0000000001326675

AUTHOR

Javier Megías

showing 39 related works from this author

Systemic Candidiasis and TLR2 Agonist Exposure Impact the Antifungal Response of Hematopoietic Stem and Progenitor Cells.

2018

We have previously demonstrated that Candida albicans induces differentiation of hematopoietic stem and progenitor cells (HSPCs) toward the myeloid lineage both in vitro and in vivo in a TLR2- and Dectin-1-dependent manner, giving rise to functional macrophages. In this work, we used an ex vivo model to investigate the functional consequences for macrophages derived from HSPCs in vivo-exposed to Pam3CSK4 (a TLR2 agonist) or C. albicans infection. Short in vivo treatment of mice with Pam3CSK4 results in a tolerized phenotype of ex vivo HSPC-derived macrophages, whereas an extended Pam3CSK4 treatment confers a trained phenotype. Early during candidiasis, HSPCs give rise to macrophages trained…

0301 basic medicineMicrobiology (medical)medicine.medical_treatmenthematopoietic stem and progenitor cellsImmunologylcsh:QR1-502Colony Count MicrobialBiologyKidneyMicrobiologylcsh:Microbiology03 medical and health sciencesLipopeptidesMiceCandida albicansmedicineTLR2host-pathogen interactionsMacrophageAnimalsProgenitor cellCandida albicansinnate immunityInnate immune systemMacrophagesCandidiasisCell Differentiationbiology.organism_classificationmedicine.diseaseHematopoietic Stem CellsToll-Like Receptor 2Haematopoiesis030104 developmental biologyInfectious DiseasesCytokineImmunologySystemic candidiasisEx vivoSpleenFrontiers in cellular and infection microbiology
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Experiencia de gamificación en Docencia Universitaria: aprendizaje activo y entretenido

2016

[EN] The main objective of this paper is to describe the experience developed in university teaching using gamification as a teaching tool. Gamification is the term used to refer to the application of game mechanics in areas in which gaming is not typically used. Our working hypothesis is based on the idea that gaming can be a new methodology that favors the settlement and internalizing the concepts taught by making the learning process and integrate asset and related contents of an attractive and motivating way for students.In order to assess the experience of students we have spent an anonymous survey and we have analyzed their answers. Our conclusion is that gamification has a good welco…

Innovación educativaEducación superiorEnseñanza superiorTecnologías y educación
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Epigenetic changes underlie the aggressiveness of histologically benign meningiomas that recur

2019

Meningiomas are the most frequent primary brain tumor. Usually, they are curable by surgery, but even after seemingly complete resection, some low-grade lesions recur. Despite recent improvements, signatures having prognostic value in grade I tumors remain poorly characterized. The frequency and delicate location of these tumors suggest that the risk of recurrence might be more accurately predicted. Herein, we show an easy way to evaluate the methylation status of meningiomas and its correlation with the prognosis of the disease. A series of 120 meningiomas, including primary tumors and recurrences, were analyzed histopathologically, and 24 tumor suppressor genes (TSGs) were studied by meth…

AdultMale0301 basic medicineOncologymedicine.medical_specialtyAdolescentBrain tumorDiseaseMLH1Epigenesis GeneticPathology and Forensic MedicineMeningiomaYoung Adult03 medical and health sciences0302 clinical medicineCDKN2BInternal medicineMeningeal NeoplasmsmedicineHumansGenes Tumor SuppressorClinical significanceChildAgedAged 80 and overbusiness.industryDNA MethylationMiddle Agedmedicine.disease030104 developmental biology030220 oncology & carcinogenesisBenign MeningiomaDNA methylationFemaleNeoplasm Recurrence LocalMeningiomabusinessHuman Pathology
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Somatic copy number alterations are associated with EGFR amplification and shortened survival in patients with primary glioblastoma.

2019

Glioblastoma (GBM) is the most common malignant primary tumor of the central nervous system. With no effective therapy, the prognosis for patients is terrible poor. It is highly heterogeneous and EGFR amplification is its most frequent molecular alteration. In this light, we aimed to examine the genetic heterogeneity of GBM and to correlate it with the clinical characteristics of the patients. For that purpose, we analyzed the status of EGFR and the somatic copy number alterations (CNAs) of a set of tumor suppressor genes and oncogenes. Thus, we found GBMs with high level of EGFR amplification, low level and with no EGFR amplification. Highly amplified tumors showed histological features of…

0301 basic medicineMaleCancer ResearchBiopsyL-amp GB EGFR-low amplified glioblastomamedicine.disease_causewt wildtypeMYBPC3 myosin-binding protein C0302 clinical medicineHIC1 hypermethylated in cancer 1Gene duplicationIn Situ Hybridization FluorescenceIDH2 isocitrate dehydrogenase 2MutationRB-pat RB signaling pathwayEGFRvIII epidermal growth factor receptor variant number IIIPAH phenylalanine hydroxylaseGBM glioblastoma IDH-wildtype (glioblastoma multiforme primary glioblastoma).ANOVA ANalysis Of VArianceN-amp GB EGFR-no amplified glioblastomaMiddle AgedCDKN2A cyclin-dependent kinase inhibitor 2Alcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogensPrognosisPrimary tumorImmunohistochemistryH-amp GB EGFR-high amplified glioblastomaErbB ReceptorsTKR-pat tyrosine-kinase receptors signaling pathway030220 oncology & carcinogenesisDisease ProgressionCDK6 cyclin-dependent kinase 6CDH1 Cadherin 1FemaleCREM cAMP response element modulatorIHC immunohistochemistryAdultOriginal articleDNA Copy Number VariationsCDKN1B cyclin-dependent kinase inhibitor 1BBiologyRARB retinoic acid receptor betaCNS central nervous systemlcsh:RC254-282IDH1 isocitrate dehydrogenase 1BCL2 B-cell cll/ lymphoma 2CNAs copy number algerationsWHO World Health Organization03 medical and health sciencesYoung Adultp53-pat p53 signaling pathwaymedicineBiomarkers TumorTMA tissue microarrayPTENHumansProtein kinase BPI3K/AKT/mTOR pathwaySurvival analysisAgedGenetic heterogeneityGene AmplificationGFAP glial fibrillary acidic proteinMLPA multiplex ligation-dependent probe amplificationmedicine.diseaseFISH fluorescence in situ hibridizationSurvival AnalysisCDKN2B cyclin-dependent kinase inhibitor 2BPTEN phosphatase and tensin homologEGFR epidermal growth factor receptorCNV-load load of copy number variations030104 developmental biologyMutationPARK2 parkinCancer researchbiology.proteinTCGA The Cancer Genome AtlasLARGE1 acetylglucosaminyltransferase-like protein 1GlioblastomaCHD7 Chromodomain Helicase DNA Binding Protein 7DAPI 4′6-diamidino-2-phenylindoleNeoplasia (New York, N.Y.)
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PRR signaling during in vitro macrophage differentiation from progenitors modulates their subsequent response to inflammatory stimuli.

