2025
Interleukin-10 exhibit dose-dependent effects on macrophage phenotypes and cardiac remodeling after myocardial infarction
Zhang J, Rizk R, Li X, Lee B, Matthies M, Bietz K, Kim K, Huard J, Wang Y, Chen W. Interleukin-10 exhibit dose-dependent effects on macrophage phenotypes and cardiac remodeling after myocardial infarction. Frontiers In Physiology 2025, 15: 1481460. PMID: 39882328, PMCID: PMC11774956, DOI: 10.3389/fphys.2024.1481460.Peer-Reviewed Original ResearchIL-10 treatmentIL-10Dose-dependent effectMyocardial infarctionPost-MICardiac remodelingInterleukin-10Lower LV ejection fractionDoses of IL-10LV ejection fractionIL-10 administrationMyocardial gene expressionExogenous IL-10IL-10 secretionEffective dose rangePhenotypic transitionDose-dependent mannerLV fibrosisEjection fractionMouse MI modelCardiac functionCell infiltrationImmunomodulatory cytokinesContractile functionDose-dependently
2024
A safe insect-based chikungunya fever vaccine affords rapid and durable protection in cynomolgus macaques
Adam A, Woolsey C, Lu H, Plante K, Wallace S, Rodriguez L, Shinde D, Cui Y, Franz A, Thangamani S, Comer J, Weaver S, Wang T. A safe insect-based chikungunya fever vaccine affords rapid and durable protection in cynomolgus macaques. Npj Vaccines 2024, 9: 251. PMID: 39702442, PMCID: PMC11659317, DOI: 10.1038/s41541-024-01047-z.Peer-Reviewed Original ResearchMemory B cellsCynomolgus macaquesB cellsDose vaccinationAntigen presenting cell activationReceptor signalingCHIK feverNK cell responsesRobust type I interferonT cell responsesT cell immunityMultiple innate immune pathwaysToll-like receptor signalingWild-typeDose-dependent mannerSkin hypersensitivity reactionsType I interferonInnate immune signalingInnate immune pathwaysT cellsMechanisms of host protectionCHIKV infectionCell activationHypersensitivity reactionsAntibody responseIn 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 muscle1886-LB: Safety, PK, and Preliminary Efficacy of the Liver-Targeted Mitochondrial Protonophore TLC-6740—A Phase 1 Study
GANE E, HUSS R, SUR J, MURAKAMI E, WENG S, KIRBY B, SHAH A, SHULMAN G, SUBRAMANIAN M, VIJAYAKUMAR A, MYERS R. 1886-LB: Safety, PK, and Preliminary Efficacy of the Liver-Targeted Mitochondrial Protonophore TLC-6740—A Phase 1 Study. Diabetes 2024, 73 DOI: 10.2337/db24-1886-lb.Peer-Reviewed Original ResearchTreatment of obesityAdverse eventsSteady-state half-lifeEvaluate food effectsPhase 1 studyDose-dependent improvementDose-dependent reductionProportion of subjectsUnrelated to treatmentDose-dependent mannerMAD cohortsLab abnormalitiesSerum totalLDL-CFood effectHealthy subjectsClinical useWeight lossImpact of foodBody weightPreliminary efficacyObesityHalf-lifeTreatmentMitochondrial uncoupling1734-P: ADP Privation of Human Beta-Cell Mitochondria by Pyruvate Kinase
RUZ-MALDONADO I, CARDONE R, KIBBEY R. 1734-P: ADP Privation of Human Beta-Cell Mitochondria by Pyruvate Kinase. Diabetes 2024, 73 DOI: 10.2337/db24-1734-p.Peer-Reviewed Original ResearchPyruvate kinaseBeta-cell mitochondriaInhibition of OxPhosBeta-cellsHuman beta-cellsModulation of enzymesIntramitochondrial ADPPhosphoenolpyruvate inhibitionADP availabilityADP/ATP exchangeKATP channelsPhosphoenolpyruvate metabolismOxidative phosphorylationPhosphoenolpyruvateMitochondrial functionOXPHOSSubstrate transportComplex IATP/ADP ratioHuman isletsMitochondrial couplingOxygen consumption ratePyruvateMitochondriaDose-dependent mannerLive Imaging to Quantify Cellular Radiosensitivity in Patient-Derived Tumor Organoids.
