1α,25(OH)D (vitamin D) is crucial for mineral homeostasis in mammals, but the precise effects of 1α,25(OH)D in adipose tissue remain to be clarified in vivo. The initial 25-hydroxylation is catalyzed by liver microsomal cytochrome P450 2R1 (CYP2R1), which is conserved in vertebrates. To probe the physiological function(s) of 1α,25(OH)D in teleosts, we generated two independent cyp2r1-deficient zebrafish lines. These mutants exhibit retarded growth and increased obesity, especially in the visceral adipose tissue (VAT). These defects could be rescued with 25(OH)D treatments. ChIP-PCR analyses demonstrated that pgc1a is the target of the vitamin D receptor in the liver and VAT of zebrafish. Significantly decreased protein levels of Pgc1a, impaired mitochondrial biogenesis, and free fatty acid oxidation are also observed in the cyp2r1 mutant VAT. Our results demonstrate that regulation of 1α,25(OH)D during lipid metabolism occurs through the regulation of Pgc1a for mitochondrial biogenesis and oxidative metabolism within zebrafish VAT.

Atherosclerosis and related cardiovascular diseases (CVD) represent one of the greatest threats to human health worldwide. The protection of vascular smooth muscle cells (VSMCs) from apoptosis in the plaque has become an important therapeutic target for atherosclerotic plaque stabilization. A significant association of selenoprotein S (SelS) gene polymorphism with atherosclerotic CVD has been reported in epidemiologic studies, but the underlying mechanism remains unknown. In this paper, SelS expression in the thoracic aorta and its role in the protection of VSMCs from apoptosis have been studied. Western blot analysis showed that SelS was highly expressed in rat thoracic aorta. SelS gene silence by small interference RNA (siRNA) rendered VSMCs more sensitive to hydrogen peroxide- or tunicamycin- induced injury and apoptosis, as determined by MTT assay, Hoechst staining, and annexin V/propidium iodide staining. SelS silence aggravated hydrogen peroxide-induced oxidative stress and phosphorylation of p38 MAPK and c-Jun N-terminal kinase (JNK) in VSMCs. Furthermore, SelS silence enhanced endoplasmic reticulum (ER) stress induced by hydrogen peroxide or tunicamycin, as showed by the increased protein levels of ER chaperone 78 kDa glucose-regulated protein (GRP78), ER stress transducer phosphorylated protein kinase RNA like ER kinase (PERK), and the proapoptotic transcription factor C/EBP homologous protein (CHOP). In conclusion, the present study suggested that SelS highly expressed in the blood vessel might protect VSMCs from apoptosis by inhibiting oxidative stress and ER stress. Our finding provided mechanistic insights for the potential preventive role of SelS in atherosclerotic CVD.

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It would be important to predict type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN). This study was aimed at evaluating the predicting significance of hemostatic parameters for T2DM and DN. Plasma coagulation and hematologic parameters before treatment were measured in 297 T2DM patients. The risk factors and their predicting power were evaluated. T2DM patients without complications exhibited significantly different activated partial thromboplastin time (aPTT), platelet (PLT), and D-dimer (D-D) levels compared with controls (P < 0.01). Fibrinogen (FIB), PLT, and D-D increased in DN patients compared with those without complications (P < 0.001). Both aPTT and PLT were the independent risk factors for T2DM (OR: 1.320 and 1.211, P < 0.01, resp.), and FIB and PLT were the independent risk factors for DN (OR: 1.611 and 1.194, P < 0.01, resp.). The area under ROC curve (AUC) of aPTT and PLT was 0.592 and 0.647, respectively, with low sensitivity in predicting T2DM. AUC of FIB was 0.874 with high sensitivity (85%) and specificity (76%) for DN, and that of PLT was 0.564, with sensitivity (60%) and specificity (89%) based on the cutoff values of 3.15 g/L and 245 × 109/L, respectively. This study suggests that hemostatic parameters have a low predicting value for T2DM, whereas fibrinogen is a powerful predictor for DN.

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Summary Background Hepatitis B core‐related antigen (HBcrAg) is a viral marker for the development of cirrhosis and hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). However, the relationship between HBcrAg and HBV recurrence after liver transplantation (LT) is unclear. Aim To investigate the correlation of serum HBcrAg level with HBV recurrence post‐LT to evaluate the prognostic role of the pre‐LT HBcrAg level. Methods This retrospective cohort study enrolled 357 CHB patients who received LT for a median of 36.6 months. Univariate and multivariate analyses and time‐dependent receiver operating characteristic (ROC) curves for markers associated with HBV recurrence were analysed. Results 48 patients (13.4%) had HBV recurrence after LT. HBcrAg, detectable HBV DNA, HCC and HCC recurrence were associated with HBV recurrence. In a multivariate analysis, HBcrAg level was independently associated with HBV recurrence, and the relationship between HBcrAg level and incident HBV recurrence was significant and graded (HR: 3.17 per unit; 95% CI: 1.97‐5.11; P for trend < .001). Additionally, HBcrAg level was superior to HBV DNA level in predicting HBV recurrence by time‐dependent ROC analysis. Patients with an HBcrAg ≥ 5.0 log U/mL had a significantly higher 5‐year cumulative recurrence rate than those with an HBcrAg < 5.0 log U/mL (37.6% vs 6%, P < .001); the adjusted hazard ratio was 5.27 (95% CI 2.47‐11.25, P < .001). Conclusion An elevated serum HBcrAg level was independently associated with the risk of HBV recurrence in patients with CHB after LT.

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