2017

Toll-like receptor (TLR) agonists drive hematopoietic stem and progenitor cells (HSPCs) to differentiate along the myeloid lineage in vitro and also in vivo following infection. In this study, we used an in vitro model of HSPC differentiation to investigate the functional consequences (cytokine production) that exposing HSPCs to various pathogen-associated molecular patterns (PAMPs) and Candida albicans cells have on the subsequently derived macrophages. Mouse HSPCs (Lin- cells) were cultured with GM-CSF to induce macrophage differentiation in the presence or absence of the following pattern recognition receptor (PRR) agonists: Pam3CSK4 (TLR2 ligand), LPS (TLR4 ligand), depleted zymosan (wh…

0301 basic medicinemedicine.medical_treatmentClinical BiochemistryImmunologyProinflammatory cytokineMajor Histocompatibility Complex03 medical and health scienceschemistry.chemical_compoundMicemedicineEscherichia coliImmunology and AllergyAnimalsAntigens LyProgenitor cellCells CulturedChemistryMacrophagesZymosanPattern recognition receptorCell DifferentiationFlow CytometryCell biologyMice Inbred C57BLHaematopoiesisTLR2030104 developmental biologyCytokineReceptors Pattern RecognitionTLR4CytokinesFemaleSignal TransductionEuropean cytokine network
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The CO-releasing molecule CORM-2 is a novel regulator of the inflammatory process in osteoarthritic chondrocytes

2008

Previous work has shown that the CO-releasing molecule CORM-2 protects against cartilage degradation. The aim of this study was to examine whether CORM-2 can control the production of inflammatory mediators in osteoarthritic chondrocytes and determine the mechanisms involved.Primary cultures of chondrocytes from OA patients were stimulated with IL-1beta. The production of reactive oxygen species, nitrite, PGE(2), TNF-alpha and IL-1 receptor antagonist (IL-1Ra) were measured in the presence or absence of CORM-2. The expression of nitric oxide synthase-2 (NOS-2), cyclo-oxygenase-2 (COX-2) and microsomal PG E synthase-1 (mPGES-1) was followed by western blot and real-time PCR. Activation of nu…

Malemedicine.medical_specialtymedicine.drug_classmedicine.medical_treatmentInterleukin-1betaNitric Oxide Synthase Type IINitric Oxidemedicine.disease_causeDinoprostoneChondrocyteNitric oxidechemistry.chemical_compoundChondrocytesRheumatologyWestern blotInternal medicineOsteoarthritisOrganometallic CompoundsmedicineHumansPharmacology (medical)Cells CulturedAgedProstaglandin-E SynthasesAged 80 and overchemistry.chemical_classificationReactive oxygen speciesDose-Response Relationship Drugmedicine.diagnostic_testTumor Necrosis Factor-alphabusiness.industryNF-kappa BHypoxia-Inducible Factor 1 alpha SubunitReceptor antagonistMolecular biologyIntramolecular OxidoreductasesInterleukin 1 Receptor Antagonist ProteinEndocrinologymedicine.anatomical_structureCytokinechemistryCyclooxygenase 2PhosphorylationFemaleReactive Oxygen SpeciesbusinessOxidative stressRheumatology
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Direct Toll-Like Receptor-Mediated Stimulation of Hematopoietic Stem and Progenitor Cells Occurs In Vivo and Promotes Differentiation Toward Macropha…

2012

Abstract As Toll-like receptors (TLRs) are expressed by hematopoietic stem and progenitor cells (HSPCs), they may play a role in hematopoiesis in response to pathogens during infection. We show here that TLR2, TLR4, and TLR9 agonists (tripalmitoyl-S-glyceryl-L-Cys-Ser-(Lys)4 [Pam3CSK4], lipopolysaccharide [LPS], and CpG oligodeoxynucleotide [ODN]) induce the in vitro differentiation of purified murine lineage negative cells (Lin−) as well as HSPCs (identified as Lin− c-Kit+ Sca-1+ IL-7Rα− [LKS] cells) toward macrophages (Mph), through a myeloid differentiation factor 88 (MyD88)-dependent pathway. In order to investigate the possible direct interaction of soluble microorganism-associated mol…

Hematopoietic stem and progenitor cellsBiologyCell LineMicemedicineAnimalsProgenitor cellToll-like receptorInnate immune systemMacrophagesToll-Like ReceptorsTLR9Cell DifferentiationCell BiologyFlow CytometryHematopoietic Stem CellsMyD88Molecular biologyToll-Like Receptor 2Toll-like receptorsMice Inbred C57BLToll-Like Receptor 4TLR2Haematopoiesismedicine.anatomical_structureMyeloid Differentiation Factor 88TLR4Molecular MedicineBone marrowDevelopmental BiologySignal Transduction
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Antioxidant and Antiinflammatory Properties of Heme Oxygenase-1 in Osteoarthritic Articular Cells

