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Inulin Can Alleviate Metabolism Disorders in ob/ob Mice by Partially Restoring Leptinrelated Pathways Mediated by Gut Microbiota

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Genomics, Proteomics & Bioinformatics 2019年第1期17卷 64-75页

作者： Xiaofeng Song Liang Zhong Na Lyu Fei Liu Boxing Li Yanan Hao Yong Xue Jing Li Yuqing Feng Yue Ma Yongfei Hu Baoli Zhu CAS key laboratory of Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences Savaid Medical School University of Chinese Academy of Sciences beijing key laboratory of Microbial drug resistance and resistome College of Food Science and Nutritional Engineering China Agricultural University State key laboratory of Animal Nutrition College of Animal Science and Technology China Agricultural University Department of Pathogenic Biology School of Basic Medical Sciences Southwest Medical University

Inulin has been used as a prebiotic to alleviate glucose and lipid metabolism disorders in mice and humans by modulating the gut microbiota. However, the mechanism underlying the alleviation of metabolic disorders by inulin through interactions between the gut microbiota and host cells is unclear. We use ob/ob mice as a model to study the effect of inulin on the cecal microbiota by16 S rRNA gene amplicon sequencing and its interaction with host cells by transcriptomics. The inulin-supplemented diet improved glucose and lipid metabolism disorder parameters in ob/ob mice,alleviating fat accumulation and glucose intolerance. The a diversity of gut microbial community of ob/ob mice was reduced after inulin treatment, while the b diversity tended to return to the level of wild type mice. Interestingly, Prevotellaceae UCG 001(family Prevotellaceae) was obviously enriched after inulin treatment. A comparative analysis of the gene expression profile showed that the cecal transcriptome was changed in leptin gene deficiency mice, whereas the inulin-supplemented diet partially reversed the changes in leptin gene-related signaling pathways, especially AMPK signaling pathway, where the levels of gene expression became comparable to those in wild type *** analysis indicated that Prevotellaceae UCG 001 was positively correlated with the AMPK signaling pathway, which was negatively correlated with markers of glycolipid metabolism disorders. Our results suggest that the inulin-supplemented diet alleviates glucose and lipid metabolism disorders by partially restoring leptin related pathways mediated by gut microbiota.

关键词： Prebiotics Gut microbiota Obesity Transcriptome Metabolic disorders

The antibiotic resistome： gene flow in environments, animals and human beings

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Frontiers of Medicine 2017年第2期11卷 161-168页

作者： Yongfei Hu George F. Gao Baoli Zhu CAS key laboratory of Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences Beijing 100101 China beijing key laboratory of Microbial drug resistance and resistome Beijing 100101 China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases The First Affiliated Hospital Zhejiang University Hangzhou 310006 China Research Network of lmmunity and Health (RNIH) Beijing Institutes of Life Science Chinese Academy of Sciences Beijing 100101 China Office of Director-General Chinese Center for Disease Control and Prevention (China CDC) Beijing 102206 China

The antibiotic resistance is natural in bacteria and predates the human use of antibiotics. Numerous antibiotic resistance genes （ARGs） have been discovered to confer resistance to a wide range of antibiotics. The ARGs in natural environments are highly integrated and tightly regulated in specific bacterial metabolic networks. However, the antibiotic selection pressure conferred by the use of antibiotics in both human medicine and agriculture practice leads to a significant increase of antibiotic resistance and a steady accumulation of ARGs in bacteria. In this review, we summarized, with an emphasis on an ecological point of view, the important research progress regarding the collective ARGs （antibiotic resistome） in bacterial communities of natural environments, human and animals, i.e., in the one health settings. We propose that the resistance gene flow in nature is ＂from the natural environments＂ and ＂to the natural environments＂; human and animals, as intermediate recipients and disseminators, contribute greatly to such a resistance gene ＂circulation.＂

关键词： antibiotic resistance resistome microbiome gene flow

Recent progresses of exosome-liposome fusions in drug delivery

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Chinese Chemical Letters 2024年第2期35卷 107-117页

作者： Lulu Zheng Bo Hu Deyao Zhao Wenjing Liu Qing Liu Yuanyu Huang Shaobo Ruan School of Life Science Advanced Research Institute of Multidisciplinary ScienceSchool of Medical TechnologyKey Laboratory of Molecular Medicine and BiotherapyKey Laboratory of Medical Molecule Science and Pharmaceutics EngineeringBeijing Institute of TechnologyBeijing 100081China Department of Radiation Oncology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000China beijing key laboratory of drug resistance Tuberculosis Research Beijing Tuberculosis and Thoracic Tumor Research Instituteand Beijing Chest HospitalCapital Medical UniversityBeijing 101149China

Exosomes are membrane-bound nanoscale extracellular vesicles,which produced by almost all *** to the excellent biocompatibility,long circulation time as well as low immunogenicity,exosomes as naturally-derived drug delivery carriers have experienced explosive growth over the past ***,issues such as insufficient loading efficiency,heterogeneous delivery efficiency,uncontrollable targeting ability,and low production limit their wide ***,the emerging exosome-liposome fusion strategy has become a potential approach to solve such ***,this review mainly focuses on the currently developed exosome-liposome fusion strategy and their application in drug delivery as well as disease *** review aims to shed light on the advantages of fusion strategy in drug delivery and provides a better understanding for more rational *** current challenge and future perspective regarding their clinical translation and application will also be discussed.

