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| 1 | Ledipasvir and Sofosbuvir for Untreated HCV Genotype 1 Infection显示文摘 | Nezam Afdhal Stefan Zeuzem Paul Kwo Mario Chojkier Norman Gitlin Massimo Puoti Manuel Romero-Gomez Jean-Pierre Zarski Kosh Agarwal Peter Buggisch Graham R. Foster Norbert Br?u Maria Buti Ira M. Jacobson G. Mani Subramanian Xiao Ding Hongmei Mo Jenny C. Ya | 2014 | The New England Journal of Medicine2014，，： | 6 |
| 2 | Role of interleukin-1 and its antagonism of hepatic stellate cell proliferation and liver fibrosis in the Abcb4^(-/-) mouse model显示文摘AIM: To study the interleukin-1(IL-1) pathway as a therapeutic target for liver fibrosis in vitro and in vivo using the ATP-binding cassette transporter b4^(-/-)(Abcb4^(-/-)) mouse model.METHODS: Female and male Abcb4^(-/-) mice from 6 to 13 mo of age were analysed for the degree of cholestasis(liver serum tests), extent of liver fibrosis(hydroxyproline content and Sirius red staining) and tissue-specific activation of signalling pathways such as the IL-1 pathway [quantitative polymerase chain reaction(q PCR)]. For in vivo experiments, murine hepatic stellate cells(HSCs) were isolated via pronasecollagenase perfusion followed by density gradient centrifugation using female mice. Murine HSCs were stimulated with up to 1 ng/m L IL-1β with or without 2.5 μg/m L Anakinra, an IL-1 receptor antagonist, respectively. The proliferation of murine HSCs was assessed via the Brd U assay. The toxicity of Anakinra was evaluated via the fluorescein diacetate hydrolysis(FDH) assay. In vivo 8-wk-old Abcb4^(-/-) mice with an already fully established hepatic phenotype were treated with Anakinra(1 mg/kg body-weight daily intraperitoneally) or vehicle and liver injury and liver fibrosis were evaluated via serum tests, q PCR, hydroxyproline content and Sirius red staining. RESULTS: Liver fibrosis was less pronounced in males than in female Abcb4^(-/-) animals as defined by a lower hydroxyproline content(274 ± 64 μg/g vs 436 ± 80 μg/g liver, respectively; n = 13-15; P < 0.001; MannWhitney U-test) and lower m RNA expression of the profibrogenic tissue inhibitor of metalloproteinase-1(TIMP)(1 ± 0.41 vs 0.66 ± 0.33 fold, respectively; n = 13-15; P < 0.05; Mann-Whitney U-test). Reduced liver fibrosis was associated with significantly lower levels of F4/80 m RNA expression(1 ± 0.28 vs 0.71 ± 0.41 fold, respectively; n = 12-15; P < 0.05; Mann-Whitney U-test) and significantly lower IL-1β m RNA expression levels(1 ± 0.38 vs 0.44 ± 0.26 fold, respectively; n = 13-15; P < 0.001; Mann-Whitney U-test). No gender differences in the serum liver parameters [bilirubin; alanine aminotransferase(ALT); aspartate aminotransferase and alkaline phosphatase(AP)] were found. In vitro, the administration of IL-1β resulted in a significant increase in HSC proliferation [0.94 ± 0.72 arbitrary units(A.U.) in untreated controls, 1.12 ± 0.80 A.U. at an IL-1β concentration of 0.1 ng/m L and 1.18 ± 0.73 A.U. at an IL-1β concentration of 1 ng/m L in samples from n = 6 donor animals; P < 0.001; analyses of variance(ANOVA)]. Proliferation was reduced significantly by the addition of 2.5 μg/m L Anakinra(0.81 ± 0.60 A.U. in untreated controls, 0.92 ± 0.68 A.U. at an IL-1β concentration of 0.1 ng/m L, and 0.91 ± 0.69 A.U. at an IL-1β concentration of 1 ng/m L; in samples from n = 6 donor animals; P < 0.001; ANOVA) suggesting an anti-proliferative effect of this clinically approved IL-1 receptor antagonist. The FDH assay showed this dose to be non-toxic in HSCs. In vivo, Anakinra had no effect on the hepatic hydroxyprolinecontent, liver serum tests(ALT and AP) and profibrotic(collagen 1α1, collagen 1α2, transforming growth factor-β, and TIMP-1) and anti-fibrotic [matrix metalloproteinase 2(MMP2), MMP9 and MMP13 ] gene expression after 4 wk of treatment. Furthermore, the hepatic IL-1β and F4/80 m RNA expression levels were unaffected by Anakinra treatment.CONCLUSION: IL-1β expression is associated with the degree of liver fibrosis in Abcb4^(-/-) mice and promotes HSC proliferation. IL-1 antagonism shows antifibrotic effects in vitro but not in Abcb4^(-/-) mice. | Florian P Reiter Ralf Wimmer Lena Wottke Renate Artmann Jutta M Nagel Manuel O Carranza Doris Mayr Christian Rust Peter Fickert Michael Trauner Alexander L Gerbes Simon Hohenester Gerald U Denk | 2016 | World Journal of Hepatology2016，8，8： | 3 |
