RESUMEN
Objective: This study aimed to investigate the regulatory role of astrocyte-derived exosomes and their microRNAs (miRNAs) in modulating neuronal pyroptosis during cerebral ischemia. Methods: Astrocyte-derived exosomes were studied for treating cerebral ischemia in both in vitro and in vivo models. The effects of astrocyte-derived exosomes on neuroinflammation were investigated by analyzing exosome uptake, nerve damage, and pyroptosis protein expression. High throughput sequencing was used to identify astrocyte-derived exosomal miRNAs linked to pyroptosis, followed by validation via qRTâPCR. The relationship between these miRNAs and NLRP3 was studied using a dual luciferase reporter assay. This study used miR-378a-5p overexpression and knockdown to manipulate OGD injury in nerve cells. The impact of astrocyte-derived exosomal miR-378a-5p on the regulation of cerebral ischemic neuroinflammation was assessed through analysis of nerve injury and pyroptosis protein expression. Results: Our findings demonstrated that astrocyte-derived exosomes were internalized by neurons both in vitro and in vivo. Additionally, Astrocyte-derived exosomes displayed a neuroprotective effect against OGD-induced neuronal injury and brain injury in the ischemic cortical region of middle cerebral artery occlusion (MCAO) rats while also reducing pyroptosis. Further investigations revealed the involvement of astrocyte-derived exosomal miR-378a-5p in regulating pyroptosis by inhibiting NLRP3. The overexpression of miR-378a-5p mitigated neuronal damage, whereas the knockdown of miR-378a-5p increased NLRP3 expression and exacerbated pyroptosis, thus reversing this neuroprotective effect. Conclusion: Astrocyte-derived exosomal miR-378a-5p has a neuroprotective effect on cerebral ischemia by suppressing neuroinflammation associated with NLRP3-mediated pyroptosis.Further research is required to comprehensively elucidate the signaling pathways by which astrocyte-derived exosomal miR-378a-5p modulates neuronal pyroptosis.
Asunto(s)
Astrocitos , Isquemia Encefálica , Exosomas , MicroARNs , Proteína con Dominio Pirina 3 de la Familia NLR , Enfermedades Neuroinflamatorias , Piroptosis , Animales , Piroptosis/genética , MicroARNs/genética , Exosomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Astrocitos/metabolismo , Ratas , Masculino , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/etiología , Isquemia Encefálica/metabolismo , Isquemia Encefálica/genética , Ratas Sprague-Dawley , Modelos Animales de Enfermedad , Neuronas/metabolismo , Neuronas/patología , Infarto de la Arteria Cerebral Media/metabolismoRESUMEN
Meaning in life refers to an individual's capacity to understand and grasp the meaning of their own existence, as well as being aware of the goals, tasks, or missions in their personal life. Previous studies have found that college students lack meaning in life, but physical exercise can enhance it. In this study, 3,196 college students completed self-report questionnaires to assess self-efficacy, life satisfaction, physical exercise, and meaning in life. The results revealed that the physical exercise not only influenced an individual's perceived meaning in life directly, but also influenced it through self-efficacy. Furthermore, it confirmed the chain mediating role of self-efficacy and life satisfaction, whereby engaging in physical exercise can ultimately impact meaning in life through self-efficacy and life satisfaction. This discovery can help educators create interventions to improve college students' physical exercise engagement and overall life satisfaction.
