2025
Evaluating pathogenicity of TPM1 variants of unknown significance using in-silico and in-vitro models
Halder S, Bellitto J, Rynkiewicz M, Cheung F, Liu D, Firlar I, Bongiorno A, Barry M, Sewanan L, Moore J, Lehman W, Campbell S. Evaluating pathogenicity of TPM1 variants of unknown significance using in-silico and in-vitro models. The Journal Of Precision Medicine Health And Disease 2025, 2: 100008. DOI: 10.1016/j.premed.2025.100008.Peer-Reviewed Original ResearchIn vitro motilityFilament motilityContext of cardiomyopathyVariant classificationGenetic screeningTwitch contraction forceComputational pipelineMyosin activityEvaluate pathogenicityDiversity changesFunctional studiesIn silicoTropomyosinTPM1VUSMotilityInherited cardiomyopathyCa2+ sensitivityVariantsIn vitro modelIn vitro dataReduced abilityIPSC-derived cardiomyocytesLow Ca2+Ca2+From Single Stem Cells to an In Vitro Model of the Post-implantation Human Embryo: A Step-by-Step Guide
Gassaloglu S, Pedroza M, Sozen B. From Single Stem Cells to an In Vitro Model of the Post-implantation Human Embryo: A Step-by-Step Guide. Methods In Molecular Biology 2025, 1-16. PMID: 40397281, DOI: 10.1007/7651_2025_647.Peer-Reviewed Original ResearchTyphoid toxin causes neuropathology by disrupting the blood–brain barrier
Zhao H, Catarino J, Stack G, Albizu A, Lara-Tejero M, Horvath T, Galán J. Typhoid toxin causes neuropathology by disrupting the blood–brain barrier. Nature Microbiology 2025, 10: 1340-1351. PMID: 40341334, DOI: 10.1038/s41564-025-02000-z.Peer-Reviewed Original ResearchConceptsTyphoid toxinTyphoid feverBlood-brain barrierBlood brain barrier disruption in vivoDisruption in vivoManifestations of typhoid feverVirulence factorsSalmonella typhiCatalytic subunitBlood-brain barrier permeability changesToxin actionLife-threatening complicationsSevere neurological manifestationsTyphoidIn vitro modelToxinNeurological complicationsGlial cellsTherapeutic interventionsFeverToxin exposureVirulenceComplicationsNeuropathologyEncephalopathyAdrenomedullin Enhances Vascular Integrity and Endothelial Cell Maturation in Bioengineered Lung Models
YOON Y, Kirk S, Promnares K, Karki P, Birukov K, Yuan Y. Adrenomedullin Enhances Vascular Integrity and Endothelial Cell Maturation in Bioengineered Lung Models. Physiology 2025, 40: 1257. DOI: 10.1152/physiol.2025.40.s1.1257.Peer-Reviewed Original ResearchVascular barrier functionEndothelial cell maturationShear stressElectric cell impedance sensingCell maturationBarrier functionMicrovascular nicheAngiopoietin-1Single-cell RNA sequencingParacrine signalingVascular modelLung modelEndothelial cell barrier functionVascular integrityEndothelial cell markersCell barrier functionEndothelial cell integrityAdjacent cell typesAnti-inflammatory responseRNA sequencingNative vasculatureCellular phenotypesFluid flowIn vitro modelGene expression
2024
Prolonged intracranial catheter dwell time exacerbates penumbral stress and worsens stroke thrombectomy outcomes
