1Department of Sport Medicine, Huashan Hospital, Fudan University；2Department of Orthopedic Surgery, Hainan Province Clinical Medical Center, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine；3Department of Basic Medicine,Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University；4Department of Neurosurgery, Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University；5Department of Orthopedics, Shanghai General Hospital,School of Medicine Shanghai Jiao Tong University；6Department of Infectious Diseases, Children’s Hospital of Fudan University, National Children’s Medical Center；7Department of Rehabilitation, The Second Affiliated Hospital of Shandong First Medical University
刊名
Neural Regeneration Research
年份
2025
卷号
第20卷
期号
第4期
页码
1135-1152
ISSN
1673-5374
分类号
R739.41
摘要
Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiquitin-like modifier protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of SUMOylation.We used machine learning to create the exe rcise and SUMO-related gene signature.This signature shows how physical activity might he...更多
Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiquitin-like modifier protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of SUMOylation.We used machine learning to create the exe rcise and SUMO-related gene signature.This signature shows how physical activity might help improve the outlook for low-grade glioma and other cancers.We demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2,a component of the ESLRS,can be targeted by nutlin-3.This underscores the intricate relationship between natural compounds such as nutlin-3 and immune regulation.Using comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma progression.We also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2inhibitor through molecular docking and dynamic simulation.Nutlin-3a inhibited glioma cell proliferation and activated the p53 pathway.Its efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or exercise.Experiments using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway regulation.Notably,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from M DM 2-overexpressing cells.These results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma management.Our research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.收起
