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Quorum sensing-based interactions among drugs,microbes,and diseases

Science China(Life Sciences) 2023年第1期66卷 137-151页

作者： Shengbo Wu Shujuan Yang Manman Wang Nan Song Jie Feng Hao Wu Aidong Yang Chunjiang Liu Yanni Li Fei Guo Jianjun Qiao School of Chemical Engineering and Technology Tianjin UniversityTianjin 300072China School of Computer Science and Engineering Central South UniversityChangsha 410083China State Key Laboratory of Chemical Engineering Tianjin UniversityTianjin 300072China Collaborative Innovation Center of Chemical Science and Engineering(Tianjin) Tianjin 300072China Key Laboratory of Systems Bioengineering Ministry of Education(Tianjin University)Tianjin 300072China School of Computer Science and Technology College of Intelligence and ComputingTianjin UniversityTianjin 300350China Department of Engineering Science University of OxfordOxford OX13PJUK Institute of Shaoxing Tianjin UniversityShaoxing 312300China

Many diseases and health conditions are closely related to various microbes,which participate in complex interactions with diverse drugs;nonetheless,the detailed targets of such drugs remain to be elucidated.Many existing studies have reported causal associations among drugs,gut microbes,or diseases,calling for a workflow to reveal their intricate interactions.In this study,we developed a systematic workflow comprising three modules to construct a Quorum Sensing-based Drug-Microbe-Disease(QSDMD)database(http://***/),which includes diverse interactions for more than 8,000 drugs,163 microbes,and 42 common diseases.Potential interactions between microbes and more than 8,000 drugs have been systematically studied by targeting microbial QS receptors combined with a docking-based virtual screening technique and in vitro experimental validations.Furthermore,we have constructed a QS-based drug-receptor interaction network,proposed a systematic framework including various drug-receptor-microbe-disease connections,and mapped a paradigmatic circular interaction network based on the QS-DMD,which can provide the underlying QS-based mechanisms for the reported causal associations.The QS-DMD will promote an understanding of personalized medicine and the development of potential therapies for diverse diseases.This work contributes to a paradigm for the construction of a molecule-receptor-microbe-disease interaction network for human health that may form one of the key knowledge maps of precision medicine in the future.

关键词： quorum sensing drugs microbe-disease association microbe-host interaction gut microbiota personalized medicine

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Chemo-drugs in cell microparticles reset antitumor activity of macrophages by activating lysosomal P450 and nuclear hnRNPA2B1

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Signal Transduction and Targeted Therapy 2023年第2期8卷 757-770页

作者： Keke Wei Huafeng Zhang Shuaishuai Yang Yuxiao Cui Bingxia Zhang Jincheng Liu Liang Tang Yaoyao Tan Simin Liu Shiqi Chen Wu Yuan Xiao Luo Chen Chen Fei Li Junwei Liu Jie Chen Pingwei Xu Jiadi Lv Ke Tang Yi Zhang Jingwei Ma Bo Huang Department of Immunology Tongji Medical CollegeHuazhong University of Science&TechnologyWuhan 430030China Department of Pathology School of Basic MedicineTongji Medical CollegeHuazhong University of Science&TechnologyWuhan 430030China Department of Biochemistry&Molecular Biology Tongji Medical CollegeHuazhong University of Science&TechnologyWuhan 430030China Cardiovascular Surgery Union HospitalHuazhong University of Science&TechnologyWuhan 430071China Department of Immunology&National Key Laboratory of Medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Sciences(CAMS)&Peking Union Medical CollegeBeijing 100005China Translational Medicine Laboratory First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang 325035China Biotherapy Center and Cancer Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China

Macrophages in tumors(tumor-associated macrophages,TAMs),a major population within most tumors,play key homeostatic functions by stimulating angiogenesis,enhancing tumor cell growth,and suppressing antitumor immunity.Resetting TAMs by simple,efficacious and safe approach(s)is highly desirable to enhance antitumor immunity and attenuate tumor cell malignancy.Previously,we used tumor cell-derived microparticles to package chemotherapeutic drugs(drug-MPs),which resulted in a significant treatment outcome in human malignant pleural effusions via neutrophil recruitments,implicating that drug-MPs might reset TAMs,considering the inhibitory effects of M2 macrophages on neutrophil recruitment and activation.Here,we show that drug-MPs can function as an antitumor immunomodulator by resetting TAMs with M1 phenotype and IFN-βrelease.Mechanistically,drug molecules in tumor MPs activate macrophage lysosomal P450 monooxygenases,resulting in superoxide anion formation,which further amplifies lysosomal ROS production and pH value by activating lysosomal NOX2.Consequently,lysosomal Ca^(2+)signaling is activated,thus polarizing macrophages towards M1.Meanwhile,the drug molecules are delivered from lysosomes into the nucleus where they activate DNA sensor hnRNPA2B1 for IFN-βproduction.This lysosomal-nuclear machinery fully arouses the antitumor activity of macrophages by targeting both lysosomal pH and the nuclear innate immunity.These findings highlight that drug-MPs can act as a new immunotherapeutic approach by revitalizing antitumor activity of macrophages.This mechanistic elucidation can be translated to treat malignant ascites by drug-MPs combined with PD-1 blockade.