Alawieh A, Elawady S, Zohdy Y, Chalhoub R, Cunningham C, Howard B, Cawley C, Barrow D, Akbik F, Pabaney A, Tong F, Al Kasab S, Jabbour P, Goyal N, Arthur A, Siddiqui F, Yoshimura S, Park M, Brinjikji W, Matouk C, Romano D, Altschul D, Williamson R, Moss M, De Leacy R, Ezzeldin M, Kan P, Levitt M, Grandhi R, Mascitelli J, Grossberg J, Spiotta A. Prolonged intracranial catheter dwell time exacerbates penumbral stress and worsens stroke thrombectomy outcomes. Journal Of NeuroInterventional Surgery 2024, 17: e303-e312. PMID: 39542713, DOI: 10.1136/jnis-2024-022271.Peer-Reviewed Original ResearchSymptomatic intracranial hemorrhageAcute ischemic strokeModified Rankin ScaleMechanical thrombectomyRecanalization successIncreasing SICHDuration of catheter useBlood flowCatheter dwell timeNegative predictors of outcomeAnalysis of patientsMulticenter international registryPropensity scorePredictors of outcomeInternal carotid arteryCerebral artery blood flowMiddle cerebral arteryArtery blood flowIn vitro modelIntracranial hemorrhageCatheter placementCatheter useCaliber catheterProcedure timeAIS patientsMechanical power is maximized during contractile ring-like formation in a biomimetic dividing cell model
Sakamoto R, Murrell M. Mechanical power is maximized during contractile ring-like formation in a biomimetic dividing cell model. Nature Communications 2024, 15: 9731. PMID: 39523366, PMCID: PMC11551154, DOI: 10.1038/s41467-024-53228-y.Peer-Reviewed Original ResearchConceptsMyosin-induced stressContractile ring assemblyCell division mechanismActin filamentsActin cortexCleavage furrowDivision planeActomyosin flowsGiant unilamellar vesiclesRing assemblyCell divisionMyosin activityContractile ring-like structureShape changesRing-like structureDivision mechanismEnergetic costSymmetric divisionActinRing-like formationCell modelUnilamellar vesiclesIn vitro modelFurrowCellsIn silico and in vitro models reveal the molecular mechanisms of hypocontractility caused by TPM1 M8R
Creso J, Gokhan I, Rynkiewicz M, Lehman W, Moore J, Campbell S. In silico and in vitro models reveal the molecular mechanisms of hypocontractility caused by TPM1 M8R. Frontiers In Physiology 2024, 15: 1452509. PMID: 39282088, PMCID: PMC11392859, DOI: 10.3389/fphys.2024.1452509.Peer-Reviewed Original ResearchDilated CardiomyopathyManifestation of dilated cardiomyopathyTropomyosin-actin interactionsIntact cardiac muscleIsometric twitch forceCardiac muscle disordersSevere heart failureHuman engineered heart tissueGenotype-phenotype relationshipsDose-dependent mannerDuration of contractionIn silico predictionIn vitro modelDepressed contractilityMutant tissueCardiac sarcomereLinkage studiesHeart failureTropomyosin chainTwitch contractionsCardiac thin filamentsInherited disorderMuscle disordersMutation pathogenicityCardiac muscleDantrolene corrects cellular disease features of Darier disease and may be a novel treatment
Hunt M, Wang N, Pupinyo N, Curman P, Torres M, Jebril W, Chatzinikolaou M, Lorent J, Silberberg G, Bansal R, Burner T, Zhou J, Kimeswenger S, Hoetzenecker W, Choate K, Bachar-Wikstrom E, Wikstrom J. Dantrolene corrects cellular disease features of Darier disease and may be a novel treatment. EMBO Molecular Medicine 2024, 16: 1986-2001. PMID: 39060641, PMCID: PMC11392931, DOI: 10.1038/s44321-024-00104-3.Peer-Reviewed Original ResearchDarier's diseaseER stressCell adhesionER calcium levelsUpregulation of ER stressInhibited calcium releaseRyanodine receptor antagonistEndoplasmic reticulum calcium homeostasisTarget pathogenic mechanismsFeatures of Darier's diseaseIdentified dysregulated genesMechanisms of DDNon-dermatological indicationsCellular calcium dynamicsCellular functionsER calciumHomeostasis pathwaysATP2A2 geneIn vitro modelReceptor antagonistPumps calciumCalcium releasePromote cell adhesionIsoform 2Suppressed apoptosisA human autoimmune organoid model reveals IL-7 function in coeliac disease
