The role of microRNA-21-5p (miR-21-5p) in sepsis-induced acute kidney injury (AKI) has been seldom discussed. Therefore, the objective of this present study was to investigate the mechanism of endothelial progenitor cells-derived exosomes (EPCs-exos) in sepsis-induced AKI via miR-21-5p/runt-related transcription factor 1 (RUNX1) axis. miR-21-5p was downregulated and RUNX1 was upregulated in the kidney of cecal ligation and puncture (CLP) rats, and miR-21-5p targeted RUNX1. Elevation of miR-21-5p improved renal function and renal tissue pathological damage, attenuated serum inflammatory response, as well as reduced apoptosis and oxidative stress response in renal tissues, and regulated endothelial glycocalyx damage marker proteins syndecan-1 and heparanase-1 in CLP rats. Overexpression of RUNX1 abolished the impacts of elevated miR-21-5p in CLP rats. Also, EPCs-exos upregulated miR-21-5p expression, and functioned similar to elevation of miR-21-5p for CLP rats. Downregulating miR-21-5p partially reversed the effects of EPCs-exos on sepsis-induced AKI. Collectively, our study suggests that EPCs release miR-21-5p-containing exosomes to alleviate sepsis-induced AKI through RUNX1 silencing.

Background: Prostate cancer is the most commonly diagnosed non-cutaneous malignancy in men and is the second-leading cause of cancer-related death. Castration-resistant pr ostate cancer (CRPC) persists despite low testosterone levels. Methods: In this study, we investigated the combined effect of Celastrol and bicaluta mide on prostate cancer cells. We evaluated cytotoxicity, apoptosis, oxidative stress, ferro ptosis and the activation of the immune system in vivo and in vitro . Results: Our findings revealed that the co-administration of Celastrol with bicalutamide enhanced cytotoxicity against prostate cancer cells, promoted cell apoptosis, induced oxi dative stress and ferroptosis. Importantly, it assisted bicalutamide in activating the immune system, triggering immunogenic cell death (ICD), and thereby enhancing immune thera py. This synergy resulted in a stronger anti-CRPC effect, improving the overall therapeutic efficacy. Conclusion: Our study demonstrates the potential of the Celastrol and bicalutamide combination in treating castration-resistant prostate cancer. Further studies are warranted to explore the clinical application of this approach and its potential in improving patient outcomes. Funding information: The author(s) declare that financial support was received for the research and/or publication of this article. This work was supported by Beijing Municipal Natural Science F oundation (grant no. BFHHQS20240003).