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| 1 | Alcoholic liver disease and hepatitis C:A frequently underestimated combination显示文摘Alcoholic liver disease(ALD) and hepatitis C virus(HCV) infection represent, either alone or in combination, more than two thirds of all patients with liver disease in the Western world.This review discusses the epidemiology and combined impact of ALD and HCV on the progres sion of liver disease.ALD and HCV affect the progres sion of liver disease to liver cirrhosis and hepatocellular carcinoma(HCC) in a synergistic manner.Thus, the risk for HCC increases f ive times with a daily alcohol con sumption of 80 g;in the presence of HCV it is increased 20fold, and a combination of both risk factors leads to a more than 100fold risk for HCC development.Alcohol consumption also decreases the response to interferon treatment which is probably due to a lack of compliance than a direct effect on HCV replication.Several molecu lar mechanisms are discussed that could explain the synergistic interaction of alcohol and HCV on disease progression.They include modulation of the immune response and apoptosis, increased oxidative stress via induction of CYP2E1 and the hepatic accumulation of iron.Thus, both HCV and alcohol independently cause hepatic iron accumulation in > 50% of patients probably due to suppression of the liversecreted systemic iron hormone hepcidin.A better understanding of hepcidin regulation could help in developing novel therapeutic approaches to treat the chronic disease in the future.For now, it can be generally concluded that HCVinfect ed patients should abstain from alcohol and alcoholicsshould be encouraged to participate in detoxification programs. | Sebastian Mueller Gunda Millonig Helmut K Seitz | 2009 | World Journal of Gastroenterology2009，15，28： | 18 |
| 2 | Non-invasive diagnosis of alcoholic liver disease显示文摘Alcoholic liver disease(ALD)is the most common liver disease in the Western world.For many reasons,it isunderestimated and underdiagnosed.An early diagnosis is absolutely essential since it(1)helps to identify patients at genetic risk for ALD;(2)can trigger efficient abstinence namely in non-addicted patients;and(3)initiate screening programs to prevent life-threateningcomplications such as bleeding from varices,spontaneous bacterial peritonitis or hepatocellular cancer.The two major end points of ALD are alcoholic liver cirrhosis and the rare and clinically-defined alcoholic hepatitis(AH).The prediction and early diagnosis of both entities is still insufficiently solved and usually relies on acombination of laboratory,clinical and imaging findings.It is not widely conceived that conventional screeningtools for ALD such as ultrasound imaging or routine laboratory testing can easily overlook ca.40%of manifest alcoholic liver cirrhosis.Non-invasive methods such as transient elastography(Fibroscan),acoustic radiation force impulse imaging or shear wave elastography have significantly improved the early diagnosis of alcoholiccirrhosis.Present algorithms allow either the exclusion or the exact definition of advanced fibrosis stages in ca.95%of patients.The correct interpretation of liver stiffness requires a timely abdominal ultrasound and actual transaminase levels.Other non-invasive methods such as controlled attenuation parameter,serum levels of M30 or M65,susceptometry or breath tests are under current evaluation to assess the degree of steatosis,apoptosis and iron overload in these patients.Liver biopsy still remains an important option to rule out comorbidities and to confirm the prognosis namely for patients with AH. | Sebastian Mueller Helmut Karl Seitz Vanessa Rausch | 2014 | World Journal of Gastroenterology2014，20，40： | 15 |
