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Leptin administration exacerbates thioacetamide-induced liver fibrosis in mice

World Journal of Gastroenterology 2005年第31期11卷 4822-4826页

作者： Kai Dai Jun-ying Qi de-ying tian department of Infectious Diseases Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 Hubei Province China

AIM： To investigate the effects of leptin administration on liver fibrosis induced by thioacetamide （TAA）. METHODS： Twenty-four male C57BI/6 mice were randomly allocated into four groups, which were intra-peritoneally given saline （2 mL/kg）, leptin （1 mg/kg）, TAA （200 mg/kg）, TAA （200 mg/kg） plus leptin （1 mg/kg） respectively, thrice a week. All mice were killed after 4 wk. The changes in biochemical markers, such as the levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in serum and superoxide dismutase （SOD）, malondialdehyde （MDA） in liver were determined. For histological analysis, liver tissues were fixed with 10% buffered formalin, embedded with paraffin. Hematoxylin-eosin （HE） staining and picric acid-Sirius red dyeing were performed. The level of α1（I） procollagen mRNA in liver tissues was analyzed by RT-PCR. RESULTS： Apparent liver fibrosis was found in TAA group and TAA plus leptin group. Compared to saline group, the levels of ALT and AST in serum and MDA in liver increased in TAA group （205.67±27.69 U/L vs 50.67±10.46 U/L, 177.50±23.65 U/L vs76.33±12.27 U/L, 2.60±0.18 nmol/mg pro vs 1.91±0.14 nmol/mg pro, P〈0.01） and in TAA plus leptin group （256.17±22.50 U/L vs 50.67±10.46 U/L, 234.17±27.37 U/L vs76.33±12.27 U/L, 2.97±0.19 nmol/mg pro vs 1.91±0.14 nmol/mg pro, P〈0.01）. The level of SOD in livers decreased （51.80±8.36 U/mg pro vs 81.52±11.40 U/mg pro, 35.78±6.11 U/mg pro vs81.52± 11.40 U/mg pro, P〈0.01） and the level of α1（I） procollagen mRNA in liver tissues also increased （0.28±0.04 vs0.11± 0.02, 0.54±0.07 vs0.11±0.02, P〈0.01）. But no significant changes were found in leptin group and saline group. Compared to TAA group, ALT, AST, MDA, and α1（I） procollagen mRNA and grade of liver fibrosis in TAA plus leptin group increased （256.17±22.50 U/L vs 205.67± 27.69 U/L, P〈0.05; 234.17±27.37 U/L vs 177.50±23.65 U/L, P〈0.05; 2.97±0.19 nmol/mg pro vs 2.60±0.18 nmol/mgpro, P〈0.05, 0.54±0.07 vs0.28±0.04, P〈0.01, 3.17 vs 2.00, P〈0.05）, and

关键词： Liver fibrosis Leptin α1(I) procollagen

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Significance of serum IgA in patients with acute hepatitis E virus infection

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World Journal of Gastroenterology 2006年第24期12卷 3919-3923页

作者： de-ying tian Yan Chen Ning-Shao Xia department of Infectious Diseases Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 Hubei Provice China Ning-Shao xia Key Laboratory of Education for Cell Biology and Tumor Cell Engineering Xiamen University Xiamen 361005 Fujian Provice China Key Laboratory of Education for Cell Biology and Tumor Cell Engineering Xiamen University Xiamen 361005 Fujian Provice China

AIM： To study the significance of serum anti-hepatitis E virus （HEV） IgA in patients with hepatitis E. METHODS： A new method was established to assay anti-HEY IgA, which could be detected in the middle phase of the infection. We compared anti-HEV IgA assay with anti-HEV IgM and anti-HEV IgG assay in sera from 60 patients with positive HEV-RNA. RESULTS： The 60 patients with positive HEV-RNA had both anti-HEV IgA and anti-HEV IgM and 410 patients with negative HEV-RNA were used as control. Periodic serum samples obtained from 60 patients with hepatitis E were tested for HEV RNA, anti-HEV IgM, anti-HEV IgA and anti-HEV IgG. Their HEV-RNA was detectable in the serum until 20 ±11 d. We used anti-HEV IgM and anti-HEV IgA assay to detect HEV infection and positive results were found in 90 ± 15 d and 120 ±23 d respectively, the positive rate of anti-HEV IgA was higher than that of anti-HEV IgM and HEV-RNA （P 〈0.05）. CONCLUSION： The duration of anti-HEV IgA in serum is longer than that of anti-HEV IgM, and anti-HEV IgA assay is a good method to detect HEV infection.

