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| 1 | Liver-specific gene expression in mesenchymal stem cells is induced by liver cells显示文摘AIM: The origin of putative liver cells from distinct bone marrow stem cells, e.g. hematopoietic stem cells or multipotent adult progenitor cells was found in recent in vitro studies. Cell culture experiments revealed a key role of growth factors for the induction of liver-specific genes in stem cell cultures. We investigated the potential of rat mesenchymal stem cells (MSC) from bone marrow to differentiate into hepatocytic cells in vitro. Furthermore,we assessed the influence of cocultured liver cells on induction of liver-specific gene expression.METHODS: Mesenchymal stem cells were marked with green fluorescent protein (GFP) by retroviral gene transduction. Clonal marked MSC were either cultured under liver stimulating conditions using fibronectin-coated culture dishes and medium supplemented with SCF, HGF,EGF, and FGF-4 alone, or in presence of freshly isolated rat liver cells. Cells in cocultures were harvested and GFP+ or GFP- cells were separated using fluorescence activated cell sorting. RT-PCR analysis for the stem cell marker Thy1 and the hepatocytic markers CK-18, albumin, CK-19,and AFP was performed in the different cell populations.RESULTS: Under the specified culture conditions, rat MSC cocultured with liver cells expressed albumin-, CK-18,CK-19, and AFP-RNA over 3 weeks, whereas MSC cultured alone did not show liver specific gene expression.CONCLUSION: The results indicate that (1) rat MSC from bone marrow can differentiate towards hepatocytic lineage in vitro, and (2) that the microenvironment plays a decisive role for the induction of hepatic differentiation of rMSC. | Claudia Lange Philipp Bassler Michael V. Lioznov Helge Bruns Dietrich Kluth Axel R. Zander Henning C. Fiegel | 2005 | World Journal of Gastroenterology2005，11，29： | 31 |
| 2 | 重组活化因子Ⅶ在急性颅内出血中的应用 | Mayer S.A. Brun N.C. Begtrup K. 郭俊 | 2005 | 世界核心医学期刊文摘(神经病学分册)2005，0，8： | 32 |
| 3 | Risk factors and outcome of bacterial infections in cirrhosis显示文摘Viable and non-viable pathological bacterial translocation promote a self-perpetuating circle of dysfunctional immune activation and systemic inflammation facilitating infections and organ failure in advanced cirrhosis.Bacterial infections and sepsis are now recognized as a distinct stage in the natural progression of chronic liver disease as they accelerate organ failure and contribute to the high mortality observed in decompensated cirrhosis.The increasing knowledge of structural,immunological and hemodynamic pathophysiology in advanced cirrhosis has not yet translated into significantly improved outcomes of bacterial infections over the last decades.Therefore,early identification of patients at the highest risk for developing infections and infectionrelated complications is required to tailor the currently available measures of surveillance,prophylaxis and therapy to the patients in need in order to improve the detrimental outcome of bacterial infections in cirrhosis. | Tony Bruns Henning W Zimmermann Andreas Stallmach | 2014 | World Journal of Gastroenterology2014，20，10： | 24 |
