Abstract:
BACKGROUND & AIMS:In this study, adenoviral vectors encoding an antisense RNA complementary to the 5' non-coding region (5'NCR) of the HCV-genome were generated to inhibit HCV-RNA gene expression in cell culture and in vivo. METHODS:First and second-generation (with E4-deletion) adenoviruses encoding the HCV5'NCR in antisense direction (Ad-NCRas and Ad-E4del-NCRas) were generated. Inhibition of HCV gene expression was analyzed in hepatoma cells stably transfected with the HCV5'NCR cDNA fused to the firefly luciferase gene (NCRluc), as well as in the HCV subgenomic replicon (genotypes 1b and 2a) and the fully infectious HCV JFH-1 cell culture systems. For in vivo experiments, an adenovirus encoding the NCRluc-gene was injected intravenously to achieve a NCR-dependent luciferase-expression in the liver of C3H/HeNcrl-mice. RESULTS:Forty eight hours after transduction with GFP-encoding adenoviruses, >85% of HepG2-, CCL13-and Huh7-cells expressed GFP. Surprisingly, GFP-expression of E4-deleted adenoviruses was considerably reduced at the same MOI. Using antisense first-generation adenoviruses (Ad-NCRas), a significant inhibition of the 5'NCR-dependent HCV-gene expression (54±19% in HepG2-cells and 66.2±15% in Huh7-cells) was achieved 48h after transduction. In Huh7-cells containing the HCV subgenomic replicons and in infectious HCV JFH-1 cell cultures, adenovirus-mediated transcription of antisense 5'NCR significantly blocked HCV-replication (40% and 76%, respectively). Corresponding to low transgene expression, the maximal inhibition reached with Ad-delE4-NCRas was 30%. In vivo, antisense adenoviral vectors also showed a significant inhibition (40%) of NCR-dependent luciferase expression compared to control adenoviruses (p<0.05). CONCLUSIONS:The data indicate that HCV gene expression can be inhibited by antisense RNA encoding adenoviruses in the tested settings.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
González-Carmona MA,Vogt A,Heinicke T,Quasdorff M,Hoffmann P,Yildiz Y,Schneider C,Serwe M,Bartenschlager R,Sauerbruch T,Caselmann WHdoi
10.1016/j.jhep.2010.11.010subject
Has Abstractpub_date
2011-07-01 00:00:00pages
19-28issue
1eissn
0168-8278issn
1600-0641pii
S0168-8278(10)01080-9journal_volume
55pub_type
杂志文章abstract::Extracellular vesicles are membrane-bound vesicles containing proteins, lipids, RNAs and microRNAs. They can originate from both healthy and stressed cells, and provide a snapshot of the cell of origin in physiological and pathological circumstances. Various processes that may give rise to the release of extracellular...
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pub_type: 杂志文章,评审
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更新日期:2020-12-01 00:00:00
abstract:Background & Aims:Liver enzyme abnormalities are common in patients with coronavirus disease 2019 (COVID-19). Whether or not severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to liver damage per se remains unknown. Herein, we reported the clinical characteristics and liver pathological man...
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abstract:BACKGROUND/AIMS:Recently, a novel DNA virus was isolated from the serum of a patient with post-transfusion non-A-G hepatitis and named TT virus. The aim of this study was to determine the prevalence and clinical characteristics of TT virus infection in patients with sporadic acute hepatitis of unknown etiology. METHOD...
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doi:10.1016/s0168-8278(99)80309-2
更新日期:1999-12-01 00:00:00
abstract:BACKGROUND/AIMS:A distinct subgroup of angiotensin II type 1 receptor (AT1R) blockers (ARBs) have been reported to suppress the development of hepatic steatosis. These effects were generally explained by selective peroxisome proliferator-activated receptor (PPAR) gamma modulating properties of ARBs, independent of thei...
