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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 | 一种房颤风险评分系统的建立(Framingham心脏研究):基于社区的队列研究显示文摘背景房颤导致了发病率和病死率的显著上升。本研究旨在建立一种预测个体罹患房颤绝对风险的风险评分系统,并提供研究人员评价新危险因素的流程。方法作者评估了Framingham心脏研究中于1968年6月至1987年9月间进行了8044次检测的4764例参与者(55%为女性,年龄45~95岁)。此后,参与者被随访至房颤首发,随访期最长达10年。多变量Coxi回归确认出1(1年内罹患房颤的临床危险因素。次级分析纳入了常规超声心动图检测指标(5152例4参与者,7156次检测)对房颤风险进行再分层评估,并评价超声检测指标能否提高风险预测能力。结果4764例参与者中的457例4(10%)罹患房颤。年龄、性别、体重指数、收缩压、降压治疗、PR间期、有临床意义的心脏杂音及心力衰竭与房颤相关,并被纳入了风险评分模型(除体重指数P=0.08外,其余均为P〈0.05),模型的C统计量为0.78(95%CI0.76~0.80)。10年房颤风险随年龄变化:年龄〈65岁的人群中53例(1%)风险高于15%,而〉65岁的人群中为783例(27%)。为提高预测能力而纳入超声检测指标仅使模型C统计量略微增高,由0.78(95%C10.75~0.80)增至0.79(95%CI0.77~0.82:P=0.005)。超声心动图检测指标并不能改善风险再分层评估(P=0.18)。结论基于社区医疗中易得的临床因素建立的风险评分系统,有助于确认社区个体罹患房颤的风险,评估技术或标志物能否改善风险预测,以及针对高危个体采取预防措施。 | Renate B Schnabel Lisa M Sullivan Daniel Levy Michael J Pencina Joseph M Massaro Ralph B D'Agostino Sr Christopher Newton-Cheh Jennifer F Yamamoto Jared W Magnani Thomas M Tadros William B Kannel Thomas J Wang Patrick T Ellinor Philip A Wolf Ramachanclran S Vasan Emelia J Benjamin 黄刚(译) | 2009 | 世界临床医学2009，，9： | 2 |
| 3 | Diagnostic efficacy of gadoxetic acid (Primovist)-enhanced MRI and spiral CT for a therapeutic strategy: comparison with intraoperative and histopathologic findings in focal liver lesions显示文摘 | Renate Hammerstingl Alexander Huppertz Josy Breuer Thomas Balzer Anthony Blakeborough Rick Carter Lluis Castells Fusté Gertraud Heinz-Peer Werner Judmaier Michael Laniado Riccardo M. Manfredi Didier G. Mathieu Dieter Müller Koenraad Mortelè Peter Reimer M | 2008 | European Radiology2008，，： | 2 |
| 4 | Ethylene resistance in flowering ornamental plants – improvements and future perspectives显示文摘Various strategies of plant breeding have been attempted in order to improve the ethylene resistance of flowering ornamental plants. These approaches span from conventional techniques such as simple cross-pollination to new breeding techniques which modify the plants genetically such as precise genome-editing. The main strategies target the ethylene pathway directly;others focus on changing the ethylene pathway indirectly via pathways that are known to be antagonistic to the ethylene pathway, e.g. increasing cytokinin levels. Many of the known elements of the ethylene pathway have been addressed experimentally with the aim of modulating the overall response of the plant to ethylene. Elements of the ethylene pathway that appear particularly promising in this respect include ethylene receptors as ETR1, and transcription factors such as EIN3. Both direct and indirect approaches seem to be successful, nevertheless, although genetic transformation using recombinant DNA has the ability to save much time in the breeding process, they are not readily used by breeders yet. This is primarily due to legislative issues, economic issues, difficulties of implementing this technology in some ornamental plants, as well as how these techniques are publically perceived, particularly in Europe. Recently, newer and more precise genome-editing techniques have become available and they are already being implemented in some crops. New breeding techniques may help change the current situation and pave the way toward a legal and public acceptance if products of these technologies are indistinguishable from plants obtained by conventional techniques. | Andreas Olsen Henrik Lütken Josefine Nymark Hegelund Renate Müller | 2015 | Horticulture Research2015，2，1： | 2 |
| 5 | Chronic hepatitis C:Treat or wait? Medical decision making in clinical practice显示文摘AIM:To analyzes the decision whether patients with chronic hepatitis C virus (HCV) infection are treated or not.METHODS:This prospective cohort study included 7658 untreated patients and 6341 patients receiving pegylated interferon α2 a/ribavirin,involving 434 physicians/institutions throughout Germany (377 in private practice and 57 in hospital settings).A structured questionnaire had to be answered prior to the treatment decision,which included demographic data,information about the personal life situation of the patients,anamnesis and symptomatology of hepatitis C,virological data,laboratory data and data on concomitant diseases.A second part of the study analyzes patients treated