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关键词： cardioprotection   dapagliflozin   doxorubicin   SIRT1/SIRT3   ferroptosis   mitochondrial dysfunction  

摘要： Cardiac dysfunction can be aggravated by chemotherapeutic agents, including doxorubicin, through mechanisms involving mitochondrial dysfunction, elevated oxidative stress, suppression of sirtuin (SIRT1/SIRT3) signaling, and activation of apoptotic and ferroptotic pathways. Dapagliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, has been demonstrated to possess cardioprotective effects; however, the interplay between sirtuin signaling and ferroptosis in dapagliflozin-mediated cardioprotection under doxorubicin-induced stress remains unclear. In the present study, dapagliflozin restored cellular function in H9c2 cardiomyoblasts exposed to doxorubicin by reducing apoptosis, oxidative stress, and lipid peroxidation, while preserving mitochondrial respiration and glycolytic function. Dapagliflozin reversed doxorubicin-induced downregulation of SIRT1, SIRT3, GPX4, BCL2, OPA1, and PGC1α, and mitigated the upregulation of ACSL4, BAX, and DNM1 at both transcriptional and translational levels. The cardioprotective efficacy of dapagliflozin under cellular stress depends critically on SIRT1/SIRT3 signaling and ferroptosis regulation, as pharmacological inhibition of these sirtuins abolished its protective potentials; conversely, these effects were enhanced by ferroptosis suppression and attenuated by its induction. Furthermore, dapagliflozin-mediated inhibition of ferroptosis downregulated SIRT1/SIRT3 expression, suggesting a potential feedback mechanism under chemotherapeutic stress. Notably, sirtuin inhibition compromised these protective responses despite ferroptosis blockade, highlighting SIRT1/SIRT3 as upstream regulators of dapagliflozin-mediated cardioprotection and underscoring the necessity of sirtuin activity for ferroptosis suppression. Collectively, these findings reveal that dapagliflozin mitigates doxorubicin-induced cardiotoxicity via the coordinated regulation of SIRT1/SIRT3 signaling and ferroptosis pathways, involving key mediators of apop

关键词： Esophageal squamous cell carcinoma   anti-PD-1 antibody   PD-L1 expression   metastatic   recurrent   locally advanced  

摘要： IntroductionAnti-PD-1 antibodies in pharmacotherapy for esophageal cancer have caused a paradigm shift in the treatment strategy. New evidence is being generated not only for metastatic or recurrent cases, but also in the perioperative setting, and the role of anti-PD-1 antibodies in the treatment of esophageal cancer will continue to *** coveredThis review summarizes the clinical role of approved anti-PD-1 antibodies, including nivolumab and pembrolizumab, and discusses additional agents supported by phase 3 evidence. We emphasize current standards of care across metastatic and perioperative settings while briefly addressing emerging strategies under clinical *** opinionAnti-PD-1 antibodies containing therapies have become central to ESCC management, improving survival in both metastatic and perioperative settings. Regional phase 3 trials have expanded therapeutic options, although differences in regulatory approval influence global accessibility. Despite these advances, optimal patient selection remains challenging, and predictive biomarkers are urgently needed. Future progress will depend on biomarker development, treatment sequencing, and integration of emerging strategies supported by robust clinical evidence.