2012

Heme oxygenase-1 (HO-1) is induced in cells by various stimuli as a defense system against oxidative stress. It is known that reactive oxygen species (ROS) participates in the initiation and progression of osteoarthritis (OA) and several antioxidant systems may protect cartilage components. HO-1 induction or CO release from CORM-2 counteracts oxidative stress and protects against proinflammatory and catabolic effects of interleukin-1β in OA chondrocytes, osteoblasts, and synoviocytes as well as in OA osteochondral explants. Both approaches have been able to downregulate the production of mediators such as reactive oxygen species, nitric oxide, matrix metalloproteinases, prostaglandin E2, cy…

chemistry.chemical_classificationReactive oxygen speciesCartilagemedicine.disease_causeProinflammatory cytokineCell biologyHeme oxygenasechemistry.chemical_compoundmedicine.anatomical_structurechemistrymedicineProstaglandin E2HemeOxidative stressAggrecanmedicine.drug
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Identification of a Novel BRCA1 Alteration in Recurrent Melanocytoma Resulting in Increased Proliferation

2020

Abstract Primary meningeal melanocytomas are rare tumors of the central nervous system. Although they are considered benign neoplasms, some reports describe recurrent rates up to 45%. Little is known about their genetic and epigenetic landscape because of their infrequency. Even less has been described about markers with prognostic value. Here we describe a patient who developed a primary meningeal melanocytoma, suffered 3 recurrences in a period of 6 years and died of the tumor. The genetic and epigenetic changes explored confirmed GNAQ mutation as an initiating event. We found an epigenetic alteration of GSTP1, a feature that has recently been described in meningiomas, from the beginning …

Pathologymedicine.medical_specialtyMitotic indexProliferation indexDiseasePathology and Forensic MedicineMeningiomaLoss of heterozygosity03 medical and health sciencesCellular and Molecular NeuroscienceFatal Outcome0302 clinical medicineMeningeal NeoplasmsmedicineHumansEpigeneticsMelanomaCell ProliferationBRCA1 Proteinbusiness.industryGeneral MedicineMiddle Agedmedicine.diseaseGlutathione S-Transferase piNeurology030220 oncology & carcinogenesisMutationGTP-Binding Protein alpha Subunits Gq-G11FemaleNeurology (clinical)Neoplasm Recurrence LocalMelanocytomabusiness030217 neurology & neurosurgeryGNAQJournal of Neuropathology & Experimental Neurology
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Retinal microglia are activated by systemic fungal infection

2014

Purpose: To determine whether systemic fungal infection could cause activation of retinal microglia and therefore could be potentially harmful for patients with retinal degenerative diseases. Methods: Activation of retinal microglia was measured in a model of sublethal invasive candidiasis in C57BL/6J mice by (i) confocal immunofluorescence and (ii) flow cytometry analysis, using anti-CD11b, anti-Iba1, anti-MHCII and anti-CD45 antibodies. Results: Systemic fungal infection causes activation of retinal microglia, with phenotypic changes in morphology, surface markers expression, and microglial re-location in retinal layers. Conclusions: As an excessive or prolonged microglial activation may …

Retinal Ganglion CellsSystemic mycosisFarmacologíaBiología CelularAxonal TransportRetinachemistry.chemical_compoundMicemedicineAnimalsMicroglial activationInflammationMicroscopy ConfocalMicrogliabusiness.industryRetinal DegenerationCandidiasisRetinalFlow CytometryImmunohistochemistryMice Inbred C57BLDisease Models Animalmedicine.anatomical_structurechemistryImmunologyChristian ministryFemaleMicrogliabusinessInfection
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Gamificación en la universidad: una experiencia basada en el “bring your own device” en educación superior

2016

[EN] Technological development offers several new opportunities to improve the quality of teaching. Under the ongoing task as a teachers of motivating and teaching how to learn to our students, we present the results of a session that consisted of two gamificated and groupal activities (quiz format) and a single self-assessment, based all of them on the use of their own electronic enabled devices (bring your own device). This implies an enriching, fun and practical experience to approach the course, and it provided interesting feedback to continue implementing new technologies at the university.

Innovación educativaGamificaciónConcursoRendimientoEducación superior"Bring your own device"Enseñanza superiorMotivaciónTecnologías y educación
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COX-2 and sPLA2 inhibitory activity of aqueous extract and polyphenols of Rhizophora mangle (red mangrove)

2006

The aqueous extract of Rhizophora mangle bark and its polyphenolic fractions showed remarkable in vitro antiinflammatory activity in a preliminary study. The low molecular weight fraction exhibited cyclooxygenase-2 inhibitory activity while the total aqueous extract and the low molecular weight fraction showed secretory phospholipase A(2) inhibitory activity.

