based on bacterial indicators. This study explores the use of molecular detection methods of enteric viruses as indicators of fecal contamination. Four viruses, enterovirus, norovirus genogroups I and II, and male-specific FRNA coliphage, were tested in this study. Highly sensitive RT-PCR methods developed at the University of Hawaii at Manoa were utilized to evaluate environmental samples collected from three lakes in Wuhan, Hubei Province, China. Sixteen of twenty-five sites tested positive for at least one virus. Enterovirus was the most commonly detected virus, followed by norovirus genogroup I. These findings support the use of molecular detection methods to test for enteric virus presence in recreational freshwater sources in China as alternative water quality indicators, and utilize recently developed, highly sensitive methods of detection of these viruses. In addition, these findings suggest that there is substantial fecal contamination of the three lakes tested in this study.

Physical Activity and Lung Function Growth in a Cohort of Chinese School Children: A Prospective Study.

Backgrounds/objectives Evidence on the association between physical activity and lung function in children is sparse. The aim of this study was to evaluate children’s lung function growth in relation to their physical activity level in Chinese children. Methods A total of 1713 school children aged 9.89±0.86 years who were asthma-free at baseline were followed-up for 18 months from 2006 to 2008 in Guangzhou, China. Information on physical activity and other socio-economic status were obtained from self-administered questionnaires. Lung function tests were performed with a standard procedure. Results At the baseline survey, physically active girls had significantly higher forced vital capacity (FVC) than inactive girls (1.79 l vs. 1.75 l, p<0.05). The growth rates for lung function indices were significantly higher for girls who were physically active at either or both follow-up surveys than those inactive at both surveys during the follow-up period forced expiratory flows at 25% (FEF25) difference per year (dpy) (0.20 l/s vs. 0.15 l/s), forced expiratory flows at 75% (FEF75) dpy (0.57 l/s vs. 0.45 l/s) and forced expiratory flows between 25% and 75% (FEF25-75) dpy (0.36 l/s vs. 0.28 l/s) (all p<0.05). Conclusions Physical activity is positively associated with lung function growth among Chinese school-aged girls. Promotion of physical activity among children is of great importance.

Determinants of metabolic syndrome in Chinese schoolchildren.

The objective of this study was to identify the potential risk factors of metabolic syndrome (MetS) among Chinese schoolchildren. A cross-sectional study among 624 children (357 boys and 267 girls, aged 9.6 ± 0.7 years) was conducted in Wuhan, China, from May to June 2010. MetS was defined according to the criteria proposed by De Ferranti and the International Diabetes Federation (IDF) criteria. Data on cardiorespiratory fitness (CRF), household income, parental hypertension, and children’s personal information, including birth weight, preterm birth, and breast-feeding, reported by their parents were obtained. Multiple logistic regression showed that CRF (odds ratio [OR] = 0.68; 95% confidence interval [CI] = 0.60-0.77), breast-feeding (OR = 0.32; 95% CI = 0.10-0.97), and paternal hypertension (OR = 5.06; 95% CI = 1.20-21.37) were all independently associated with MetS. In conclusion, low CRF and paternal hypertension significantly increase the risk, whereas breast-feeding may reduce the risk of MetS among Chinese schoolchildren.