2025
Notch1 Signalling Is Downregulated by Aerobic Exercise, Leading to Improvement of Hepatic Metabolism in Obese Mice
Gaspar R, Macêdo A, Nakandakari S, Muñoz V, Abud G, Vieira R, de Sousa Neto I, Pavan I, da Silva L, Simabuco F, da Silva A, Salgado W, Marchini J, Nonino C, Cintra D, Ropelle E, Pajvani U, de Freitas E, Pauli J. Notch1 Signalling Is Downregulated by Aerobic Exercise, Leading to Improvement of Hepatic Metabolism in Obese Mice. Liver International 2025, 45: e70068. PMID: 40078075, DOI: 10.1111/liv.70068.Peer-Reviewed Original ResearchConceptsNotch1 signalingAerobic exerciseRegulation of hepatic glucoseObese miceImpact of aerobic exerciseEffects of Notch1 signalingAerobic exercise trainingMTORC1 pathway activationNotch1 pathwayObese individualsTissue of obese miceCross-sectional studyNotch1 mRNA levelsMitochondrial respirationExercise trainingLivers of obese individualsTreadmill runningGluconeogenic enzymesHepG2 cell lineLipid accumulationTraining groupHepatic glucoseHepatic metabolismNotch1 proteinPathway activationTime-restricted feeding reduces inflammatory markers and downregulates JAG1 and NICD protein levels in the liver of aged mice
Macêdo A, de Sousa Neto I, Antonio G, Gaspar R, de Lima R, Dias L, Vieira R, Muñoz V, Brunelli D, da Silva A, Cintra D, Ropelle E, Pauli J. Time-restricted feeding reduces inflammatory markers and downregulates JAG1 and NICD protein levels in the liver of aged mice. Nutrition 2025, 133: 112691. PMID: 39983606, DOI: 10.1016/j.nut.2025.112691.Peer-Reviewed Original ResearchConceptsRNA-seq datasetsNotch1 intracellular domainMitochondrial respirationTime-restricted feedingAged miceInflammatory markersAd libitum dietIntracellular domainHepatic mitochondrial respirationATP productionLiver mitochondrial respirationCellular longevityLiver of aged miceLibitum dietDisease Activity ScoreCompared to adult animalsNotch1 signalingProtein contentTime-restricted feeding protocolsUpregulation of Notch1Investigated metabolic parametersProtein levelsNotch1Adult miceCollagen fibers
2024
Downregulation of adipose LPL by PAR2 contributes to the development of hypertriglyceridemia
Huang Y, Chen L, Li L, Qi Y, Tong H, Wu H, Xu J, Leng L, Cheema S, Sun G, Xia Z, McGuire J, Rodrigues B, Young L, Bucala R, Qi D. Downregulation of adipose LPL by PAR2 contributes to the development of hypertriglyceridemia. JCI Insight 2024, 9: e173240. PMID: 38973609, PMCID: PMC11383372, DOI: 10.1172/jci.insight.173240.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorDevelopment of hypertriglyceridemiaWhite adipose tissueAdipose LPLPAR2 expressionLevels of macrophage migration inhibitory factorElevated plasma TG levelsLPL expressionLipoprotein lipaseIncrease PAR2 expressionPlasma MIF levelsPlasma TG levelsMigration inhibitory factorPalmitic acid dietInhibited Akt phosphorylationMIF levelsLipoprotein lipase geneTG levelsObese humansPlasma TGHypertriglyceridemiaAkt phosphorylationLipid storageInhibitory factorAdipose tissueCBLs downregulation foretells T cell ubiquitination leading to autoimmunity