Charpentier M, Bloy N, Formenti S, Galluzzi L, Demaria S. Live Imaging to Quantify Cellular Radiosensitivity in Patient-Derived Tumor Organoids. Journal Of Visualized Experiments 2024 PMID: 38647326, DOI: 10.3791/66680.Peer-Reviewed Original ResearchConceptsPatient-derived tumor organoidsClonogenic assayRadiation therapyTumor organoidsCancer cellsIrradiated cancer cellsMeasure of radiosensitivityClinical cancer managementNon-irradiated (controlDose-dependent mannerSingle-cell suspensionsMalignant cellsTumor modelCancer managementCellular radiosensitivitySensitive to irradiationComplex tumor modelsOxidative DNA damageRepair oxidative DNA damageCancer typesDelayed mannerIonizing raysSingle-cell dissociationFlow cytometry-Radiosensitivity
2023
Sis2 regulates yeast replicative lifespan in a dose-dependent manner
Ölmez T, Moreno D, Liu P, Johnson Z, McGinnis M, Tu B, Hochstrasser M, Acar M. Sis2 regulates yeast replicative lifespan in a dose-dependent manner. Nature Communications 2023, 14: 7719. PMID: 38012152, PMCID: PMC10682402, DOI: 10.1038/s41467-023-43233-y.Peer-Reviewed Original ResearchConceptsYeast replicative lifespanReplicative lifespanRNA-seq experimentsCoenzyme A biosynthesis pathwayYeast lifespanYeast strainsStrain librariesLifespan regulationRNA-seqGene networksDose-dependent mannerLifespan extensionTranscriptional increaseYeastLifespan measurementsWild-typeGenesMachinery componentsStrainMicrofluidic platformApplications of microfluidic platformsLifespanDeletionCoenzymePathwayMaresin1 prevents sepsis-induced acute liver injury by suppressing NF-κB/Stat3/MAPK pathways, mitigating inflammation
Sun S, Wang L, Wang J, Chen R, Pei S, Yao S, Lin Y, Yao C, Xia H. Maresin1 prevents sepsis-induced acute liver injury by suppressing NF-κB/Stat3/MAPK pathways, mitigating inflammation. Heliyon 2023, 9: e21883. PMID: 38027581, PMCID: PMC10665730, DOI: 10.1016/j.heliyon.2023.e21883.Peer-Reviewed Original ResearchSepsis-induced acute liver injuryAcute liver injuryAnti-inflammatory effectsLiver injuryNeutrophil infiltrationBacterial loadSurvival rateDocosahexaenoic acidNormal saline 1Peritoneal lavage fluidPro-inflammatory moleculesTreatment of sepsisUncontrolled inflammatory responseAnti-inflammatory moleculesSepsis-induced injuryEffects of MaR1Body weight changesSepsis-related diseasesDose-dependent mannerSaline 1Septic miceCecal ligationLavage fluidLiver functionAcute inflammationAdoption of Emergency Department–Initiated Buprenorphine for Patients With Opioid Use Disorder
Gao E, Melnick E, Paek H, Nath B, Taylor R, Loza A. Adoption of Emergency Department–Initiated Buprenorphine for Patients With Opioid Use Disorder. JAMA Network Open 2023, 6: e2342786. PMID: 37948075, PMCID: PMC10638655, DOI: 10.1001/jamanetworkopen.2023.42786.Peer-Reviewed Original ResearchConceptsHealth care systemED initiationOpioid use disorderBuprenorphine initiationCare systemUse disordersEmergency Department-Initiated BuprenorphineSecondary analysisClinician's roleEmergency department initiationClinical decision support interventionClinical decision support toolProportional hazard modelingCare of patientsNetwork of cliniciansDecision support interventionsAdvanced practice practitionersDose-dependent mannerUnique cliniciansTime-dependent covariatesTrial interventionNonintervention groupED clustersMore effective interventionsNumber of exposuresTransforming Growth Factor Beta and Epithelial to Mesenchymal Transition Alter Homologous Recombination Repair Gene Expression and Sensitize BRCA Wild-Type Ovarian Cancer Cells to Olaparib
