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UDP-glucuronosyltransferases mediate coffee-associated reduction of liver fibrosis in bile duct ligated humanized transgenic UGT1A mice

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Hepatobiliary Surgery and Nutrition 2021年第6期10卷 766-781页

作者： Steffen Landerer Sandra Kalthoff christian P.Strassburg Department of Internal Medicine I University Hospital BonnVenusberg-Campus 1BonnGermany

Background:Coffee consumption has been shown to reduce the risk of liver fibrosis and is capable of inducing human UDP-glucuronosyltransferase(UGT)1A ***1A enzymes act as indirect antioxidants catalyzing the elimination of reactive metabolites,which in turn are potent initiators of profibrotic *** aim of this study was to analyze the role of UGT1A genes as effectors of the protective properties of coffee in bile duct ligation(BDL)induced liver ***:Fourteen days BDL with and without coffee pre-and co-treatment was performed in htgUGT1A-WT and htgUGT1A-SNP *** UGT1A mRNA expression levels,serum bilirubin and aminotransferase activities were *** fibrosis was assessed by collagen deposition,computational analysis of Sirius red tissue staining and expression of profibrotic marker *** stress was measured by hepatic peroxidase concentrations and immunofluorescence ***:UGT1A transcription was differentially activated in the livers of htgUGT1A-WT mice after BDL,in contrast to a reduced or absent induction in the presence of ***-treated(coffee+BDL)htgUGT1A-WT-mice showed significantly increased UGT1A expression and protein levels and a considerably higher induction compared to water drinking WT mice(BDL),whereas in co-treated htgUGT1A-SNP mice absolute expression levels remained below those observed in htgUGT1A-WT *** deposition,oxidative stress and the expression of profibrotic markers inversely correlated with UGT1A expression levels in htgUGT1A-WT and SNP mice after BDL and coffee+BDL ***:Coffee exerts hepatoprotective and antioxidative effects via activation of UGT1A *** hepatic fibrosis as a result of coffee-mediated UGT1A induction during cholestasis was detected,while the protective action of coffee was lower in a common low-function UGT1A SNP haplotype present in 10%of the Caucasian *** study suggests that coffee consumption might

关键词： Glucuronidation cholestasis liver fibrosis coffee oxidative stress

Hepatic steatosis prevents heme oxygenase-1 induction by isoflurane in the rat liver

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World Journal of Gastroenterology 2011年第37期17卷 4184-4190页

作者： Patrick Stoll christian I Schwer Ulrich Goebel Hartmut Buerkle Alexander Hoetzel Rene Schmidt Department of Anesthesiology and Critical Care Medicine Freiburg University Medical Center

aim:To characterize the inductive effects of isoflurane(ISO) on hepatic heme oxygenase-1(HO-1) in an animal model of hepatic ***:Lean(LEAN) and obese(FAT) Zucker rats were randomized into 4 groups:1:LEAN + pentobarbital sodium(PEN);2:LEAN + ISO;3:FAT + PEN;4:FAT + *** animals were mechanically ventilated for 6 *** vitro analyses of liver tissue included determination of HO-1 mRNA and protein expression as well as measurement of HO enzyme activity and immunohistochemical ***:Compared to PEN treatment,ISO administration profoundly induced hepatic HO-1 mRNA and protein expression and significantly increased HO enzyme activity in lean Zucker *** contrast,no difference in HO-1 gene expression was observed after ISO or PEN anesthesia in obese Zucker ***:The present study demonstrates that ISO is an inducer of hepatic HO-1 gene expression in non-steatotic organs but failed to upregulate HO-1 in steatotic livers.

关键词： Isoflurane Heme oxygenase Hepatic steatosis Heme oxygenase-1 Volatile anesthetics

High-dose interferon-α2b induction therapy in combination with ribavirin for treatment of chronic hepatitis C in patients with non-response or relapse after interferon-a monotherapy

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World Journal of Gastroenterology 2005年第34期11卷 5342-5346页