Vidyarthi A, Craft J. CBLs downregulation foretells T cell ubiquitination leading to autoimmunity. Cell Chemical Biology 2024, 31: 1239-1241. PMID: 39029453, DOI: 10.1016/j.chembiol.2024.06.010.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAutoimmunityDown-RegulationHumansProto-Oncogene Proteins c-cblT-LymphocytesUbiquitinationHeterogeneous gene expression during early arteriovenous fistula remodeling suggests that downregulation of metabolism predicts adaptive venous remodeling
Ohashi Y, Protack C, Aoyagi Y, Gonzalez L, Thaxton C, Zhang W, Kano M, Bai H, Yatsula B, Alves R, Hoshina K, Schneider E, Long X, Perry R, Dardik A. Heterogeneous gene expression during early arteriovenous fistula remodeling suggests that downregulation of metabolism predicts adaptive venous remodeling. Scientific Reports 2024, 14: 13287. PMID: 38858395, PMCID: PMC11164895, DOI: 10.1038/s41598-024-64075-8.Peer-Reviewed Original ResearchConceptsGene expression patternsArteriovenous fistula groupArteriovenous fistulaExpression patternsHeterogeneous gene expressionGene expression changesOutcomes of arteriovenous fistulaVenous remodelingArteriovenous fistula maturationPostoperative day 7Reduce patient morbidityRNA sequencingUpregulation of metabolismBioinformatics analysisGene expressionDownregulation of metabolismMetabolic pathwaysExpression changesGenesAVF maturationAVF remodelingFistula creationC57BL/6 miceClinical outcomesPatient morbidity
2023
Differential outcomes of high‐fat diet on age‐related rescaling of cochlear frequency place coding
Zhang Y, Lin G, Xue N, Wang Y, Du T, Liu H, Xiong W, Shang W, Wu H, Song L. Differential outcomes of high‐fat diet on age‐related rescaling of cochlear frequency place coding. The FASEB Journal 2023, 37: e23167. PMID: 37651093, DOI: 10.1096/fj.202300457rr.Peer-Reviewed Original ResearchConceptsAge-related hearing lossHigh-fat dietHearing lossEffects of HFDLoss of OHCsActivation of TRPV1Sensorineural hearing lossCBA/CaJPlace codingCochlear frequency selectivityTRPV1 expressionOHC functionInflammatory responseCommon causeHFD cohortGenetic backgroundYounger ageArachidonic acidCochlear lengthHair cellsPrestin levelsLipid homeostasisRescuing effectCochlear amplificationAgeExportin 1 inhibition prevents neuroendocrine transformation through SOX2 down-regulation in lung and prostate cancers
Quintanal-Villalonga A, Durani V, Sabet A, Redin E, Kawasaki K, Shafer M, Karthaus W, Zaidi S, Zhan Y, Manoj P, Sridhar H, Shah N, Chow A, Bhanot U, Linkov I, Asher M, Yu H, Qiu J, de Stanchina E, Patel R, Morrissey C, Haffner M, Koche R, Sawyers C, Rudin C. Exportin 1 inhibition prevents neuroendocrine transformation through SOX2 down-regulation in lung and prostate cancers. Science Translational Medicine 2023, 15: eadf7006. PMID: 37531417, PMCID: PMC10777207, DOI: 10.1126/scitranslmed.adf7006.Peer-Reviewed Original ResearchConceptsPatient-derived xenograftsProstatic adenocarcinomaNE transformationXenograft modelExportin 1Associated with poor prognosisProstate adenocarcinoma cell lineInactivation of TP53Adenocarcinoma xenograft modelEctopic SOX2 expressionEGFR inhibitor osimertinibAdenocarcinoma cell lineNE phenotypeNeuroendocrine transformationSelinexor treatmentStandard cytotoxicsProstate cancerLineage plasticityPotential therapeutic targetNE featuresPoor prognosisProstateSOX2 expressionAdenocarcinomaLungAmygdala downregulation training using fMRI neurofeedback in post-traumatic stress disorder: a randomized, double-blind trial
