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| 1 | Examination of the therapeutic potential of Delta-24-RGD in brain tumor stem cells: role of autophagic cell death显示文摘 | Jiang H Gomez-Manzano C Aoki H Alonso MM Kondo S McCormick F Xu J Kondo Y Bekele BN Colman H Lang FF Fueyo J | 2007 | 中国神经肿瘤杂志2007，5，3： | 24 |
| 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 | Interplay between post-translational cyclooxygenase-2 modifications and the metabolic and proteomic profile in a colorectal cancer cohort显示文摘BACKGROUND Colorectal cancer(CRC) is the second most common cause of cancer death worldwide. It is broadly described that cyclooxygenase-2(COX-2) is mainly overexpressed in CRC but less is known regarding post-translational modifications of this enzyme that may regulate its activity, intracellular localization and stability. Since metabolic and proteomic profile analysis is essential for cancer prognosis and diagnosis, our hypothesis is that the analysis of correlations between these specific parameters and COX-2 state in tumors of a high number of CRC patients could be useful for the understanding of the basis of this cancer in humans.AIM To analyze COX-2 regulation in colorectal cancer and to perform a detailed analysis of their metabolic and proteomic profile.METHODS Biopsies from both healthy and pathological colorectal tissues were taken under informed consent from patients during standard colonoscopy procedure in the University Hospital of Bellvitge(Barcelona, Spain) and Germans Trias i Pujol University Hospital(Campus Can Ruti)(Barcelona, Spain). Western blot analysis was used to determine COX-2 levels. Deglycosylation assays were performed in both cells and tumor samples incubating each sample with peptide N-glycosidase F(PNGase F). Prostaglandin E2(PGE2) levels were determined using a specific ELISA. 1 H high resolution magic angle spinning(HRMAS) analysis was performed using a Bruker AVIII 500 MHz spectrometer and proteomic analysis was performed in a nano-liquid chromatography-tandem mass spectrometer(nano LC-MS/MS) using a QExactive HF orbitrap MS.RESULTS Our data show that COX-2 has a differential expression profile in tumor tissue of CRC patients vs the adjacent non-tumor area, which correspond to a glycosylated and less active state of the protein. This fact was associated to a lesser PGE2 production in tumors. These results were corroborated in vitro performing deglycosylation assays in HT29 cell line where COX-2 protein profile was modified after PNGase F incubation, showing higher PGE2 levels. Moreover,HRMAS analysis indicated that tumor tissue has altered metabolic features vs non-tumor counterparts, presenting increased levels of certain metabolites such as taurine and phosphocholine and lower levels of lactate. In proteomic experiments, we detected an enlarged number of proteins in tumors that are mainly implicated in basic biological functions like mitochondrial activity,DNA/RNA processing, vesicular trafficking, metabolism, cytoskeleton and splicing.CONCLUSION In our colorectal cancer cohort, tumor tissue presents a differential COX-2 expression pattern with lower enzymatic activity that can be related to an altered metabolic and proteomic profile. | Patricia Prieto Rafael I Jaén Daniel Calle María Gómez-Serrano Estefanía Nú?ez María Fernández-Velasco Paloma Martín-Sanz Sergio Alonso Jesús Vázquez Sebastián Cerdán Miguel ángel Peinado Lisardo Boscá | 2019 | World Journal of Gastroenterology2019，25，4： | 4 |
