Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment

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(SUMO)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 exercise and SUMO-related gene signature(ESLRS).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(MDM2),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 MDM2 inhibitor 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 MDM2-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.

Ginkgo biloba active compounds can modulate the development of acute mountain sickness and ischemic stroke as discovered by network pharmacology and molecular docking

Background:A combination of molecular docking,molecular dynamics simulations,and herbal network pharmacology was used to investigate the shared key targets and potential mechanisms underlying the preventive effects of Ginkgo biloba active compounds against acute mountain sickness(AMS)and ischemic stroke(IS).Material and Methods:The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was used to screen the main active compounds of Ginkgo biloba and their corresponding targets.We obtained AMS-related genes by mining several databases and cross-correlated them with key active compounds of Ginkgo biloba to identify relevant action targets for treating AMS.The STRING database was used to construct a protein–protein interaction network of the effect of Ginkgo biloba active compounds on AMS targets.The expression of genes in the network was analyzed in an IS dataset to identify common key targets of Ginkgo biloba active compounds for both AMS and IS prevention.Results:The intersection between the targets of Ginkgo biloba active compounds and AMS-related genes identified 43 overlapping genes.Analysis of the protein–protein interaction network showed that VEGFA,TP53,SERPINE1,and PTGS2 were among the key hub genes.Analysis of the IS dataset identified significant differences in the expression levels of CAT,TP53,CXCL8,NFKBIA,and PTGS2.These genes were used to construct a visual nomogram prediction model for IS prognosis with promising clinical implications.Molecular docking and molecular dynamics simulations indicated that sesamin stably targeted and bound to PTGS2.Conclusions:Active ingredients of Ginkgo biloba,including luteolin,quercetin,and sesamin,have the potential to modulate the development of AMS and IS through targeted interactions with key proteins,including TP53,CXCL8,NFKBIA,PTGS2,and CAT.