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| 1 | Alcoholic liver disease:Utility of animal models显示文摘Alcoholic liver disease(ALD) is a major cause of acute and chronic liver injury. Extensive evidence has been accumulated on the pathological process of ALD during the past decades. However, effective treatment options for ALD are very limited due to the lack of suitable in vivo models that recapitulate the full spectrum of ALD. Experimental animal models of ALD, particularly rodents, have been used extensively to mimic human ALD. An ideal animal model should recapitulate all aspects of the ALD process, including significant steatosis, hepatic neutrophil infiltration, and liver injury. A better strategy against ALD depends on clear diagnostic biomarkers, accurate predictor(s) of its progression and new therapeutic approaches to modulate stop or even reverse the disease. Numerous models employing rodent animals have been established in the last decades to investigate the effects of acute and chronic alcohol exposure on the initiation and progression of ALD. Although significant progress has been made in gaining better knowledge on the mechanisms and pathology of ALD, many features of ALD are unknown, and require further investigation, ideally with improved animal models that more effectively mimic human ALD. Although differences in the degree and stages of alcoholic liver injury inevitably exist between animal models and human ALD, the acquisition and translational relevance will be greatly enhanced with the development of new and improved animal models of ALD. | Arantza Lamas-Paz Fengjie Hao Leonard J Nelson Maria Teresa Vázquez Santiago Canals Manuel Gómez del Moral Eduardo Martínez-Naves Yulia A Nevzorova Francisco Javier Cubero | 2018 | World Journal of Gastroenterology2018，24，45： | 26 |
| 2 | Dissecting the molecular pathophysiology of drug-induced liver injury显示文摘Drug-induced liver injury(DILI) has become a major topic in the field of Hepatology and Gastroenterology. DILI can be clinically divided into three phenotypes: hepatocytic, cholestatic and mixed. Although the clinical manifestations of DILI are variable and the pathogenesis complicated, recent insights using improved preclinical models, have allowed a better understanding of the mechanisms that trigger liver damage. In this review, we will discuss the pathophysiological mechanisms underlying DILI. The toxicity of the drug eventually induces hepatocellular damage through multiple molecular pathways, including direct hepatic toxicity and innate and adaptive immune responses. Drugs or their metabolites, such as the common analgesic, acetaminophen, can cause direct hepatic toxicity through accumulation of reactive oxygen species and mitochondrial dysfunction. The innate and adaptive immune responses play also a very important role in the occurrence of idiosyncratic DILI. Furthermore, we examine common forms of hepatocyte death and their association with the activation of specific signaling pathways. | Hui Ye Leonard J Nelson Manuel Gómez del Moral Eduardo Martínez-Naves Francisco Javier Cubero | 2018 | World Journal of Gastroenterology2018，24，13： | 19 |
| 3 | Efficacy of neoadjuvant therapy and surgical rescue for locally advanced hepatoblastomas:10 year single-center experience and literature review显示文摘AIM:To report our experience with long-term outcomes after multimodal management therapy.METHODS:An observational retrospective study was performed containing seven patients with hepatoblastoma(Hbl)treated in our institution,a tertiary referral center,from 2003 to 2011.Demographic,preoperative,surgical,and outcome variables were collected.A survival analysis and a review of the current literature related to combination neoadjuvant chemotherapy and surgical resection on Hbl were performed.RESULTS:The median age at surgery was 14.4 mo,with a male to female ratio of 4:3.Pretext staging at diagnosis was as follows:stageⅠ,4 cases;stageⅡ,2 patients;and stageⅢ,1 case.Mean pretreatment tumor volume was 735 cm3.Five out of seven patients received neoadjuvant chemotherapy according to SIOPEL-3 or SIOPEL-6 protocols.Tumor volume and alphafetoprotein levels significantly dropped after neoadjuvant therapy.Surgical procedures performed included hemihepatectomies,segmentectomies and atypical resection.All patients received chemotherapy after surgery.Median postoperative hospital stay was 8 d.All patients were alive and disease-free after a median follow-up period of 23 mo.With regards to the literature review,seventeen articles were found that were related to our search.CONCLUSION:Our series shows how multimodal management of Hbl,exhaustive control and a meticulous surgical approach leads to almost 100%complete resection with optimal postoperative results. | Dolores Ayllon Teran Oscar Gómez Beltran Rubén Ciria Bru Elena Mateos González María José Pea Rosa Antonio Luque Molina Pedro López Cillero Javier Briceo Delgado | 2014 | World Journal of Gastroenterology2014，20，29： | 12 |
