Comparative efficacy and safety of SGLT2is and ns-MRAs in patients with diabetic kidney disease: a systematic review and network meta-analysis.

Objectives: To evaluate the efficacy and safety of non-steroid mineralocorticoid receptor antagonists (ns-MRAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) in patients with diabetic kidney disease (DKD). Methods: Systematic literature searches were performed using PubMed, Embase and Web of Science encompassing inception until January 20, 2024. Randomized control trials (RCTs) comparing ns-MRAs and SGLT2is in DKD were selected. The efficacy outcomes of interest included kidney-specific composite outcome, cardiovascular (CV)-specific composite outcome, end-stage kidney disease (ESKD), and overall mortality. We also investigated safety outcomes, including acute kidney injury (AKI) and hyperkalemia. Results: A total of 10 randomized clinical trials with 35,786 patients applying various treatments were included. SGLT2is (SUCRA 99.84%) have potential superiority in kidney protection. SGLT2is (RR 1.41, 95%CI 1.26 to 1.57) and ns-MRAs (RR 1.17, 95% CI 1.08 to 1.27) were associated with significantly lower kidney-specific composite outcome than the placebo. Regarding the reduction in CV-specific composite outcome and ESKD, SGLT2is (SUCRA 91.61%; 91.38%) have potential superiority in playing cardiorenal protection. Concerning the CV-specific composite outcome (RR 1.27, 95%CI 1.09 to 1.43) and ESKD (RR 1.43, 95%CI 1.20 to 1.72), SGLT2is significantly reduced the risks compared to placebo. Regarding the reduction in overall mortality, SGLT2is (SUCRA 83.03%) have potential superiority in postponing mortality. Concerning the overall mortality, SGLT2is have comparable effects (RR 1.27, 95%CI 1.09 to 1.43) with placebo to reduce the risk of overall mortality compared to placebo. For AKI reduction, ns-MRAs (SUCRA 63.58%) have potential superiority. SGLT2is have comparable effects (RR 1.24, 95%CI 1.05 to 1.46) with placebo to reduce the risk of AKI. For hyperkalemia reduction, SGLT2is (SUCRA 93.12%) have potential superiority. SGLT2is have comparable effects (RR 1.24, 95%CI 1.05 to 1.46) with placebo to reduce the risk of AKI. Concerning hyperkalemia reduction, nsMRAs (RR 1.24 95%CI 0.39 to 3.72) and SGLT2is (RR 1.01 95%CI 0.40 to 3.02) did not show significant benefit compared to placebo. Conclusion: Concerning the efficacy and safety outcomes, SGLT2is may be recommended as a treatment regimen for maximizing kidney and cardiovascular protection, with a minimal risk of hyperkalemia in DKD. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023458613.

Ferroptosis in renal fibrosis: a mini-review.

Ferroptosis is a novel form of programmed cell death that is iron-dependent and distinct from autophagy, apoptosis, and necroptosis. It is primarily characterised by a decrease in glutathione peroxidase 4 (GPX4) activity, or by the accumulation of lipid peroxidation and reactive oxygen species (ROS). Renal fibrosis is a common pathological change in the progression of various primary and secondary renal diseases to end-stage renal disease and poses a serious threat to human health with high morbidity and mortality. Multiple pathways contribute to the development of renal fibrosis, with ferroptosis playing a crucial role in renal fibrosis pathogenesis due to its involvement in the production of ROS. Ferroptosis is related to several signalling pathways, including System Xc-/GPX4, abnormal iron metabolism and lipid peroxidation. A number of studies have indicated that ferroptosis is closely involved in the process of renal fibrosis caused by various kidney diseases such as glomerulonephritis, renal ischaemia-reperfusion injury, diabetic nephropathy and renal calculus. Identifying the underlying molecular mechanisms that determine cell death would open up new insights to address a therapeutic strategy to renal fibrosis. The review aimed to browse and summarise the known mechanisms of ferroptosis that may be associated with biological reactions of renal fibrosis.

Serum S100B levels may be associated with cerebral infarction: a meta-analysis.

