Network toxicology and cell experiments reveal the mechanism of DEHP-induced diabetic nephropathy via Wnt signaling pathway.

Di(2-ethylhexyl) phthalate (DEHP), a widely recognized endocrine disruptor, has been linked to the pathogenesis of diabetic nephropathy (DN) through its interference with hormonal and metabolic homeostasis. This study integrates network toxicology with cell-based assays to elucidate the molecular mechanisms of DEHP-induced DN, seeking to identify novel targets for toxicity assessment and therapeutic intervention. Through comprehensive screening across multiple toxicology and disease-related databases, six core genes (CTNNB1, EGFR, TNF, CCND1, BCL2, CASP3) were identified as shared mediators of DEHP exposure and DN.

Polydatin: a potential NAFLD therapeutic drug that regulates mitochondrial autophagy through SIRT3-FOXO3-BNIP3 and PINK1-PRKN mechanisms - a network pharmacology and experimental investigation.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disorder that is linked to metabolic syndrome, mitochondrial dysfunction and impaired autophagy. Polydatin (PD), a natural polyphenol from Polygonum cuspidatum, exhibits various pharmacological effects and protects against NAFLD. The aim of this study was to reveal the molecular mechanisms and therapeutic potential of PD for NAFLD, with a focus on the role of mitochondrial autophagy mediated by sirtuin 3 (SIRT3), fork-head box O3 (FOXO3) and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), and by PTEN-induced putative kinase 1 (PINK1) and parkin (PRKN).