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| 1 | Arachidyl amido cholanoic acid improves liver glucose and lipid homeostasis in nonalcoholic steatohepatitis via AMPK and mTOR regulation显示文摘BACKGROUND Arachidyl amido cholanoic acid(Aramchol)is a potent downregulator of hepatic stearoyl-CoA desaturase 1(SCD1)protein expression that reduces liver triglycerides and fibrosis in animal models of steatohepatitis.In a phase IIb clinical trial in patients with nonalcoholic steatohepatitis(NASH),52 wk of treatment with Aramchol reduced blood levels of glycated hemoglobin A1c,an indicator of glycemic control.AIM To assess lipid and glucose metabolism in mouse hepatocytes and in a NASH mouse model[induced with a 0.1%methionine and choline deficient diet(0.1MCD)]after treatment with Aramchol.METHODS Isolated primary mouse hepatocytes were incubated with 20μmol/L Aramchol or vehicle for 48 h.Subsequently,analyses were performed including Western blot,proteomics by mass spectrometry,and fluxomic analysis with 13C-uniformly labeled glucose.For the in vivo part of the study,male C57BL/6J mice were randomly fed a control or 0.1MCD for 4 wk and received 1 or 5 mg/kg/d Aramchol or vehicle by intragastric gavage for the last 2 wk.Liver metabolomics were assessed using ultra-high-performance liquid chromatography-time of flight-MS for the determination of glucose metabolism-related metabolites.RESULTS Combination of proteomics and Western blot analyses showed increased AMPK activity while the activity of nutrient sensor mTORC1 was decreased by Aramchol in hepatocytes.This translated into changes in the content of their downstream targets including proteins involved in fatty acid(FA)synthesis and oxidation[PACCα/β(S79),SCD1,CPT1A/B,HADHA,and HADHB],oxidative phosphorylation(NDUFA9,NDUFB11,NDUFS1,NDUFV1,ETFDH,and UQCRC2),tricarboxylic acid(TCA)cycle(MDH2,SUCLA2,and SUCLG2),and ribosome(P-p70S6K[T389]and P-S6[S235/S236]).Flux experiments with 13Cuniformely labeled glucose showed that TCA cycle cataplerosis was reduced by Aramchol in hepatocytes,as indicated by the increase in the number of rounds that malate remained in the TCA cycle.Finally,liver metabolomic analysis showed that glucose homeostasis was improved by Aramchol in 0.1MCD fed mice in a dose-dependent manner,showing normalization of glucose,G6P,F6P,UDP-glucose,and Rbl5P/Xyl5P.CONCLUSION Aramchol exerts its effect on glucose and lipid metabolism in NASH through activation of AMPK and inhibition of mTORC1,which in turn activate FAβ-oxidation and oxidative phosphorylation. | David Fernández-Ramos Fernando Lopitz-Otsoa Laura Delacruz-Villar Jon Bilbao Martina Pagano Laura Mosca Maider Bizkarguenaga Marina Serrano-Macia Mikel Azkargorta Marta Iruarrizaga-Lejarreta Jesús Sot Darya Tsvirkun Sebastiaan Martijn van Liempd Felix M Goni Cristina Alonso María Luz Martínez-Chantar Felix Elortza Liat Hayardeny Shelly C Lu JoséM Mato | 2020 | World Journal of Gastroenterology2020，26，34： | 5 |
| 2 | 哮喘治疗的新进展显示文摘没有强有力的循证医学证据表明饮食方法或Buteyko技术对哮喘的临床管理有很大益处需要进一步研究确定当哮喘控制欠佳时患者应该怎么做小剂量吸入皮质激素可以和长效β2激动剂联合应用,以提供安全有效的哮喘控制静脉镁制剂和白三烯受体拮抗剂对急性哮喘可能具有一些作用,但仍需进一步评价将来哮喘治疗是否能得到炎症生物标志或患者基因型认识的帮助。 | Graeme P Currie Graham S Devereux Daniel K C Lee Jon G Ayres 刘艳(译) 代华平(校) | 2005 | 英国医学杂志中文版2005，8，4： | 3 |
| 3 | Vascular endothelial growth factor-D and its receptor VEGFR- 3 : two novel independent prognostic markers in gastric adenocarcinoma显示文摘 | JUTTNER S WISSMANN C JONS T | 2006 | J Clin Oncol2006，24，： | 1 |
