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| 1 | Biomarkers and subtypes of deranged lipid metabolism in nonalcoholic fatty liver disease显示文摘Nonalcoholic fatty liver disease(NAFLD)is a heterogeneous and complex disease that is imprecisely diagnosed by liver biopsy.NAFLD covers a spectrum that ranges from simple steatosis,nonalcoholic steatohepatitis(NASH)with varying degrees of fibrosis,to cirrhosis,which is a major risk factor for hepatocellular carcinoma.Lifestyle and eating habit changes during the last century have made NAFLD the most common liver disease linked to obesity,type 2 diabetes mellitus and dyslipidemia,with a global prevalence of 25%.NAFLD arises when the uptake of fatty acids(FA)and triglycerides(TG)from circulation and de novo lipogenesis saturate the rate of FAβ-oxidation and verylow density lipoprotein(VLDL)-TG export.Deranged lipid metabolism is also associated with NAFLD progression from steatosis to NASH,and therefore,alterations in liver and serum lipidomic signatures are good indicators of the disease’s development and progression.This review focuses on the importance of the classification of NAFLD patients into different subtypes,corresponding to the main alteration(s)in the major pathways that regulate FA homeostasis leading,in each case,to the initiation and progression of NASH.This concept also supports the targeted intervention as a key approach to maximize therapeutic efficacy and opens the door to the development of precise NASH treatments. | José M Mato Cristina Alonso Mazen Noureddin Shelly C Lu | 2019 | World Journal of Gastroenterology2019，25，24： | 19 |
| 2 | 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 |
| 3 | Successful operation of a cooperative SLR station of China and Argentina in San Juan显示文摘We introduced the observations and researches using a Satellite Laser Ranging (SLR) system with high precision, which was designed and made in China and installed in the Observatory of San Juan Uni- versity, Argentina, the capability of the system and the achievement of the cooperative procedure be- tween China and Argentina. The SLR station in San Juan, set up by China and Argentina, is quite sig- nificant for improving the distribution of SLR stations and enhancing the orbital coverage of the whole earth. Since the SLR system started to work in the Observatory of San Juan University in the beginning of 2006, the operation is rather good, and rich data with high precision have been obtained. Further plan of the cooperation for the near future is also presented. | HAN YanBen LIU WeiDong E ACTIS R PODESTA WANG TanQiang GUO TangYong QU Feng A M PACHECO A A GONZALEZ E ALONSO XIANG QingGe HUANG DongPing YIN ZhiQiang | 2008 | Chinese Science Bulletin2008，53，16： | 2 |
| 4 | Oxidative stress in apoptosis and cancer: an update显示文摘 | José M. Matés Juan A. Segura Francisco J. Alonso Javier Márquez | 2012 | Archives of Toxicology2012，，11： | 2 |
| 5 | Supercritical water oxidation process under energetically self-sufficient operation 显示文摘 | Cocero M J Alonso E Sanz M T | 2002 | Journal of Supercritical Fluids2002，24，1： | 2 |
| 6 | Occurrence of Organochlorine Insecticides, PCBs and PCB Congeners in waters and Sediments of the Ebro River (Spain) 显示文摘 | Fernandez M A Alonso C Gonzalez M J | 1999 | Chemosphere1999，38，： | 2 |
| 7 | Measurement of fractional flow reserve to assess moderately severe coronary lesions: correlation with dobutamine stress echocardiography显示文摘 | Jimenez Navarro M Alonso Briales J H Hernandez Garcia M J | 2001 | J Interv Cardiol2001，14，5： | 2 |
| 8 | 遗传性肥胖与心房颤动的关系显示文摘观察性研究已经确定了体质量指数(body mass index,BMI)与心房颤动之间的关联。然而,从观察性研究中推断因果关系会受到混杂因素、逆因果关系和偏倚的影响。该研究的主要目的是应用BMI的遗传学预测因子评估BMI与心房颤动之间的因果关系。方法:纳入1987-2002年期间在美国、冰岛和荷兰实施的7个前瞻性人群队列研究中基线无心房颤动的欧洲血统个体51 646人, | 刘莉 叶鹏 Chatterjee NA Giulianini F Geelhoed B Lunetta KL Misialek JR Niemeijer MN Rienstra M Rose LM Smith AV Arking DE Ellinor PT Heeringa J Lin H Lubitz SA Soliman EZ Verweij N Alonso A Benjamin EJ Gudnason V Stricker BH van der Harst P Chasman DI Albert CM | 2017 | 中华高血压杂志2017，25，2： | 2 |
| 9 | 3, 5-Bis (trifluoromethyl) phenyl sulfones in the modified julia olefination: application to the synthesis of resveratrol 显示文摘 | Alonso D A Najera C Varea M | 2004 | Tetrhaedron Lett2004，45，： | 1 |
| 10 | An improved time domain arc furnace model for harmonic analysis显示文摘 | ALONSO M A P DONSION M P | 2004 | IEEE Transactions on Power Delivery2004，19，1： | 1 |
| 11 | Long-term results and survival rate of implants treated with guided bone regeneration: a 5-year case series prospective study显示文摘 | Blanco J Alonso A Sanz M | 2005 | Clin Oral hnplants Res2005，16，3： | 1 |
| 12 | Is cisplatin-induced cell death always produced by apoptosis?显示文摘 | GONZALEZ V M FUERTES M A ALONSO C | 2001 | Mol Pharmaeol2001，59，4： | 1 |
| 13 | Mantis shrimp allergy 显示文摘 | Alonso R E Zavala B B Escoda J M | 2006 | J Investig Allergol Clin Immunol2006，16，6： | 1 |
| 14 | The effect of ammonium sulphate and ammonia on the liquid-liquid extraction of zinc using LIX54显示文摘 | Alguacil F J Alonso M | 1999 | Hydrometallurgy1999，53，2： | 1 |
| 15 | A novelstrategy for radar imaging based on compressive sensing显示文摘 | Alonso M T López-Dekker P and MallorquíJ J | 2010 | IEEE Transactions on Geoscience and Remote Sensing2010，48，12： | 1 |
| 16 | Determinants of Release Rate of Tetanus Vaccine from Polyester Microspheres显示文摘 | ALONSO M J COHEN S PARK T G | 1993 | Pharm Res1993，10，： | 1 |
| 17 | Suppressive subtraction Libraries to Identify interferon-inducible genes in fish显示文摘 | Alonso M Leong J A | 2002 | Mar Biotechnol2002，4，1： | 1 |
| 18 | Complex magnetism and magnetic structures of the metastable HoMnO3 perovskite显示文摘 | Munoz A Casals M T Alonso J A | 2001 | Inorg Chem2001，40，： | 1 |
| 19 | Physiopathology of bacterial translocation and spontaneous bacterial peritonitisin cirrhosis显示文摘 | Gonzalez Alonso R Gonzalez Garcia M Albillos Martinez A | 2007 | Gastroenterol Hepatol2007，30，2： | 1 |
| 20 | On-line preconcentration using chelating and ion-exchange minicolumns for the speciation of chromium(iii) and chrontium(vi) and their quantitative determination in natural waters by inductively coupled plasma mass spectrometry显示文摘 | GUERRERO M M L ALONSO E V PAVON J M C | 2012 | Journal of Analytical Atomic Spectrometry2012，27，4： | 1 |
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