Santos A, van Unen V, Lin Z, Chirieleison S, Ha N, Batish A, Chan J, Cedano J, Zhang E, Mu Q, Guh-Siesel A, Tomaske M, Colburg D, Varma S, Choi S, Christophersen A, Baghdasaryan A, Yost K, Karlsson K, Ha A, Li J, Dai H, Sellers Z, Chang H, Dunn J, Zhang B, Mellins E, Sollid L, Fernandez-Becker N, Davis M, Kuo C. A human autoimmune organoid model reveals IL-7 function in coeliac disease. Nature 2024, 632: 401-410. PMID: 39048815, PMCID: PMC11747932, DOI: 10.1038/s41586-024-07716-2.Peer-Reviewed Original ResearchMeSH KeywordsAutoantibodiesAutoimmunityB-LymphocytesBiopsyCeliac DiseaseDuodenumEpitopesGlutensGTP-Binding ProteinsHLA-DQ AntigensHumansInterleukin-7Intestinal MucosaKiller Cells, NaturalModels, BiologicalMyeloid CellsOrganoidsProtein Glutamine gamma Glutamyltransferase 2Receptors, Antigen, B-CellReceptors, Antigen, T-CellT-LymphocytesConceptsInterleukin-7Major histocompatibility complexT cellsEpithelial destructionNatural killer (NK) cellsCoeliac diseaseTissue-resident immune cellsB cell receptor repertoiresOrganoid modelsModels of autoimmunityAir-liquid interfaceGluten-free dietActive CeDRemission diseaseIn vitro modelImmune microenvironmentEndoscopic biopsyMyeloid subsetsAutoantibody productionMyeloid cellsPatient biopsiesHLA-DQ8Immune cellsAnti-transglutaminasePlasma cellsNS8593 inhibits chondrocyte ferroptosis and alleviates cartilage injury in rat adjuvant arthritis through TRPM7 / HO-1 pathway
Hao W, Zhu R, Zhang H, Chen Y, Li S, Zhou F, Hu W, Zhou R. NS8593 inhibits chondrocyte ferroptosis and alleviates cartilage injury in rat adjuvant arthritis through TRPM7 / HO-1 pathway. The International Journal Of Biochemistry & Cell Biology 2024, 174: 106618. PMID: 39053766, DOI: 10.1016/j.biocel.2024.106618.Peer-Reviewed Original ResearchTransient receptor potential melastatin 7Inhibit TRPM7 channelsHeme oxygenase-1TRPM7 channelsTRPM7 inhibitorRheumatoid arthritisHeme oxygenase-1 pathwayRat adjuvant arthritisExpression of heme oxygenase-1Treatment of RAChondrocyte ferroptosisFerroptosis inducer erastinIn vitro modelCartilage destructionAA ratsNS8593Oxidative stress injuryRestoring redox balanceArticular cartilage damageAdjuvant arthritisPotential novel drugOxygenase-1Restored cell viabilityArticular cartilage destructionReduced cytotoxicityTranscobalamin receptor antibodies in autoimmune vitamin B12 central deficiency
Pluvinage J, Ngo T, Fouassier C, McDonagh M, Holmes B, Bartley C, Kondapavulur S, Hurabielle C, Bodansky A, Pai V, Hinman S, Aslanpour A, Alvarenga B, Zorn K, Zamecnik C, McCann A, Asencor A, Huynh T, Browne W, Tubati A, Haney M, Douglas V, Louine M, Cree B, Hauser S, Seeley W, Baranzini S, Wells J, Spudich S, Farhadian S, Ramachandran P, Gillum L, Hales C, Zikherman J, Anderson M, Yazdany J, Smith B, Nath A, Suh G, Flanagan E, Green A, Green R, Gelfand J, DeRisi J, Pleasure S, Wilson M. Transcobalamin receptor