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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 | Toll-like receptor 4 polymorphisms and bacterial infections in patients with cirrhosis and ascites显示文摘AIM To assess the relationship between the presence of toll-like receptor 4(TLR4) polymorphisms and bacterial infections in cirrhotic patients with ascites. METHODS We prospectively included consecutive patients with cirrhosis and ascites hospitalized during a 6-year period. Patients with human immunodeficiency virus(HIV) infection or any other immunodeficiency, patients with advanced hepatocellular carcinoma(beyond Milan's criteria) or any other condition determining poor short-term prognosis, and patients with a permanent urinary catheter were excluded. The presence of D299 G and/or T399 I TLR4 polymorphisms was determined by sequencing and related to the incidence and probability of bacterial infections, other complications of cirrhosis, hepatocellular carcinoma, and mortality during follow-up. A multivariate analysis to identify predictive variables of mortality in the whole series was performed. RESULTS We included 258 patients: 28(10.8%) were carriers of D299G and/or T399I TLR4 polymorphisms(polymorphism group) and 230 patients were not(wildtype group). The probability of developing any bacterial infection at one-year follow-up was 78% in the polymorphism group and 69% in the wild-type group(P = 0.54). The one-year probability of presenting infections caused by gram-negative bacilli(51% vs 44%, P = 0.68), infections caused by gram-positive cocci(49% vs 40%, P = 0.53), and spontaneous bacterial peritonitis(29% vs 34%, respectively, P = 0.99) did not differ between the two groups. The oneyear probability of transplant-free survival was 55% in the polymorphism group and 66% in the wild-type group(P = 0.15). Multivariate analysis confirmed that age, Child-Pugh score, active alcohol intake, previous hepatic encephalopathy, hepatocellular carcinoma and serum creatinine were associated with a higher risk of death during follow-up. CONCLUSION Genetic polymorphisms D299 G and/or T399 I of TLR4 do not seem to play a relevant role in the predisposition of cirrhotic patients with ascites to bacterial infections. | Edilmar Alvarado-Tapias Carlos Guarner-Argente Elida Oblitas Elisabet Sánchez Silvia Vidal Eva Román Mar Concepción Maria Poca Cristina Gely Oana Pavel Juan Camilo Nieto Cándido Juárez Carlos Guarner Germán Soriano | 2018 | World Journal of Hepatology2018，10，1： | 3 |
| 3 | Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection显示文摘Severe Acute Respiratory Syndrome Coronavirus(SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components.Dendritic cells(DCs)play a key role in the defense against viral infections,for instance plasmacytoid DCs(pDCs),have the capacity to produce vast amounts of interferon-alpha(IFN-α).In COVID-19 there is a deficit in DC numbers and IFN-αproduction,which has been associated with disease severity.In this work,we described that in addition to the DC deficiency,several DC activation and homing markers were altered in acute COVID-19 patients,which were associated with multiple inflammatory markers.Remarkably,previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+myeloid DCs and pDCs seven months after SARS-CoV-2 infection.Moreover,the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients,while no restoration of integrinβ7 and indoleamine 