| 3 | Heme oxygenase-1 as a therapeutic target in inflammatory disorders of the gastrointestinal tract显示文摘Heme oxygenase (HO)-1 is the inducible isoform of the first and rate-limiting enzyme of heme degradation. HO-1 not only protects against oxidative stress and apoptosis, but has received a great deal of attention in recent years because ofits potent anti-inflammatory functions. Studies with HO-1 knockout animal models have led to major advances in the understanding of how HO-1 might regulate inflammatory immune responses, although little is known on the underlying mechanisms. Due to its beneficial effects the targeted induction of this enzyme is considered to have major therapeutic po- tential for the treatment ofinflammatory disorders. This review discusses current knowledge on the mechanisms that mediate anti-inflammatory protection by HO-1. More specifically, the article deals with the role of HO-1 in the pathophysiology of viral hepatitis, inflammatorybowel disease, and pancreatitis. The effects of specific HO-1 modulation as a potential therapeutic strategy in experimental cell culture and animal models of these gastrointestinal disorders are summarized. In conclusion, targeted regulation of HO-1 holds major promise for future clinical interventions in inflammatory diseases of the gastrointestinal tract. | Vijith Vijayan Sebastian Mueller Eveline Baumgart-Vogt Stephan Immenschuh | 2010 | World Journal of Gastroenterology2010，16，25： | 13 |
| 4 | Increased liver stiffness in alcoholic liver disease:Differentiating fibrosis from steatohepatitis显示文摘AIM:To test if inflammation also interferes with liver stiffness (LS) assessment in alcoholic liver disease (ALD) and to provide a clinical algorithm for reliable fibrosis assessment in ALD by FibroScan (FS).METHODS:We first performed sequential LS analysis before and after normalization of serum transaminases in a learning cohort of 50 patients with ALD admitted for alcohol detoxification. LS decreased in almost all patients within a mean observation interval of 5.3 d. Six patients (12%) would have been misdiagnosed with F3and F4 fibrosis but LS decreased below critical cut-off values of 8 and 12.5 kPa after normalization of trans-aminases. RESULTS:Of the serum transaminases,the decrease in LS correlated best with the decrease in glutamic oxaloacetic transaminase (GOT). No significant chang-es in LS were observed below GOT levels of 100 U/L. After establishing the association between LS and GOT levels,we applied the rule of GOT < 100 U/L for reliable LS assessment in a second validation cohort of 101 patients with histologically confi rmed ALD. By ex-cluding those patients with GOT > 100 U/L at the time of LS assessment from this cohort,the area under the receiver operating characteristic (AUROC) for cirrhosis detection by FS improved from 0.921 to 0.945 while specificity increased from 80% to 90% at a sensitivity of 96%. A similar AUROC could be obtained for lower F3 fibrosis stage if LS measurements were restricted to patients with GOT < 50 U/L. Histological grading of inflammation did not further improve the diagnostic accuracy of LS.CONCLUSION:Coexisting steatohepatitis markedly increases LS in patients with ALD independent of fibrosis stage. Postponing cirrhosis assessment by FS during alcohol withdrawal until GOT decreases to < 100 U/mL signif icantly improves the diagnostic accuracy. | Sebastian Mueller Gunda Millonig Lucie Sarovska Stefanie Friedrich Frank M Reimann Maria Pritsch Silke Eisele Felix Stickel Thomas Longerich Peter Schirmacher Helmut Karl Seitz | 2010 | World Journal of Gastroenterology2010，16，8： | 10 |
| 5 | Does pressure cause liver cirrhosis? The sinusoidal pressure hypothesis显示文摘Independent of their etiology, all chronic liver diseases ultimately lead to liver cirrhosis, which is a majorhealth problem worldwide. The underlying molecular mechanisms are still poorly understood and no efficient treatment strategies are available. This paper introduces the sinusoidal pressure hypothesis(SPH), which identifies an elevated sinusoidal pressure(SP) as cause of fibrosis. SPH has been mainly derived from recent studies on liver stiffness. So far, pressure changes have been exclusively seen as a consequ-ence of cirrhosis. According to the SPH, however, an elevated SP is the major upstream event that initiates fibrosis via biomechanic signaling by stretching of perisinusoidal cells such as hepatic stellate cells or fibroblasts(SPH part?Ⅰ: initiation). Fibrosis progression is determined by the degree and time of elevated SP. The SPH predicts that the degree of extracellular matrix eventually matches SP with critical thresholds > 12 mmH g and > 4 wk. Elevated arterial flow and final arterialization of the cirrhotic liver represents the self-perpetuating key event exposing the low-pressure-organ to pathologically high pressures(SPH part?Ⅱ: perpetuation). It also defines the 'point of no return' where fibrosis progression becomes irreversible. The SPH is able to explain the macroscopic changes of cirrhotic livers and the uniform fibrotic response to various etiologies. It also opens up new views on the role of fat and disease mechanisms in other organs. The novel concept will hopefully stimulate the search for new treatment strategies. | Sebastian Mueller | 2016 | World Journal of Gastroenterology2016，22，48： | 5 |