关键词： Hepatitis E virus RNA Anti-HEV IgM Anti-HEV IgA

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Effects of hepatitis E virus infection on interferon production via ISG15

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World Journal of Gastroenterology 2018年第20期24卷 2173-2180页

作者： Min Wang ying Huang Man He Wen-Ju Peng de-ying tian Tongji Hospital Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030Hubei ProvinceChina The First Affiliated Hospital of Sun Yat-sen University Guangzhou 510700Guangdong ProvinceChina

AIM To assess the effects of hepatitis E virus(HEV) on the production of type Ⅰ interferons(IFNs) and determine the underlying *** We measured the production of interferon(IFN)-alpha and-beta(-α/β) in genotype 3 HEV-infected C3 A cells at different time points(0, 8, 12, 24, 48, 72 and 120 h) by enzyme-linked immunosorbent assay(ELISA). The expression levels of IFN-stimulated gene(ISG)15 in HEVinfected C3A cells at different time points were tested by western blotting. The plasmid-expressing open reading frame 3(ORF3) or control plasmids(green fluorescent protein-expressing) were transfected into C3A cells, and the levels of IFN-α/β and ISG15 were evaluated, respectively. Furthermore, the plasmid-expressing ISG15 or small interfering RNA-inhibiting ISG15 was transfected into infected C3A cells. Then, the production of IFN-α/β was also measured by *** We showed that genotype 3 HEV could enhance the production of IFN-α/β and induce elevation of ISG15 in C3A cells. HEV ORF3 protein could enhance the production of IFN-α/β and the expression of ISG15. Additionally, ISG15 silencing enhanced the production of IFN-α/β. Overexpression of ISG15 resulted in the reduction of IFN-α/β.CONCLUSION HEV may promote production of IFN-α/β and expression of ISG15 via ORF3 in the early stages, and increased ISG15 subsequently inhibited the production of IFN-α/β.

关键词： open reading frame 3 interferon-stimulated gene 15 interferon-alpha Hepatitis E virus interferonbeta

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Hepatitis B virus upregulates host expression of α-1,2-mannosidases via the PPARα pathway

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World Journal of Gastroenterology 2016年第43期22卷 9534-9543页

作者： Song Hu Li-Bin Jiang Xiao-Jing Zou Wei Yi de-ying tian Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

AIM To assess the effects of hepatitis B virus(HBV) on the expression of host α-1,2-mannosidases and determine the underlying *** We measured the expression levels of MAN1A1, MAN1A2, MAN1B1, and MAN1C1 in cell lines HepG 2.2.15, HepN 10, HepA D38 and Hep G2 by Western blot. Viral antigens(HBs Ag and HBe Ag) in the culture medium were measured using the chemiluminescence method. HBV DNA quantification assays were performed using a commercial real-time PCR kit. Protein levels of human liver tissue α-1,2-mannosidases were also evaluated by Western blot. Plasmids containing seven individual viral genes of HBV(PTT22-HBx, PTT22-HBs, PTT22-pre S2, PTT22-pre S1, PTT22-HBc, PTT22-HBe, and PTT22-HBp) or control plasmids(PTT22-vector) were transfected into Hep G2 cells. MK886(PPARα) and GW9662(PPARγ) inhibitors were used to explore the effects of HBV on α-1,2-mannosidase expression after the PPARα and PPARγ pathways were *** We showed that the expression of α-1,2-mannosidases was higher in stably transfected HBV cells than in controls. The expression levels of α-1,2-mannosidase were higher in AD38 cells than those in ND10 cells, which were in turn greater than those in G2.2.15 cells, and positively correlated with the expression of HBsA gin all the cell lines. Levels of α-1,2-mannosidase in nontumorous liver tissues of HBV-related HCC patients were also higher than in the tissues from non-HBVrelated HCC patients. Moreover, transfecting Hep G2 cells with a component of the HBV viral envelope also increased the expression of α-1,2-mannosidases. However, this envelope protein component could not induce MAN1C1 expression in the presence of a PPARα inhibitor, MK886. We also found that MK886 did not affect the expression of MAN1C1 in AD38 cells without tetracycline in the culture medium. This phenomenon was not observed in the case of *** Our results indicate that HBV increases the expression of α-mannosidases both in vitro and in vivo via ac

