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Transcription networks in liver development and acute liver failure

Liver Research 2023年第1期7卷 47-55页

作者： Rilu Feng roman liebe Hong-Lei Weng Department of Medicine II Section Molecular HepatologyUniversity Medical Center MannheimMedical Faculty MannheimHeidelberg UniversityMannheimGermany Clinic of Gastroenterology Hepatology and Infectious DiseasesHeinrich Heine UniversityDüsseldorfGermany Department of Medicine II Saarland University Medical CentreSaarland UniversityHomburgGermany

Acute liver failure(ALF)is a medical emergency due to massive hepatocyte *** such a harsh condition,maintaining transcriptional regulation in the remaining hepatocytes while activating similar transcription factor networks in liver progenitor cells(LPCs)to ensure essential liver functions are two critical processes to rescue patients from liver failure and *** this review,we discuss the formation and functions of transcription networks in ALF and liver *** focus on a hierarchical network of transcription factors that responds to different pathophysiological circumstances:(1)Under normal circumstances,pioneer factor forkhead box protein A2(FOXA2)coordinates several constitutive hepatic transcription factors,such as hepatic nuclear factor 4 alpha(HNF4a)and CCAAT-enhancer binding protein a(C/EBPa),which ensure normal liver function;(2)When the expression of both HNF4a and C/EBPa in hepatocytes are disrupted by severe inflammation,retinoic acid receptor(RAR)is the alternative transcription factor that compensates for their absence;(3)When massive hepatic necrosis occurs,a similar transcription network including FOXA2 and HNF4a,is activated as a“rescue network”in LPCs to maintain vital liver functions when hepatocytes fail,and thus ensures *** of these master transcription factors in hepatocytes and LPCs is tightly regulated by hormone signals and *** performance of this hierarchical transcription network,in particularly the“rescue network”described above,significantly affects the clinical outcome of ALF.

关键词： Pioneer transcription factor Lineage-determining transcription factor Signal-driven transcription factor Hepatocyte Massive hepatic necrosis Liver progenitor cell

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Computed tomography vs liver stiffness measurement and magnetic resonance imaging in evaluating esophageal varices in cirrhotic patients:A systematic review and meta-analysis

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World Journal of Gastroenterology 2020年第18期26卷 2247-2267页

作者： Yue Li Lei Li Hong-Lei Weng roman liebe Hui-Guo Ding Department of Gastroenterology and Hepatology Beijing You’an Hospital Affiliated with Capital Medical UniversityBeijing 100069China Department of Medicine Ⅱ Section Molecular HepatologyMedical Faculty MannheimHeidelberg UniversityMannheim 68167Germany Department of Medicine Ⅱ Saarland University Medical CenterHomburg 66424Germany

BACKGROUND Computed tomography(CT),liver stiffness measurement(LSM),and magnetic resonance imaging(MRI)are non-invasive diagnostic methods for esophageal varices(EV)and for the prediction of high-bleeding-risk EV(HREV)in cirrhotic ***,the clinical use of these methods is *** To evaluate the accuracy of LSM,CT,and MRI in diagnosing EV and predicting HREV in cirrhotic *** We performed literature searches in multiple databases,including Pub Med,Embase,Cochrane,CNKI,and Wanfang databases,for articles that evaluated the accuracy of LSM,CT,and MRI as candidates for the diagnosis of EV and prediction of HREV in cirrhotic *** sensitivity and specificity,positive likelihood ratio and negative likelihood ratio,diagnostic odds ratio,and the areas under the summary receiver operating characteristic curves were *** quality of the articles was assessed using the quality assessment of diagnostic accuracy studies-2 *** was examined by Q-statistic test and I2 index,and sources of heterogeneity were explored using metaregression and subgroup *** bias was evaluated using Deek’s funnel *** statistical analyses were conducted using Stata12.0,Meta Disc1.4,and Rev *** Overall,18,17,and 7 relevant articles on the accuracy of LSM,CT,and MRI in evaluating EV and HREV were retrieved.A significant heterogeneity was observed in all analyses(P<0.05).The areas under the summary receiver operating characteristic curves of LSM,CT,and MRI in diagnosing EV and predicting HREV were 0.86(95%confidence interval[CI]:0.83-0.89),0.91(95%CI:0.88-0.93),and 0.86(95%CI:0.83-0.89),and 0.85(95%CI:0.81-0.88),0.94(95%CI:0.91-0.96),and 0.83(95%CI:0.79-0.86),respectively,with sensitivities of 0.84(95%CI:0.78-0.89),0.91(95%CI:0.87-0.94),and 0.81(95%CI:0.76-0.86),and 0.81(95%CI:0.75-0.86),0.88(95%CI:0.82-0.92),and 0.80(95%CI:0.72-0.86),and specificities of 0.71(95%CI:0.60-0.80),0.75(95%CI:0.68-0.82),and 0.82(9

