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World Journal of Gastroenterology 2015年第10期21卷 2875-2882页

作者： Jordi Camps Jorge Joven unitat de recerca biomèdica Hospital Universitari de Sant Joan Institut d’Investigació Sanitària Pere Virgili Universitat Rovira i Virgili

The incidence and prevalence of non-alcoholic fatty liver disease(NAFLD)is constantly *** this is apparently associated with the growing increase in obesity,insulin resistance and obesity-related metabolic disturbances their presence is not a necessary or sufficient condition to explain the accumulation of fatin the ***,NAFLD is a predictor of other metabolic *** is currently the most frequent chronic liver disease but should not be considered benign or anecdotic because a considerable proportion of patients with NAFLD progress to cirrhosis and endstage liver ***,the search for alternative molecular mechanisms with therapeutic implications in NAFLD and associated disorders deserves a careful *** are possible targets as these organelles generate energy from nutrient *** findings,generated in patients with extreme obesity and in murine models,support the notion that NAFLD could be a mitochondrial *** is plausible because mitochondrial dysfunction affects the accumulation of lipids in hepatocytes and promotes lipid peroxidation,the production of reactive oxygen species,the release of cytokines causing inflammation and cell *** we discuss basic research and mechanistic studies targeting the role of chemokine ligand 2 in liver inflammation and that of the paraoxonases in the oxidative *** combination and association with mitochondrial dysfunction may uncover mechanisms underlying the progression of NAFLD and may help to identify novel therapeutic targets.

关键词： biomarkers Cytokines Inflammation Metabolism Mitoc

Liver fat deposition and mitochondrial dysfunction in morbid obesity:An approach combining metabolomics with liver imaging and histology

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World Journal of Gastroenterology 2015年第24期21卷 7529-7544页

作者： Nahum Calvo Raúl Beltrán-debón Esther Rodríguez-Gallego Anna Hernández-Aguilera Maria Guirro Roger Mariné-Casadó Lidón Millá Josep M Alegret Fàtima Sabench Daniel del Castillo María Vinaixa Miguelàngel Rodríguez Xavier Correig Roberto García-álvarez Javier A Menendez Jordi Camps Jorge Joven unitat de recerca biomèdica Hospital Universitari de Sant JoanInstitut d’Investigacio Sanitària Pere VirgiliUniversitat Rovira i VirgiliCampus of International Excellence Southern Catalonia Servei de Cirurgia General i de l’Aparell Digestiu Hospital Universitari de Sant Joan de ReusUniversitat Rovira i Virgili Metabolomics Platform Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas AsociadasIISPVUniversitat Rovira i Virgili Research and Collaborations General Electric Healthcare Metabolism and Cancer Group Transla-tional Research LaboratoryCatalan Institute of OncologyGirona Biomedical Research Institute

AIM: To explore the usefulness of magnetic resonance imaging(MRI) and spectroscopy(MRS) for assessment of non-alcoholic fat liver disease(NAFLD) as compared with liver histological and metabolomics findings. METHODS: Patients undergoing bariatric surgery following procedures involved in laparoscopic sleeve gastrectomy were recruited as a model of obesityinduced NAFLD in an observational, prospective, singlesite, cross-sectional study with a pre-set duration of 1 year. Relevant data were obtained prospectively and surrogates for inflammation, oxidative stress and lipid and glucose metabolism were obtained through standard laboratory measurements. To provide reliable data from MRI and MRS, novel procedures were designed to limit sampling variability and other sources of error using a 1.5T Signa HDx scanner and protocols acquired from the 3D or 2D Fat SAT FIESTA prescription manager. We used our previously described 1H NMRbased metabolomics assays. Data were obtained immediately before surgery and after a 12-mo period including histology of the liver and measurement of metabolites. Values from 1H NMR spectra obtained after surgery were omitted due to technical ***: MRI data showed excellent correlation with the concentration of liver triglycerides, other hepatic lipid components and the histological assessment, w h i c h e xc l u d e d t h e p r e s e n c e o f n o n-a l c o h o l i c steatohepatitis(NASH). MRI was sufficient to follow up NAFLD in obese patients undergoing bariatric surgery and data suggest usefulness in other clinical situations. The information provided by MRS replicated that obtained by MRI using the-CH3 peak(0.9 ppm), the-CH2- peak(1.3 ppm, mostly triglyceride) and the-CH=CH- peak(2.2 ppm). No patient depicted NASH. After surgery all patients significantly decreased their body weight and steatosis was virtually absent even in patients with previous severe disease. Improvement was also observed in the serum concentrations of selected

关键词： Fatty liver disease Magnetic resonanceimaging Lipids Magnetic resonance spectroscopy Metabolomics Mitochondrial function Morbid obesity Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis

Severe ulcerative colitis: At what point should we define resistance to steroids?

