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| 1 | INT-767 improves histopathological features in a dietinduced ob/ob mouse model of biopsy-confirmed nonalcoholic steatohepatitis显示文摘AIM To characterize the efficacy of the dual FXR/TGR5 receptor agonist INT-767 upon histological endpoints in a rodent model of diet-induced and biopsy-confirmed non-alcoholic steatohepatitis(NASH).METHODS The effects of INT-767 on histological features of NASH were assessed in two studies using Lep^(ob/ob)(ob/ob) NASH mice fed the AMLN diet(high fat with transfat, cholesterol and fructose). In a proof-of-conceptstudy, Lep^(ob/ob)(ob/ob) NASH mice were first dosed with INT-767(3 or 10 mg/kg for 8 wk). A second ob/ob NASH study compared INT-767(3 and 10 mg/kg) to obeticholic acid(OCA)(10 or 30 mg/kg; 16 wk). Primary histological endpoints included qualitative and quantitative assessments of NASH. Other metabolic and plasma endpoints were also assessed. A comparative assessment of INT-767 and OCA effects on drug distribution and hepatic gene expression was performed in C57 Bl/6 mice on standard chow. C57 Bl/6 mice were orally dosed with INT-767 or OCA(1-30 mg/kg) for 2 wk, and expression levels of candidate genes were assessed by RNA sequencing and tissue drug levels were measured by liquid chromatography tandem-mass spectrometry.RESULTS INT-767 dose-dependently(3 and 10 mg/kg, PO, QD, 8 wk) improved qualitative morphometric scores on steatohepatitis severity, inflammatory infiltrates and fibrosis stage. Quantitative morphometric analyses revealed that INT-767 reduced parenchymal collagen area, collagen fiber density, inflammation(assessed by Galectin-3 immunohistochemistry) and hepatocyte lipid droplet area following INT-767 treatment. In a comparative study(16 wk), the FXR agonists OCA(10 and 30 mg/kg) and INT-767(3 and 10 mg/kg) both improved NASH histopathology, with INT-767 exerting greater therapeutic potency and efficacy than OCA. Mechanistic studies suggest that both drugs accumulate similarly within the liver and ileum, however, the effects of INT-767 may be driven by enhanced hepatic, but not ileal, FXR function. CONCLUSION These findings confirm the potential utility of FXR and dual FXR/TGR5 activation as disease intervention strategies in NASH. | Jonathan D Roth Michael Feigh Sanne S Veidal Louise KD Fensholdt Kristoffer T Rigbolt Henrik H Hansen Li C Chen Mathieu Petitjean Weslyn Friley Niels Vrang Jacob Jelsing Mark Young | 2018 | World Journal of Gastroenterology2018，24，2： | 7 |
| 2 | Next-Generation Stool DNA Test Accurately Detects Colorectal Cancer and Large Adenomas显示文摘 | David A. Ahlquist Hongzhi Zou Michael Domanico Douglas W. Mahoney Tracy C. Yab William R. Taylor Malinda L. Butz Stephen N. Thibodeau Linda Rabeneck Lawrence F. Paszat Kenneth W. Kinzler Bert Vogelstein Niels Chr. Bjerregaard S?ren Laurberg Henrik Toft S? | 2012 | Gastroenterology2012，，2： | 7 |
| 3 | Metabolic and hepatic effects of liraglutide,obeticholic acid and elafibranor in diet-induced obese mouse models of biopsy-confirmed nonalcoholic steatohepatitis显示文摘AIM To evaluate the pharmacodynamics of compounds in clinical development for nonalcoholic steatohepatitis(NASH) in obese mouse models of biopsy-confirmedNASH.METHODS Male wild-type C57 BL/6 J mice(DIO-NASH) and Lep^(ob/ob)(ob/ob-NASH) mice were fed a diet high in trans-fat(40%), fructose(20%) and cholesterol(2%) for 30 and 21 wk, respectively. Prior to treatment, all mice underwent liver biopsy for confirmation and stratification of liver steatosis and fibrosis, using the nonalcoholic fatty liver disease activity score(NAS) and fibrosis staging system. The mice were kept on the diet and received vehicle, liraglutide(0.2 mg/kg, SC, BID), obeticholic acid(OCA, 30 mg/kg PO, QD), or elafibranor(30 mg/kg PO, QD) for eight weeks. Within-subject comparisons were performed on changes in steatosis, inflammation, ballooning degeneration, and fibrosis scores. In addition, compound effects were evaluated by quantitative liver histology, including percent fractional area of liver fat, galectin-3, and collagen 1 a1.RESULTS Liraglutide and elafibranor, but not OCA, reduced body weight in both models. Liraglutide improved steatosis scores in DIO-NASH mice only. Elafibranor and OCA reduced histopathological scores of hepatic steatosis and inflammation in both models, but only elafibranor reduced