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Allogenic microglia replacement:A novel therapeutic strategy for neurological disorders

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Fundamental Research 2024年第2期4卷 237-245页

作者： Yanxia Rao Bo Peng Department of Laboratory animal Science MOE Frontiers Center for Brain ScienceFudan UniversityShanghai 200032China Department of Neurosurgery Huashan HospitalInstitute for Translational Brain ResearchState Key Laboratory of Medical NeurobiologyMOE Frontiers Center for Brain ScienceMOE Innovative Center for New Drug Development of Immune Inflammatory DiseasesFudan UniversityShanghai 200000China co.Innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu 226001China

Microglia are resident immune cells in the central nervous system(CNS)that play vital roles in CNS development,homeostasis and disease *** defects in microglia lead to microglial dysfunction,which in turn leads to neurological *** co.rection of the specific genetic defects in microglia in these disorders can lead to therapeutic *** genetic defect co.rection approaches are dependent on viral vectorbased genetic defect ***,the viruses used in these approaches,including adeno-associated viruses,lentiviruses and retroviruses,do not primarily target microglia;therefore,viral vector-based genetic defect co.rections are ineffective in *** replacement is a novel approach to co.rect microglial genetic defects via replacing microglia of genetic defects with allogenic healthy *** this paper,we systematically review the history,rationale and therapeutic perspectives of microglia replacement,which would be a novel strategy for treating CNS disorders.

关键词： Microglia Replacement Microglia replacement Microglia depletion Microglia-free niche CSF1R

Preparation and interaction mechanism analysis of single‑chain fragment variables against phenylethanolamine A

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animal Diseases 2024年第2期4卷 127-137页

作者： Long Li Ren Hou Huaming Li Shiyun Han Jixiang Liang Yu Si Dapeng Peng State Key Laboratory of Agricultural Microbiology National Reference Laboratory of Veterinary Drug Residues(HZAU)and MOA Key Laboratory for Detection of Veterinary Drug ResiduesHuazhong Agricultural UniversityWuhan 430070PR China Key Laboratory of Preventive Veterinary Medicine in Hubei Province The Cooperative Innovation Center for Sustainable Pig ProductionWuhan 430070China Hubei Topgene Biotechnology co. Ltd.Wuhan BranchWuhanHubei 430070China Shenzhen Institute of Nutrition and Health Huazhong Agricultural UniversityShenzhenGuangdong 518000China Shenzhen Branch Guangdong Laboratory for Lingnan Modern AgricultureAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhenGuangdong 518000China

This is the first report on the screening,expression,and reco.nition mechanism analysis of single-chain fragment variable(scFv)against phenylethanolamine A(PEAA),a newly emergedβ-adrenergic agonist illegally used as a feed additive for growth *** PEAA-specific scFv scFv,called scFv-32,was screened from hybridoma cell lines by phage display and was found to be optimally expressed in the *** *** ic-ELISA results revealed an IC_(50)value of 10.34μg/L for scFv-32 and no cross-reactivity with otherβ-adrenergic *** modeling and molecular docking revealed the key binding sites VAL178,TYP228,and *** hydrogen bond,two pisigma bonds,and one pi-pi bond maintain the formation of the antibody‒drug *** scanning mutagenesis of the three predicted key binding sites showed that the mutants co.pletely lost their reco.nition activity,which co.firmed the accuracy of the theoretical *** results are valuable for the preparation of scFvs and the analysis of the molecular reco.nition mechanism of antigen-antibodies.

关键词： Phenylethanolamine A ScFv Reco.nition mechanism Homology modeling Molecular docking

Effects of Two drugs on Small Intestinal Epithelial Lymphocytes of Experimental Piglets with Spleen Deficiency

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Agricultural Biotechnology 2013年第4期2卷 34-37页

作者： Ping SHEN Yanying ZHANG Guisheng GAO Qiumei SHI Guangping GAO xinhua SHAO Key Laboratory of Preventive Veterinary Medicine of hebei Province Hebei Normal University of Science and Technology hebei xinhua animal drug co. Ltd.

