Search results for "LEM"

showing 10 items of 23327 documents

Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer.

2016

Abstract As a master regulator of chromatin function, the lysine methyltransferase EZH2 orchestrates transcriptional silencing of developmental gene networks. Overexpression of EZH2 is commonly observed in human epithelial cancers, such as non–small cell lung carcinoma (NSCLC), yet definitive demonstration of malignant transformation by deregulated EZH2 remains elusive. Here, we demonstrate the causal role of EZH2 overexpression in NSCLC with new genetically engineered mouse models of lung adenocarcinoma. Deregulated EZH2 silences normal developmental pathways, leading to epigenetic transformation independent of canonical growth factor pathway activation. As such, tumors feature a transcrip…

0301 basic medicineModels MolecularLung Neoplasmsmedicine.medical_treatmentMolecular ConformationGene ExpressionAntineoplastic Agentsmacromolecular substancesBiologymedicine.disease_causeArticleMalignant transformationTargeted therapy03 medical and health sciencesMiceStructure-Activity RelationshipCell Line TumormedicineAnimalsHumansEnhancer of Zeste Homolog 2 ProteinMolecular Targeted TherapyLung cancerPromoter Regions GeneticGene Expression ProfilingEZH2Cancermedicine.diseaseMagnetic Resonance ImagingXenograft Model Antitumor AssaysChromatinrespiratory tract diseasesGene Expression Regulation NeoplasticDisease Models Animal030104 developmental biologyCell Transformation NeoplasticEnhancer Elements GeneticOncologyDrug DesignCancer researchAdenocarcinomaKRASEpigenetic therapyCancer discovery
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Bioactive triterpenes of protium heptaphyllum gum resin extract display cholesterol-lowering potential

2021

Hypercholesterolemia is one of the major causes of cardiovascular disease, the risk of which is further increased if other forms of dyslipidemia occur. Current therapeutic strategies include changes in lifestyle coupled with drug administration. Statins represent the most common therapeutic approach, but they may be insufficient due to the onset of resistance mechanisms and side effects. Consequently, patients with mild hypercholesterolemia prefer the use of food supplements since these are perceived to be safer. Here, we investigate the phytochemical profile and cholesterol-lowering potential of Protium heptaphyllum gum resin extract (PHE). Chemical characterization via HPLC-APCI-HRMS2 and…

0301 basic medicineModels MolecularProtein ConformationDrug Evaluation Preclinical030204 cardiovascular system & hematologyPharmacologyPPARαTerpenelcsh:ChemistryPCSK9chemistry.chemical_compound0302 clinical medicineCatalytic DomainSettore BIO/10 - BiochimicaPlant Gumslcsh:QH301-705.5SpectroscopyChromatography High Pressure LiquidFlame IonizationMonacolinChemistryAnticholesteremic AgentsGeneral MedicineComputer Science ApplicationsMolecular Docking SimulationCholesterolPhytochemicalMolecular dockinglipids (amino acids peptides and proteins)Breu brancoStatinmedicine.drug_classHypercholesterolemiaArticleCatalysisGas Chromatography-Mass SpectrometryInorganic Chemistry03 medical and health sciencesNutraceuticalmedicineHumansLovastatinPhysical and Theoretical ChemistryMolecular BiologyOleananeHMGCREnzymatic activityCholesterolPCSK9Organic ChemistryStatinSettore CHIM/08 - Chimica FarmaceuticaTriterpenes030104 developmental biologyhypercholesterolemia; gene expression; HMGCR; PCSK9; PPARα; enzymatic activity; molecular docking; statin; monacolin; breu brancolcsh:Biology (General)lcsh:QD1-999Breu branco; Enzymatic activity; Gene expression; HMGCR; Hypercholesterolemia; Molecular docking; Monacolin; PCSK9; PPARα; StatinLDL receptorDietary SupplementsHepatocytesSettore BIO/14 - FarmacologiaGene expressionHydroxymethylglutaryl-CoA Reductase InhibitorsResins PlantHydrogen
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Immunmodulatory and Antiproliferative Properties of Rhodiola Species.

2016

The traditional medicines of Asia and Europe have long used various Rhodiola species, which are endemic to the subarctic areas of the northern hemisphere, as tonic, adaptogen, antidepressant, and anti-inflammatory drugs. In order to establish the therapeutic uses of these plants in modern medicine, the pharmacological effects of Rhodiola sp. have been widely studied. Indeed, the most amply researched species, Rhodiola rosea, has been shown to possess antioxidant, adaptogenic, antistress, antimicrobial, immunomodulatory, angiomodulatory, and antitumoral effects. Salidroside (p-hydroxyphenethyl-β-D-glucoside), a major compound in Rhodiola, seems to be responsible for many of the effects obser…

