miR-146a promotes M2 macrophage polarization and accelerates diabetic wound healing by inhibiting the TLR4/NF-κB axis.

We tried to unveil the clinical significance of miR-146a as a biomarker in M2 macrophage polarization in diabetic wound healing. Initially, we found reduced miR-146a in macrophages of diabetic patients. Next, dual-luciferase assay verified that toll-like receptor 4 (TLR4) was a target gene of miR-146 and was negatively regulated by miR-146. Moreover, after ectopic expression and depletion experiments of miR-146 and/or TLR4, lipopolysaccharide-induced inflammatory response of macrophages was detected. The results revealed that overexpression of miR-146a promoted the M2 macrophage polarization by suppressing the TLR4/nuclear factor-kappaB (NF-κB) axis, so as to enhance wound healing in diabetic ulcers. Further, mouse models with diabetic ulcers were established to investigate the effects of miR-146a on diabetic wound healing in vivo, which revealed that miR-146a promoted wound healing in diabetic ulcers by inhibiting the TLR4/NF-κB axis. In conclusion, we demonstrate that miR-146a can induce M2 macrophage polarization to enhance wound healing in diabetic ulcers by inhibiting the TLR4/NF-κB axis.

Vitamin D and iodine status was associated with the risk and complication of type 2 diabetes mellitus in China.

The purpose of this study was to assess the relationship between 25-hydroxyvitamin D (25(OH)D), urinary iodine concentration (UIC), and type 2 diabetes mellitus (T2DM) risk and complications and to establish a model to predict T2DM in the general population. A total of 567 adults (389 T2DM patients and 178 controls) were enrolled, and the levels of 25(OH)D, iodine, and blood biochemical parameters were measured. Pearson's correlation analysis showed an inverse correlation between 25(OH)D level, UIC, and T2DM risk. Low 25(OH)D level was a risk factor for developing T2DM (OR, 0.81; 95% CI, 1.90-2.63; P = 0.043) after adjustment for multiple risk factors. 25(OH)D level and UIC were inversely correlated with short-term and long-term glucose levels. 25(OH)D deficiency was also associated with a high incidence of T2DM complicated with thyroid dysfunction. A prediction model based on 25(OH)D, iodine status, and other risk factors was established and recommended to screen high-risk T2DM in the general population and provide early screening and timely treatment for them.

LncRNA RNCR3 promotes endothelial cell proliferation and inflammatory cytokine secretion via regulating miR-185-5p/cyclin D2 axis.

Endothelial cell is one critical structure of blood vessels, and irregular migration and proliferation of endothelial cell might cause progression of several vascular diseases such as atherosclerosis and restenosis. We showed that TNF-α, PDGF-bb, and IL-1ß promote RNCR3 expression in a dose-dependent manner inhuman endothelial cell. RNCR3 level is higher in serum of atherosclerosis patients compared with those in control volunteers. Overexpression of RNCR3 promotes cell proliferation and three inflammatory cytokine secretion including IL-6, IL-1ß, and TNF-α in endothelial cell. We illustrated that overexpression of RNCR3 inhibits miR-185-5p expression in endothelial cell. Furthermore, we indicated that miR-185-5p level is lower in the serum of patients with atherosclerosis compared with those in control volunteers. There is a negative correlation between miR-185-5p and RNCR3 expression in serum of patients with atherosclerosis. Using Targetscan, it predicted that miR-185-5p may bind to cyclin D2 and miR-185-5p is one potential target of miR-185-5p. Luciferase reporter data indicated that miR-185-5p suppresses luciferase value of wild-type cyclin D2 while it has no influence of cyclin D2 mutant. Overexpression of RNCR3 enhances cyclin D2 expression in endothelial cell. Moreover, RNCR3 induces cell growth and enhances inflammatory cytokine secretion through modulating cyclin D2 expression in endothelial cell. These results suggested that RNCR3 may serve as one new target for the treatment of atherosclerosis.

Reduced Serum Levels of Brain-Derived Neurotrophic Factor Are Related to Mild Cognitive Impairment in Chinese Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is involved in obesity, type 2 diabetes mellitus (T2DM), and cognitive dysfunction. The present study sought to assess the role of serum levels of BDNF in the pathophysiological process of mild cognitive impairment (MCI), a preclinical phase of dementia in 715 Chinese patients with T2DM. METHODS: Cross-sectional data were obtained from 715 patients with T2DM recruited from a Chinese diabetes center. Serum levels of BDNF were measured with sandwich enzyme-linked immunosorbent assay. The influence of BDNF on MCI was examined using univariate and multivariate binary logistic regression analyses. RESULTS: In univariate and multivariate logistic regression analyses, for each one-unit increase of BDNF, the unadjusted and adjusted risk of MCI decreased by 9% (OR 0.91; 95% CI 0.88-0.93, p < 0.001) and 6% (0.94; 0.87-0.98, p < 0.001) respectively. In multivariate models comparing the first (Q1), second and third quartiles against the fourth quartile of BDNF, BDNF in Q1 and Q2 were associated with MCI, and increased risk of MCI by 275% (OR 3.75; 95% CI 2.38-6.03) and 155% (2.55; 1.32-4.02). These results suggested that for each 1 ng/mL increase of serum level of BDNF, the association became stronger among obese diabetic patients (OR 0.91, 95% CI 0.85-0.96; p < 0.001) versus nonobese diabetic patients (OR 0.95, 95% CI 0.86-0.98; p = 0.001). CONCLUSION: The present data demonstrated that reduced serum levels of BDNF were associated with increased risk of MCI and might be useful for identifying diabetic patients at risk of dementia for early prevention strategies.