| 4 | Hepatocytic differentiation of mesenchymal stem cells in cocultures with fetal liver cells显示文摘瞄准:为了与胎儿的肝细胞(FLC ) 和可能性在合作文化调查间充质的干细胞(MSC ) 的 hepatocytic 区别膨胀,区分了 hepatocytic 房间。方法:MSC 被制动火箭与绿荧光灯的蛋白质(GFP ) 标记病毒的基因转导变异。同种细胞的显著 MSC 在用与干细胞补充的fibronectin涂的培养皿和媒介刺激条件的肝下面是也有教养的因素( SCF ), hepatocyte 生长因素( HGF ),表皮的生长因素( EGF ),和成纤维细胞生长因素 4 ( FGF-4 )独自一个,或在刚孤立的 FLC 的存在。在合作文化的房间被收获,并且 GFP+ 或 GFP- 房间用荧光被分开激活的房间排序。为肝 specific 标记 cytokeratin-18 (CK-18 ) 的反向的抄写聚合酶链反应(RT-PCR )( 法新社) ,白朊,和 alpha-fetoprotein 在不同房间人口被执行。结果:在指定文化条件下面,与 FLC co 有教养的老鼠 MSC 超过二个星期表示了白朊, CK-18,和 AFP-RNA。在 wk 3, MSC 失去了 hepatocytic 基因表示,可能由于 cocultured FLC 的增生。FLC 也在合作文化和一个很高的生长潜力显示出稳定的肝 specific 基因表情。结论:从骨髓的老鼠 MSC 能面对 FLC 在试管内区分 hepatocytic 房间,在合作文化的 MSC 的存在也为 FLC 的扩大和区别提供有益的环境。 | Claudia Lange Helge Bruns Dietrich Kluth Axel R Zander Henning C Fiegel | 2006 | World Journal of Gastroenterology2006，12，15： | 23 |
| 5 | Dual-sugar tests of small intestinal permeability are poor predictors of bacterial infections and mortality in cirrhosis: a prospective study显示文摘AIM: To prospectively analyze the impact of increased intestinal permeability(IP) on mortality and the occurrence of infections in patients with cirrhosis.METHODS: IP was quantified using the lactulose/mannitol(L/M) test in 46 hospitalized patients with cirrhosis(25 Child-Pugh A/B, 21 Child-Pugh C) and in 16 healthy controls. Markers of inflammation [LPSbinding protein, Interleukin-6(IL-6)] and enterocyte death [intestinal fatty-acid binding protein(I-FABP)] were determined in serum using enzyme-linked immunosorbent assays. Patients were followed for one year and assessed for survival, liver transplantation, the necessity of hospitalization and the occurrence of bacterial infections. The primary endpoint of the study was defined as differences in survival between patients with pathological and without pathological lactulose/mannitol test.RESULTS: Thirty-nine(85%) patients with cirrhosis had a pathologically increased IP index(L/M ratio > 0.07) compared to 4(25%) healthy controls(P < 0.0001). The IP index correlated with the ChildPugh score(r = 0.484, P = 0.001) and with serum IL-6(r = 0.342, P = 0.02). Within one year, nineteen(41%) patients developed a total of 33 episodes of hospitalization with bacterial or fungal infections. Although patients who developed spontaneous bacterial peritonitis(SBP)(n = 7) had a higher IP index than patients who did not(0.27 vs 0.14, P = 0.018), the baseline IP index did not predict time to infection, infection-free survival or overall survival, neither when assessed as linear variable, as tertiles, nor dichotomized using an established cut-off. In contrast, model for end-stage liver disease score, Child-Pugh score, the presence of ascites, serum IL-6 and I-FABP were univariate predictors of infection-free survival.CONCLUSION: Although increased IP is a frequent phenomenon in advanced cirrhosis and may predispose to SBP, it failed to predict infection-free and overall survival in this prospective cohort study. | Anika Vogt Philipp A Reuken Sven Stengel Andreas Stallmach Tony Bruns | 2016 | World Journal of Gastroenterology2016，22，11： | 8 |
| 6 | 大鼠肾移植1000例经验总结显示文摘目的:对大鼠肾移植进行经验总结以指导实验与临床研究。方法:作者在2004-01/2009-07海德堡大学移植中心期间,采用大鼠肾动、静脉与腹主动脉、腔静脉行端侧吻合。对于急性肾移植模型,输尿管直接植入膀胱内;对于慢性肾移植模型,输尿管采用端端吻合法。术中直接切除对侧肾脏,完成大鼠肾移植1000例,并对其进行总结。结果:只要供体肾脏冲洗良好,吻合时暖缺血时间小于30min,手术时间60min左右,吻合技术娴熟,移植成功率达98%以上。结论:该实验模型安全、方便、可行。肾移植成功的关键是手术技术。 | 李占清 关晓海 王世军 陈晶 伊雪 邬鹏宇 肖志 Nickkholgh Arash Bruns Helge Hoffmann Katrin Schemmer Peter | 2011 | 中国组织工程研究与临床康复2011，15，5： | 7 |
