ABSTRACT
Podocytes maintain renal filtration integrity when the glomerular filtration barrier (GFB) is integrated. Impairment or attrition of podocytes, leading to compromised GFB permeability, constitutes the primary etiology of proteinuria and is a hallmark pathological feature of diabetic nephropathy (DN). This study centers on Heterogeneous Nuclear Ribonucleoprotein I (HNRNP I), an RNA-binding protein, delineating its role in facilitating DN-induced renal damage by modulating podocyte health. Comparative analyses in renal biopsy specimens from DN patients and high-glucose-challenged podocyte models in vitro revealed a marked downregulation of HNRNP I expression relative to normal renal tissues and podocytes. In vitro assays demonstrated that high-glucose conditions precipitated a significant reduction in podocyte viability and an escalation in markers indicative of apoptosis. Conversely, HNRNP I overexpression was found to restore podocyte viability and attenuate apoptotic indices. IRAK1, a gene encoding a protein integral to inflammatory signaling, was shown to interact with HNRNP I, which promotes IRAK1 degradation. This interaction culminates in suppressing the PI3K/AKT/mTOR signaling pathway, thereby diminishing podocyte apoptosis and mitigating renal damage in DN. This investigation unveils the mechanistic role of HNRNP I in DN for the first time, potentially informing novel therapeutic strategies for DN renal impairment.
ABSTRACT
BACKGROUND: The effect of synbiotic supplementation on glycemic status in pregnant women remained controversial and this meta-analysis aimed to explore the efficacy of synbiotic supplementation on glycemic status in pregnant women. METHODS: We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases and randomized controlled trials (RCTs) assessing the effect of synbiotic on glycemic status in pregnant women were included. The meta-analysis was performed using the random-effect model. RESULTS: Four RCTs were included in the meta-analysis. Overall, compared with control intervention in pregnant women, synbiotic supplementation was associated with significantly reduced serum insulin (SMD = -0.69; 95%CI = -1.06 to -0.32; p = .0002) and homoeostasis model assessment of insulin resistance (HOMA-IR, SMD = -0.53; 95%CI = -0.87 to -0.18; p = .003), but had no significant effect on fasting plasma glucose (FPG, SMD = -0.16; 95%CI = -0.43 to 0.11; p = .24), quantitative insulin sensitivity check index (QUICKI, SMD = 0.54; 95%CI = -0.10 to 1.18; p = .10) or CRP (SMD = -0.29; 95%CI = -1.23 to 0.64; p = .54). CONCLUSIONS: Synbiotic supplementation was beneficial to glycemic control in pregnant women.