作者： Holger G. Hass christian Kreysel Johannes Fischinger Josef Menzel Stephan Kaiser Department of Gastroenterology and Hepatology University of Tuebingen Germany Department of Gastroenterology Klinikum Krefeld Germany Department of Gastroenterology and Hepatology University of Saarland Germany Department of Gastroenterology and Hepatology University of Muenster Germany

aim： To evaluate the daily high-dose induction therapy with interferon-α2b （IFN-α2b） in combination with ribavirin for the treatment of patients who failed with interferon monotherapy and had a relapse, based on the assumption that the viral burden would decline faster, thus increasing the likelihood of higher response rates in this difficult-totreat patient group. METHODS： Seventy patients were enrolled in this study. Treatment was started with 10 NU IFN-α2b daily for 3 wk, followed by IFN-α2b 5 NU/TIW in combination with ribavirin （1 000-1 200 mg/d） for 21 wk. In case of a negative HCV RNA PCR, treatment was continued until wk 48 （IFN-α2b 3MU/TIW＋1000-1200 mg ribavirin/daily）. RESULTS： The dose of IFN-α2b or ribavirin was reduced in 16% of patients because of hematologic side effects, and treatment was discontinued in 7% of patients. An early viral response （EVR） was achieved in 60% of patients. Fifty percent of all patients achieved an end-oftreatment response （EOT） and d0% obtained a sustained viral response （SVR）. Patients with no response had a significantly lower response rate than those with a former relapse （SVR 30% vs 53%; P=0.049）. Furthermore, lower response rates were observed in patients infected with genotype la/b than in patients with non-1-genotype （SVR 28% vs7d%; P=0.001）. As a significant predictive factor for a sustained response, a rapid initial decline of HCV RNA could be identified. No patient achieving a negative HCV-RNA PCR at wk 18 or later eventually eliminated the virus. CONCLUSION： Daily high-dose induction therapy with interferon-α2b is well tolerated and effective for the treatment of non-responders and relapsers, when interferon monotherapy fails. A fast decline of viral load during the first 12 wk is strongly associated with a sustained viral response.

关键词： Chronic hepatitis C High-dose interferon-α induction therapy Ribavirin Nonresponder Relapse

Long-term results of an anatomically implanted hip arthroplasty with a short stem prosthesis (MiniHip^(TM))

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World Journal of Orthopedics 2018年第10期9卷 210-219页

作者： Lars V von Engelhardt Andreas Breil-Wirth christian Kothny Jorn Bengt Seeger christian Grasselli Joerg Jerosch Faculty of Health University of Witten/Herdecke Department of Trauma Surgery Orthopedics and Sports Medicine Katholisches Karl-Leisner Klinikum Department of Orthopedics Trauma Surgery and Sports MedicineJohanna Etienne Hospital Munich Ortho Center Department of Orthopaedics and Orthopaedic Surgery University Hospital Giessen and Marburg Department of Orthopaedics and Traumatology Waldburg-Zeil Clinic Tettnang

aim To evaluate the clinical and radiological outcome nineand ten years after short-stemmed, bone preserving and anatomical hip arthroplasty with the MiniHip^(TM) system. METHODS In a prospective study, 186 patients underwent hip arthroplasty with a partial neck preserving short stem(MiniHip^(TM), Corin). Elderly patients were not excluded from this study, thus the mean age at the time of surgery was 59.3 years(range 32 to 82 years). Surgery and the follow-up assessments were performed at two Centers. Up until now, the mean follow-up was 112.5 ± 8.2 mo. The Oxford Hip Score(OHS) and the Hip Dysfunction Osteoarthritis and Outcome Score(HOOS) was assessed pre-and each year after surgery. The clinical follow-up was accompanied by standardized a.p. and axial radiological examinations. Periprosthetic lucencies, hypertrophies within the Gruen zones one to fourteen were assessed. A subsidence of the stem was investigated according to Morray and heterotopic ossifications were assessed according to *** The OHS and HOOS improved from 18 ± 3.3 to 46 ± 2.0 and from 30 ± 8.3 to 95 ± 4.6 points, P 0.05). Two stems were revised due to a symptomatic subsidence four and twelve months postoperatively. Thus, the survivorship for aseptic loosening at nine to ten years was 98.66%. Including one stem revision due to a symptomatic exostosis, bursitis and thigh pain as well as one revision because of a septic stem loosening, the overall survival for the stem with revision for any reason was 97.32%. Besides one asymptomatic patient, radiological signs of a proximal stress-shielding, such as bone resorptions within the proximal Gruen zones, were not noticed. Findings suggesting a distal loading, e.g., bony hypertrophies or bone appositions of more than 2 mm, were also not detected. CONCLUSION Regarding these first long-term results on the MiniHip^(TM), the implant performed excee

关键词： Primary hip arthroplasty Long-term results Short stem endoprothesis Prospective follow-up study Stress-shielding

Creative Chinese Countryside? Township-Village Enterprises as Incubators

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Built Heritage 2019年第4期3卷 72-91页

作者： Mengchuan Liu Yi-Wen Wang christian Nolf School of Environmental Science University of LiverpoolLiverpoolUnited Kingdom Department of Urban Planning and Design Xi'an Jiaotong Liverpool UniversitySuzhouChina

