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MAGED4B Promotes Glioma Progression via Inactivation of the TNF-α-induced Apoptotic Pathway by Down-regulating TRIM27 Expression

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Neuroscience Bulletin 2023年第2期39卷 273-291页

作者： Can Liu Jun Liu Juntang Shao Cheng Huang Xingliang Dai Yujun Shen Weishu Hou Yuxian Shen Yongqiang Yu Department of Radiology The First Afliated Hospital of Anhui Medical UniversityHefei 230022China biopharmaceutical Research Institute Anhui Medical UniversityHefei 230032China School of Basic Medical Sciences Anhui Medical UniversityHefei 230032China Department of Pathology The First Afliated Hospital of Anhui Medical UniversityHefei 230022China Department of Neurosurgery The First Afliated Hospital of Anhui Medical UniversityHefei 230022China

MAGED4B belongs to the melanoma-associated antigen family;originally found in melanoma,it is expressed in various types of cancer,and is especially enriched in ***,the functional role and molecular mechanisms of MAGED4B in glioma are still *** this study,we found that the MAGED4B level was higher in glioma tissue than that in non-cancer tissue,and the level was positively co.related with glioma grade,tumor diameter,Ki-67 level,and patient *** patients with higher levels had a worse prognosis than those with lower MAGED4B *** glioma cells,MAGED4B overexpression promoted proliferation,invasion,and migration,as well as decreasing apoptosis and the chemosensitivity to cisplatin and *** the co.trary,MAGED4B knockdown in glioma cells inhibited proliferation,invasion,and migration,as well as increasing apoptosis and the chemosensitivity to cisplatin and ***4B knockdown also inhibited the growth of gliomas implanted into the rat *** interaction between MAGED4B and tripartite motif-co.taining 27(TRIM27)in glioma cells was detected by co.immunoprecipitation assay,which showed that MAGED4B was co.localized with *** addition,MAGED4B overexpression down-regulated the TRIM27 protein level,and this was blocked by carbobenzoxyl-L-leucyl-L-leucyl-L-leucine(MG132),an inhibitor of the *** the co.trary,MAGED4B knockdown up-regulated the TRIM27 ***,MAGED4B overexpression increased TRIM27 ubiquitination in the presence of ***,MAGED4B down-regulated the protein levels of genes downstream of ubiquitin-specific protease 7(USP7)involved in the tumor necrosis factor-alpha(TNF-α)-induced apoptotic *** findings indicate that MAGED4B promotes glioma growth via a TRIM27/USP7/receptor-interacting serine/threonine-protein kinase 1(RIP1)-dependent TNF-α-induced apoptotic pathway,which suggests that MAGED4B is a potential target for glioma diagnosis and treatment.

关键词： Glioma MAGE family member D4B Tripartite motif-co.taining Apoptosis

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Antibody-dependent cellular cytotoxicity response to SARS-co.-2 in co.ID-19 patients

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Signal Transduction and Targeted Therapy 2021年第10期6卷 3132-3141页

作者： Yuanling Yu Meiyu Wang Xiaoai Zhang Shufen Li Qingbin Lu Haolong Zeng Hongyan Hou Hao Li Mengyi Zhang Fei Jiang Jiajing Wu Ruxia Ding Zehua Zhou Min Liu Weixue Si Tao Zhu Hangwen Li Jie Ma Yuanyuan Gu Guangbiao She Xiaokun Li Yulan Zhang Ke Peng Weijin Huang Wei Liu Youchun Wang Division of HIV/AIDS and Sex-transmitted Virus Vaccines Institute for Biological Product ControlNational Institutes for Food and Drug Control(NIFDC)BeijingChina Graduate School of Peking Union Medical co.lege Chinese Academy of Medical SciencesPeking Union Medical CollegeBeijingChina State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyBeijingChina State Key Laboratory of Virology Wuhan Institute of VirologyChinese Academy of SciencesWuhanHubeiChina Department of Laboratorial Science and Technology School of Public HealthPeking UniversityBeijingChina Department of Laboratory Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Sinovac Biotech co. LtdBeijingChina Cansino Biotech Inco.poration TianjinChina Stemirna Therapeutics LtdShanghaiChina anhui zhifeilongcom biopharmaceutical co. LtdHefeiChina University of Chinese Academy of Sciences BeijingChina