PharmacognosyPhospholipases Alaw.inventionchemistry.chemical_compoundPhenolslawDrug DiscoveryPlant BarkHumansPhenolsEnzyme InhibitorsRhizophora mangleFlavonoidsPharmacologyCyclooxygenase 2 InhibitorsDose-Response Relationship DrugTraditional medicinebiologyPlant ExtractsChemistryMembrane ProteinsPolyphenolsRhizophoraceaeGeneral Medicinebiology.organism_classificationCyclooxygenase 2Polyphenolvisual_artPlant Barkvisual_art.visual_art_mediumRhizophoraceaeBarkPhytotherapyPhytotherapyFitoterapia
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CANDIDA ALBICANS INDUCES SELECTIVE DEVELOPMENT OF MACROPHAGES AND MONOCYTE DERIVED DENDRITIC CELLS BY A TLR2 DEPENDENT SIGNALLING

2011

As TLRs are expressed by haematopoietic stem and progenitor cells (HSPCs), these receptors may play a role in haematopoiesis in response to pathogens during infection. We have previously demonstrated that in in vitro defined conditions inactivated yeasts and hyphae of Candida albicans induce HSPCs proliferation and differentiation towards the myeloid lineage by a TLR2/MyD88 dependent pathway. In this work, we showed that C. albicans invasive infection with a low virulence strain results in a rapid expansion of HSPCs (identified as LKS cells: Lin(-) c-Kit(+) Sca-1(+) IL-7R alpha(-)), that reach the maximum at day 3 post-infection. This in vivo expansion of LKS cells in TLR2(-/-) mice was del…

MaleImmune CellsCellular differentiationImmunologylcsh:MedicineMycologyMicrobiologyMonocytesMiceCandida albicansAnimalsLymphopoiesisProgenitor celllcsh:ScienceCandida albicansBiologyImmune ResponseCells CulturedMice KnockoutMultidisciplinarybiologyMacrophageslcsh:RFungal DiseasesCandidiasisCell DifferentiationHematologyDendritic CellsFlow Cytometrybiology.organism_classificationToll-Like Receptor 2Corpus albicansHematopoiesisCell biologyHost-Pathogen InteractionToll-Like Receptor 4HaematopoiesisTLR2Infectious DiseasesMyeloid Differentiation Factor 88Medicinelcsh:QFemaleStem cellInfectious Disease ModelingResearch ArticleSignal Transduction
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Molecular Progression in Unusual Recurrent Non-Pediatric Intracranial Clear Cell Meningioma

2017

We report a case of a recurrent clear cell meningioma (CCM) in the frontal lobe of the brain of a 67-year-old man. The patient developed three recurrences: at 3, 10, and 12 years after his initial surgery. Histopathology observations revealed a grade 2 CCM with positivity for vimentin and epithelial membrane antigen. Expression of E-cadherin was positive only in the primary tumour and in the first available recurrence. Fluorescence in situ hybridization analyses demonstrated 1p and 14q deletions within the last recurrence. Multiplex ligation-dependent probe amplification studies revealed a heterozygous partial NF2 gene deletion, which progressed to total loss in the last recurrence. The las…

medicine.medical_specialtyPathologyrecurrenceCase ReportVimentin03 medical and health sciences0302 clinical medicineCDKN2ACDKN2BmedicineClear Cell MeningiomaNeoplasmgeneticstumour suppressor genesbiologymedicine.diagnostic_testbusiness.industryintracranial diseaseClear cell meningiomamedicine.diseaseFrontal lobemolecular progressionNF2030220 oncology & carcinogenesisbiology.proteinHistopathologynon-pediatric diseasebusiness030217 neurology & neurosurgeryFluorescence in situ hybridizationCurrent Oncology
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Gamificación en la universidad II: aprendemos a divertirnos enseñando. Se divierten aprendiendo

2017

[EN] After the success last year using gamification as a motivating method in the degree of Biomedical Engineering (UV-UPV), we introduce it this year in degree in Podiatry (UV). On the basis of the results of our first study, we focus on the use of Kahoot application in order to improve our students’ motivation and subsequently, their califications. Despite the short timeexperience, the improvement in academic results has been evident. Although it could be due to many causes, it has been influenciated by this action. In addition, during the development of this type of activity the involvement and fun of our students does not cease to amaze us. They enjoy their successes and also their fail…

Innovación educativaGamificaciónTICKAHOOTEducación superiorEnseñanza superiorMotivaciónTecnologías y educaciónLudificaciónm-learningLibro de Actas IN-RED 2017 - III Congreso Nacional de Innovación Educativa y de Docencia en Red
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Dectin-1 Stimulation of Hematopoietic Stem and Progenitor Cells Occurs In Vivo and Promotes Differentiation Toward Trained Macrophages via an Indirec…

2020

Invasive candidiasis is an increasingly frequent cause of serious and often fatal infections. Understanding host defense is essential to design novel therapeutic strategies to boost immune protection against Candida albicans. In this article, we delve into two new concepts that have arisen over the last years: (i) the delivery of myelopoiesis-inducing signals by microbial components directly sensed by hematopoietic stem and progenitor cells (HSPCs) and (ii) the concept of “trained innate immunity” that may also apply to HSPCs. We demonstrate that dectin-1 ligation in vivo activates HSPCs and induces their differentiation to trained macrophages by a cell-autonomous indirect mechanism. This p…

MaleMyeloidbeta-Glucanshematopoietic stem and progenitor cellstlr2BiologyMicrobiologyHost-Microbe Biology03 medical and health sciencesMicetrained immunity0302 clinical medicineImmune systemVirologymedicineAnimalsLectins C-TypeProgenitor cell030304 developmental biologyMice Knockout0303 health sciencesInnate immune systemStem CellsCandidiasisCell DifferentiationHematopoietic Stem CellsImmunity InnateToll-Like Receptor 2QR1-502Cell biologymacrophagesTransplantationMice Inbred C57BLTLR2Haematopoiesismedicine.anatomical_structureMyeloid Differentiation Factor 88Femalecandida albicansBone marrowdectin-1030215 immunologyResearch ArticleSignal TransductionmBio
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Detection of a TLR2 agonist by hematopoietic stem and progenitor cells impacts the function of the macrophages they produce

2013

Several groups have shown that detection of microbial components by TLRs on hematopoietic stem and progenitor cells (HSPCs) instructs myeloid cell generation, raising interest in the possibility of targeting TLRs on HSPCs to boost myelopoiesis. However, although "TLR-derived" cells exhibit myeloid cell characteristics (phagocytosis, cytokine production, antigen presentation), it is not clear whether they are functionally equivalent to macrophages derived in the absence of TLR activation. Our in vitro and in vivo studies show that macrophages derived from mouse and human HSPC subsets (including stem cells) exposed to a TLR2 agonist prior to or during macrophage differentiation produce lower …