antibodies in autoimmune vitamin B12 central deficiency. Science Translational Medicine 2024, 16: eadl3758. PMID: 38924428, PMCID: PMC11520464, DOI: 10.1126/scitranslmed.adl3758.Peer-Reviewed Original ResearchConceptsBlood-brain barrierCerebrospinal fluidNeurological deficitsAutoimmune neurological conditionsCohort of patientsCellular uptake of cobalaminVitamin B12B12 transportCerebrospinal fluid samplesMeasurement of vitamin B12Low-density lipoprotein receptorProgrammable phage displayImmunosuppressive treatmentIn vitro modelNeuropsychiatric lupusImmunomodulatory treatmentReceptor antibodiesClinical improvementUptake of cobalaminB12 deficiencyUnknown etiologyHematopoietic cellsTranscobalamin receptorCentral deficiencyB12 supplementationA simulacrum of proliferative vitreoretinopathy (PVR): development and proteomics-based validation of an in vitro model
Sharma S, Thakur A, Sharma M, Katoch D, Bansal R, Singh R, Dogra M, Luthra-Guptasarma M. A simulacrum of proliferative vitreoretinopathy (PVR): development and proteomics-based validation of an in vitro model. Journal Of Proteins And Proteomics 2024, 15: 105-118. DOI: 10.1007/s42485-024-00140-0.Peer-Reviewed Original ResearchRetinal pigment epitheliumCell culture-based modelsEpithelial-mesenchymal transitionProliferative vitreoretinopathyCell epithelial-mesenchymal transitionEpiretinal membraneRetinal detachmentCulture-based modelsRetinal pigment epithelium cellsVitreous humorRetinal reattachment surgeryTractional retinal detachmentBlood-retinal barrierAssociated with epithelial-mesenchymal transitionExpression of fibronectinOccurrence of epithelial-mesenchymal transitionTesting of therapeuticsSubretinal fluidReattachment surgeryOcular traumaIn vitro modelPigment epitheliumVision lossDisease progressionExtracellular matrixSingle-cell transcriptomic analysis of human pleura reveals stromal heterogeneity and informs in vitro models of mesothelioma
Obacz J, Valer J, Nibhani R, Adams T, Schupp J, Veale N, Lewis-Wade A, Flint J, Hogan J, Aresu G, Coonar A, Peryt A, Biffi G, Kaminski N, Francies H, Rassl D, Garnett M, Rintoul R, Marciniak S. Single-cell transcriptomic analysis of human pleura reveals stromal heterogeneity and informs in vitro models of mesothelioma. European Respiratory Journal 2024, 63: 2300143. PMID: 38212075, PMCID: PMC10809128, DOI: 10.1183/13993003.00143-2023.Peer-Reviewed Original ResearchConceptsSingle-cell transcriptome atlasSingle-cell levelSingle-cell transcriptome analysisTranscriptome dataTranscriptomic atlasTranscriptomic characterisationMesothelial cellsCell atlasDevelopment of targeted therapiesMalignant mesothelial cellsModel of mesotheliomaUniversal fibroblastsIn vitro model
2023
Nonsense Variant PRDM16-Q187X Causes Impaired Myocardial Development and TGF-β Signaling Resulting in Noncompaction Cardiomyopathy in Humans and Mice