关键词： drugs lysosomal immunity

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UNC13A Gene Brings New Hope for ALS Disease-Modifying drugs

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Neuroscience Bulletin 2022年第11期38卷 1431-1434页

作者： Xi Chen Heling Chu Yi Dong Department of Neurology National Center for Neurological DisordersHuashan HospitalFudan UniversityShanghai 200040China Department of Gerontology Shanghai Jiao Tong University Afliated Sixth People’s HospitalShanghai 200233China

Amyotrophic lateral sclerosis(ALS)is an idiopathic and fatal neurodegenerative disorder leading to progressive muscle atrophy,dysarthria,dysphagia,and respiratory failure[1].More than 80 different drugs have been test... 详细信息

关键词： drugs respiratory atrophy

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Mechanisms of drugs in the treatment of type 2 diabetes mellitus

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Chinese Medical Journal 2023年第4期136卷 394-396页

作者： Tao Yang Hongmei Wang Caili Li Haogang Duan Zhuanglang People’s Hospital PingliangGansu 744600China Department of Pharmacy The First Hospital of Lanzhou UniversityLanzhouGansu 730000China

Type 2 diabetes mellitus(T2DM),more commonly known as chronic metabolic disease,is characterized by insufficient insulin secretion or insulin resistance.Due to the rise of T2DM globally,it is of great importance to decrease the number of complications,consequential morbidity,and mortality stemming from hyperglycemia.[1]The normal steady-state blood glucose level has become an important metric for T2DM prognosis and is recognized as one of the major results of drug therapies for diabetes.[2]This review outlines nine major types of antidiabetic drugs,relevance to functional mechanisms,which could provide a reference for the research and development of T2DM treatment drugs.

关键词： T2DM drugs treatment

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A Cascade Analysis of Community Transmission Risks for HIV among People Who Inject drugs Living with HIV in Iran

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Biomedical and Environmental Sciences 2023年第12期36卷 1171-1176页

作者： Monireh Faghir-Ganji Mostafa Shokoohi Saharnaz Nedjat Afarin Rahimi-Movaghar Kamran Yazdani James G.Khan Ali Mirzazadeh Department of Epidemiology School of Public HealthIran University of Medical SciencesTehranIran Department of Epidemiology and Biostatistics School of Public HealthTehran University of Medical SciencesTehranIran HIV/STI Surveillance Research Center and WHO Collaborating Center for HIV SurveillanceInstitute for Futures Studies in HealthKerman University of Medical SciencesKermanIran Iranian National Center for Addiction Studies(INCAS) Tehran University of Medical SciencesTehranIran University of California San Francisco San FranciscoCAUSA Department of Epidemiology and Biostatistics Institute for Global Health SciencesUniversity of California San FranciscoSan FranciscoCAUSA

There are 22 times as many people living with HIV in the population of drug users as in the general population.This is because the injection and sexually risky behaviors prevalent in this population.Having multiple sexual partners and maintaining sexual networks with people who inject drugs (PWIDs),can increase the risk of contracting a sexually transmitted infection^([1]).More than 65%of all HIVrelated cases in Iran can be traced back to people who inject drugs (PWID),and the number is estimated to be between 200,000 and 230,000 in Iran overall.Effective prevention,resources allocation and monitoring require an accurate estimate of the population of people who use illicit drugs^([2]).

关键词： drugs prevention injection

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Development of a biosensor assessing SARS-CoV-2 main protease proteolytic activity in living cells for antiviral drugs screening

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Virologica Sinica 2022年第3期37卷 459-461页

作者： Yuan Zhang Chunjie Li Xianliang Ke Dan Luo Yan Liu Quanjiao Chen Hanzhong Wang Xiaohui Song Zhenhua Zheng Key Laboratory of Special Pathogens and Biosafety Center for Emerging Infectious DiseasesWuhan Institute of VirologyChinese Academy of SciencesWuhan430071China Department of Gastroenterology Wuhan Children's HospitalTongji Medical CollegeHuazhong University of Science&TechnologyWuhan430015China Department of Obstetrics Wuhan Children's HospitalWuhan Maternal and Child Healthcare HospitalTongji Medical CollegeHuazhong University of Science&TechnologyWuhan430015China University of the Chinese Academy of Sciences Beijing100049China

Dear Editor,The Coronavirus disease 2019(COVID-19)pandemic is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The genome of this virus encodes two overlapping polyproteins,pp1a and pp1ab(Wu et al.,2020;Zhou et al.,2020).The functional polypeptides are released from those two polyproteins by extensive proteolytic events.