关键词： Multidetector computed tomography imaging Magnetic resonance imaging Liver stiffness measurement Liver cirrhosis Esophageal varices Meta-analysis

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Can a fibrotic liver afford epithelial-mesenchymal transition?

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World Journal of Gastroenterology 2017年第26期23卷 4661-4668页

作者： Stefan Munker Yong-Le Wu Hui-Guo Ding roman liebe Hong-Lei Weng Department of MedicineⅡ Section Molecular HepatologyMedical Faculty MannheimHeidelberg University Department of MedicineⅠ University Medical CenterRegensburg University Department of Gastroenterology and Hepatology Beijing You’an Hospital affiliated to Capital Medical University Major infectious diseases Collaborative Innovation Center Department of MedicineⅡ Saarland University Medical CenterSaarland University

The question whether epithelial-mesenchymal transition (EMT) occurs during liver fibrogenesis is a controversial issue. In vitro studies confirm that hepatocytes or cholangiocytes undergo EMT upon transforming growth factor beta (TGF-beta) stimulation, whereas in vivo experiments based on genetic fate mapping of specific cell populations suggest that EMT does not occur in fibrotic animal models. In this review we present current data supporting or opposing EMT in chronic liver disease and discuss conditions for the occurrence of EMT in patients. Based on the available data and our clinical observations we hypothesize that EMT-like alterations in liver cirrhosis are a side effect of high levels of TGF-beta and other pro-fibrotic mediators rather than a biological process converting functional parenchyma, i.e., hepatocytes, into myofibroblasts at a time when essential liver functions are deteriorating.

关键词： Epithelial-mesenchymal transition Liver fibrosis Liver cirrhosis Transforming growth factor-beta

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Crosstalk between hepatic stellate cells and tumor cells in the development of hepatocellular carcinoma

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Chinese Medical Journal 2021年第21期134卷 2544-2546页

作者： Ya-Nan Ma Shan-Shan Wang roman liebe Hui-Guo Ding Department of Gastroenterology and Hepatology Beijing Youan Hospital Affiliated with Capital Medical UniversityBeijing 100069China Department of Molecular Biology Beijing Institute of HepatologyBeijing Youan HospitalCapital Medical UniversityBeijing100069China Department of Gastroenterology Hepatology and Infectious DiseasesUniversity Hospital DusseldorfDusseldorfGermany

Hepatocellular carcinoma(HCC)ranks sixth in population age-standardized incidence(ASI)and fourth in population age-standardized mortality(ASM)globally and is the fourth ASI and the second ASM.

关键词： mortality hepatic carcinoma

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Elevated core-fucosylated Ig G is a new marker for hepatitis B virus-related hepatocellular carcinoma

Elevated core-fucosylated Ig G is a new marker for hepatitis...

