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BackgroundMembranous nephropathy (MN) is a common pathological phenotype for adult nephrotic syndrome (NS). The occurrence of MN is increasing across China, but diagnostic methods for MN still rely on kidney biopsy and PLA2R and THSD7A detection in plasma and kidney tissue, and there has been no new biomarker for MN discovered since 2014. Immune infiltration status in MN patients suffers from the dearth of associated studies. In the present study, we aimed to find new bio-markers for MN and evaluate the role of immune cells infiltration in MN pathology.MethodsWe downloaded MN expression profile from the Gene Expression Omnibus database and used R-project to screen differentially expressed genes (DEGs) and performed functional correlation analysis. Least absolute shrinkage and selection operator (LASSO) logistic regression and Radom Forest algorithms were used to screen and verify the bio-markers of MN. Finally, CIBERSORT was used to evaluate the infiltration of immune cells in MN tissues.ResultsA total of 463 DEGs were screened from the MN tissue in this study. ETS2 was identified as bio-marker for MN. The CIBERSORT results showed that there were statistical differences in monocytes, plasma cells, regulatory T cells, and memory B cells. In addition, ETS2 was positively related to monocytes, M1 phase macrophages, and neutrophils and negatively correlated to plasma cells, CD4+ T memory cells, M2 macrophages, CD8+ T cells, memory B cells, and resting mast cells.Conclusion(1) Machine learning algorithms reveals Ets2 as a novel target for membranous nephropathy patients. (2) Immune infiltration plays an important part in membranous nephropathy. (3) Ets2 expression is related to immune cells infiltration.

Unraveling the complex regulatory pathways that mediate the effects of phosphate on vascular smooth muscle cells (VSMCs) may provide novel targets and therapies to limit the destructive effects of vascular calcification (VC) in patients with chronic kidney disease (CKD). Our previous studies have highlighted several signaling networks associated with VSMC autophagy, but the underlying mechanisms remain poorly understood. Thereafter, the current study was performed to characterize the functional relevance of O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) in high phosphate-induced VC in CKD settings. We generated VC models in 5/6 nephrectomized rats in vivo and VSMC calcification models in vitro. Artificial modulation of OGT (knockdown and overexpression) was performed to explore the role of OGT in VSMC autophagy and VC in thoracic aorta, and in vivo experiments were used to substantiate in vitro findings. Mechanistically, co-immunoprecipitation (Co-IP) assay was performed to examine interaction between OGT and kelch like ECH associated protein 1 (KEAP1), and in vivo ubiquitination assay was performed to examine ubiquitination extent of nuclear factor erythroid 2-related factor 2 (NRF2). OGT was highly expressed in high phosphate-induced 5/6 nephrectomized rats and VSMCs. OGT silencing was shown to suppress high phosphate-induced calcification of VSMCs. OGT enhances KEAP1 glycosylation and thereby results in degradation and ubiquitination of NRF2, concurrently inhibiting VSMC autophagy to promote VSMC calcification in 5/6 nephrectomized rats. OGT inhibits VSMC autophagy through the KEAP1/NRF2 axis and thus accelerates high phosphate-induced VC in CKD.

Background/Aims: Autophagy is an evolutionarily conserved mechanism that affects the survival and functions of vascular smooth muscle cells (VSMCs). We explored the role of microRNAs (miRNAs) in regulating autophagy in VSMCs exposed to high phosphorus (Pi) levels. Methods: VSMCs were isolated from the thoracic aorta of rats and were cultured primarily. Real-time PCR was used to measure the mRNA expression of indicated genes. Western blotting was performed to detect the protein expression of autophagy-related markers. Results: We found that treatment with high Pi levels (1 and 3 mM) activated LC3II expression and promoted autophagic flux in VSMCs. Conversely, treatment with an autophagy inhibitor decreased LC3II expression. Pi stimulation dysregulated the expression of several miRNAs such as miR-18a, miR-21, miR-23a, miR-30b, and miR-31a. However, miR-30b overexpression decreased Pi-induced expression of autophagy-related marker genes such as BECN1, ATG5, and LC3b, whereas miR-30b downregulation increased Pi-induced expression of these genes. In addition, we found that miR-30b directly targeted BECN1. Conclusions: These data suggest that miR-30b plays an important role in the regulation of high Pi level-induced autophagy in VSMCs by targeting BECN1.

To evaluate the efficacy and safety of the low-fluence 1,064-nm Q-switched neodymium-doped yttrium aluminium garnet (QSNY) laser in treating infraorbital dark circles. Thirty women with infraorbital dark circles (predominant color dark brown) participated in this open-label study. Participants underwent eight sessions of low-fluence QSNY laser treatment at 4.2 J/cm at 3- to 4-day intervals. A spot size of 3.5 mm was used, with a pulse duration of 8 ns. The melanin deposition in the lesional skin was observed in vivo using reflectance confocal microscopy (RCM). Morphologic changes were evaluated using a global evaluation, an overall self-assessment, a narrow-band reflectance spectrophotometer, and a skin hydration measurement instrument. Twenty-six of 30 patients showed global improvement that they rated as excellent or good. Twenty-eight rated their overall satisfaction as excellent or good. The melanin index indicated a substantial decrease, from 225.84 at baseline to 182.65 ( p<.05). RCM results showed a dramatic decrease of melanin deposition in the upper dermis. Adverse effects were minimal. The characteristic finding for dark-brown infraorbital dark circles is melanin deposition in the upper dermis. Treatment of infraorbital dark circles using low-fluence 1,064-nm QSNY laser is safe and effective. The authors have indicated no significant interest with commercial supporters. [ABSTRACT FROM AUTHOR]