2,3-dyoxigenase(IDO)levels were observed.These findings contribute to a better understanding of the immunological sequelae of COVID-19. | Alberto Pérez-Gómez Joana Vitallé Carmen Gasca-Capote Alicia Gutierrez-Valencia María Trujillo-Rodriguez Ana Serna-Gallego Esperanza Muñoz-Muela María de los Reyes Jiménez-Leon Mohamed Rafii-El-Idrissi Benhnia Inmaculada Rivas-Jeremias Cesar Sotomayor Cristina Roca-Oporto Nuria Espinosa Carmen Infante-Domínguez Juan Carlos Crespo-Rivas Alberto Fernández-Villar Alexandre Pérez-González Luis Fernando López-Cortés Eva Poveda Ezequiel Ruiz-Mateos JoséMiguel Cisneros Sonsoles Salto-Alejandre Judith Berastegui-Cabrera Pedro Camacho-Martínez Carmen Infante-Domínguez Marta Carretero-Ledesma Juan Carlos Crespo-Rivas Eduardo Márquez JoséManuel Lomas Claudio Bueno Rosario Amaya JoséAntonio Lepe Jerónimo Pachón Elisa Cordero Javier Sánchez-Céspedes Manuela Aguilar-Guisado Almudena Aguilera Clara Aguilera Teresa Aldabo-Pallas Verónica Alfaro-Lara Cristina Amodeo Javier Ampuero María Dolores Avilés Maribel Asensio Bosco Barón-Franco Lydia Barrera-Pulido Rafael Bellido-Alba Máximo Bernabeu-Wittel Candela Caballero-Eraso Macarena Cabrera Enrique Calderón Jesús Carbajal-Guerrero Manuela Cid-Cumplido Yael Corcia-Palomo Juan Delgado Antonio Domínguez-Petit Alejandro Deniz Reginal Dusseck-Brutus Ana Escoresca-Ortega Fátima Espinosa Nuria Espinosa Michelle Espinoza Carmen Ferrándiz-Millón Marta Ferrer Teresa Ferrer Ignacio Gallego-Texeira Rosa Gámez-Mancera Emilio García Horacio García-Delgado Manuel García-Gutiérrez María Luisa Gascón-Castillo Aurora González-Estrada Demetrio González Carmen Gómez-González Rocío González-León Carmen Grande-Cabrerizo Sonia Gutiérrez Carlos Hernández-Quiles Inmaculada Concepción Herrera-Melero Marta Herrero-Romero Luis Jara Carlos Jiménez-Juan Silvia Jiménez-Jorge Mercedes Jiménez-Sánchez Julia Lanseros-Tenllado Carmina López Isabel López Álvaro López-Barrios Luis F.López-Cortés Rafael Luque-Márquez Daniel Macías-García Guillermo Martín-Gutiérrez Luis Martín-Villén JoséMolina Aurora Morillo María Dolores Navarro-Amuedo Dolores Nieto-Martín Francisco Ortega María Paniagua-García Amelia Peña-Rodríguez Esther Pérez Manuel Poyato Julia Praena-Segovia Rafaela Ríos Cristina Roca-Oporto Jesús F.Rodríguez María Jesús Rodríguez-Hernández Santiago Rodríguez-Suárez Ángel Rodríguez-Villodres Nieves Romero-Rodríguez Ricardo Ruiz Zida Ruiz de Azua Celia Salamanca Sonia Sánchez Víctor Manuel Sánchez-Montagut César Sotomayor Alejandro Suárez Benjumea Javier Toral | 2021 | Cellular & Molecular Immunology2021，18，9： | 2 |
| 4 | Diabetes mellitus, revascularization and outcomes in elderly patients with myocardial infarction-related cardiogenic shock显示文摘Background The prognostic role of diabetes mellitus(DM)in elderly patients with myocardial infarction-related cardiogenic shock(MI-CS)remains controversial.Little information exists about the impact of intensive cardiac care unit(ICCU)and revascularization on outcomes of elderly patients with MI-CS.We aimed to assess the prognostic impact of DM according to age in patients with MI-CS,and to analyze the impact ICCU management and revascularization on in-hospital mortality in MI-CS patients at older ages.Methods Discharge episodes with diagnosis of CS associated with MI were selected from the Spanish National Health System’s Basic Data Set.Centers were classified according to their availability of ICCU.Main