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Discovery and repurposing of artemisinin

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Frontiers of Medicine 2022年第1期16卷 1-9页

作者： qiaoli shi Fei Xia Qixin Wang Fulong Liao Qiuyan Guo Chengchao Xu Jigang Wang Artemisinin Research Center and Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China Central People’s Hospital of Zhanjiang Zhanjiang 524045China Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Geriatrics The Second Clinical Medical College of Jinan UniversityThe First Affiliated Hospital of Southern University of Science and TechnologyShenzhen People’s HospitalShenzhen 518020China

Malaria is an ancient infectious disease that threatens millions of lives globally even today.The discovery of artemisinin,inspired by traditional Chinese medicine(TCM),has brought in a paradigm shift and been recognized as the“best hope for the treatment of malaria”by World Health Organization.With its high potency and low toxicity,the wide use of artemisinin effectively treats the otherwise drug-resistant parasites and helps many countries,including China,to eventually eradicate malaria.Here,we will first review the initial discovery of artemisinin,an extraordinary journey that was in stark contrast with many drugs in western medicine.We will then discuss how artemisinin and its derivatives could be repurposed to treat cancer,inflammation,immunoregulation-related diseases,and COVID-19.Finally,we will discuss the implications of the“artemisinin story”and how that can better guide the development of TCM today.We believe that artemisinin is just a starting point and TCM will play an even bigger role in healthcare in the 21st century.

关键词： artemisinin drug repurposing cancer inflammation COVID-19 traditional Chinese medicine

18beta-glycyrrhetinic acid induces ROS-mediated apoptosis to ameliorate hepatic fibrosis by targeting PRDX1/2 in activated HSCs

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Journal of Pharmaceutical Analysis 2022年第4期12卷 570-582页

作者： Qian Zhang Piao Luo Liuhai Zheng Jiayun Chen Junzhe Zhang Huan Tang Dandan Liu Xueling He qiaoli shi Liwei Gu Jiahao Li Qiuyan Guo Chuanbin Yang Yin Kwan Wong Fei Xia Jigang Wang Artemisinin Research Center and Institute of Chinese Materia Medica Chinese Academy of Chinese Medical SciencesBeijing100700China Department of Biological Sciences National University of SingaporeSingapore117543Singapore Department of Geriatrics Shenzhen People's Hospital(The Second Clinical Medical CollegeJinan University)Shenzhen518020China

Hepatic stellate cells(HSCs)are essential drivers of fibrogenesis.Inducing activated-HSC apoptosis is a promising strategy for treating hepatic fibrosis.18beta-glycyrrhetinic acid(18b-GA)is a natural compound that exists widely in herbal medicines,such as Glycyrrhiza uralensis Fisch,which is used for treating multiple liver diseases,especially in Asia.In the present study,we demonstrated that 18b-GA decreased hepatic fibrosis by inducing the apoptosis in activated HSCs.18b-GA inhibited the expression of a-smooth muscle actin and collagen type Ⅰ alpha-1.Using a chemoproteomic approach derived from activity-based protein profiling,together with cellular thermal shift assay and surface plasmon resonance,we found that 18b-GA covalently targeted peroxiredoxin 1(PRDX1)and peroxiredoxin 2(PRDX2)proteins via binding to active cysteine residues and thereby inhibited their enzymatic activities.18b-GA induced the elevation of reactive oxygen species(ROS),resulting in the apoptosis of activated HSCs.PRDX1 knockdown also led to ROS-mediated apoptosis in activated HSCs.Collectively,our findings revealed the target proteins and molecular mechanisms of 18b-GA in ameliorating hepatic fibrosis,highlighting the future development of 18b-GA as a novel therapeutic drug for hepatic fibrosis.

