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Pleiotropy within gene variants associated with nonalcoholic fatty liver disease and traits of the hematopoietic system

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World Journal of Gastroenterology 2021年第4期27卷 305-320页

作者： Carlos Jose Pirola Adrian Salatino Silvia Sookoian Department of Molecular Genetics and Biology of Complex diseases National Scientific and Technical Research Council(CONICET)University of Buenos AiresInstitute of Medical Research(IDIM)Ciudad Autónoma de Buenos Aires C1427AROArgentina institute of Medical Research A Lanari University of Buenos AiresSchool of MedicineCiudad Autónoma de Buenos AiresCiudad Autónoma de Buenos Aires C1427AROArgentina Department of Clinical and Molecular Hepatology National Scientific and Technical Research Council(CONICET)University of Buenos AiresInstitute of Medical Research(IDIM)Ciudad Autónoma de Buenos Aires C1427AROArgentina

Genome-wide association studies of complex diseases,including nonalcoholic fatty liver disease(NAFLD),have demonstrated that a large number of variants are implicated in the susceptibility of multiple traits—a phenomenon known as pleiotropy that is increasingly being explored through phenome-wide association *** focused on the analysis of pleiotropy within variants associated with hematologic traits and *** used information retrieved from large public National Health and Nutrition Examination Surveys,Genome-wide association studies,and phenome-wide association studies based on the general population and explored whether variants associated with NAFLD also present associations with blood cell-related ***,we applied systems biology approaches to assess the potential biological connection/s between genes that predispose affected individuals to NAFLD and nonalcoholic steatohepatitis,and genes that modulate hematological-related traits—specifically platelet *** reasoned that this analysis would allow the identification of potential molecular mediators that link NAFLD with *** associated with platelet count are most highly expressed in the liver,followed by the pancreas,heart,and ***,genes associated with NAFLD presented high expression levels in the brain,lung,spleen,and *** mapping,gene prioritization,and functional analysis of the most significant loci(P<1×10-8)revealed that loci involved in the genetic modulation of platelet count presented significant enrichment in metabolic and energy balance *** conclusion,variants in genes influencing NAFLD exhibit pleiotropic associations with hematologic traits,particularly platelet ***,significant enrichment of related genes with variants influencing platelet traits was noted in metabolic-related ***,this approach yields novel mechanistic insights into NAFLD pathogenesis.

关键词： Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis Platelets Leukocytes Hematologic traits Genetics

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Different infection routes of avian influenza A (H5N1) virus in mice

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Integrative Zoology 2009年第4期4卷 402-408页

作者： Ruiqin SUN Jing LUO Yunying GAO Hongxuan HE National Research Center For Wildlife Born diseases and Key Laboratory of Animal Ecology and Conservation Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Northwest Agriculture and Forestry University YanglingShanxiChina

The continuing outbreaks of avian influenza A H5N1 virus infection in Asia and Africa have caused worldwide concern because of the high mortality rates in poultry,suggesting its potential to become a pandemic influenza virus in *** transmission route of the virus among either the same species or different species is not yet *** and BABL/c mice were inoculated with the H5N1 strain of influenza A virus isolated from *** animals were inoculated with 0.1 mL 106.83 TCID50 of H5N1 virus oronasally,intraperitoneally and using eye *** viruses were examined by virological and pathological *** addition,to detect horizontal transmission,in each group,healthy chicks and mice were mixed with those *** were detected in homogenates of the heart,liver,spleen,kidney and blood of the infected mice and *** antigen was not detected in the spleen,kidney or gastrointestinal tract,but detected by Plaque Forming Unit(PFU)assay in the brain,liver and lung without degenerative change in these organs(in the group inoculated using eye *** detection results for mice inoculated using eye drops suggest that this virus might have a different tissue tropism from other influenza viruses mainly restricted to the respiratory tract in *** chicken samples tested positive for the virus,regardless of the method of *** influenza A H5N1 viruses are highly pathogenic to chickens,but its virulence in other animals is not yet *** sum up,the results suggest that the virus replicates not only in different animal species but also through different routes of *** addition,the virus was detection not only in the respiratory tract but also in multiple extra-respiratory *** study demonstrates that H5N1 virus infection in mice can cause systemic disease and spread through potentially novel routes within and between mammalian hosts.

关键词： Avian influenza H5N1 virus inoculation route mice virulence.

