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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 | Intracerebral Hemorrhage With Severe Ventricular Involvement: Lumbar Drainage for Communicating Hydrocephalus显示文摘 | Hagen B. Huttner Simon Nagel Elena Tognoni Martin K?hrmann Eric Jüttler Berk Orakcioglu Peter D. Schellinger Stefan Schwab Jürgen Bardutzky | 2007 | Stroke2007，，1： | 1 |
| 3 | 1,25-(OH) 2 -vitamin D 3 prevents activation of hepatic stellate cells in vitro and ameliorates inflammatory liver damage but not fibrosis in the Abcb4 ?/? model显示文摘 | Florian P. Reiter Simon Hohenester Jutta M. Nagel Ralf Wimmer Renate Artmann Lena Wottke Marie-Christine Makeschin Doris Mayr Christian Rust Michael Trauner Gerald U. Denk | 2015 | Biochemical and Biophysical Research Communicatio2015，，2： | 1 |
| 4 | Cardiac Magnetic Resonance Imaging findings and the risk of cardiovascular events in patients with recent myocardial infarction or suspected or known coronary artery disease – a systematic review of prognostic studies显示文摘 | Hamza El Aidi Arthur Adams Karel G.M. Moons Hester M. Den Ruijter Willem P.Th.M. Mali Pieter A. Doevendans Eike Nagel Simon Schalla Michiel L. Bots Tim Leiner | 2013 | Journal of the American College of Cardiology2013，，： | 1 |
| 5 | Simplified cellular automaton model for city traffic显示文摘 | SIMON P M NAGEL K | 1995 | Physical Review E1995，58，2： | 1 |
| 6 | Simplified Cellular Automaton Model for City Traffic 显示文摘 | SIMON P M NAGEL K | 1998 | Physical Review E1998，58，2： | 1 |
| 7 | Suberoylanilide hydroxamic acid(SAHA)potentiates paclitaxel-induced apoptosis in ovarian cancer cell lines显示文摘 | Dietrich CS 3rd Greenberg VL De Simone CP Modesitt SC van Nagell JR Craven R | 2010 | Gynecol Oncol2010，116，1： | 1 |
| 8 | Simple queueing model appli- ed to the city of Portland显示文摘 | Simon P M Nagel K | 1999 | International Journal of Modern Physics C1999，10，5： | 1 |
| 9 | Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID- 19 pandemic显示文摘Background During the COVID-19 pandemic,decreased volumes of stroke admissions and mechanical thrombectomy were reported.The study’s objective was to examine whether subarachnoid haemorrhage(SAH)hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines.Methods We conducted a cross-sectional,retrospective,observational study across 6 continents,37 countries and 140 comprehensive stroke centres.Patients with the diagnosis of SAH,aneurysmal SAH,ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases,10th Revision,codes.The 3-month cumulative volume,monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before(1 year and immediately before)and during the pandemic,defined as 1 March-31 May 2020.The prior 1-year control period(1 March-31 May 2019)was obtained to account for seasonal variation.Findings There was a significant decline in SAH hospitalisations,with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic,representing a relative decline of 22.5%(95%CI−24.3%to−20.7%,p<0.0001).Embolisation of ruptured aneurysms declined with 1170-1035 procedures,respectively,representing an 11.5%(95%CI−13.5%to−9.8%,p=0.002)relative drop.Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations,a 24.9%relative decline(95%CI−28.0%to−22.1%,p<0.0001).A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1%(95%CI 32.3%to 50.6%,p=0.008)despite a decrease in SAH admissions in this tertile.Interpretation There was a relative decrease in the volume of SAH hospitalisations,aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic.These findings in SAH are consistent with a decrease in other emergencies,such as stroke and myocardial infarction. | Thanh N Nguyen Diogo C Haussen Muhammad M Qureshi Hiroshi Yamagami Toshiyuki Fujinaka Ossama Y Mansour Mohamad Abdalkader Michael Frankel Zhongming Qiu Allan Taylor Pedro Lylyk Omer F Eker Laura Mechtouff Michel Piotin Fabricio Oliveira Lima Francisco Mont'Alverne Wazim Izzath Nobuyuki Sakai Mahmoud Mohammaden Alhamza R Al-Bayati Leonardo Renieri Salvatore Mangiafico David Ozretic Vanessa Chalumeau Saima Ahmad Umair Rashid Syed Irteza Hussain Seby John Emma Griffin John Thornton Jose Antonio Fiorot Rodrigo Rivera Nadia Hammami Anna M Cervantes-Arslanian Hormuzdiyar H Dasenbrock Huynh Le Vu Viet Quy Nguyen Steven Hetts Romain Bourcier Romain Guile Melanie Walker Malveeka Sharma Don Frei Pascal Jabbour Nabeel Herial Fawaz Al-Mufti Atilla Ozcan Ozdemir Ozlem Aykac Dheeraj Gandhi Chandril Chugh Charles Matouk Pascale