Antibody-dependent cellular cytotoxicity(ADCC)responses to viral infection are a form of antibody regulated immune responses mediated through the Fc *** severe acute respiratory syndrome co.onavirus 2(SARS-co.-2)triggered ADCC responses co.tributes to co.ID-19 disease development is currently not well *** understand the potential co.relation between ADCC responses and co.ID-19 disease development,we analyzed the ADCC activity and neutralizing antibody response in 255 individuals ranging from asymptomatic to fatal infections over 1 year post *** was elicited by 10 days post-infection,peaked by 11-20 days,and remained detectable until 400 days *** general,patients with severe disease had higher ADCC ***,patients who had severe disease and reco.ered had higher ADCC activities than patients who had severe disease and ***,ADCC activities were mediated by a diversity of epitopes in SARS-co.-2-infected mice and induced to co.parable levels against SARS-co.-2 variants of co.cern(VOCs)(B.1.1.7,B.1.351,and P.1)as that against the D614G mutant in human patients and vaccinated *** study indicates anti-SARS-co.-2 ADCC as a major trait of co.ID-19 patients with various co.ditions,which can be applied to estimate the extra-neutralization level against co.ID-19,especially lethal co.ID-19.

关键词： patients ADCC Antibody

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Ferulic acid reduces inflammatory response induced by radiation through Sirt1-NLRP3 pathway

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Acupuncture and Herbal Medicine 2024年第3期4卷 367-374页

作者： Yao Nie Mingyue Huang Tingyu Yang Yu Mei Huiting Zhang Xue Wei Yue Gao Zengchun Ma Beijing Institute of Radiation Medicine BeijingChina anhui Zhifei Longco. biopharmaceutical co. Ltd.HefeiChina Tianjin University of Traditional Chinese Medicine TianjinChina School of Traditional Chinese Medicine Guangdong Pharmaceutical UniversityGuangzhouChina

Objective:A model of inflammatory damage was induced by radiation to investigate whether ferulic acid(FA)can reduce the inflammatory response through the Sirt1-NLRP3 inflammatory *** will help disco.er radiation-protective drugs and elucidate the molecular mechanisms related to radiation-induced inflammatory ***:A mouse model of radiation-induced immunoinflammatory injury was established to verify the anti-inflammatory effects of FA in vivo.C57BL/6J mice were randomly divided into six groups,and 5 Gy whole-body irradiation was used for *** were administered a gastric solvent,amifostine,or 25,50,or 100 mg/kg FA daily for 12 days,co.secutively,before *** serum of mice was co.lected 24 hour after irradiation to observe the co.tent of inflammatory factors interleukin(IL)-1β,IL-18,IL-6,and tumor necrosis factor(TNF)-α.The spleen and thymus tissues of mice were weighed and the organ index was calculated for pathological testing and immunofluorescence ***:FA reduced the radiation-induced decrease in the spleen and thymus *** significantly reduced the secretion of inflammatory factors in the serum and reversed the radiation-induced reduction in lymphocytes in the spleen and thymus of *** activated Sirt1 and inhibited the expression of the NLRP3 inflammasome to alleviate the inflammatory ***:FA reduced radiation-induced inflammation in animals,possibly by activating Sirt1 and reducing nucleotide oligomerization domain(NOD)-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome expression,thereby reducing the secretion of inflammatory factors.

关键词： Ferulic acid NLRP3 inflammasome Radiation inflammation Sirt1

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Allosteric inhibition reveals SHP2-mediated tumor immunosuppression in co.on cancer by single-cell transcriptomics

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Acta Pharmaceutica Sinica B 2022年第1期12卷 149-166页

作者： Jian Gao Zhigui Wu Mingxia Zhao Rui Zhang Manru Li Dongdong Sun Haibo Cheng Xianjia Qi Yuxian Shen Qiang Xu Hongqi Chen Dijun Chen Yang Sun State Key Laboratory of Pharmaceutical Biotechnology Chemistry and Biomedicine Innovation Center(Chem BIC)School of Life SciencesNanjing UniversityNanjin 210023China biopharmaceutical Research Institute School of Basic Medical SciencesAnhui Medical UniversityHefei 230032China Department of co.orectal Surgery Cancer Hospital of China Medical UniversityLiaoning Cancer Hospital&InstituteShenyang 110042China The First Clinical co.lege of Nanjing University of Chinese Medicine Nanjing 210023China Shanghai Xu Ran Biotechnology co. Ltd.Shanghai 201109China Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical UniversityXuzhou 221004China Department of General Surgery Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai 200233China

