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Cyclooxygenase 2 in liver dysfunction and carcinogenesis: Facts and perspectives

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World Journal of Gastroenterology 2017年第20期23卷 3572-3580页

作者： Paloma Martín-Sanz marta casado Lisardo Boscá Department of Metabolism and Cell Signaling Institute of Biomedical Research Alberto Sols Biomedical Network Center for the Study of Hepatic and Digestive Disease and Cardiovascular Diseases Metabolic Experimental Pathology Unit Biomedical Institute of ValenciaJaume Roig 11

The biosynthesis of prostaglandins and thromboxanes has been a focus of interest in the management of many liver *** are the enzymes involved in the first step of the biosynthesis of these lipid mediators and selective inhibitors for these isoenzymes as well as pharmacological analogues of prostaglandins have been developed and are currently applied *** we discuss the implications of these enzymes in the onset of metabolic and lipid disorders in the liver and their potential role in the progression of the diseases towards fibrosis and hepatocellular carcinogenesis.

关键词： Cyclooxygenase-2 NAS Prostaglandin Non-alcoholic steatohepatitis Hepatocellular carcinoma

Post-translational modifications of prostaglandin-endoperoxide synthase 2 in colorectal cancer:An update

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World Journal of Gastroenterology 2018年第48期24卷 5454-5461页

作者： Rafael I Jaén Patricia Prieto marta casado Paloma Martín-Sanz Lisardo Boscá Department of Metabolism and Physiopathology of Inflammatory Diseases Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM) Department of Biomedicine Instituto de Biomedicina de Valencia (CSIC) Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares y Hepáticas y DigestivasISCⅢ Unidad Asociada IIBMULPGC Universidad de las Palmas de Gran Canaria (ULPGC)

The biosynthesis of prostanoids is involved in both physiological and pathological processes. The expression of prostaglandin-endoperoxide synthase 2(PTGS2; also known as COX-2) has been traditionally associated to the onset of several pathologies, from inflammation to cardiovascular, gastrointestinal and oncologic events. For this reason, the search of selective PTGS2 inhibitors has been a focus for therapeutic interventions. In addition to the classic non-steroidal anti-inflammatory drugs, selective and specific PTGS2 inhibitors, termed coxibs, have been generated and widely used. PTGS2 activity is less restrictive in terms of substrate specificity than the homeostatic counterpart PTGS1, and it accounts for the elevated prostanoid synthesis that accompanies several pathologies. The main regulation of PTGS2 occurs at the transcription level. In addition to this, the stability of the mRNA is finely regulated through the interaction with several cytoplasmic elements, ranging from specificmicroR NAs to proteins that control mR NA degradation. Moreover, the protein has been recognized to be the substrate for several post-translational modifications that affect both the enzyme activity and the targeting for degradation via proteasomal and non-proteasomal mechanisms. Among these modifications, phosphorylation, glycosylation and covalent modifications by reactive lipidic intermediates and by free radicals associated to the proinflammatory condition appear to be the main changes. Identification of these post-translational modifications is relevant to better understand the role of PTGS2 in several pathologies and to establish a correct analysis of the potential function of this protein in diseases progress. Finally, these modifications can be used as biomarkers to establish correlations with other parameters, including the immunomodulation dependent on molecular pathological epidemiology determinants, which may provide a better frame for potential therapeutic interventions.

关键词： Prostaglandins Prostaglandin-endoperoxide synthase 2 Post-translational modifications Glycosylation Colorectal cancer Inflammation

CECRE:Supervision and Control of Spanish Renewable Energies in the Last 15 years

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Journal of Modern Power Systems and Clean Energy 2022年第2期10卷 269-276页

作者： Gema Garcia Platero Mayte Garcia casado marta Perez Garcia Paula Junco Madero David Alvira Baeza the Red Electrica de Espafia MaridSpain

From its commissioning in 2006 to the present,the Spanish Control Centre for Renewable Energies(CECRE)has been a worldwide pioneer and reference centre in the integration of renewable energies in the electrical *** the last 15 years,CECRE has allowed a high penetration of renewable energies in Spanish electrical system by means of the supervision and control of renewable facilities,while ensuring the power supply *** paper defines the bases of renewable en-ergy operation in CECRE and introduces forecasting systems for renewable ***,this paper describes the participation of renewable energies in balancing services and congestion ***,new challenges for Spanish transmission system operator(TSO)are presented for the integration of renewable energies along with the energy transition and decarbonization.

