Wogonin upregulates SOCS3 to alleviate the injury in Diabetic Nephropathy by inhibiting TLR4-mediated JAK/STAT/AIM2 signaling pathway.

BACKGROUND: Diabetic nephropathy (DN) is a life-threatening renal disease and needs urgent therapies. Wogonin is renoprotective in DN. This study aimed to explore the mechanism of how wogonin regulated high glucose (HG)-induced renal cell injury. METHODS: Diabetic mice (db/db), control db/m mice, and normal glucose (NG)- or HG-treated human tubule epithelial cells (HK-2) were used to evaluate the levels of suppressor of cytokine signaling 3 (SOCS3), Toll-like receptor 4 (TLR4), inflammation and fibrosis. Lentivirus was used to regulate SOCS3 and TLR4 expressions. After oral gavage of wogonin (10 mg/kg) or vehicle in db/db mice, histological morphologies, blood glucose, urinary protein, serum creatinine values (Scr), blood urea nitrogen (BUN), superoxide dismutase (SOD), glutathione (GSH), and reactive oxygen species (ROS) were assessed. RT-qPCR and Western blot evaluated inflammation and fibrosis-related molecules. RESULTS: HG exposure induced high blood glucose, severe renal injuries, high serumal Src and BUN, low SOD and GSH, and increased ROS. HG downregulated SOCS3 but upregulated TLR4 and JAK/STAT, fibrosis, and inflammasome-related proteins. Wogonin alleviated HG-induced renal injuries by decreasing cytokines, ROS, Src, and MDA and increasing SOD and GSH. Meanwhile, wogonin upregulated SOCS3 and downregulated TLR4 under HG conditions. Wogonin-induced SOCS3 overexpression directly decreased TLR4 levels and attenuated JAK/STAT signaling pathway-related inflammation and fibrosis, but SOCS3 knockdown significantly antagonized the protective effects of wogonin. However, TLR4 knockdown diminished SOCS3 knockdown-induced renal injuries. CONCLUSION: Wogonin attenuates renal inflammation and fibrosis by upregulating SOCS3 to inhibit TLR4 and JAK/STAT pathway.

Time-Dependent Factors Influencing Cardiocerebral Vascular Events in Chronic Hemodialysis Patients: Insights from a Longitudinal Study.

BACKGROUND Cardiocerebral vascular events (CVCs) are significant complications in patients undergoing hemodialysis (HD). Given the increased morbidity and mortality associated with CVCs in this population, understanding the factors influencing CVC occurrence over time is crucial. This study aimed to investigate these time-dependent factors in HD patients. MATERIAL AND METHODS A total of 228 HD patients from 2 dialysis centers, with at least 3 months of treatment between 2017 and 2021, were included. Annual clinical data were collected, and patients were monitored until CVC development. Kaplan-Meier analysis and a time-dependent Cox regression model were used for data analysis. RESULTS The mean age of 228 patients was 55.0±15.0 years, and 64.76% were male. For 5 years of monitoring, the mean follow-up interval was 3.1±1.0 years for patients to develop CVCs. The 1-year, 3-year, and 5-year CVC-free rates were 97.47%, 81.31%, and 70.71%, respectively. Time-dependent Cox regression revealed that C-reactive protein was an independent time-dependent risk factor in HD patients and blood flow rate was an independent time-dependent protective factor. The male subgroup and non-diabetic subgroup had these same results. The following were was the independent time-dependent risk factors: white blood cell count for the female subgroup; blood flow rate for the non-elderly subgroup; and C-reactive protein for the diabetic subgroup. None were risk factors for the elderly subgroup. CONCLUSIONS It took an average of 3.1±1.0 years for patients with HD to develop CVCs. C-reactive protein and blood flow rate emerged as key time-dependent influencing factors for CVCs in this population.