Roberts C, Rojas-Alexandre M, Hanna R, Lin Z, Ratner E. Transforming Growth Factor Beta and Epithelial to Mesenchymal Transition Alter Homologous Recombination Repair Gene Expression and Sensitize BRCA Wild-Type Ovarian Cancer Cells to Olaparib. Cancers 2023, 15: 3919. PMID: 37568736, PMCID: PMC10417836, DOI: 10.3390/cancers15153919.Peer-Reviewed Original ResearchEpithelial ovarian cancerRepair gene expressionPARP inhibitorsHomologous recombinationGene expressionDNA repair gene expressionCancer cellsLethal gynecologic malignancyDrug-resistant recurrenceDownregulation of genesOvarian cancer cellsGrowth factor betaWild-type cancer cellsDose-dependent mannerDNA repair genesGynecologic malignanciesMesenchymal tumorsOvarian tumorsEpithelial cell lineOvarian cancerMetastatic spreadClinical utilityEOC cellsFunctions of EMTFactor betaThe human milk component myo-inositol promotes neuronal connectivity
Paquette A, Carbone B, Vogel S, Israel E, Maria S, Patil N, Sah S, Chowdhury D, Kondratiuk I, Labhart B, Morrow A, Phillips S, Kuang C, Hondmann D, Pandey N, Biederer T. The human milk component myo-inositol promotes neuronal connectivity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2221413120. PMID: 37433002, PMCID: PMC10374161, DOI: 10.1073/pnas.2221413120.Peer-Reviewed Original ResearchConceptsHuman milkNeuronal connectionsInfant brainBreast milk componentsExcitatory synapse densityCultured rat neuronsMature brain tissueHuman milk samplesAbility of neuronsHuman excitatory neuronsDose-dependent mannerExcitatory postsynaptic sitesSlice culture systemSynapse densityExcitatory neuronsDietary supplementationPostsynaptic sitesRat neuronsNeuronal connectivityOrganotypic slicesBrain tissuePostsynaptic specializationsOrganotypic slice culture systemBrain developmentBrain connectivityAssociation of maternal body mass index with success and outcomes of attempted operative vaginal delivery
Grasch J, Venkatesh K, Grobman W, Silver R, Saade G, Mercer B, Yee L, Scifres C, Parry S, Simhan H, Reddy U, Frey H. Association of maternal body mass index with success and outcomes of attempted operative vaginal delivery. American Journal Of Obstetrics & Gynecology MFM 2023, 5: 101081. PMID: 37422004, DOI: 10.1016/j.ajogmf.2023.101081.Peer-Reviewed Original ResearchConceptsMaternal body mass indexBody mass indexOperative vaginal deliveryVaginal delivery attemptComposite maternal morbidityComposite neonatal morbidityVaginal deliveryMass indexNeonatal morbidityCesarean deliveryMaternal morbidityAdverse outcomesSecond-stage cesarean deliveryBody mass index groupsBody mass index categoriesNulliparous Pregnancy Outcomes StudyNonanomalous singleton pregnanciesNeonatal adverse outcomesMultivariable logistic regressionPregnancy Outcomes StudyNulliparous individualsDose-dependent mannerSecondary outcomesSingleton pregnanciesPrimary outcomeRottlerin-Liposome Inhibits the Endocytosis of Feline Coronavirus Infection
Choi J, Jung S, Choi I, Kang Y, Lee D, Lee S, Park S, Song C, Choi I, Lee J, Oh C. Rottlerin-Liposome Inhibits the Endocytosis of Feline Coronavirus Infection. Veterinary Sciences 2023, 10: 380. PMID: 37368766, PMCID: PMC10302841, DOI: 10.3390/vetsci10060380.Peer-Reviewed Original ResearchFeline infectious peritonitisFeline coronavirus infectionSystemic granulomatous inflammationDose-dependent mannerFCoV replicationGranulomatous inflammationAntiviral effectInfectious peritonitisPotential treatmentFatal diseaseHigh mortalityCoronavirus infectionFeline coronavirusAntiviral propertiesWorth further investigationFurther investigationCellular levelFCoV.Inhibition efficacyPeritonitisInflammationRottlerinLater stagesGenetic variants of glucose metabolism and exposure to smoking in African American breast cancer.