关键词： Hepatitis B Pattern recognition receptors α-Mannosidase Glycosylation dendritic cells

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Serological prevalence and risk factor analysis of hepatitis G virus infection in Hubei Province of China

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World Journal of Gastroenterology 2000年第4期6卷 585-587页

作者： de ying tian Dao Feng Yang Ning Shao Xia Zheng Gang Zhang Hong Bo Lei Yuan Cheng Huang department of Infectious Diseases Tongji HospitalTongji Medical UniversityWuhan 430030Hubei ProvinceChina Unit of National Genetic Engineering Xiamen UniversityXiamen 361005Fujian ProvinceChina

Hepatitis G virus (HGV),also known as GB virus C, is a recently cloned virus which may be associated with human non A-E hepatitis[1，2] It is parenterally transmitted and usually coinfected or superinfected with hepatitis B or hepatitis C virus[3-5]. Some investigations have been reported on the seroprevalence and molecular prevalence of HGV infection in different areas and different population[6-15]. Current infection of HGV is diagnosed by detection of HGV RNA, and past infection with HGV is detectable by testing anti-HGV envelope protein (E2)[16-17]. To investigate the prevalence of HGV in Hubei Province, a central area of the People's Republic of China, ELISA and RT-PCR were employed to detect serum anti-HGV and HGV RNA in 1516 patients who were divided into 16 groups.

关键词： hepatitis G virus enzyme linked immunoabsorbent assay risk factors polymerase chain reaction prevalence transcription genetic

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Uric acid enhances T cell immune responses to hepatitis B surface antigen-pulsed-dendritic cells in mice

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World Journal of Gastroenterology 2007年第7期13卷 1060-1066页

作者： Xiao-Jun Ma de-ying tian Dong Xu Dao-Feng Yang Hui-Fen Zhu Zhi-Hui Liang Zheng-Gang Zhang department of Infectious Diseases TongjiHospital Tongji Medical College Huazhong University ofScience and Technology Wuhan 430030 Hubei Province China department of Immunology Tongji Medical College Huazhong University of Science andTechnology Wuhan 430030 Hubei Province China

AIM： To study the induction of T cellular immune responses in BALB/c mice immunized with uric acid and dendritic cells （DCs） pulsed with hepatitis B virus surface antigen （HBsAg）. METHODS： DCs were generated from bone-marrow cells of BABL/c mice, and then pulsed or unpulsed with HBsAg protein （HBsAg-pulsed-DCs or unpulsed-DCs） in vitro. BABL/c mice were immunized with HBsAg-pulsed- DCs （1 × 10^6） and uric acid, injected through the tail vein of each mouse. The mice in control groups were immunized with HBsAg-pulsed-DCs alone, unpulsed- DCs alone or 200 μg uric acid alone or PBS alone. The immunization was repeated 7 d later. Cytotoxic T lymphocytes （CTLs） in vivo were determined by the CFSE labeled spleen lysis assay. Spleen cells or spleen T cells were isolated, and re-stimulated in vitro with HBsAg for 120 h or 72 h. Production of IFN-γ, and IL-4 secreted by spleen cells were determined by ELISA method; proliferation of spleen T cells were detected by flow cytometry. RESULTS： The cytotoxicities of HBsAg-specific-CTLs, generated after immunization of HBsAg-pulsed-DCs and uric acid, were 68.63% ±11.32% and significantly stronger than that in the control groups （P 〈 0.01）. Compared with control groups, in mice treated with uric acid and HBsAg-pulsed-DCs, the spleen T cell proliferation to HBsAg re-stimulation was stronger （1.34 ± 0.093 vs 1.081±0.028, P 〈 0.01）, the level of IFN-t, secreted by splenocytes was higher （266.575 ± 51.323 vs 135.223 ±32.563, P 〈 0.01） , and IL-4 level wasower （22.385 ± 2.252 vs 40.598 ± 4.218, P 〈 0.01）. CONCLUSION： Uric acid can strongly enhance T cell immune responses induced by HBsAg-pulsed-DCs vaccine. Uric acid may serve as an effective adjuvant of DC vaccine against HBV infection.