| 7 | Acoustic radiation force impulse imaging for assessing liver fibrosis in alcoholic liver disease显示文摘AIM: To evaluate the performance of elastography by ultrasound with acoustic radiation force impulse(ARFI) in determining fibrosis stage in patients with alcoholic liver disease(ALD) undergoing alcoholic detoxification in relation to biopsy.METHODS: Eighty-three patients with ALD undergoing detoxification were prospectively enrolled. Each patient underwent ARFI imaging and a liver biopsy onthe same day. Fibrosis was staged according to the METAVIR scoring system. The median of 10 valid ARFI measurements was calculated for each patient.RESULTS: Sixty-nine males and thirteen females(one patient excluded due to insufficient biopsy size) were assessed with a mean alcohol consumption of 132.4 ± 128.8 standard drinks per week and mean cumulative year duration of 17.6 ± 9.5 years. Sensitivity and specificity were respectively 82.4%(0.70-0.95) and 83.3%(0.73-0.94)(AUROC = 0.87) for F ≥ 2 with a cut-off value of 1.63m/s; 82.4%(0.64-1.00) and 78.5%(0.69-0.89)(AUROC = 0.86) for F ≥ 3 with a cut-off value of 1.84m/s; and 92.3%(0.78-1.00] and 81.6%(0.72-0.90)(AUROC = 0.89) for F = 4 with a cut-off value of 1.94 m/s.CONCLUSION: ARFI is an accurate, non-invasive and easy method for assessing liver fibrosis in patients with ALD undergoing alcoholic detoxification. | Anita Kiani Vanessa Brun Fabrice Lainé Bruno Turlin Jeff Morcet Sophie Michalak Antonia Le Gruyer Ludivine Legros Edouard Bardou-Jacquet Yves Gandon Romain Moirand | 2016 | World Journal of Gastroenterology2016，22，20： | 6 |
| 8 | Anti-hepatitis C virus potency of a new autophagy inhibitor using human liver slices model显示文摘AIM: To evaluate the antiviral potency of a new antihepatitis C virus(HCV) antiviral agent targeting the cellular autophagy machinery. METHODS: Non-infected liver slices, obtained from human liver resection and cut in 350 μm-thick slices(2.7 × 106 cells per slice) were infected with cell culture-grown HCV Con1b/C3 supernatant(multiplicity of infection = 0.1) cultivated for up to ten days. HCV infected slices were treated at day 4 post-infection with GNS-396 for 6 d at different concentrations. HCV replication was evaluated by strand-specific real-time quantitative reverse transcription- polymerase chain reaction. The infectivity titers of supernatants were evaluated by foci formation upon inoculation into naive Huh-7.5.1 cells. The cytotoxic effect of the drugs was evaluated by lactate dehydrogenase leakage assays. RESULTS: The antiviral efficacy of a new antiviral drug, GNS-396, an autophagy inhibitor, on HCV infection of adult human liver slices was evidenced in a dosedependent manner. At day 6 post-treatment, GNS-396 EC50 was 158 nmol/L without cytotoxic effect(compared to hydroxychloroquine EC50 = 1.17 μmol/L).CONCLUSION: Our results demonstrated that our ex vivo model is efficient for evaluation the potency of autophagy inhibitors, in particular a new quinoline derivative GNS-396 as antiviral could inhibit HCV infection in a dosedependent manner without cytotoxic effect. | Sylvie Lagaye Sonia Brun Jesintha Gaston Hong Shen Ruzena Stranska Claire Camus Clarisse Dubray Géraldine Rousseau Pierre-Philippe Massault Jerome Courcambeck Firas Bassisi Philippe Halfon Stanislas Pol | 2016 | World Journal of Hepatology2016，8，21： | 5 |
| 9 | Distinct Populations of Cancer Stem Cells Determine Tumor Growth and Metastatic Activity in Human Pancreatic Cancer显示文摘 | Patrick C. Hermann Stephan L. Huber Tanja Herrler Alexandra Aicher Joachim W. Ellwart Markus Guba Christiane J. Bruns Christopher Heeschen | 2007 | Cell Stem Cell2007，，3： | 5 |