| 6 | Transient micro-elastography:A novel non-invasive approach to measure liver stiffness in mice显示文摘AIM:To develop and validate a transient micro-elastography device to measure liver stiffness(LS) in mice.METHODS:A novel transient micro-elastography(TME) device,dedicated to LS measurements in mice with a range of measurement from 1-170 kPa,was developed using an optimized vibration frequency of 300 Hz and a 2 mm piston.The novel probe was validated in a classical fibrosis model(CCl4) and in a transgenic murine model of systemic amyloidosis.RESULTS:TME could be successfully performed in control mice below the xiphoid cartilage,with a mean LS of 4.4 ± 1.3 kPa,a mean success rate of 88%,and an excellent intra-observer agreement(0.98).Treatment with CCl4 over seven weeks drastically increased LS as compared to controls(18.2 ± 3.7 kPa vs 3.6 ± 1.2 kPa).Moreover,fibrosis stage was highly correlated with LS(Spearman coefficient = 0.88,P < 0.01).In the amyloidosis model,much higher LS values were obtained,reaching maximum values of > 150 kPa.LS significantly correlated with the amyloidosis index(0.93,P < 0.0001) and the plasma concentration of mutant hapoA-□(0.62,P < 0.005).CONCLUSION:Here,we have established the first non-invasive approach to measure LS in mice,and have successfully validated it in two murine models of high LS. | Cécile Bastard Matteo R Bosisio Michèle Chabert Athina D Kalopissis Meriem Mahrouf-Yorgov Hélène Gilgenkrantz Sebastian Mueller Laurent Sandrin | 2011 | World Journal of Gastroenterology2011，17，8： | 4 |
| 7 | Liver stiffness reversibly increases during pregnancy and independently predicts preeclampsia显示文摘AIM To study liver stiffness(LS) during pregnancy and its association with complications during pregnancy.METHODS In this observational, diagnostic study, 537 pregnant women were prospectively enrolled at the Department of Obstetrics and Gynecology, University hospital Heidelberg and Salem Medical Center. LS was measured using the Fibroscan device(Echosens, Paris) in all women and in 41 cases 24 h after delivery. Clinical and morphological data were recorded and abdominal ultrasound and standard laboratory tests were performed. No complications were observed in 475 women(controls) while preeclampsia and intrahepatic cholestasis of pregnancy(ICP) developed in 22 and 40 women, respectively.RESULTS In controls, LS increased significantly from initially 4.5 ± 1.2 kPa in the second trimester to 6.0 ± 2.3 kPa(P < 0.001) in the third trimester. In the third trimester, 41% of women had a LS higher than 6 kPa. Elevated LS in controls was significantly correlated with alkaline phosphatase, leukocytes, gestational age and an increase in body weight and body mass index(BMI). In women with pregnancy complications, LS was significantly higher as compared to controls(P < 0.0001). Moreover, in multivariate analysis, LS was an independent predictor for preeclampsia with an odds ratio of 2.05(1.27-3.31) and a cut-off value of 7.6 kPa. In contrast, ICP could not be predicted by LS. Finally, LS rapidly decreased in all women within 24 h after delivery from 7.2 ± 3.3 kPa down to 4.9 ± 2.2 kPa(P < 0.001).CONCLUSION During pregnancy, LS significantly and reversibly increases in the final trimester of pregnant women without complications. In women with preeclampsia, LS is significantly elevated and an independent noninvasive predictor. | Franziska J Ammon Anna Kohlhaas Omar Elshaarawy Johannes Mueller Thomas Bruckner Christof Sohn Gabriele Fluhr Herbert Fluhr Sebastian Mueller | 2018 | World Journal of Gastroenterology2018，24，38： | 2 |
| 8 | Pharmacological blockage of CYP2E1 and alcohol-mediated liver cancer: is the time ready?显示文摘Chronic alcohol consumption is a major risk factor worldwide affecting significantly both mortality and years of life lost (YLL) (1). Ca. 5% of the western world show risky alcohol consumption and in some countries such as China a regional yearly increase of alcohol consumption of over 400% has been observed recently (2,3). The liver | Sebastian Mueller | 2013 | Chinese Journal of Cancer Research2013，25，3： | 2 |
