Numerous original studies and 4 published meta-analyses have reported the association between the Vitamin D receptor ( VDR ) BsmI, FokI, ApaI, and TaqI polymorphisms and type 2 diabetes mellitus (T2DM) risk. However, the results were inconsistent. Therefore, an updated meta-analysis was performed to further explore these issues. To further explore the association between the VDR BsmI, FokI, ApaI, and TaqI polymorphisms and T2DM risk. PubMed, EMBASE, Scopus, and Wanfang databases were searched. The following search strategy were used: ( VDR OR vitamin D receptor) AND (polymorphism OR variant OR mutation) AND (diabetes OR mellitus OR diabetes mellitus). Pooled crude odds ratios with 95% confidence intervals were applied to evaluate the strength of association in 5 genetic models. Statistical heterogeneity, the test of publication bias, and sensitivity analysis were carried out using the STATA software (Version 12.0). To evaluate the credibility of statistically significant associations, we applied the false-positive report probabilities (FPRP) and Bayesian false discovery probability (BFDP) test. Overall, the VDR BsmI polymorphism was associated with a significantly decreased T2DM risk in Asians; the VDR FokI polymorphism was associated with a significantly decreased T2DM risk in Asians, African countries, and Asian countries; the VDR ApaI polymorphism was associated with a significantly decreased T2DM risk in Caucasians and North American countries. On the VDR ApaI polymorphism, a significantly increased T2DM risk was found in a mixed population. However, when we further performed a sensitivity analysis, FPRP, and BFDP test, less-credible positive results were identified (all FPRP > 0.2 and BFDP > 0.8) in any significant association. In summary, this study strongly indicates that all significant associations were less credible positive results, rather than from true associations.

This study aims to investigate the apoptosis-inducing effect of fructose 1,6-bisphosphate (F1,6BP) on the related mechanism of papillary thyroid carcinoma W3 and T cells. W3 cells were treated with F1,6BP alone or in combination with antioxidant catalase (CAT) or N-acetyl-L-cysteine (NAC). The changes of cell viability and cell nucleus morphology were examined by cell proliferation assay and Hoechst staining, and apoptosis levels of these cells were measured with flow cytometry. The changes of reactive oxygen species (ROS) level and the percentage of oxidized glutathione in total glutathione in W3 cells were detected by 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining or colorimetry assay. At the same time, real-time fluorescence quantitative PCR was adopted to evaluate the expression levels of CAT and glutathione peroxidase (GSH-Px) mRNAs in W3 cells. F1,6BP inhibited the growth of W3 cells significantly, coupling with an increase in intracellular ROS level and the percentage of oxidized glutathione in total glutathione. Typical apoptotic morphological changes of the cell nucleus happened. The apoptosis rate and GSH-Px and CAT mRNAs expression levels were upregulated after F1,6BP treatment. The antitumor effect of F1,6BP was significantly decreased after W3 cells were pretreated with NAC and CAT. F1,6BP can induce the apoptosis of W3 cells through upregulating the generation of ROS, especially the production of H2O2.

BackgroundThe previous published data on the association between the X-ray repair cross-conplementation group 1 (XRCC1) polymorphisms and thyroid cancer risk remained controversial. Hence, we performed a meta-analysis on all available studies that provided 1729 cases and 3774 controls (from 11 studies) for XRCC1 Arg399Gln, 1040 cases and 2487 controls for Arg194Trp (from 7 studies), and 1432 cases and 3356 controls for Arg280His (from 8 studies).Methodology/Principal FindingsPubMed, CNKI, and EMBASE database were searched to identify relevant studies. Overall, no significant association was found between XRCC1 Arg399Gln (recessive model: OR = 0.95, 95% CI = 0.77–1.15; dominant model: OR = 0.89, 95% CI = 0.75–1.05; homozygote model: OR = 0.92, 95% CI = 0.69–1.23; Heterozygote model: OR = 0.91, 95% CI = 0.80–1.03; additive model: OR = 0.93, 95% CI = 0.81–1.07), Arg194Trp (recessive model: OR = 1.41, 95% CI = 0.62–3.23; dominant model: OR = 1.01, 95% CI = 0.77–1.34; homozygote model: OR = 1.42, 95% CI = 0.55–3.67; Heterozygote model: OR = 1.03, 95% CI = 0.85–1.26; additive model: OR = 1.08, 95% CI = 0.81–1.42), and Arg280His (recessive model: OR = 1.08, 95% CI = 0.56–2.10; dominant model: OR = 1.01, 95% CI = 0.84–1.22; homozygote model: OR = 1.00, 95% CI = 0.51–1.96; Heterozygote model: OR = 1.04, 95% CI = 0.75–1.42; additive model: OR = 1.03, 95% CI = 0.86–1.23) and thyroid cancer risk when all the eligible studies were pooled into the meta-analysis. In the further stratified and sensitivity analyses, significant association was still not found in these three genetic polymorphisms.Conclusions/SignificanceIn summary, this meta-analysis indicates that XRCC1 Arg399Gln, Arg280His, and Arg194Trp are not associated with thyroid cancer.

Purpose: To investigate the regulatory role of miR-126 in inflammation-associated gene expression in vascular smooth muscle (VSMCs) cells of diabetic rats. Methods: Diabetes was induced in rats by intraperitoneal injection of streptozocin (STZ) at a dose of 50 mg/kg. VSMCs were isolated from the aortic intimal-medial layers of the rats by a standard protocol. Expression of miR-126 was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Transfection was performed with Lipofectamine 2000 reagent. Results: Expression of miR-126 was significantly (p < 0.05) downregulated in the VSMCs of diabetic rats. Similarly, expressions of SOD, APX and CAT were downregulated, while those of COX, LOX and NOS were significantly upregulated in VSMCs. However, transfection-induced miR-126 overexpression in the VSMCs of diabetic rats led to significant (p < 0.05) upregulation of SOD, CAT, APX and downregulation of COX, LOX and NOS. TargetScan analysis revealed that miR-126 exerted these effects by targeting SIRT1 gene. Furthermore, qRT-PCR and western blotting revealed that miR-126 overexpression in diabetic VMSCs caused significant (p < 0.05) upregulation of the expression of SIRT-1. Conclusion: The results indicate that miR-126 regulates the expression of inflammation-related genes by targeting SIRT-1 genes in vascular smooth muscle cells of diabetic rats. Thus, miR-126 may be beneficial in the management of diabetes.