| 4 | 高温环境中训练和比赛的共识性建议显示文摘高温环境中运动会引起体温调节和其它生理压力,继而可导致耐力运动能力的损害。本共识性声明的目的是提供最新的建议以使热环境中体育活动时的运动能力最优化。可用于降低热应激压力和优化运动能力的最重要干预方式是热习服,其应包括1~2周以上反复的运动—高温环境暴露。此外,运动员应在正常水合状态下开始比赛和训练,并将运动中的脱水最小化。随着商用降温系统(如降温背心)的发展,在高温环境中训练或比赛前,运动员可以采取降温策略来促进热的散发或提高蓄热能力。而且,赛事组织者应该设计大面积的遮阳区域,并提供降温和补水设施,按照最小化运动员的健康风险来安排赛事,尤其是在大众参与的赛事中及一年之中炎热天气开始之初。以最近的2008年奥运会和2014年国际足联世界杯为例,当比赛在高温环境中举行时,赛事主管机构应考虑在比赛中或比赛之间允许额外的(或更长的)恢复期以提供补水和降温的时机。 | Sébastien Racinais Juan-Manuel Alonso Aaron J.Coutts Andreas D.Flouris Olivier Girard José González -Alonso Christophe Hausswirth Ollie Jay Jason K.W.Lee Nigel Mitchell George P.Nassis Lars Nybo Babette M.Pluim Bart Roelands Michael N.Sawka Jonathan Wingo Julien D.Périard. 徐金成 高璨 赵杰修 | 2016 | 中国运动医学杂志2016，35，2： | 4 |
| 5 | Nonbismuth Quadruple (Concomitant) Therapy: Empirical and Tailored Efficacy versus Standard Triple Therapy for Clarithromycin‐Susceptible Helicobacter pylori and versus Sequential Therapy for Clarithromycin‐Resistant Strains显示文摘 | Javier Molina‐Infante Carmen Pazos‐Pacheco Gema Vinagre‐Rodriguez Belen Perez‐Gallardo Carmen Due?as‐Sadornil Moisés Hernandez‐Alonso Guadalupe Gonzalez‐Garcia Jose M. Mateos‐Rodriguez Miguel Fernandez‐Bermejo Javier P. Gisbert | 2012 | Helicobacter2012，，4： | 4 |
| 6 | Diagnostic yield and clinical outcomes after capsule endoscopy in 100 consecutive patients with obscure gastrointestinal bleeding显示文摘 | Emilio Estévez Benito González-Conde José Luis Vázquez-Iglesias Maria de los Angeles Vázquez-Millán Sonia Pértega Pedro A. Alonso Joan Clofent Eva Santos José Luis Ulla Eloy Sánchez | 2006 | European Journal of Gastroenterology & Hepatology2006，，8： | 3 |
| 7 | 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 |
| 8 | Tan pathology in Alzheimer disease and other tauopathies显示文摘 | Iqbal K Alonso Adel C Chen S | 2005 | Biochim BiophysActa2005，1739，23： | 1 |
| 9 | Production of free conjugated linoleic acid by Lactobacillus acidophilus and Lactobacillus casei of human intestinal origin显示文摘 | ALONSO L CUESTA E P GILLILAND S E | 2003 | J Dairy Sci2003，86，6： | 1 |
| 10 | Contact pressures in the flexed hip joint during lateral trochanteric loading显示文摘 | Sparks D R Beason D P Etheridge B S Alonso J E Eberhardt A W | 2005 | J Orthop Res2005，23，： | 1 |
| 11 | 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 |
| 12 | ion homeostasis during salt stress in plants显示文摘 | Ramon S Alonso R N | 2001 | Current Opinion in Cell Biology2001，13，： | 1 |
| 13 | Ion homeostasis during salt stress in plants显示文摘 | Ramon S Alonso R N | 2001 | Current Opinion in Cell Biology2001，13，： | 1 |
| 14 | Quantitative study of fluvial landscapes:Case study in Madrid, Spain显示文摘 | Castil o V. S Antonio D Alonso S. G | | 0，，1： | 1 |
| 15 | A consensus model for group decision making problems with unbalanced fuzzy linguistic information显示文摘 | Cabrerizo F J Alonso S Herrera-Viedma E | 2009 | Int J of Information Technology and Decision Making2009，8，1： | 1 |
| 16 | Transcription regulatory sequences and mRNA expression levels in the coro- navirus transmissible gastroenteritis virus 显示文摘 | Alonso S Izeta A Sola I | 2002 | Journal of Virology2002，76，3： | 1 |
| 17 | Widespread changes in dendritic spines in a model of Alzheimer's disease 显示文摘 | Knafo S Alonso Nanclares L Gonzalez-Soriano J | 2009 | Cereb Cortez2009，19，3： | 1 |
| 18 | Interactive effects of ozone and drought stress on pigments and activities of antioxidantive enzymes in Pinus halepensis 显示文摘 | Alonso R Elvira S Castillo F J | 2001 | Plant Cell Environ2001，24，： | 1 |
| 19 | Influence of therapeutic hypothermia on matrix metalloproteinase activity after traumatic brain injury in rats 显示文摘 | Truettner J S Alonso O F Dalton Dietrich W | 2005 | Cereb Blood Flow Metab2005，25，11： | 1 |
| 20 | Biogenic amine production by Oenococcus oeni isolates from malolactic fermentation of Tempranillo wine显示文摘 | IZQUIERDO-CANAS P M GOMEZ ALONSO S RUIZ PEREZ P | 2009 | Journal of Food Protection2009，72，4： | 1 |
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