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Bone-derived MSCs encapsulated in alginate hydrogel prevent collagen-induced arthritis in mice through the activation of adenosine A_(2A/2B)receptors in tolerogenic dendritic cells

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Acta Pharmaceutica Sinica B 2023年第6期13卷 2778-2794页

作者： Gaona Shi Yu Zhou Wenshuai Liu Chengjuan Chen Yazi Wei Xinlong Yan Lei Wu Weiwei Wang Lan Sun Tiantai Zhang State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Tianjin Key Laboratory of Biomaterial Research Institute of Biomedical EngineeringChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China Faculty of Environmental and Life Sciences Beijing University of TechnologyBeijing 100124China

Tolerogenic dendritic cells(tol DCs)facilitate the suppression of autoimmune responses by differentiating regulatory T cells(Treg).The dysfunction of immunotolerance results in the development of autoimmune diseases,such as rheumatoid arthritis(RA).As multipotent progenitor cells,mesenchymal stem cells(MSCs),can regulate dendritic cells(DCs)to restore their immunosuppressive function and prevent disease ***,the underlying mechanisms of MSCs in regulating DCs still need to be better ***,the delivery system for MSCs also influences their ***,MSCs are encapsulated in alginate hydrogel to improve cell survival and retention in situ,maximizing efficacy in *** three-dimensional co-culture of encapsulated MSCs with DCs demonstrates that MSCs can inhibit the maturation of DCs and the secretion of pro-inflammatory *** the collagen-induced arthritis(CIA)mice model,alginate hydrogel encapsulated MSCs induce a significantly higher expression of CD39^(+)CD73^(+)on *** enzymes hydrolyze ATP to adenosine and activate A_(2A/2B)receptors on immature DCs,further promoting the phenotypic transformation of DCs to tol DCs and regulating naive T cells to ***,encapsulated MSCs obviously alleviate the inflammatory response and prevent CIA *** finding clarifies the mechanism of MSCs-DCs crosstalk in eliciting the immunosuppression effect and provides insights into hydrogel-promoted stem cell therapy for autoimmune diseases.

关键词： Mesenchymal stem cells Alginate hydrogel Tolerogenic dendritic cells Immunotolerance Adenosine A_(2A/2B)receptor CD39/CD73 Treg Rheumatoid arthritis

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Spatiotemporal pharmacometabolomics based on ambient mass spectrometry imaging to evaluate the metabolism and hepatotoxicity of amiodarone in HepG2 spheroids

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Journal of Pharmaceutical Analysis 2023年第5期13卷 483-493页

作者： Limei Li Qingce Zang Xinzhu Li Ying Zhu Shanjing Wen Jiuming He Ruiping Zhang Zeper Abliz State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100050China Key Laboratory of Mass Spectrometry Imaging and Metabolomics(Minzu University of China) National Ethnic Affairs CommissionBeijing100081China Center for Imaging and Systems Biology College of Life and Environmental SciencesMinzu University of ChinaBeijing100081China

Three-dimensional(3D)cell spheroid models combined with mass spectrometry imaging(MSI)enables innovative investigation of in vivo-like biological processes under different physiological and pathological ***,airflow-assisted desorption electrospray ionization-MSI(AFADESI-MSI)was coupled with 3D HepG2 spheroids to assess the metabolism and hepatotoxicity of amiodarone(AMI).High-coverage imaging of>1100 endogenous metabolites in hepatocyte spheroids was achieved using *** AMI treatment at different times,15 metabolites of AMI involved in Ndesethylation,hydroxylation,deiodination,and desaturation metabolic reactions were identified,and according to their spatiotemporal dynamics features,the metabolic pathways of AMI were ***,the temporal and spatial changes in metabolic disturbance within spheroids caused by drug exposure were obtained via metabolomic *** main dysregulated metabolic pathways included arachidonic acid and glycerophospholipid metabolism,providing considerable evidence for the mechanism of AMI *** addition,a biomarker group of eight fatty acids was selected that provided improved indication of cell viability and could characterize the hepatotoxicity of *** combination of AFADESI-MSI and HepG2 spheroids can simultaneously obtain spatiotemporal information for drugs,drug metabolites,and endogenous metabolites after AMI treatment,providing an effective tool for in vitro drug hepatotoxicity evaluation.

关键词： Mass spectrometry imaging HepG2 spheroids Hepatotoxicity Drug metabolism Amiodarone

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Thermal proteome profiling of protein-centric interactions and modifications

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Trends in biochemical sciences 2025年第6期50卷 544-545页

作者： Zhenghui Chen Anhui Wang Yiqun Geng State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China. State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China. Electronic address: gengyiqun@***.