Zhao Z, Duek O, Seidemann R, Gordon C, Walsh C, Romaker E, Koller W, Horvath M, Awasthi J, Wang Y, O’Brien E, Fichtenholtz H, Hampson M, Harpaz-Rotem I. Amygdala downregulation training using fMRI neurofeedback in post-traumatic stress disorder: a randomized, double-blind trial. Translational Psychiatry 2023, 13: 177. PMID: 37230984, PMCID: PMC10209552, DOI: 10.1038/s41398-023-02467-6.Peer-Reviewed Original ResearchMeSH KeywordsAmygdalaDown-RegulationHumansMagnetic Resonance ImagingNeurofeedbackStress Disorders, Post-TraumaticConceptsPost-traumatic stress disorderControl groupAmygdala activityPTSD treatmentDouble-blind clinical trialStress disorderDouble-blind trialSecondary outcome measurementsTrauma recallNeurofeedback trainingGreater improvementAmygdala controlsPotential clinical applicationsSymptom scoresActive groupClinical trialsTreatment successOutcome measurementsTrauma scriptsSymptom reductionNeurofeedback interventionPTSD symptomsFMRI neurofeedbackAmygdalaNeural markersTemsavir blocks the immunomodulatory activities of HIV-1 soluble gp120
Richard J, Prévost J, Bourassa C, Brassard N, Boutin M, Benlarbi M, Goyette G, Medjahed H, Gendron-Lepage G, Gaudette F, Chen H, Tolbert W, Smith A, Pazgier M, Dubé M, Clark A, Mothes W, Kaufmann D, Finzi A. Temsavir blocks the immunomodulatory activities of HIV-1 soluble gp120. Cell Chemical Biology 2023, 30: 540-552.e6. PMID: 36958337, PMCID: PMC10198848, DOI: 10.1016/j.chembiol.2023.03.003.Peer-Reviewed Original ResearchConceptsAntibody-dependent cellular cytotoxicityUninfected bystander CD4Gp120-CD4 interactionCytokine burstBystander CD4Immunomodulatory activityMultiple immune cellsHIV-1 attachment inhibitorsOverall antigenicityADCC responsesClinical benefitSoluble gp120Immune cellsCellular cytotoxicityAttachment inhibitorsCD4 interactionGp120 bindsCD4Gp120Viral entryEnvelope glycoproteinCD4 downregulationTemsavirCellsAntigenicityDownregulation of a tumor suppressor gene LKB1 in lung transplantation as a biomarker for chronic murine lung allograft rejection
Rahman M, Ravichandran R, Sankpal N, Bansal S, Sureshbabu A, Fleming T, Perincheri S, Bharat A, Smith M, Bremner R, Mohanakumar T. Downregulation of a tumor suppressor gene LKB1 in lung transplantation as a biomarker for chronic murine lung allograft rejection. Cellular Immunology 2023, 386: 104690. PMID: 36812767, PMCID: PMC11019891, DOI: 10.1016/j.cellimm.2023.104690.Peer-Reviewed Original ResearchConceptsLung allograft rejectionLung transplantationAllograft rejectionChronic lung allograft rejectionBronchiolitis obliterans syndromeLung transplant recipientsTumor suppressor gene LKB1Phosphorylated mammalian targetBEAS-2B cellsObliterans syndromeChronic rejectionTransplant recipientsDonor lungsSingle lungB6D2F1 miceMurine modelDBA/2J miceMTOR expressionMammalian targetLKB1 overexpressionSignificant downregulationLungLKB1 knockdownA549 cellsLKB1 activity
2022
Downregulation of Sirt6 by CD38 promotes cell senescence and aging