Sun B, Rouzbehani O, Kramer R, Ghosh R, Perelli R, Atkins S, Fatahian A, Davis K, Szulik M, Goodman M, Hathaway M, Chi E, Word T, Tunuguntla H, Denfield S, Wehrens X, Whitehead K, Abdelnasser H, Warren J, Wu M, Franklin S, Boudina S, Landstrom A. Nonsense Variant PRDM16-Q187X Causes Impaired Myocardial Development and TGF-β Signaling Resulting in Noncompaction Cardiomyopathy in Humans and Mice. Circulation Heart Failure 2023, 16: e010351. PMID: 38113297, PMCID: PMC10752244, DOI: 10.1161/circheartfailure.122.010351.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCardiomyopathiesCardiomyopathy, DilatedCell ProliferationCells, CulturedChild, PreschoolDNA-Binding ProteinsFemaleGene Knock-In TechniquesHeart FailureHumansInfant, NewbornIsolated Noncompaction of the Ventricular MyocardiumMaleMiceMyocardiumMyocytes, CardiacSignal TransductionTransforming Growth Factor betaConceptsInduced pluripotent stem cell-derived cardiomyocytesLeft ventricular noncompaction cardiomyopathyPluripotent stem cell-derived cardiomyocytesStem cell-derived cardiomyocytesVentricular noncompaction cardiomyopathyNoncompaction cardiomyopathyCell-derived cardiomyocytesTGF-b signalingMyocardial developmentTGF-bCardiomyopathy developmentTGF-b expressionLoss-of-function variantsKnock-in mouse modelTranscriptional dysregulation of genesStatistically significant impairmentIn vitro modelAge-dependent lossDysregulation of genesMyocyte proliferationVentricular dimensionsHeart failureCardiac maturationCardiomyopathyMouse model
2020
The dynamics of morphogenesis in stem cell-based embryology: Novel insights for symmetry breaking
Sozen B, Cornwall-Scoones J, Zernicka-Goetz M. The dynamics of morphogenesis in stem cell-based embryology: Novel insights for symmetry breaking. Developmental Biology 2020, 474: 82-90. PMID: 33333067, PMCID: PMC8259461, DOI: 10.1016/j.ydbio.2020.12.005.Peer-Reviewed Original ResearchConceptsSignaling gradientsMorphogen signaling gradientsAnteroposterior axis specificationMammalian embryosBody planAxis specificationSymmetry breakingModel of embryogenesisEmbryonic symmetryEmbryonic cellsPatterns in vivoMolecular processesAdult organismBiochemical mechanismsDynamics of morphogenesisEmbryogenesisIn vitro modelEmbryosModel systemIn vitroCritical processCellsMorphogenMorphogenesisStem cells
2012
Accuracy of aortic annular measurements obtained from three-dimensional echocardiography, CT and MRI: human in vitro and in vivo studies
Tsang W, Bateman M, Weinert L, Pellegrini G, Mor-Avi V, Sugeng L, Yeung H, Patel A, Hill A, Iaizzo P, Lang R. Accuracy of aortic annular measurements obtained from three-dimensional echocardiography, CT and MRI: human in vitro and in vivo studies. Heart 2012, 98: 1146. PMID: 22773684, DOI: 10.1136/heartjnl-2012-302074.Peer-Reviewed Original ResearchConceptsCardiac magnetic resonanceMulti-slice CTThree-dimensional echocardiographyIntraclass correlation coefficientAgatston scoreIn vivo studiesAortic valve Agatston scoreCardiac magnetic resonance measurementsCardiac magnetic resonance imagingAortic annular measurementsIn vivo human modelExplanted human heartsHuman heartHuman in vitroIn vivo modelsIn vitro modelAnnular dimensionsAortic annulusCalcium burdenInter-measurement variabilityAnnular measurementsClinical indicationsImaging modalitiesEchocardiographyEx vivo human heartsACCURACY OF AORTIC ANNULI MEASUREMENTS OBTAINED FROM THREE-DIMENSIONAL ECHOCARDIOGRAPHY, COMPUTED TOMOGRAPHY AND MAGNETIC RESONANCE IMAGING USING AN IN VITRO MODEL
