Association between polymorphisms in the promoter region of pri-miR-34b/c and risk of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths worldwide. MicroRNA-34 (miR-34) gene plays a key role in altering the apoptotic cycle and pathways of downstream cells, and therefore influences carcinogenesis. In this case-control study, we assessed the role of the pri-miR-34b/c rs4938723 polymorphism in HCC risk. The pri-miR-34b/c polymorphic genotype was determined in 286 patients with HCC and 572 controls using polymerase chain reaction-restriction fragment length polymorphism. The male gender (X2 = 12.95, P < 0.001), regular alcohol consumption (X2 = 16.81, P < 0.001), and a family history of cancer (X2 = 11.88, P = 0.001) were associated with HCC risk. However, the age (t = 1.19, P = 0.12) and tobacco smoking habit (X2 = 0.64, P = 0.42) of HCC patients were comparable to those of the controls. The TC (adjusted OR = 1.46, 95%CI = 1.06-2.01) and CC (adjusted OR = 3.07, 95%CI = 1.77-5.34) genotypes of pri-miR-34b/c rs4938723 were correlated with a higher risk of HCC compared to the TT genotype. Moreover, the TC+CC genotype was correlated with an increased risk of HCC compared to the TT genotype (adjusted OR = 1.64, 95%CI = 1.21-2.22). In the recessive model, the CC genotype of pri-miR-34b/c rs4938723 was significantly correlated with an elevated risk of HCC compared to the TT+TC genotype (adjusted OR = 2.50, 95%CI = 1.49-4.22). Further large-scale and multi-center studies are required to confirm these results.

Effect of IL-1ß, IL-8, and IL-10 polymorphisms on the development of myocardial infarction.

Myocardial infarction (MI) is currently a leading cause of death worldwide, and is caused by various environmental and genetic factors. We therefore conducted a case-control study to investigate the association between polymorphisms in interleukins IL-1ß, IL-8, and IL-10 and MI risk. This study recruited 260 MI patients and 285 control subjects. Genotyping of IL-1ß +3954C/T, IL-8 -251T/A, IL-10 -1082A/G, and IL-10 -819C/T were assessed using the polymerase chain reaction-restriction fragment length polymorphism method. By comparing the risk factors of MI between the case and control groups, we discovered that MI patients were more likely to have smoking and drinking habits, have a history of hypertension and diabetes, have higher triglycerides and low-density lipoprotein cholesterol levels, and a lower high-density lipoprotein cholesterol level (P < 0.05). Unconditional regression analyses showed that subjects carrying the GG genotype of the IL-10 -1082A/G polymorphism were associated with increased risk of MI, and the OR (95%CI) was 2.04 (1.15-3.65). Our study found that the IL-10 -1082A/G polymorphism plays an important role in influencing the development of MI.

Effects of Astragaloside IV on diabetic nephropathy in rats.

The aims of this study were to explore the effects of Astragaloside IV on diabetic nephropathy (DN) rats. A total of 38 male Sprague-Dawley (SD) rats were divided into three groups: 10 in the normal (control) group, 14 in the DN model group, and 14 in the AS-IV group. Treatment began one week after the streptozotocin DN model was successfully established. Blood glucose and urine micro-albumin levels were measured every four weeks. After being treated for 12 weeks, all SD rats were sacrificed for blood and renal specimen collec-tion. Renal cortex specimens were observed after hematoxylin and eo-sin and Masson staining. Expression levels of protein ß1, ß1-integrin-linked protein kinase (ILK) and α-actinin-4 were also measured. After eight weeks of intervention, blood glucose levels in the AS-IV group decreased significantly when compared with those of the model group (P < 0.01). By the end of the twelfth week, the urine micro-albumin levels showed significant differences (P < 0.01) between the AS-IV and model groups, and the expression levels of integrin ß1, ILK, and α-actinin-4 also showed significant differences (P < 0.05, respectively). Concomitantly, expression levels of integrin ß1, ILK, and α-actinin-4 in the model group were significantly different from those of normal group (P < 0.05). These results suggest that AS-IV can be quite effective in decreasing blood glucose levels, reducing urine albumin excretion, and improving the adhesion function of potocytes, and can thus delay the development of DN.

