Background: Glucose cotransporter (SGLT) 2 suppression provides potent renal protective effect during diabetic kidney disease (DKD). This work aimed to explore how empagliflozin (EMPA, the selective and strong inhibitor of SGLT2) affected renal lipid deposition among patients undergoing type 2 diabetes mellitus (T2DM), a T2DM mouse model and human renal proximal tubular epithelial (HK-2) cells. Methods: This work divided subjects as 3 groups: non-diabetic volunteers, patients treated with metformin and those treated with metformin plus EMPA. In an in vivo study, EMPA was adopted for treating db/db mice that were raised with the basal diet or the high-advanced glycation end products (AGEs) diet. In addition, AGEs and/or EMPA was utilized to treat HK-2 cells in vitro. Results: Results showed that diabetic patients treated with metformin plus EMPA had lower AGEs levels and renal fat fraction (RFF) than those treated with metformin. Moreover, a significant and positive association was found between AGEs and RFF. Results from the basic study showed that EMPA decreased cholesterol level, tubular lipid droplets, and protein levels related to cholesterol metabolism in AGEs-mediated HK-2 cells, kidneys of db/db mice and those fed with the high-AGEs diet. Additionally, EMPA decreased AGEs levels in serum while inhibiting the expression of receptor of AGEs (RAGE) in vitro and in vivo. Conclusion: EMPA inhibited the AGEs-RAGE pathway, thereby alleviating diabetic renal tubular cholesterol accumulation.

Introduction. Cyclin-dependent kinase-5 (CDK5) is a key kinase involved in brain development and function and recently found to be involved in neuronal and astroglial apoptosis, neural stem/progenitor cell stemness, mitochondrial fission, and synaptic transmission. But the specific mechanism of CDK5-mediated anti-inflammatory remains unclear in ICH. The aim of the present study was to explore the role of CDK5 in mediating microglia activity through activated DRP1 phosphorylation in a rat ICH model. Methods. We measured behavioral change after ICH; detected the expression of CDK5 in the rat brain using immunohistochemistry; and measured the protein levels of CDK5, p35, p25, p-histone H1, and p-DRP1 using Western blot analysis. Coimmunoprecipitation analysis indicated interaction of CDK5 and DRP1. Tumor necrosis factor-α, interleukin- (IL-) 1β, and IL-6 levels were measured using enzyme-linked immunosorbent assay (ELISA). Results. After ICH, CDK5 protein level and kinase activity increased. Western blot data showed that CDK5 expression increased from 6 h and peaked at 2 d after ICH ( ), and the expression of p35 was lowest at 12 h, while the expression of p25 peaked at 2 d after ICH. Besides, p-DRP1 expression change follows with CDK5 kinase activity change. Coimmunoprecipitation showed that interaction between CDK5 and DRP1 certainly exists in microglia. Then, knockdown CDK5 or p35 expression by siRNA reduced the expression level of p-DRP1. ELISA data showed that the protein levels of proinflammatory mediators, such as TNF-α, IL-1β, and IL-6, were decreased by knockdown of CDK5. Conclusion. CDK5 may regulate DRP1 by direct phosphorylation in microglia and further induce microglia secreting proinflammation factor.

Objective: To detect serum C1Q/TNF-related protein 4 (CTRP4) concentrations in patients with newly diagnosed type 2 diabetes mellitus (T2DM) and evaluate the correlation between CTRP4 and other variables in T2DM. Method: Sixty-five patients with newly diagnosed T2DM and eighty-nine healthy volunteers were enrolled in this study. Anthropometric and biochemical data of the study participants was collected, and serum CTRP4 concentrations were detected by enzyme-linked immunosorbent assay (ELISA) kit. The correlation between serum CTRP4 and other indexes was analyzed by Spearman correlation analysis. Trend χ² test and binary multivariate stepwise logistic regression were performed to assess the correlation between CTRP4 and the risk of T2DM. Results: Serum CTRP4 concentrations in the T2DM group were significantly lower than those in the control group ( P < .01). Spearman correlation analysis showed that CTRP4 concentrations were negatively correlated with BMI, hs-CRP, HOMA-IR, FBG and TG ( r = - 0.430, - 0.453, - 0.371, - 0.361, - 0.506, P < .05), and positively correlated with HDL-c ( r = 0.303, P < .05). Trend χ² test indicated that with the increase of CTRP4 levels in the population, the risk of T2DM presented a general downward trend ( P < .01). Binary multivariate stepwise logistic regression suggested that serum CTRP4 was an independent impact factor for T2DM and high serum CTRP4 levels were related to the decreased risk of T2DM (P < .05). Conclusions: Serum CTRP4 concentrations decrease in patients with newly diagnosed T2DM. Serum CTRP4 levels are negatively associated with the risk of T2DM.