co.orectal cancer(CRC), a malignant tumor worldwide co.sists of microsatellite instability(MSI) and stable(MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing wasperformed to explore the role of SHP2 in all cell types of tumor microenvironment(TME) from murine MC38 xenografts. Intratumoral cells were found to be functionally heterogeneous and responded significantly to SHP099, a SHP2 allosteric inhibitor. The malignant evolution of tumor cells was remarkably arrested by SHP099. Mechanistically, STING-TBK1-IRF3-mediated type I interferon signaling was highly activated by SHP099 in infiltrated myeloid cells. Notably, CRC patients with MSS phenotype exhibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68;macrophages than MSI-high phenotypes, suggesting the potential role of macrophagic SHP2 in TME. co.lectively,our data reveals a mechanism of innate immunosuppression mediated by SHP2, suggesting that SHP2 is a promising target for co.on cancer immunotherapy.

关键词： Tumor microenvironment PTPN11 SHP099 STING Type I interferon co.orectal cancer scRNA-seq Macrophage

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Effect and safety of anaprazole in the treatment of duodenal ulcers:a randomized,rabeprazole-co.trolled,phase Ⅲ non-inferiority study

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Chinese Medical Journal 2022年第24期135卷 2941-2949页

作者： Huiyun Zhu Xue Pan Li Zhang Hongxin Sun Huizhen Fan Zhongwei Pan Caibin Huang Zhenwang Shi Jin Ding Qi Wang Yiqi Du Nonghua Lyu Zhaoshen Li Department of Gastroenterology Changhai Hospital of Navy Military Medical UniversityShanghai 200433China Drug Clinical Trial Institution Changhai Hospital of Navy Military Medical UniversityShanghai 200433China Department of Gastroenterology Yichun People’s HospitalYichunJiangxi 336028China Department of Gastroenterology Meihekou Central HospitalMeihekouJilin 135099China Department of Gastroenterology The First Affiliated Hospital of Gannan Medical CollegeGanzhouJiangxi 341001China Department of Gastroenterology Hefei Second People’s HospitalHefeiAnhui 230011China Department of Gastroenterology Jinhua Central HospitalJinhuaZhejiang 321099China Department of Gastroenterology Anqing Municipal HospitalAnqingAnhui 246004China Department of Gastroenterology The First Affiliated Hospital of Nanchang UniversityNanchangJiangxi 330006China

Background:The pharmaco.inetic and clinical behaviors of many proton pump inhibitors(PPIs)in peptic ulcer treatment are altered by CYP2C19 genetic *** non-inferiority study evaluated the efficacy and safety of the novel PPI anaprazole co.pared with *** also explored the influence of Helico.acter pylori(***)infection status and CYP2C19 polymorphism on ***:In this multicenter,randomized,double-blind,double-dummy,positive-drug parallel-co.trolled,phase Ⅲ study,Chinese patients with duodenal ulcers were randomized 1:1 to receive rabeprazole 10 mg+anaprazole placebo or rabeprazole placebo+anaprazole 20 mg once daily for 4 *** primary efficacy endpoint was the 4-week ulcer healing rate assessed by blinded independent *** endpoints were the proportion of patients with improved overall and individual duodenal ulcer symptoms at 4 ***,exploratory subgroup analysis of the primary endpoint by *** status and CYP2C19 polymorphism was *** events were monitored for ***-inferiority analysis was co.ducted for the primary ***:The study enrolled 448 patients(anaprazole,n=225;rabeprazole,n=223).The 4-week healing rates were 90.9%and 93.7%for anaprazole and rabeprazole,respectively(difference,-2.8%[95%co.fidence interval,-7.7%,2.2%]),demonstrating non-inferiority of anaprazole to *** duodenal ulcer symptoms improved in 90.9%and 92.5%of patients,*** rates of individual symptoms were similar between the *** rates did not significantly differ by *** status or CYP2C19 genotype for either treatment *** incidence of treatment-emergent adverse events was similar for anaprazole(72/220,32.7%)and rabeprazole(84/219,38.4%).co.clusions:The efficacy of anaprazole is non-inferior to that of rabeprazole in Chinese patients with duodenal ***:***,NCT04215653.

关键词： Cytochrome P-450 CYP2C19 Non-inferiority trial Peptic ulcer Polymorphism Genetic Proton pump inhibitors Anaprazole Rabeprazole

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