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showing 10 items of 31559 documents

Oxidative Stress and Vascular Dysfunction in the Retina: Therapeutic Strategies

2020

Many retinal diseases, such as diabetic retinopathy, glaucoma, and age-related macular (AMD) degeneration, are associated with elevated reactive oxygen species (ROS) levels. ROS are important intracellular signaling molecules that regulate numerous physiological actions, including vascular reactivity and neuron function. However, excessive ROS formation has been linked to vascular endothelial dysfunction, neuron degeneration, and inflammation in the retina. ROS can directly modify cellular molecules and impair their function. Moreover, ROS can stimulate the production of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) causing inflammation and cel…

0301 basic medicineCell signalingProgrammed cell deathPhysiologyClinical BiochemistryInflammationReviewmedicine.disease_causeBiochemistryProinflammatory cytokine03 medical and health sciences0302 clinical medicinemedicineoxidative stressEndothelial dysfunctionMolecular Biologyreactive oxygen speciesRetinabusiness.industrylcsh:RM1-950Cell Biologymedicine.diseaseCell biology030104 developmental biologymedicine.anatomical_structurelcsh:Therapeutics. Pharmacology030221 ophthalmology & optometryTumor necrosis factor alpharetinal diseasemedicine.symptombusinessvascular endotheliumOxidative stressAntioxidants
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Food Sensation Modulates Locomotion by Dopamine and Neuropeptide Signaling in a Distributed Neuronal Network

2018

Finding food and remaining at a food source are crucial survival strategies. We show how neural circuits and signaling molecules regulate these food-related behaviors in Caenorhabditis elegans. In the absence of food, AVK interneurons release FLP-1 neuropeptides that inhibit motorneurons to regulate body posture and velocity, thereby promoting dispersal. Conversely, AVK photoinhibition promoted dwelling behavior. We identified FLP-1 receptors required for these effects in distinct motoneurons. The DVA interneuron antagonizes signaling from AVK by releasing cholecystokinin-like neuropeptides that potentiate cholinergic neurons, in response to dopaminergic neurons that sense food. Dopamine al…

0301 basic medicineCell signalingSensory Receptor CellsInterneuronDopamineSensationNeuropeptideOptogeneticsBiologyReceptors DopamineAnimals Genetically Modified03 medical and health sciencesChannelrhodopsinsDopamineNeural PathwaysBiological neural networkmedicineAnimalsCaenorhabditis elegansCaenorhabditis elegans ProteinsGeneral NeuroscienceNeuropeptidesdigestive oral and skin physiologyDopaminergicOptogenetics030104 developmental biologymedicine.anatomical_structureFoodDopamine receptorCalciumNeuroscienceLocomotionmedicine.drugNeuron
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MYC Induces a Hybrid Energetics Program Early in Cell Reprogramming

2018

Summary Cell reprogramming is thought to be associated with a full metabolic switch from an oxidative- to a glycolytic-based metabolism. However, neither the dynamics nor the factors controlling this metabolic switch are fully understood. By using cellular, biochemical, protein array, metabolomic, and respirometry analyses, we found that c-MYC establishes a robust bivalent energetics program early in cell reprogramming. Cells prone to undergo reprogramming exhibit high mitochondrial membrane potential and display a hybrid metabolism. We conclude that MYC proteins orchestrate a rewiring of somatic cell metabolism early in cell reprogramming, whereby somatic cells acquire the phenotypic plast…

0301 basic medicineCell signalingSomatic cellCèl·lulesCellOxidative phosphorylationcell reprogramming cell signaling metabolism mitochondrial dynamicsBiologyHybrid CellsBiochemistryMitochondrial DynamicsArticleOxidative PhosphorylationMitocondrisProto-Oncogene Proteins c-myc03 medical and health sciencesMetabolomicsCDC2 Protein KinaseGeneticsmedicinecell signalingAnimalsHumansGlycolysisPhosphorylationlcsh:QH301-705.5Membrane potentialMembrane Potential Mitochondriallcsh:R5-920cell reprogrammingCell BiologyCellular ReprogrammingCell biologyMitochondriaMice Inbred C57BL030104 developmental biologymedicine.anatomical_structurelcsh:Biology (General)lcsh:Medicine (General)ReprogrammingmetabolismGlycolysisDevelopmental Biology
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A novel 3D heterotypic spheroid model for studying extracellular vesicle-mediated tumour and immune cell communication

2017

Cancer-derived extracellular vesicles (EVs) have emerged as important mediators of tumour-host interactions, and they have been shown to exert various functional effects in immune cells. In most of the studies on human immune cells, EVs have been isolated from cancer cell culture medium or patients' body fluids and added to the immune cell cultures. In such a setting, the physiological relevance of the chosen EV concentration is unknown and the EV isolation method and the timing of EV administration may bias the results. In the current study we aimed to develop an experimental cell culture model to study EV-mediated effects in human T and B cells at conditions mimicking the tumour microenvi…

