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Memory T cells: strategies for optimizing tumor immunotherapy

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Protein & Cell 2020年第8期11卷 549-564页

作者： Qingjun Liu Zhongjie Sun ligong chen School of Pharmaceutical Sciences Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology(Ministry of Education)Tsinghua UniversityBeijing 100084China Newish Technology(Beijing)Co. Ltd.Xihuan South Road 18Economic&Technical Development ZoneBeijing 100176China Moon(Guangzhou)Biotech Co. Ltd.Room 301Building B5Enterprise AcceleratorNo.11 Kaiyuan AvenueHuangpu DistrictGuangzhou 510000China Advanced Innovation Center for Human Brain Protection Beijing Tiantan HospitalCapital Medical UniversityBeijing 100088China

Several studies have demonstrated that memory T cells including stem cell memory (Tscm) T cells and central memory (Tcm) T cells show superior persistence and antitumor immunity compared with effector memory T (Tem) cells and effector T (Teff) ***,the Tcm/Teff ratio has been reported to be a predictive biomarker of immune responses against some ***,a system-level understanding of the mechanisms underlying the differentiation of effector and memory T cells is of increasing importance for developing immunological strategies against various *** review focuses on recent advances in efficacy against tumors,the origin,formation mechanisms of memory T cells,and the role of the gut microbiota in memory T cell ***,we summarize strategies to generate memory T cells in (ex) vivo that,might be applicable in clinical practice.

关键词： memory T cells tumor immunology metabolism gut microbiota

The physiological role of drug transporters

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Protein & Cell 2015年第5期6卷 334-350页

作者： Yu Liang Siqi Li ligong chen Department of Pharmacology and Pharmaceutical Sciences School of Medicine Tsinghua University Beijing 100084 China Collaborative Innovation Center for Biotherapy State Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University Chengdu 610041 China

Transporters comprise the largest family of membrane proteins in human organism, including members of solute carrier transporter and ATP-binding cassette transporter families. They play pivotal roles in the absorption, distribution and excretion of xenobiotic and endogenous molecules. Transporters are widely expressed in various human tissues and are routinely evaluated during the process of drug development and approval. Over the past decade, increasing evidence shows that drug transporters are important in both normal physiology and disease. Currently, transporters are utilized as therapeutic targets to treat numerous diseases such as diabetes, major depression, hypertension and constipation. Despite the steady growth of the field of transporter biology, more than half of the members in transporter superfamily have little information available about their endogenous substrate（s） or physiological functions. This review outlines current research methods in transporter studies, and summarizes the drug-transporter interactions including drug-drug and drug-endogenous substrate interactions. In the end, we also discuss the therapeutic perspective of transporters based on their physiological and pathophysiological roles.

关键词： transporter physiological role therapeuticimplication

Metabolic basis of solute carrier transporters in treatment of type 2 diabetes mellitus

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Acta Pharmaceutica Sinica B 2024年第2期14卷 437-454页

作者： Jiamei Le Yilong chen Wei Yang ligong chen Jianping Ye Shanghai Key Laboratory of Molecular Imaging Zhoupu HospitalShanghai University of Medicine and Health SciencesShanghai 201318China School of Health Science and Engineering University of Shanghai for Science and TechnologyShanghai 200093China Metabolic Disease Research Center Zhengzhou Central Hospital Affiliated to Zhengzhou UniversityZhengzhou 450007China School of Pharmaceutical Sciences Tsinghua UniversityBeijing 100084China Research Center for Basic Medicine Academy of Medical SciencesZhengzhou UniversityZhengzhou 450052China

Solute carriers(SLCs) constitute the largest superfamily of membrane transporter *** transporters, present in various SLC families, play a vital role in energy metabolism by facilitating the transport of diverse substances, including glucose, fatty acids, amino acids, nucleotides, and *** actively participate in the regulation of glucose metabolism at various steps, such as glucose uptake(e.g., SLC2A4/GLUT4), glucose reabsorption(e.g., SLC5A2/SGLT2), thermogenesis(e.g., SLC25A7/UCP-1), and ATP production(e.g., SLC25A4/ANT1 and SLC25A5/ANT2). The activities of these transporters contribute to the pathogenesis of type 2 diabetes mellitus(T2DM). Notably, SLC5A2 has emerged as a valid drug target for T2DM due to its role in renal glucose reabsorption, leading to groundbreaking advancements in diabetes drug discovery. Alongside SLC5A2, multiple families of SLC transporters involved in the regulation of glucose homeostasis hold potential applications for T2DM therapy. SLCs also impact drug metabolism of diabetic medicines through gene polymorphisms, such as rosiglitazone(SLCO1B1/OATP1B1) and metformin(SLC22A1-3/OCT1-3 and SLC47A1, 2/MATE1, 2). By consolidating insights into the biological activities and clinical relevance of SLC transporters in T2DM, this review offers a comprehensive update on their roles in controlling glucose metabolism as potential drug targets.