fibrosis severity. Liraglutide and OCA reduced total liver fat, collagen 1 a1, and galectin-3 content, driven by significant reductions in liver weight. The individual drug effects on NASH histological endpoints were supported by global gene expression(RNA sequencing) and liver lipid biochemistry.CONCLUSION DIO-NASH and ob/ob-NASH mouse models show distinct treatment effects of liraglutide, OCA, and elafibranor, being in general agreement with corresponding findings in clinical trials for NASH. The present data therefore further supports the clinical translatability and utility of DIO-NASH and ob/ob-NASH mouse models of NASH for probing the therapeutic efficacy of compounds in preclinical drug development for NASH. | Kirstine S Tolbol Maria NB Kristiansen Henrik H Hansen Sanne S Veidal Kristoffer TG Rigbolt Matthew P Gillum Jacob Jelsing Niels Vrang Michael Feigh | 2018 | World Journal of Gastroenterology2018，24，2： | 5 |
| 4 | Voltage rise mitigation for solar PV integration at LV grids Studies from PVNET.dk显示文摘Solar energy from photovoltaic(PV)is among the fastest developing renewable energy systems worldwide.Driven by governmental subsidies and technological development,Europe has seen a fast expansion of solar PV in the last few years.Among the installed PV plants,most of them are situated at the distribution systems and bring various operational challenges such as power quality and power flow management.The paper discusses the modelling requirements for PV system integration studies,as well as the possible techniques for voltage rise mitigation at low voltage(LV)grids for increasing PV penetration.Potential solutions are listed and preliminary results are presented. | Guangya YANG Francesco MARRA Miguel JUAMPEREZ Søren Bækhøj KJÆR Seyedmostafa HASHEMI JacobØSTERGAARD Hans Henrik IPSEN Kenn H.B.FREDERIKSEN | 2015 | Journal of Modern Power Systems and Clean Energy2015，3，3： | 5 |
| 5 | Identification of biomarkers of human pancreatic adenocarcinomas by expression profiling and validation with gene expression analysis in endoscopic ultrasound-guided fine needle aspiration samples显示文摘瞄准:比较胰腺的腺癌织物标本的基因表示侧面,胰腺的人和腺癌和白血病房间线和正常的胰取样以便区分差别的冒号表示了基因并且在内视镜的指导超声的好针渴望( 指导EUS 的 FNA )由量的即时 RT-PCR ( RT-QPCR )验证基因的一个子集的微分表示标本。方法:包含 1176 基因的商业地奉献的癌症 cDNA 宏数组(地图集人癌症 1.2 ) 被使用。不同统计途径(层次聚类的、主要部件分析(PCA ) 和 SAM ) 被用来分析表示数据。RT-QPCR 和免疫组织化学的研究被用于结果的确认。结果:RT-QPCR 验证了 LCN2 的增加的表示(lipocalin 2 ) 并且第一次在恶意的胰的小块地(织物类型 plasminogen 使活跃之物或 tPA ) 同样与正常相比胰。Immunohistochemical 分析证实了在癌入侵的管的上皮细胞局部性的 LCN2 蛋白质的增加的表示。在与胰腺的腺癌从病人通过指导 EUS 的 FNA 获得的 12 件样品的小块地和 LCN2 抄本的分析与在正常纸巾发现的那些比较显示出显著地增加的表示层次,显示高质量的 RNA 的足够的数量能与这种技术被获得。结论:表示介绍是一个有用方法识别简历标记和潜在的目标基因。在胰腺的癌症的指导 EUS 的 FNA 样品的分子的分析为胰腺的腺癌的诊断作为珍贵策略出现。 | Henrik Laurell Michèle Bouisson Philippe Berthelémy Philippe Rochaix Sébastien Déjean Philippe Besse Christiana Susini Lucien Pradayrol Nicole Vaysse Louis Buscail | 2006 | World Journal of Gastroenterology2006，12，21： | 5 |
| 6 | Nutrition in chronic pancreatitis显示文摘The pancreas is a major player in nutrient digestion.In chronic pancreatitis both exocrine and endocrine insufficiency may develop leading to malnutrition over time.Maldigestion is often a late complication of chronic pancreatic and depends on the severity of the underlying disease.The severity of malnutrition is correlated with two major factors:(1)malabsorption and depletion of nutrients(e.g.,alcoholism and pain)causes impaired nutritional status;and(2)increased metabolic activity due to the severity of the disease.Nutritional deficiencies negatively affect outcome if they are not treated.Nutritional assessment and the clinical severity of the disease are important for planning any nutritional intervention.Good nutritional practice includes screening to identify patients at risk,followed by a thoroughly nutritional assessment and nutrition plan for risk patients.Treatment should be multidisciplinary and the mainstay of treatment is abstinence from alcohol,pain treatment,dietary modifications and pancreatic enzyme supplementation.To achieve energy-end protein requirements,oral supplementation might be beneficial.Enteral nutrition may be used when patients do not have sufficient calorie intake as in pylero-duodenalstenosis,inflammation or prior to surgery and can be necessary if weight loss continues.Parenteral nutrition is very seldom used in patients with chronic pancreatitis and should only be used in case of GI-tract obstruction or as a supplement to enteral nutrition. | Henrik Hφjgaard Rasmussen φivind Irtun Sφren Schou Olesen Asbjφrn Mohr Drewes Mette Holst | 2013 | World Journal of Gastroenterology2013，19，42： | 4 |