OBJECTIVE: The aim of this paper is to explore the potential association of serum human soluble protein-100B protein (S100B) levels with the diagnosis and prognosis of cerebral infarction (CI). METHODS: Potential relevant studies were searched for in PubMed, Springerlink, Wiley, EBSCO, Ovid, Web of Science, Wanfang databases, China National Knowledge Infrastructure (CNKI) databases and VIP databases. Two investigators extracted data and assessed studies independently. Statistical analyses were carried out with the version 12.0 STATA statistical software. RESULTS: A total of 10 case-control studies that assessed the correlation of S100B serum level with CI, including 1211 subjects (patients=773, healthy controls=438) were included. The results showed that S100B serum levels in CI victims were significantly higher compared with those of the control group. According to the subgroup analysis by ethnicity, S100B serum level in CI victims was statistically significant in Asians and the control group, but no statistical significance was found in Caucasians. An additional subgroup analysis was carried out based on sample size, revealing that the S100B serum levels in CI victims in small samples were of statistical significance; however, no statistical significance was discovered in large samples. CONCLUSIONS: Elevator S100B serum levels might be negatively correlated with CI, suggesting that higher serum levels of S100B could lead to more serious condition and worse prognoses for CI patients. Therefore, S100B serum levels could be regarded as a biomarker for CI, and furthermore, S100B could aide in the diagnosis and prognosis of CI.

Control of self-assembled 2D nanostructures by methylation of guanine.

Methylation of DNA nucleobases is an important control mechanism in biology applied, for example, in the regulation of gene expression. The effect of methylation on the intermolecular interactions between guanine molecules is studied through an interplay between scanning tunneling microscopy (STM) and density functional theory with empirical dispersion correction (DFT-D). The present STM and DFT-D results show that methylation of guanine can have subtle effects on the hydrogen-bond strength with a strong dependence on the position of methylation. It is demonstrated that the methylation of DNA nucleobases is a precise means to tune intermolecular interactions and consequently enables very specific recognition of DNA methylation by enzymes. This scheme is used to generate four different types of artificial 2D nanostructures from methylated guanine. For instance, a 2D guanine windmill motif that is stabilized by cooperative hydrogen bonding is revealed. It forms by self-assembly on a graphite surface under ambient conditions at the liquid-solid interface when the hydrogen-bonding donor at the N1 site of guanine is blocked by a methyl group.

[Effects of shenshuning recipe on expression of hepatocyte growth factor in rats with glomerulosclerosis].

OBJECTIVE: To investigate the effects of Shenshuning Recipe (SSNR) on gene expression of hepatocyte growth factor (HGF) in renal tissues in rats with glomerulosclerosis. METHODS: Glomerulosclerosis was induced in 42 rats by unilateral nephrectomy and intravenous injection of doxorubicin. Then these 42 rats were randomly divided into three groups: untreated group, SSNR-treated group and benazepril-treated group. Another eight rats were included into sham-operation group. The rats in the SSNR-treated group and the benazepril-treated group were fed SSNR or benazepril respectively for 8 weeks. The levels of 24 h urine protein (Upr), serum creatinine (Cr) and blood urea nitrogen (BUN) of rats in each group were examined. The renal morphological changes were observed under microscope, and the diameter of glomerular capillary, mesangial matrix and glomerulosclerosis index were analyzed by image analysis software. Reverse transcription-polymerase chain reaction (RT-PCR) method was used to detect the gene expression of HGF in the renal tissues. RESULTS: The levels of 24 h Upr, serum Cr and BUN in the untreated group were remarkably increased than those in the sham-operation group (P<0.01). The pathological morphological changes in the untreated group showed that the glomerulosclerosis was diffused around the renal tissue and the capillaries were shrunk. The expression level of mesangial matrix was up-regulated and the glomerulosclerosis index was 3.32+/-0.35. The expression level of HGF mRNA in the untreated group was obviously lower than that in the sham-operation group (P<0.05). The levels of 24 h Upr, serum Cr and BUN in the SSNR-treated group and the benazepril-treated group were remarkably decreased as compared with those in the untreated group, while the expression levels of HGF mRNA were both obviously higher than that in the untreated group (P<0.01). The pathological morphological changes in the SSNR-treated group and the benazepril-treated group were both alleviated. There was no significant difference in therapeutic effect between the SSNR-treated group and the benazepril-treated group. CONCLUSION: Shenshuning Recipe can up-regulate the expression of HGF mRNA, decrease the mesangial matrix, and improve the renal function, so that it may retard the development of glomerulosclerosis.