Diabetic kidney disease (DKD) is one of the major microvascular complications in patients with type 1 and/or type 2 diabetes, the first cause of end-stage renal disease (ESRD) in several countries and regions. However, the pathogenesis of DKD and the mechanisms through which it leads to ESRD remain unknown. Thus, in this study, we aimed to elucidate some of these mechanisms. The expression of microRNA (miRNA or miR)-342-3p and SRY-box 6 (SOX6) in the renal tissues of mice with DKD and mouse renal mesangial cells (MCs) was determined by RT-qPCR and western blot analysis. The diabetic kidney environment was established using high-glucose medium. SOX6 was verified as a target gene of miR-342-3p by dual-luciferase activity assay. In addition, western blot analysis was employed to determine the changes in the levels of several biomarkers of fibrosis [transforming growth factor (TGF)-β1, fibronectin (FN), collagen IV (referred to as C-IV) and phosphatase and tensin homolog (PTEN)]. Compared with THE control mice, the expression of miR-342-3p in the kidney tissues of mice with DKD was down-regulated, whereas that of SOX6 was upregulated. The same phenomenon was observed in the MCs cultured in high-glucose medium. Subsequently, miR-342-3p inhibited SOX6 expression, promoted cell proliferation and inhibited the apoptosis of MCs. Moreover, the overexpression of miR-342-3p suppressed high glucose-induced renal interstitial fibrosis. In addition, it was found that miR-342-3p inhibited SOX6 expression by binding to the 3′-UTR of SOX6. On the whole, the findings of this study demonstrate that miR-342-3p suppresses the progression of DKD by inducing the degradation of SOX6. Thus, the miR-342-3p/SOX6 axis may serve as a novel therapeutic target in the treatment of DKD.
ABSTRACT. Alzheimer's disease (AD) is a progressive neurodegenerative disorder that contributes to dementia in the elderly population. Genome-wide linkage analysis has identified chromosome 12p as the AD-susceptible region, which includes lectin-like oxidized low-density lipoprotein receptor 1 (OLR1). The OLR1 +1073 C/T single-nucleotide polymorphism is located in the 3'-untranslated region of the gene and may influence the binding of regulatory microRNAs (miRNAs) and OLR1 protein homeostasis. A number of studies have reported an association between this variant and AD. However, the results are controversial. A meta-analysis of case-control studies examining the relationship between the OLR1 +1073 C/T singlenucleotide polymorphism and AD risk was performed. Five studies were selected that included 2419 cases and 2381 controls. The results revealed a significantly decreased AD risk in the recessive model (TT vs TC + CC: odds ratio (OR) = 0.79, 95% confidence interval (CI) = 0.65-0.96). The control group in one of the studies was in HardyWeinberg disequilibrium, so we performed additional meta-analysis excluding this study. The significance was much more pronounced in Using miRanda and RNA hybrid methods, the polymorphic allele was shown to influence the binding of various miRNAs. Our results suggested that the +1073 C/T polymorphism decreased the risk of AD. The polymorphic allele was also predicted to affect the binding site of many miRNAs, which may explain the relationship between the +1073 C/T variant and AD.
The real time domain interferometry for the photodetachment dynamics driven by the oscillating electric field has been studied for the first time. Both the geometry of the detached electron trajectories and the electron probability density are shown to be different from those in the photodetachment dynamics in a static electric field. The influence of the oscillating electric field on the detached electron leads to a surprisingly intricate shape of the electron waves, and multiple interfering trajectories generate complex interference patterns in the electron probability density. Using the semiclassical open-orbit theory, we calculate the interference patterns in the time-dependent electron probability density for different electric field strengths, different frequencies and phases in the oscillating electric field. This method is universal, and can be extended to study the photoionization dynamics of the atoms in the time-dependent electric field. Our study can guide the future experimental researches in the photodetachment or photoionization microscopy of negative ions and atoms in the oscillating electric field.
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