Jung S, Papp J, Sobel E, Pellegrini M, Yu H. Genetic variants of glucose metabolism and exposure to smoking in African American breast cancer. Endocrine Related Cancer 2023, 30 PMID: 36705562, PMCID: PMC10095926, DOI: 10.1530/erc-22-0184.Peer-Reviewed Original ResearchConceptsInsulin resistanceBC riskLifestyle factorsSingle nucleotide polymorphismsAA womenRisk genotypesAfrican American postmenopausal womenAfrican-American breast cancerRisk of BCBreast cancer developmentDose-dependent mannerPostmenopausal womenPositive BCPredictive markerRisk factorsFemale hormonesBreast cancerGlucose metabolismMetabolic biomarkersGene-environment interaction analysisSmokingPreventive interventionsCancer developmentWhite womenIndividual single nucleotide polymorphismsPTEN phosphatase inhibits metastasis by negatively regulating the Entpd5/IGF1R pathway through ATF6
Yu Y, Dai M, Huang L, Chen W, Yu E, Mendoza A, Michael H, Khanna C, Bosenberg M, McMahon M, Merlino G. PTEN phosphatase inhibits metastasis by negatively regulating the Entpd5/IGF1R pathway through ATF6. IScience 2023, 26: 106070. PMID: 36824269, PMCID: PMC9942123, DOI: 10.1016/j.isci.2023.106070.Peer-Reviewed Original ResearchProtein phosphatase activityPhosphatase activityPTEN protein phosphatase activityER stress sensor ATF6ER stressPTEN phosphatase activityPTEN expressionMelanoma cell invasivenessNovel candidate therapeutic targetInhibits metastasisIGF1R pathwayIGF1R levelsHuman melanoma samplesTumor suppressorCandidate therapeutic targetCell invasivenessATF6Melanoma samplesMetastatic progressionTherapeutic targetExpressionDose-dependent mannerPathwayMouse melanoma modelMutant melanoma
2022
Conjugation of Listeriolysin O to Anti-CD47 mAb: Harnessing Listeria Toxin to Weaponize Macrophages against Tumor Cells
Schrank B, Wang Y, Jiang W. Conjugation of Listeriolysin O to Anti-CD47 mAb: Harnessing Listeria Toxin to Weaponize Macrophages against Tumor Cells. International Journal Of Radiation Oncology • Biology • Physics 2022, 114: s42. DOI: 10.1016/j.ijrobp.2022.07.408.Peer-Reviewed Original ResearchAnti-CD47 mAbBone marrow-derived macrophagesTumor cell phagocytosisMarrow-derived macrophagesAntigen presentationTumor cellsIntratumoral injectionWildtype miceCGAS-STING activationCell phagocytosisNon-Hodgkin's lymphomaCell line MDA-MB-468Hematopoietic tumor cellsMonocytic cell line THP-1Treatment of malignanciesMouse bone marrow-derived macrophagesBreast cancer cell line MDA-MB-468Cell line THP-1Suppressed tumor growthListeriolysin O toxinMacrophage-mediated phagocytosisBlood cell countHuman breast cancer cell line MDA-MB-468Dose-dependent mannerListeriolysin OKetone body augmentation decreases methacholine hyperresponsiveness in mouse models of allergic asthma
Mank M, Reed L, Fastiggi V, Peña-García P, Hoyt L, Van Der Vliet K, Ather J, Poynter M. Ketone body augmentation decreases methacholine hyperresponsiveness in mouse models of allergic asthma. Journal Of Allergy And Clinical Immunology Global 2022, 1: 282-298. PMID: 36466740, PMCID: PMC9718535, DOI: 10.1016/j.jacig.2022.08.001.Peer-Reviewed Original ResearchKetone ester supplementationMethacholine hyperresponsivenessAllergic asthmaAirway epithelial cellsKetogenic dietDose-dependent mannerKetone bodiesMouse modelElicit anti-inflammatory activityAllergic asthmatic individualsBronchial smooth muscle cellsChronic allergic asthmaHuman airway epithelial cellsEpithelial cellsProinflammatory cytokine secretionIL-8 secretionAnti-inflammatory activityBHB concentrationsSmooth muscle cellsKetone body precursorsRange of mildHDM sensitizationObese asthmaCell typesCorticosteroid treatmentNicotine dose-dependent epigenomic-wide DNA methylation changes in the mice with long-term electronic cigarette exposure.