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Research advances in peptide-drug conjugates

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Acta Pharmaceutica Sinica B 2023年第9期13卷 3659-3677页

作者： Liming Gong Heming Zhao Yanhong Liu Hao Wu Chao Liu Shuangyan Chang Liqing Chen Mingji Jin Qiming Wang Zhonggao Gao Wei Huang State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Beijing Key Laboratory of Drug Delivery Technology and Novel Formulations Department of PharmaceuticsInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Department of Pharmacy Yanbian UniversityYanji 133000China

Peptide-drug conjugates(PDCs)are drug delivery systems consisting of a drug covalently coupled to a multifunctional peptide via a cleavable *** an emerging prodrug strategy,PDCs not only preserve the function and bioactivity of the peptides but also release the drugs responsively with the cleavable property of the *** the ability to significantly improve the circulation stability and targeting of drugs in vivo and reduce the toxic side effects of drugs,PDCs have already been extensively applied in drug ***,we review the types and mechanisms of peptides,linkers and drugs used to construct PDCs,and summarize the clinical applications and challenges of PDC drugs.

关键词： Peptide-drug conjugates Peptides Linkers Drug delivery systems Prodrug strategy

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Promise of spatially resolved omics for tumor research

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Journal of Pharmaceutical Analysis 2023年第8期13卷 851-861页

作者： Yanhe Zhou Xinyi Jiang Xiangyi Wang Jianpeng Huang Tong Li Hongtao Jin Jiuming He State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100050China New Drug Safety Evaluation Center Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100050China NMPA Key Laboratory for Safety Research and Evaluation of Innovative Drug Beijing10050China

Tumors are spatially heterogeneous tissues that comprise numerous cell types with intricate *** interacting with the microenvironment,tumor cells undergo dynamic changes in gene expression and metabolism,resulting in spatiotemporal variations in their capacity for proliferation and *** recent years,the rapid development of histological techniques has enabled efficient and high-throughput biomolecule *** preserving location information while obtaining a large number of gene and molecular data,spatially resolved metabolomics(SRM)and spatially resolved transcriptomics(SRT)approaches can offer new ideas and reliable tools for the in-depth study of *** review provides a comprehensive introduction and summary of the fundamental principles and research methods used for SRM and SRT techniques,as well as a review of their applications in cancer-related fields.

关键词： Tumor Spatially resolved transcriptomics Spatially resolved metabolomics

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Lp-PLA2 inhibition prevents Ang Ⅱ-induced cardiac inflammation and fibrosis by blocking macrophage NLRP3 inflammasome activation

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中国药理学报（英文版） 2021年第12期42卷 2016-2032页

作者： Si-lin Lv Zi-fan Zeng Wen-qiang Gan Wei-qi Wang Tie-gang Li Yu-fang Hou Zheng Yan Ri-xin Zhang Min Yang State Key Laboratory of Bioactive Substances and Function of Natural Medicine Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Macrophage-mediated inflammation plays an important role in hypertensive cardiac remodeling,whereas effective pharmacological treatments targeting cardiac inflammation remain ***-associated phospholipase A2 (Lp-PLA2)contributes to vascular inflammation-related diseases by mediating macrophage migration and ***,the most advanced Lp-PLA2 inhibitor,has been evaluated in phase Ⅲ trials in atherosclerosis ***,the role of darapladib in inhibiting hypertensive cardiac fibrosis remains *** a murine angiotensin Ⅱ (Ang Ⅱ) infusion-induced hypertension model,we found that Pla2g7 (the gene of Lp-PLA2) was the only upregulated PLA2 gene detected in hypertensive cardiac tissue,and it was primarily localized in heart-infiltrating *** expected,darapladib significantly prevented Ang Ⅱ-induced cardiac fibrosis,ventricular hypertrophy,and cardiac dysfunction,with potent abatement of macrophage infiltration and inflammatory *** sequencing revealed that darapladib strongly downregulated the expression of genes and signaling pathways related to inflammation,extracellular matrix,and ***,darapladib substantially reduced the Ang Ⅱinfusion-induced expression of nucleotide-binding oligomerization domain-like receptor with pyrin domain 3 (NLRP3) and interleukin (IL)-1β and markedly attenuated caspase-1 activation in cardiac ***,darapladib ameliorated Ang Ⅱ-stimulated macrophage migration and IL-1β secretion in macrophages by blocking NLRP3 inflammasome *** also effectively blocked macrophage-mediated transformation of fibroblasts into myofibroblasts by inhibiting the activation of the NLRP3 inflammasome in ***,our study identifies a novel anti-inflammatory and anti-cardiac fibrosis role of darapladib in Lp-PLA2 inhibition,elucidating the protective effects of suppressing NLRP3 inflammasome ***-PLA2 inhibition by darapladib represents a nove

关键词： NLRP3 inflammasome lipoprotein-associated phospholipase A2 macrophage cardiac inflammation hypertension cardiac fibrosis angiotensin II darapladib

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Guajamers A-I, Rearranged Polycyclic Phloroglucinol Meroterpenoids from Psidium guajava Leaves and Their Antibacterial Activity

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Chinese Journal of Chemistry 2021年第5期39卷 1129-1137页

