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| 1 | 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 |
| 2 | CYP24A1 inhibition facilitates the anti-tumor effect of vitamin D3 on colorectal cancer cells显示文摘AIM:The effects of vitamin D3 have been investigated on various tumors, including colorectal cancer (CRC). 25-hydroxyvitamin-D3-24-hydroxylase (CYP24A1), the enzyme that inactivates the active vitamin D3 metabolite 1,25-dihydroxyvitamin D3 (1,25-D3), is considered to be the main enzyme determining the biological halflife of 1,25-D3. During colorectal carcinogenesis, the expression and concentration of CYP24A1 increases significantly, suggesting that this phenomenon could be responsible for the proposed efficacy of 1,25-D3 in the treatment of CRC. The aim of this study was to investigate the anti-tumor effects of vitamin D3 on the human CRC cell line Caco-2 after inhibition of the cytochrome P450 component of CYP24A1 activity. METHODS:We examined the expression of CYP24A1 mRNA and the effects of 1,25-D3 on the cell line Caco-2 after inhibition of CYP24A1. Cell viability and proliferation were determined by means of sulforhodamine-B staining and bromodeoxyuridine incorporation, respectively, while cytotoxicity was estimated via the lactate dehydrogenase content of the cell culture supernatant. CYP24A1 expression was measured by realtime reverse transcription polymerase chain reaction. A number of tetralone compounds were synthesized to investigate their CP24A1 inhibitory activity. RESULTS:In response to 1,25-D3, CYP24A1 mRNA expression was enhanced significantly, in a time- and dose-dependent manner. Caco-2 cell viability and proliferation were not influenced by the administration of 1,25-D3 alone, but were markedly reduced by coadministration of 1,25-D3 and KD-35, a CYP24A1-inhibiting tetralone. Our data suggest that the mechanism of action of co-administered KD-35 and 1,25-D3 does not involve a direct cytotoxic effect, but rather the inhibition of cell proliferation. CONCLUSION:These findings demonstrate that the selective inhibition of CYP24A1 by compounds such as KD-35 may be a new approach for enhancement of the anti-tumor effect of 1,25-D3 on CRC. | János P Kósa Péter Horváth János Wlfling Dóra Kovács Bernadett Balla Péter Mátyus Evelin Horváth Gábor Speer István Takács Zsolt Nagy Henrik Horváth Péter Lakatos | 2013 | World Journal of Gastroenterology2013，19，17： | 5 |
| 3 | Relationship between depression and diabetes in pregnancy: A systematic review显示文摘AIM To systematically review the literature on women with both diabetes in pregnancy(DIP) and depression during or after pregnancy. METHODS In this systematic literature review, PubM ed/MEDLINE and EMBASE were searched(13 November 2015) using terms for diabetes(type 1, type 2, or gestational), depression, and pregnancy(no language or date restrictions). Publications that reported on women who had both DIP(any type) and depression or depressive symptoms before, during, or within one year after pregnancy were considered for inclusion. All study types were eligible for inclusion; conference abstracts, narrative reviews, nonclinical letters, editorials, and commentaries were excluded, unless they provided treatment guidance.RESULTS Of 1189 articles identified, 48 articles describing women with both DIP and depression were included(sample sizes 36 to > 32 million). Overall study quality was poor; most studies were observational, and only 12 studies(mostly retrospective database studies) required clinical depression diagnosis. The prevalence of concurrent DIP(any type) and depression in general populations of pregnant women ranged from 0% to 1.6%(median 0.61%; 12 studies). The prevalence of depression among women with gestational diabetes ranged from 4.1% to 80%(median 14.7%; 16 studies). Many studies examined whether DIP was a risk factor for depression or depression was a risk factor for DIP. However, there was no clear consensus for either relationship. Importantly, we found limited guidance on the management of women with both DIP and depression. CONCLUSION Given the increasing prevalence of diabetes and depression, high-quality research and specific guidance for management of pregnant women with both conditions are warranted. | Glynis P Ross Henrik Falhammar Roger Chen Helen Barraclough Ole Kleivenes Ian Gallen | 2016 | World Journal of Diabetes2016，7，19： | 3 |