关键词： Exosome Liposome Membrane fusion drug delivery Disease treatment

The biology,function,and applications of exosomes in cancer

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Acta Pharmaceutica Sinica B 2021年第9期11卷 2783-2797页

作者： Jinyi Liu Liwen Ren Sha Li Wan Li Xiangjin Zheng Yihui Yang Weiqi Fu Jie Yi Jinhua Wang Guanhua Du The State key laboratory of Bioactive Substance and Function of Natural Medicines Beijing 100050China key laboratory of drug Target Research and drug Screen Institute of Materia MedicaChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100050China Department of Clinical laboratory Peking Union Medical College HospitalBeijing 100730China

Exosomes are cell-derived nano vesicles with diameters from 30 to 150 nm,released upon fusion of multi vesicular bodies with the cell *** can transport nucleic acids,proteins,and lipids for intercellular communication and activate signaling pathways in target *** cancers,exosomes may participate in growth and metastasis of tumors by regulating the immune response,blocking the epithelial-mesenchymal transition,and promoting *** are also involved in the development of resistance to chemotherapeutic *** in liquid biopsies can be used as non-invasive biomarkers for early detection and diagnosis of *** of their amphipathic structure,exosomes are natural drug delivery vehicles for cancer therapy.

关键词： Exosomes Tumor immunity Tumor metastasis drug resistance Biomarkers drug delivery

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Journal of Tuberculosis Research 2013年第2期1卷 17-27页

作者： Yuhui Xu Weicong Ren Yi Liu Xuxia Zhang Chuanyou Li Zhaogang Sun beijing key laboratory of drug resistance in Tuberculosis Beijing Chest Hospital Capital Medical University Beijing China

Background: More effective biomarkers for use intuberculosis prevention,diagnosis, and treatmentare urgently needed. The?potential of miRNAsfor use as biomarkers of human disease has received much attention;however, suitable miRNA biomarkers for use in tuberculosis (TB) diagnosis and treatment have not yet been identified. Methods: We used human miRNA arrays to identify miRNAs in Peripheral Blood Mononuclear Cells (PBMCs) that are differentially expressed in subjects with active disease, those with latent TB infections (LTBI) and healthy individuals. The relationship between differentially-expressed miRNAs and mRNAs was examined using Tar- getScanS, Pic-Tar and miRanda. The expression profiles of selected miRNAs in subjects with active disease, those with LTBI and healthy individuals were validated by qRT-PCR. Results: miRNA array analysis of PBMCs from subjects with active disease, those with LTBI and healthy individuals identified 26 differentially-expressed miRNAs. Analysis of gene expression levels in THP-1 cells using mRNA arrays identified 87 differentially-expressed genes, 80 of which were up-regulated (ratio >2) and 7 of which were down-regulated (ratio In silico miRNA target prediction identified target mRNAs for 15of the 26 differentially-expressed miRNAs. Differentially-expressed miRNAs were identified for 90 of the 178 differentially-expressed genes. has-miR-21* and has-miR-26b had the highestnumbers of differentially-expressed target *** validation of has-miR-21* and has-miR- 15b* demonstrated the fidelity of our microarray results. Conclusion: Whole-genome transcriptional profiling identified differentially-expressed mRNAs and miRNAs. Differentially-expressed miRNAs?combined with predicted differentially-expressed mRNAs from the same whole-genome transcriptional profiling may be used as the new ways to better understand?TB *** discovery of differentially-expressed?miRNAsand mRNAs provides a resource for further studies on the role?of miR

关键词： miRNA Tuberculosis Biomarker Differently-Expressed Genes

Design,synthesis and antimycobacterial activity of novel nitrobenzamide derivatives

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Chinese Chemical Letters 2019年第2期30卷 413-416页

作者： Hongjian Wang Kai Lv Xiaoning Li Bo Wang Apeng Wang Zeyu Tao Yunhe Geng Bin Wang Menghao Huang Mingliang Liu Huiyuan Guo Yu Lu Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences Peking Union Medical College beijing key laboratory of drug resistance Tuberculosis Research Department of Pharmacology Beijing Tuberculosis and Thoracic Tumor Research InstituteBeijing Chest Hospital Capital Medical University Division of Gastroenterology and Hepatology Department of Medicine Indiana University School of Medicine

We report herein the design and synthesis of a series of novel nitrobenzamide derivatives. Results reveal that many of them display considerable in vitro antitubercular activity. Four N-benzyl or N- (pyridine-2-yl)methyl 3,5-dinitrobenzamides A6, All, Cl and C4 have not only the same excellent MIC values ofdrug-sensitive MTB strain H37 Rv and two drug-resistant clinical isolates as PBTZ169 and the lead 1, but also acceptable safety indices (SI > 1500), opening a new direction for further development.