关键词： Uric acid dendritic cells Hepatitis B virussurface antigen Cytotoxic T lymphocytes Mouse

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Fibrinogen-like protein 2 fibroleukin expression and its correlation with disease progression in murine hepatitis virus type 3-induced fulminant hepatitis and in patients with severe viral hepatitis B

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World Journal of Gastroenterology 2005年第44期11卷 6936-6940页

作者： Chuan-Long Zhu Wei-Ming Yan Fan Zhu Yong-Fen Zhu Dong Xi de-ying tian Gary Levy Xiao-Ping Luo Qin Ning Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 Hubei Province China Toronto General Hospital of University of Toronto Toronto MSG 2N2 Canada

AIM： To evaluate the expression of fibrinogenlike protein 2 （fgl2） and its correlation with disease progression in both mice and patients with severe viral hepatitis. METHODS： Balb/cJ or A/J mice were infected intraperitoneally （ip） with 100 PFU of murine hepatitis virus type 3 （MHV-3）, liver and serum were harvested at 24, 48, and 72 h post infection for further use. Liver tissues were obtained from 23 patients with severe acute chronic （AOC） hepatitis B and 13 patients with mild chronic hepatitis B. Fourteen patients with mild chronic hepatitis B with cirrhosis and 4 liver donors served as normal controls. In addition, peripheral blood mononuciear cells （PBMC） were isolated from 30 patients （unpaired） with severe AOC hepatitis B and 10 healthy volunteers as controls. Procoagulant activity representing functional prothrombinase activity in PBMC and white blood cells was also assayed. A polyclonal antibody against fgl2 was used to detect the expression of both mouse and human fgl2 protein in liver samples as well as in PBMC by immunohistochemistry staining in a separate set of studies. Alanine aminotransferase （ALT） and total bilirubin （TBil） in serum were measured to assess the severity of liver injury.RESULTS： Histological changes were found in liver sections 12-24 h post MHV-3 infection in Balb/cJ mice. In association with changes in liver histology, marked elevations in serum ALT and TBil were observed. House fgl2 （mfgl2） protein was detected in the endothelium of intrahepatic veins and hepatic sinusoids within the liver 24 h after MHV-3 infection. Liver tissues from the patients with severe AOC hepatitis B had classical pathological features of acute necroinflammation. Human fgl2 （hfgl2） was detected in 21 of 23 patients （91.30%） with severe AOC hepatitis B, while only 1 of 13 patients （7.69%） with mild chronic hepatitis B and cirrhosis had hfgl2 mRNA or protein expression. Twenty-eight of thirty patients （93.33%） with severe AOC hepatitis B and 1 of 10 wit

关键词： Viral hepatitis Fgl2 Murine hepatitis virus Gene expression

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The Clinical Effects Study of Hepatic Failure by Intraperitoneal Injection of Antibiotics,Intravenous Injection of Terlipressin,and Combined Therapy of Coloclysis and Plasma Exchange

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国际感染病学（电子版） 2012年第1期1卷 51-57页

作者： Hui Li Ya-ling Wang de-ying tian department of Liver Diseases No.3 Municipal People's Hospital of Kunming department of Infectious Diseases Tongji HospitalTongji MedicalCollegeHuazhong University of Science and Technology

Objective To observe the therapeutic effects of intraperitoneal injection of antibiotics,intravenous injection of terlipressin,and combined treatment of coloclysis and plasma exchange on hepatic failure(HF),the subjects included 494 inpatient cases of hepatic failure who were treated in department of Infectious Diseases,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China from 1997 *** The patients that met the inclusion criteria were divided into intraperitoneal antibiotic injection group,intravenous terlipressin injection group,coloclysis group,plasma exchange group,combination group of coloclysis and plasma exchange in terms of treatment given and a control group was set up for each of the treatment *** the intraperitoneal injection group,the prognosis and changes in clinical manifestations were observed in HF patients complicated with spontaneous peritonitis(SBP).In terlipressin injection group,HF patients complicated with hepatorenal syndrome(HRS) were observed for prognosis and changes in serum *** the combination group,the improvement in serum total bilirubin and prothrombin activity were *** Two weeks after intraperitoneal injection of antibiotics,the ease ratios of abdominal pain,pressure pain and rebound tenderness were 87.64%,82.02%and 82.02%in the intraperitoneal injection group,respectively and the volume of ascites obviously decreased in 69 patients(77.53%).The survival rate in intraperitoneal injection group was significantly higher than in control group(P = 0.004).Four to eight days after the intravenous injection of terlipressin,the survival rate and the rate of serum creatinine decline of the treatment group were significantly higher than those in the control group(P = 0.003,P = 0.000).After 4 weeks of treatment,the ratio of clinical symptoms improvement(acratia,anorexia,abdominal distension,constipation) in coloclysis group were60.27%,57.53%,91.78%and 94.52%,in plas