| 4 | Gut microbiota disturbance during antibiotic therapy: a multi-omic approach显示文摘 | Ana Elena Pérez-Cobas María José Gosalbes Anette Friedrichs Henrik Knecht Alejandro Artacho Kathleen Eismann Wolfgang Otto David Rojo Rafael Bargiela Martin von Bergen Sven C Neulinger Carolin D?umer Femke-Anouska Heinsen Amparo Latorre Coral Barbas Jana | 2013 | Gut2013，，11： | 2 |
| 5 | IL-6 trans-signaling promotes pancreatitis-associated lung injury and lethality显示文摘 | Zhang Hong Neuh?fer Patrick Song Liang Rabe Bj?rn Lesina Marina Kurkowski Magdalena U Treiber Matthias Wartmann Thomas Regnér Sara Thorlacius Henrik Saur Dieter Weirich Gregor Yoshimura Akihiko Halangk Walter Mizgerd Joseph P Schmid Roland | 2013 | Journal of Clinical Investigation2013，，3： | 2 |
| 6 | 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 |
| 7 | Low Field 1H nuclear magnetic resonance and chemo metrics combined for simultaneous determination of water, oil, and protein contents in oilseeds显示文摘 | P Henrik M Lars B E S-ren | 2000 | JAOCS2000，77，10： | 1 |
| 8 | Microsomal Triglyceride transfer protein gene expression and triglyceride accumulation in hypoxic human hearts显示文摘 | Lars B Nielsen M P Henrik A | 2002 | Arterioscler Thromb Vasc Biol2002，22，2： | 1 |
| 9 | A prospective, randomized, controlled trial comparing intermittent portal triad clamping versus ischemic preconditioning with continuous clamping for major liver resection显示文摘 | Henrik P Lucas MC Marzha T | 2006 | Ann Surg2006，244，3： | 1 |
| 10 | Immunohistochemical detection of interleukin-8 in inflamed porcine tissues显示文摘 | Henriette Laursen Henrik E. Jensen Páll S. Leifsson Louise K. Jensen Johanna G. Christiansen Ramona Trebbien Ole L. Nielsen | 2014 | Veterinary Immunology and Immunopathology2014，，： | 1 |
| 11 | Early Prediction of Water-Holding Capacity in Meat by Multivariate Vibrational Spectroscopy 显示文摘 | DORTHE K P SOPHIE M HENRIK J A | 2003 | Meat Science2003，65，： | 1 |
| 12 | Effect of a multifactorial intervention on mortality in type 2 diabetes显示文摘 | Peter G Henrik LA Hans-Henrik P | 2008 | N Engl J Med2008，358，6： | 1 |
| 13 | Solvothermal synthesis of new metal-organic framework structures in the zinc-terephthalic acid-dimethyl forrnamide system显示文摘 | Henrik F C Rasmus D P Andrew D B el al | 2005 | J Solid State Chem2005，178，11： | 1 |
| 14 | Low-Field 1H nuclear magnetic resonance and cbemometrics combined for simultaneous determination of water,oil, and protein contents in oilseeds 显示文摘 | Henrik T P Lars M Sren B E | 2000 | JAOCS2000，77，10： | 1 |
| 15 | Models of white matter injury: comparison of infections, hypoxic-ischemic, and excitotoxic insults 显示文摘 | Henrik H Donald P Carina M | 2002 | Mental Ret2002，8，： | 1 |
| 16 | Water distribution and mobility in meat during the conversion of muscle to meat andageing and the impacts on fresh meat quality attributes-A review显示文摘 | Kelly L P Katja R Henrik J A | 2011 | Meat Science2011，89，2： | 1 |
| 17 | Habitat and feeding preferences of crustacean meso-herbivores inhabiting the brown seaweed Ascophyllum nodosum and its epiphytic macro-algae 显示文摘 | Henrik P Herman C Per A | 1999 | J Exp Mar Biol Ecol1999，236，1： | 1 |
| 18 | Microsomal Triglyceride Transfer Protein Gene Expression and tfiglyceride Accumulation in Hypoxic Human Hearts 显示文摘 | Lars B Nielsen M P Henrik A | 2002 | Arterioscler Thromb Vasc Biol2002，22，2： | 1 |
| 19 | Reviews of Governing as Governance显示文摘 | Henrik P B | 2007 | Public Administration2007，，1： | 1 |
| 20 | Changes in the North Sea fish community: evidence of indirect effects of fishing 显示文摘 | Niels D Henrik G John G P | 2005 | ICES J Mar Sci2005，62，2： | 1 |
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