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| 1 | 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 |
| 2 | 欧洲城市绿地在老年人护理设施中的作用显示文摘城市绿地(UGS)对城市人类福祉的重要性日益得到认可,但大部分研究只针对公园、社区花园、城市森林等绿地,而缺乏对不同人群的城市绿地需求与使用情况的考虑,也未能将城市绿地与社会基础设施联系起来。老龄化已成为目前全球性的人口发展趋势。已有研究发现,到城市绿地的良好可达性对于居住在绿地周围步行距离中的老人而言具有正面的健康影响,并且可以增加他们的寿命。 | ARTMANN M CHEN X IOJA C | 2017 | 城市规划学刊2017，，5： | 3 |
| 3 | 精明增长与绿色基础设施如何相互支持:紧凑绿色城市的概念框架显示文摘紧凑型城市被规划师和研究者认为是更可持续发展的城市形态。然而,紧凑城市的局限性之一在于绿地率较低,而这将危害城市生态系统服务的充足供应。本文试图整合以紧凑型城市形态为特征的精明增长以及以多尺度绿色空间网络为特征的绿色基础设施,从而系统性地提出紧凑绿色城市(compact and green cities)的概念框架。 | ARTMANN M KOHLER M MEINEL G | 2018 | 城市规划学刊2018，，1： | 3 |
| 4 | Dual energy CT-a new perspective in the diagnosis of gout显示文摘 | Artmann A Ratzenbock M Noszian I | 2010 | RoFo2010，182，3： | 1 |
| 5 | Rheokinetic investigations on the thermal cure of phenol-formaldehyde novolac resins 显示文摘 | ARTMANN A BIANCHI O SOARES M R | 2010 | Materials Science and Engineering: C2010，30，8： | 1 |
| 6 | Rheo- kinetic investigations on the thermal cure of phenol- formaldehyde novolac resins显示文摘 | ARTMANN A BIANCHI O SOARES M R | 2010 | Materials Science and Engineering ( C )2010，30，8： | 1 |
| 7 | Rheokinetic investigations on the thermal cure of phenol-formaldehyde novolac resins显示文摘 | Artmann A Bianchi O Soares M R | 2010 | Mater Sci Eng2010，30，8： | 1 |
| 8 | Rheokinetic investigations on the thermal cure of phenol-formaldehyde novolac resins 显示文摘 | Artmann A Bianchi O Soares M R | 2010 | Materials Science and Engineering2010，30，8： | 1 |
| 9 | 冠状动脉钙化程度对双源CT冠状动脉CTA图像质量的影响显示文摘 | Artmann A Enayati S Ratzenbck M 杨岷 | 2009 | 放射学实践2009，24，10： | 0 |
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