关键词： Balancing services controllability forecasting system observability Control Centre for Renewable Energies(CECRE) renewable energy photovoltaic(PV) wind.

Role of hypoxia preconditioning in therapeutic potential of mesenchymal stem-cell-derived extracellular vesicles

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World Journal of Stem Cells 2022年第7期14卷 453-472页

作者： Victoria Pulido-Escribano Bárbara Torrecillas-Baena marta Camacho-Cardenosa Gabriel Dorado MaríaÁngeles Gálvez-Moreno Antonio casado-Díaz Unidad de Gestión Clínica de Endocrinología y Nutrición-GC17 Instituto Maimónides de Investigación Biomédica de CórdobaHospital Universitario Reina SofíaCórdoba 14004Spain Dep.Bioquímica y Biología Molecular Campus Rabanales C6-1-E17Campus de Excelencia Internacional Agroalimentario(ceiA3)Universidad de CórdobaCIBERFESCórdoba 14071Spain

The use of mesenchymal stem-cells(MSC)in cell therapy has received considerable attention because of their *** properties include high expansion and differentiation in vitro,low immunogenicity,and modulation of biological processes,such as inflammation,angiogenesis and ***,the regenerative effect of MSC is partly due to their paracrine *** has prompted numerous studies,to investigate the therapeutic potential of their secretome in general,and specifically their extracellular vesicles(EV).The latter contain proteins,lipids,nucleic acids,and other metabolites,which can cause physiological changes when released into recipient ***,contents of EV can be modulated by preconditioning MSC under different culture *** them,exposure to hypoxia stands out;these cells respond by activating hypoxia-inducible factor(HIF)at low O_(2) *** has direct and indirect pleiotropic effects,modulating expression of hundreds of genes involved in processes such as inflammation,migration,proliferation,differentiation,angiogenesis,metabolism,and cell *** of these genes is reflected in the contents of secreted ***,numerous studies show that MSC-derived EV conditioned under hypoxia have a higher regenerative capacity than those obtained under *** this review,we show the implications of hypoxia responses in relation to tissue *** addition,hypoxia preconditioning of MSC is being evaluated as a very attractive strategy for isolation of EV,with a high potential for clinical use in regenerative medicine that can be applied to different pathologies.

关键词： Cell priming Extracellular vesicles Hypoxia Hypoxia-inducible factor Mesenchymal stemcells Regenerative medicine

Effects of normobaric cyclic hypoxia exposure on mesenchymal stem-cell differentiation–pilot study on bone parameters in elderly

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World Journal of Stem Cells 2020年第12期12卷 1667-1690页

作者： marta Camacho-Cardenosa JoséManuel Quesada-Gómez Alba Camacho-Cardenosa Alejo Leal GabrielDorado Bárbara Torrecillas-Baena Antonio casado-Díaz Facultad Ciencias del Deporte Universidad De ExtremaduraCáceres 10003Spain CIBER De Fragilidad Y Envejecimiento Saludable(CIBERFES) Unidad De Gestión Clínica De Endocrinología Y NutriciónInstituto Maimónides De Investigación Biomédica De CórdobaHospital Universitario Reina SofíaCórdoba 14004Spain Servicio de Traumatología Hospital de CáceresCáceres 10004Spain Departamento Bioquímica y Biología Molecular Campus Rabanales C6-1-E17Campus de Excelencia Internacional Agroalimentario(ceiA3)Universidad de Córdoba-CIBERFES14071 CórdobaSpain