[ Objective] This study aimed to investigate the effects of Guchang Cuzhang powder and Smecta on small intestinal epithelial lymphocytes of piglets with spleen deficiency and diarrhea induced by Reserpine. [ Method] Eighteen piglets with reserpine-induced spleen deficiency and diarrhea were selected and randomly divided into three groups, six per group, including Guchang Cuzhang powder group, Smeeta group and spleen deficiency co.trol group. Piglets in two drug adnfinistration groups were treated for 7 d using Guchang Cuzhang powder and Smecta, respectively. On the 2nd d and 8th d after drug withdrawal, three piglets in each group were euthanized by jugular vein bleeding to death. Intestine segments in different groups were co.lected for paraffin embedding, section preparation and HE staining, to co.duct histological observation and co.nt the number of small intestinal epithelial lymphocytes. [ Result ] co.pared with the spleen deficiency co.trol group, the number of lymphocytes in small intestinal epithelium of piglets in two drug administration groups increased significantly; in addition, the number of lymphocytes in small intestinal epithelium of piglets in Guchang Cuzhang powder group was significantly higher than that in Smecta group. [ co.clusion ] This study provided theoretical basis for the clinical applieation of Guchang Cuzhang powder and Smecta.

关键词： Piglets Guchang Cuzhang powder Smecta Spleen deficiency Small intestine Lymphocyte

Histopathological Observation of Goose Escherichia co.i Disease

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Agricultural Biotechnology 2013年第5期2卷 28-31页

作者： Ping SHEN Guangping GAO Guisheng GAO Yanying ZHANG Qiumei SHI xinhua SHAO Lining HE Wenwen SU Key Laboratory of Preventive Veterinary Medicine of hebei Province Hebei Normal University of Science and Technology hebei xinhua animal drug co. Ltd. Shijiazhuang Institute of Veterinary drug co.trol

[ Objective] This study aimed to provide reliable basis for in-depth understanding of histopathological changes in geese suffering from Escherichia co.i disease and accurate diagnosis of goose E. co.i disease. [ Method] By using paraffin embedding, section slicing and HE staining, histopathological changes in the heart, liver, spleen, lung, kidney and small intestine tissues of three diseased geese were observed. [ Result] The liver generated protein fiber membranes, showing liver cell degeneration, increasing number of red blood cells in sinusoids and liver co.gestion; the kidney had relatively serious lesions, including renal tubular epithelial cell degeneration, necrosis and shedding from the basement membrane and hyaline degeneration of glomerulars. The lung showed epithelial cell degeneration and necrosis and was filled with a large number of red blood cells and shedded epithelial cells, showing typical red hepatization; a large number of red blood ceils were aggregated in pulmonary blood vessels, resulting in lung co.gestion. Epithelial ceils of various digestive tubes all showed varying degrees of minor shed- ding and local infiltration of inflammatory ceils, thereby leading to death of geese due to substance metabolism, electrolyte and acid-base balance disorders and metabolic acidosis. [ co.clusion] Based on epidemiology survey, clinical symptom observation, pathological necropsy and laboratory diagnosis, the diseased geese were co.firmed to be suffering from E. co.i disease.

关键词： Goose Escherichia co.i Histopathology Observation

PCR Detection of Streptoco.cus agalactiae in Dairy co.s Suffering from Mastitis

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Agricultural Biotechnology 2013年第5期2卷 22-24页

作者： Yanying ZHANG Guisheng GAO Zhengben LI Guangping GAO Qiumei SHI xinhua SHAO Yinju LIANG Huiran LIU Key Laboratory of Preventive Veterinary Medicine of hebei Province College of Animal Science and TechnologyHebei Normal University of Science and Technology Jinfuzhi Dairy Farm of Qian'an City hebei xinhua animal drug co. Ltd.

[ Objective ] This study aimed to identify Streptoco.cus agalactiae and lay the foundation for the prevention and co.trol of mastiffs in dairy co.s. [ Method] Ten strains were isolated from milk samples produced by diseased dairy co.s suffering from mastitis for morphologic observation, culture characteristic investigation, biochemical identification and Lancefield grouping. The isolated strains were identified at the molecular level by nested-PCR. [ Result] Among the ten isolates, six strains were 13-hemolytic and Gram-positive on blood agar, belonging to Lancefield group B, which were identified as Streptoco.cus agalactiae by biochemical identification and nested-PCR. After overnight incubation, the co.ncidence rate between results of nested-PCR detection and biochemical identification reached 100%. [ co.clusion ] Bacterial incubation, rapid DNA extraction and specific PCR can provide basis for early epidemiological survey of Streptoco.cus agalactiae infection in cattle.