| 4 | Association between Helicobacter spp.infections and hepatobiliary malignancies:A review显示文摘Hepatobiliary cancers are highly lethal cancers that comprise a spectrum of invasive carcinomas originating in the liver hepatocellular carcinoma,the bile ducts intrahepatic cholangiocarcinoma and extrahepaticcholangiocarcinoma,the gallbladder and the ampulla of Vater(collectively known as biliary tract cancers).These tumors account for approximately 13% of all annual cancer-related deaths worldwide and for 10%-20% of deaths from hepatobiliary malignancies.Cholangiocarcinoma(CCA) is a devastating disease that displays a poor survival rate for which few therapeutic options are available.Population genetics,geographical and environmental factors,cholelithiasis,obesity,parity,and endemic infection with liver flukes have been identified as risk factors that influence the development of biliary tract tumors.Other important factors affecting the carcinogenesis of these tumors include chronic inflammation,obstruction of the bile ducts,and impaired bile flow.It has been suggested that CCA is caused by infection with Helicobacter species,such as Helicobacter bilis and Helicobacter hepaticus,in a manner that is similar to the reported role of Helicobacter pylori in distal gastric cancer.Due to the difficulty in culturing these Helicobacter species,molecular methods,such as polymerase chain reaction and sequencing,or immunologic assays have become the methods of choice for diagnosis.However,clinical studies of benign or malignant biliary tract diseases revealed remarkable variability in the methods and the findings,and the use of uniform and validated techniques is needed. | Fany Karina Segura-López Alfredo Güitrón-Cantú Javier Torres | 2015 | World Journal of Gastroenterology2015，21，5： | 9 |
| 5 | The role of leptin/adiponectin ratio in metabolic syndrome and diabetes显示文摘 | Patricio López-Jaramillo Diego Gómez-Arbeláez Jose López-López Cristina López-López Javier Martínez-Ortega Andrea Gómez-Rodríguez Stefany Triana-Cubillos | 2014 | Hormone Molecular Biology and Clinical Investigation2014，，1： | 4 |
| 6 | The European high-speed train network显示文摘 | Javier Gutiérrez Rafael González Gabriel Gómez | 1996 | Journal of Transport Geography1996，，4： | 3 |
| 7 | Bacterial infections in cirrhosis: Epidemiological changes with invasive procedures and norfloxacin prophylaxis显示文摘 | Javier Fernández Miquel Navasa Juliá Gómez Jordi Colmenero Jordi Vila Vicente Arroyo Juan Rodés | 2002 | Hepatology2002，，1： | 3 |
| 8 | Preclinical evaluation of azathioprine plus buthionine sulfoximine in the treatment of human hepatocarcinoma and colon carcinoma显示文摘AIM: To evaluate the efficacy and the safety of azathioprine (AZA) and buthionine sulfoximine (BSO) bylocalized application into HepG2 tumor in vivo.METHODS: Different hepatoma and colon carcinoma cell lines (HepG2, HuH7, Chang liver, LoVo, RKO, SW-48, SW-480) were grown in minimal essencial medium supplemented with 10% fetal bovine serum and 1% antibiotic/antimycotic solution and maintained in a humidified 37 ℃ incubator with 5% CO2. These cells were pretreated with BSO for 24 h and then with AZA for different times. We examined the effects of this combination on some proteins and on cellular death. We also studied the eff icacy and the safety of AZA (6 mg/kg per day) and BSO (90 mg/kg per day) in HepG2 tumor growth in vivo using athymic mice. We measured safety by serological markers such as aminotransferases and creatine kinase.RESULTS: The in vitro studies revealed a new mechanism of action for the AZA plus BSO combination in the cancer cells compared with other thiopurines (6-mercaptopurine, 6-methylmercaptopurine, 6-thioguanine and 6-methylthioguanine) in combination with BSO. The cytotoxic effect of AZA plus BSO in HepG2 cells resulted from necroptosis induction in a mitochondrial-dependent manner. From kinetic studies we suggest that glutathione (GSH) depletion stimulates c-Jun amino-terminal kinase and Bax translocation in HepG2 cells with subsequent deregulation of mitochondria (cytochrome c release, loss of membrane potential), and proteolysis activation leading to