关键词： Glycyrrhetinic acid Hepatic fibrosis Peroxiredoxin Reactive oxygen species Apoptosis

A highly efficient protein corona-based proteomic analysis strategy for the discovery of pharmacodynamic biomarkers

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Journal of Pharmaceutical Analysis 2022年第6期12卷 879-888页

作者： Yuqing Meng Jiayun Chen Yanqing Liu Yongping Zhu Yin-Kwan Wong Haining Lyu qiaoli shi Fei Xia Liwei Gu Xinwei Zhang Peng Gao Huan Tang Qiuyan Guo Chong Qiu Chengchao Xu Xiao He Junzhe Zhang Jigang Wang Artemisinin Research Center and Institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing100700China Department of Biological Sciences National University of Singapore117543Singapore Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety Institute of High Energy PhysicsChinese Academy of SciencesBeijing100049China

The composition of serum is extremely complex,which complicates the discovery of new pharmacodynamic biomarkers via serum proteome for disease prediction and diagnosis.Recently,nanoparticles have been reported to efficiently reduce the proportion of high-abundance proteins and enrich lowabundance proteins in serum.Here,we synthesized a silica-coated iron oxide nanoparticle and developed a highly efficient and reproducible protein corona(PC)-based proteomic analysis strategy to improve the range of serum proteomic analysis.We identified 1,070 proteins with a median coefficient of variation of 12.56%using PC-based proteomic analysis,which was twice the number of proteins identified by direct digestion.There were also more biological processes enriched with these proteins.We applied this strategy to identify more pharmacodynamic biomarkers on collagen-induced arthritis(CIA)rat model treated with methotrexate(MTX).The bioinformatic results indicated that 485 differentially expressed proteins(DEPs)were found in CIA rats,of which 323 DEPs recovered to near normal levels after treatment with MTX.This strategy can not only help enhance our understanding of the mechanisms of disease and drug action through serum proteomics studies,but also provide more pharmacodynamic biomarkers for disease prediction,diagnosis,and treatment.

关键词： Protein corona Nanoparticles Mass spectrometry Proteomic analysis Pharmacodynamic biomarkers

基于常规超声联合超声造影的列线图预测临床淋巴结阴性甲状腺乳头状癌中央区淋巴结转移

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中国医学影像学杂志 2024年第1期32卷 28-33,41页

作者：张晓梅李巧莉葛肖艳石丽楠康燕飞李军石河子大学第一附属医院超声科新疆石河子832008 国家卫健委中亚高发病防治重点实验室(石河子大学第一附属医院) 新疆石河子832008

目的基于常规超声联合超声造影(CEUS)指标,构建预测临床淋巴结阴性(CN0)的甲状腺乳头状癌(PTC)发生颈部中央区淋巴结转移(CLNM)的风险概率列线图。资料与方法回顾性分析2015年9月—2022年3月于石河子大学第一附属医院行甲状腺手术及预... 详细信息

目的基于常规超声联合超声造影(CEUS)指标,构建预测临床淋巴结阴性(CN0)的甲状腺乳头状癌(PTC)发生颈部中央区淋巴结转移(CLNM)的风险概率列线图。资料与方法回顾性分析2015年9月—2022年3月于石河子大学第一附属医院行甲状腺手术及预防性颈部中央区淋巴结清扫的单发CN0 PTC 359例,根据术后病理结果分为CLNM阳性组116例与阴性组243例。记录患者性别、年龄、结节常规超声及CEUS指标,筛选出CN0 PTC发生CLNM的风险因素并构建预测模型。绘制受试者工作特征曲线并比较预测模型的曲线下面积(AUC),选取最佳预测模型构建风险概率列线图,分析列线图模型的预测效能及临床适用性。结果性别、年龄、结节最大径、被膜侵犯及CEUS强化方式为CN0 PTC发生CLNM的风险因素(P均<0.05),5个指标联合建立预测模型1的AUC为0.753,剔除CEUS指标建立预测模型2的AUC为0.704,两者AUC差异有统计学意义(Z=2.473,P=0.013)。选择预测模型1构建CN0 PTC发生CLNM的风险概率列线图,模型的C-指数为0.753,校准曲线结果表明一致性良好,临床决策曲线分析表明阈值概率为10.7%~81.5%时,列线图模型可获得较好的净收益。结论性别、年龄、结节最大径、被膜侵犯及CEUS强化方式是CN0 PTC发生CLNM的风险因素,以上指标联合建立的列线图模型可有效预测CLNM的发生概率,且CEUS指标可显著提高模型的预测效能。