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abstract:BACKGROUND & AIMS:Although there is increasing interest in its use, definitive evidence demonstrating a benefit for postmortem normothermic regional perfusion (NRP) in controlled donation after circulatory death (cDCD) liver transplantation is lacking. The aim of this study was to compare results of cDCD liver transpla...
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更新日期:2019-04-01 00:00:00
abstract:BACKGROUND/AIMS:The pathogenic relevance of the hepatitis G virus (HGV) and its sensitivity to interferon are currently under investigation. This study aimed to investigate the prevalence of HGV infection in patients with chronic hepatitis C and to elucidate if HGV co-infection modifies the clinical course and the resp...
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doi:10.1016/s0168-8278(97)80243-7
更新日期:1997-04-01 00:00:00
abstract:BACKGROUND/AIMS:Interaction between CYP2E1, ethanol metabolites, and enhanced lipid peroxidation is linked to the pathogenesis of alcoholic liver disease. This study was conducted to compare the expression of various cytochrome enzymes and the appearance of aldehyde adducts in humans. METHODS:Acetaldehyde- and lipid p...
journal_title:Journal of hepatology
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doi:10.1016/s0168-8278(00)80120-8
更新日期:2000-12-01 00:00:00
abstract::The prolylhydroxylase inhibitor HOE 077 which has proven to be liver-selective in animals was tested in general pharmacological and toxicological studies for unwanted effects and safety. The results of these studies permit clinical development. A single-dose study in healthy volunteers was performed which showed that ...
journal_title:Journal of hepatology
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更新日期:1991-01-01 00:00:00
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doi:10.1016/0168-8278(95)80037-9
更新日期:1995-12-01 00:00:00
abstract:BACKGROUND & AIMS:Data on the natural history of chronic hepatitis C virus (HCV) genotype 6 is lacking. METHODS:We compared the natural history of 138 HCV genotype 1 patients (median age: 50) with 78 HCV genotype 6 patients (median age: 46.5). Baseline demographic data including gender, route of transmission, liver bi...
journal_title:Journal of hepatology
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更新日期:2010-09-01 00:00:00
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doi:10.1016/s0168-8278(98)80121-9
更新日期:1998-12-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/s0168-8278(98)80156-6
更新日期:1998-10-01 00:00:00
abstract:BACKGROUND/AIMS:Primary sclerosing cholangitis (PSC) is a cholestatic liver disease of unknown etiology. Although the primary defect affects cholangiocytes, cholestatic injury of hepatocytes may promote further liver damage. Since down-regulation of hepatocellular organic anion transporters is implicated in the molecul...
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doi:10.1016/s0168-8278(02)00052-1
更新日期:2002-06-01 00:00:00
abstract:BACKGROUND & AIMS:Cholangiocarcinoma (CCA) represents a primary hepatic malignancy with incidence and mortality rising globally. Surgical treatment has remained the only potentially curative treatment option, but it is still unclear which patients benefit most from extended liver surgery, highlighting the need for new ...
