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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 | Long-term follow-up study of gastroduodenal lesions after radioembolization of hepatic tumors显示文摘AIM:To evaluate the long-term natural history of the gastroduodenal lesions secondary to extrahepatic embolization with Ytrium 90(90 Y) spheres.METHODS:From September 2003 to January 2012,379 procedures of liver radioembolization(RE) using resin microspheres loaded with 90 Y were performed in our center.We have retrospectively compiled the data from 379 RE procedures performed in our center.We report a comprehensive clinical,analytical,endoscopic and histologic long-term follow-up of a series of patients who developed gastroduodenal lesions after the treatment.RESULTS:Six patients(1.5%) developed gastrointestinal symptoms and had gastrointestinal lesions as shown by upper endoscopy in the next 12 wk after RE.The mean time between RE and the appearance of symptoms was 5 wk.Only one patient required endoscopic and surgical treatment.The incidence of gastrointestinal ulcerations was 3.75%(3/80) when only planar images were used for the pre-treatment evaluation.It was reduced to 1%(3/299) when singlephoton emission computed tomography(SPECT) images were also performed.The symptoms that lasted for a longer time were nausea and vomiting,until 25 mo after the treatment.CONCLUSION:All patients were free from severe symptoms at the end of follow-up.The routine use of SPECT has decreased the incidence of gastrointestinal lesions due to unintended deployment of 90 Y particles. | Iago Rodríguez-Lago Cristina Carretero Maite Herráiz José C Subtil Maite Betés Macarena Rodríguez-Fraile Jesús J Sola José I Bilbao Miguel Muoz-Navas Bruno Sangro | 2013 | World Journal of Gastroenterology2013，19，19： | 2 |
| 3 | Induction of Sensitivity to ganciclovir in human hepatocellular Carcinoma cells by adenovirus - mediated gene transfer of herpes simplex virus thymidine Kinase显示文摘 | Bilbao R Bruna O | 1995 | Hepatology1995，22，： | 1 |
| 4 | Drying kinetics of apple cylinders under combined hot air - microwave dehydration显示文摘 | ANDRES A BILBAO C FITO P | 2004 | Journal of Food Engineering2004，63，1： | 1 |
| 5 | The relationship between microsatellite instability and PTEN gene mutations in endometrial cancer显示文摘 | Bilbao C Rodriguez G Ramirez R | 2006 | Int J Cancer2006，119，3： | 1 |
| 6 | Drying kinetics of apple cylinders under combined hot air-microwave dehydration 显示文摘 | Andres A Bilbao C Fito P | 2004 | Journal of Food Engineering2004，63，1： | 1 |
| 7 | Drying kinetics of apple cylinders under combined hot air-microwave dehydration显示文摘 | ANDRES A BILBAO C FITO P | 2004 | Journal of Food Engineering2004，63，1： | 1 |
| 8 | Portal hypertension: diagnostic imaging and imaging -guided therapy显示文摘 | Bilbao JI Vivasl Delgado C Martinez Cuesta A | 2000 | Springer2000，11，： | 1 |
| 9 | Charge storage of electrospun fiber mats of poly (phenylene ether)/polystyrene blends 显示文摘 | LOVERA D BILBAO C SCHREIER P | 2009 | Polymer Engineering Science2009，49，： | 1 |
| 10 | FK506 in the maturation of dendritic cells显示文摘 | Cos J Villalba T Parra R Gallardo D Bilbao I Margarit C | 2002 | Haematologica2002，87，7： | 1 |
| 11 | Induction of sensitivity to ganciclovir in human hepatocellular carcinoma cells by adenovirus-mediated gene transfer of herpes simplex virus thymidine kinase显示文摘 | Qian C Bilbao R Bruna O | 1995 | Hepatology1995，22，1： | 1 |
| 12 | Longitudinal analysis of cognitive performances and structural brain changes in late-life bi- polar disorder显示文摘 | Delaloye C Moy G de Bilbao F | 2011 | Int J Geriatr Psychiatry2011，26，12： | 1 |
| 13 | Sodium 4-phenylbutyrate protects against liver isehemia reperfusion injury by inhibition of endoplasmic reticulum-stress mediated apoptosis 显示文摘 | Vilatoba M Eckstein C Bilbao G | 2005 | Surgery2005，138，2： | 1 |
| 14 | Drying kinetics of apple cylin- ders under combined hot air - microwave dehydration 显示文摘 | Andres A Bilbao C Fito P | 2004 | Journal of Food Engineering2004，63，1： | 1 |
| 15 | Longitudinal analysis of cognitive performances and structural brain changes in late-life bipolar disorder 显示文摘 | Delaloye C Moy G de Bilbao F | 2011 | Int J Geriatr Psychiatry2011，6，： | 1 |
| 16 | Sodium 4 phenylbu- tyrate protects against liver ischemia reperfusion injury by in- hibition of endoplasmic reticulum - stress mediated apoptosis 显示文摘 | Vilatoba M Eckstein C Bilbao G | 2005 | Surgery2005，138，： | 1 |
| 17 | A prospective ran- domized trial comparing tacrolimus and steroids with ta- crolimus monotherapy in liver transplantation: the impact on recurrence of hepatitis C显示文摘 | Margarit C Bilbao I Castells L | 2005 | Transplant lnt2005，18，12： | 1 |
| 18 | Drying kinetics of apple cylinders under combined hot air-microwave dehydration显示文摘 | Andres A Bilbao C Fito P | | 0，，63： | 1 |
| 19 | Drying kinetics of apple cylinders under combined hot air microwave dehydration 显示文摘 | Andres A Bilbao C | 2004 | Journal of Food Engineering2004，，63： | 1 |
| 20 | Induction of sensitivity to ganciclovir in human hepatocellular carcinoma cells by adenovirus mediated gene transfer ofherps simplex virus thymidine kinase 显示文摘 | Qian c Bilbao R Bruna O | 1995 | Hepatology1995，22，1： | 1 |
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