Since the turn of the century,creative industries have displayed considerable power in transforming the social and economic landscapes of most global metropolises,including such Chinese mega-cities as Beijing and ***,the story of creative industries does not end *** studies have focused on the role of creative sector in the *** has been argued that the creative sector can effectively contribute to diversifying socio-economic development in rural areas by increasing employment,enhancing the quality of life,and promoting social inclusion and community *** the aim to chart new paths for China’s rural revitalisation and address the country’s‘three rural issues’(***,rural areas and farmers),this paper examines the potentials and challenges to developing the creative sector in rural *** first reviews the academic debate about expanding the development of creative industries from urban to rural *** on the research and classification of creative industries in rural Western Ireland,this study identifies industries characterised by‘content creation and production’and‘creative design services’,which would have potential in rural *** major impediments to and crucial factors for developing rural creative industries in China are investigated and appraised within the framework of‘creative people,creative place,and creative support’.After analysing emerging practices in Jiangsu Province,this paper highlights the potential of abandoned industrial complexes in rural parts of China’s coastal regions,which can act as incubators for creative *** former manufacturing plants are the remains of township-village enterprises(TVEs),which constituted part of China’s flagship policy for rural regeneration in the *** only do they have special architectural attributes favourable for creative production,but also represent the socio-economic entity of the village collective and are the carriers of

关键词： cultural and creative industries China rural revitalisation township-village enterprises(TVEs) adaptive reuse industrial heritage

Low-k integration: Gas screening for cryogenic etching and plasma damage mitigation

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Frontiers of Chemical Science and Engineering 2019年第3期13卷 511-516页

作者： Romain Chanson Remi Dussart Thomas Tillocher P. Lefaucheux christian Dussarrat Jean Francois de M arneffe IMEC v.z.w. 3001 LeuvenBelgium GREMI/University of Orleans OrleansFrance Air Liquide Laboratories TsukubaJapan

The integration of porous organo-silicate low-k materials has met a lot of technical *** of the main issues is plasma-induced damage,occurring for all plasma steps involved during interconnects *** the present paper,we focus on porous SiOCH low-k damage mitigation using cryogenic temperature so as to enable micro-capillary *** aim is to protect the porous low-k from plasma-induced damage and keep the k-value of the material unchanged,in order to limit the RC delay of interconnexion levels while shrinking the microchip *** cryogenic temperature is used to condense a gas inside the porous low-k ***,the etching process is performed at the temperature of condensation in order to keep the condensate trapped inside the material during the *** the first part of this work,the condensation properties of several gases are screened,leading to a down selection of five ***,their stability into the porous structure is evaluated at different *** of them are used for plasma damage mitigation *** mitigation is effective and shows negligible damage for one of the gases at-50℃.

关键词： low-A nanotechnology micro-electronics cryo-etching plasma processing

Ephrin-B reverse signaling induces expression of wound healing associated genes in IEC-6 intestinal epithelial cells

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World Journal of Gastroenterology 2005年第29期11卷 4511-4518页

作者： christian Hafner Stefanie Meyer Ilja Hagen Bernd Becker Alexander Roesch Michael Landthaler Thomas Vogt Department of Dermatology University Hospital of Regensburg Regensburg D-93042 Germany

aim： Eph receptors and ephrin ligands play a pivotal role in development and tissue maintenance. Since previous data have indicated an involvement of ephrin-B2 in epithelial healing, we investigated the gene expression and downstream signaling pathways induced by ephrin-B mediated cell-cell signaling in intestinal epithelial cells. METHODS： Upon stimulation of ephrin-B pathways in IEC-6 cells with recombinant rat EphB1-Fc, gene expression was analyzed by Affymetrix rat genome 230 high density arrays at different time points. Differentially expressed genes were confirmed by real-time RT-PCR. In addition, MAP kinase pathways and focal adhesion kinase （FAK） activation downstream of ephrin-B were investigated by immunoblotting and fluorescence microscopy. RESULTS： Stimulation of the ephrin-B reverse signaling pathway in IEC-6 cells induces predominant expression of genes known to be involved into wound healing/cell migration, antiapoptotic pathways, host defense and inflammation. Cox-2, c-Fos, Egr-1, Egr-2, and MCP-1 were found among the most significantly regulated genes. Furthermore, we show that the expression of repair- related genes is also accompanied by activation of the ERKI/2 MAP kinase pathway and FAK, two key regulators of epithelial restitution. CONCLUSION： Stimulation of the ephrin-B reverse signaling pathway induces a phenotype characterized by upregulation of repair-related genes, which may partially be mediated by ERK1/2 pathways.

