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Acta Pharmaceutica Sinica B 2022年第3期12卷 1514-1522页

作者： Chenxue Mao Juan Chen ting Zou Yuankang Zhou Junyan {2. xi li xiangping li Min li Pinhua Pan Wei Zhuo Yang Gao Shuo Hu Desheng xiao lin Wu Zhan wang Heng Xu wen Yang {12.ngjie Xu Haihua xiao Kazuhiko Hanada Wei Zhang Honghao Zhou Jiye {12.n Zhaoqian {2. departments of Clinical {2. and Pharmacy Hunan Key Laboratory of Pharmacogeneticsand National Clinical Research Center for Geriatric DisordersXiangya HospitalCentral South UniversityChangsha 410008China Institute of Clinical pharmacology Engineering Research Center of Applied Technology of PharmacogenomicsMinistry of EducationCentral South UniversityChangsha 410078China department of Respiratory Xiangya HospitalCentral South UniversityChangsha 410008China department of Thoracic Surgery Xiangya HospitalCentral South UniversityChangsha 410008China department of Nuclear Medicine Xiangya HospitalCentral South UniversityChangsha 410008China department of Pathology Xiangya HospitalCentral South UniversityChangsha 410014China department of Thoracic Medicine Hunan Cancer HospitalChangsha 410014China department of Medical Oncology Lung Cancer and Gastrointestinal UnitHunan Cancer HospitalChengdu 610000China State key laboratory of Biotherapy and Cancer Center West China HospitalSichuan University and Collaborative Innovation Center of BiotherapyChengdu 610000China department of Molecular and Cellular Biochemistry School of MedicineShanghai Jiaotong UniversityShanghai 200025China beijing National laboratory for Molecular S{2.ences State Key Laboratory of Polymer Physics and ChemistryInstitute of ChemistryChinese Academy of SciencesBeijing 100190China department of Pharmacometrics and Pharmacokinetics Meiji Pharmaceutical University Tokyo 204-8588Japan

To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma(NSCLC),we performed a two-cohort of genome-wide association studies(GWAS),including 34 for WES-based and 433 for microarray-based analyses,as well as two independent va{2.dation *** integrating the results of two studies,the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples,and their potential functional impact were investigated by eQTL analysis and in vitro cell *** found that a total of 68 variations were significant at P1×10^(-3)in cohort 1 discovery stage,of which 3 SNPs were verified in 2.2.independent samples.A total of541 SNPs were significant at P1×10^(-4)in cohort 2.discovery stage,of which 8 SNPs were verified in 347 independent *** the va{2.dated SNPs in two GWAS,ADCY1 gene was verified in both independent *** results of fine-mapping showed that the G allele carriers of ADCY1rs2.80496 and C allele carriers of rs189178649 were more {2.kely to be resistant to platinum-based *** conclusion,our study found that rs2.80496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.

关键词： Pharmacogenomics NSCLC Platinum GWAS WES ADCY1 Precious medicine SNPs

The Chinese Society of Clinical Oncology(CSCO)clinical guidelines for the diagnosis and treatment of nasopharyngeal carcinoma

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Cancer Communications 2021年第11期41卷 1195-1227页