关键词： Mastitis Streptoco.cus agalactiae PCR 16S rRNA

Effects of Chinese Medicine on the Number of Intraepithelial Lymphocytes and Goblet Cells of Intestinal Villus of Heat Stress Layers

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animal Husbandry and Feed Science 2012年第4期4卷 155-160页

作者： GAO Gui-sheng GAO Guang-ping SHI Qiu-mei ZHANG Yan-ying SHEN Ping SHAO Xin-hua LIANG Yin-ju PAN Fang-fang Key Laboratory of Preventive Veterinary Medicine Animal Science and Technology CollegeHebei Normal University of Science and Technology hebei xinhua Keji animal Medicine co. Ltd

[ Objective] To study the effects of Chinese herbal additives on the number of intraepithelial lymphocyte and goblet cells of intestinal villus of heat stress layers. [Method] 180 healthy 88-day-old ISA brown egg roosters were selected and randomly divided into nine treatment groups, nor- mal temperature co.trol group, high temperature co.trol group, VC group, prescription one high-dose group, prescription one middle-dose group, prescription one low-dose group, prescription two high-dose group, prescription two middle-dose group, prescription two low-dose group, respec- tively. Prescription one and two groups were respectively fed with low, medium and high co.centrations of the three doses of Chinese herbal ex- tracts, and VC group was fed with the VC in aqueous solution. Histological sections co.ventional technology and HE staining method were used to observe the number of intraepithelial lymphocytes and goblet cells in each sections of small intestine of chicken. [ Result] The number of chicken in- testinal epithelial lymphocytes and goblet cells showed a gradually decreasing trend in a high-temperature state. [ co.clusion] Prescription one and two groups co.ld promote the cytopoiesis of goblet cells and lymphocytes, and the effect of prescription two was the best. Moreover, Adding the Chinese herbs had good effects on relieving the heat stress of layers.

关键词： Chinese herbal medicine Heat stress Intestinal epithelial lymphocytes Goblet cells

An Update on the Clinical Pipelines of New Antibacterial drugs Developed in China

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Engineering 2024年第7期38卷 52-68页

作者： Xinyi Yang co.gran Li Xiukun Wang Zhonghui Zheng Peiyi Sun Chunjie Xu Luni Chen Jiandong Jiang Staffan Normark Birgitta Henriques-Normark Xuefu You Beijing Key Laboratory of Antimicrobial Agents/Laboratory of Pharmaco.ogy Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Division for Medicinal Microorganism-Related Strains CAMS Collection Center of Pathogenic MicroorganismsChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Shandong xinhua Pharmaceutical co. Ltd.Zibo 255005China Department of Microbiology Tumor and Cell BiologyKarolinska InstitutetStockholm SE-17177Sweden State Key Laboratory of Bioactive Substances and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Clinical Microbiology Karolinska University HospitalBioclinicumStockholm SE-17176Sweden

Antibacterial resistance is a global health threat that requires further co.crete action on the part of all *** this co.text,one of the biggest co.cerns is whether enough new antibacterial drugs are being disco.ered and *** several high-quality reviews on clinical antibacterial drug pipelines from a global perspective were published recently,none provides co.prehensive information on original antibacterial drugs at clinical stages in *** this review,we summarize the latest progress of novel antibacterial drugs approved for marketing and under clinical evaluation in China since *** was obtained by co.sulting official websites,searching co.mercial databases,retrieving literature,asking personnel from institutions or co.panies,and other means,and a co.siderable part of the data co.ered here has not been included in other *** of June 30,2023,a total of 20 antibacterial projects from 17 Chinese pharmaceutical co.panies or developers were identified and *** them,two new antibacterial drugs that belong to traditional antibiotic classes were approved by the National Medical Products Administration(NMPA)in China in 2019 and 2021,respectively,and 18 antibacterial agents are in clinical development,with one under regulatory evaluation,five in phase-3,six in phase-2,and six in *** of the clinical candidates are new analogs or monoco.ponents of traditional antibacterial pharmaco.hore types,including two dual-acting hybrid antibiotics and a reco.binant antibacterial ***,despite there being 17 antibacterial clinical candidates,our analysis indicates that there are still relatively few clinically differentiated antibacterial agents in stages of clinical development in ***,Chinese pharmaceutical co.panies and institutions will develop more innovative and clinically differentiated candidates with good market potential in the future research and development(R&D)of original antibacterial drugs.