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World Journal of Gastroenterology 2008年第36期14卷 5504-5507页

作者： Maria Esteve Javier P Gisbert department of Gastroenterology Hospital Universitari Mútua de Terrassa Fundació per la Recerca Mútua de Terrassa University of Barcelona Terrassa Catalonia Spain department of Gastroenterology Hospital Universitario de la Princesa Madrid and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas Spain

Corticoesteroids are still the first-line treatment for active ulcerative colitis more than 50 years after the publication of trials assessing their beneficial effect, with about a 50% remission rate in cases of severe disease. The mortality related to severe attacks of ulcerative colitis has decreased dramatically, to less than 1%, in experienced centers, due to the appropriate use of intensive therapeutic measures (intravenous steroids, fluids and electrolytes, artificial nutritional support, antibiotics, etc), along with timely decision-making about second-line medical therapy and early identification of patients requiring colectomy. One of the most difficult decisions in the management of severe ulcerative colitis is knowing for how long corticosteroids should be administered before deciding that a patient is a non-responder. Studies assessing the outcome of acute attacks after steroid initiation have demonstrated that, in steroid-sensitive patients, the response generally occurs early on, in the first days of treatment. Different indexes to predict treatment failure, when applied on the third day of treatment, have demonstrated a high positive predictive value for colectomy. In contrast to this resolute approach, which is the most widely accepted, other authors have suggested that in some patients a completeand prolonged response to steroids may take longer. Either way, physicians taking care of these patients need to recognize that severe ulcerative colitis may be life-threatening, and they need to be careful with excessively prolonged medical treatment and delayed surgery.

关键词： Ulcerative colitis Steroids Severe Resistance

Further the liquid biopsy:Gathering pieces of the puzzle of genometastasis theory

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World Journal of Clinical Oncology 2017年第5期8卷 378-388页

作者： Ana García-Casas Dolores C García-Olmo Damián García-Olmo Universidad Complutense de Madrid Centre de recerca Experimental biomèdica Aplicada(CREBA) IRBLLEIDA department of Surgery Universidad Autónoma de MadridInstituto de Investigación SanitariaFundación Jiménez Díaz

Metastasis is the major cause of mortality in cancer disease and still constitutes one of the most controversial mechanism,not yet fully *** is almost beyond doubt is that circulatory system is crucial for cancer *** this system,much attention has been recently paid to liquid *** technique is aimed to detect circulating tumor cells (CTCs) and circulating nucleic acids so it can be used as a tool for diagnostic,prognostic and follow-up of *** CTCs tend to be scarce in serum and plasma from cancer patient,abundant circulating nucleic acids can be detected in the same *** fact,together with the genetic origin of cancer,stands out the relevance of circulating nucleic acids and shed light into the role of nucleic acids as drivers of metastasis,a recently discovered phenomenon called *** innovative theory supports the transfer of oncogenes from cancer cells to normal and susceptible cells located in distant target organs through circulatory *** is more,many biological processes haven been described to deliver and secrete circulating nucleic acids into the circulation which can allow such horizontal transfer of *** this review,we focus not only on these mechanisms but also we demonstrate its putative role in cancer propagation and give insights about possible therapeutic strategies based on this *** objective is to demonstrate how findings about cell-to-cell communications and previous results can agree with this unprecedented theory.

关键词： Genometastasis Cancer metastasis Circulating Nucleic acids:Circulating tumor cells Liquid biopsy Exosomes Virtosomes

Neurodegeneration and neuroinflammation: two processes, one target

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Neural Regeneration Research 2015年第10期10卷 1581-1583页

作者： Paulina Carriba Joan X.Comella Institut de recerca de l’Hospital Universitari de la Vall d’Hebron (VHIR) Institut de Neurociències Departament de Bioquímica i Biologia Molecular Facultat de Medicina Universitat Autònoma de Barcelona Centro de Investigación biomèdica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)

The etiology of neurodegenerative diseases is diverse,however most of them share common characteristics：accumulation of misfolded proteins,chronic and sustained neuroinflammation,and the dysfunction and death of cert... 详细信息

关键词： FAIM Neurodegeneration and neuroinflammation two processes ADDLs TNFR

Activation of Wnt/β-catenin signaling in abdominal aortic aneurysm:A potential therapeutic opportunity?