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Cytotoxic effect of specific T cells from mice with experimental autoimmune uveitis on murine photoreceptor cells

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International Journal of Ophthalmology(English edition) 2020年第8期13卷 1180-1186页

作者： Zheng-Feng Liu Feng Zhang Da-Dong Guo Xue-Mei Pan Hong-Sheng Bi Medical School of Ophthalmology&Optometry Shandong University of Traditional Chinese MedicineJinan250355Shandong ProvinceChina Shandong Provincial Hospital Affiliated to Shandong University Jinan250021Shandong ProvinceChina Shandong Maternity&Child Health Care Hospital Jinan 250014Shandong ProvinceChina Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine Jinan250002Shandong ProvinceChina Shandong Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular diseases Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases in Universities of ShandongEye Institute of Shandong University of Traditional Chinese MedicineJinan 250002Shandong ProvinceChina

AIM:To investigate the cytotoxic effect of specific T cells from mice with experimental autoimmune uveitis(EAU)as well as their secreted interferon(IFN)-γand interleukin(IL)-17A on murine photoreceptor(661 W)***:An EAU model was established in female mice by injection of interphotoreceptor retinoid binding protein(IRBP)emulsion supplemented with complete Freund’s adjuvant(CFA)and Mycobacterium tuberculosis(TB).On day 12 after induction of EAU,specific T cells from spleen and lymph node tissues were isolated and cultured for 4 d and the levels of IFN-γand IL-17A in the supernatants were determined by enzyme-linked immunosorbent assays(ELISAs).T cells and their supernatants were added to 661 W cells to observe the alteration of cell morphology;IFN-γand IL-17A were separately added to 661 W cells to observe the effect of IFN-γand IL-17A on cell ***:The levels of IFN-γand IL-17A in the T cell supernatants were 1568.64±38.79 pg/m L and 1456.57±46.98 pg/mL,*** supernatants apparently inhibited 661 W cell proliferation(P<0.05).T cells could also attach to the surface of 661 W cells,and IFN-γshowed a more serious cytotoxic effect on 661 W cells than IL-17A,inhibiting cell proliferation(P<0.01).CONCLUSION:IFN-γand IL-17A from T cells of EAU mice model can exert cytotoxic effects on murine photoreceptor cell proliferation,and IFN-γshows more serious cytotoxic effects on murine photoreceptor cells than IL-17A.

关键词： T cell murine photoreceptor cell IFN-γ IL-17A experimental autoimmune uveitis mouse

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Infection-associated Hemophagocytic Syndrome in Critically Ill Patients with COVID-19

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Current Medical Science 2021年第1期41卷 39-45页

作者： Kun YANG Ming-you XING Ling-yu JIANG Yan-ping CAI Li-li YANG Na-na XIE Jia CHEN Wen-xia WANG Li WANG Ji-ling ZHU Ding-yu ZHANG Qiu-rong RUAN Jian-xin SONG Department of Dermatology and Venereology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Infectious diseases Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Clinical Immunology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Wuhan Jinyintan Hospital Wuhan 430011China institute of Pathology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Infectious diseases Renmin Hospital of Wuhan UniversityWuhan 430060China Department of Pathology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Infection-associated hemophagocytic syndrome(IAHS),a severe complication of various infections,is potentially *** study aims to determine whether IAHS occurs in critically ill patients with coronavirus disease 2019(COVID-19).We conducted a retrospective observational study on 268 critically ill patients with COVID-19 between February 1st,2020 and February 26th,***,clinical characteristics,laboratory results,information on concurrent treatments and outcomes were collected.A diagnosis of secondary hemophagocytic lymphohistiocytosis(sHLH)was made when the patients had an HScore greater than *** examinations were performed to confirm the presence of *** 268 critically ill patients with confirmed SARS-CoV-2 infection,17(6.3%)patients had an HScore greater than *** the 17 patients with sHLH *** interval from the onset of symptom of COVID-19 to the time of a diagnosis of sHLH made was 19 days and the interval from the diagnosis of sHLH to death was 4 ***(59%)patients were infected with only *** in the spleen and the liver,as well as lymphocyte infiltration in the liver on histopathological examinations,was found in 3 sHLH autopsy *** in sHLH patients with COVID-19 is *** SARS-CoV-2 is a potential trigger for *** recognition of IAHS in critically ill patients with COVID-19 could be beneficial for improving clinical outcomes.