0301 basic medicineCell signalingT cellPopulationBiophysicsCell CommunicationBiochemistryExtracellular Vesicles03 medical and health sciences0302 clinical medicineImmune systemCell Line TumorSpheroids CellularmedicineHumanseducationMolecular Biologyeducation.field_of_studyChemistryNeoplasms ExperimentalCell BiologyExtracellular vesicleCoculture TechniquesCell biology030104 developmental biologymedicine.anatomical_structureCell culture030220 oncology & carcinogenesisCancer cellLeukocytes MononuclearCD8Biochemical and Biophysical Research Communications
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Alkaline phosphatase dual-binding sites for collagen dictate cell migration and microvessel assembly in vitro

2020

Interactions between cell types, growth factors, and extracellular matrix components involved in angiogenesis are crucial for new vessel formation leading to tissue regeneration. This study investigated whether cocultures of fibroblasts and endothelial cells (ECs; from macro- or microvasculature) play a role in the formation of microvessel-like structures by ECs, as well as modulate fibroblast differentiation and growth factors production (vascular endothelial cell growth factor, basic fibroblast growth factor, active transforming growth factor-beta 1, and interleukin-8), which are important for vessel sprouting and maturation. Data obtained revealed that in vitro coculture systems of fibro…

0301 basic medicineCell typeAngiogenesisProtein ConformationBasic fibroblast growth factorNeovascularization PhysiologicIn Vitro TechniquesBiochemistryExtracellular matrix03 medical and health scienceschemistry.chemical_compound0302 clinical medicineCell MovementmedicineHumansFibroblastMolecular BiologyMicrovesselCells CulturedCell ProliferationBinding SitesChemistryHealth sciences Medical and Health sciencesCiências médicas e da saúdeCell migrationCell DifferentiationCell BiologyFibroblastsAlkaline PhosphataseCell biology030104 developmental biologymedicine.anatomical_structure030220 oncology & carcinogenesisMicrovesselsMedical and Health sciencesAlkaline phosphataseCollagenEndothelium VascularCiências da Saúde Ciências médicas e da saúde
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The Fate Choice Between Effector and Memory T Cell Lineages: Asymmetry, Signal Integration, and Feedback to Create Bistability

2018

Abstract CD8+ T cells clear primary infections with intracellular pathogens and provide long-term immunity against reinfection. Two different types of CD8+ T cells are responsible for these functions: short-lived effector T cells and memory T cells. The cellular relationship between these two types of CD8+ T cells has been subject to much investigation. Both cell types can derive from a single naive CD8+ T cell precursor. Their generation requires a fate choice early during a T cell response. As a result, two populations of T cells emerge. One of these consists of terminally differentiated short-lived effector T cells. The other contains cells able to develop into long-lived memory T cells.…

0301 basic medicineCell typeCell divisionNaive T cellT cellNotch signaling pathwayBiologyCell biology03 medical and health sciences030104 developmental biologymedicine.anatomical_structureAsymmetric cell divisionmedicineMemory T cellCD8
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Mast cells crosstalk with B cells in the gut and sustain IgA response in the inflamed intestine.

2021

B lymphocytes are among the cell types whose effector functions are modulated by mast cells (MCs). The B/MC crosstalk emerged in several pathological settings, notably the colon of inflammatory bowel disease (IBD) patients is a privileged site in which MCs and IgA+ cells physically interact. Herein, by inducing conditional depletion of MCs in red MC and basophil (RMB) mice, we show that MCs control B cell distribution in the gut and IgA serum levels. Moreover, in dextran sulfate sodium (DSS)-treated RMB mice, the presence of MCs is fundamental for the enlargement of the IgA+ population in the bowel and the increase of systemic IgA production. Since both conventional B-2 and peritoneal-deriv…

0301 basic medicineCell typeColon[SDV]Life Sciences [q-bio]ImmunologyPopulationInflammationBasophilBiologySettore MED/08 - Anatomia Patologicabehavioral disciplines and activitiesInflammatory bowel diseasecell-to-cell interplay colitis IgAinnate-like B cells mast cells03 medical and health sciencesMice0302 clinical medicinemedicineImmunology and AllergyAnimalsMast CellsColitisIntestinal MucosaeducationB cellComputingMilieux_MISCELLANEOUSInflammationeducation.field_of_studyB-LymphocytesTumor Necrosis Factor-alphaDextran Sulfatemedicine.diseaseColitisInflammatory Bowel DiseaseshumanitiesInnate-like B cellsGastrointestinal MicrobiomeImmunoglobulin AMice Inbred C57BLCrosstalk (biology)030104 developmental biologymedicine.anatomical_structureCell-to-cell interplayCell-to-cell interplay; Colitis; IgA; Innate-like B cells; Mast cellsImmunologymedicine.symptomIgA030215 immunologyEuropean journal of immunologyReferences
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The Drosophila Hox gene Ultrabithorax acts both in muscles and motoneurons to orchestrate formation of specific neuromuscular connections

