Objective To observe the protective effects of unfractionated heparin (UFH) on high-mobility group box-1 protein (HMGB1) induced increased permeability of endothelial cells, and investigate the protective mechanism of UFH on HMGB1 induced defective expression of zonula occludens-1 (ZO-1). Methods Human umbilical vascular endothelial cells (HUVECs) were culturedin vitro and divided into 4 groups (n=5), namely a control group, a HMGB1 group (100 ng/ml), a heparin group (UFH 10 U/ml), a HMGB1/heparin group (100 ng/ml HMGB1 + UFH 10 U/ml). Endothelial cell viability was measured by methyl thiazolyl tetrazolium (MTT) colorimetric method. Endothelial permeability was determination by Transwell chamber method. Immunofluorescence and laser confocal microscopy were used to assess the distribution of ZO-1. The protein expressions of tight junction protein ZO-1 and nuclear factor kappa B (NF-κB) were detected by Western blot. Results HMGB1 (100 ng/ml) had no inhibitory effect on endothelial cell viability (P＞0.05). UFH pretreatment could reduce the permeability increment of endothelial cells induced by HMGB1. UFH pretreatment could reduce the close loop reduction and damage of ZO-1 induced by HMGB1, enhance the fluorescence intensity and expression of ZO-1, and decrease the NF-κB translocation. Conclusions UFH can protect HMGB1-mediated defect of ZO-1 expression and increased permeability of the endothelial cells. The mechanism may be related to the decreased nuclear translocation of NF-κB.
ObjectiveTo systematically evaluate the effects of vitamin D supplementation on fasting blood glucose, insulin resistance, β cell function in type 2 diabetes mellitus. MethodsDatabases including PubMed, The Cochrane Library (Issue 12, 2015), Web of Science, ScienceDirect Online, VIP, CNKI, WanFang Data, and CBM were searched to collect randomized controlled trials (RCTs) about vitamin D supplementation for type 2 diabetes mellitus from inception to December 2015. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then meta-analysis was conducted by RevMan 5.3 and Stata12.0 softwares. ResultsA total of 22 RCTs involving 1 756 patients were included. The results of meta-analysis showed that, compared with the control group, the vitamin D supplementation group had a significant improvement in insulin resistance (SMD=–0.68, 95%CI –1.23 to –0.12, P=0.02), but there were no significant differences in levels of FPG, HbA1c and HOMA-β between the two groups (all P value > 0.05). Subgroup analysis showed that, the levels of FPG and HOMA-IR were significantly decreased in the vitamin D supplementation group in Middle Easterners and patients whose follow-up duration was less than three months. ConclusionVitamin D supplementation could improve HOMA-IR but could not improve the levels of FPG, HbA1c and HOMA-β. However, the evidence is weak to recommend vitamin D as a means of improving glycemic control, insulin resistance and β cell function in type 2 diabetes mellitus. Further larger, high quality trials are warranted.