Lavoie Randall Edgell Andre Beer-Furlan Michael Chen Monika Killer-Oberpfalzer Vitor Mendes Pereira Patrick Nicholson Vikram Huded Nobuyuki Ohara Daisuke Watanabe Dong Hun Shin Pedro SC Magalhaes Raghid Kikano Santiago Ortega-Gutierrez Mudassir Farooqui Amal Abou-Hamden Tatsuo Amano Ryoo Yamamoto Adrienne Weeks Elena A Cora Rotem Sivan-Hoffmann Roberto Crosa Markus Möhlenbruch Simon Nagel Hosam Al-Jehani Sunil A Sheth Victor S Lopez Rivera James E Siegler Achmad Fidaus Sani Ajit S Puri Anna Luisa Kuhn Gianmarco Bernava Paolo Machi Daniel G Abud Octavio M Pontes-Neto Ajay K Wakhloo Barbara Voetsch Eytan Raz Shadi Yaghi Brijesh P Mehta Naoto Kimura Mamoru Murakami Jin Soo Lee Ji Man Hong Robert Fahed Gregory Walker Eiji Hagashi Steve M Cordina Hong Gee Roh Ken Wong Juan F Arenillas Mario Martinez-Galdamez Jordi Blasco Alejandro Rodriguez Vasquez Luisa Fonseca M Luis Silva Teddy Y Wu Simon John Alex Brehm Marios Psychogios William J Mack Matthew Tenser Tatemi Todaka Miki Fujimura Roberta Novakovic Jun Deguchi Yuri Sugiura Hiroshi Tokimura Rakesh Khatri Michael Kelly Lissa Peeling Yuichi Murayama Hugh Stephen Winters Johnny Wong Mohamed Teleb Jeremy Payne Hiroki Fukuda Kosuke Miyake Junsuke Shimbo Yusuke Sugimura Masaaki Uno Yohei Takenobu Yuji Matsumaru Satoshi Yamada Ryuhei Kono Takuya Kanamaru Masafumi Morimoto Junichi Iida Vasu Saini Dileep Yavagal Saif Bushnaq Wenguo Huang Italo Linfante Jawad Kirmani David S Liebeskind Viktor Szeder Ruchir Shah Thomas G Devlin Lee Birnbaum Jun Luo Anchalee Churojana Hesham E Masoud Carlos Ynigo Lopez Brendan Steinfort Alice Ma Ameer E Hassan Amal Al Hashmi Mollie McDermott Maxim Mokin Alex Chebl Odysseas Kargiotis Georgios Tsivgoulis Jane G Morris Clifford J Eskey Jesse Thon Leticia Rebello Dorothea Altschul Oriana Cornett Varsha Singh Jeyaraj Pandian Anirudh Kulkarni Pablo M Lavados Veronica V Olavarria Kenichi Todo Yuki Yamamoto Gisele Sampaio Silva Serdar Geyik Jasmine Johann Sumeet Multani Artem Kaliaev Kazutaka Sonoda Hiroyuki Hashimoto Adel Alhazzani David Y Chung Stephan A Mayer Johanna T Fifi Michael D Hill Hao Zhang Zhengzhou Yuan Xianjin Shang Alicia C Castonguay Rishi Gupta Tudor G Jovin Jean Raymond Osama O Zaidat Raul G Nogueira SVIN COVID-19 Registry,the Middle East North Africa Stroke and Interventional Neurotherapies Organization(MENA-SINO),Japanese Society of Vascular and Interventional Neurology Society(JVIN) | 2021 | Stroke & Vascular Neurology2021，6，4： | 0 |
| 10 | Efficacy and safety of bridging thrombolysis initiated before transfer in a drip-and-ship stroke service显示文摘Objective Data regarding the efficacy and safety of bridging thrombolysis(BT)initiated before transfer for evaluation of endovascular therapy is heterogeneous.We,therefore,analyse efficacy and safety of BT in patients treated within a drip-and-ship stroke service.Methods Consecutive adult patients suffering from acute ischaemic stroke and large-vessel occlusions(LVO)transferred to our comprehensive stroke centre for evaluation of endovascular therapy in 2017–2020 were identified from a local prospective stroke database and categorised according to BT and no-BT.BT was defined as intravenous thrombolysis initiated before transfer.LVO was assessed before and after transfer.Functional outcome before stroke and at 3 months using the modified Rankin scale(mRS)was determined.Excellent outcome was defined as mRS 0–1 or return to prestroke mRS.For safety analysis,intracranial haemorrhages and mortality at 3 months were analysed.Main analysis was limited to patients with anterior circulation stroke.Results Of N=714 patients,n=394(55.2%)received BT.More patients in the BT group with documented LVO before transfer recanalised without endovascular therapy(n=46,11.7%)than patients who did not receive BT before transfer(n=4,1.3%,p<0.001).In multivariate analysis,BT was the strongest independent predictor of early recanalisation(adjusted OR 10.9,95%CI 3.8 to 31.1,p<0.001).BT tended to be an independent predictor of an excellent outcome at 3 months(adjusted OR 1.38,95%CI 0.97 to 1.96,p=0.077).There were no differences in safety between the BT and no-BT groups.Conclusions BT initiated before transfer was a strong independent predictor of early recanalisation. | Jan Christoph Purrucker Miriam Heyse Simon Nagel Christoph Gumbinger Fatih Seker Markus Mohlenbruch Peter Arthur Ringleb | 2022 | Stroke & Vascular Neurology2022，7，1： | 0 |
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