作者： ling-Long Tang Yu-Pei Chen Chuan-Ben Chen Ming-Yuan Chen Nian-Yong Chen xiao-Zhong Chen xiao-Jing Du wen-Feng fang Mei Feng Jin Gao Fei Han xia He Chao-Su Hu De-sheng Hu Guang-Yuan Hu Hao Jiang Wei Jiang Feng Jin Jin-yi Lang Jin-Gao li Shao-Jun lin Xu liu Qiu-fang liu lin Ma Hai-Qiang Mai Ji-Yong Qin liang-fang Shen ying sun Pei-Guo wang Ren-Sheng wang Ruo-Zheng wang xiao-Shen wang ying wang Hui Wu Yun-Fei xia Shao-wen xiao Kun-Yu Yang Jun-lin yi xiao-Dong Zhu Jun Ma department of Radiation Oncology State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center of Cancer MedicineGuangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapySun Yat-sen University Cancer Center651 Dongfeng Road EastGuangzhouGuangdong 510060P.R.China department of Radiation Oncology Fujian Provincial Cancer HospitalFujian Medical University Department of Radiation OncologyTeaching Hospital of Fujian Medical University Provincial Clinical CollegeCancer Hospital of Fujian Medical UniversityFuzhouFujian 350014P.R.China department of Nasopharyngeal Carcinoma State Key Laboratory of Oncology in South ChinaCollaborative Innovation Centre for Cancer MedicineGuangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapySun Yat-sen University Cancer CenterGuangzhouGuangdong 510060P.R.China department of Radiation Oncology Cancer CenterWest China HospitalSichuan UniversityChengduSichuan 610041P.R.China Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)Institute of Cancer and Basic Medicine(IBMC)Chinese Academy of Sciences HangzhouZhejiang 310000P.R.China State key laboratory of Oncology in South {2. Collaborative Innovation Center for Cancer MedicineMedical Oncology DepartmentSun Yat-Sen University Cancer CenterGuangzhouGuangdong 510060P.R.China department of Radiation Oncology Sichuan Cancer Hospital and InstituteSichuan Cancer CenterSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuan 610041P.R.China department of Radiation Oncology Anhui Provincial Hospital Affiliated to Anhui Medical UniversityHefeiAnhui 230001P.R.China department of Clinical {2. Affiliated Cancer Hospital of Nanjing Medical UniversityJiangsu Cancer HospitalJiangsu Institute of Cancer ResearchNanjingJiangsu 210000P.R.China department of Radiation Oncology Fudan University Shanghai Cancer CenterShanghai 200032P.R.China department of Radiotherapy Hubei Cancer HospitalTong

Nasopharyngeal carcinoma(NPC)is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North *** develop these comprehensive guidelines for the diagnosis and management of NPC,the Chinese Society of Clinical Oncology(CSCO)arranged a multi-disciplinary team comprising of experts from all sub-specialties of NPC to write,discuss,and revise the *** on the findings of evidencebased medicine in {12. and abroad,domestic experts have iteratively developed these guidelines to provide proper management of ***,the guidelines describe the screening,clinical and pathological diagnosis,staging and risk assessment,therapies,and follow-up of NPC,which aim to improve the management of NPC.

关键词： Chinese Society of Clinical Oncology CSCO Nasopharyngeal carcinoma Diagnosis Staging Risk Radiotherapy Chemotherapy Surgery Immunotherapy

Morroniside antagonizes tau hyperphosphorylation against neurodegeneration:a cell culture study

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中国药理学与毒理学杂志 2015年第S1期29卷 42-43页

作者： Xue-xian KUai Cui-cui YANG {2.-bin GAO lin li Lan ZHANG department of pharmacology Xuanwu Hospital of Capital Medical UniversityBeijing Institute for Brain disorderKey Laboratory for Neurodegenerative Diseases of Ministry of Education

OBJECTIVE Protein phosphatase 2.(PP2.),a major protein phosphatase,have been reported to be involved in the microtubule-associated protein tau hyperphosphorylation and aggregation in Alzheime disease(AD).Morroniside(MOR)is the isolated component from Cornus officina{2.s *** *** present study is to investigate the inhibitory effect of MOR on tau hyperphosphorylation and the underlying *** SK-N-SH cells were pretreated with MOR 50-2.0μmol·L-1 for 2. hand then treated with okadaic acid(OA)(2.nmol·L-1)for 6h to induce tau hyperphosphorylation by inhibiting PP2. *** determine whether the inhibitory effect of MOR on tau hyperphosphorylation was dependent on PP2. directly,we transfected PP2.c siRNA into HEK2.3 *** morphology was visua{2.zed under contrast *** blotting was used to measure the expressions of phosphorylated tau,total tau,Protein phosphatase-2.(PP2.),phosphorylated PP2.Aat Tyr307(P-PP2.),demethylated PP2.Aat Leu309(DM-PP2.),protein phosphatase methylesterase 1(PME-1),Leucine carboxyl methyltransferase 1(LCMT-1),phosphorylated Src at Tyr416 and Tyr52.,total Src,glycogen synthase kinase-3β(GSK-3β)and phospho-GSK3β(Ser9).The activity of PP2.A was measured by aprotein phosphatases activity assay *** Compared with the control,the OA-treated cells became retracted and rounded up and their tau phosphorylation levels at pSer199/2.2.pT2.5,pT2.2.pS2.4,pT2.7 markedly *** with MOR improved the cellular morphology and reduced OA-induced tau *** addition,MOR treatment increased PP2.Aactivity accompanied by a decrease of DM-PP2.Aand P-PP2.*** decreased PME-1expression and the ratio of PME/***,MOR treatment altered the level of Src phosphorylated at Tyr416,which can regulate phosphorylation of PP2.***2.c siRNA could inhibit PP2.c expression and induce tau *** had no effect on PP2.c expression,correspondingly,didn′t affect tau hype