关键词： Solute carriers(SLCs) Energ ymetabolism ATP production Type 2 diabetes mellitus(T2DM) Glucose homeostasis Polymorphisms

Solute carrier transporters: the metabolic gatekeepers of immune cells

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Acta Pharmaceutica Sinica B 2020年第1期10卷 61-78页

作者： Wenxin Song Danyuan Li Lei Tao Qi Luo ligong chen School of Pharmaceutical Sciences Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology(Ministry of Education)Tsinghua UniversityBeijing 100084China Advanced Innovation Center for Human Brain Protection Capital Medical UniversityBeijing 100088China Collaborative Innovation Center for Biotherapy State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalWest China Medical SchoolSichuan UniversityChengdu 610065China

Solute carrier(SLC)transporters meditate many essential physiological functions,including nutrient uptake,ion influx/efflux,and waste *** its protective role against tumors and infections,the mammalian immune system coordinates complex signals to support the proliferation,differentiation,and effector function of individual cell *** research in this area has yielded surprisingfindings on the roles of solute carrier transporters,which were discovered to regulate lymphocyte signaling and control their differentiation,function,and fate by modulating diverse metabolic pathways and balanced levels of different *** this review,we present current information mainly on glucose transporters,amino-acid transporters,and metal ion transporters,which are critically important for mediating immune cell homeostasis in many different pathological conditions.

关键词： Solute carrier Lymphocytes Glucose Glutamine Metalion

The solute carrier transporters and the brain:Physiological and pharmacological implications

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Asian Journal of Pharmaceutical Sciences 2020年第2期15卷 131-144页

作者： chengliang Hu Lei Tao Xizhi Cao ligong chen School of Pharmaceutical Sciences Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology(Ministry of Education)Tsinghua UniversityBeijing 100084China Advanced Innovation Center for Human Brain Protection Beijing Anding HospitalCapital Medical UniversityBeijing 100088China Collaborative Innovation Center for Biotherapy State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalWest China Medical SchoolSichuan UniversityChengdu 610041China

Solute carriers(SLCs)are the largest family of transmembrane transporters that determine the exchange of various substances,including nutrients,ions,metabolites,and drugs across biological *** date,the presence of about 287 SLC genes have been identified in the brain,among which mutations or the resultant dysfunctions of 71 SLC genes have been reported to be correlated with human brain *** increasing interest in SLCs have focused on drug development,SLCs are currently still under-explored as drug targets,especially in the *** summarize the main substrates and functions of SLCs that are expressed in the brain,with an emphasis on selected SLCs that are important physiologically,pathologically,and pharmacologically in the blood-brain barrier,astrocytes,and *** suggests that a fraction of SLCs are regulated along with the occurrences of brain disorders,among which epilepsy,neurodegenerative diseases,and autism are *** the review of SLCs involved in the onset and procession of brain disorders,we hope these SLCs will be screened as promising drug targets to improve drug delivery to the brain.

关键词： Solute carrier transporter Brain disorder Blood-brain barrier Drug

The SLC transporter in nutrient and metabolic sensing, regulation, and drug development

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Journal of Molecular Cell Biology 2019年第1期11卷 1-13页

作者： Yong Zhang Yuping Zhang Kun Sun Ziyi Meng ligong chen School of Pharmaceutical Sciences Tsinghua University Beijing 100084 China Advanced Biotechnology and Application Research Center School of Chemistry and Biological Engineering University of Science and Technology Beijing Beijing 100024 China

The prevalence of metabolic diseases is growing worldwide. Accumulating evidence suggests that solute carrier (SLC) transporters contribute to the etiology of various metabolic diseases. Consistent with metabolic characteristics, the top five organs in which SLC transporters are highly expressed are the kidney, brain, liver, gut, and heart. We aim to understand the molecular mechanisms of important SLC transporter-mediated physiological processes and their potentials as drug targets. SLC transporters serve as Metabolic gate’ of cells and mediate the transport of a wide range of essential nutrients and metabolites such as glucose, amino acids, vitamins, neurotransmitters, and inorganic/metal ions. Gene-modified animal models have demonstrated that SLC transporters participate in many important physiological functions including nutrient supply, metabolic transformation, energy homeostasis, tissue development, oxidative stress, host defense, and neurological regulation. Furthermore, the human genomic studies have identified that SLC transporters are susceptible or causative genes in various diseases like cancer, metabolic disease, cardiovascular disease, immunological disorders, and neurological dysfunction? Importantly, a number of SLC transporters have been successfully targeted for drug developments。 This review will focus on the current understanding of SLCs in regulating physiology, nutrient sensing and uptake, and risk of diseases.

