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Hepatocyte nuclear factor 4α induces a tendency of differentiation and activation of rat hepatic stellate cells

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World Journal of Gastroenterology 2015年第19期21卷 5856-5866页

作者： Kai Liu Ming-Gao Guo Xiao-Li Lou Xiao-Ya Li Yang Xu Wei-Dan Ji Xuan-Dong Huang Jia-He Yang Ji-Cheng Duan Department of Molecular Oncology and Laparoscopic Surgery Eastern Hepatobiliary Surgical Hospital and National Center of Liver Cancer Second Military Medical University Department of Surgery Shanghai Sixth People’s Hospital Shanghai Jiao-Tong University Department of Plastic and Reconstructive Surgery Changhai Hospital Second Military Medical University Department of Oncological Surgery Second People’s Hospital of Huai’an

AIM: To investigate the effect of hepatocyte nuclear factor 4α(HNF4α) on the differentiation and transformation of hepatic stellate cells(HSCs).METHODS: By constructing the recombinant adenovirus vector expressing HNF4α and HNF4αshRNA vector, and manipulating HNF4α expression in HSC-T6 cells, we explored the influence of HNF4α and its induction capacity in the differentiation of rat HSCs into ***: With increased expression of HNF4αmediated by AdHNF4α, the relative expression of Nanog was downregulated in HSC-T6 cells(98.33 ±12.33 vs 41.33 ± 5.67, P < 0.001). Consequently, the expression of G-P-6 and PEPCK was upregulated(G-P-6:14.34 ± 3.33 vs 42.53 ± 5.87, P < 0.01; PEPCK: 10.10± 4.67 vs 56.56 ± 5.25, P < 0.001), the expression of AFP and ALB was positive, and the expression of Nanog, Type Ⅰ collagen, α-SMA, and TIMP-1 was significantly decreased. HNF4α also downregulated vimentin expression and enhanced E-cadherin expression. The ultrastructure of HNF4α-induced cells had more mitochondria and ribosomes compared with the parental cells. After silencing HNF4α expression,EPCK, E-cadherin, AFP, and ALB were downregulated and α-SMA and vimentin were ***: HNF4α can induce a tendency of differentiation of HSCs into hepatocyte-like cells. These findings may provide an effective way for the treatmentof liver diseases.

关键词： Hepatocyte nuclear factor 4α Hepaticstellate cells adenovirus vector Differentiation Rat

Killing effect of adenoviral mediated cytosine deaminase gene on human pancreatic cancer cell line PaTu8988

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Journal of Medical Colleges of PLA(China) 2001年第4期16卷 281-284页

作者：潘雪李兆申许国铭崔龙张素贞龚燕芳屠振兴 Department of Gastroenterology Changhai Hospital Second Military Medical UniversityShanghai 200433 China Department of Surgery Changhai Hospital Second Military Medical UniversityShanghai 200433 China

Objective:To evaluatethein vitro killingeffectsof cytosinedeaminasegene mediatedby adenovirusvector on ***:CytosineDeaminase(CD)genewas clonedintopAdTrack-CMV-CD,pAd-Track-CMV-CDandpAdEasy-1wererecombinedinbacteria,andtheproductscontaininggreenfluorescentprotein(GFP)werepropagatedin293cellsandpurifiedby ***8988wereinfectedwiththisvirus,then5-FCwasadded;XTTassaywasusedto estimatetherelativenumbersof viable ***:Thepositivecloneswereconfirmedby usingendonucleasedigestion,andthetiterof theviruscontaining CD genewas2×10 11 pfu/***5-FCpossessedsignificantcytotoxicactivitiesforCD genetransfected8988cellline,buthadlittleeffectson ***:CD genemediatedby adenovirus hasa highinfectivityandis efficientforkillingculturedpancreaticcarcinomacells,indicatingsuicidegenemaybe effec-tiveforpancreaticcancerinfuture.

关键词： pancreatic cancer adenovirus vector cytosine deaminase gene therapy

Effect of adenoviral vector-mediated rat antisense AT1B gene transfer on neointima proliferation after rat carotid injury

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Journal of Medical Colleges of PLA(China) 1999年第4期14卷 261-265页

作者：欧阳平许顶立黄洪莲刘伊丽侯玉清宋后燕戴云

Objective: Angiotensin Ⅱ is a growth-promoting factor for vascular smooth muscle cells in culture andin the intact animal. The biological effects of angiotensin Ⅱ are manifested only by binding to specific receptors oncell membranes. In the study, we observed that the effect of rat antisense AT1B gene transfer mediated by adenoviral vector-on neointimal proliferation following rat carotid injury. Methods: Antisense AT1B gene was transductedinto the carotid by adenoviral vector after carotid bal1oon injury and the restenosis model was established in SD *** measured neointima/media area ratio in local artery at day 21 after gene transfer. Results: Rat antisense AT1Bgene was successfully transducted into local carotid after the carotid balloon injury. Neointima/media area ratiowas significantly reduced (47 %, P<0. 01) at day 21 after gene transfer compared with the control group. Conclusion: The results suggest it is possible that antisense AT1B gene transfer as a potential therapeutic approach prevent neointimal hyperplasia.