Myeloidmedicine.medical_treatmentCellular differentiationImmunologyBiologyCell biologyHaematopoiesisCytokinemedicine.anatomical_structuremedicineImmunology and AllergyMacrophageMyelopoiesisStem cellProgenitor cellEuropean Journal of Immunology
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In vitro differentiation of murine hematopoietic progenitor cells toward the myeloid lineage occurs in response to Staphylococcus aureus and yeast sp…

2013

We have studied the effect of inactivated microbial stimuli (Candida albicans, Candida glabrata, Saccharomyces boulardii, and Staphylococcus aureus) on the in vitro differentiation of lineage negative (Lin−) hematopoietic progenitor mouse cells. Purified Lin− progenitors were co-cultured for 7 days with the stimuli, and cell differentiation was determined by flow cytometry analysis. All the stimuli assayed caused differentiation toward the myeloid lineage. S. boulardii and particularly C. glabrata were the stimuli that induced in a minor extent differentiation of Lin− cells, as the major population of differentiated cells corresponded to monocytes, whereas C. albicans and S. aureus induced …

Staphylococcus aureusMyeloidLineage (genetic)FarmacologíaPattern-recognition receptorsCandida glabratamedicine.disease_causeMicrobiologyMicrobiologySaccharomycesCandida albicansmedicineAnimalsMouse hematopoietic progenitorsCandida albicansbiologyCandida glabrataCell DifferentiationFlow CytometryHematopoietic Stem Cellsbiology.organism_classificationCoculture TechniquesYeastIn vitroMice Inbred C57BLSaccharomyces boulardiiInfectious Diseasesmedicine.anatomical_structureStaphylococcus aureusReceptors Pattern RecognitionHematopoietic progenitor cellsFemaleMicrobial Pathogenesis
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Análisis de la percepción del alumnado ante la metodología de trabajar en grupos tutorizados

2017

[EN] The main objective of this paper is to analyze the opinion and perspective that the students have in view of the methodology of working in tutored groups. This methodology adopted in the teaching-learning process is important for the development of competences. The ability to work in a team and the ability to communicate are very significant transversal competences that have a great impact or potential in student learning. This paper presents an analysis of student assessments collected through anonymous opinions after the elaboration of a tutorial work carried out in a group in the Medicine Degree of the University of Valencia during the years 2015-2016 and 2016- 2017. It is essential…

Innovación educativaGrupo tutorizadoEducación superiorCompetenciasEducación universitariaEnseñanza superiorTecnologías y educaciónTrabajo en equipo
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The Carbon Monoxide-Releasing Molecule Tricarbonyldichlororuthenium(II) Dimer Protects Human Osteoarthritic Chondrocytes and Cartilage from the Catab…

2008

We have investigated the effects of a carbon monoxide-releasing molecule, tricarbonyldichlororuthenium(II) dimer (CORM-2), on catabolic processes in human osteoarthritis (OA) cartilage and chondrocytes activated with interleukin-1beta. In these cells, proinflammatory cytokines induce the synthesis of matrix metalloproteinases (MMPs) and aggrecanases, including members of a disintegrin and metalloproteinase with thrombospondin domain (ADAMTS) family, which may contribute to cartilage loss. CORM-2 down-regulated MMP-1, MMP-3, MMP-10, MMP-13, and ADAMTS-5 in OA chondrocytes, and it inhibited cartilage degradation. These effects were accompanied by increased aggrecan synthesis and collagen II e…

MaleInterleukin-1betaDown-RegulationMatrix metalloproteinaseProtective AgentsProinflammatory cytokineExtracellular matrixChondrocytesOsteoarthritisOrganometallic CompoundsmedicineExtracellularHumansAggrecansCollagen Type IIAggrecanAgedPharmacologyCarbon MonoxideThrombospondinChemistryCartilageADAMTSMatrix MetalloproteinasesCell biologyCartilagemedicine.anatomical_structureBiochemistryMolecular MedicineFemaleJournal of Pharmacology and Experimental Therapeutics
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Identification of New Genetic Clusters in Glioblastoma Multiforme: EGFR Status and ADD3 Losses Influence Prognosis

2020

Glioblastoma multiforme (GB) is one of the most aggressive tumors. Despite continuous efforts to improve its clinical management, there is still no strategy to avoid a rapid and fatal outcome. EGFR amplification is the most characteristic alteration of these tumors. Although effective therapy against it has not yet been found in GB, it may be central to classifying patients. We investigated somatic-copy number alterations (SCNA) by multiplex ligation-dependent probe amplification in a series of 137 GB, together with the detection of EGFRvIII and FISH analysis for EGFR amplification. Publicly available data from 604 patients were used as a validation cohort. We found statistical associations…

IDHMaleOncologymedicine.medical_specialtyDNA Copy Number VariationsEGFRSCNAsurvivalArticleText miningCDKN2AInternal medicineHumansMedicineMultiplexlcsh:QH301-705.5<i>IDH</i>Brain Neoplasmsbusiness.industryGene AmplificationglioblastomaGeneral MedicineMiddle AgedADD3Prognosismedicine.diseaseSurvival AnalysisErbB ReceptorsMSH6high throughout techniqueslcsh:Biology (General)ADD3Multigene FamilyCalmodulin-Binding ProteinsFemaleprecisionIdentification (biology)businessSignal TransductionGlioblastomaCells
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Study of the activation of TLR receptors in neurospheres from glioblastoma cells in vitro

2018

Oncologybusiness.industryNeurosphereCancer researchMedicineHematologybusinessmedicine.diseaseReceptorIn vitroGlioblastomaAnnals of Oncology
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Heme oxygenase-1 inhibits apoptosis in Caco-2 cells via activation of Akt pathway