outcome measured was in-hospital mortality.Results A total of 23,590 episodes of MI-CS were identified,of whom 12,447(52.8%)were in patients aged≥75 years.The impact of DM on in-hospital mortality was different among age subgroups.While in younger patients,DM was associated to a higher mortality risk(0.52 vs.0.47,OR=1.12,95%CI:1.06–1.18,χ^2<0.001),this association became non-significant in older patients(0.76 vs.0.81,χ^2=0.09).Adjusted mortality rate of MI-CS aged≥75 years was lower in patients admitted to hospitals with ICCU(adjusted mortality rate:74.2%vs.77.7%,P<0.001)and in patients undergoing revascularization(74.9%vs.77.3%,P<0.001).Conclusions Prognostic impact of DM in patients with MI-CS was different according to age,with a significantly lower impact at older ages.The availability of ICCU and revascularization were associated with better outcomes in these complex patients. | Miquel Gual Albert Ariza-Solé María García Márquez Cristina Fernández JoséL Bernal Francesc Formiga María-Isabel Barrionuevo JoséC Sánchez-Salado Victòria Lorente Júlia Pascual Isaac Llaó Oriol Alegre Angel Cequier Javier Elola | 2020 | Journal of Geriatric Cardiology2020，17，10： | 2 |
| 5 | Complete regression of myocardial involvement associated with lymphoma following chemotherapy显示文摘Cardiac involvement as an initial presentation of malignant lymphoma is a rare occurrence.We describe the case of a 26 year old man who had initially been diagnosed with myocardial infiltration on an echocardiogram,presenting with a testicular mass and unilateral peripheral facial paralysis.On admission,electrocardiograms(ECG)revealed negative T-waves in all leads and ST-segment elevation in the inferior leads.On twodimensional echocardiography,there was infiltration of the pericardium with mild effusion,infiltrative thickening of the aortic walls,both atria and the interatrial septum and a mildly depressed systolic function of both ventricles.An axillary biopsy was performed and reported as a T-cell lymphoblastic lymphoma(T-LBL).Following the diagnosis and staging,chemotherapy was started.Twenty-two days after finishing the first cycle of chemotherapy,the ECG showed regression of T-wave changes in all leads and normalization of the ST-segment elevation in the inferior leads.A followup two-dimensional echo confirmed regression of the myocardial infiltration.This case report illustrates a lymphoma presenting with testicular mass,unilateral peripheral facial paralysis and myocardial involvement,and demonstrates that regression of infiltration can be achieved by intensive chemotherapy treatment.To our knowledge,there are no reported cases of T-LBL presenting as a testicular mass and unilateral peripheral facial paralysis,with complete regression of myocardial involvement. | Juan Pablo Vinicki Tomás F Cianciulli Gustavo A Farace María C Saccheri Jorge A Lax Lucía R Kazelián Adolfo Wachs | 2013 | World Journal of Cardiology2013，5，9： | 2 |
| 6 | SSJD15011600007878显示文摘 | María A. Mejía-Benítez Amélie Bonnefond Lo?c Yengo Marlène Huyvaert Aurélie Dechaume Jesús Peralta-Romero Miguel Klünder-Klünder Jaime García Mena Julia S. El-Sayed Moustafa Mario Falchi Miguel Cruz Philippe Froguel | 2015 | Diabetologia2015，，2： | 2 |
| 7 | Air-borne ultrasound application in the convective drying of strawberry显示文摘 | Juliana Gamboa-Santos Antonia Montilla Juan Andrés Cárcel Mar Villamiel Jose V. Garcia-Perez | 2013 | Journal of Food Engineering2013，，： | 1 |