| 3 | Least squares approximation of Bezier coefficients provides best degree reduction in the Lz-norm显示文摘 | Peters J Reif U | 2000 | Journal of Approximation Theory2000，104，1： | 1 |
| 4 | EB-PVD thermal barrier coatings for aeroengines and gas turbines显示文摘 | PETERS M LEYENS C CHULZ U KAYSSER W A | 2001 | Advanced Engineering Materials2001，3，4： | 1 |
| 5 | Autism in Angelman syndrome:implications for autism research显示文摘 | Peters S U Beaudet A L Madduri N | | 0，，06： | 1 |
| 6 | Urinary mutagenesis and fried red meat intake: Influence of cooking temperature, phenotype, and genotype of metabolizing enzymes in a con- trolled feeding study 显示文摘 | Peters U Sinha R Bell D A | 2004 | Environmental and Molecular Mu- tagenesis2004，43，1： | 1 |
| 7 | Reduction in thyroid volume after radioiodine therapy of Graves' hyperthyroidism:results of a prospective,randomized,multicentre study显示文摘 | Peters H Fischer C Bogner U | 1996 | Eur J Clin Invest1996，26，1： | 1 |
| 8 | Dietary fiber and risk of colorectal cancer in the Breast Cancer Detection Demonstration Project (BCDDP) follow-up cohort显示文摘 | MAI V FLOOD A PETER U | 2003 | Int J Epidemiol2003，32，： | 1 |
| 9 | Cloning of Fatso (Fto), a novel gene deleted by the Fused toes (Ft) mouse mutation 显示文摘 | PETERS T AUSMEIER K RUTHER U | 1999 | Mammalian Genome1999，10，10： | 1 |
| 10 | The interaction of beta-am- yloid protein with cellular membranes stimulates its own production 显示文摘 | Peters I Igbavboa U Schtitt T | 2009 | Biochim Biophys Acta2009，1788，5： | 1 |
| 11 | defining the roles of nucleotide excision repair and recombination in the repair of DNA interstrand cross-links in mammalian cells显示文摘 | Inusha U Peter JM Peter HC | 2001 | Mol Cell Biol2001，20，21： | 1 |
| 12 | 11 Years of Cyanopyrrolidines as DPP-IV Inhibi- tors 显示文摘 | Peters J U | 2007 | Curt Top Med Chem2007，7，6： | 1 |
| 13 | Effect of ageing of HZSM-5 zeolite during coupled methanol hydrocarbon cracking (CMHC) 显示文摘 | MARTIN A PETER S WOLF U | 1991 | Reaction Kinetic Catalysis Letter1991，44，1： | 1 |
| 14 | Dietary fiber and colorectal adenoma in a colorectal cancer early detection programme显示文摘 | PETERS U | 2003 | Thelancer2003，361，： | 1 |
| 15 | Increased formation of reactive oxygen species after permanent and reversible middle cere- bral artery occlusion in the rat显示文摘 | Peter O Back T Lindauer U | 1998 | J Cereb Blood Flow Metab1998，18，： | 1 |
| 16 | Detection of the trend and seasonal variation in tropospheric NO2 over China 显示文摘 | VANDER R J PETERS D H M U ESKES H | 2006 | Journal of Geophysical Research2006，111，： | 1 |
| 17 | Support for family carers who care for anelderly person at home-a systematic literature review显示文摘 | Peter S Giggi U | 2004 | Nordic College of Caring Sciences2004，，18： | 1 |
| 18 | Cloning of Fatso(Fto),anovel gene deleted by the Fused toes(Ft)mouse mutation显示文摘 | PETERS T AUSMEIER K RUTHER U | 1999 | Mamm Genome1999，10，10： | 1 |
| 19 | Cardiac resynchronization therapy improves central sleep apnea and Cheyne-Stokes respiration in patients with chronic heart failure显示文摘 | Anil-Martin Sinha Erik C Skobel Ole-Alexander Breithardt Christine Norra Kai U Markus Christian Breuer Peter Hanrath Christoph Stellbrink | 2004 | Journal of the American College of Cardiology2004，，1： | 1 |
| 20 | Three-component condensation leading to fl-amino acid diamides: Con- vergent assembly of/3-peptide analogues ganem 显示文摘 | Oaksmith J M Peters U Ganem B | 2004 | J Am Chem Soc2004，126，13： | 1 |
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