关键词： Hepatic failure Intraperitoneal injection of antibiotics Elevation coloclysis Terlipressin Plasma exchange

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An Analysis of Epidemiological Characteristics and the Clinical Features of 394 Cases of Sporadic Acute Hepatitis E in Southwest China from 2008 to 2010

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国际感染病学（电子版） 2014年第3期3卷 114-121页

作者： Hui Li Xiao-Dong Yang Yong-Rui Yang Si-Yuan Gao de-ying tian Quan Yuan department of Liver Diseases No. 3rd People’s Hospital of Kunming department of Infectious Diseases Tongji Hospital Tongji Medical College Huazhong University of Science and Technology National Institute of Diagnostics and Vaccine development in Infectious Diseases School of Life Science Xiamen University

Background and Aims Recently, epidemiology studies of hepatitis E in different areas are attracted more attention. Extensive studies of prevalent status and clinical manifestations could help us to broaden our knowledge, so as to excellently prevent and treat hepatitis E. The study analyzed the epidemiological characteristics and clinical features of 394 cases of sporadic acute hepatitis E(AHE) in Southwest of China from 2008 to 2010. Methods The clinical data of 394 cases with sporadic AHE in Southwest of China from 2008 to 2010 were *** In the 394 cases with sporadic AHE, the ratio of male/female was 1.432∶1, and the mean age was(31.53 ± 18.12) years. Totally, 94(23.86%) patients aged under 18, 271(68.78%) patients aged between 18 and 60, and 29(7.36%) patients aged above 60. The incidence rate was significantly increased in summer(P = 0.000), especially in May(14.72%) and July(13.71%). In addition, the characteristics of occupation and ethnic group distribution were migrant laborers(106/394, 26.90%) and Han people(365/394, 92.64%). The length of stay, incidence of jaundice, the peak value of total bilirubin and alanine aminotransferase in male patients were all higher than those in female patients significantly(P decreased levels of ALT/ALB/CHE, increased levels of TBil, and increased incidence of jaundice and fatigue were associated with older age significantly(P dexes among anti-HEV-Ig G positive group, anti-HEV-Ig M positive group and antiHEV-Ig M/Ig G both positive group(P > 0.05).Conclusions Four epi

关键词： Acute hepatitis E Epidemiology Clinical feature Sporadic infection Hepatitis Evirus

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慢性乙型重型肝炎与血清血小板活化因子的相关性

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世界华人消化杂志 2009年第36期17卷 3740-3744页

作者：马科许东田德英华中科技大学同济医学院附属同济医院感染科湖北省武汉市430030

目的:探讨血小板活化因子变化在慢性乙型重型肝炎预后评估中的临床价值.方法:将49例慢性乙型重型肝炎患者分为好转组(n=26)和死亡组(n=23),另选择20例健康体检者作为对照组.重型肝炎患者均采用综合治疗.分别检测治疗前和治疗后血清内毒... 详细信息

目的:探讨血小板活化因子变化在慢性乙型重型肝炎预后评估中的临床价值.方法:将49例慢性乙型重型肝炎患者分为好转组(n=26)和死亡组(n=23),另选择20例健康体检者作为对照组.重型肝炎患者均采用综合治疗.分别检测治疗前和治疗后血清内毒素和人血小板活化因子值,统计慢性乙型重型肝炎患者死亡率.结果:49例慢性乙型重型肝炎患者内毒素血症发生率为85.71%(42/49),死亡组和好转组血清内毒素浓度均高于正常对照组(均P<0.01);好转组治疗后血清ET浓度明显低于治疗前(P<0.01);死亡组和好转组的血清PAF含量均高于正常对照组(均P<0.01);好转组治疗后血清PAF浓度明显低于治疗前(P<0.01);发生内毒素血症的患者PAF浓度明显高于未发生内毒素血症的患者(P<0.05);经Logistic回归分析,TBIL、ET、PAF与慢性乙型重型肝炎患者预后成正相关(P<0.05或0.01,OR=0.799、0.040、2.007),PTA与慢性乙型重型肝炎患者预后成负相关(P<0.05,OR=0.015),其中以PAF与预后的关系最为密切.结论:血小板活化因子下降与肝功能改善、临床表现好转有密切关系,慢性乙型重型肝炎患者血小板活化因子含量可作为评价重型肝炎预后的指标之一.

关键词：慢性乙型重型肝炎血小板活化因子内毒素血症预后

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