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第十届全国免疫学学术大会

作者： Chang-Hong Yi Hong-Lei Weng Fei-Guo Zhou Meng Fang Jun Ji Cheng Cheng Hao Wang roman liebe Steven Dooley Chun-Fang Gao Department of Laboratory Medicine Eastern Hepatobiliary Surgery Hospital Second Military Medical University Molecular Alcohol Research in Gastroenterology Department of Medicine II Germany Faculty of Medicine at Mannheim University of Heidelberg Department of Hepatic Surgery VI Eastern Hepatobiliary Surgery Hospital Second Military Medical University Department of Laboratory Medicine Changzheng Hospital Second Military Medical University

Immunoglubulin G(Ig G)and its abnormal glycosylations are associated with *** present study investigates the relationship between cancer-derived Ig G and clinicopathological characteristics in hepatocellular carcinoma(HCC),assesses the value of serum N-glycosylated Ig G in diagnosing and monitoring hepatitis B virus(HBV)-related *** microarray analysis of 90 HCC tissues showed that HCC patients with Ig G immune positivity had higher

关键词： IgG tissue array diagnosis Lens culinaris agglutinin(LCA) non-invasive biomarker hepatocellular carcinoma(HCC)

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Cis-hydroxyproline-induced inhibition of pancreatic cancer cell growth is mediated by endoplasmic reticulum stress

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World Journal of Gastroenterology 2006年第10期12卷 1569-1576页

作者： Christoph Mueller Joerg Emmrich Robert Jaster Dagmar Braun Stefan liebe Gisela Sparmann Department of Medicine Division of Gastroenterology University of RostockGermany Riemser Arzneimittel AG Greifswald Germany Supported by the Bundeministerium für Bildung und Forschunggrant 01ZZ0108

AIM： To investigate the biological effects of cishydroxyproline （CHP） on the rat pancreatic carcinoma cell line DSL6A, and to examine the underlying molecular mechanisms. METHODS： The effect of CHP on DSL6A cell proliferation was assessed by using BrdU incorporation. The expression of focal adhesion kinase （FAK） was characterized by Western blotting and immunofluorescence. Induction of endoplasmic reticulum （ER） stress was investigated by using RT-PCR and Western blotting for the glucose-related protein-78 （GRP78） and growth arrest and DNA inducible gene （GADD153）. Cell viability was determined through measuring the metabolic activity based on the reduction potential of DSL6A cells. Apoptosis was analyzed by detection of caspase-3 activation and cleavage of poly（ADP-ribose） polymerase （PARP） as well as DNA laddering. RESULTS： In addition to inhibition of proliferation, incubation with CHP induced proteolytic cleavage of FAK and a delocalisation of the enzyme from focal adhesions, followed by a loss of cell adherence. Simultaneously, we could show an increased expression of GRP78 and GADD153, indicating a CHP-mediated activation of the ER stress cascade in the DSL6A cell line. Prolonged incubation of DSL6A cells with CHP finally resulted in apoptotic cell death. Beside L-proline, the inhibition of intracellular proteolysis by addition of a broad spectrum protease inhibitor could abolish the effects of CHP on cellular functions and the molecular processes. In contrast, impeding the activity of apoptosis-executing caspases had no influence on CHP-mediated cell damage.CONCLUSION： Our data suggest that the initiation of ER stress machinery by CliP leads to an activation of intracellular proteolytic processes, including caspaseindependent FAK degradation, resulting in damaging pancreatic carcinoma cells.

关键词： Cis-hydroxyproline Pancreatic cancer cell endoplasrnic reticulurn stress FAK Caspase-3

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甜点师速成记

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美食与美酒 2012年第7期 32-34页

作者： Anita(编译) Ryan liebe(摄影)

F＆W的编辑Grace Parisi跟着出生在突尼斯的甜点师Ghaya Oliveira，上了一堂甜点速成课，我们看看她都学了哪些手艺。

关键词：甜点速成 Grace 突尼斯

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Expression of tissue factor in pancreatic adenocarcinoma is associated with activation of coagulation

