miRNA-193a-mediated WT1 suppression triggers podocyte injury through activation of the EZH2/ß-catenin/NLRP3 pathway in children with diabetic nephropathy.

Diabetic nephropathy (DN), an eminent etiology of renal disease in patients with diabetes, involves intricate molecular mechanisms. Recent investigations have elucidated microRNA-193a (miR-193a) as a pivotal modulator in DN, although its precise function in podocyte impairment remains obscure. The present study investigated the role of miR-193a in podocyte injury via the WT1/EZH2/ß-catenin/NLRP3 pathway. This study employed a comprehensive experimental approach involving both in vitro and in vivo analyses. We utilized human podocyte cell lines and renal biopsy samples from pediatric patients with DN. The miR-193a expression levels in podocytes and glomeruli were quantified via qRT‒PCR. Western blotting and immunofluorescence were used to assess the expression of WT1, EZH2, ß-catenin, and NLRP3 inflammasome components. Additionally, the study used luciferase reporter assays to confirm the interaction between miR-193a and WT1. The impact of miR-193a manipulation was observed by overexpressing WT1 and inhibiting miR-193a in podocytes, followed by analysis of downstream pathway activation and inflammatory markers. We found upregulated miR-193a in podocytes and glomeruli, which directly targeted and suppressed WT1, a crucial podocyte transcription factor. WT1 suppression, in turn, activated the EZH2/ß-catenin/NLRP3 pathway, leading to inflammasome assembly and proinflammatory cytokine production. Overexpression of WT1 or inhibition of miR-193a attenuated these effects, protecting podocytes from injury. This study identified a novel mechanism by which miR-193a-mediated WT1 suppression triggers podocyte injury in DN via the EZH2/ß-catenin/NLRP3 pathway. Targeting this pathway or inhibiting miR-193a may be potential therapeutic strategies for DN.

MiR-33a Overexpression Exacerbates Diabetic Nephropathy Through Sirt6-dependent Notch Signaling.

INTRODUCTION: Diabetic nephropathy (DN) belongs to the major cause of end-stage kidney disease. We probed the functions of a microRNA miR-33a in inducing podocytes injury during childhood  DN (CDN). METHODS: Kidney samples were collected from 20 children with DN. Matrix deposition and glomerular basement membranes thickness were examined by periodic acid-Schiff staining. Immunofluorescence staining was performed to assess kidney function-related proteins. MicroRNA (MiR)-33a mimic together with miR-33a inhibitor was transfected into podocytes for determining the roles of miR-33a. Glomerular podocyte apoptosis was determined by terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) staining along with flow cytometry. RESULTS: Down-regulation of Nephrin and Podocin and increased podocyte apoptosis rate were observed in the glomerulus of CDN as well as podocytes treated with high glucose. MiR-33a was up regulated in the glomeruli and glucose-treated podocytes. Injury in podocytes was aggravated with miR-33a elevation but alleviated with miR-33a inhibition. Moreover, the expression of Sirtuin 6 (Sirt6) was decreased while the levels of notch receptor 1 (Notch1) and notch receptor 4 (Notch4) were elevated in the glomerulus and glucose-treated podocytes. Decreased level of Sirt6 upon glucose treatment was abrogated by miR-33a inhibition, and the podocytes injury induced by glucose exposure was relieved by Sirt6 via Notch signaling. CONCLUSION: These findings indicated that miR-33a promoted podocyte injury via targeting Sirt6-dependent Notch signaling in CDN, which might provide a novel sight for CDN treatment. DOI: 10.52547/ijkd.7904.

Risk Factors of Convulsions in Children With Rotavirus Gastroenteritis and Construction of a Nomogram Prediction Model.

OBJECTIVE: This study aims to investigate and analyze the risk factors of convulsions in children with rotavirus gastroenteritis and to construct a nomogram prediction model. METHODS: A retrospective analysis was performed on 940 cases of pediatric patients with rotavirus gastroenteritis treated in our hospital from December 2017 to December 2022. Based on whether convulsions occurred during hospitalization, patients were divided into the convulsion group (n = 135) and the convulsion-free group (n = 805). Clinical information of patients in both groups was collected, logistic regression analysis was carried out to analyze the convulsion risk factors pertaining to children with rotavirus gastroenteritis, and a nomogram prediction model was constructed. RESULTS: The univariate analysis revealed that fever, frequency of diarrhea, white blood cell count, blood calcium level, blood glucose level, CO 2 CP, creatine kinase myocardial band (CK-MB), and blood pH value were all factors that display statistically significant differences at the level of P = 0.05. Then, logistic regression analysis was carried out, taking the occurrence of such convulsions as the dependent variable and the aforementioned factors as independent variables. The results show that fever, frequency of diarrhea, blood calcium, CO 2 CP, and CK-MB were the independent risk factors ( P < 0.05), whereas the area under the receiver operating characteristic curve (area under the curve) of the constructed nomogram prediction model based on these factors was 0.842 (95% confidence interval, 0.821-0.914). CONCLUSIONS: Frequency of diarrhea, blood calcium, CO 2 CP, and CK-MB are independent risk factors for the occurrence of convulsions in children with rotavirus gastroenteritis. The nomogram prediction model constructed based on these risk factors provides guidance and value in effectively preventing and controlling convulsions in children with rotavirus gastroenteritis.

[Clinical effect of recombinant human interferon α1b adjuvant therapy in infectious mononucleosis: a prospective randomized controlled trial].

OBJECTIVE: To study the clinical effect of recombinant human interferon α1b assisting acyclovir on immune function, inflammatory factors, and myocardial zymogram in children with infectious mononucleosis (IM). METHODS: A total of 182 children with IM who were admitted to the hospital from January to December, 2018, were divided into an observation group with 91 children and a control group with 91 children using a random number table. The children in the control group were treated with intravenous drip of acyclovir, and those in the observation group were treated with inhalation of recombinant human interferon α1b in addition to the treatment in the control group. The two groups were compared in terms of clinical symptoms, immune function, inflammatory response, myocardial zymogram, and adverse reactions. RESULTS: Compared with the control group, the observation group had significantly shorter time to body temperature recovery and disappearance of isthmopyra, cervical lymph node enlargement, hepatomegaly, and splenomegaly (P<0.05). After treatment, both groups had significant increases in CD4+, CD4+/CD8+, and CD19+, and the observation group had significantly higher levels of these markers than the control group (P<0.05). After treatment, both groups had significant reductions in the levels of CD8+, tumor necrosis factor-α, interlukin-6, creatine kinase, and creatine kinase-MB, and the treatment group had significantly lower levels of these markers than the control group (P<0.05). There was no significant difference in the incidence rate of adverse reactions between the two groups after treatment (P>0.05). CONCLUSIONS: For children with IM, recombinant human interferon α1b assisting acyclovir can effectively improve immune function, inhibit inflammatory reaction, reduce myocardial injury, and thus alleviate clinical symptoms.