关键词：甲状腺癌乳头状中央区淋巴结转移列线图超声造影超声检查

A new luciferase immunoprecipitation system assay provided serological evidence for missed diagnosis of severe fever with thrombocytopenia syndrome

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Virologica Sinica 2022年第1期37卷 107-114页

作者： Shengyao Chen Minjun Xu Xiaoli Wu Yuan Bai Junming shi Min Zhou qiaoli Wu Shuang Tang Fei Deng Bo Qin Shu Shen State Key Laboratory of Virology and National Virus Resource Center Wuhan Institute of VirologyChinese Academy of SciencesWuhan430071China Shaoxing Women and Children©s Hospital No.305 East Street RoadShaoxing312000China University of Chinese Academy of Sciences Beijing100049China Shaoxing People©s Hospital Zhejiang University School of MedicineShaoxing312000China

Severe fever with thrombocytopenia syndrome(SFTS),caused by SFTS virus(SFTSV)infection,was first reported in 2010 in China with an initial fatality of up to 30%.The laboratory confirmation of SFTSV infection in terms of detection of viral RNA or antibody levels is critical for SFTS diagnosis and therapy.In this study,a new luciferase immunoprecipitation system(LIPS)assay based on p REN2 plasmid expressing SFTSV NP gene and tagged with Renilla luciferase(Rluc),was established and used to investigate the levels of antibody responses to SFTSV.Totally 464 serum samples from febrile patients were collected in the hospital of Shaoxing City in Zhejiang Province in 2019.The results showed that 82 of the 464 patients(17.7%)had antibody response to SFTSV,which were further supported by immunofluorescence assays(IFAs).Further,q RT-PCR and microneutralization tests showed that among the 82 positive cases,15 patients had viremia,10 patients had neutralizing antibody,and one had both(totally 26 patient).However,none of these patients were diagnosed as SFTS in the hospital probably because of their mild symptoms or subclinical manifestations.All the results indicated that at least the 26 patients having viremia or neutralizing antibody were the missed diagnosis of SFTS cases.The findings suggested the occurrence of SFTS and the SFTS incidence were higher than the reported level in Shaoxing in 2019,and that LIPS may provide an alternative strategy to confirm SFTSV infection in the laboratory.

关键词： Severe fever with thrombocytopenia syndrome(SFTS) Severe fever with thrombocytopenia syndrome virus(SFTSV) Luciferase immunoprecipitation systems(LIPS) Shaoxing Serological evidence Missed diagnosis

木制家具制造业噪声所致听力损失职业健康风险评估

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职业与健康 2024年第2期40卷 170-175页

作者：杨亚君余巧利付晓兰段勇石雄杰王成重庆市长寿区疾病预防控制中心职业卫生科重庆401220

目的评估木制家具制造业噪声所致作业人员听力损失的职业健康风险,确定关键风险点。方法 2021—2023年在重庆市长寿区高新区内抽取39家木制家具制造企业工作场所及852名木制家具噪声作业人员为调查对象。对企业工作场所噪声强度进行检... 详细信息