0301 basic medicineModern medicineRhodiola algidaImmunologic Factorsmedicine.medical_treatmentPharmaceutical SciencePharmacologyAnalytical Chemistry03 medical and health scienceschemistry.chemical_compound0302 clinical medicineGlucosidesPhenolsSpecies SpecificityDrug DiscoveryAdaptogenRhodiolamedicineAnimalsHumansImmunologic FactorsRhodiola crenulataCell ProliferationPharmacologybiologyTraditional medicinePlant ExtractsOrganic ChemistrySalidrosidebiology.organism_classificationAntineoplastic Agents Phytogenic030104 developmental biologyRhodiola roseaComplementary and alternative medicinechemistry030220 oncology & carcinogenesisMolecular MedicineRhodiolaPlanta medica
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CitA (citrate) and DcuS (C4-dicarboxylate) sensor kinases in thermophilic Geobacillus kaustophilus and Geobacillus thermodenitrificans

2015

The thermophilic Geobacillus thermodenitrificans and Geobacillus kaustophilus are able to use citrate or C4-dicarboxylates like fumarate or succinate as the substrates for growth. The genomes of the sequenced Geobacillus strains (nine strains) each encoded a two-component system of the CitA family. The sensor kinase of G. thermodenitrificans (termed CitAGt) was able to replace CitA of Escherichia coli (CitAEc) in a heterologous complementation assay restoring expression of the CitAEc-dependent citC-lacZ reporter gene and anaerobic growth on citrate. Complementation was specific for citrate. The sensor kinase of G. kaustophilus (termed DcuSGk) was able to replace DcuSEc of E. coli. It respon…

0301 basic medicineMolecular Sequence Data030106 microbiologyHeterologousBacillus subtilismedicine.disease_causeMicrobiologyGeobacillusCitric Acid03 medical and health sciencesBacterial ProteinsProtein-fragment complementation assaymedicineDicarboxylic AcidsAmino Acid SequenceEscherichia colibiologyThermophileGeobacillusGene Expression Regulation Bacterialbiology.organism_classificationComplementationBiochemistryHeterologous expressionProtein KinasesSequence AlignmentMicrobiology
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Inhibition of human monoamine oxidase A and B by flavonoids isolated from two Algerian medicinal plants

2017

Abstract Background Monoamine oxidases (MAOs) are outer mitochondrial membrane flavoenzymes. They catalyze the oxidative deamination of a variety of neurotransmitters. MAO-A and MAO-B may be considered as targets for inhibitors to treat neurodegenerative diseases and depression and for managing symptoms associated with Parkinson's and Alzheimer's diseases. Purpose The objective was to evaluate the inhibitory effect of Hypericum afrum and Cytisus villosus against MAO-A and B and to isolate the compounds responsible for the MAO-inhibitory activity. Methods The inhibitory effect of extracts and purified constituents of H. afrum and C. villosus were investigated in vitro using recombinant human…

0301 basic medicineMonoamine Oxidase InhibitorsMonoamine oxidaseDrug Evaluation PreclinicalPharmaceutical ScienceGenisteinMixed inhibitionArticleMass SpectrometryInhibitory Concentration 5003 medical and health scienceschemistry.chemical_compoundDrug DiscoveryHumansChrysinMonoamine OxidaseIC50CytisusFlavonoidsPharmacologyPlants MedicinalMolecular Docking Simulation030104 developmental biologyComplementary and alternative medicinechemistryBiochemistryDocking (molecular)AlgeriaMolecular MedicineQuercetinMyricetinQuercetinHypericumPhytomedicine
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Transcriptomic data from panarthropods shed new light on the evolution of insulator binding proteins in insects : Insect insulator proteins.

2016

Background Body plan development in multi-cellular organisms is largely determined by homeotic genes. Expression of homeotic genes, in turn, is partially regulated by insulator binding proteins (IBPs). While only a few enhancer blocking IBPs have been identified in vertebrates, the common fruit fly Drosophila melanogaster harbors at least twelve different enhancer blocking IBPs. We screened recently compiled insect transcriptomes from the 1KITE project and genomic and transcriptomic data from public databases, aiming to trace the origin of IBPs in insects and other arthropods. Results Our study shows that the last common ancestor of insects (Hexapoda) already possessed a substantial number …

0301 basic medicineMost recent common ancestormedia_common.quotation_subjectInsectDipluraGene evolutionEvolution Molecular03 medical and health sciencesArthropod evolutionGeneticsAnimalsEnhancerArthropodsPhylogenymedia_commonGeneticsbiologyGene Expression ProfilingfungiComparative transcriptomic analysesbiology.organism_classificationInsulator binding proteinsNeopteraDNA-Binding Proteins030104 developmental biologyBody planDrosophila melanogasterEnhancer Elements GeneticInsulator ElementsDrosophila melanogasterHomeotic geneTranscriptomeBiotechnologyResearch ArticleBMC genomics
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Evaluation of permeability applicability based on continuum mechanics law in fluid flow through graphene membrane

