Inhibition of excessive autophagy alleviates renal injury and inflammation in a rat model of immunoglobulin A nephropathy.

The pathogenesis of immunoglobulin A nephropathy (IgAN) is closely related to immunity and inflammation. The clinical process of IgAN varies greatly, making the assessment of prognosis challenging and limiting progress on effective treatment measures. Autophagy is an important pathway for the development of IgAN. However, the role of autophagy in IgAN is complex, and the consequences of autophagy may change during disease progression. In the present study, we evaluated the dynamic changes in autophagy during IgAN. Specifically, we examined autophagy in the kidney of a rat model of IgAN at different time points. We found that autophagy was markedly and persistently induced in IgAN rats, and the expression level of inflammation was also persistently elevated. The autophagy enhancer rapamycin and autophagy inhibitor 3-methyladenine were used in this study, and the results showed that 3-methyladenine can alleviate renal injury and inflammation in IgAN rats. Our study provides further evidence for autophagy as a therapeutic target for IgAN.

N-/T-Type vs. L-Type Calcium Channel Blocker in Treating Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

Renin-angiotensin system (RAS) inhibitors and calcium channel blockers (CCB) are often used together in chronic kidney disease (CKD). The PubMed, EMBASE, and Cochrane Library databases were searched to identify randomized controlled trials (RCTs) in order to explore better subtypes of CCB for the treatment of CKD. This meta-analysis of 12 RCTs with 967 CKD patients who were treated with RAS inhibitors demonstrated that, when compared with L-type CCB, N-/T-type CCB was superior in reducing urine albumin/protein excretion (SMD, -0.41; 95% CI, -0.64 to -0.18; p < 0.001) and aldosterone, without influencing serum creatinine (WMD, -3.64; 95% CI, -11.63 to 4.35; p = 0.37), glomerular filtration rate (SMD, 0.06; 95% CI, -0.13 to 0.25; p = 0.53), and adverse effects (RR, 0.95; 95% CI, 0.35 to 2.58; p = 0.93). In addition, N-/T-type CCB did not decrease the systolic blood pressure (BP) (WMD, 0.17; 95% CI, -1.05 to 1.39; p = 0.79) or diastolic BP (WMD, 0.64; 95% CI, -0.55 to 1.83; p = 0.29) when compared with L-type CCB. In CKD patients treated with RAS inhibitors, N-/T-type CCB is more effective than L-type CCB in reducing urine albumin/protein excretion without increased serum creatinine, decreased glomerular filtration rate, and increased adverse effects. The additional benefit is independent of BP and may be associated with decreased aldosterone (PROSPERO, CRD42020197560).

Effects of modified Huangqi Chifeng decoction on the IL-17 signaling pathway in an IgA nephropathy rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Immunoglobulin A nephropathy (IgAN) is an immune-related primary glomerular disease prevalent worldwide, with complicated clinical manifestations and an unclear pathogenesis. IgAN is the main cause of chronic renal failure and places a significant burden on patients and society. The modified Huangqi Chifeng decoction (MHCD) is an effective prescription for the clinical treatment of IgAN while its specific mechanism remains to be further elucidated. AIM OF THE STUDY: Based on the findings of previous network pharmacology-related method-based studies, this study aimed to further explore the mechanism of action of MHCD for IgAN treatment. MATERIALS AND METHODS: IgAN rat model was established by bovine serum protein + carbon tetrachloride + lipopolysaccharide. After successful modeling, the rats in the original model group were divided into 5 group: model group, telmisartan group, and MHCD high-, medium- and low-dose groups by random number table (n = 10 respectively). The corresponding drugs were applied for 8 weeks, and the experiment lasted for 21 weeks. At the end of the experiment, 24h urine protein quantification, serum biochemistry and IL-6 and IL-17A levels were measured. The pathological changes of kidney were observed by light microscope, immunofluorescence microscope and the changes of glomerular ultrastructure were observed by transmission electron microscope. The expression levels of IL-17 signaling pathway related proteins (HSP90, MMP9, NF-κB P65 and p-NF-κB P65) were detected by Western Blot and immunohistochemistry. RESULT: Telmisartan and MHCD treatment can reduce the 24h urinary protein level and improved blood stasis states of IgAN rats, alleviate the renal pathological injury, decrease the serum levels of IL-6, IL-17A and the expression levels of HSP90, MMP9 and p-NF-κB P65 related proteins in IL-17 signaling pathway. CONCLUSION: MHCD can down-regulate the expression of IL-17 signaling pathway-related factors in IgAN model rats, improve the state of blood stasis, and alleviate the pathological damage of kidney in rats.

Analysis of Ferroptosis-Related Gene Expression and Prognostic Factors of Renal Clear Cell Carcinoma Based on TCGA Database.

INTRODUCTION: Renal clear cell carcinoma (ccRCC) is a common tumor of the urinary system, most of which are primary malignant tumors with high metastatic rate and remaining incurable. Ferroptosis is a newly discovered form of iron-dependent programmed cell necrosis in recent years, which is inextricably linked to the occurrence and development of tumors progression. Due to the complexity of the interaction between genes in ccRCC, the research on the pathogenesis of ccRCC is still not remarkably accurate. Therefore, whether ferroptosis-related genes (FRGs) can play a role in predicting prognosis in ccRCC needs to be discussed. METHODS: We entered the Cancer Genome Mapping Project (TCGA) database and downloaded the relevant genes and clinical research data of ccRCC patients. Lasso Cox regression was used to construct a multi-gene prognostic model in the TCGA cohort. R language software was used for drawing pictures related to our study. RESULTS: Most of the genes involved in ferroptosis (86.2%) existing differences between the tumor and normal tissues in the TCGA public gene database. In terms of univariate Cox regression analysis, 20 differentially expressed genes (DEGs) were associated with prognosis and survival (P<0.05). A prognostic model of 12 FRGs was constructed, and patients were segmented into two different groups depending on how risky they are. Considering overall survival, the high-risk group is dramatically lower than the low-risk group (P<0.001). In multivariate Cox regression analysis, risk scores and stage turned out be an independent prognostic factor (P<0.001). GO and KEGG analysis and ssGSEA analysis of DEGs revealed that these genes were related to immune-related pathways (P<0.05). CONCLUSION: This study established and identified the changes in FRGs expression and prognostic factors of ccRCC, which can be helpful for prognosis evaluation and clinical treatment of this disease.