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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 | Mobilization of hematopoietic progenitor cells in patients with liver cirrhosis显示文摘AIM:To test the hypothesis that liver cirrhosis is associated with mobilization of hematopoietic progenitor cells. METHODS:Peripheral blood samples from 72 patients with liver cirrhosis of varying etiology were analyzed by flow cytometry.Identified progenitor cell subsets were immunoselected and used for functional assays in vitro. Plasma levels of stromal cell-derived factor-1(SDF-1) were measured using an enzyme linked immunosorbent assay.RESULTS:Progenitor cells with a CD133 + /CD45 + CD14 + phenotype were observed in 61%of th patients.Between 1%and 26%of the peripheral bloo mononuclear cells(MNCs)displayed this phenotype Furthermore,a distinct population of c-kit + progenito cells(between 1%and 38%of the MNCs)could b detected in 91%of the patients.Additionally,18% of the patients showed a population of progenito cells(between 1%and 68%of the MNCs)that wa characterized by expression of breast cancer resistanc protein-1.Further phenotypic analysis disclosed tha the circulating precursors expressed CXC chemokin receptor 4,the receptor for SDF-1.In line with thi finding,elevated plasma levels of SDF-1 were presen in all patients and were found to correlate with th number of mobilized CD133 + progenitor cells. | Ursula M Gehling Marc Willems Kathleen Schlagner Ralf A Benndorf Maura Dandri Jrg Petersen Martina Sterneck Joerg-Matthias Pollok Dieter K Hossfeld Xavier Rogiers | 2010 | World Journal of Gastroenterology2010，16，2： | 4 |
| 3 | Molecular imaging of human thrombus with novel abciximab immunobubbles and ultrasound显示文摘 | Alonso A Della Martina A Stroick M | 2007 | Stroke2007，38，： | 1 |
| 4 | Aqueous geochemical and surface science investigation of the effect of phosphate on pyrite oxidation显示文摘 | Aliciar E Martina A S Danielr S | 2001 | Environmental Science and Technology2001，35，11： | 1 |
| 5 | Fea- sibility of CHP-plants with thermal stores in the German spot market 显示文摘 | STRECKIENE G MARTINAITIS V ANDERSEN A N | 2009 | Applied Energy2009，86，11： | 1 |
| 6 | Effect of preoperative radiological treatment of hepatocellular carcinoma before liver transplantation: a retrospective study 显示文摘 | Vehri A Grosso M Martina MC et at | 1998 | Cardiovasc Intervent Radiol1998，21，： | 1 |
| 7 | In vivo ligation of CD3 on neonatal scid thymocytes blocks -irradiation-induced TCR rearrangements and thymic lymphomagenesis显示文摘 | Martina C Wayne J Bell A | 2003 | Immunology Letters2003，85，3： | 1 |
| 8 | Carotid plaque pat- hology: thrombosis,ulceration, and stroke pathgenesis 显示文摘 | Fisher M Paganini-Hill A MartinA | 2005 | Stroke2005，36，： | 1 |
| 9 | Predictor factors for renal outcome in renal artery stenosis显示文摘 | Cianci R Martina P Gigante A | 2013 | European Review for Medical and Pharmacological Sciences2013，17，4： | 1 |
| 10 | Normal breast tissue stiffness measured by a new ultrasound technique:virtual touch tissue imaging quantification(VTIQ)显示文摘 | Golatta M Martina MS Harcosa A | 2013 | Eur J Radiol2013，82，： | 1 |
| 11 | Model evidence for a significant source of secondary organic aerosol from isoprene 显示文摘 | Donkelaara A Martina R Park R 2007 | 2007 | 41 : 1267-12742007，41，： | 1 |
| 12 | Evaluation of virtual touch tissue imaging quantification,a new shear wave velocity imaging method,for breast lesion assessment by ultrasound显示文摘 | Golatta M Martina MS Harcosa A | 2014 | Bio Med Res Int2014，，96： | 1 |
| 13 | Recombinant modified vaccinia virus Ankara expressing glycoprotein E2 of cbikungunya virus protects AG129 mice against lethal challenge 显示文摘 | van den Doel P Volz A Roose JM Sewbalaksing VD Pijlman GP van Middelkoop 1 Duiverman V van de Wetering E Sutter G Osterhaus AD Martina BE | 2014 | PLoS Negl Trop Dis2014，8，9： | 1 |
| 14 | Social anxiety disorder and the risk of depression显示文摘 | Murry BS Martina A | 2001 | Arch Gen Psychiatry2001，57，： | 1 |
| 15 | Electric Field-Induced Aligned Multi-Wall Carbon Nanotube Networks in Epoxy Composites显示文摘 | Martina C A Sandlera J K W Windlea A H | 2005 | Polymer2005，46，： | 1 |
| 16 | Can the quantity of cell-free fetal DNA predict preeclampsia:a systematic review 显示文摘 | Martin A Krishna I Martina B | 2014 | Prenat Di- agn2014，34，7： | 1 |
| 17 | Thin Solid Films显示文摘 | Bendavid A Martina P J Takikawa H | 2000 | 360:241-2492000，360，： | 1 |
| 18 | A multi-model approach for describing crude oil price dynam- ics显示文摘 | Bernabe A Martina E Alvarez-Ramirez J | 2004 | Physica A2004，338，4： | 1 |
| 19 | Inverse Jet Electrochemical Machining for Functional Edge Shaping of Micro Bores 显示文摘 | OSCHTZCHENA M H MARTINA A MEICHSNER G | 2013 | Procedia CIRP2013，，6： | 1 |
| 20 | Sequential toxicity idenitrification evaluation(TIE) for characterizing toxicity of Venice Lagoon sediments:Comparison of two different approaches显示文摘 | Marco P A Martina B Elisa V | 2009 | Ecotoxicology and Environmental Safety2009，72，： | 1 |
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