Zhou H, Liu S, Zhang N, Fang K, Zong J, An Y, Chang X. Downregulation of Sirt6 by CD38 promotes cell senescence and aging. Aging 2022, 14: 9730-9757. PMID: 36490326, PMCID: PMC9792202, DOI: 10.18632/aging.204425.Peer-Reviewed Original ResearchConceptsCD38 expressionSIRT6 expressionC3GCD38 siRNACell senescenceIncreased SIRT6 expressionMechanism of CD38H9c2 cellsInduced to senescenceTelomerase reverse transcriptase levelsReverse transcriptase levelsNK cell levelsPresence of C3GNicotinamide adenine dinucleotidePromote cell senescenceReduced reactive oxygen speciesTNF-a levelsDecreased SIRT6 expressionReactive oxygen speciesD-gal induced senescenceHexokinase 2OSS-128167Myocardial H9c2 cellsStimulate cell proliferationSiRNADownregulation of hepatic ceruloplasmin ameliorates NAFLD via SCO1-AMPK-LKB1 complex
Xie L, Yuan Y, Xu S, Lu S, Gu J, Wang Y, Wang Y, Zhang X, Chen S, Li J, Lu J, Sun H, Hu R, Piao H, Wang W, Wang C, Wang J, Li N, White M, Han L, Jia W, Miao J, Liu J. Downregulation of hepatic ceruloplasmin ameliorates NAFLD via SCO1-AMPK-LKB1 complex. Cell Reports 2022, 41: 111498. PMID: 36261001, PMCID: PMC10153649, DOI: 10.1016/j.celrep.2022.111498.Peer-Reviewed Original ResearchConceptsNon-alcoholic fatty liver diseaseFatty liver diseaseLipid metabolism diseasesLipid catabolismHepatic lipid catabolismFatty acid oxidationDetectable hepatotoxicityCopper deficiencyNAFLD developmentLiver diseaseMetabolic diseasesMetabolism diseasesNormal levelsDiseaseMitochondrial biogenesisAcid oxidationAMPK activityAMPKAblationDeficiencyCatabolismLKB1HepatotoxicityFluid shear stress enhances proliferation of breast cancer cells via downregulation of the c-subunit of the F1FO ATP synthase
Park HA, Brown SR, Jansen J, Dunn T, Scott M, Mnatsakanyan N, Jonas EA, Kim Y. Fluid shear stress enhances proliferation of breast cancer cells via downregulation of the c-subunit of the F1FO ATP synthase. Biochemical And Biophysical Research Communications 2022, 632: 173-180. PMID: 36209586, PMCID: PMC10024463, DOI: 10.1016/j.bbrc.2022.09.084.Peer-Reviewed Original ResearchN-nitrosamines-mediated downregulation of LncRNA-UCA1 induces carcinogenesis of esophageal squamous by regulating the alternative splicing of FGFR2
Wang X, Sun M, Gao Z, Yin L, Pu Y, Zhu Y, Wang X, Liu R. N-nitrosamines-mediated downregulation of LncRNA-UCA1 induces carcinogenesis of esophageal squamous by regulating the alternative splicing of FGFR2. The Science Of The Total Environment 2022, 855: 158918. PMID: 36169023, DOI: 10.1016/j.scitotenv.2022.158918.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingCarcinogenesisCell Line, TumorCell MovementCell ProliferationDown-RegulationEpigenesis, GeneticEsophageal NeoplasmsEsophageal Squamous Cell CarcinomaGene Expression Regulation, NeoplasticHeterogeneous-Nuclear Ribonucleoprotein Group F-HHumansMicroRNAsNitrosaminesPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReceptor, Fibroblast Growth Factor, Type 2RNA, Long NoncodingConceptsFibroblast growth factor receptor 2Alternative splicingEsophageal squamous cell carcinomaExact molecular mechanismsHet-1A cellsDownregulation of UCA1Epithelial-mesenchymal transitionPI3K-AKT axisFGFR2-IIIcMolecular mechanismsPI3K-AktF proteinUnknown mechanismESCC cellsESCC progressionSplicingN-nitrosamine exposureGrowth factor receptor 2Squamous cell carcinomaDigestive system tumorsRegulation levelESCC tissuesFactor receptor 2High incidence areaLncRNA UCA1Downregulation of SATB1 by miRNAs reduces megakaryocyte/erythroid progenitor expansion in preclinical models of Diamond–Blackfan anemia