关键词： protease drugs

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Historic recurrences in medicinal chemistry:nature-inspired structures as a new opportunity for novel multi-target anti-Alzheimer's drugs

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Neural Regeneration Research 2023年第12期18卷 2671-2672页

作者： Luca Piemontese Universitàdegli Studi di Bari Aldo Moro Dipartimento di Farmacia-Scienze del Farmacovia E.OrabonaBariItaly

Alzheimer 's disease(AD) is an alarming noncommunicable, multi-factorial, and non-treatable disease. Its underlying neurodegenerative events have not yet been fully explained and its early diagnosis is very difficult. The appearance of the disease is associated with clinical features such as the degeneration of several cholinergic nuclei of the brain.

关键词： Alzheimer drugs diagnosis

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Criteria and regulatory considerations for the conditional approval of innovative antitumor drugs in China:from the perspective of clinical reviewers

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Cancer Communications 2023年第2期43卷 171-176页

作者： Limin Zou Yueli Qi Yongling Jiang Ling Tang Yu Du Boyuan Zhao Yanzhe Sun Meiyi Xiang Jun Ma Zhimin Yang Office of Clinical Evaluation 1 Center for Drug EvaluationNational Medical Products AdministrationBeijing 100022P.R.China Office of Management and Communication Center for Drug EvaluationNational Medical Products AdministrationBeijing 100022P.R.China Harbin Institute of Hematology and Oncology Harbin 150010HeilongjiangP.R.China

1 BACKGROUND Before the State Council of the People’s Republic of China issued the“Opinions on the Reform of the Examination and Approval System of Pharmaceutical and Medical Devices”[1],several problems existed in China’s drug evaluation and approval system.The long approval time and low efficiency of new drug marketing seriously affected the enthusiasm for drug innovation.To this end,the current“Drug Registration Regulation”(DRR)[2]was initiated by the National Medical Products Administration of China and officially implemented on July 1,2020.To encourage clinical value-oriented drug innovation,four expedited drug programs were first proposed,including breakthrough therapy drugs,conditional approval,priority review,and special approval procedures.For drugs listed in the expedited programs,the drug regulatory authorities and professional technical institutions should provide policy and technical support,prioritize the allocation of communication and review resources,and thereafter shorten the review time as much as possible.

关键词： approval drugs breakthrough

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Cell models with inducible oncogenic translocations allow to evaluate the potential of drugs to favor secondary translocations

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Cancer Communications 2023年第1期43卷 154-158页

作者： Anna Shmakova Nikolai Lomov Vladimir Viushkov Tatyana Tsfasman Yana Kozhevnikova Darina Sokolova Vadim Pokrovsky Marina Syrkina Diego Germini Mikhail Rubtsov Yegor Vassetzky UMR9018 UniversitéParis-SaclayCentre national de la recherche scientifiqueGustave RoussyVillejuif 94805France Koltzov Institute of Developmental Biology Russian Academy of SciencesMoscow 119334Russia Department of Molecular Biology Faculty of BiologyLomonosov Moscow State UniversityLeninskie GoryMoscow 119991Russia Institute of Experimental Cardiology National Medical Research Centre of CardiologyMoscow 121552Russia Faculty of Medicine Lomonosov Moscow State UniversityMoscow 119991Russia Laboratory of Combined Treatment Blokhin Cancer Research CenterMoscow 115478Russia Department of Biochemistry Peoples’Friendship University of RussiaMoscow 117198Russia Center of Genetics and Life Sciences Sirius University of Science and TechnologyFederal Territory SiriusSochi 354340Russia Department of Biochemistry Center for Industrial Technologies and EntrepreneurshipSechenov First Moscow State Medical UniversityMoscow 119991Russia

Dear Editor,Chromosomal translocations result from the interchange of geneticmaterial between non-homologous chromosomes.Chromosomal translocations are formed by erroneous repair of double-stranded breaks(DSBs)via non-homologous end joining(NHEJ)[1].Some genotoxic drugs produce DSBs and thus present a major risk factor for the development of oncogenic chromosomal translocations.The risk factors that interfere with translocationprone DSB repair,once DSBs are already formed,are obscure,and potential effects of drugs on translocation formation during this step have never been explored.

关键词： drugs potential chromosomal

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Nano“Undercover Agents”Lodge in Cartilage to Treat Osteoarthritis

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Bulletin of the Chinese Academy of Sciences 2024年第1期38卷 6-7页

The relentless pain and disability caused by osteoarthritis stem from the body’s own cartilage cells going rogue under inflammatory conditions.They secrete enzymes that devour the cushioning cartilage matrix,leading ... 详细信息

关键词： Osteoarthritis drugs cartilage

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