关键词： Alzheimer′s disease tau protein protein phosphatas

Photoprotective effect of the N-terminal 5-mer peptide analog P165 of amyloid precursor protein in human dermal fibroblasts

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Chinese Medical Journal 2014年第4期127卷 718-723页

作者： wang ying Chen Hui {2. Yuying wang wen wang Rong lian Shi Zhu Wei department of Dermatology and Venereology Xuanwu Hospital Capital Medical University Beijing 100053 China department of pharmacology Xuanwu Hospital Capital Medical UniversityKey Laboratory for Neurodegenerative Diseases of Ministry of Education Beijing 100053 China department of Central laboratory Xuanwu Hospital Capital Medical University Beijing 100053 China department of Dermatology and Venereology Capital Medical University Beijing 100069 China

Background We showed in our previous study that the N-terminal 17-mer peptide of amyloid precursor protein （APP17-mer peptide）,an active peptide segment with trophic and antioxidative effects,protects skin fibroblasts against ultraviolet （UV） damage and downregulates matrix metalloproteinase 1 （MMP-1） *** aim of the current study was to explore the protective effects of P165,the N-terminal 5-mer peptide analog of amyloid precursor protein that is resistant to enzymolysis,on UVA-induced damage in human dermal fibroblasts （HDFs）.Methods HDFs were cultured in Dulbecco＆#39;s modified Eagle＆#39;s medium without and with P165 （concentrations were 1,10,and 100 μJmol/L）.Then,15 J/cm2.UVA irradiation was used to obtain the UV-irradiated *** proliferation was analyzed using MTT *** collagen type Ⅰ and MMP-1 contents in cell lysate were determined by enzyme-linked immunosorbent assay （EliSA）.Fluorometric assays were performed to detect the formation of intracellular reactive oxygen species （ROS） in the *** P165 significantly protected the HDFs against UVA-induced *** with the UVA-irradiated control,1,10,and 100 μmol/L P165 elevated cell proliferation by 14.98% （P〈0.05）,17.52. （P〈0.01） and 2..34% （P〈0.001）,***,10 and 100 μmol/L P165 increased collagen type Ⅰ content （both P〈0.05）.Moreover,P165 treatment （all concentrations） also markedly suppressed the UVA-induced MMP-1 expression （all P〈0.001）.P165 at 1,10,and 100 μmol/L also reduced UVA-induced ROS generation by 11.2.%,13.69% （both P〈0.05）,and 2..48% （P〈0.001）,*** P165 could protect the HDFs against UVA-induced photodamage,including cytotoxicity,and MMP-1 ***,it also increased the collagen type Ⅰ content in the *** inhibitory effect on intracellular ROS generation might be involved in these photoprotective ***,P165 may be a useful candidate in the prevention and treatment of skin photoaging.

关键词： 5-mer peptide analog of amyloid precursor protein (P165) ultraviolet A matrix metalloproteinase 1 reactive oxygen species

Ribosome biogenesis in disease:new players and therapeutic targets

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Signal Transduction and Targeted Therapy 2023年第2期8卷 484-505页

作者： lijuan Jiao Yuzhe liu {2.-Yong Yu {2.angbin Pan Yu Zhang Junchu Tu Yao-Hua Song Yang{2.n li Institute for Cardiovascular Science and department of Cardiovascular Surgery First Affiliated Hospital and Medical College of Soochow UniversityCollaborative Innovation Center of HematologySoochow UniversitySuzhouJiangsu215123P.R.China department of Orthopedics the Second Hospital of Jilin UniversityChangchunJilin130000P.R.China key laboratory of Molecular Target&C{2.ical pharmacology and the NMPA State key laboratory of Respiratory Disease Guangzhou Medical UniversityGuangzhouGuangdong511436P.R.China department of Structural Heart Disease National Center for Cardiovascular DiseaseChina&Fuwai HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingP.R.China key laboratory of Cardiovascular Appratus Innovation Beijing100037P.R.China Cyrus Tang Hematology Center Collaborative Innovation Center of HematologySoochow UniversityNational Clinical Research Center for Hematologic Diseasesthe First Affiliated Hospital of Soochow UniversitySuzhouP.R.China State key laboratory of Radiation Medi{2.ne and Protection Soochow UniversitySuzhou215123P.R.China