2019

AbstractGraphene is expected to be used in separation applications such as desalination. However, it is difficult to predict the flow phenomena at the nanoscale using the conventional continuum law. Particularly at a Knudsen number (Kn) of >0.1, which is applied in filtration, it has been reported that not even slip boundary conditions can be applied. In this study, to identify the parameters that affect the applicability of the continuum law, we conducted a fluid permeation simulation using graphene. The deviation of the permeability from that of the continuum model was calculated by changing the channel width, fluid temperature, and fluid type. The result showed that the channel width …

0301 basic medicineNanoscale materialsMultidisciplinaryMaterials scienceContinuum mechanicsContinuum (measurement)lcsh:Rlcsh:MedicineSlip (materials science)PermeationArticleMechanical engineering03 medical and health sciencesPermeability (earth sciences)030104 developmental biology0302 clinical medicineLawFluid dynamicslcsh:QKnudsen numberBoundary value problemGraphenelcsh:Science030217 neurology & neurosurgeryScientific Reports
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Protein-Free Hapten-Carbon Nanotube Constructs Induce the Secondary Immune Response

2017

Carbon nanotubes are novel technological tools with multiple applications. The interaction between such nanoparticles and living organisms is nowadays a matter of keen research by academic and private institutions. In this study, carbon nanotube constructs were investigated as delivery vehicles for immunostimulation and induction of the secondary immune response to a small organic molecule, namely, a hapten. Two types of nanoconstructs were prepared: on one hand, carbon nanotubes carrying a protein bioconjugate of a hapten covalently linked to the carbon surface, and on the other hand, covalent carbon nanotube constructs of the same model chemical compound without the carrier protein. Nanot…

0301 basic medicineNanotubeBiomedical EngineeringPharmaceutical ScienceNanoparticlechemistry.chemical_elementBioengineeringNanotechnologychemical and pharmacologic phenomena02 engineering and technologyCarbon nanotubelaw.invention03 medical and health sciencesAdjuvants ImmunologiclawMoleculeHumansPharmacologyBioconjugationNanotubes CarbonOrganic Chemistry021001 nanoscience & nanotechnology030104 developmental biologychemistryCovalent bondBiophysicsImmunization0210 nano-technologyCarrier ProteinsHaptenCarbonHaptensBiotechnology
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Fetal neurogenesis: breathe HIF you can.

2016

Blood vessels are part of the stem cell niche in the developing cerebral cortex, but their in vivo role in controlling the expansion and differentiation of neural stem cells (NSCs) in development has not been studied. Here, we report that relief of hypoxia in the developing cerebral cortex by ingrowth of blood vessels temporo‐spatially coincided with NSC differentiation. Selective perturbation of brain angiogenesis in vessel‐specific Gpr124 null embryos, which prevented the relief from hypoxia, increased NSC expansion at the expense of differentiation. Conversely, exposure to increased oxygen levels rescued NSC differentiation in Gpr124 null embryos and increased it further in WT embryos, s…

0301 basic medicineNeurogenesisNicheNeovascularization PhysiologicBiologyCell fate determinationGeneral Biochemistry Genetics and Molecular Biology03 medical and health sciencesMiceFetusNeural Stem CellsmedicineAnimalsHumansNews & ViewsHypoxiaMolecular BiologyCentral elementreproductive and urinary physiologyCell ProliferationCerebral CortexFetusGeneral Immunology and MicrobiologyGeneral NeuroscienceNeurogenesisCell DifferentiationArticlesHypoxia-Inducible Factor 1 alpha Subunitnervous system diseasesOxygen030104 developmental biologymedicine.anatomical_structurenervous systemCerebral cortexImmunologyNeuronStem cellbiological phenomena cell phenomena and immunityNeuroscienceGlycolysisThe EMBO journal
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Pathogenesis of antiphospholipid syndrome: recent insights and emerging concepts

2018

Introduction: Even though our understanding of the antiphospholipid syndrome (APS) has improved tremendously over the last decades, we are still not in a position to replace symptomatic anticoagulation by pathogenesis based causal treatments. Areas covered: Recent years have provided further insights into pathogenetically relevant mechanisms. These include a differentiation of pathogenic subtypes of antiphospholipid antibodies (aPL), novel mechanisms modulating disease activity, for example, extracellular vesicles and microRNA, and novel players in pathogenesis, for example, neutrophils and neutrophil extracellular traps (NETs). Expert commentary: It is evident that aPL induce a proinflamma…

0301 basic medicineNeutrophilsImmunologyBioinformaticsExtracellular TrapsExtracellular vesiclesProinflammatory cytokinePathogenesisExtracellular VesiclesGenetic Heterogeneity03 medical and health sciences0302 clinical medicineimmune system diseasesAntiphospholipid syndromemicroRNAHumansImmunology and AllergyMedicineFetal lossBlood CoagulationComplement Activation030203 arthritis & rheumatologybusiness.industryNeutrophil extracellular trapsAntiphospholipid Syndromemedicine.diseaseMicroRNAs030104 developmental biologyAntibodies AntiphospholipidSignal transductionbusinessExpert Review of Clinical Immunology
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