with pegylated interferon α2a.All questionnaires included reasons against treatment mentioned by the physician.RESULTS:Overall treatment uptake was 45%.By multivariate analysis,genotype 1/4/5/6,HCV-RNA ≤ 520 000 IU/mL,normal alanine aminotransferase (ALT),platelets ≤ 142 500/μL,age > 56 years,female gender,infection length > 12.5 years,concomitant diseases,human immunodeficiency virus co-infection,liver biopsy not performed,care in private practice,asymptomatic disease,and unemployment were factors associated with reduced treatment rate.Treatment and sustained viral response rates in migrants (1/3 of cohort) were higher than in German natives although 1/3 of migrants had language problems.Treatment rate and liver biopsy were higher in clinical settings when compared to private practice and were low when ALT and HCV-RNA were low.CONCLUSION:Some reasons against treatment were medically based whereas others were related to fears,socio-economical problems,and information deficits both on the side of physicians and patients. | Claus Niederau Dietrich Hüppe Elmar Zehnter Bernd Mller Renate Heyne Stefan Christensen Rainer Pfaff Arno Theilmeier Ulrich Alshuth Stefan Mauss | 2012 | World Journal of Gastroenterology2012，18，12： | 2 |
| 6 | Mesoscopic structureand viscoelastic properties of β-1actoglobulin gels at low pH and low ionic strength 显示文摘 | Leonard M C Cecile V Renate G | 2002 | Food Hydrocolloids2002，16，3： | 1 |
| 7 | Polybrominated diphenyl ethers (PBDEs) and alternative brominated flame retardants in air and seawater of the European Arctic显示文摘 | Axel M?ller Zhiyong Xie Renate Sturm Ralf Ebinghaus | 2011 | Environmental Pollution2011，，6： | 1 |
| 8 | Dynamical Shannon Entropy and Information Tsallis Entropy in Complex Systems显示文摘 | Renat M Y Natalya A E Faii M G | 2004 | Physica A:Statistical Mechanics and its Applications2004，341，： | 1 |
| 9 | Early atherosclerosis in obese is associated with low serum levels of adiponectin显示文摘 | Stefan P Renate H Reinhard M | 2005 | J Clin Endocrinol Metab2005，90，8： | 1 |
| 10 | Stress produced ethylene produc-tion, ethyleue binding,the response to the response to the ethyene显示文摘 | Renate M Edward C M Margrethe S | 2000 | Hort-science2000，35，2： | 1 |
| 11 | Hydrophobic silica membranes for gas separation显示文摘 | RENATE M de Vos WILHELM F Maier VERWEIJ Henk | 1999 | Journal of Membrane Science1999，158，： | 1 |
| 12 | Hydrophobic silica membranes for gas separation 显示文摘 | de VOS Renate M MAIERB Wilhelm F VERWEIJ Henk | 1999 | J Membr Sci1999，158，： | 1 |
| 13 | Character- istics of the Supervisor--subordinate Relationship as Predictors of Psychological Contract Breach 显示文摘 | Suaw Mark M Turnley William H Mai--Dahon Renate R | 2008 | Journal of Managerial Issues2008，，22： | 1 |
| 14 | Stress induced ethylene production, ethylene binding, and the response to the ethylene action inhibitor 1-MCP in miniature roses 显示文摘 | Renate M Edward C M Margrethe S | 2000 | Scientia Horticuhurae2000，83，： | 1 |
| 15 | Comparison of Al-induced gene expression in sensitive and tolerant soybean cultivar显示文摘 | Vladimir E Winfriede W Renate M | 2003 | Journal of Experiment Botany2003，54，： | 1 |
| 16 | Hippocampal pathology in refractory temporal lobe epilepsy显示文摘 | Regula S Renate M Samuel F | 2002 | Neurology2002，58，： | 1 |
| 17 | Diagnostic efficacy of gadoxetic acid (Primovist)-enhanced MRI and spiral CT for a therapeutic strategy: comparison with intraoperative and histopathologic findings in focal liver lesions显示文摘 | Renate Hammerstingl Alexander Huppertz Josy Breuer Thomas Balzer Anthony Blakeborough Rick Carter Lluis Castells Fusté Gertraud Heinz-Peer Werner Judmaier Michael Laniado Riccardo M. Manfredi Didier G. Mathieu Dieter Müller Koenraad Mortelè Peter Reimer M | 2008 | European Radiology2008，，3： | 1 |
| 18 | Role of nuclear factor κb in synovial inflammation显示文摘 | Ulf Müller-Ladner MD Renate E. Gay MD Steffen Gay MD | 2002 | Current Rheumatology Reports2002，，3： | 1 |
| 19 | Improved performace of silica membranes for gas separation显示文摘 | Renate M de Vos Henk Verweij | 1998 | J Membr Sci1998，143，： | 1 |
| 20 | Ex vivo gene transfer in the years to come显示文摘 | Thomas P Renate E G Ulf M | 2002 | Arthritis Res2002，4，： | 1 |
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