Changes in cardiac aldosterone and its synthase in rats with chronic heart failure: an intervention study of long-term treatment with recombinant human brain natriuretic peptide

The physiological mechanisms involved in isoproterenol (ISO)-induced chronic heart failure (CHF) are not fully understood. In this study, we investigated local changes in cardiac aldosterone and its synthase in rats with ISO-induced CHF, and evaluated the effects of treatment with recombinant human brain natriuretic peptide (rhBNP). Sprague-Dawley rats were divided into 4 different groups. Fifty rats received subcutaneous ISO injections to induce CHF and the control group (n=10) received equal volumes of saline. After establishing the rat model, 9 CHF rats received no further treatment, rats in the low-dose group (n=8) received 22.5 μg/kg rhBNP and those in the high-dose group (n=8) received 45 μg/kg rhBNP daily for 1 month. Cardiac function was assessed by echocardiographic and hemodynamic analysis. Collagen volume fraction (CVF) was determined. Plasma and myocardial aldosterone concentrations were determined using radioimmunoassay. Myocardial aldosterone synthase (CYP11B2) was detected by quantitative real-time PCR. Cardiac function was significantly lower in the CHF group than in the control group (P<0.01), whereas CVF, plasma and myocardial aldosterone, and CYP11B2 transcription were significantly higher than in the control group (P<0.05). Low and high doses of rhBNP significantly improved hemodynamics (P<0.01) and cardiac function (P<0.05) and reduced CVF, plasma and myocardial aldosterone, and CYP11B2 transcription (P<0.05). There were no significant differences between the rhBNP dose groups (P>0.05). Elevated cardiac aldosterone and upregulation of aldosterone synthase expression were detected in rats with ISO-induced CHF. Administration of rhBNP improved hemodynamics and ventricular remodeling and reduced myocardial fibrosis, possibly by downregulating CYP11B2 transcription and reducing myocardial aldosterone synthesis.

Changes in cardiac aldosterone and its synthase in rats with chronic heart failure: an intervention study of long-term treatment with recombinant human brain natriuretic peptide.

The physiological mechanisms involved in isoproterenol (ISO)-induced chronic heart failure (CHF) are not fully understood. In this study, we investigated local changes in cardiac aldosterone and its synthase in rats with ISO-induced CHF, and evaluated the effects of treatment with recombinant human brain natriuretic peptide (rhBNP). Sprague-Dawley rats were divided into 4 different groups. Fifty rats received subcutaneous ISO injections to induce CHF and the control group (n=10) received equal volumes of saline. After establishing the rat model, 9 CHF rats received no further treatment, rats in the low-dose group (n=8) received 22.5 µg/kg rhBNP and those in the high-dose group (n=8) received 45 µg/kg rhBNP daily for 1 month. Cardiac function was assessed by echocardiographic and hemodynamic analysis. Collagen volume fraction (CVF) was determined. Plasma and myocardial aldosterone concentrations were determined using radioimmunoassay. Myocardial aldosterone synthase (CYP11B2) was detected by quantitative real-time PCR. Cardiac function was significantly lower in the CHF group than in the control group (P<0.01), whereas CVF, plasma and myocardial aldosterone, and CYP11B2 transcription were significantly higher than in the control group (P<0.05). Low and high doses of rhBNP significantly improved hemodynamics (P<0.01) and cardiac function (P<0.05) and reduced CVF, plasma and myocardial aldosterone, and CYP11B2 transcription (P<0.05). There were no significant differences between the rhBNP dose groups (P>0.05). Elevated cardiac aldosterone and upregulation of aldosterone synthase expression were detected in rats with ISO-induced CHF. Administration of rhBNP improved hemodynamics and ventricular remodeling and reduced myocardial fibrosis, possibly by downregulating CYP11B2 transcription and reducing myocardial aldosterone synthesis.

Association of adult weight gain and nonalcoholic fatty liver in a cross-sectional study in Wan Song Community, China.