Tsang W, Bateman M, Weinert L, Pellegrini G, Mor-Avi V, Sugeng L, Yeung H, Patel A, Hill A, lazzo P, Lang R. ACCURACY OF AORTIC ANNULI MEASUREMENTS OBTAINED FROM THREE-DIMENSIONAL ECHOCARDIOGRAPHY, COMPUTED TOMOGRAPHY AND MAGNETIC RESONANCE IMAGING USING AN IN VITRO MODEL. Journal Of The American College Of Cardiology 2012, 59: e2144. DOI: 10.1016/s0735-1097(12)62145-7.Peer-Reviewed Original ResearchDuration of deep hypothermia during aortic surgery and the risk of perioperative blood transfusion
Mazzeffi M, Marotta M, Lin H, Fischer G. Duration of deep hypothermia during aortic surgery and the risk of perioperative blood transfusion. Annals Of Cardiac Anaesthesia 2012, 15: 266-273. PMID: 23041683, DOI: 10.4103/0971-9784.101855.Peer-Reviewed Original ResearchConceptsHypothermia durationCPB timePerioperative bleedingDeep hypothermiaRBC transfusionAortic surgeryRisk of perioperative blood transfusionDeep hypothermic circulatory arrestAssociated with coagulation abnormalitiesShorter CPB timePerioperative blood transfusionPost-operative bleedingThoracic aortic surgeryAortic surgery patientsHypothermic circulatory arrestThoracic aortic surgery patientsAmount of bleedingDegree of bleedingPerioperative transfusionIn vitro modelPlatelet transfusionsRetrospective reviewCoagulation abnormalitiesBlood transfusionCirculatory arrest
2007
Neuronal and astrocytic cells, obtained after differentiation of human neural GFAP-positive progenitors, present heterogeneous expression of PrPc
Witusik M, Gresner S, Hulas-Bigoszewska K, Krynska B, Azizi S, Liberski P, Brown P, Rieske P. Neuronal and astrocytic cells, obtained after differentiation of human neural GFAP-positive progenitors, present heterogeneous expression of PrPc. Brain Research 2007, 1186: 65-73. PMID: 17996224, DOI: 10.1016/j.brainres.2007.10.039.Peer-Reviewed Original ResearchConceptsProgenitor cellsCharacteristics of stem/progenitor cellsCell differentiationMultiplex PCR assayNeuronal cellsExpression of PrPcExpression of PrP(CCellular isoformGFAP-positive cellsIn vitro modelIn vivo studiesUndifferentiated cell populationsPrion proteinWestern blot analysisStem/progenitor cellsHeterogeneous expressionGlial cellsDifferentiated cellsPhysiological roleCell populationsBlot analysisHuman neurogenesisAstrocytic cellsExpression levelsIn vitro
2001
Relaxin Positively Regulates Matrix Metalloproteinase Expression in Human Lower Uterine Segment Fibroblasts Using a Tyrosine Kinase Signaling Pathway
Palejwala S, Stein D, Weiss G, Monia B, Tortoriello D, Goldsmith L. Relaxin Positively Regulates Matrix Metalloproteinase Expression in Human Lower Uterine Segment Fibroblasts Using a Tyrosine Kinase Signaling Pathway. Endocrinology 2001, 142: 3405-3413. DOI: 10.1210/en.142.8.3405.Peer-Reviewed Original ResearchTissue inhibitor of metalloproteinase-1Matrix metalloproteinase expressionPhorbol-12-myristate-13-acetate-Tissue inhibitorReceptor tyrosine kinase inhibitorsMetalloproteinase-1Protein expressionMatrix metalloproteinasesMetalloproteinase expressionMRNA levelsEffects of relaxinTyrosine kinase inhibitorsCervical connective tissueExpression of matrix metalloproteinasesRegulation of matrix metalloproteinasesTyrosine kinase receptorsSignaling pathwayPreterm deliveryIn vitro modelTyrosine kinase signaling pathwaysKinase inhibitorsRelaxin actionRelaxin receptorKinase Signaling PathwayKinase receptors
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