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Background Glomerular damage is a common clinical indicator of nephrotic syndrome. High-dose hormone treatment often leads to hormone resistance in patients. How to avoid resistance and improve the efficiency of hormone therapy draws much attention to clinicians. Methods Adriamycin (ADR) was used to induce nephropathy model in SD rats. The rats were treated with dexamethasone (DEX), icariin (ICA), and DEX + ICA combination therapy. The changes in urinary protein (UP), urea nitrogen (BUN), and serum creatinine (SCR) contents in rats were detected by enzyme-linked immunosorbent assay (ELISA), and the degree of pathological injury and the expression level of podocin were detected by HE staining and immunohistochemistry, to test the success of the model and the therapeutic effects of three different ways. The effect of treatments on podocytes autophagy was evaluated via transfection of mRFP-GFP-LC3 tandem adenovirus in vitro. Results The contents of UP, SCR, and BUN were significantly increased, the glomerulus was seriously damaged, and the expression of Nephrosis2 (NPHS2) was significantly decreased in the ADR-induced nephrotic syndrome rat model compared to that of the control group. DEX, ICA, and the DEX + ICA combined treatment significantly alleviated these above changes induced by ADR. The combined treatment of DEX + ICA exhibited better outcome than single treatment. The combined treatment also restored the podocyte autophagy, increased the expression of microtubule-associated protein light-chain 3II (LC3II), and reduced the expression of p62 in vitro. The combined treatment protects podocytes by mediating the PI3K/AKT/mTOR (rapamycin complex) signaling pathway. Conclusion ICA enhances the therapeutic effect of DEX on the nephrotic syndrome.

Background: This research sought to elucidate the effects of peroxiredoxin 6 (PRDX6) on the biological processes in diabetic nephropathy (DN) and to identify the underlying regulatory mechanism related to tolllike receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling. Methods:To induce an in vitro DN cellular model, human kidney 2 (HK-2) cells were treated with high glucose (HG). The mitochondrial membrane potential, adenosine triphosphate level, reactive oxygen species generation, and oxidative stress of the cells were then evaluated. After the PRDX6 level had been determined, the effects of its overexpression on the mitochondrial membrane potential, adenosine triphosphate level, reactive oxygen species generation, and oxidative stress of the cells were assessed. Next, cytochrome c expression, cell viability, cell apoptosis, the inflammatory level, and the TLR4/NF-κB signaling-related factors were assessed. After the addition of the TLR4 activator CRX-527 or the NF-κB activator phorbol 12-myristate 13-acetate (PMA), cell viability, cell apoptosis and the inflammatory level were evaluated again. Results:The results revealed that HG exposure triggered mitochondrial dysfunction and oxidative stress and decreased PRDX6 expression in the HK-2 cells. PRDX6 elevation exacerbated cell viability while alleviating mitochondrial membrane potential loss, oxidative stress, apoptosis, and inflammation in the HGtreated HK-2 cells. Further, PRDX6 inhibited HG-induced TLR4/NF-κB activation. The administration of CRX-527 or PMA reversed the effects of PRDX6 on the cell viability, apoptosis, and inflammation of the HG-exposed HK-2 cells.Conclusions: To conclude, PRDX6 appears to protect HG-exposed HK-2 cells against inflammation and apoptosis by inhibiting TLR4/NF-κB signaling.

Background: Evidence suggesting a role for including calcineurin inhibitors(CNIs) in early therapy remains limited for low quality and mainly based on small observation cohort study. We will conduct a systematic reviews to explore the effect and adverse effect of calcineurin inhibitors compared with other interventions in the treatment of primary focal segmental glomerulosclerosis (FSGS). Methods: A comprehensive literature search of MEDLINE (through PubMed), EMBASE, The Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL) will be conducted. Two investigators will independently select studies, extract data and assess the quality of the included study. Extracted information will include study characteristics, the contents of included randomized controlled trials, outcomes, the quality of randomized controlled trials and etc. A risk of bias tool will be used to assess the methodological quality. Any disagreement will be resolved by the third investigator. There is no requirement of ethical approval and informed consent. Results: This study will provide high-quality evidence for treatment of FSGS in terms of effectiveness and safety. Conclusion: This systematic review aims to provide evidence for treatment of FSGS in different CNIs. Registration: The systematic review and meta-analysis is registered in the OSF REGISTERS (10.17605/OSF.IO/3B7DE) international prospective register of systematic review.