目的评估木制家具制造业噪声所致作业人员听力损失的职业健康风险,确定关键风险点。方法 2021—2023年在重庆市长寿区高新区内抽取39家木制家具制造企业工作场所及852名木制家具噪声作业人员为调查对象。对企业工作场所噪声强度进行检测,并对噪声作业岗位人员噪声接触水平进行测量,采用GBZ/T 229.4—2012《工作场所职业病危害作业分级》评估不同岗位噪声危害程度,使用WS/T 754—2016《噪声职业病危害风险管理指南》预测不同岗位噪声作业人员在50、55、60岁时发生高频听力损失(high frequency hearing loss,HFHL)和职业性噪声聋(occupational noise-induced deafness,ONID)的风险。结果木制家具制造业工作场所噪声超标率为32.7%;10个噪声作业岗位工人接触的8h等效声级或每周40 h等效声级最大值为87.3~96.5 dB(A)。除擦板和喷漆岗位外,制板、封边、精裁、雕刻和打磨岗位噪声危害程度为中度危害,而下料、制作和异型岗位噪声危害程度为重度危害,存在较大的噪声危害风险。各噪声岗位作业人员HFHL异常检出率为15.7%,ONID异常检出率为6.6%。各岗位噪声所致作业人员HFHL和ONID的风险随着暴露年数的增加而增加,其中下料工、制作工、异型工、精裁工、雕刻工在≥50岁时发生HFHL的风险均为较高风险;除擦板和喷漆工外其余工种作业工人工作到60岁时发生HFHL的风险均为较高风险。下料工、制作工、异型工、封边工、精裁工、雕刻工、打磨工在≥50岁时发生ONID的风险均为较高风险;其中下料工和制作工作业工人工作到60岁时发生ONID的风险均为高风险。结论木制家具制造行业工作场所噪声强度较大;下料、制作、异型、封边、精裁、雕刻和打磨岗位是关键风险点,作业人员发生高频听力损失和职业性噪声聋的风险等级较高。

关键词：木制家具制造业噪声职业健康听力损失风险评估

热轧+电脉冲处理对超导用Cu-14Sn-0.3Ti合金组织及性能的影响

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稀有金属材料与工程 2024年第4期53卷 1155-1162页

作者：王宇轩邹军涛冯巧丽白云飞程军胜石林宋大拙孙利星姜伊辉张志伟西安理工大学材料科学与工程学院陕西省电工材料与熔(浸)渗技术重点实验室导电材料与复合技术教育部工程研究中心陕西西安710048 中国科学院电工研究所北京100190

采用热轧+电脉冲处理的方式实现了Cu-14Sn-0.3Ti合金强度与延伸率的协同提升,Cu-14Sn-0.3Ti合金在经过70%热轧+10 min电脉冲处理后,延伸率由4.7%提升至40%,强度由298 MPa提升至530 MPa。通过调控热轧及电脉冲处理工艺,研究了形变储能,... 详细信息

采用热轧+电脉冲处理的方式实现了Cu-14Sn-0.3Ti合金强度与延伸率的协同提升,Cu-14Sn-0.3Ti合金在经过70%热轧+10 min电脉冲处理后,延伸率由4.7%提升至40%,强度由298 MPa提升至530 MPa。通过调控热轧及电脉冲处理工艺,研究了形变储能,脉冲电流对减少层错,促进孪晶生长的影响。结果表明,Cu-14Sn-0.3Ti合金的强度与密度随着形变储能的增加而提升。在焦耳热和电子风力的共同作用下,Cu-14Sn-0.3Ti合金组织中的δ相发生溶解,层错减少。电脉冲处理后孪晶的形成为位错的运动提供了额外的滑移系,提升了Cu-14Sn-0.3Ti合金的延伸率。一方面孪晶的出现对晶粒进行了分割,细化了晶粒,另一方面,孪晶界的产生阻碍了Cu-14Sn-0.3Ti合金形变时位错的运动,使得Cu-14Sn-0.3Ti合金的强度得到提升。

关键词： Cu-14Sn-0.3Ti合金热轧电脉冲处理强度延伸率

Characterization and immunogenicity of bone marrow-derived mesenchymal stem cells under osteoporotic conditions