关键词： severe acute respiratory coronavirus 2 coronavirus disease 2019 infection-associated hemophagocytic syndrome

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Preparation and Determination of Immunological Activities of Anti-HBV Egg Yolk Extraction

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Cellular & Molecular Immunology 2006年第1期3卷 67-71页

作者： Yanping Xu Weimin Zou Xuejun Zhan Shuhua Yang Daze Xie Sailiang Peng Laboratory of Immunology Jiangxi Institute of Medical Science Nanchang 330006 China Jiangxi institute of Medical Science Nanchang 330006 China

To prepare an effective immune preparation to treat hepatitis B, hens were immunized with hepatitis B vaccines, and then anti-HBV egg yolk extraction （anti-HBV EYE） was refined from egg yolk by a dialyzable method. Its chemical characteristics were identified by ultraviolet spectrum, HPLC, Lowry analysis and pharmacopocia-raleted methods. The specific immunological activity was examined by leukocyte adherence inhibition （LAI） in vitro and delayed type hypersensitivity （DTH） in vivo. Anti-HBV EYE was a small dialyzable substance with molecular weight less than 12 kD containing 18 kinds of amino acids. The preparation could obviously inhibit LAI and DTH which was similar to hepatitis B virus-specific transfer factor of pig spleen. However, there were no similar effects observed in the nonspecific transfer factor （NTF） group, control egg yolk extraction （CEYE） group and hepatitis A virus （HAV） group. The results suggested that anti-HBV EYE contained hepatitis B virus-specific transfer factor （STF） and had the antigen-specific cell immune activity similar to PSHBV-TF. The STF obtained from egg yolk of the hens immunized with specific antigen, might be a potential candidate for immunoregulation in hepatitis B prevention and treatment.

关键词： egg yolk extraction hepatitis B virus specific transfer factor immunological activity

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Thioredoxin peroxidase secreted by Echinococcus granulosus induces the alternative activation of macrophages

Thioredoxin peroxidase secreted by Echinococcus granulosus i...

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第十届全国免疫学学术大会

作者： Hui Wang Jun Li Wenbao Zhang Hao Wen State Key Laboratory Incubation Base of Xinjiang Major diseases Research Clinical Medical Research Institute The First Affiliated Hospital of Xinjiang Medical University

Background: Alternatively activated macrophages(AAMacs) are key to promoting Th2 responses and have been associated with a variety of roles during helminth infection. Echinococcus infection induces a polarized Th2 immune response in its intermediate hosts. Here we investigated the effects of Echinococcus infection and a secreted protein, thioredoxin peroxidase(TPx) derived from E.g, on murine macrophage phenotype in vivo and in vitro. Methods: Peritoneal exudate cells(PECs) from E.g and E.m infection mice were harvested by adherence method and then the activation status of macrophages was analyzed by evaluating the expression of genetic markers of alternativeactivation(Fizz1, Ym1, and Arg1). Then we constructed the recombinant Eg TPx and its inactive recombinant variant(rv Eg TPx) with active site Cys residues replaced by Gly and injected hydatid cyst fluid(HCF) or purified Eg TPx and rv Eg TPx intraperitoneally 6 or 9 times, delivered on alternate days. After 2 days of the final injection, PECs were harvested and analyzed the activation status of macrophages. T-cell cytokine production was assessed by culturing spleen cells with HCF and/or recombinant Eg TPx. Supernatants were removed after 72 h and the concentrations of cytokines were measured by CBA kit. Results: AAMacs were recruited to the peritoneum of mice after E.g and E.m infection. Administration of HCF and recombinant Eg TPx or rv Eg TPx could also induced the recruitment of AAMacs to the peritoneum indicated that the immunomodulatory property of Eg TPx is not due to its antioxidant activity, as an inactive recombinant variant could also induce AAMacs and Th2 responses. In addition, in vitro studies showed that HCF and Eg TPx or rv Eg TPx can directly converts bone marrow macrophages to an alternatively activated phenotype. Conclusion: Our data suggest that the Eg TPx, a secreted antioxidant enzyme, activates macrophages as an initial step in the induction of Th2 responses by E.g infection to defense agai

关键词： macrophage Echinococcosis secretory protein EgTPx

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Pro-inflammatory microenvironment and systemic accumulation of CXCR3+cell exacerbate lung pathology of old rhesus macaques infected with SARS-CoV-2