关键词： Nitrobenzamides Synthesis Antimycobacterial activity Tuberculosis

N-(2-Phenoxy)ethyl imidazo[1,2-a]pyridine-3-carboxamides containing various amine moieties:Design,synthesis and antitubercular activity

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Chinese Chemical Letters 2020年第2期31卷 409-412页

作者： Linhu Li Apeng Wang Bin Wang Mingliang Liu Kai Lv Zeyu Tao Chao Ma Xican Ma Bing Han Aoyu Wang Yu Lu Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Limin Chemical Co. Ltd.Xinyi 221422China beijing key laboratory of drug resistance Tuberculosis Research Department of PharmacologyBeijing Tuberculosis and Thoracic Tumor Research InstituteBeijing Chest HospitalCapital Medical UniversityBeijing 100149China

Seven 2,6-disubstituted N-(2-phenoxy)ethyl imidazo[1,2-a]pyridine-3-carboxamide series containing various amine moieties were designed and synthesized as new anti-TB *** of them show excellent in vitro activity against both drug-sensitive MTB strain H37Rv and two MDR-MTB clinical isolates(MIC:<0.002-0.030 μg/mL).Compounds 2f,5e and 5g display acceptable safety and pharmacokinetic profiles,opening a new direction for further development.

关键词： N-(2-Phenoxy)ethyl imidazo[1,2-α]pyridine Design Synthesis Antimycobacterial activity

Association between interferon gamma receptor 1-56C/T gene polymorphism and tuberculosis susceptibility： a meta-analysis

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Chinese Medical Journal 2014年第21期127卷 3782-3788页

作者： Wang Wei Ren Weicong Zhang Xuxia Liu Yi Li Chuanyou beijing key laboratory of drug resistance Tuberculosis Research Beijing Chest Hospital Capital Medical University Beijing Tuberculosis and Thoracic Tumor Research Institute Beijing 101149 China

Background Genetic variations in the interferon-gamma （IFN-γ） receptor 1 gene （IFNGR1） may contribute to tuberculosis （TB） risk in different *** studies have investigated the relationship between IFNGR1 56C/T polymorphism and the susceptibility to TB,but have yielded conflicting results.A comprehensive meta-analysis is needed to provide a more accurate estimation of the relationship between *** A literature search based on a combination of manual and computer-based methods was conducted on four English databases （PubMed,Science Direct,SpringerLink,and EBSCO） and three Chinese databases （Wanfang,CQVIP,and Chinese National Knowledge Infrastructure databases）.Pooled odds ratios （ORs） and 95％ confidence intervals （95％ Cls） were calculated using either the fixed-effects model or the random-effects model for different genetic models based on the heterogeneity *** A total of six studies comprising 1 497 confirmed TB cases and 1 802 controls were included in this ***,no significant association was observed between IFNGR1-56C/T polymorphism and TB susceptibility （C vs.T,OR=0.90,95％ Cl 0.69-1.17; CC ***,OR=0.87,95％ Cl 0.65-1.18; TC ***,OR=-1.031,95％ Cl 0.872-1.219; CC＋TC ***,OR=0.89,95％ Cl 0.64-1.26; CC ***＋TT,OR=0.92,95％ Cl 0.66-1.29）.In subgroup analysis,a significant association was found in the dominant model （CC＋TC ***,OR=1.24,95％ Cl 1.02-1.51） in Africans,but not in Asians or *** Our meta-analysis did not provide enough powerful evidence to identify a significant association between IFNGR1-56C/T polymorphism and TB susceptibility in the overall *** subgroup analysis,it indicates that IFNGR1-56C/T is possibly associated with increased TB risk in Africans,but not in Asians or ***,larger sample size and better-designed case-control studies are needed to validate these findings.

关键词： interferon gamma receptor 1 polymorphism tuberculosis susceptibility meta-analysis

Nanocarrier-mediated co-delivery of chemotherapeutic drugs and gene agents for cancer treatment

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Acta Pharmaceutica Sinica B 2015年第3期5卷 169-175页

作者： Lin Kang Zhonggao Gao Wei Huang Mingji Jin Qiming Wang State key laboratory of Bioactive Substance and Function of Natural Medicines Beijing City Key Laboratory of Drug Delivery Technology and Novel FormulationsInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical College

The efficacy of chemotherapeutic drug in cancer treatment is often hampered by drug resistance of tumor cells,which is usually caused by abnormal gene *** interference mediated by si RNA and mi RNA can selectively knock down the carcinogenic genes by targeting specific m ***,combining chemotherapeutic drugs with gene agents could be a promising strategy for cancer *** to poor stability and solubility associated with gene agents and drugs,suitable protective carriers are needed and have been widely researched for the *** this review,we summarize the most commonly used nanocarriers for co-delivery of chemotherapeutic drugs and gene agents,as well as the advances in co-delivery systems.

关键词： Nanocarrier Co-delivery Chemotherapeutic drug Gene Liposome Micelle Dendrimer Supramolecular system