Context Genistein (Gen) has shown protective effects against ageing process. Objective To explore the role of Gen on the senescence of H2O2-induced human umbilical vein endothelial cells (HUVECs) and investigate the possible mechanism. Materials and methods HUVECs were treated with different concentrations of H2O2 (50, 100, 200 and 400 mu mol/L) for 1 h or Gen administration (20, 40, 80 and 160 mu g/mL) for 24 h. Functional experiments (cell counting kit-8, beta-galactosidase staining and flow cytometry) were used to detect the effect of Gen on H2O2-induced HUVECs. After HUVECs were transfected with TXNIP overexpression plasmids, the expression of p16, p21, thioredoxin-interacting protein (TXNIP), nucleotide-binding and oligomerization domain-like receptor 3 (NLRP3), cleaved caspase-3 and cleaved caspase-1 in HUVECs were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Results H2O2 (200 and 400 mu mol/L) inhibited the proliferation of HUVECs. At concentrations of >50 mu mol/L, H2O2 induced the cell cycle progression arrests in G1 phase and promoted cell senescence of HUVECs. Gen had no obvious cytotoxicity to HUVECs below 160 mu g/mL. H2O2-induced HUVEC senescence and the expression of TXNIP and NLRP3 in HUVECs were down-regulated by Gen (40 and 80 mu g/mL). Expressions of TXNIP and NLRP3 in HUVECs were up-regulated by H2O2 but down-regulated by Gen. Overexpressed TXNIP partially reversed the suppressive effect of Gen on H2O2-induced senescence and apoptosis of HUVECs. Expressions of p16, p21, TXNIP, NLRP3, cleaved caspase-3 and cleaved caspase-1 in H2O2-treated HUVECs were inhibited by Gen, while the inhibition as such was partially reversed by overexpressed TXNIP. Discussion and conclusions H2O2-induced HUVEC senescence was alleviated by Gen via suppressing the TXNIP/NLRP3 axis, which may offer a potential therapeutic approach for improving HUVEC senescence and provide a new direction for the treatment of cardiovascular disease.

BACKGROUND:The aim of this study was to investigate the correlation between serum uric acid level and central body fat distribution in patients with type 2 diabetes (T2DM).METHODS:A total of 867 patients with T2DM were enrolled. Measurements of central fat distribution were obtained by dual energy X-ray absorptiometry. Patients were stratified into three groups according to their levels of serum uric acid (SUA). Multiple linear regression analysis was used to determine the association between SUA and central body fat distribution. Logistic regression analysis was used to estimate the risk factors for hyperuricemia (HUA). Mediation analysis was applied to assess the overall, direct, and indirect mediators of SUA levels.RESULTS:Multiple linear regression analysis showed that SUA levels were significantly positively correlated with waist circumference (WC), body mass index (BMI), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), Android fat mass, Gynoid fat mass, fasting c-peptide (F-CP), and area under the curve of C-peptide (P < 0.05 for all). VAT [odds ratio (OR), 2.367; 95% confidence interval (CI), 1.078-5.197; P < 0.001)], WC (OR, 1.041; 95% CI, 1.011-1.072; P < 0.001), high-density lipoprotein (OR, 0.274; 95% CI, 0.104-0.727; P < 0.001), and estimated glomerular filtration rate (OR, 0.966; 95% CI, 0.959-0.973; P < 0.001) were found to be independent risk factors for T2DM patients with HUA. After mediation analysis, BMI and central obesity were found to have different partial effects on the association between SUA and F-CP (P < 0.001).CONCLUSION:In patients with T2DM, HUA was positively correlated with F-CP and central body fat distribution, especially VAT. These results suggest that central obesity may play a role in the positive correlation between HUA and insulin resistance (IR).

Background Dysimmunity plays a key role in diabetes, especially type 1 diabetes mellitus. Islet-specific autoantibodies (ISAs) have been used as diagnostic markers for different phenotypic classifications of diabetes. This study was aimed to explore the relationships between ISA titers and the clinical characteristics of diabetic patients. Methods A total of 509 diabetic patients admitted to Department of Endocrinology and Metabolism at the Affiliated Hospital of Nantong University were recruited. Anthropometric parameters, serum biochemical index, glycosylated hemoglobin, urinary microalbumin/creatinine ratio, ISAs, fat mass, and islet β-cell function were measured. Multiple linear regression analysis was performed to identify relationships between ISA titers and clinical characteristics. Results Compared with autoantibody negative group, blood pressure, weight, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), visceral fat mass, fasting C-peptide (FCP), 120 minutes C-peptide (120minCP) and area under C-peptide curve (AUCCP) of patients in either autoantibody positive or glutamate decarboxylase antibody (GADA) positive group were lower. Body mass index (BMI), waist circumference, triglycerides (TGs), body fat mass of patients in either autoantibody positive group were lower than autoantibody negative group. GADA titer negatively correlated with TC, LDL-C, FCP, 120minCP, and AUCCP. The islet cell antibody and insulin autoantibody titers both negatively correlated with body weight, BMI, TC, TG, and LDL-C. After adjusting confounders, multiple linear regression analysis showed that LDL-C and FCP negatively correlated with GADA titer. Conclusion Diabetic patients with a high ISA titer, especially GADA titer, have worse islet β-cell function, but less abdominal obesity and fewer features of the metabolic syndrome.