| 7 | Towards a standard diet-induced and biopsy-confirmed mouse model of non-alcoholic steatohepatitis: Impact of dietary fat source显示文摘BACKGROUND The trans-fat containing AMLN(amylin liver non-alcoholic steatohepatitis,NASH)diet has been extensively validated in C57BL/6J mice with or without the Lep^ob/Lep^ob(ob/ob)mutation in the leptin gene for reliably inducing metabolic and liver histopathological changes recapitulating hallmarks of NASH.Due to a recent ban on trans-fats as food additive,there is a marked need for developing a new diet capable of promoting a compatible level of disease in ob/ob and C57BL/6J mice.AIM To develop a biopsy-confirmed mouse model of NASH based on an obesogenic diet with trans-fat substituted by saturated fat.METHODS Male ob/ob mice were fed AMLN diet or a modified AMLN diet with trans-fat(Primex shortening)substituted by equivalent amounts of palm oil[Gubra amylin NASH,(GAN)diet]for 8,12 and 16 wk.C57BL/6J mice were fed the same diets for 28 wk.AMLN and GAN diets had similar caloric content(40%fat kcal),fructose(22%)and cholesterol(2%)level.RESULTS The GAN diet was more obesogenic compared to the AMLN diet and impaired glucose tolerance.Biopsy-confirmed steatosis,lobular inflammation,hepatocyte ballooning,fibrotic liver lesions and hepatic transcriptome changes were similar in ob/ob mice fed the GAN or AMLN diet.C57BL/6J mice developed a mild to moderate fibrotic NASH phenotype when fed the same diets.CONCLUSION Substitution of Primex with palm oil promotes a similar phenotype of biopsyconfirmed NASH in ob/ob and C57BL/6J mice,making GAN diet-induced obese mouse models suitable for characterizing novel NASH treatments. | Michelle L Boland Denise Oro Kirstine S T■lb■l Sebastian T Thrane Jens Christian Nielsen Taylor S Cohen David E Tabor Fiona Fernandes Andrey Tovchigrechko Sanne S Veidal Paul Warrener Bret R Sellman Jacob Jelsing Michael Feigh Niels Vrang James L Trevaskis Henrik H Hansen | 2019 | World Journal of Gastroenterology2019，25，33： | 3 |
| 8 | Improved Prediction of Signal Peptides: SignalP 3.0显示文摘 | Jannick Dyrl?v Bendtsen Henrik Nielsen Gunnar von Heijne S?ren Brunak | 2004 | Journal of Molecular Biology2004，，4： | 2 |
| 9 | Persistent postsurgical pain: risk factors and prevention显示文摘 | Henrik Kehlet Troels S Jensen Clifford J Woolf | 2006 | The Lancet . 2006 (9522)2006，，9522： | 2 |
| 10 | Predicting Subcellular Localization of Proteins Based on their N-terminal Amino Acid Sequence显示文摘 | Olof Emanuelsson Henrik Nielsen S?ren Brunak Gunnar von Heijne | 2000 | Journal of Molecular Biology2000，，4： | 2 |
| 11 | Incidence and prognosis of cholangiocarcinoma in Danish patients with and without inflammatory bowel disease: a national cohort study, 1978–2003显示文摘 | Rune Erichsen Peter Jepsen Hendrik Vilstrup Anders Ekbom Henrik Toft S?rensen | 2009 | European Journal of Epidemiology2009，，9： | 2 |
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| 13 | Penetration into concrete by truncated projectiles显示文摘 | Jan A T Henrik S | | 0，，： | 1 |
| 14 | Adaptive Control of Heterogeneous Marine Sensor Platforms in an Autonomous Sensor Network显示文摘 | Donald P E Michael R B Henrik S | 2006 | IEEE/RSJ Transactions on AES2006，45，1： | 1 |
| 15 | An overview of sigma-Delta eonverters显示文摘 | Pervez M A Henrik V S Jan VDS | 1996 | IEEE1996，13，1： | 1 |
| 16 | Transformation of barley by microinjection into isolated zygote protoplasts显示文摘 | Preben Bach Holm Ole Olsen Martin Schnorf Henrik Brinch-Pedersen S?ren Knudsen | 2000 | Transgenic Research2000，，1： | 1 |
| 17 | Molecular cloning and characterization of a cDNA encoding poplar UDP-glucose dehydrogenase, a key gene of hemicellulose/pectin formation显示文摘 | Henrik J Fredrik S Bahram A | 2002 | Biochimica et Biophysica Acta2002，1576，： | 1 |
| 18 | Changing the Amylopectin - Sodium Dodecyl Sulphate Interaction by Modifying the Exterior Chain Length 显示文摘 | Henrik L Gunilla S | 2002 | Starch2002，54，： | 1 |
| 19 | Oxalate production by Sclero- tinia sclerotiorum deregulates guard ceils during infection 显示文摘 | REJANE L G HENRIK U S | 2004 | Plant Physiology2004，136，： | 1 |
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