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

Neural Regeneration Research 2025年第4期20卷 1135-1152页

作者： Yisheng Chen Zhongcheng Fan Zhiwen Luo Xueran Kang Renwen Wan Fangqi Li Weiwei Lin Zhihua Han beijie qi Jinrong Lin Yaying Sun Jiebin Huang Yuzhen Xu Shiyi Chen Department of Sport Medicine Huashan HospitalFudan UniversityShanghaiChina Department of Orthopedic Surgery Hainan Province Clinical Medical CenterHaikou Affiliated Hospital of Central South University Xiangya School of MedicineHaikouHainan ProvinceChina Department of Basic Medicine Shanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Neurosurgery Second Affiliated Hospital of Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina Department of Orthopedics Shanghai General HospitalSchool of Medicine Shanghai Jiao Tong UniversityShanghaiChina Department of Infectious Diseases Children’s Hospital of Fudan UniversityNational Children’s Medical CenterShanghaiChina Department of Rehabilitation The Second Affiliated Hospital of Shandong First Medical UniversityTaianShandong ProvinceChina

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.

关键词： exercise and SUMO-related gene signatures(ESLRS) glioblastoma management low-grade glioma natural bioactives neural regeneration physical exercise

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Human bone marrow mesenchymal stem cell-derived extracellular vesicles inhibit shoulder stiffness via let-7a/Tgfbr1 axis

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Bioactive Materials 2022年第11期7卷 344-359页

作者： Zhiwen Luo Yaying Sun beijie qi Jinrong Lin Yisheng Chen Yuzhen Xu Jiwu Chen Department of Sports Medicine Shanghai General HospitalShanghai Jiao Tong UniversitySchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Sports Medicine Huashan HospitalFudan UniversityShanghaiChina Department of Rehabilitation The Second Affiliated Hospital of Shandong First Medical UniversityShandong ProvinceChina

Shoulder stiffness(SS)is a common shoulder disease characterized by increasing pain and limited range of motion.SS is considered to be an inflammatory and fibrotic disorder pathologically.However,there is no consensus on the most effective conservative treatment for fibrosis.Given that human Bone Marrow Mesen-chymal Stem Cell-derived extracellular vesicles(BMSC-EVs)displayed promising therapeutic effects for various tissues,we investigated the therapeutic effect of BMSC-EVs on fibrosis in a mice immobilization model and two cell models.By conducting a series of experiments,we found that BMSC-EVs can significantly inhibit the fibrogenic process both in vitro and in vivo.In detail,BMSC-EVs suppressed the aberrant proliferation,high collagen production capacity,and activation of fibrotic pathways in TGF-β-stimulated fibroblasts in vitro.Besides,in vivo,BMSC-EVs reduced cell infiltration,reduced fibrotic tissue in the shoulder capsule,and improved shoulder mobility.In addition,via exosomal small RNA sequencing and qPCR analysis,let-7a-5p was verified to be the highest expressed miRNA with predicted antifibrotic capability in BMSC-EVs.The antifibrotic capacity of BMSC-EVs was significantly impaired after the knockdown of let-7a-5p.Moreover,we discovered that the mRNA of TGFBR1(the membrane receptor of transforming growth factorβ)was the target of let-7a-5p.Together,these findings elucidated the antifibrotic role of BMSC-EVs in shoulder capsular fibrosis.This study clarifies a new approach using stem cell-derived EVs therapy as an alternative to cell therapy,which may clinically benefit patients with SS in the future.

关键词： Shoulder stiffness Adhesive capsulitis Extracellular vesicles Human bone marrow mesenchymal stem cell MicroRNA Fibrosis

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2021年广东省广州市一株埃可病毒11型菌株的分离与鉴定

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疾病监测 2024年第5期39卷 655-660页

作者：李贝杰陈澜范前进刘文宽孙晖郑雅匀罗雪莲山西医科大学公共卫生学院山西太原030001 中国疾病预防控制中心传染病预防控制所北京102206 南开大学医学院天津300071 呼吸疾病全国重点实验室国家呼吸系统疾病临床医学研究中心广州医科大学附属第一医院广州呼吸健康研究院广东广州510210

目的探索疑似埃可病毒病原体感染标本的分离鉴定,了解埃可病毒11型(ECHO 11)生长特性及进化特征。方法将2021年广东省广州市发热、急性扁桃体炎患儿的咽拭子标本接种人横纹肌肉瘤细胞(RD)进行病毒分离培养通过巢式反转录聚合酶链反应及... 详细信息

目的探索疑似埃可病毒病原体感染标本的分离鉴定,了解埃可病毒11型(ECHO 11)生长特性及进化特征。方法将2021年广东省广州市发热、急性扁桃体炎患儿的咽拭子标本接种人横纹肌肉瘤细胞(RD)进行病毒分离培养通过巢式反转录聚合酶链反应及一步法聚合酶链反应等方法对疑似埃可病毒病原体进行鉴定;扩增分离株VP1基因全长序列,选择全球有代表性流行株,绘制进化树,确定分离株的基因型并研究分离株在细胞中的生长动力学。结果从患者咽拭子标本中分离出ECHO 11毒株,命名为qi-2023。分离株在RD细胞中能有效增殖,病毒滴度随着复制时间的增加而上升,3~12 h之间病毒增殖最快。进化树结果表明该分离株与D型代表株聚类在一起,VP1基因核苷酸相似性为84.42%~99.08%。且与D5亚型同源性最高,VP1基因核苷酸相似性99.08%。结论从疑似肠道病毒感染患者的咽拭子中成功分离出一株ECHO 11,为D5亚型。这些研究将为ECHO 11感染防控提供实验室数据参考。

关键词：肠道病毒埃可病毒11型分离鉴定 VP1基因

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探究附子与白附子治疗痹症网络机制的差异

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中药与临床 2021年第3期12卷 65-68页

作者：杨杰彭启伦郭步伐王米渠毕节医学高等专科学校基础医学系贵州毕节551700 成都中医药大学基础医学院四川成都610075

目的:基于网络药理学策略探讨附子与白附子治疗痹症药效差异的原因。方法:应用中医药系统生物学数据和分析平台获取附子和白附子的化合物。以口服生物利用度(OB)≥30%和类药性(DL)≥0.18来筛选活性成分,并预测相应靶标。以类风湿性关节... 详细信息

目的:基于网络药理学策略探讨附子与白附子治疗痹症药效差异的原因。方法:应用中医药系统生物学数据和分析平台获取附子和白附子的化合物。以口服生物利用度(OB)≥30%和类药性(DL)≥0.18来筛选活性成分,并预测相应靶标。以类风湿性关节炎为关键词,经人类基因数据库搜索、收集相应疾病靶标,随后产生附子、白附子抗类风湿性关节炎靶标。采用蛋白质相互作用数据库(String datebase)构建疾病靶标网络并分析其关键靶标。最后对附子、白附子抗类风湿性关节炎靶标进行KEGG通络富集分析。结果:附子与白附子的共同活性成分为谷甾醇。附子抗类风湿性关节炎的主要节点在于调控PTGS2和PTGS1。白附子抗类风湿性关节炎的主要节点在于调控BCL2、BAX、CASP9、JUN、CASP3、CASP8等凋亡相关蛋白。结论:附子与白附子治疗痹症网络机制的差异可能与附子抑制前列腺素代谢,白附子抑制前列腺素代谢和细胞凋亡相关信号通路有关。

关键词：附子白附子类风湿性关节炎网络机制 KEGG通路富集分析蛋白质相互作用数据库

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