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Genes & Diseases 2023年第3期10卷 639-642页

作者： Lídia Puertas-Umbert Saray Varona Carme Ballester-Servera Judith Alonso Silvia Aguiló Mar Orriols Ernesto Martínez-Martínez Antonio Rodríguez-Sinovas JoséMartínez-González Cristina Rodríguez Institut de recerca Hospital de la Santa Creu i Sant Pau(IRHSCSP) Barcelona 08025Spain Instituto de Investigación biomédica Sant Pau Barcelona 08036Spain CIBER de Enfermedades Cardiovasculares ISCIIIMadrid 28029Spain Instituto de Investigaciones biomédicas de Barcelona-Consejo Superior de Investigaciones Científicas(IIBB-CSIC) Barcelona 08036Spain Facultad de Medicina Universidad Complutense de MadridInstituto de Investigación Sanitaria Gregorio MarañónMadrid 28040Spain Cardiovascular Diseases Research Group Vall d’Hebron Institut de RecercaVall d’Hebron Hospital UniversitariVall d’Hebron Barcelona Hospital CampusBarcelona 08035Spain

Abdominal aortic aneurysm (AAA) is a common degenerative vascular disease with a prevalence up to 8% in males over 60 years of age.1 This is a complex disorder characterized by permanent and focal dilation of abdominal aorta that exceeds at least 50% of the normal diameter. In these patients, the aortic diameter progressively expands boosted by smoking and aging as major risk factors. Unfortunately, aneurysm growth increases the risk of aortic rupture, a life-threatening emergency that carries a mortality rate of 80%. despite the increasing effort of the scientific community to identify therapeutic strategies for AAA, there are currently no pharmacological tools that ameliorate aneurysm expansion, while the underlying mechanisms involved in this disease are not completely understood.

关键词： aneurysm aortic therapeutic

Cytokine production in patients with cirrhosis and TLR4 polymorphisms

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World Journal of Gastroenterology 2014年第46期20卷 17516-17524页

作者： Juan Camilo Nieto Elisabet Sánchez Eva Román Silvia Vidal Laia Oliva Carlos Guarner-Argente Maria Poca Xavier Torras Cándido Juárez Carlos Guarner German Soriano department of Immunology Institut de Recerca-IIB Sant PauUniversitat Autònoma de Barcelona08025 BarcelonaSpain department of Gastroenterology Hospital de la Santa Creu i Sant Pau08025 BarcelonaSpain department of Gastroenterology Instituto de Salud Carlos Ⅲ Institut de Recerca-IIB Sant PauUniversitat Autònoma de Barcelona08025 BarcelonaSpain department of Gastroenterology Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas08025 BarcelonaSpain Instituto de Salud Carlos Ⅲ Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas08025 BarcelonaSpain department of Gastroenterology Escola Universitària d’Infermeria Sant Pau08025 BarcelonaSpain department of Gastroenterology Universitat Autònoma de Barcelona08025 BarcelonaSpain

AIM: To analyze the cytokine production by peripheral blood cells from cirrhotic patients with and without TLR4 D299G and/or T399I polymorphisms.

关键词： Inflammatory response Hepatic encephalopathy Genetic factors Infections

Austrian syndrome:Resurgence of an old and deadly triad

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Journal of Intensive Medicine 2024年第2期4卷 261-264页

作者： Kristian Rivera Dolors Viles Marta Zielonka Carlos Izurieta Tania Ramírez Martínez Diego Menéndez department of Cardiology University Hospital Arnau de VilanovaInstitut de Recerca Biomèdica de Lleida(IRBLleida)LleidaSpain

Introduction The Gram-positive bacterium,Streptococcus pneumoniae(***),often colonizes the nasopharynx;however,it is one of the major microorganisms that cause pneumonia and meningitis.[[1],[2],[3]]It presents several virulence factors,such as surface proteins and enzymes,pneumolysin toxin,and a polysaccharide capsule,which is mainly responsible for the immune response;the capsule also facilitates classification of the bacterium into several serotypes.[1,2]In vulnerable individuals,the bacterium may lead to the development of invasive pneumococcal disease(IPD),which is defined as an infection of normally sterile locations.

