Background Sensorineural hearing loss (SNHL) poses a major threat to both physical and mental health; however, there is still a lack of effective drugs to treat the disease. Recently, novel biological therapies, such as mesenchymal stem cells (MSCs) and their products, namely, exosomes, are showing promising therapeutic potential due to their low immunogenicity, few ethical concerns, and easy accessibility. Nevertheless, the precise mechanisms underlying the therapeutic effects of MSC-derived exosomes remain unclear. Results Exosomes derived from MSCs reduced hearing and hair cell loss caused by neomycin-induced damage in models in vivo and in vitro. In addition, MSC-derived exosomes modulated autophagy in hair cells to exert a protective effect. Mechanistically, exogenously administered exosomes were internalized by hair cells and subsequently upregulated endocytic gene expression and endosome formation, ultimately leading to autophagy activation. This increased autophagic activity promoted cell survival, decreased the mitochondrial oxidative stress level and the apoptosis rate in hair cells, and ameliorated neomycin-induced ototoxicity. Conclusions In summary, our findings reveal the otoprotective capacity of exogenous exosome-mediated autophagy activation in hair cells in an endocytosis-dependent manner, suggesting possibilities for deafness treatment.
Death happening due to massive hemorrhage has been involved in military conflicts, traffic accidents, and surgical injuries of various human disasters. Achieving rapid and effective hemostasis to save lives is crucial in urgent massive bleeding situations. Herein, a covalent cross‐linked AG‐PEG glue based on extracellular matrix‐like amino‐gelatin (AG) and PEG derivatives is developed. The AG‐PEG glue gelatinizes fast and exhibits firm and indiscriminate close adhesion with various moist tissues upon being dosed. The formed glue establishes an adhesive and robust barrier to seal the arterial, hepatic, and cardiac hemorrhagic wounds, enabling it to withstand up to 380 mmHg blood pressure in comparison with normal systolic blood pressure of 60–180 mmHg. Remarkably, massive bleeding from a pig cardiac penetrating hole with 6 mm diameter is effectively stopped using the glue within 60 s. Postoperative indexes of the treated pig gradually recover and the cardiac wounds regrow significantly at 14 days. Possessing on‐demand solubility, self‐gelling, and rapid degradability, the AG‐PEG glue may provide a fascinating stop‐bleeding approach for clinical hemostasis and emergency rescue.