loss of membrane integrity, release of lactate dehydrogenase and DNA degradation. Some of this biochemical and cellular changes could be reversed by N-acetylcysteine (a GSH replenisher). In vivo studies showed that HepG2 tumor growth was inhibited when AZA was combined with BSO.CONCLUSION: Our studies suggest that a combination of AZA plus BSO could be useful for localizedtreatment of hepatocellular carcinoma as in the currently used transarterial chemoembolization method. | Borja Hernández-Breijo Jorge Monserrat Sara Ramírez-Rubio Eva P Cuevas Diana Vara Inés Díaz-Laviada M Dolores Fernández-Moreno Irene D Román Javier P Gisbert Luis G Guijarro | 2011 | World Journal of Gastroenterology2011，17，34： | 2 |
| 9 | The influence of post-harvest UV-C hormesis on lycopene, β-carotene, and phenolic content and antioxidant activity of breaker tomatoes显示文摘 | Sergio Bravo Javier García-Alonso Gala Martín-Pozuelo Victoria Gómez Marina Santaella Inmaculada Navarro-González María Jesús Periago | 2012 | Food Research International2012，，1： | 2 |
| 10 | Conservative management of perforated duodenal diverticulum: A case report and review of the literature显示文摘Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs. | David Martínez-Cecilia Alvaro Arjona Sánchez Manuel Gómez álvarez Eva Torres Tordera Antonio Luque Molina Victor Valentí Azcárate Javier Briceo Delgado Francisco Javier Padillo Pedro López-Cillero Sebastián Rufián Pea | 2008 | World Journal of Gastroenterology2008，14，12： | 2 |
| 11 | Translational pancreatic cancer research:a comparative study on patient-derived xenograft models显示文摘AIM To assess the viability of orthotopic and heterotopic patient-derived pancreatic cancer xenografts implanted into nude mice.METHODS This study presents a prospective experimental analytical follow-up of the development of tumours in mice upon implantation of human pancreatic adenocarcinoma samples. Specimens were obtained surgically from patients with a pathological diagnosis of pancreatic adenocarcinoma. Tumour samples from pancreatic cancer patients were transplanted into nude mice in three different locations(intraperitoneal, subcutaneous and pancreatic). Histological analysis(haematoxylin-eosin and Masson's trichrome staining) and immunohistochemical assessment of apoptosis(TUNEL), proliferation(Ki-67), angiogenesis(CD31) and fibrogenesis(α-SMA) were performed. When a tumour xenograft reached the target size, it was reimplanted in a new nude mouse. Three sequential tumour xenograft generations were generated(F1, F2 and F3).RESULTS The overall tumour engraftment rate was 61.1%. The subcutaneous model was most effective in terms of tissue growth(69.9%), followed by intraperitoneal(57.6%) and pancreatic(55%) models. Tumour development was faster in the subcutaneous model(17.7 ± 2.6 wk) compared with the pancreatic(23.1 ± 2.3 wk) and intraperitoneal(25.0 ± 2.7 wk) models(P = 0.064). There was a progressive increase in the tumour engraftment rate over successive generations for all three models(F1 28.1% vs F2 71.4% vs F3 80.9%, P < 0.001). There were no significant differences in tumour xenograft differentiation and cell proliferation between human samples and the three experimental models among the sequential generations of tumour xenografts. However, a progressive decrease in fibrosis, fibrogenesis, tumour vascularisation and apoptosis was observed in the three experimental models compared with the human samples. All three pancreatic patient-derived xenograft models presented similar histological and immunohistochemical characteristics.CONCLUSION In our experience, the faster development andgreatest number of viable xenografts could make the subcutaneous model the best option for experimentation in pancreatic cancer. | Mercedes Rubio-Manzanares Dorado Luis Miguel Marín Gómez Daniel Aparicio Sánchez Sheila Pereira Arenas Juan Manuel Praena-Fernández Juan Jose Borrero Martín Francisco Farfán López Miguel ángel Gómez Bravo Jordi Muntané Relat Javier Padillo Ruiz | 2018 | World Journal of Gastroenterology2018，24，7： | 2 |
| 12 | 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 |