关键词： SLC transporters disease loci nutrient and metabolic sensing drug development

Tribological Properties of Functionalized Ionic Liquids Containing Ester-group as Lubricants for Steel-Steel System

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China Petroleum Processing & Petrochemical Technology 2012年第2期14卷 60-65页

作者： Zhu Liye chen ligong Xiang Shuo chen Guoxu Yang Xin Department of Oil Application&Management Engineering PLA Logistical Engineering UniversityChongqing 401311

A series of functionalized ionic liquids （ILs） containing ester-group were synthesized and their tribological prop- erties as lubricants for steel-steel contact were studied and compared with a non-functionalized ionic liquid and perfluo- ropolyethers （PFPE）. The morphology and chemical composition of the worn scars were analyzed by scanning electron mi- croscopy and X-ray photoelectron spectroscopy, respectively, and the possible lubrication mechanism of ILs was discussed. As a result, all ILs demonstrated a better lubricity and a much higher load-carrying capacity than PFPE used as lubricants for the steel-steel tribomates system. The functionalized ILs with ester-group showed slightly worse friction reducing abil- ity than their nonfunctionalized counterparts at relatively lower loads owing to their higher viscosity, but then exhibited better antiwear ability because the ester group they contained had not only physical but also strong chemical reactions with the freshly exposed steel surface and formed chemical adsorption boundary films on the worn surface during friction pro- cess. Under high loads, some triboehemical reactions took place between the active elements, such as fluorine which were released from the ILs, and fresh metal surfaces of rubbing pairs to form the admixture reaction films, which were mainly composed of ferric fluoride mixed with ferric oxide, leading to lower friction coefficients and good wear resistance.

关键词： functionalized ionic liquid 1-ethoxycarbonylmethyl-3-methyl bis(trifluoromethylsulfonyl)imide tribological behavior lubricant

Regulation of glucose and lipid metabolism in health and disease

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Science China(Life Sciences) 2019年第11期62卷 1420-1458页

作者： ligong chen Xiao-Wei chen Xun Huang Bao-Liang Song Yan Wang Yiguo Wang School of Pharmaceutical Sciences Beijing Advanced Innovation Center for Structural BiologyKey Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology(Ministry of Education)Tsinghua UniversityBeijing 100084China State Key Laboratory of Membrane Biology Institute of Molecular MedicinePeking-Tsinghua Center for Life SciencesPeking UniversityBeijing 100871China State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China Hubei Key Laboratory of Cell Homeostasis College of Life SciencesWuhan UniversityWuhan 430072China MOE Key Laboratory of Bioinformatics Tsinghua-Peking Joint Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijing 100084China

Glucose and fatty acids are the major sources of energy for human body. Cholesterol, the most abundant sterol in mammals, is a key component of cell membranes although it does not generate ATP. The metabolisms of glucose, fatty acids and cholesterol are often intertwined and regulated. For example, glucose can be converted to fatty acids and cholesterol through de novo lipid biosynthesis pathways. Excessive lipids are secreted in lipoproteins or stored in lipid droplets. The metabolites of glucose and lipids are dynamically transported intercellularly and intracellularly, and then converted to other molecules in specific compartments. The disorders of glucose and lipid metabolism result in severe diseases including cardiovascular disease, diabetes and fatty liver. This review summarizes the major metabolic aspects of glucose and lipid, and their regulations in the context of physiology and diseases.

关键词： cholesterol fatty acid glucose lysosome endoplasmic reticulum lipid droplet metabolic disease

Diester Derivatives from Chemically Modified Waste Cooking Oil as Substitute for Petroleum Based Lubricating Oils

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China Petroleum Processing & Petrochemical Technology 2015年第2期17卷 76-83页

作者： Xiang Shuo chen ligong Xu Lan Li Liang Yang Xin Zhu Liye Department of Military Oil Application & Management Engineering Logistical Engineering University of PLA School of Chemistry and Chemical Engineering Southwest University Oil Technical Supervision Office Logistical Department of Chengdu Military Area

In order to provide a new way for waste cooking oil(WCO) resource utilization, several diester derivatives were obtained from WCO through a three-step chemical modifications, viz.: transesterification, epoxidation and oxirane ring opening with carboxylic acids. The effects of the chain length of side chain groups on the viscosity, acid value, low temperature fluidity, thermo-oxidative stability, tribological properties and surface tension of diester derivatives were investigated. The results showed that increasing the chain length of side chain groups had a positive influence on the viscosity, viscosity index, acid value, pour point, friction coefficient and wear scar diameter along with a negative influence on the oxidation onset temperature, volatile loss, insoluble deposit, maximum non-seizure load and surface tension. These diester derivatives exhibited improved physicochemical and tribological properties that make themselves promising environmentally friendly biolubricant basestocks.

关键词： waste cooking oil diester derivative lubricating oil physicochemical property tribological property