Wilkes MC, Scanlon V, Shibuya A, Cepika AM, Eskin A, Chen Z, Narla A, Glader B, Roncarolo MG, Nelson SF, Sakamoto KM. Downregulation of SATB1 by miRNAs reduces megakaryocyte/erythroid progenitor expansion in preclinical models of Diamond–Blackfan anemia. Experimental Hematology 2022, 111: 66-78. PMID: 35460833, PMCID: PMC9255422, DOI: 10.1016/j.exphem.2022.04.005.Peer-Reviewed Original ResearchConceptsMegakaryocyte/erythroid progenitorsDiamond-Blackfan anemiaRibosomal proteinsPathogenesis of DBAErythroid progenitorsHuman hematopoietic stemInherited bone marrow failure syndromeChromatin regulatorsRibosomal insufficiencyErythroid differentiationProgenitor expansionBone marrow failure syndromesCancer predispositionHematopoietic stemMiR-30MiR-34Molecular pathwaysMegakaryocyte expansionMarrow failure syndromesNormal erythropoiesisProgenitor cellsCoordinated actionSATB1ProgenitorsDifferentiationDownregulation of MEIS1 mediated by ELFN1-AS1/EZH2/DNMT3a axis promotes tumorigenesis and oxaliplatin resistance in colorectal cancer
Li Y, Gan Y, Liu J, Li J, Zhou Z, Tian R, Sun R, Liu J, Xiao Q, Li Y, Lu P, Peng Y, Peng Y, Shu G, Yin G. Downregulation of MEIS1 mediated by ELFN1-AS1/EZH2/DNMT3a axis promotes tumorigenesis and oxaliplatin resistance in colorectal cancer. Signal Transduction And Targeted Therapy 2022, 7: 87. PMID: 35351858, PMCID: PMC8964798, DOI: 10.1038/s41392-022-00902-6.Peer-Reviewed Original ResearchConceptsOxaliplatin resistanceColorectal cancerTumor growthMEIS1 expressionCell sensitivity to oxaliplatinPreventing DNA damage repairCombination of oxaliplatinSurvival of CRC patientsTreatment of colorectal cancerSensitivity to oxaliplatinEZH2 inhibitor GSK126Suppressed tumor growthReverse oxaliplatin resistanceFrontline treatmentAcquired resistanceCRC patientsInhibitor GSK126OxaliplatinFEN1 expressionTherapeutic strategiesDNA damage repairELFN1-AS1Cell survivalMeis1PatientsCaloric restriction in humans reveals immunometabolic regulators of health span
Spadaro O, Youm Y, Shchukina I, Ryu S, Sidorov S, Ravussin A, Nguyen K, Aladyeva E, Predeus AN, Smith SR, Ravussin E, Galban C, Artyomov MN, Dixit VD. Caloric restriction in humans reveals immunometabolic regulators of health span. Science 2022, 375: 671-677. PMID: 35143297, PMCID: PMC10061495, DOI: 10.1126/science.abg7292.Peer-Reviewed Original ResearchMeSH Keywords1-Alkyl-2-acetylglycerophosphocholine EsteraseAdipose TissueAdultAgingAnimalsCaloric RestrictionDown-RegulationEnergy MetabolismFemaleHumansImmune SystemInflammasomesInflammationLongevityLymphopoiesisMacrophagesMaleMiceMiddle AgedMitochondriaNLR Family, Pyrin Domain-Containing 3 ProteinThermogenesisThymus GlandTranscriptomeConceptsCaloric restrictionAge-related inflammationHealth spanAnti-inflammatory responseNLRP3 inflammasome activationEctopic lipidsMetabolic healthInflammasome activationHealthy humansAdipose tissueImmunometabolic effectsFactor acetyl hydrolaseImmune defenseInflammationAcetyl hydrolaseMitochondrial bioenergeticsHumansLife spanLipoatrophyPLA2G7ThymopoiesisMiceOxidative stress induces inflammation of lens cells and triggers immune surveillance of ocular tissues