The ribosome is a multi-unit complex that translates mRNA into *** biogenesis is the process that generates ribosomes and plays an essential role in cell proliferation,differentiation,apoptosis,development,and *** mTORC1,Myc,and noncoding RNA signaling pathways are the primary mediators that work jointly with RNA polymerases and ribosome proteins to control ribosome biogenesis and protein *** of mTORC1 is required for normal fetal growth and development and tissue regeneration after *** is implicated in cancer development by enhancing RNA Pol II activity,leading to uncontrolled cancer cell *** deregulation of noncoding RNAs such as microRNAs,long noncoding RNAs,and circular RNAs is involved in developing blood,neurodegenerative {2.,and *** review the similarities and differences between eukaryotic and bacterial ribosomes and the molecular mechanism of ribosome-targeting antibiotics and bacterial *** also review the most recent findings of ribosome dysfunction in COVID-19 and other conditions and discuss the consequences of ribosome frameshifting,ribosome-stalling,and *** summarize the role of ribosome biogenesis in the development of various ***,we review the current clinical trials,prospective vaccines for COVID-19,and therapies targeting ribosome biogenesis in cancer,cardiovascular disease,aging,and neurodegenerative disease.

关键词： mTORC1 consequences jointly

新形势·新策略--网络药理学与中药新药研发

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中国药理学与毒理学杂志 2018年第11期32卷 827-828页

作者：韩露程肖蕊伯晓晨曹亮陈纯陈洛南陈禹保段大跃方坚松高丽高莉高耀李美娜李学军刘艾林刘骏秦雪梅 Bauer RUDOLF 宋文婷 Alastair STEWART 孙蓉孙妩弋田俊生王永华王忠魏伟肖伟徐峰徐筱杰张文娟张媛媛赵静周文霞张永祥北京药理毒理研究所北京100850 北京辐射医学研究所北京100850 江苏康缘药业股份有限公司江苏连云港222001 福建医科大学福建福州350122 中国科学院上海生命科学研究院上海200031 北京市计算中心北京100094 美国内华达州立大学医学院药理系美国内华达广州中医药大学临床药理研究所广州广东510006 山西大学中医药现代研究中心山西太原030006 新疆维吾尔医药研究所新疆乌鲁木齐830001 墨尔本大学澳大利亚墨尔本北京大学基础医学院北京100191 中国医学科学院北京协和医学院北京100730 中国中医科学院中医临床基础医学研究所北京100700 格拉茨卡尔弗朗森大学奥地利格拉茨中国中医科学院西苑医院北京100091 墨尔本大学ARC个性化治疗技术转换中心澳大利亚墨尔本山东大学高等医学研究院山东济南250012 安徽医科大学临床药理研究所安徽合肥230032 西北大学生命科学学院陕西西安710127 上海交通大学附属第六人民医院南院上海200030 北京大学化学与分子工程学院北京100871 四川大学华西基础医学与法医学院四川成都610041 上海中医药大学交叉科学研究院上海200032

"网络药理学与生物医药发展国际论坛"于2.18年8月2.-2.日在江苏省连云港市召开。本次论坛由中国科协海智办、国际药理学联合会天然药物药理学分会、中国药理学会、中国药学会、江苏省科学技术协会、江苏省食品药品监督管理局和连云港市... 详细信息

"网络药理学与生物医药发展国际论坛"于2.18年8月2.-2.日在江苏省连云港市召开。本次论坛由中国科协海智办、国际药理学联合会天然药物药理学分会、中国药理学会、中国药学会、江苏省科学技术协会、江苏省食品药品监督管理局和连云港市人民政府共同主办,中国药理学会网络药理学专业委员会承办,江苏康缘药业股份有限公司协办,中国药理学会网络药理学专业委员会主任委员周文霞教授和常务委员、江苏康缘药业股份有限公司董事长肖伟教授共同担任论坛主席。有来自美国、澳大利亚、奥地利、中国大陆和中国澳门等多个国家和地区的97名代表出席本次论坛。国家卫生健康委员会科技教育司监察刘登峰专员应邀参会。论坛针对国际、国内网络药理学研究的现状、最新进展和发展前沿等有关问题进行了综合讨论,展示了该研究领域的新技术、新进展和新应用。为促进国内外学术交流,本文对部分专家的观点和意见进行了整理,以期为促进我国网络药理学和生物医药研究与发展起到积极的推动作用。

关键词：网络药理学生物医药中药