| 10 | Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms显示文摘The infusion of coronavirus disease 2019(COVID-19)patients with mesenchymal stem cells(MSCs)potentially improves clinical symptoms,but the underlying mechanism remains unclear.We conducted a randomized,single-blind,placebo-controlled(29 patients/group)phase II clinical trial to validate previous findings and explore the potential mechanisms.Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay(P=0.0198)and less time required for symptoms remission(P=0.0194)than those who received placebo.Based on chest images,both severe and critical patients treated with MSCs showed improvement by day 7(P=0.0099)and day 21(P=0.0084).MSC-treated patients had fewer adverse events.MSC infusion reduced the levels of C-reactive protein,proinflammatory cytokines,and neutrophil extracellular traps(NETs)and promoted the maintenance of SARS-CoV-2-specific antibodies.To explore how MSCs modulate the immune system,we employed single-cell RNA sequencing analysis on peripheral blood.Our analysis identified a novel subpopulation of VNN2+hematopoietic stem/progenitorlike(HSPC-like)cells expressing CSF3R and PTPRE that were mobilized following MSC infusion.Genes encoding chemotaxis factors—CX3CR1 and L-selectin—were upregulated in various immune cells.MSC treatment also regulated B cell subsets and increased the expression of costimulatory CD28 in T cells in vivo and in vitro.In addition,an in vivo mouse study confirmed that MSCs suppressed NET release and reduced venous thrombosis by upregulating kindlin-3 signaling.Together,our results underscore the role of MSCs in improving COVID-19 patient outcomes via maintenance of immune homeostasis. | Rongjia Zhu Tingdong Yan Yingmei Feng Yan Liu Hongcui Cao Gongxin Peng Yanlei Yang Zhen Xu Jingqi Liu Wei Hou Xiaoyue Wang Zhe Li Luchan Deng Shihua Wang Jing Li Qin Han Hongling Li Guangliang Shan Yinghao Cao Xingyan An Jianshe Yan Zhonghui Zhang Huafei Li Xuebin Qu Jiaqi Zhu Shumin Zhou Jiao Wang Fengchun Zhang Jinming Gao Ronghua Jin Dayong Xu Yan-Qing Ma Tao Huang Shuang Peng Zhi Zheng Ilia Stambler Eric Gilson Lee Wei Lim Alexey Moskalev Antonio Cano Sasanka Chakrabarti Brun Ulfhake Huanxing Su Haoying Xu Sihuan Xu Feng Wei Holly MBrown-Borg Kyung-Jin Min Georgina Ellison-Hughes Calogero Caruso Kunlin Jin Robert Chunhua Zhao | 2021 | Cell Research2021，31，12： | 5 |
| 11 | 内燃机车动车液力传动装置的发展水平显示文摘从1932年和1934年起,液力传动装置先后在内燃动车和内燃机车上开始得到应用。60年来液力传动装置的效率、牵引性能和大修周期得到了很大的提高,所传递的功率达到了2200kW。目前利用电子组件与液力传动装置相结合的技术,使工况机构可以在机车运行中实现换档,从而进一步扩大了液力传动装置的工作范围,使内燃机车动车液力传动装置达到了新的技术水平。在未来铁路机车动车传动方式造型中,是一种很经济的选择。 | Hermann Bruns 涂俊武 | 1994 | 国外内燃机车1994，，5： | 5 |
| 12 | Safety and Efficacy of Antigen-Specific Regulatory T-Cell Therapy for Patients With Refractory Crohn’s Disease显示文摘 | Pierre Desreumaux Arnaud Foussat Matthieu Allez Laurent Beaugerie Xavier Hébuterne Yoram Bouhnik Maria Nachury Valérie Brun Hervé Bastian Nathalie Belmonte Michel Ticchioni Agnès Duchange Patricia Morel–Mandrino Virginie Neveu Nathalie Clerget–Chossat Mig | 2012 | Gastroenterology2012，，5： | 4 |
| 13 | Prognostic value of CA 19-9, CEA, CRP, LDH and bilirubin levels in locally advanced and metastatic pancreatic cancer: results from a multicenter, pooled analysis of patients receiving palliative chemotherapy显示文摘 | Michael Haas Volker Heinemann Frank Kullmann Rüdiger P. Laubender Christina Klose Christiane J. Bruns Stefan Holdenrieder Dominik P. Modest Christoph Schulz Stefan Boeck | 2013 | Journal of Cancer Research and Clinical Oncology2013，，4： | 4 |
