Polydatin impairs mitochondria fitness and ameliorates podocyte injury by suppressing Drp1 expression.

Polydatin (PD), a resveratrol glycoside, has been shown to protect renal function in diabetic nephropathy (DN), but the underlying molecular mechanism remains unclear. This study demonstrates that PD stabilize the mitochondrial morphology and attenuate mitochondrial malfunction in both KKAy mice and in hyperglycemia (HG)-induced MPC5 cells. We use Western blot analysis to demonstrate that PD reversed podocyte apoptosis induced by HG via suppressing dynamin-related protein 1 (Drp1). This effect may depend on the ability of PD to inhibit the generation of cellular reactive oxygen species (ROS). In conclusion, we demonstrate that PD may be therapeutically useful in DN, and that, podocyte apoptosis induced by HG can be reversed by PD through suppressing Drp1 expression.

Integrative analyses of biomarkers and pathways for metformin reversing cisplatin resistance in head and neck squamous cell carcinoma cells.

OBJECTIVES: In this study, transcriptome sequencing were performed to elucidate the molecular mechanism by which metformin inhibits head and neck squamous cell carcinoma (HNSCC) cells progression and sensitizes HNSCC cells to chemotherapy. We aimed to propose a novel chemotherapeutic approach with high efficacy and few side effects and provide a new strategy for HNSCC treatment. DESIGN: The effects of metformin on the biological behaviors of HNSCC cells were validated by CCK8 cell proliferation assays, would healing assays and flow cytometric apoptosis assays. The appropriate metformin concentrations for the experimental pretreatment of HNSCC cells were selected based on experimental results, and the treated cells were subjected to transcriptome sequencing. After bioinformatics analysis and intersection with a post-chemotherapy resistance dataset from the GEO database numbered GSE102787, the genes were identified and used to predict potential metformin targets after functional enrichment analysis. RESULTS: Metformin significantly inhibited the proliferation and migration and induced the apoptosis of Cal27 and FaDu cells. A total of 284 genes that are potentially targeted by metformin during HNSCC cell sensitization were identified by bioinformatics, and ten hub genes with high connectivity were selected. In particular, Fen1 overexpression was associated with poor prognosis in HNSCC patients. CONCLUSIONS: Our study demonstrates that Fen1 is overexpressed in HNSCC tissues compared with normal tissues and that Fen1 overexpression is a poor prognostic factor in HNSCC patients. Metformin enhances the ability of cisplatin to inhibit HNSCC progression. Further studies are needed to explore the therapeutic value of Fen1 in HNSCC.