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Signal Transduction and Targeted Therapy 2021年第10期6卷 3033-3044页

作者： Hong-Yi Zheng Xiao-Yan He Wei Li Tian-Zhang Song Jian-Bao Han Xiang Yang Feng-Liang Liu Rong-Hua Luo Ren-Rong Tian Xiao-Li Feng Yu-Hua Ma Chao Liu Ming-Hua Li Yong-Tang Zheng Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnanChina Kunming College of Life Science University of Chinese Academy of SciencesKunmingYunnanChina Kunming National High-Level Biosafety Research Center for Non-Human Primates Center for Biosafety Mega-ScienceKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnanChina National Resource Center for Non-Human Primates National Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnanChina Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory) GuangzhouChina

Understanding the pathological features of severe acute respiratory syn drome coronavirus 2(SARS-CoV-2)infect io n in an animal model is crucial for the treatment of coronavirus disease 2019(COVID-19).Here,we compared imnnunopathological changes in young and old rhesus macaques(RMs)before and after SARS-CoV-2 infection at the tissue *** analysis of multiplex immunofluoresce nee staining images of formali n-fixed paraffi n-embedded(FFPE)sections showed that SARS-CoV-2 infectio n specifically induced elevated levels of apoptosis,autophagy,and nuclear factor kappa-B(NF-kB)activation of angiotensirv convert!ng enzyme 2(ACE2)+cells,and increased interferon a(IFN-a)-and interleukin 6(IL-6)-secreting cells and C-X-C motif chemokine receptor 3(CXCR3)+cells in lung tissue of old *** pathological pattern,which may be related to the age-related pro-inflammatory microenvironment in both lungs and spleens,was significantly correlated with the systemic accumulation of CXCR3+cells in lungs,spleens,and peripheral ***,the ratio of CXCR3+to T-box protein expression in T cell(T-bet)+(CXCR3+/T-bet+ratio)in CD8+cells may be used as a predictor of severe *** findings uncovered the impact of aging on the immunopathology of early SARS-CoV-2 infection and demonstrated the potential application of CXCR3+cells in predicting severe COVID-19.

关键词： CXCR3 spleen lung

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Highly Sensitive and Specific Monoclonal Antibody-Based Serological Methods for Rice Ragged Stunt Virus Detection in Rice Plants and Rice Brown Planthopper Vectors

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Journal of Integrative Agriculture 2014年第9期13卷 1943-1951页

作者： LIU Huan SONG Xi-jiao NI Yue-qun LU Li-na ZHOU Xue-ping WU Jian-xiang institute of Biotechnology College of Agriculture & Biotechnology Zhejiang University

Rice ragged stunt virus（RRSV） is a serious rice disease in Asia, causing serious yield losses on rice. The capsid protein（CP） gene of the major outer capsid protein of RRSV was expressed in Escherichia coli BL21（DE3） using the pMAL-C2 X expression vector. The recombinant protein was used as the immunogen to immunize BALB/c mice. A hybridoma cell line 8A12 secreting monoclonal antibody（MAb） against RRSV was obtained by fusing mouse myeloma cells（Sp 2/0） with spleen cells from the immunized BALB/c mice. Western blot analysis showed that the MAb 8A12 can specifically react with RRSV CP. Using the MAb, an antigen-coated-plate enzyme-linked immunosorbent assay（ACP-ELISA）, a dot enzyme-linked immunosorbent assay（dot-ELISA）, and immunocapture-RT-PCR（IC-RT-PCR） assay were developed to detect RRSV. The established ACP-ELISA, dot-blot ELISA and IC-RT-PCR methods could detect RRSV in infected rice tissue crude extracts with dilutions of 1：40 960, 1：1 280 and 1：655 360（w/v, g mL-1）, respectively. The ACP-ELISA and dot-blot ELISA methods could detect RRSV in infected insect vector crude extracts with dilutions of 1：12 800 and 1：1 600（an individual planthopper μL-1）, respectively. The field survey revealed that Rice ragged stunt disease occurs on rice in Hainan, Yunnan, Guangxi, Sichuan, Guizhou, Fujian, Hunan, Jiangxi and Zhejiang in China.