关键词： capsule sterile infection

SNARE complex in axonal guidance and neuroregeneration

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Neural Regeneration Research 2018年第3期13卷 386-392页

作者： Fausto Ulloa Tiziana Cotrufo delia Ricolo Eduardo Soriano Sofia J. Araújo department of Cell Biology Physiology and Immunology School of Biology and Institute of Neurosciences University of Barcelona Barcelona Spain Centro de Investigación biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) Instituto de Salud Carlos III (ISCIII) Madrid Spain Institut de Biologia Molecular de Barcelona (IBMB-CSIC) Parc Cientific de Barcelona Barcelona Spain department of Genetics Microbiology and Statistics School of Biology University of Barcelona Barcelona Spain Vail d 'Hebron Institut de recerca (VHIR) Barcelona Spain

Through complex mechanisms that guide axons to the appropriate routes towards their targets, axonal growth and guidance lead to neuronal system formation. These mechanisms establish the synaptic circuitry necessary for the optimal performance of the nervous system in all organisms. Damage to these networks can be repaired by neuroregenerative processes which in turn can re-establish synapses between injured axons and postsynaptic terminals. Both axonal growth and guidance and the neuroregenerative response rely on correct axonal growth and growth cone responses to guidance cues as well as correct synapses with appropriate targets. With this in mind, parallels can be drawn between axonal regeneration and processes occurring during embryonic nervous system development. However, when studying parallels between axonal development and regeneration many questions still arise; mainly, how do axons grow and synapse with their targets and how do they repair their membranes, grow and orchestrate regenerative responses after injury. Major players in the cellular and molecular processes that lead to growth cone development and movement during embryonic development are the Soluble N-ethylamaleimide Sensitive Factor （NSF） Attachment Protein Receptor （SNARE） proteins, which have been shown to be involved in axonal growth and guidance. Their involvement in axonal growth, guidance and neuroregeneration is of foremost importance, due to their roles in vesicle and membrane trafficking events. Here, we review the recent literature on the involvement of SNARE proteins in axonal growth and guidance during embryonic development and neuroregeneration.

关键词： SNARE vesicle associated membrane protein synaptosomal associated protein axon guidance neuroregeneration nervous system cell membrane

New real-time-PCR method to identify single point mutations in hepatitis C virus

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World Journal of Gastroenterology 2016年第43期22卷 9604-9612页

作者： Qian Chen Irene Belmonte Maria Buti Leonardo Nieto Damir Garcia-Cehic Josep Gregori Celia Perales Laura Ordeig Meritxell Llorens Maria Eugenia Soria Rafael Esteban Juan Ignacio Esteban Francisco Rodriguez-Frias Josep Quer Liver Unit Internal Medicine Lab. Malalties Hepàtiques Vall d’Hebron Institut Recerca-Hospital Universitari Vall d’ Hebron08035 Barcelona Spain Centro de Investigación biomédica en Red Enfermedades Hepáticas y Digestivas Instituto de Salud Carlos Ⅲ28029 madrid Spain Liver Pathology Unit Departments of Biochemistry and Microbiology Hospital Universitari Vall d’Hebron Autonomous University of Barcelona 08035 Bareelona Spain Centro de Investigación biomédica en Red de Enfermedades Hepáticas y Digestivas del Instituto de Salud Carlos Ⅲ 28029 Madrid Spain Universitat Autònoma de Barcelona 08193 Bareelona Spain

AIM To develop a fast, low-cost diagnostic strategy to identify single point mutations in highly variable genomes such as hepatitis C virus(HCV).METHODS In patients with HCV infection, resistance-associated amino acid substitutions within the viral quasispecies prior to therapy can confer decreased susceptibility to direct-acting antiviral agents and lead to treatment failure and virological relapse. One such naturally occurring mutation is the Q80 K substitution in the HCV-NS3 protease gene, which confers resistance to PI inhibitors, particularly simeprevir. Low-cost, highly sensitive techniques enabling routine detection of these single point mutations would be useful to identify patients at a risk of treatment failure. Light Cycler methods, based on real-time PCR with sequencespecific probe hybridization, have been implemented in most diagnostic laboratories. However, this technique cannot identify single point mutations in highly variable genetic environments, such as the HCV genome. To circumvent this problem, we developed a new method to homogenize all nucleotides present in a region except the point mutation of interest. RESULTS Using nucleotide-specific probes Q, K, and R substitutions at position 80 were clearly identified at a sensitivity of 10%(mutations present at a frequency of at least 10% were detected). The technique was successfully applied to identify the Q80 K substitution in 240 HCV G1 serum samples, with performance comparable to that of direct Sanger sequencing, the current standard procedure for this purpose. The new method was then validated in a Catalonian population of 202 HCV G1-infected individuals. Q80 K was detected in 14.6% of G1 a patients and 0% of G1 b in our setting. CONCLUSION A fast, low-cost diagnostic strategy based on real-time PCR and fluorescence resonance energy transfer probe melting curve analysis has been successfully developed to identify single point mutations in highly variable genomes such as hepatitis C virus. This

关键词： Hepatitis C virus Resistance-associated amino acid substitutions Low-cost test Single-point mutations Q80K