关键词： antisense AT1B adenovirus vector restenosis neointima hyperplasia gene therapy

A study on the change of autophagy in skeletal muscle of patients with chronic kidney disease

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China Medical Abstracts(Internal Medicine) 2013年第3期30卷 179-180页

作者：黄娟 Dept Nephrol Affil 1st People's HospShanghai Jiaotong Univ

Objective To study skeletal muscle atrophy and the change of autophagy in skeletal muscle of patients with chronic kidney *** Mean muscle cross sectional area,mRNA and protein expression

关键词： skeletal autophagy sectional atrophy elective adenovirus interacting peritoneal staining dialysis

Gene transfer and therapy with adenoviral vector in rats with diethylnitrosamine-induced hepatocellular carcinoma

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中国实验血液学杂志 1997年第3期5卷 301-302页

作者： Miguel Idoate Roberto Bilbao Bruno Sangro Oscar Bruna Jesus Vazquez Jesus Prieto Experimental Pathology University Clinic and School of Medicine University of Navarra Pamplona SpainDepartment of Internal Medicine Department of Internal Medicine Department of Internal Medicine Experimental Pathology University Clinic and School of Medicine University of Navarra Pamplona SpainDepartment of Internal Medicine

Viral-mediated gene transfer of thymidine kinase ofherpes simplex virus (HSV-tk) has been used to confercytotoxic sensitivity to ganciclovir (GCV) in a variety oftnmor cells. HSV-tk converts GCV into a phosphorylatedc... 详细信息

关键词： thymidine simplex nodules cytotoxic adenovirus nude dividing inhibit orthotopic affects

Roles of transcriptional corepressor RIP140 and coactivator PGC-1αin energy state of chronically infarcted rat hearts and mitochondrial function ofcardio myocytes

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Roles of transcriptional corepressor RIP140 and coactivator ...

2013年广东省药师周大会

作者： Yanfang Chen Yuhua Wang Jianwen Chen Xi Chen Weiwei Cao Shaorui Chen Suowen Xu Heqing Huang Peiqing Liu Department of Pharmacology and Toxicology School of Pharmaceutical SciencesSun Yat-sen University Institute of Pharmacy and Pharmacology Nanhua University

Transcriptional coactivator PPARγcoactivator-1α(PGC-1α) and corepressor receptor-interacting protein 140(RIP 140) are opposing-functional regulators in maintaining energy balance of most metabolic tissues and ***,the relative contributions of both factors to energy metabolism in cardiomyocytes remain largely ***,we reported that the relative protein levels of RIP140/PGC-1αwere up-regulated in the failing hearts after chronic myocardial infarction(MI),and correlated negatively with the energy state indexphosphocreatine(PCr)/ATP ratios. Real-time PCR analysis revealed that mRNA expressions of estrogen related receptorα(ERRα),peroxisome proliferate activated receptorαandβ(PPARα,PPARβ), nuclear respiratory factor 1(NRF1) and their target genes were repressed by RIP140 and induced by PGC-1αin a dose dependent manner in neonatal rat cardiomyocytes. We also observed that overexpression of RIP140 through adenovirus delivery can abrogate the PGC-1α-mediated induction of mitochondrial membrane potential elevation and mitochondrial biogenesis,and activate both autophagy and apoptosis *** conclude that RIP140 and PGC-1αexert antagonistic role in regulating cardiac energy state and mitochondrial biogenesis.

关键词： PGC-1α RIP 140 Heart failure adenovirus Metabolism Mitochondrial biogenesis

Microbiota improve immune defense against hepadnavirus infection through promoting hepatic γδT-17 cells

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Microbiota improve immune defense against hepadnavirus infec...