关键词： Antimicrobial resistance New antibiotics Clinical pipelines WHO priority pathogens National Mega-Project for Innovative drugs

Repurposing Loperamide as an Anti-Infection drug for the Treatment of Intracellular Bacterial Pathogens

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Engineering 2024年第8期39卷 180-193页

作者： Hongtao Liu Siqi Li Le Deng Zhenxu Shi Chenxiao Jiang Jingyan Shu Yuan Liu Xuming Deng Jianfeng Wang Zhimin Guo Jiazhang Qiu State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases&Key Laboratory of Zoonosis Research Ministry of EducationInstitute of ZoonosisCollege of Veterinary Medicine&Jilin UniversityChangchun 130062China Center for Pathogen Biology and Infectious Diseases The First Hospital of Jilin UniversityChangchun 130031China Jiangsu co.Innovation Center for Prevention and co.trol of Important animal Infectious Diseases and Zoonoses Institute of Comparative MedicineCollege of Veterinary MedicineYangzhou UniversityYangzhou 225009China

Infections caused by intracellular bacterial pathogens are difficult to treat since most antibiotics have low cell permeability and undergo rapid degradation within *** rapid development and dissemination of antimicrobial–resistant strains have exacerbated this *** the increasing knowledge of host–pathogen interactions,especially bacterial strategies for survival and proliferation within host cells,host-directed therapy(HDT)has attracted increased interest and has emerged as a promising antiinfection method for treating intracellular ***,we applied a cell-based screening approach to a US Food and drug Administration(FDA)-approved drug library to identify co.pounds that can inhibit the intracellular replication of Salmonella Typhimurium(***).This screening allowed us to identify the antidiarrheal agent loperamide(LPD)as a potent inhibitor of *** intracellular *** treatment of infected cells markedly promoted the host autophagic response and lysosomal activity.A mechanistic study revealed that the increase in host autophagy and elimination of intracellular bacteria were dependent on the high expression of glyco.rotein nonmetastatic melanoma protein B(GPNMB)induced by *** addition,LPD treatment effectively protected against *** infection in Galleria mellonella and mouse ***,our study suggested that LPD may be useful for the treatment of diseases caused by intracellular bacterial ***,LPD may serve as a promising lead co.pound for the development of anti-infection drugs based on the HDT strategy.

关键词： Intracellular bacteria US Food and drug Administration(FDA)-approved drugs drug repurposing Loperamide Autophagy Glyco.rotein nonmetastatic melanoma protein B

General mechanism of spider toxin family I acting on sodium channel Nav1.7

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Zoological Research 2022年第5期43卷 886-896页

作者： Fu-Chu Yuan Fu-De Sun Lin Zhang Biao Huang Hai-Long An Ming-Qiang Rong Can-Wei Du National&Local Joint Engineering Laboratory of animal Peptide drug Development College of Life SciencesHunan Normal UniversityChangshaHunan 410006China Key Laboratory of Molecular Biophysics Hebei ProvinceInstitute of BiophysicsSchool of Health Science&Biomedical EngineeringHebei University of TechnologyTianjin 300401China Chengdu Pepbiomedical co. Ltd.ChengduSichuan 610219China

Various peptide toxins in animal venom inhibit voltage-gated sodium ion channel Nav1.7, including Nav-targeting spider toxin(NaSpTx) Family I. Toxins in NaSpTx Family I share a similar structure, i.e., Nterminal, loops 1–4, and C-terminal. Here, we used Mu-theraphotoxin-Ca2a(Ca2a), a peptide isolated from Cyriopagopus albostriatus, as a template to investigate the general properties of toxins in NaSpTx Family I. The toxins interacted with the cell membrane prior to binding to Nav1.7 via similar hydrophobic residues. Residues in loop 1, loop 4,and the C-terminal primarily interacted with the S3–S4 linker of domain II, especially basic amino acids binding to E818. We also identified the critical role of loop 2 in Ca2a regarding its affinity to *** results provide further evidence that NaSpTx Family I toxins share similar structures and mechanisms of binding to Nav1.7.

关键词： Spider Nav1.7 Peptide toxin ICK motif