作者： Ji-Wu Huang Chuang-Jun Li Jing-Zhi Yang Chuan Li Yu Zhang Ke Liu Yue Yu Jian-Dong Jiang Dong-Ming Zhang State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Eight new polycyclic phloroglucinol meroterpenoids guajamers A-H(1-8),a methylated benzoylphloroglucinol meroterpenoid guajamer I(9)representing a new skeleton,and two known analogues(10 and 11)were isolated from the leaves of Psidium *** structures of new molecules were elucidated by detailed analysis of spectroscopic data,and those of 1,2,8,and 9 were unambiguously confirmed by single-crystal X-ray diffraction ***,compounds 1-8 were sesquiterpene and monoterpene-based meroterpenoids with rearranged skeletons,while compound 9 was the first case of 3-alkyl-5-formyl-benzoylphloroglucinol-coupled sesquiterpene containing an unusual C-l-spiro-fused 6/6/9/4 polycyclic *** addition,all the isolated compounds were evaluated for their antibacterial activity against three bacterial strains,and most of them(compounds 2-7,10,and 11)showed antibacterial activity against Staphylococcus aureus and Staphylococcus epidermidis with MIC values of 8-32 μmol/*** findings suggested that meroterpenoids isolated from Psidium guajava can be considered as potential antibacterial leading compounds for pharmaceutical industry.

关键词： Psidium guajava Meroterpenoids X-ray crystal structure Structural elucidation Antibacterial activity

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Long non-coding RNAs: From disease code to drug role

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Acta Pharmaceutica Sinica B 2021年第2期11卷 340-354页

作者： Yuanyuan Chen Zhaojun Li Xiaoguang Chen Sen Zhang State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia MedicaChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100050China

Enormous studies have corroborated that long non-codig RNAs(LncRNAs)extensively participate in crucial physiological processes such as metabolism and immunity,and are closely related to the occurrence and development of tumors,cardiovascular diseases,nervous system disorders,nephropathy,and other *** application of lncRNAs as biomarkers or intervention targets can provide new insights into the diagnosis and treatment of *** paper has focused on the emerging research into lncRNAs as pharmacological targets and has reviewed the transition of IncRNAs from the role of disease coding to acting as drug candidates,including the current status and progress in preclinical ***-edge strategies for lncRNA modulation have been summarized,including the sources of LncRNA-related drugs,such as genetic technology and small-molecule compounds,and related delivery *** current progress of clinical trials of lncRNA-targeting drugs is also *** information will form a latest updated reference for research and development of lncRNA-based drugs.

关键词： LncRNAs Targeted drug Gene therapy Small molecules Delivery ASncmtRNA Translational medicine Clinical trials

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New triterpenoid saponins from the leaves of Ilex chinensis and their hepatoprotective activity

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Chinese Journal of natural medicines 2021年第5期19卷 376-384页

作者： SHAO Si-Yuan LI Ruo-Fei SUN Hua LI Shuai State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

Seven new triterpenoid saponins,including five ursane-type saponins,ilexchinenosides R–V(1–5),and two oleananetype saponins,ilexchinenosides W–X(6–7),with four known triterpenoid saponins(8–11)were isolated from the leaves of Ilex *** structures were elucidated by comprehensive spectroscopic 1 D and 2 D NMR and HR-ESI-MS *** sugar moieties were determined by HPLC analysis compared with standards after hydrolysis and *** 1,2,4,9 and 10 exhibited potential hepatoprotective activity against N-acetyl-p-aminophenol(APAP)-induced Hep G2 cell injury in vitro.

关键词： Ilex chinensis Ursane and oleanane Triterpenoid saponins Hepatoprotective activity

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Repurposing clinical drugs is a promising strategy to discover drugs against Zika virus infection

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Frontiers of Medicine 2021年第3期15卷 404-415页

作者： Weibao Song Hongjuan Zhang Yu Zhang Rui Li Yanxing Han Yuan Lin Jiandong Jiang State Key Laboratory of Bioactive Substances and Function of Natural Medicine Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Zika virus(ZIKV)is an emerging pathogen associated with neurological complications,such as Guillain–Barrésyndrome in adults and microcephaly in fetuses and *** mosquito-borne flavivirus causes important social and sanitary problems owing to its rapid ***,the development of antivirals against ZIKV is *** various strategies have been used to study anti-ZIKV agents,approved drugs or vaccines for the treatment(or prevention)of ZIKV infections are currently *** clinically approved drugs could be an effective approach to quickly respond to an emergency outbreak of ZIKV *** well-established safety profiles and optimal dosage of these clinically approved drugs could provide an economical,safe,and efficacious approach to address ZIKV *** review focuses on the recent research and development of agents against ZIKV infection by repurposing clinical *** characteristics,targets,and potential use in anti-ZIKV therapy are *** review provides an update and some successful strategies in the search for anti-ZIKV agents are given.

关键词： Zika virus clinical drugs ZIKV inhibitors antivirals repurposing

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