Thompson B, Davidson EA, Chen Y, Orlicky DJ, Thompson DC, Vasiliou V. Oxidative stress induces inflammation of lens cells and triggers immune surveillance of ocular tissues. Chemico-Biological Interactions 2022, 355: 109804. PMID: 35123994, PMCID: PMC9136680, DOI: 10.1016/j.cbi.2022.109804.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcysteineAnimalsButhionine SulfoximineCell LineChemokine CCL7CytokinesDown-RegulationEpithelial CellsEpithelial-Mesenchymal TransitionEyeGlutamate-Cysteine LigaseImmunity, InnateLens, CrystallineLeukocytesMiceMice, Inbred C57BLMice, KnockoutOxidative StressReactive Oxygen SpeciesUp-RegulationConceptsPosterior capsule opacificationCytokine expressionKO miceImmune surveillanceOxidative stressLens epithelial cellsOcular structuresLens cellsDevelopment of PCOEpithelial cellsInnate immune cellsExpression of cytokinesEx vivo inductionOcular surface tissuesExpression of markersImmune response genesCON miceControl miceCapsule opacificationImmune cellsPostnatal dayΑ-SMAMouse modelOcular tissuesVivo induction
2021
Distinct roles of KLF4 in mesenchymal cell subtypes during lung fibrogenesis
Chandran RR, Xie Y, Gallardo-Vara E, Adams T, Garcia-Milian R, Kabir I, Sheikh AQ, Kaminski N, Martin KA, Herzog EL, Greif DM. Distinct roles of KLF4 in mesenchymal cell subtypes during lung fibrogenesis. Nature Communications 2021, 12: 7179. PMID: 34893592, PMCID: PMC8664937, DOI: 10.1038/s41467-021-27499-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell ProliferationDisease Models, AnimalDown-RegulationExtracellular MatrixFemaleFibroblastsFibrosisHumansKruppel-Like Factor 4LungLung InjuryMaleMesenchymal Stem CellsMiceMice, Inbred C57BLMyofibroblastsReceptor, Platelet-Derived Growth Factor betaRespiratory Tract DiseasesSignal TransductionTransforming Growth Factor betaConceptsMesenchymal cell typesPlatelet-derived growth factor receptorSmooth muscle actinLung fibrosisKruppel-like factor 4Forkhead box M1Growth factor receptorCell transitionCell typesExtracellular matrixDistinct rolesKLF4Box M1C chemokine ligandMesenchymal cell subtypesFactor receptorPro-fibrotic effectsFactor 4PDGFRMesenchymeCellsMacrophage accumulationKLF4 levelsChemokine ligandLung fibrogenesisPossible role of intravenous administration of mesenchymal stem cells to alleviate interstitial cystitis/bladder pain syndrome in a Toll-like receptor-7 agonist-induced experimental animal model in rat
Tabata H, Sasaki M, Kataoka-Sasaki Y, Shinkai N, Ichihara K, Masumori N, Kocsis JD, Honmou O. Possible role of intravenous administration of mesenchymal stem cells to alleviate interstitial cystitis/bladder pain syndrome in a Toll-like receptor-7 agonist-induced experimental animal model in rat. BMC Urology 2021, 21: 156. PMID: 34774029, PMCID: PMC8590770, DOI: 10.1186/s12894-021-00923-3.Peer-Reviewed Original ResearchConceptsHunner-type ICBladder pain syndromeAnti-inflammatory pathwayMSC groupMesenchymal stem cellsPain syndromeAnimal modelsToll-like receptor 7 agonistTherapeutic efficacyBehavior testsRight external jugular veinFemale Sprague-Dawley ratsGFP-positive mesenchymal stem cellsReceptor 7 agonistChronic pelvic painAnti-inflammatory effectsEfficacious treatment optionExperimental animal modelsSprague-Dawley ratsExternal jugular veinReal-time polymerase chain reactionMRNA expression levelsPositive mesenchymal stem cellsStem cellsHunner lesions
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