2005

Heme oxygenase-1 can play a protective role against cellular stress. In colon cancer cells, these effects would be relevant to oncogenesis and resistance to chemotherapy. The aim of the study was to examine the effects of heme oxygenase-1 induction on cell survival in a human colon cancer cell line, Caco-2. Serum deprivation induced apoptosis, reduced Akt and p38 phosphorylation, and increased p21(Cip/WAF1) levels. Heme oxygenase-1 induction by treatment with cobalt protoporphyrin IX resulted in resistance to apoptosis, activation of Akt, reduction in p21(Cip/WAF1) levels and modification of bcl2/bax ratio towards survival. Indomethacin reduced apoptosis but in contrast to heme oxygenase-1,…

Cyclin-Dependent Kinase Inhibitor p21BiliverdinCell SurvivalChemistryBilirubinp38 mitogen-activated protein kinasesProtoporphyrinsApoptosisCell BiologyBiochemistryCulture Media Serum-FreeCell biologyHeme oxygenasechemistry.chemical_compoundApoptosisEnzyme InductionHumansCaco-2 CellsProto-Oncogene Proteins c-aktHemeProtein kinase BHeme Oxygenase-1PI3K/AKT/mTOR pathwayThe International Journal of Biochemistry &amp; Cell Biology
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Candida albicansstimulatesin vivodifferentiation of haematopoietic stem and progenitor cells towards macrophages by a TLR2-dependent signalling

2013

Toll-like receptors (TLRs) are expressed by haematopoietic stem and progenitor cells (HSPCs), and may play a role in haematopoiesis in response to pathogens during infection. We have previously demonstrated that (i) inactivated yeasts of Candida albicans induce in vitro differentiation of HSPCs towards the myeloid lineage, and (ii) soluble TLR agonists induce in vivo their differentiation towards macrophages. In this work, using an in vivo model of HSPCs transplantation, we report for the first time that HSPCs sense C. albicans in vivo and subsequently are directed to produce macrophages by a TLR2-dependent signalling. Purified lineage-negative cells (Lin(-)) from bone marrow of C57BL/6 mic…

Innate immune systemMyeloidCellular differentiationImmunologyBiologyMicrobiologyCell biologyTransplantationHaematopoiesisTLR2medicine.anatomical_structureVirologyImmunologymedicineBone marrowProgenitor cellCellular Microbiology
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Alteration of major vault protein in human glioblastoma and its relation with EGFR and PTEN status.

2014

Glioblastoma (GBM) is the most frequent and malignant primary brain tumor. Conventional therapy of surgical removal, radiation and chemotherapy is largely palliative. Major vault protein (MVP), the main component of the vault organelle has been associated with multidrug resistance by reducing cellular accumulation of chemotherapeutic agents. With regard to cancer, MVP has been shown to be overexpressed in drug resistance development and malignant progression. The aim of the present study was to evaluate the MVP gene dosage levels in 113 archival samples from GBM and its correlation with patients' survival and epidermal growth factor receptor (EGFR) and phosphatase and tensin homolog (PTEN) …

AdultMaleBiologyGene dosageStatistics NonparametricYoung AdultMajor vault proteinmedicinePTENTensinHumansEpidermal growth factor receptorMultiplex ligation-dependent probe amplificationAgedVault Ribonucleoprotein ParticlesPolysomyBrain NeoplasmsGeneral NeurosciencePTEN PhosphohydrolaseCancerMiddle Agedmedicine.diseaseErbB ReceptorsGene Expression Regulation NeoplasticMutationCancer researchbiology.proteinFemaleGlioblastomaChromosomes Human Pair 7Neuroscience
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Heme oxygenase-1 induction modulates microsomal prostaglandin E synthase-1 expression and prostaglandin E2 production in osteoarthritic chondrocytes

2009

Pro-inflammatory cytokines such as interleukin-1beta (IL-1beta) may participate in the pathogenesis of cartilage damage in osteoarthritis (OA) through the production of catabolic enzymes and inflammatory mediators. Induction of heme oxygenase-1 (HO-1) has previously been shown to exert anti-inflammatory effects in different cell types. We have investigated whether HO-1 induction may modify chondrocyte viability and the production of relevant mediators such as oxidative stress and prostaglandin E(2) (PGE(2)) elicited by IL-1beta in OA chondrocytes. Chondrocytes were isolated from OA cartilage and used in primary culture. Cells were stimulated with IL-1beta in the absence or presence of the H…

Transcriptional Activationmedicine.medical_specialtyCell Survivalmedicine.medical_treatmentBiologymedicine.disease_causeProstaglandin E synthaseBiochemistryDinoprostoneChondrocyteChondrocytesMicrosomesInternal medicineOsteoarthritismedicineHumansProstaglandin E2Cells CulturedAggrecanProstaglandin-E SynthasesPharmacologyCOPPMolecular biologyIntramolecular OxidoreductasesHeme oxygenasemedicine.anatomical_structureEndocrinologybiology.proteinHeme Oxygenase-1Oxidative stressProstaglandin Emedicine.drugBiochemical Pharmacology
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Cellusim: Un simulador 3D en entorno videojuego para la docencia del laboratorio de cultivos celulares

2018

[EN] Cell cultures allow the maintenance of living cells outside the body. This technique is fundamental to study the biological, biochemical and physiological properties of cells and can be used as an experimental model in vitro in the field of biomedical research. The teaching in the laboratory of this technique presents numerous difficulties at a practical, logistical and economic level. On the other hand, the learning of cell culture protocols is an important part of the student's training in Cell Biology. Based on the routine practices carried out within a cell culture laboratory, we have developed the virtual 3D simulator of a cell culture laboratory "Cellusim". In "Cellusim" you can …