| 13 | Adipokines,cytokines and body fat stores in hepatitis Cvirus liver steatosis显示文摘AIM: To identify patients with or without liver steatosis and its severity in treatment-na?ve patients affected by hepatitis C virus(HCV) infection.METHODS: We included 56 HCV infected patients, and assessed the amount of liver fat by histomorphometry, and its relationships with fat and lean mass at different parts of the body(by densitometry), hormones [insulin, homeostatic model assessment(HOMA)], adipokines(resistin, adiponectin, leptin), and cytokines(tumor necrosis factor α, interleukin-6).RESULTS: Although the intensity of liver steatosis is related to trunk fat mass and HOMA, 33% of patients showed no liver steatosis, and this finding was not related to body mass index or genotype. Besides trunkfat mass, no other factor was related to the presence or not of liver steatosis, or to the intensity of it, by multivariate analysis. Lean mass was not related to liver steatosis. Adiponectin levels were lower among patients. No differences were observed in leptin and resistin.CONCLUSION: Steatosis in HCV infection is common(67.2%), and closely related to trunk fat, and insulin resistance, but not with leg fat mass or adipokines. | emilio gonzález-reimers javier lópez-prieto geraldine quintero-platt ricardo pelazas-gonzález m remedios alemán-valls onán pérez-hernández m joséde-la-vega-prieto m angeles gómez-rodríguez candelaria martín-gonzález francisco santolaria-fernández | 2016 | World Journal of Hepatology2016，8，1： | 2 |
| 14 | A review of rescue regimens after clarithromycin-containing triple therapy failure (for Helicobacter pylori eradication)显示文摘 | Alicia C Marin Adrian G McNicholl Javier P Gisbert | 2013 | Expert Opinion on Pharmacotherapy2013，，7： | 2 |
| 15 | Genetic and Epigenetic Silencing of MicroRNA-203 Enhances ABL1 and BCR-ABL1 Oncogene Expression显示文摘 | María J. Bueno Ignacio Pérez de Castro Marta Gómez de Cedrón Javier Santos George A. Calin Juan C. Cigudosa Carlo M. Croce José Fernández-Piqueras Marcos Malumbres | 2008 | Cancer Cell2008，，： | 2 |
| 16 | Norfloxacin vs Ceftriaxone in the Prophylaxis of Infections in Patients With Advanced Cirrhosis and Hemorrhage显示文摘 | Javier Fernández Luis Ruiz del Arbol Cristina Gómez Rosa Durandez Regina Serradilla Carlos Guarner Ramón Planas Vicente Arroyo Miguel Navasa | 2006 | Gastroenterology2006，，4： | 2 |
| 17 | N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis: Randomized,placebo-controlled pilot study显示文摘AIM: To evaluate the effectiveness and safety of oral N-acetyl-L-cysteine (NAC) co-administration with mesalamine in ulcerative colitis (UC) patients. METHODS: Thirty seven patients with mild to moderate UC were randomized to receive a four-wk course of oral mesalamine (2.4 g/d) plus N-acetyl-L-cysteine (0.8 g/d) (group A) or mesalamine plus placebo (group B). Patients were monitored using the Modified Truelove-Witts Severity Index (MTWSI). The primary endpoint was clinical remission (MTWSI ≤ 2) at 4 wk. Secondary endpoints were clinical response (defined as a reduction from baseline in the MTWSI of ≥ 2 points) and drug safety. The serum TNF-α, interleukin-6, interleukin-8 and MCP-1 were evaluated at baseline and at 4 wk of treatment. RESULTS: Analysis per-protocol criteria showed clinical remission rates of 63% and 50% after 4 wk treatment with mesalamine plus N-acetyl-L-cysteine (group A) and mesalamine plus placebo (group B) respectively (OR = 1.71; 95% CI: 0.46 to 6.36; P = 0.19; NNT = 7.7). Analysis of variance (ANOVA) of data indicated a significant reduction of MTWSI in group A (P = 0.046) with respect to basal condition without significant changes in the group B (P = 0.735) during treatment. Clinical responses were 66% (group A) vs 44% (group B) after 4 wk of treatment (OR = 2.5; 95% CI: 0.64 to 9.65; P = 0.11; NNT = 4.5). Clinical improvement in group A correlated with a decrease of IL-8 and MCP-1. Rates of adverse events did not differ significantly between both groups. CONCLUSION: In group A (oral NAC combined with mesalamine) contrarily to group B (mesalamine alone), the clinical improvement correlates with a decrease of chemokines such as MCP-1 and IL-8. NAC addition not produced any side effects. | Luis G Guijarro Jose Mate Javier P Gisbert Jose Luis Perez-Calle Ignacio Marín-Jimenez Encarna Arriaza Tomás Olleros Mario Delgado Maria S Castillejo David Prieto-Merino Venancio Gonzalez Lara Amado Salvador Pea | 2008 | World Journal of Gastroenterology2008，14，18： | 2 |
| 18 | Recovery of metal ions by chitosan: sorption mechanisms and influence of metal speciation显示文摘 | Ricardo N Javier G Imelda S | 2003 | Macromol Biosci2003，，3： | 1 |
| 19 | Plants against the global epidemic of arsenic poisoning显示文摘 | Itziar A Javier H A Carlos G | 2004 | Environment International2004，30，： | 1 |
| 20 | Robust Array Beamforming with Sidelobe Control Using Support Vector Machines 显示文摘 | Cesar C G Ignacio S Javier V | 2007 | IEEE Trans on Signal Processing2007，55，2： | 1 |
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