BACKGROUND Mesenchymal stem cells(MSC)of bone marrow are the progenitor of osteoblasts and *** tend to differentiate into adipocytes,instead of osteoblasts,with *** favors the loss of bone mass and development of *** induces hypoxia inducible factor 1αgene encoding transcription factor,which regulates the expression of genes related to energy metabolism and *** allows a better adaptation to low O2 *** hypoxia has negative effects on bone metabolism,favoring bone ***,surprisingly,cyclic hypoxia(CH),short times of hypoxia followed by long times in normoxia,can modulate MSC differentiation and improve bone health in *** To evaluate the CH effect on MSC differentiation,and whether it improves bone mineral density in *** MSC cultures were induced to differentiate into osteoblasts or adipocytes,in CH(3%O2 for 1,2 or 4 h,4 d a week).Extracellular-matrix mineralization and lipid-droplet formation were studied in MSC induced to differentiate into osteoblast or adipocytes,*** addition,gene expression of marker genes,for osteogenesis or adipogenesis,have been quantified by quantitative real time polymerase chain *** in vivo studies with elderly(>75 years old;n=10)were carried out in a hypoxia chamber,simulating an altitude of 2500 m above sea level,or in normoxia,for 18 wk(36 CH sessions of 16 min each).Percentages of fat mass and bone mineral density from whole body,trunk and right proximal femur(femoral,femoral neck and trochanter)were assessed,using dual-energy X-ray *** CH(4 h of hypoxic exposure)inhibited extracellular matrix mineralization and lipid-droplet formation in MSC induced to differentiate into osteoblasts or adipocytes,***,both parameters were not significantly affected by the other shorter hypoxia times *** longest periods of hypoxia downregulated the expression of genes related to extracellular matrix

关键词： Normobaric cyclic hypoxia Mesenchymal stem cells Cellular differentiation Osteoblasts Adipocytes Bone health

Prevalence of Helicobacter pylori infection among patients with esophageal carcinoma

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World Journal of Gastroenterology 2024年第29期30卷 3479-3487页

作者： Miriam López-Gómez Maria Morales Rebeca Fuerte marta Muñoz Pedro-David Delgado-López Jorge Francisco Gómez-Cerezo Enrique casado Department of Medical Oncology Precision Oncology LaboratoryInfanta Sofía University HospitalSan Sebastián de los Reyes 28231MadridSpain Department of Medical Oncology Infanta Sofía University HospitalSan Sebastián de los Reyes 28702Spain Department of Internal Medicine Infanta Sofía University HospitalSan Sebastián de los Reyes 28703MadridSpain Department of Pathology Infanta Sofía University HospitalSan Sebastián de los Reyes 28702Spain Department of Neurosurgery Burgos University HospitalBurgos 09006Spain Department of Internal Medicine Infanta Sofía University Hospital and Henares University Hospital Foundation for Biomedical Research and InnovationSan Sebastian de los Reyes 28702MadridSpain Department of Medical Oncology Infanta Sofia University Hospital and Henares University Hospital Foundation for Biomedical Research and InnovationSan Sebastian de los Reyes 28702MadridSpain

BACKGROUND Helicobacter pylori(***)is a widespread microorganism related to gastric adenocarcinoma(AC).In contrast,it has been reported that an inverse association exists between *** infection and esophageal *** mechanisms underlying this supposedly protective effect remain *** To determine the prevalence of *** infection in esophageal carcinoma patients,we performed a retrospective observational study of esophageal tumors diagnosed in our *** We retrospectively reviewed the prevalence of *** infection in a cohort of patients diagnosed with esophageal *** or previous proton pump inhibitor(PPI)usage was also *** A total of 89 patients with esophageal carcinoma(69 males,77.5%),with a mean age of 66 years(range,26-93 years)were *** was the most frequent pathological variant(n=47,52.8%),followed by squamous cell carcinoma(n=37,41.6%).Fourteen ACs(29.8%)originated in the gastroesophageal junction and 33(70.2%)in the esophageal ***,54 patients(60.7%)presented at stages III and *** *** infection occurred only in 4 patients(4.5%),3 with AC(6.3%of all ACs)and 1 with squamous cell carcinoma(2.7%of all squamous cell tumors).All patients with previous *** infection had stage *** one patient had received prior *** eradication therapy,whereas 86(96.6%)had received previous or concomitant PPI *** In our cohort of patients,and after histologic evaluation of paraffin-embedded primary tumors,we found a very low prevalence of previous *** *** also reviewed the medical history of the patients,concluding that the majority had received or were on PPI *** minimal prevalence of *** infection found in this cohort of patients with esophageal carcinoma suggests a protective role.