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pub_type: 杂志文章
doi:10.1016/j.jhep.2017.06.020
更新日期:2017-10-01 00:00:00
abstract:BACKGROUND/AIMS:Herpes simplex virus (HSV) is known to induce fulminant hepatic failure. The aim of this study is to clarify the molecular basis of liver injury in HSV-induced hepatitis. METHODS:Immunocompetent mice were inoculated with HSV or ultraviolet-inactivated HSV (UV-HSV) intravenously. Extent of liver injury ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(03)00385-4
更新日期:2003-11-01 00:00:00
abstract:BACKGROUND & AIMS:To follow the local tissue delivery of doxorubicin in HCC explants from patients embolized with drug-eluting beads and to compare it with histologic modifications. METHODS:Six patients with HCC underwent chemoembolization with doxorubicin-eluting beads (caliber 100-300 μm, dose 75-150 mg) followed by...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2011.03.024
更新日期:2011-12-01 00:00:00
abstract:BACKGROUND/AIM:Steatosis is commonly present in chronic hepatitis C. Our aim was to evaluate host- and disease-specific factors associated with its occurrence. METHODS:Histologic findings in 60 patients were correlated with body mass index, human leukocyte antigens, and other conventional parameters. Comparisons were ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(98)80004-4
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journal_title:Journal of hepatology
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doi:10.1016/j.jhep.2013.01.006
更新日期:2013-05-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2014.10.007
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pub_type: 杂志文章
doi:10.1016/s0168-8278(05)80188-6
更新日期:1993-08-01 00:00:00
abstract::A technique is described for the isolation and culture of Kupffer cells (Kc) from needle and surgical liver biopsies of humans and rats. The isolation procedure is based on puncture perfusion of the specimen with collagenase and pronase, and subsequent gradient centrifugation. The ultrastructure of the cultured cells ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(88)80505-1
更新日期:1988-08-01 00:00:00
abstract::The Hepatitis Delta Virus (HDV), a defective ribonucleic acid virus dependent on the Hepatitis B Virus (HBV) is a cause of severe liver disease that often leads to cirrhosis and death. Since the HDV finds in the HBV infection a biological niche in which to thrive indefinitely, the major victims of its infection are th...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1986-01-01 00:00:00
abstract::Design and endpoints of clinical trials in hepatocellular carcinoma. Llovet JM, Di Bisceglie AM, Bruix J, Kramer BS, Lencioni R, Zhu AX, Sherman M, Schwartz M, Lotze M, Talwalkar J, Gores GJ; for the Panel of Experts in HCC-Design Clinical Trials. The design of clinical trials in hepatocellular carcinoma (HCC) is comp...
journal_title:Journal of hepatology
pub_type: 评论,杂志文章
doi:10.1016/j.jhep.2008.07.012
更新日期:2008-10-01 00:00:00
abstract:BACKGROUND/AIMS:Natural killer T (NKT) cells are present in the liver of mice. We examined whether NKT cells and other leukocytes were associated with hepatic inflammation after partial hepatectomy. METHODS:Approximately 70% of the liver was removed from mice using the method described by Higgins and Anderson. RESULT...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2003.10.017
更新日期:2004-02-01 00:00:00
abstract:BACKGROUND/AIMS:Septins are ubiquitous and multifunctional scaffold proteins involved in cytoskeletal organization, exocytosis and other cellular processes. We disclose the quiescent hepatic stellate cells (HSCs)-specific expression of a septin subunit Sept4 in the liver, and explore the significance of the septin syst...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2008.05.026
更新日期:2008-11-01 00:00:00
abstract:BACKGROUND & AIMS:It is widely recognized that in the early stages of liver regeneration after partial hepatectomy, the hepatocytes accumulate a significant amount of lipids. The functional meaning of this transient steatosis and its effect on hepatocellular proliferation are not well defined. In addition, the basic me...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2013.05.026
更新日期:2013-10-01 00:00:00
abstract:BACKGROUND/AIMS:Circulatory abnormalities with activation of vasoconstrictor systems after large-volume paracentesis are generally considered secondary to an increased extravasation of fluid from the intravascular compartment to the extravascular space with subsequent reduction in plasma volume. To test this hypothesis...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(97)80081-5
更新日期:1997-10-01 00:00:00
abstract::The liver contributes to immune surveillance against pathogens entering via the gut and is itself influenced by alterations in mucosal immune responses and the microbiome. Mucosal immunity is also implicated in autoimmune liver diseases that associate with inflammatory bowel disease (IBD), and in steatohepatitis where...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2015.12.002
更新日期:2016-05-01 00:00:00
abstract:BACKGROUND & AIMS:Hepatic stellate cell (HSC) transdifferentiation into collagen-producing myofibroblasts is a key event in hepatic fibrogenesis, but the transcriptional network that controls the acquisition of the activated phenotype is still poorly understood. In this study, we explored whether the nuclear receptor c...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2016.11.003
更新日期:2017-04-01 00:00:00