关键词： Rice ragged stunt virus rice brown planthopper monoclonal antibody antigen-coated-plate enzyme-linked immunosorbent assay(ACP-ELISA) dot-blot ELISA immunocapture RT-PCR

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Antigen-capture ELISA for grass carp reovirus 873

Antigen-capture ELISA for grass carp reovirus 873

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中国水产学会鱼病专业委员会2013年学术研讨会

作者： Jing Hongli Gao long ying Zhang Min Wang Na lin xiangmei Wu shaoqiang Research Centre of Aquatic Animal diseases the Institute of Animal QuarantineChinese Academy of Inspection and Quarantine Shen zhen Entry-exit Inspection and Quarantine Bureau

An antigen-capture ELISA for grass carp reovirus 873(GCRV 873)was *** employs polyclonal antiserum directed against grass carp reovirus *** antigen boundby the capture mAb(16B7)was detected by addition of the goat anti-mouse Ig peroxidaseconjugation,followed by addition of the enzyme ***-873 was detected in culturesupernatants(6.25×105pfu/ml)and in ectracts of kidney and spleen of infected grass *** was highly specific:Viral hemorrhagic septicemia virus,Infectious haematopoietic necrosisvirus,spring viraemia of carp virus,Epizootic haematopoietic necrosis virus,Chinook salmonreovirus could not be detected by the antigen-capture ELISA for GCRV 873.

关键词： Grass carp reovirus(GCRV) fish viral diseases Antigen-capture ELISA

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Preliminary study on investigation of zoonotic visceral leishmaniasis in endemic foci of Ethiopia by detecting Leishmania infections in rodents

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Asian Pacific Journal of Tropical Medicine 2017年第4期10卷 396-400页

作者： Wossenseged Lemma Asrat Bizuneh Habte Tekie Habtamu Belay Hirut Wondimu Aysheshm Kassahun Welelta Shiferaw Meshesha Balkew Ibrahim Abassi Gad Baneth Asrat Hailu Department of Medical Parasitology School of Biomedical and Laboratory SciencesCollege of Medicine and Health SciencesUniversity of Gondar Department of Microbiology Immunology and ParasitologySchool of MedicineAddis Ababa University Department of Zoological Sciences College of Natural ScienceAddis Ababa University Department of Parasitology Faculty of ScienceCharles University in Prague Aklilu Lemma institute of Pathobiology Addis Ababa University Department of Microbiology and Molecular Genetics the Institute for Medical Research Israel-Canadathe Kuvin Centre for the Study of Infectious and Tropical Diseasesthe Hebrew University-Hadassah Medical School School of Veterinary Medicine Hebrew University

Objective:To investigate the zoonotic visceral leishmaniasis(ZVL) by identification of the most probable reservoir hosts using parasite isolation and analysis of a possible transmission dynamics of the disease in extra-domestic agricultural fields and rural ***:Rodents were collected from selected study sites in kala-azar endemic areas based on information for localities of kala-azar cases for screening of Leshmania infections using parasitological,serological and polymerase chain reaction(PCR) from March.2013 to January,***(Clorketam Veterinary) was used to anaesthesize the rodents according the prescribed dosage(average 2 mg/kg for intra-venous route).The blood obtained using sterile needle was dropped into sterile filter paper and allowed to air dry before sealing in plastic *** tissues from liver,spleen and skin were macerated in Locke's solution before transferring them into NNN *** and touch smears of liver,spleen,skin and bone marrow were prepared for fixing using methanol and staining by Giemsa stain for *** tissues were also ascd for DNA extractions and PCR amplification of Leishmania ***:A total of 335 rodents(13 species) were analyzed by sampling internal *** infection rate by PCR was 11.1%(6/54) for Arvicanthis nilothicas compared to 17.6%(3/17) and 12.5%(2/16) for Acomys cahirinus and Tarera(C) robustus *** all the infections were found from bone marrow samples(8/48 or 16.7%) compared with 1/91(1.1%) liver,2/87(2.2%) spleen and 0/87(0%) *** all study sites with past human VL cases,rodents and proved vectors shared similar ***:Leishmania donovani might circulate among different species of rodents in kala-azar endemic lowlands and valleys of Ethiopia by Phlebotamus orientalis and Phlebotomus *** studies to substantiate the preliminary data on the possible role of these rodents arc urgently needed.

关键词： Zoonotic visceral leishmaniasis Phlebotomus orientalis Phlebotomus martini Leishmania donovani Reservoir hosts Ethiopia

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