关键词： Helicobacter pylori Eradication Esophageal tumor Dysbiosis Proton pump inhibitors Carcinogenesis Microbiota Incidence

Clinical-pathological and molecular characterization of long-term survivors with advanced non-small cell lung cancer

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Cancer Biology & Medicine 2020年第2期17卷 444-457页

作者： Juan Moreno-Rubio Santiago Ponce Rosa Alvarez Maria Eugenia Olmedo Sandra Falagan Xabier Mielgo Fatima Navarro Patricia Cruz Luis Cabezon-Gutierrez Carlos Aguado Gonzalo Colmenarejo marta Munoz-Fernandez de Leglaria Ana Belen Enguita Maria Cebollero Amparo Benito Isabel Alemany Carolina del Castillo Ricardo Ramos Ana Ramirez de Molina Enrique casado Maria Sereno Ana Ramirez de Molina1 Enrique Casado5Maria Sereno5 XIMDEA Food InstituteCEI UAM+CSICMadrid 28702Spain 12 de Octubre University Hospital Madrid 28041Spain Gregorio Maranon University Hospital Madrid 28009Spain Ramon y Cajal University Hospital Madrid 28034Spain Infanta Sofia University Hospital San Sebastian De Los ReyesMadrid 28702Spain Fundacion Alcorcon University Hospital AlcorconMadrid 28922Spain Prlncipe de Asturias University Hospital Alcala De HenaresMadrid 28805Spain La Paz University Hospital Madrid 28046Spain University Hospital of Torrejon Torrejon De ArdozMadrid 28850Spain Clinico San Carlos University Hospital Madrid 28040Spain Parque Cientifico de Madrid Foundation Madrid 28049Spain

Objective:Long-term survivors(LS)of non-small cell lung cancer(NSCLC)without driver alterations,displaying an overall survival(OS)of more than 3 years,comprise around 10%of cases in several series treated with *** are classical prognosis factors for these cases[stage,Eastern Cooperative Oncology Group(ECOG),etc.],but more data are required in the *** this multi-center study,we focused on LS of advanced NSCLC with OS above 36 months to perform a clinical-pathological and molecular ***:In the first step,we conducted a clinical-pathological characterization of the ***,we carried out a genetic analysis by comparing LS to a sample of short-term survivors(SS)(with an OS less than 9 months).We initially used whole-genome RNA-seq to identify differentiating profiles of LS and SS,and later confirmed these with reverse transcription-polymerase chain reaction(RT-PCR)for the rest of the ***:A total of 94 patients were included,who were mainly men,former smokers,having adenocarcinoma(AC)-type NSCLC with an ECOG of *** obtained an initial differential transcriptome expression,displaying 5 over-and 33 under-expressed genes involved in different pathways:namely,the secretin receptor,surfactant protein,trefoil factor 1(T FF1),serpin,Ca-channels,and Tolllike receptor(TLRs)***,RT-PCR analysis of 40(20 LS/20 SS)samples confirmed that four genes(surfactant proteins and SFTP)were significantly down-regulated in SS compared to LS by using an analysis of covariance(ANCOVA)model:SFTPA1(P=0.023),SFTPA2(P=0.027),SFTPB{P=0.02),and SFT PC(P=0.047).Conclusions:We present a sequential genetic analysis of a sample of NSCLCLS with no driver alterations,obtaining a differential RNA-seq/RT-PCR profile showing an abnormal expression of SF genes.