Our objective was to examine associations of adult weight gain and nonalcoholic fatty liver disease (NAFLD). Cross-sectional interview data from 844 residents in Wan Song Community from October 2009 to April 2010 were analyzed in multivariate logistic regression models to examine odds ratios (OR) and 95% confidence intervals (CI) between NAFLD and weight change from age 20. Questionnaires, physical examinations, laboratory examinations, and ultrasonographic examination of the liver were carried out. Maximum rate of weight gain, body mass index, waist circumference, waist-to-hip ratio, systolic blood pressure, diastolic blood pressure, fasting blood glucose, cholesterol, triglycerides, uric acid, and alanine transaminase were higher in the NAFLD group than in the control group. HDL-C in the NAFLD group was lower than in the control group. As weight gain increased (measured as the difference between current weight and weight at age 20 years), the OR of NAFLD increased in multivariate models. NAFLD OR rose with increasing weight gain as follows: OR (95%CI) for NAFLD associated with weight gain of 20+ kg compared to stable weight (change <5 kg) was 4.23 (2.49-7.09). Significantly increased NAFLD OR were observed even for weight gains of 5-9.9 kg. For the "age 20 to highest lifetime weight" metric, the OR of NAFLD also increased as weight gain increased. For the "age 20 to highest lifetime weight" metric and the "age 20 to current weight" metric, insulin resistance index (HOMA-IR) increased as weight gain increased (P<0.001). In a stepwise multivariate regression analysis, significant association was observed between adult weight gain and NAFLD (OR=1.027, 95%CI=1.002-1.055, P=0.025). We conclude that adult weight gain is strongly associated with NAFLD.

Association of adult weight gain and nonalcoholic fatty liver in a cross-sectional study in Wan Song Community, China

Our objective was to examine associations of adult weight gain and nonalcoholic fatty liver disease (NAFLD). Cross-sectional interview data from 844 residents in Wan Song Community from October 2009 to April 2010 were analyzed in multivariate logistic regression models to examine odds ratios (OR) and 95% confidence intervals (CI) between NAFLD and weight change from age 20. Questionnaires, physical examinations, laboratory examinations, and ultrasonographic examination of the liver were carried out. Maximum rate of weight gain, body mass index, waist circumference, waist-to-hip ratio, systolic blood pressure, diastolic blood pressure, fasting blood glucose, cholesterol, triglycerides, uric acid, and alanine transaminase were higher in the NAFLD group than in the control group. HDL-C in the NAFLD group was lower than in the control group. As weight gain increased (measured as the difference between current weight and weight at age 20 years), the OR of NAFLD increased in multivariate models. NAFLD OR rose with increasing weight gain as follows: OR (95%CI) for NAFLD associated with weight gain of 20+ kg compared to stable weight (change <5 kg) was 4.23 (2.49-7.09). Significantly increased NAFLD OR were observed even for weight gains of 5-9.9 kg. For the “age 20 to highest lifetime weight” metric, the OR of NAFLD also increased as weight gain increased. For the “age 20 to highest lifetime weight” metric and the “age 20 to current weight” metric, insulin resistance index (HOMA-IR) increased as weight gain increased (P<0.001). In a stepwise multivariate regression analysis, significant association was observed between adult weight gain and NAFLD (OR=1.027, 95%CI=1.002-1.055, P=0.025). We conclude that adult weight gain is strongly associated with NAFLD.

Maternal MTHFR C677T polymorphism and congenital heart defect risk in the Chinese Han population: a meta-analysis.

Numerous studies have evaluated the association between the maternal C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene and congenital heart defect (CHD) risk in the Chinese Han population. However, the specific association is still controversial. Six separate studies with 1089 subjects in the Chinese Han population on the relationship between the C677T polymorphism and CHDs were analyzed by meta-analysis, upon database search. The fixed-effect model or random-effect model was selected to calculate the pooled odds ratio (ORs) and its corresponding 95% confidence interval (95%CI) when appropriate. The Begg test was used to measure publication bias. Sensitivity analyses were performed to insure authenticity of the outcome. Meta-analysis of the results showed significant associations between the maternal C677T polymorphism and CHD risk (CC vs TT: OR = 0.65, 95%CI = 0.44-0.96). Limiting the analysis to the studies with controls in the Hardy-Weinberg equilibrium and the results indicate that the meta-analysis was statistically significant. Results of Begg's funnel plot showed that there was no publication bias (all P > 0.05). The present meta-analysis suggested that the maternal C677T polymorphism is a risk factor for CHDs in the Chinese Han population.