第九届全国免疫学学术大会

作者：李凤磊陈永艳魏海明孙汭田志刚中国科学技术大学免疫学研究所

Backgroud:Though microbiota products derived from gut obviously shape the liver immune microenvironment,few direct evidences and mechanisms were ***:To study the role and the mechanism of microbiota in shaping liver antiviral immune ***:adenovirus was used as a typical hepadnavirus which can induce a series of immune responses mediated by many different kinds of immune cells in *** treated with antibiotics(referred as Atb mice)were used as Microbiota depleted *** assay was used to analyze the immune cell composition and cytokines ***:Atb mice displayed an enhanced susceptibility to adenovirus infection,which is associated with the defect innate antiviral immune ***γδT-17 cells but not Kupffer cells or NK cells displayed a key role in this process,because it decreased in Atb mice and IL-17 injection restored Atb mice’s antiviral *** study indicated hepaticγδT-17 cells resident in the na(i|¨)ve mice liver in a microbiota dependent *** researches demonstrated that commensal derived CD1d presentedγδTCR antigen but not TLR ligands or cytokines are key factors that promote the hepaticγδT-17 ***:our study first interpret the correlation between microbiota and hepaticγδT-17 cells,providing new theoretical basis for the study of the intestine-liver immune crosstalk.

关键词： Liver Gut Microbiota adenovirus γδT cell Interleukin-17

Macrophage-specific expression of antimicrobial peptide PR-39 inhibits intracellular growth of Burkholderia pseudomallei in mouse macrophage cells and lung

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Macrophage-specific expression of antimicrobial peptide PR-3...

2013海南省第五届生命科学联合学术会议

作者： XIA Qian-feng Fu Qiong-yao Wu qiang QIAN Shi-Yun QIN Xi The department of laboratory medicine Hainan Medical College

Objective To construct an adenovirus expression vector encoding antimicrobial peptide PR39,and to observe its expression and antimicrobial activity in mouse macrophage RAW264.7 cells and *** Recombinant adenovirus vector pAd-PR39 was used to infect mouse macrophage RAW264.7 cells and lungs and its antimicrobial activity against Burkholderia pseudomal lei was *** expression of PR39 gene in mouse macrophage RAW264.7 cells and lungs was detected by *** Recombinant adenovirus Ad-PR39 were infected into macrophage RAW264.7 cells and lung for stable or transient expression of ***-39 expression in macrophage cells was subsequently confirmed by immunocytochemistry and showed stronger antibacterial ability against Burkholderia pseudomallei than control *** These results demonstrated that macrophage-specific expression of antimicrobial peptide PR-39 in macrophages could inhibit the growth of intracellular Burkholderia pseudomal lei and indicated it to be a novel and promising approach for the control of refractory intracellular infection.

关键词： antimicrobial peptide PR39 adenovirus macrophage,Burkholderia pseudomallei

Recombinant adenoviral vector expressing the tumor necrosis factor-related apoptosis-inducing ligand gene suppresses human pancreatic cancer growth

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Recombinant adenoviral vector expressing the tumor necrosis ...

中华医学会第十一届全国胰腺外科学术研讨会

作者： RUI TIAN RENYI QIN Department of Biliary-Pancreatic Surgery,Affiliated Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,430030,P.R.China

＜正＞Tumor necrosis factor-Related Apoptosis-Inducing Ligand（TRAIL）has been reported to specifically kill malignant cells but to he relatively nontoxic to normal *** therefore investigated how far adenovirus-delivered TRAIL gene transfection may serve as a therapeutic option for pancreatic cancer in vitro and in *** the present work, TRAIL gene was transfected to pancreatic cancer cell line Panc-1 by an adenovirus vector（Ad-TRAIL）.Level of TRAIL mRNA expression was determined using RT-PCR,and TRAIL protein synthesis was evaluated with western blot. Cell-growth activities were determined by MTT assay and bystander effect was observed by co-culturing the Panc-1 cells with and without the transfected TRAIL gene at different *** in pancreatic cancer cells was detected by flow cytometry and proaspase-8 and procaspase-3 were determined by western *** invasion ability of Panc-1 cells was examined using a modified Transwell chamber *** in vivo efficacy of TRAIL was characterized in an athymic mice xenograft *** overexpression of TRAIL was detected in Panc-1 cells infected with ***-TRAIL significantly inhibited of cell viability of Pane-1 cells,and cocnlture of cancer cells transfected with Ad-TRAIL with that nontransfected resulted in the cell death of both ***,flow cytometric assay showed TRAIL transfection can induce apoptosis,as confirmed by caspase-8,caspase-3 cleavage and *** chamber assay demonstrated that Ad-TRAIL inhibited cell invasion in pancreatic cancer ***,in vivo,multiple-center intratumoral injection of Ad-TRAIL suppressed the outgrowth of human pancreatic cancer cell in athymic *** results suggested that Ad-TRAIL has antitumor effects on pancreatic cancer and demonstrated its potential use as an alternative approach to treatment of human malignancy.

关键词： pancreatic cancer TRAIL adenovirus apoptosis