| 14 | Smart biomaterials: Surfaces functionalized with proteolytically stable osteoblast-adhesive peptides显示文摘Engineered scaffolds for bone tissue regeneration are designed to promote cell adhesion,growth,proliferation and differentiation.Recently,covalent and selective functionalization of glass and titanium surfaces with an adhesive peptide(HVP)mapped on[351e359]sequence of human Vitronectin allowed to selectively increase osteoblast attachment and adhesion strength in in vitro assays,and to promote osseointegration in in vivo studies.For the first time to our knowledge,in this study we investigated the resistance of adhesion sequences to proteolytic digestion:HVP was completely cleaved after 5 h.In order to overcome the enzymatic degradation of the native peptide under physiological conditions we synthetized three analogues of HVP sequence.A retro-inverted peptide D-2HVP,composed of D amino acids,was completely stable in serum-containing medium.In addition,glass surfaces functionalized with D-2HVP increased human osteoblast adhesion as compared to the native peptide and maintained deposition of calcium.Interestingly,D-2HVP increased expression of IBSP,VTN and SPP1 genes as compared to HVP functionalized surfaces.Total internal reflection fluorescence microscope analysis showed cells with numerous filopodia spread on D-2HVP-functionalized surfaces.Therefore,the D-2HVP sequence is proposed as new osteoblast adhesive peptide with increased bioactivity and high proteolytic resistance. | Annj Zamuner Paola Brun Michele Scorzeto Giuseppe Sica Ignazio Castagliuolo Monica Dettin | 2017 | Bioactive Materials2017，2，3： | 3 |
| 15 | Arrhythmogenic right ventricular cardiomyopathy: From genetics to diagnostic and therapeutic challenges显示文摘Arrhythmogenic right ventricular cardiomyopathy(ARVC) is a genetic disease characterized by myocyte loss and fibro-fatty tissue replacement. Diagnosis of ARVC remains a clinical challenge mainly at its early stages and in patients with minimal echocardiographic right ventricular(RV) abnormalities. ARVC shares some common features with other cardiac diseases, such as RV outflow ventricular tachycardia, Brugada syndrome, and myocarditis, due to arrhythmic expressivity and biventricular involvement. The identification of ARVC can be often challenging, because of the heterogeneous clinical presentation, highly variable intra- and inter-family expressivity and incomplete penetrance. This genotypephenotype 'plasticity' is largely unexplained. A familial history of ARVC is present in 30% to 50% of cases, and the disease is considered a genetic cardiomyopathy, usually inherited in an autosomal dominant pattern with variable penetrance and expressivity; in addition, autosomal recessive forms have been reported(Naxos disease and Carvajal syndrome). Diagnosis of ARVC relays on a scoring system, with major or minorcriteria on the Revised Task Force Criteria. Implantable cardioverter defibrillators(ICDs) are increasingly utilized in patients with ARVC who have survived sudden death(SD)(secondary prevention). However, there are few data available to help identifying ARVC patients in whom the prophylactic implantation of an ICD is truly warranted. Prevention of SD is the primary goal of management. Pharmacologic treatment of arrhythmias, catheter ablation of ventricular tachycardia, and ICD are the mainstay of treatment of ARVC. | Bruno Pinamonti Francesca Brun Luisa Mestroni Gianfranco Sinagra | 2014 | World Journal of Cardiology2014，6，12： | 3 |