| 8 | Excitotoxic damage,disrupted energy metabolism,and oxidative stress in the rat brain:antioxidant and neuroprotective effects of L-carnitine显示文摘 | DANIELA S A VERONICA P D C MARA N H M | 2008 | Jonrnal of Neurochemistry2008，105，： | 1 |
| 9 | Systematic re- view of perioperative and quality of-life outcomes fol lowing surgical management of localised renal cancer 显示文摘 | MaeLennan S Imamura M Lapitan M C ()mar M I Lain T B Hilvano-Cabungcal A M | 2012 | Eur Urol2012，62，： | 1 |
| 10 | Interactions between arbuscular mycorrhizal fungi and other microbial inoculants (Azospirillum, Pseudomonas, Trichoderma) and their effects on microbial population and enzyme activities in the rhizosphere of maize plants 显示文摘 | Mar Vázquez M César S Azcón R | 2000 | Applied Soil Ecology2000，15，： | 1 |
| 11 | Effect of eight benthic diatoms as feed on the growth of red abalone (Haliotis rufescens) postlarvae显示文摘 | JUAN G C R MAIADEL P S S MARíA T V | | 0，，04： | 1 |
| 12 | Genetic variability related to serum uric acid concentration and risk of Parkinson’s disease显示文摘 | Isabel González‐Aramburu Pascual Sánchez‐Juan Silvia Jesús Ana Gorostidi Eduardo Fernández‐Juan Fátima Carrillo María Sierra Pilar Gómez‐Garre María T. Cáceres‐Redondo José Berciano Javier Ruiz‐Martínez Onofre Combarros Pablo Mir Jon Infante | 2013 | Mov Disord2013，，： | 1 |
| 13 | Genetic Polymorphisms in MTHFR (C677T, A1298C), MTR (A2756G) and MTRR (A66G) Genes Associated With Pathological Characteristics of Prostate Cancer in the Ecuadorian Population显示文摘 | Andrés López-Cortés Gabriela Jaramillo-Koupermann María J. Mu?oz Alejandro Cabrera Carolina Echeverría Felipe Rosales Nicolás Vivar César Paz-y-Mi?o | 2013 | The American Journal of the Medical Sciences2013，，： | 1 |
| 14 | On the band gap anomaly in Ⅰ-Ⅲ-Ⅵ2,Ⅰ-Ⅲ3-Ⅵ5,and Ⅰ-Ⅲ5-Ⅵafamilies of Cu ternaries显示文摘 | Wasim S M Rincón C Marín G | | 0，，01： | 1 |
| 15 | Value of the American College of Cardiology/American Heart Association angiographic classification of coronary lesion morphology in patients with in-stent restenosis显示文摘 | Fernando Alfonso Angel Cequier Juan Angel Vicens Martí Javier Zueco Armando Bethencourt Ramón Mantilla José R. López-Minguez Manuel Gómez-Recio César Morís María J. Perez-Vizcayno Cristina Fernández Carlos Macaya Ricardo Seabra-Gomes | 2006 | American Heart Journal2006，，3： | 1 |
| 16 | Lycopene inhibits the growth of the HL-60 promyelocytic leukemia cell line显示文摘 | Countryman C Bankson D Collins S Mar B Lin W | 1991 | Clinical Chemistry1991，37，： | 1 |
| 17 | High noise vehicle plate recognition using grey system显示文摘 | Hsu Y T Lin C B Mar S C | 1998 | The Journal of Grey System1998，10，3： | 1 |
| 18 | Magnesium, calcium, potassium, and sodium intakes and risk of stroke in male smokers 显示文摘 | Larsson S C Virtanen M J Mars M | 2008 | Archives of Internal Medicine2008，168，5： | 1 |
| 19 | Isotopic fractionation of Cu and Zn between chloride and nitrate solutions and malachite or smithsonite at 30℃ and 50℃显示文摘 | Maréchal C N Sheppard S M F | 2002 | Geochim Cosmochim Acta2002，66，1： | 1 |
| 20 | Aβ increases neural stem cell activity in senescence-accelerated SAMP8 mice显示文摘 | María Díaz-Moreno Rafael Hortigüela Ania Gon?alves Irmina García-Carpio Gemma Manich Edurne García-Bermúdez Mireia Moreno-Estellés César Eguiluz Jordi Vilaplana Carme Pelegrí Mar?al Vilar Helena Mira | 2013 | Neurobiology of Aging2013，，： | 1 |
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