Innovación educativaVideojuegos para docenciaBiología celularUnityExperimental modelLineaSimulador 3DEstablished cell lineEducación superiorDocencia en ciencias de la saludEnseñanza superiorLaboratorio virtualTecnologías y educaciónHumanitiesLibro de Actas IN-RED 2018: IV Congreso Nacional de Innovación Educativa y Docencia en Red
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Haem oxygenase-1 regulates catabolic and anabolic processes in osteoarthritic chondrocytes

2007

Pro-inflammatory cytokines, matrix metalloproteinases (MMPs) and other catabolic factors participate in the pathogenesis of cartilage damage in osteoarthritis (OA). Pro-inflammatory cytokines such as interleukin-1β (IL-1β) mediate cartilage degradation and might be involved in the progression of OA. Previously, we found that haem oxygenase-1 (HO-1) is down-regulated by pro-inflammatory cytokines and up-regulated by IL-10 in OA chondrocytes. The aim of this study was to determine whether HO-1 can modify the catabolic effects of IL-1β in OA cartilage and chondrocytes. Up-regulation of HO-1 by cobalt protoporphyrin IX significantly reduced glycosaminoglycan degradation elicited by IL-1β in OA …

Cartilage ArticularMaleMAP Kinase Signaling Systemmedicine.medical_treatmentInterleukin-1betaProtoporphyrinsMatrix metalloproteinaseChondrocytePathology and Forensic MedicineExtracellular matrixChondrocytesmedicineExtracellularHumansInsulin-Like Growth Factor ICollagen Type IICells CulturedAggrecanAgedbiologyChemistryCartilageGrowth factorOsteoarthritis KneeMatrix MetalloproteinasesCell biologymedicine.anatomical_structureProteoglycanImmunologybiology.proteinFemaleProteoglycansHeme Oxygenase-1The Journal of Pathology
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TLR2, TLR4 and Dectin-1 signalling in hematopoietic stem and progenitor cells determines the antifungal phenotype of the macrophages they produce

2016

TLRs represent an attractive target for the stimulation of myeloid cell production by HSPCs. We have previously demonstrated that HSPCs use TLR2 to sense Candida albicans in vivo and induce the production of macrophages. In this work, we used an in vitro model of HSPCs differentiation to investigate the functional consequences for macrophages of exposure of HSPCs to various PAMPs and C. albicans cells. Mouse HSPCs (Lin(-) cells) were cultured with M-CSF to induce macrophage differentiation, in the presence or absence of the following PRR agonists: Pam3CSK4 (TLR2 ligand), LPS (TLR4 ligand), depleted zymosan (which only activates Dectin-1), or C. albicans yeasts (which activate several PRRs, …

Lipopolysaccharides0301 basic medicineMacrophage colony-stimulating factorCellular differentiationImmunologyBiologyMicrobiologyMicrobiologyProinflammatory cytokineLipopeptidesMice03 medical and health sciences0302 clinical medicineCandida albicansAnimalsLectins C-TypeProgenitor cellCandida albicansInnate immune systemMacrophage Colony-Stimulating FactorMacrophagesZymosanCell DifferentiationHematopoietic Stem Cellsbiology.organism_classificationToll-Like Receptor 2Cell biologyMice Inbred C57BLToll-Like Receptor 4TLR2030104 developmental biologyInfectious DiseasesTLR4Female030215 immunologyMicrobes and Infection
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The Status of EGFR Modulates the Effect of miRNA-200c on ZEB1 Expression and Cell Migration in Glioblastoma Cells

2020

Migration of glioblastoma cells into surrounding tissue is one of the main features that makes this tumor incurable. We evaluated whole-genome miRNA expression profiling associated with different EGFR amplification patterns in 30 cases of primary glioblastoma. From the 64 miRNAs that showed differential expression between tumors with a high level of EGFR amplification and tumors without EGFR amplification, 40% were related with cell migration, being miR-200c the most differentially expressed between these two groups. We investigated the effect of miR-200c on ZEB1 expression and cell migration in an in vitro transfection model with a miR-200c mimic, a miR-200c inhibitor and siRNA targeting E…

cell migrationEGFR AmplificationApoptosisBiologyArticleCatalysismiR-200clcsh:ChemistryInorganic ChemistryDownregulation and upregulationCell MovementmicroRNABiomarkers TumorTumor Cells CulturedmedicineZEB1HumansGene silencingEGFR amplificationPhysical and Theoretical Chemistrylcsh:QH301-705.5Molecular BiologySpectroscopyCell ProliferationOrganic ChemistryglioblastomaGene AmplificationZinc Finger E-box-Binding Homeobox 1Cell migrationGeneral MedicineTransfectionPrognosismedicine.diseaseComputer Science ApplicationsErbB ReceptorsGene Expression Regulation NeoplasticMicroRNAslcsh:Biology (General)lcsh:QD1-999Cell cultureMutationCancer researchGlioblastomaInternational Journal of Molecular Sciences
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Carbon Monoxide-Releasing Molecules: A Pharmacological Expedient to Counteract Inflammation

2008

Carbon monoxide (CO) mediates many of the biological effects that are attributed to heme oxygenase (HO), the enzyme responsible for CO production in mammals. Antioxidant and anti-inflammatory activities of HO-1, the inducible isoform of heme oxygenase, have been demonstrated in a variety of disease models and a therapeutic exploitation of this pathway is currently under scrutiny. In this context, the liberation of CO from CO-releasing molecules (CO-RMs) is extremely attractive as these compounds may form the basis of a new class of pharmaceuticals. Recent investigations indicate that HO-1 and CO modulate important processes in chronic inflammation; these include the control of immune respon…

Anti-Inflammatory AgentsContext (language use)InflammationOsteoarthritisPharmacologyRutheniumArthritis RheumatoidDegenerative diseaseImmune systemOsteoarthritisDrug DiscoveryOrganometallic CompoundsAnimalsHumansMedicineInflammationPharmacologyCarbon Monoxidebusiness.industrymedicine.diseaseCarbon monoxide-releasing moleculesHeme oxygenaseOxidative StressImmunologyMetalloproteasesCytokinesmedicine.symptomSignal transductionbusinessHeme Oxygenase-1Signal TransductionCurrent Pharmaceutical Design
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New molecular targets for the treatment of osteoarthritis.

