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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 | 创伤后深静脉血栓的预防机械预防和药物预防的前瞻性、随机性比较显示文摘背景:骨创伤后的深静脉血栓是十分重要的问题,但相关研究甚少。本研究的目的是评估两种不同方法对预防钝性创伤后深静脉血栓和肺栓塞的有效性。
方法:共有224例住院患者参与此项预防创伤后静脉血栓形成的前瞻性随机性研究。200例患者最终完成研究,比较两种不同的预防方案。A组患者在钝性创伤后24-48h内使用依诺肝素(30mg,皮下,每天两次)。B组患者在人院后使用脉冲式足泵并延迟使用依诺肝素。所有患者在出院前均行静脉核磁共振和超声检查。
结果:A组共97例患者,B组共103例患者。22例患者(A组13人,B组9人)有深静脉血栓形成,其中A组2例还发生了肺栓塞。本组深静脉血栓的发生率为11%,A组13.4%,B组8.7%;A组和B组之间的差异无统计学意义。A组出现大的或闭塞性血栓共11例(发生率11.3%),B组仅3例(发生率2.9%)(p=0.025)。A组肺栓塞的发生率为2.1%,B组为0。A组有21例患者出现伤口并发症,B组为20例。住院期间发生深静脉血栓的患者人均用血7.4单位,无深静脉血栓的患者人均用血3.9单位(p〈0.05)。
结论:结果显示严重的肌肉骨骼创伤后,早期使用机械预防(足泵)并延迟使用依诺肝素对预防深静脉血栓是相当有效的。比较两组患者,B组患者大的或闭塞性血栓的发生率明显低于A组患者。
可信水平:治疗性研究,Ⅰ级。详细的可信水平描述参见作者须知。 | JAMES P. STANNARD ROBERT R. LOPEZ-BEN DAVID A. VOLGAS EDWARD R. ANDERSON MATT BUSBEE DONNA K. KARR GERALD R. McGWIN JR. JORGE E. ALONSO 罗从风(译) 费起礼(校) | 2006 | 骨科动态2006，2，3： | 2 |
| 3 | Peers' Influence On Exer- cise Enjoyment:A Self-determination Theory Approach 显示文摘 | Juan Antonio Moreno Murcia Maria Lopez de San Romfn Celestina Martinez Galindo Nestor Alonso David Gonzalez-Cutre | 2008 | Journal of Sports and Medicine2008，，1： | 1 |
| 4 | Neuronal and inducible nitric oxide synthase expression and protein nitration in rat cerebellum after oxygen and glucose deprivation 显示文摘 | Jose Rodrigo David Alonso Ana Patricia Fernandez | 2001 | Brain Res2001，909，12： | 1 |
| 5 | Production of liquid hydrocarbon transportation fuels by oligome- rization of biomass-derived C9 alkenes 显示文摘 | David Martin Alonso Jesse Q Bond Juan Carlos Serrano-Ruiz | 2010 | Green Chem2010，6，： | 1 |
| 6 | Catalytic conversion of biomass to biofuels 显示文摘 | David Martin Alonso Jesse Q Bond James A Dumesic | 2010 | Green Chemistry2010，12，： | 1 |
| 7 | Role of New Functional MRI Techniques in the Diagnosis, Staging, and Followup of Gynecological Cancer: Comparison with PET-CT显示文摘 | Elena Alvarez Moreno Mar Jimenez de la Pe?a Raquel Cano Alonso David C. Howlett | 2012 | Radiology Research and Practice2012，，： | 1 |
| 8 | POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASE IN PEDIATRIC LIVER TRANSPLANTATION: Interplay Between Primary Epstein-Barr Virus Infection and Immunosuppression显示文摘 | Kenneth A. Newell Estella M. Alonso Peter F. Whitington David S. Bruce J. Michael Millis James B. Piper E. Steve Woodle Susan M. Kelly Hartmut Koeppen John Hart Charles M. Rubin J. Richard Thistlethwaite | 1996 | Transplantation1996，，3： | 1 |
| 9 | Arabidopsis RIN4 Is a Target of the Type III Virulence Effector AvrRpt2 and Modulates RPS2-Mediated Resistance显示文摘 | David Mackey Youssef Belkhadir Jose M. Alonso Joseph R. Ecker Jeffery L. Dangl | 2003 | Cell2003，，3： | 1 |
| 10 | Microbleed Burden and Hematoma Expansion in Acute Intracerebral Hemorrhage显示文摘 | Martí-fàbregas Joan Delgado-mederos Raquel Granell Esther Morenas Rodríguez Estrella Marín Lahoz Juan Dinia Lavinia Carrera David Pérez De La Ossa Natalia Sanahuja Jordi Sobrino Tomás De Arce Ana María Alonso De Leci?ana María | 2013 | European Neurology . 2013 (3-4)2013，，3： | 1 |
| 11 | Colorectal cancer in patients with inflammatory bowel disease after liver transplantation for primary sclerosing cholangitis显示文摘 | Alonso Vera Bridget K. Gunson Val Ussatoff Peter Nightingale Daniel Candinas Simon Radley A. David Mayer John A.C. Buckels Paul McMaster James Neuberger Darius F. Mirza | 2003 | Transplantation2003，，12： | 1 |
| 12 | Outcome of liver transplantation for patients with pulmonary hypertension显示文摘 | Peter Starkel Alonso Vera Bridget Gunson David Mutimer | 2002 | Liver Transplantation2002，，4： | 1 |
| 13 | RuSn bimetallic catalysts for selective hydrogenation of levulinic acid to γ-valerolactone显示文摘 | Stephanie G. Wettstein Jesse Q. Bond David Martin Alonso Hien N. Pham Abhaya K. Datye James A. Dumesic | 2012 | Applied Catalysis B Environmental2012，，： | 1 |