关键词： Ephrin-B IEC-6 Wound healing Gene expression c-Fos Egr-1/2 COX-2

Anti-inflammatory effects of bifidobacteria by inhibition of LPS-induced NF-κB activation

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World Journal of Gastroenterology 2006年第23期12卷 3729-3735页

作者： christian U Riedel Francis Foata David Philippe Oskar Adolfsson Bernhard J Eikmanns Stephanie Blum Department of Microbiology and Biotechnology University of Ulm89068 UlmGermany Immunology GroupNutrition and Health Dept.Nestlé Research CenterPO Box 44CH-1026 LausanneSwitzerland Immunology Group Nutrition and Health Dept.Nestlé Research CenterPO Box 44CH-1026 LausanneSwitzerland Department of Microbiology and Biotechnology University of Ulm89068 UlmGermany

aim： Different strains of bifidobacteria were analysed for their effects on HT-29 intestinal epithelial cells （IECs） in in vitro models both of the non-inflamed and inflamed intestinal epithelium. METHODS： A reporter gene system in HT-29 cells was used to measure levels of NF-KB activation after challenge with bifidobacteria or after bacterial pre-treatment following LPS challenge. IL-8 protein and pro-inflammatory gene expression was investigated using normal HT-29 cells. RESULTS： None of the bifidobacteria tested induced activation of nuclear factor κB （NF-κB） indicating that bifidobacteria themselves do not induce inflammatory events in IECs. However, six out of eight bifidobacteria tested inhibited lipopolysaccharide- （LPS-） induced NF-κB activation in a dose- and strain-dependent manner. In contrast, NF-κB activation in response to challenge with tumor necrosis factor-α （TNF-α） was affected by none of the tested bifidobacteria, indicating that the inhibitory effect of bifidobacteria is specific for LPS-induced inflammation in IECs. As shown with two of the six inhibitionpositive bifidobacteria, LPS-induced inhibition of NF-κB activation was accompanied by a dose-dependent decrease of interleukin 8 （IL-8） secretion and by lower mRNA levels for IL-8, TNF-α, cyclooxygenase 2 （Cox-2）, and intercellular adhesion molecule 1（ICAM-1）. CONCLUSION： Some strains of bifidobacteria are effective in inhibiting LPS-induced inflammation and thus might be appropriate candidates for probiotic intervention in chronic intestinal inflammation.

关键词： NF-κB Bifidobacteria Anti-inflammatory LPS

Helicobacter pyloriin gastric corpus of patients 20 years after partial gastric resection

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World Journal of Gastroenterology 2004年第17期10卷 2557-2559页

作者： christian Kirsch Ahmed Madisch Petja Piehler Ekkehard Bayerdrffer Manfred Stolte Stephan Miehlke Medical Department I Technical University HospitalDresdenGermany Community Department of Internal Medicine University HospitalMarburgGermany Institute of Pathology Klinikum BayreuthGermany

aim:To determine the long-term prevalence of Helicobacter pylori(H pylori)gastritis in patients after partial gastric resection due to peptic ulcer,and to compare the severity of Hpylori-positive gastritis in the corpus mucosa between partial gastrectomy patients and matched controls. METHODS:Endoscopic biopsies were obtained from 57 patients after partial gastric resection for histological examination using hematoxylin/eosin and Warthin-Starry *** was graded according to the updated Sydney *** of corpus gastritis was compared between Hpylori-positive partial gastrectomy patients and Hpylori-positive duodenal ulcer patients matched for age and gender. RESULTS:In partial gastrectomy patients,surgery was performed 20 years(median)prior to *** 25 patients(43.8%)Hpyloriwas detected histologically in the gastric *** atrophy was more common in H pylori-positive compared to H pylori-negative partial gastrectomy patients(P<0.05).The severity of corpus gastritis was significantly lower in Hpylori-positive partial gastrectomy patients compared to duodenal ulcer patients (P<0.01).There were no significant differences in the activity of gastritis,atrophy and intestinal metaplasia between the two groups. CONCLUSION:The long-term prevalence of Hpylorigastritis in the gastric corpus of patients who underwent partial gastric resection due to peptic ulcer disease is comparable to the general *** expression of Hpylorigastritis in the gastric remnant does not resemble the gastric cancer phenotype.

关键词： Gastrectomy Helicobacter pylori Adult Aged Aged, 80 and over Female Gastric Mucosa Gastritis Helicobacter Infections Humans Male Middle Aged Peptic Ulcer Prevalence Severity of Illness Index Time Factors