2009

Osteoarthritis (OA) is a chronic degenerative joint disorder characterized by destruction of the articular cartilage, subchondral bone alterations and synovitis. Current treatments are focused on symptomatic relief but they lack efficacy to control the progression of this disease which is a leading cause of disability. Therefore, the development of effective disease-modifying drugs is urgently needed. Different initiatives are in progress to define the molecular mechanisms involved in the initiation and progression of OA. These studies support the therapeutic potential of pathways relevant in joint metabolism such as Wnt/beta-catenin, discoidin domain receptor 2 or proteinase-activated rece…

OsteoarthritisBioinformaticsBiochemistryModels BiologicalSynovitismicroRNAOsteoarthritismedicineAnimalsHumansbeta CateninPharmacologybusiness.industryCartilageADAMTSWnt signaling pathwayGenetic Therapymedicine.diseaseSymptomatic reliefWnt ProteinsMicroRNAsmedicine.anatomical_structureFrzbImmunologyCytokinesIntercellular Signaling Peptides and ProteinsbusinessBiochemical pharmacology
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The carbon monoxide-releasing molecule CORM-2 inhibits the inflammatory response induced by cytokines in Caco-2 cells

2007

Background and purpose: Recent evidence indicates that carbon monoxide-releasing molecules (CO-RMs) exhibit potential anti-inflammatory properties. In the present study, we have investigated whether tricarbonyl dichloro ruthenium(II) dimer (CORM-2) can control the inflammatory response induced by cytokines in a human colonic epithelial cell line, Caco-2. Experimental approach: Caco-2 cells were preincubated with CORM-2 for 30 minutes and then stimulated with interleukin (IL)-1β, tumor necrosis factor-α and interferon-γ for different times. Gene expression was analyzed by real-time PCR. Protein expression was investigated by Western blot and ELISA. Transcription factor activation was determi…

PharmacologySmall interfering RNACytokinep38 mitogen-activated protein kinasesEnhancer bindingmedicine.medical_treatmentGene expressionmedicineTumor necrosis factor alphaBiologyNFKB1Protein kinase AMolecular biologyBritish Journal of Pharmacology
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Introducció a les alteracions equilibrades dels cromosomes

2019

Proyecto orientado al alumnado de Medicina. Se persigue, por un lado facilitar material complementario multimedia para preparar y entender mejor los supuestos prácticas que se plantean en la asignatura de Embriología, y por otro lado, consolidar los conocimientos que se van a desarrollar a lo largo de la materia. Producción: Unidad de Biología. Con apoyo del SFPIE UV-SFPIE_RMD18-839057. ADAPTACIÓN AL VALENCIANO

2407.02 Ciencies de la Vida
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Reciprocal translocation

2019

Proyecto orientado al alumnado de Medicina. Se persigue, por un lado facilitar material complementario multimedia para preparar y entender mejor los supuestos prácticos que se plantean en la asignatura de Embriología, y por otro lado, consolidar los conocimientos que se van a desarrollar a lo largo de la materia. Producción: Unidad de Biología. Con apoyo del SFPIE UV-SFPIE_RMD18-839057. ADAPTACIÓN AL INGLÉS

2407.02 Ciencies de la Vida
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Segregació cromosòmica de la traslocació recíproca

2019

Proyecto orientado al alumnado de Medicina. Se persigue, por un lado facilitar material complementario multimedia para preparar y entender mejor los supuestos prácticos que se plantean en la asignatura de Embriología, y por otro lado, consolidar los conocimientos que se van a desarrollar a lo largo de la materia. Producción: Unidad de Biología. Con apoyo del SFPIE UV-SFPIE_RMD18-839057.ADAPTACIÓN AL VALENCIANO

2407.02 Ciencies de la Vida
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Segregació cromosòmica de la traslocació robertsoniana

2019

Proyecto orientado al alumnado de Medicina. Se persigue, por un lado facilitar material complementario multimedia para preparar y entender mejor los supuestos prácticos que se plantean en la asignatura de Embriología, y por otro lado, consolidar los conocimientos que se van a desarrollar a lo largo de la materia. Producción: Unidad de Biología. Con apoyo del SFPIE UV-SFPIE_RMD18-839057. ADAPTACIÓN AL VALENCIANO

2407.02 Ciencies de la Vida
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Robertsonian translocation

2019

Proyecto orientado al alumnado de Medicina. Se persigue, por un lado facilitar material complementario multimedia para preparar y entender mejor los supuestos prácticos que se plantean en la asignatura de Embriología, y por otro lado, consolidar los conocimientos que se van a desarrollar a lo largo de la materia. Producción: Unidad de Biología. Con apoyo del SFPIE UV-SFPIE_RMD18-839057. ADAPTACIÓN AL INGLÉS

2407.02 Ciencies de la Vida
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Introducción a las alteraciones estructurales equilibradas de los cromosomas

2018

Proyecto orientado al alumnado de Medicina. Se persigue, por un lado facilitar material complementario multimedia para preparar y entender mejor los supuestos prácticas que se plantean en la asignatura de Embriología, y por otro lado, consolidar los conocimientos que se van a desarrollar a lo largo de la materia. Música: Firefly by Techsmith library. Producción: Unidad de Biología. Con apoyo del SFPIE UV-SFPIE_RMD17-724975

2407.02 Ciencies de la Vida
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