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World Journal of Gastroenterology 2006年第30期12卷 4843-4849页

作者： Stephan L Haas Ralf Jesnowski Michael Steiner Frank Hummel Jrg Ringel Christine Burstein Horst Nizze Stefan liebe J Matthias Lhr Department of Medicine II University of Heidelberg at Mannheim Germany Department of Clinical Chemistry and Pathobiochemistry University of Rostock Rostock Germany Department of Pathology University of Rostock Rostock Germany Department of Medicine University of Rostock Rostock Germany

AIM： To study expression of tissue factor （TF） in pancreatic cancer and its role in the development of thromboembolism.METHODS： TF expression was studied in eight human pancreatic carcinoma cell lines by Northern blot and indirect immunofluorescence. Expression of alternatively spliced TF （asTF） was assessed by RT-PCR. In addition, TF expression was determined by immunofluorescence in pancreatic tissues of 19 patients with pancreatic adenocarcinoma （PCa）, 9 patients with chronic pancreatitis （CP） and 20 normal controls. Plasma samples （30 PCa-patients, 13 CP-patients and 20 controls） were investigated for soluble TF levels and coagulation activation markers [thrombin-antithrombin Ⅲ complex （TAT）, prothrombin fragment 1 ＋ 2 （F1 ＋ 2）]. RESULTS： All pancreatic carcinoma cell lines expressed TF （8/8） and most of them expressed asTF （6/8）. TF expression at the protein level did not correlate with the differentiation of the carcinoma cell line. All but two pancreatic cancer tissue samples stained positive for TF （17/19）. In all samples of CP weak staining was restricted to pancreatic duct cells, whereas only a few subendothelial cells were positive in 9/20 of normal controls. TF and TAT levels in PCa patients were significantly elevated compared to controls whereas elevated F1 ＋ 2 levels did not reach statistical significance compared to controls. In CP patients TAT and F1 ＋ 2 levels proved to be significantly elevated compared to controls, although TAT elevation was less pronounced than in PCa patients. CONCLUSION： We conclude that in addition to the upregulated expression of TF on the cell membrane, soluble TF might contribute to activation of the coagulation system in pancreatic cancer.

关键词： Coagulation activation Pancreatic carcinoma Thromboembolism Thrombosis Tissue factor

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基于微机电系统的太阳敏感器

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控制工程（北京） 2002年第6期 32-39页

作者： Carl Christian liebe Sohrab Mobasser 郑克隆

卫星姿态确定分系统广泛采用太阳敏感器来测量卫星坐标系中的太阳矢量。本文介绍一种基于微机电系统(MEMS)的实验型太阳敏感器。这台太阳敏感器样机包含一块带有数百个小孔的硅片掩模。掩模安放在一只电荷耦合器件(CCD)焦平面阵列顶上,... 详细信息

卫星姿态确定分系统广泛采用太阳敏感器来测量卫星坐标系中的太阳矢量。本文介绍一种基于微机电系统(MEMS)的实验型太阳敏感器。这台太阳敏感器样机包含一块带有数百个小孔的硅片掩模。掩模安放在一只电荷耦合器件(CCD)焦平面阵列顶上,距焦平面750μm。当太阳照射此装置时,在焦平面上形成孔径图像。对这个图像进行分析,就可以算出太阳角。试验数据表明,这种太阳敏感器可以达到的精度约为二三角分,或者更好一点。计划利用一个有源像元敏感器(APS)焦平面阵列器件,把这种太阳敏感器的体积做得像3个美国1角银币相互重叠起来那么大,其质量轻于30g,功耗低于20mW。这种太阳敏感器将成为微型与超小型卫星以及小型行星漫游车上使用的理想部件。

关键词：太阳敏感器微机电系统电荷耦合器件成像芯片超小型卫星姿态控制系统

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有理正交矩阵的构造

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驻马店师专学报 1992年第2期7卷 12-13页

作者： liebe.,H 张诚一

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