Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, plays a pivotal role in various physiological and pathological processes. In this review, we summarize the core mechanisms of ferroptosis, emphasizing its intricate connections to lipid metabolism, including fatty acid synthesis, phospholipid remodeling, and oxidation dynamics. We further highlight advancements in detection technologies, such as fluorescence imaging, lipidomics, and in vivo PET imaging, which have deepened our understanding of ferroptotic regulation. Additionally, we discuss the role of ferroptosis in human diseases, where it acts as a double-edged sword, contributing to cancer cell death while also driving ischemia-reperfusion injury and neurodegeneration. Finally, we explore therapeutic strategies aimed at either inducing or inhibiting ferroptosis, including iron chelation, antioxidant modulation, and lipid-targeted interventions. By integrating mechanistic insights, disease relevance, and therapeutic potential, this review provides a comprehensive perspective on ferroptosis as a crucial interface between lipid metabolism and oxidative stress.

The endothelial-to-mesenchymal transition (EMT) of glomerular vascular endothelial cells is considered to be pivotal in diabetic nephropathy (DN). The risk of DN can be decreased by losartan, but the potential molecular mechanism(s) are not fully understood. Extensive data show that the EMT occurs in proximal tubular endothelial cells resulting in an endothelial phenotype switch (fibrotic matrix accumulation), consequently enhancing the development of renal interstitial fibrosis. Here, we found that losartan significantly ameliorated DN-induced renal fibrosis progression via inhibition of the EMT in mice. In vivo experiments suggested that losartan significantly alleviated microalbuminuria and pathologic changes under high-fat diet-induced hyperglycemia. Immunohistochemistry indicated that losartan suppressed the EMT in glomeruli. In addition, losartan decreased oxidative stress damage and inhibited the transforming growth factor (TGF)-β1/Smad pathway. Furthermore, consistent changes were detected in vitro where losartan markedly inhibited the EMT and TGF-β1/Smad pathway induced by high glucose in glomerular endothelial cells. Together, these results suggested that losartan could alleviate the EMT in glomeruli via inhibition of oxidative stress damage and the TGF-β1/Smad signaling pathway under hyperglycemia.

Cantharidin (CTD), a natural terpenoid toxin secreted by blister beetles, acts as a potent inhibitor of protein phosphatase. As the principal active component of Mylabris, a traditional Chinese medicine, CTD has attracted considerable interest due to its dual properties, combining potent anti-tumor activity with significant toxicity. Contemporary pharmacological research demonstrates that CTD inhibits the growth and proliferation of diverse cancer cells lines. It exhibits antibacterial and antiparasitic properties, and demonstrates pesticidal activity in agricultural applications. Despite these benefits, CTD exhibits a prominent double-edged profile, marked by severe toxic effects, including cardiotoxicity, nephrotoxicity, gastrointestinal toxicity, and reproductive toxicity. Our prior research has identified the heart and liver as primary targets of CTD’s acute toxicity, where it induces apoptosis and necrosis of cardiomyocytes and hepatocytes. Recent efforts to mitigate its toxicity while preserving efficacy have focused on the structural modifications of CTD and the development of its derivatives. Additionally, CTD has been demonstrated to enhance anti-tumor efficacy when combined with other drugs, particularly against certain drug-resistant tumors. This review comprehensively evaluates CTD’s pharmacology and toxicology, synthesizes pertinent toxicological data, and explores strategies for toxicity reduction to guide future research.