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Science China(Life Sciences) 2020年第3期63卷 429-442页

作者： Yingkang Huang Yin Yin Yanzheng Gu qiaoli Gu Huilin Yang Zhengyu Zhou Qin shi Orthopedic Department the First Affiliated Hospital of Soochow UniversityMedical College of Soochow UniversityOrthopedic Institute of Soochow UniversitySuzhou 215006China Laboratory Animal Center Medical College of Soochow UniversitySoochow UniversitySuzhou 215123China Clinical Immunology Institute of Jiangsu Province the First Affiliated Hospital of Soochow UniversitySuzhou 215006China Key Laboratory of Stem Cells and Biomedical Materials of Jiangsu Province and Chinese Ministry of Science and Technology Suzhou 215123China

Mesenchymal stem cells(MSCs)are characterized by their multilineage potential and low immunogenicity.However,the properties of MSCs under pathological conditions are unclear.The current study investigated the differentiation potential and immunological characteristics of bone marrow-derived MSCs from ovariectomized-osteoporotic rats(OP-BMSCs).Although the expression of cell morphology-and stemness-related surface markers was similar between OP-BMSCs and BMSCs from healthy rats(H-BMSCs),the proliferation rate was significantly decreased compared with that of H-BMSCs.Regarding multilineage potential,osteogenesis and chondrogenesis abilities of OP-BMSCs decreased,but the adipogenesis ability was significantly enhanced compared with that of H-BMSCs.As expected,decreased osteogenesis following osteogenic induction resulted in reduced expression ofβ-catenin,osteocalcin,and runt-related transcription factor 2 in OP-BMSCs.Remarkably,the expression of the co-stimulatory proteins CD40 and CD80 was significantly higher,whereas the expression of the negative costimulatory molecule programmed cell death ligand 1 was significantly lower in the OP-BMSCs than that in H-BMSCs.Consequently,H-BMSCs inhibited the proliferation and secretion of inflammatory cytokines from anti-CD3 antibody-activated T cells,whereas OP-BMSCs did not.These results indicate that decreased osteogenesis and increased immunogenicity of OPBMSCs contribute to bone loss in osteoporosis.

关键词： mesenchymal stem cells osteogenesis chondrogenesis adipogenesis immunogenicity osteoporosis

Solvent-dependent evolution of cyclic penta-twinned rhodium icosahedral nanocrystals and their enhanced catalytic properties

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Nano Research 2018年第2期11卷 656-664页

作者： Yanan Yang Jiawei Zhang Yajing Wei qiaoli Chen Zhenming Cao Huiqi Li Jiayu Chen Jueli shi Zhaoxiong Xie Lansun Zheng State Key Laboratory for Physical Chemistry of Solid Surfaces Collaborative Innovation Center of Chemistry for Energy Materials Department of Chemistry College of Chemistry and Chemical Engineering Xiamen University Xiamen China

Cyclic penta-twinned noble metal nanocrystals exhibit promising properties due to their unique geometric and electronic structures. However, the controlled synthesis of cyclic penta-twinned nanostructures, especially of noble metals with a high cohesive energy （e.g., Rh）, is very difficult, and the corresponding growth mechanism is not fully understood. Herein, we report a facile one-pot hydrothermal approach for the synthesis of cyclic penta-twinned Rh icosahedral nanocrystals. It was found that apart from regulating the surface free energy by changing the concentration or category of the capping agents, the solvent might influence the adsorption ability of the surfactant on the Rh crystal surface, which results in a change in the surface free energy and thus allows the formation of Rh cyclic penta-twinned nanostructures. In addition, due to their unique electronic and geometric structures, the Rh icosahedral nanocrystals exhibit superior catalytic activity and stability for the electrooxidation of ethanol as compared to single-crystal Rh tetrahedral nanocrystals and commercial Rh black.

关键词： Rhrcrystal growth,icosahedron,tetrahedron,electrocatalysis