Peng G, Xi Y, Bellini C, Pham K, Zhuang ZW, Yan Q, Jia M, Wang G, Lu L, Tang MS, Zhao H, Wang H. Nicotine dose-dependent epigenomic-wide DNA methylation changes in the mice with long-term electronic cigarette exposure. American Journal Of Cancer Research 2022, 12: 3679-3692. PMID: 36119846, PMCID: PMC9442002.Peer-Reviewed Original ResearchElectronic cigarette exposureCigarette exposureMale ApoE-/- miceApoE-/- miceCytokine mRNA expressionPoor health outcomesWhite blood cellsElectronic cigarette useDose-dependent mannerE-cigarette aerosolAerosol inhalationCigarette smokingActivation of MAPKHigher nicotine concentrationsMAPK pathway activationCell-damaging effectsCpG sitesHealth outcomesCigarette useMRNA expressionNicotine concentrationsPathway activationSignificant CpG sitesBlood cellsSignificant alterationsO-306 LINZAGOLIX FOR ENDOMETRIOSIS-ASSOCIATED PAIN: SAFETY RESULTS FROM EDELWEISS 3, A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL
Donnez J, Taylor H, Gemzell-Danielsson K, Catherino W, Bestel E, Gotteland J, Humberstone A, Moore L, Garner E. O-306 LINZAGOLIX FOR ENDOMETRIOSIS-ASSOCIATED PAIN: SAFETY RESULTS FROM EDELWEISS 3, A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL. Human Reproduction 2022, 37: deac105.103. DOI: 10.1093/humrep/deac105.103.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsEndometriosis-associated painSevere endometriosis-associated painBone mineral densityMonths of treatmentSafety resultsPlacebo groupTreatment armsSerious treatment-emergent adverse eventsLumbar spine bone mineral densityZ-scoreLS bone mineral densityMulticenter phase 3 trialSpine bone mineral densityEmergent adverse eventsPhase 3 trialActive treatment armsReproductive-aged womenGnRH receptor antagonistTRIAL REGISTRATION NUMBERMean percent changePARTICIPANTS/MATERIALSROLE OF CHANCEDose-dependent mannerAdverse eventsTopical phenytoin administration accelerates the healing of acetic acid-induced colitis in rats: evaluation of transforming growth factor-beta, platelet-derived growth factor, and vascular endothelial growth factor
Fattahi N, Abdolahi A, Vahabzadeh Z, Nikkhoo B, Manoochehri F, Goudarzzadeh S, Hassanzadeh K, Izadpanah E, Moloudi M. Topical phenytoin administration accelerates the healing of acetic acid-induced colitis in rats: evaluation of transforming growth factor-beta, platelet-derived growth factor, and vascular endothelial growth factor. Inflammopharmacology 2022, 30: 283-290. PMID: 35022915, DOI: 10.1007/s10787-021-00885-w.Peer-Reviewed Original ResearchConceptsVascular endothelial growth factorPhenytoin 1%Platelet-derived growth factorEndothelial growth factorBody weight lossGrowth factor-betaGrowth factorUlcerative colitisPhenytoin administrationMicroscopic scoresUlcer indexFactor-betaTreatment protocolsTransforming growth factor-betaWeight lossEighty male Wistar ratsAccelerated ulcer healingMale Wistar ratsDose-dependent mannerGroups of shamTime-dependent mannerAcetic acid-induced colitisGlobal health problemPhenytoin doseEnema treatment
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