Diabetic Nephropathy (DN) is a serious complication of type I and II diabetes. It develops from the initial microproteinuria to end-stage renal failure. The main initiator for DN is chronic hyperglycemia. Hyperglycemia (HG) can stimulate the resident and non-resident renal cells to produce humoral mediators and cytokines that can lead to functional and phenotypic changes in renal cells and tissues, interference with cell growth, interacting proteins, advanced glycation end products (AGEs), etc., ultimately resulting in glomerular and tubular damage and the onset of kidney disease. Therefore, poor blood glucose control is a particularly important risk factor for the development of DN. In this paper, the types and mechanisms of DN cell damage are classified and summarized by reviewing the related literature concerning the effect of hyperglycemia on the development of DN. At the cellular level, we summarize the mechanisms and effects of renal damage by hyperglycemia. This is expected to provide therapeutic ideas and inspiration for further studies on the treatment of patients with DN.

Fluoride exposure can induce tissue injury and oxidative stress dysregulation, ultimately leading to organismal dysfunction and death, whereas resveratrol (RSV) has been reported to counteract diverse oxidative injuries. Despite its antioxidant potential, the application of RSV is limited by its low bioavailability. Here, using a silkworm model, we established NaF exposure, RSV treatment, and combined RSV+NaF groups to investigate the mechanism by which RSV attenuates fluorosis. Comparative analyses of body weight, histopathological damage, and oxidative stress indices showed that RSV markedly mitigated NaF-induced toxicity. Candidate genes and proteins exhibiting concordant expression changes were identified through integrated RNA-seq and TMT-based quantitative proteomics, and subsequently validated by qPCR and PRM. Among these candidates, the esterase BmeFE4 emerged as a key regulator of the RSV-mediated detoxification response. Spatiotemporal profiling revealed that BmeFE4 was expressed throughout silkworm development, with the highest levels in the midgut. RNAi-mediated knockdown of BmeFE4 significantly altered NaF-related phenotypes and modulated oxidative-stress-related parameters, including superoxide dismutase (SOD) and catalase (CAT) activities, reduced glutathione (GSH) content, and malondialdehyde (MDA) levels, as quantified by ELISA. Collectively, these results indicate that RSV alleviates fluoride toxicity at least in part by upregulating BmeFE4, identifying this esterase as a potential molecular target for developing defluoridation agents.