| 9 | Excluding infection through procalcitonin testing improves outcomes of congestive heart failure patients presenting with acute respiratory symptoms: Results from the randomized ProHOSP trial显示文摘 | Philipp Schuetz Alexander Kutz Eva Grolimund Sebastian Haubitz Désirée Demann Alaadin V?geli Fabienne Hitz Mirjam Christ-Crain Robert Thomann Claudine Falconnier Claus Hoess Christoph Henzen Robert J. Marlowe Werner Zimmerli Beat Mueller | 2014 | International Journal of Cardiology2014，，3： | 2 |
| 10 | Transient elastography with the XL probe rapidly identifies patients with nonhepatic ascites显示文摘 | Sebastian Mueller Laurent Sandrin Cecile Bastard Gunda Millonig Esteban Durango Anna Kohlhaas Helmut Karl Seitz Buchler Arianeb Mehrabi Mohammad Golriz | 2012 | Hepatic Medicine: Evidence and Research . 2012 (defa)2012，，： | 1 |
| 11 | Huge primitive neuroectodermal tumor of the pancreas:Report of a case and review of the literature显示文摘Primitive neuroectodermal tumor (PNET) of the pancreas is an extremely rare tumor that usually occurs in children or young adults. We report a case of a 33-year-old male patient with an 18 cm × 18 cm × 16 cm mass arising from the pancreatic body and tail with a one- day history of abdominal pain. Initial CT scan showed no signs of metastatic tumor spread. The tumor caused intrabdominal bleeding and the patient underwent primary tumor resection including partial gastrectomy, left pancreatic resection and splenectomy. Diagnosis of PNET was confi rmed by histology, immunohistochemistry and FISH analysis. All neoplastic cells were stained positive for MIC2-protein (CD99). Approximately one month after surgery, several liver metastases were observed and the patient underwent chemotherapy according to the Euro- Ewing protocol. Subsequent relaparotomy excluded any residual hepatic or extrahepatic abdominal metastases. Although PNET in the pancreas is an extremely rare entity, it should be considered in the diffential diagnosis of pancreatic masses, especially in young patients. This alarming case particularly illustrates that PNET in the pancreas although in an advanced stage can present with only a short history of mild symptoms. | Thilo Welsch Gunhild Mechtersheimer Sebastian Aulmann Sascha A Mueller Markus W Buechler Jan Schmidt Peter Kienle | 2006 | World Journal of Gastroenterology2006，12，37： | 1 |
| 12 | A Randomized Phase II Study of Pemetrexed in Combination With Cisplatin or Carboplatin as First-line Therapy for Patients With Locally Advanced or Metastatic Non–Small-Cell Lung Cancer显示文摘 | Wolfgang H.W. Schuette Andreas Groeschel Martin Sebastian Stefan Andreas Thomas Mueller Folker Schneller Sylvia Guetz Corinna Eschbach Sabine Bohnet Monika I. Leschinger Martin Reck | 2013 | Clinical Lung Cancer2013，，： | 1 |
| 13 | Reduction of radiation exposure and improvement of image quality with BMI-adapted prospective cardiac computed tomography and iterative reconstruction显示文摘 | Waldemar Hosch Wolfram Stiller Dirk Mueller Gitsios Gitsioudis Johanna Welzel Monika Dadrich Sebastian J. Buss Evangelos Giannitsis Hans U. Kauczor Hugo A. Katus Grigorios Korosoglou | 2011 | European Journal of Radiology2011，，11： | 1 |
| 14 | Effect of hyperglycaemia on inflammatory and stress responses and clinical outcome of pneumonia in non-critical-care inpatients: results from an observational cohort study显示文摘 | Philipp Schuetz Natalie Friedli Eva Grolimund Alexander Kutz Sebastian Haubitz Mirjam Christ-Crain Robert Thomann Werner Zimmerli Claus Hoess Christoph Henzen Beat Mueller | 2014 | Diabetologia2014，，2： | 1 |
| 15 | Evaluation of cardioprotective effects of recombinant soluble P-selectin glycoprotein ligand-immunoglobulin in myocardial ischemia-reperfusion injury by real-time myocardial contrast echocardiography显示文摘 | Alexander Hansen Anjali Kumar David Wolf Kamilla Frankenbergerova Arthur Filusch Marie-Luise Gross Sebastian Mueller Hugo Katus Helmut Kuecherer | 2004 | Journal of the American College of Cardiology2004，，4： | 1 |