2016

Hox genes are known to specify motoneuron pools in the developing vertebrate spinal cord and to control motoneuronal targeting in several species. However, the mechanisms controlling axial diversification of muscle innervation patterns are still largely unknown. We present data showing that the Drosophila Hox gene Ultrabithorax (Ubx) acts in the late embryo to establish target specificity of ventrally projecting RP motoneurons. In abdominal segments A2 to A7, RP motoneurons innervate the ventrolateral muscles VL1-4, with VL1 and VL2 being innervated in a Wnt4-dependent manner. In Ubx mutants, these motoneurons fail to make correct contacts with muscle VL1, a phenotype partially resembling t…

0301 basic medicineCell typeEmbryo Nonmammaliananimal structuresNeuromuscular JunctionGenes InsectMuscle DevelopmentNeuromuscular junctionAnimals Genetically ModifiedHox genes03 medical and health sciencesWNT4MorphogenesismedicineAnimalsDrosophila ProteinsHox geneWnt Signaling PathwayMolecular BiologyTranscription factorUltrabithoraxHomeodomain ProteinsMotor NeuronsGeneticsbiologyMusclesmusculoskeletal neural and ocular physiologyfungiGenes HomeoboxGene Expression Regulation Developmentalbiology.organism_classificationMuscle innervationSegmental patterningCell biologyMotoneuronsDrosophila melanogaster030104 developmental biologymedicine.anatomical_structurenervous system209embryonic structuresDrosophilaWnt signalling pathwayDrosophila melanogasterDrosophila ProteinTranscription FactorsResearch ArticleDevelopmental BiologyDevelopment
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Deregulated miRNAs in bone health: Epigenetic roles in osteoporosis.

2019

MicroRNA (miRNA) has shown to enhance or inhibit cell proliferation, differentiation and activity of different cell types in bone tissue. The discovery of miRNA actions and their targets has helped to identify them as novel regulations actors in bone. Various studies have shown that miRNA deregulation mediates the progression of bone-related pathologies, such as osteoporosis. The present review intends to give an exhaustive overview of miRNAs with experimentally validated targets involved in bone homeostasis and highlight their possible role in osteoporosis development. Moreover, the review analyzes miRNAs identified in clinical trials and involved in osteoporosis.

0301 basic medicineCell typeHistologyPhysiologyEndocrinology Diabetes and MetabolismOsteoporosis030209 endocrinology & metabolismBiologyBone tissueBioinformaticsBone healthBone and BonesEpigenesis Genetic03 medical and health sciences0302 clinical medicineOsteoclastSettore BIO/13 - Biologia ApplicatamicroRNAmedicineAnimalsHumansEpigeneticsmiRNA Bone Bone diseaseOsteoblastsOsteoblastCell Differentiationmedicine.diseaseMicroRNAs030104 developmental biologymedicine.anatomical_structureGene Expression RegulationOsteoporosisBone
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Epithelium‐specific MyD88 signaling, but not DCs or macrophages, control acute intestinal infection with Clostridium difficile

2019

Infection with Clostridium difficile is one of the major causes of health care acquired diarrhea and colitis. Signaling though MyD88 downstream of TLRs is critical for initiating the early protective host response in mouse models of C. difficile infection (CDI). In the intestine, MyD88 is expressed in various tissues and cell types, such as the intestinal epithelium and mononuclear phagocytes (MNP), including DC or macrophages. Using a genetic gain-of-function system, we demonstrate here that restricting functional MyD88 signaling to the intestinal epithelium, but also to MNPs is sufficient to protect mice during acute CDI by upregulation of the intestinal barrier function and recruitment o…

0301 basic medicineCell typeImmunologyBiologyMice03 medical and health sciences0302 clinical medicineDownregulation and upregulationmedicineAnimalsImmunology and AllergyIntestinal MucosaColitisEnterocolitis PseudomembranousBarrier functionClostridioides difficileMacrophagesDendritic CellsClostridium difficilemedicine.diseaseIntestinal epitheliumPhenotypeEpitheliumDisease Models Animal030104 developmental biologymedicine.anatomical_structureHost-Pathogen InteractionsMyeloid Differentiation Factor 88ImmunologySignal Transduction030215 immunologyEuropean Journal of Immunology
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