| 16 | Evaluation of copper avail- ability to plants in copper- contaminated vineyard soils显示文摘 | L A Brun J Makllet P Hinsinger | 2001 | Environ- mental Pollution2001，111，： | 3 |
| 17 | Insulin-like growth factor 1-induced enolase 2 deacetylation by HDAC3 promotes metastasis of pancreatic cancer显示文摘Enolase 2(ENO2)is a key glycolytic enzyme in the metabolic process of glycolysis,but its potential function in pancreatic ductal adenocarcinoma(PDAC)is unclear.In this study,we observed a significant overexpression of ENO2 in PDAC tissues,and its expression was correlated with metastasis and poor prognosis in PDAC patients.K394 was identified as a major acetylation site in ENO2 that regulates its enzymatic activity,cell metabolism and PDAC progression.Knockdown of ENO2 suppressed tumor growth and liver metastasis in PDAC.Re-expression of wild-type(WT)ENO2,but not the K394 acetylation mimetic mutant,could reverse the decreased tumor malignancy.We further characterized histone deacetylase 3(HDAC3)and P300/CBP-associated factor(PCAF)as the potential deacetylase and acetyltransferase for ENO2,respectively.HDAC3-mediated deacetylation was shown to lead to ENO2 activation and enhancement of glycolysis.Importantly,insulin-like growth factor-1(IGF-1)was found to decrease K394 acetylation and stimulate ENO2 activity in a dose-and time-dependent manner.The PI3K/AKT/mTOR pathway facilitated the phosphorylation of HDAC3 on S424,which promoted K394 deacetylation and activation of ENO2.Linsitinib,an oral small-molecule inhibitor of IGF-1R,could inhibit IGF-1-induced ENO2 deacetylation by HDAC3 and the PI3K/AKT/mTOR pathway.Furthermore,linsitinib showed a different effect on the growth and metastasis of PDAC depending on the overexpression of WT versus K394-mutant ENO2.Our results reveal a novel mechanism by which acetylation negatively regulates ENO2 activity in the metastasis of PDAC by modulating glycolysis.Blockade of IGF-1-induced ENO2 deacetylation represents a promising strategy to prevent the development of PDAC. | Yan Zheng Chao Wu Jimeng Yang Yue Zhao Huliang Jia Min Xue Da Xu Feng Yang Deliang Fu Chaoqun Wang Beiyuan Hu Ze Zhang Tianen Li Shican Yan Xuan Wang Peter J.Nelson Christiane Bruns Lunxiu Qin Qiongzhu Dong | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 3 |
| 18 | Immunodominance and functional alterations of tumor‐associated antigen‐specific CD8+ T‐cell responses in hepatocellular carcinoma显示文摘 | Tobias Flecken Nathalie Schmidt Sandra Hild Emma Gostick Oliver Drognitz Robert Zeiser Peter Schemmer Helge Bruns Thomas Eiermann David A. Price Hubert E. Blum Christoph Neumann‐Haefelin Robert Thimme | 2014 | Hepatology2014，，： | 2 |
| 19 | A review of earthworm impact on soil function and ecosystem services显示文摘 | M. Blouin M. E. Hodson E. A. Delgado G. Baker L. Brussaard K. R. Butt J. Dai L. Dendooven G. Peres J. E. Tondoh D. Cluzeau J.‐J. Brun | 2013 | Eur J Soil Sci2013，，2： | 2 |
| 20 | Towards a unified paradigm for sequence‐based identification of fungi显示文摘 | Urmas K?ljalg R. Henrik Nilsson Kessy Abarenkov Leho Tedersoo Andy F. S. Taylor Mohammad Bahram Scott T. Bates Thomas D. Bruns Johan Bengtsson‐Palme Tony M. Callaghan Brian Douglas Tiia Drenkhan Ursula Eberhardt Margarita Due?as Tine Grebenc Gareth W. Gri | 2013 | Mol Ecol2013，，21： | 2 |
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