关键词： Long-term survivors non-small cell lung cancer surfactant proteins

Posterior approach (Kraske procedure) for surgical treatment of presacral tumors

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World Journal of Gastrointestinal Surgery 2012年第5期4卷 126-130页

作者： José Manuel Aranda-Narváez Antonio Jesús GonzálezSánchez Custodia Montiel-casado Belinda Sánchez-Pérez Carolina Jiménez-Mazure marta Valle-Carbajo Julio Santoyo-Santoyo Department of General Digestive Surgery and Abdominal Organs TransplantationUniversity Hospital Carlos HayaCarlos Haya Avenue29010MálagaSpain

Presacral tumors are rare,but can comprise a great variety of histological *** tumors are the most *** the diagnosis is established,surgical resection is essential because of the potential for malignancy or *** biopsy is not necessary or may be even *** decide the best surgical approach(abdominal,sacral or combined) an individual and multidisciplinary analysis must be carried *** report three cases of cystic presacral masses in which a posterior approach(Kraske procedure) enabled complete resection,the only way to decrease local *** patients had a satisfactory recovery.A brief overview of retrorectal tumors is presented,focusing on classification,clinical presentation,diagnosis and surgical management.

关键词： Presacral tumors Posterior approach Surgical management

Digestive and breast cancer patients managed during the first wave of COVID-19 pandemic:Short and middle term outcomes

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World Journal of Methodology 2024年第2期14卷 107-126页

作者： Jacobo Trébol Ana Carabias-Orgaz María Carmen Esteban-Velasco Asunción García-Plaza Juan Ignacio González-Munoz Ana Belén Sánchez-casado Felipe Carlos Parreno-Manchado marta Eguía-Larrea José Antonio Alcázar-Montero Cirugía General y del Aparato Digestivo Complejo Asistencial Universitario de SalamancaSalamanca 37007SalamancaSpain Cirugía Universidad de SalamancaSalamanca 37007SalamancaSpain Oftalmología Complejo Asistencial Universitario de SalamancaSalamanca 37007SalamancaSpain

BACKGROUND The first wave of coronavirus disease 2019(COVID-19)pandemic in Spain lasted from middle March to the end of June *** population was subjected to lockdown periods and scheduled surgeries were discontinued or reduced during variable *** our centre,we managed patients previously and newly diagnosed with *** established a strategy based on limiting perioperative social contacts,preoperative screening(symptoms and reverse transcriptionpolymerase chain reaction)and creating separated in-hospital COVID-19-free pathways for non-infected *** also adopted some practice modifications(surgery in different facilities,changes in staff and guidelines,using continuously changing personal protective equipment…),that supposed new *** To analyse cancer patients with a decision for surgery managed during the first wave,focalizing on outcomes and pandemic-related *** We prospectively included adults with a confirmed diagnosis of colorectal,oesophago-gastric,liver-pancreatic or breast cancer with a decision for surgery,regardless of whether they ultimately underwent *** analysed short-term outcomes[30-d postoperative morbimortality and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection]and outcomes after 3 years(adjuvant therapies,oncological events,death,SARS-CoV-2 infection and vaccination).We also investigated modifications to usual *** From 96 included patients,seven didn’t receive treatment that period and four never(3 due to COVID-19).Operated patients:28 colon and 21 rectal cancers;laparoscopy 53.6%/90.0%,mortality 3.57%/0%,major complications 7.04%/25.00%,anastomotic leaks 0%/5.00%,3-years disease-free survival(DFS)82.14%/52.4%and overall survival(OS)78.57%/76.2%.Six liver metastases and six pancreatic cancers:no mortality,one major complication,three grade A/B liver failures,one bile leak;3-year DFS 0%/33.3%and OS 50.0%/33.3%(liver metastases/pancreatic carcinoma).5 g

关键词： COVID-19 SARS-CoV-2 Colon cancer Rectal cancer Breast cancer Liver cancer Pancreatic cancer Gastric cancer Oesophageal cancer Surgery