| 4 | Methyl farnesoate synthesis in the lobster mandibular organ: The roles of HMG-CoA reductase and farnesoic acid O-methyltrandferse显示文摘 | Li Sheng Jon A F Kenneth C H | 2010 | Comp Biochem Physiol2010，155，1： | 1 |
| 5 | An experimental investigation of the electrostatic discharge (ESD) mechanism in packaged semiconductor devices显示文摘 | M C Jon T L Welsher | 1994 | J of Electrostatics1994，32，： | 1 |
| 6 | Prior Family Business Exposure as lntergenerational Influence and Entrepreneurial Intent:a Theory of Planned Behavior Approach 显示文摘 | JON C C JENNIFER M S | 2007 | Journal of Busi- ness Research2007，60，10： | 1 |
| 7 | Vascular endothelial growth factor-D and its receptor VEGFR-3 : two novel independent prognostic markers in gastric adenocarcinoma 显示文摘 | Juttner S Wissmann C Jons T | 2006 | J Clin Oncol2006，24，： | 1 |
| 8 | Matrix converters:a technology review 显示文摘 | Patirck W Jose R Jon C | 2002 | IEEE Trans on Industrial Electronics2002，49，2： | 1 |
| 9 | Safety and tolerability of intraputaminal delivery of CERE-120 (adeno-associated virus serotype 2–neurturin) to patients with idiopathic Parkinson’s disease: an open-label, phase I trial显示文摘 | William J Marks Jill L Ostrem Leonard Verhagen Philip A Starr Paul S Larson Roy AE Bakay Robin Taylor Deborah A Cahn-Weiner A Jon Stoessl C Warren Olanow Raymond T Bartus | 2008 | Lancet Neurology2008，，5： | 1 |
| 10 | Recent advance in techniques for hyperspectral image processing显示文摘 | Antonio P Jon A B Joseph W B Jason B Lorenzo B Gustavo C V Jocelyn C Mathieu F Paolo G Anthony G Mattia M James C T Giovanna T | 2009 | Remote Sensing of Environment2009，113，： | 1 |
| 11 | Vascular endothelial growth factor-D and its receptor VEGFR-3: two novel independent prognosticmarkers in gastric adenocarcinoma 显示文摘 | Juttner S Wissmann C Jons T | 2006 | J Clin Oncol2006，24，2： | 1 |
| 12 | Flu Researchers Train Sights On Novel Tricks of Novel H1N1显示文摘 | Jon C | 2009 | Science2009，324，： | 1 |
| 13 | From 4PL to managed supplychain operations显示文摘 | Jon B Kempton C | 2002 | Logistics & Transport Focus2002，1，4： | 1 |
| 14 | Shuttle Entry Guidance 显示文摘 | Jon C Horpold Claude A Graves | 1979 | The Journal of the Astronautical Sciences July-September1979，，3： | 1 |
| 15 | Adolescents with high periodontal risk in Public Dental Service显示文摘 | Jansson L Adler L Jonés C | 2013 | Swed Dent J2013，37，4： | 1 |
| 16 | Genetic variability related to serum uric acid concentration and risk of Parkinson’s disease显示文摘 | Isabel González‐Aramburu Pascual Sánchez‐Juan Silvia Jesús Ana Gorostidi Eduardo Fernández‐Juan Fátima Carrillo María Sierra Pilar Gómez‐Garre María T. Cáceres‐Redondo José Berciano Javier Ruiz‐Martínez Onofre Combarros Pablo Mir Jon Infante | 2013 | Mov Disord2013，，： | 1 |
| 17 | Matrix Converters: A Technology Review 显示文摘 | PATRICK W WHEELER JOSI RODRfGUEZ JON C CLARE | 2002 | IEEE Transaction on Industry and Etetronics2002，49，2： | 1 |
| 18 | Sonic activation of molecularly-targeted nanoparticles accelerates transmembrane lipid delivery to cancer cells through contact-mediated mechanisms:implications for enhanced local drug delivery显示文摘 | Crowder K C Hughes Michael S Marsh Jon N | 2005 | Ultrasound in Med &Biol2005，31，： | 1 |
| 19 | Inhibition mechanism of kojic acid on polyphenol oxidase 显示文摘 | Jon S C Cheng W Marry R M | 1991 | Agricultural and Food Chemistry1991，39，11： | 1 |
| 20 | Techno-economic assessment of CO2 capture retrofit to existing power plants显示文摘 | Jon G Hannah C Mathieu L | 2011 | Energy Procedia2011，4，5： | 1 |
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