| 14 | Interconversion between γ -valerolactone and pentenoic acid combined with decarboxylation to form butene over silica/alumina显示文摘 | Jesse Q. Bond Dong Wang David Martin Alonso James A. Dumesic | 2011 | Journal of Catalysis2011，，2： | 1 |
| 15 | Randomised placebo-controlled trial of iron supplementation and malaria chemoprophylaxis for prevention of severe anaemia and malaria in Tanzanian infants显示文摘 | Clara Menendez Elizeus Kahigwa Rosmarie Hirt Penelope Vounatsou John J Aponte Fidel Font Camilo J Acosta David M Schellenberg Claudia M Galindo John Kimario Honorathy Urassa Bernard Brabin Tom A Smith Andrew Y Kitua Marcel Tanner Pedro L Alonso | 1997 | The Lancet1997，，9081： | 1 |
| 16 | Negative Pressure Wound Therapy After Severe Open Fractures: A Prospective Randomized Study显示文摘 | James P Stannard David A Volgas Rena Stewart Gerald McGwin Jorge E Alonso | 2009 | Journal of Orthopaedic Trauma2009，，8： | 1 |
| 17 | American Gastroenterological Association Institute Guideline on the Medical Management of Microscopic Colitis显示文摘 | Geoffrey C. Nguyen Walter E. Smalley Santhi Swaroop Vege Alonso Carrasco-Labra Steven L. Flamm Lauren Gerson Ikuo Hirano Joel H. Rubenstein Siddharth Singh Neil Stollman Shahnaz Sultan Sachin B. Wani David S. Weinberg Yu-Xiao Yang | 2016 | Gastroenterology2016，，1： | 1 |
| 18 | Negative Pressure Wound Therapy to Treat Hematomas and Surgical Incisions Following High-Energy Trauma显示文摘 | James P. Stannard James T. Robinson E Ratcliffe Anderson Gerald McGwin David A. Volgas Jorge E. Alonso | 2006 | The Journal of Trauma: Injury Infection and Critical Care2006，，6： | 1 |
| 19 | Estimating the expected value of fuzzy random variables in the strati- fied random sampling from finite populations显示文摘 | David G Lubiano M A Alonso M C | 2001 | Information Sciences2001，138，2： | 1 |
| 20 | Bigger or long-winged male common crossbills exhibit redder carotenoid-based plumage coloration显示文摘Carotenoid-based ornaments are often considered reliable(honest)individual condition signals because their expression implies physiological costs unaffordable for low-quality animals(handicap signals).Recently,it has been suggested that efficient cell respiration is mandatory for producing red ketocarotenoids from dietary yellow carotenoids.This implies that red colorations should be entirely unfalsifiable and independent of expression costs(index signals).In a precedent study,male common crossbills,Loxia curvirostra,showing a red plumage reported higher apparent survival than those showing yellowish-orange colors.The plumage redness in this species is due to ketocarotenoid accumulation in feathers.Here,we correlated the male plumage redness(a 4-level visual score:yellow,patchy,orange,and red)and the body morphology in more than 1,ooo adult crossbills captured in 3 Iberian localities to infer the mechanisms responsible for color evolution.A principal component analysis summarized morphometry of 10 variables(beak,wing,tarsus length,etc.).The overall body size(PC1)and the length of flight feathers regarding body size(Pc3)showed significant positive relationships with plumage redness.Plumage redness was barely correlated with bill shape measures,suggesting no constraint in acquiring carotenoids from pine cones.However,large body sizes or proportionally long flying feathers could help carotenoid acquisition via social competition or increased foraging ranges.Proportionally longer flight feathers might also be associated with a specific cell respiration profile that would simultaneously favor flying capacities and enzymatic transformations needed for ketocarotenoid synthesis.Such a phenotypic profile would agree with the hypothesis of ketocarotenoid-based colors acting as individual quality index signals. | Blanca Fernandez-Eslava Daniel Alonso David Galicia Juan Arizaga Carlos Alonso-Alvarez | 2023 | Current Zoology2023，69，2： | 0 |
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