| 16 | The Treatment of Intra-articular Calcaneus Fractures with Severe Soft Tissue Damage with a Hinged External Fixator or Internal Stabilization: Long-term Results显示文摘 | Lutz Besch Jan Soeren Waldschmidt Mark Daniels-Wredenhagen Deike Varoga Michael Mueller Ralf-Erik Hilgert Guenther Mathiak Stefanie Oestern Sebastian Lippross Andreas Seekamp | 2010 | The Journal of Foot and Ankle Surgery2010，，1： | 1 |
| 17 | On reaction pathways in the conversion of methanol to hydrocarbons on HZSM-5显示文摘 | Sun Xianyong Sebastian Mueller Liu Y | 2014 | Journal of Catalysis2014，317，： | 1 |
| 18 | Targeted Gene Knockouts Reveal Overlapping Functions of the Five Physcomitrella patens FtsZ Isoforms in Chloroplast Division, Chloroplast Shaping, Cell Patterning, Plant Development, and Gravity Sensing显示文摘叶绿体和细菌的房间由二进制分裂划分。在这个收缩部门的关键蛋白质是 FtsZ,类似于真核细胞的导管素的自我装配的 GTPase。在初核质, FtsZ 被单个基因几乎总是编码,而植物怀有几个原子编码 FtsZ 相当或相同的事物。在种子植物,在二个家庭和所有的这些蛋白质组只被进口进质体。相反,基础陆地植物 Physcomitrella 圣餐盘,苔藓,与一个成员一起编码第三个 FtsZ 家庭。这蛋白质双地被指向到质体并且到 cytosol。这里,我们在 P 在所有 ftsZ 基因的指向的基因混乱上报导。圣餐盘。单个、双的猛烈异种的随后的分析不仅在质体分割,而且在叶绿体塑造,房间 patterning,植物发展,并且严肃察觉到揭示了不同 FtsZ isoforms 的一个复杂相互作用。这些结果支持 plastoskeleton 和它的功能的集成的概念进细胞骨架,至少在苔藓 P。圣餐盘。 | Anja Martin Daniel Lang Sebastian T. Hanke Stefanie J.X. Mueller Eric Sarnighausen Marco Vervliet-Scheebaum Ralf Reski | 2009 | Molecular Plant2009，2，6： | 1 |
| 19 | Direct modulation of hepatocyte hepcidin signaling by iron显示文摘BACKGROUND Liver-secreted hepcidin is the systemic master switch of iron homeostasis and decreased levels of hepcidin are considered to cause iron overload not only in hereditary hemochromatosis but also in hemolytic anemia and chronic liver diseases.The regulation of hepcidin is complex and its response to iron is still not completely understood.AIM To study the direct effect of iron on various established hepcidin signaling pathways in hepatoma cells or primary hepatocytes.METHODS Hepcidin mRNA expression was studied by quantitative real-time(qRT)-PCR in the presence of various forms of iron including ferric ammonium citrate(FAC)in hepatoma cells(Huh7),murine primary hepatocytes and an established co-culture model of phorbol myristate acetate-differentiated THP-1 monocytes and Huh7 cells.To analyze hepcidin signaling,the response to bone morphogenetic protein 6(BMP6),interleukin(IL)-6,IL-1β,hypoxia and lipopolysaccharide(LPS)were studied.Hepcidin and small mothers against decapentaplegic 6(SMAD6)mRNA levels were assessed by qRT-PCR and the expression of phosphorylated signal transducer and activator of transcription 3(phospho-STAT3),STAT3,phospho-SMAD1/5/8 and SMAD1 proteins were analyzed by western blot.RESULTS All iron III forms including FAC efficiently blocked hepcidin mRNA expression at non-toxic dosages in Huh7 cells or primary hepatocytes in a time and dosedependent manner(P<0.001;P<0.05).Hepcidin blockage could be efficiently blunted by iron chelators salicylaldehyde isonicotinoyl hydrazone(SIH)and Desferal(P<0.001).FAC also inhibited BMP6,hypoxia,IL-1βand IL-6-mediated hepcidin induction(P<0.001;P<0.001;P<0.05;P<0.001),and FAC also inhibited LPS-mediated hepatic hepcidin induction in co-culture model(P<0.001).Moreover,FAC reduced SMAD6 mRNA and p-SMAD1/5/8 protein expression at basal or upon stimulation by BMP6(P<0.05;P<0.01),and FAC also reduced SMAD6 and p-SMAD1/5/8 expression under hypoxia(P<0.01;P<0.05).However,FAC has no significant effect on p-STAT3 protein expression at basal or upon stimulation by various stimuli.Notably,in the presence of the BMP/SMAD signaling pathway inhibitor LDN193189 Hydrochloride(LDN),FAC was unable to further decrease hepcidin,SMAD6 and p-SMAD1/5/8 expression compared with LDN alone.CONCLUSION Iron directly blocks hepatocellular hepcidin signaling through the BMP/SMAD pathway but independent of STAT3.This mechanism may contribute to continued iron overload in many pathophysiological conditions ultimately causing a vicious cycle of continued hepcidin suppression. | Lin-Na Yu Shi-Jin Wang Cheng Chen Vanessa Rausch Omar Elshaarawy Sebastian Mueller | 2021 | World Journal of Hepatology2021，13，10： | 1 |
| 20 | Association of Liver Stiffness with Hepatic Expression of Pharmacokinetically Important Genes in Alcoholic Liver Disease显示文摘 | Dirk Theile Walter Emil Haefeli Helmut Karl Seitz Gunda Millonig Johanna Weiss Sebastian Mueller | 2012 | Alcohol Clin Exp Res2012，，： | 1 |
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