2024
Phase 2A Proof-of-Concept Double-Blind, Randomized, Placebo-Controlled Trial of Nicotinamide in Early Alzheimer Disease
Grill J, Tam S, Thai G, Vides B, Pierce A, Green K, Gillen D, Teng E, Kremen S, Beigi M, Rissman R, Léger G, Balasubramanian A, Revta C, Morrison R, Jennings R, Pa J, Zhang J, Jin S, Messer K, Feldman H. Phase 2A Proof-of-Concept Double-Blind, Randomized, Placebo-Controlled Trial of Nicotinamide in Early Alzheimer Disease. Neurology 2024, 104: e210152. PMID: 39671543, PMCID: PMC11655133, DOI: 10.1212/wnl.0000000000210152.Peer-Reviewed Original ResearchConceptsTau phosphorylationP-tau<sub>181</sub>Histone deacetylasesCDR-SBAlzheimer's diseaseCSF p-tauPrimary outcomeP-tauDiagnosis of mild cognitive impairmentAlzheimer's Disease Assessment ScaleAlzheimer's Disease Cooperative Study-ActivitiesClass III histone deacetylasePrespecified secondary outcomesCellular oxidation-reduction reactionsDisease Assessment ScaleLevels of tauAD biomarkersHolm-Bonferroni procedureMild cognitive impairmentControl type I errorThreonine 231Histone deacetylase inhibitionAcademic clinical centersAssessment ScaleAdverse eventsEpigenetics-targeted drugs: current paradigms and future challenges
Dai W, Qiao X, Fang Y, Guo R, Bai P, Liu S, Li T, Jiang Y, Wei S, Na Z, Xiao X, Li D. Epigenetics-targeted drugs: current paradigms and future challenges. Signal Transduction And Targeted Therapy 2024, 9: 332. PMID: 39592582, PMCID: PMC11627502, DOI: 10.1038/s41392-024-02039-0.Peer-Reviewed Original ResearchConceptsNon-coding RNA regulationDNA base sequenceRNA modificationsRNA regulationChromatin remodelingHistone modificationsEnhancer of zeste homolog 2Epigenetic landscapeGenetic informationOrganismal developmentDNA methyltransferasesEpigenetic enzymesDNA modificationsBase sequenceHomolog 2Zeste homolog 2Histone deacetylasesHuman diseasesIsocitrate dehydrogenaseDNAPathological contextsRegulatory systemChromatinEnzymeHistoneMechanism of Hyperactive PLCγ1 Signaling in T-Cell Leukemia/Lymphoma
Zeng L, Zhang X, Xiong Y, Hajicek N, Sondek J, Su X. Mechanism of Hyperactive PLCγ1 Signaling in T-Cell Leukemia/Lymphoma. Blood 2024, 144: 48-48. DOI: 10.1182/blood-2024-193065.Peer-Reviewed Original ResearchHDACi resistancePeripheral T-cell lymphomaCutaneous T-cell lymphomaAdult T-cell leukemia/lymphomaLiquid-liquid phase separationT-cell lymphomaT-cell leukemia/lymphomaT cell proliferationHistone deacetylasesTotal internal reflection fluorescenceT cellsTCR signalingDrug resistanceDysregulation of LLPSWild typeMolecular mechanismsAberrant protein aggregationInhibitor resistanceResistance to HDAC inhibitorsMemory T cell developmentT cell receptor signalingActivation of T cellsPromote T cell proliferationT-cell malignanciesBcl-2 expression
2023
A study of using epigenetic modulators to enhance response to pembrolizumab (MK-3475) in microsatellite stable advanced colorectal cancer
Baretti M, Murphy A, Zahurak M, Gianino N, Parkinson R, Walker R, Lopez-Vidal T, Zheng L, Rosner G, Ahuja N, Kurt S, Azad N. A study of using epigenetic modulators to enhance response to pembrolizumab (MK-3475) in microsatellite stable advanced colorectal cancer. Clinical Epigenetics 2023, 15: 74. PMID: 37120591, PMCID: PMC10149019, DOI: 10.1186/s13148-023-01485-x.Peer-Reviewed Original ResearchConceptsColorectal cancer patientsAdvanced colorectal cancer patientsImmune checkpoint inhibitor therapyMedian progression-free survivalDurable partial responseHematological adverse eventsMMR-proficient tumorsCheckpoint inhibitor therapyAdvanced colorectal cancerProgression-free survivalImmune cell infiltrationHistone deacetylasesImmunologic shiftCheckpoint inhibitorsRECIST criteriaAdverse eventsCheckpoint therapyOverall survivalPartial responseInhibitor therapyMedian ageColorectal cancerFurther mechanistic investigationsCancer patientsCell infiltration
2022
Plant-specific HDT family histone deacetylases are nucleoplasmins
Bobde R, Kumar A, Vasudevan D. Plant-specific HDT family histone deacetylases are nucleoplasmins. The Plant Cell 2022, 34: 4760-4777. PMID: 36069647, PMCID: PMC9709999, DOI: 10.1093/plcell/koac275.Peer-Reviewed Original ResearchConceptsN-terminal domainHistone chaperonesH2A/H2B dimersHistones H3/H4H3/H4Nucleosome dynamicsH2B dimersSequence similarityHistone acetyltransferaseEnigmatic familyHistone acetylationFunctional characterizationNucleoplasminGene expressionHistone deacetylasesC-terminalHistone deacetylaseUrea conditionsHistone oligomersSolution structureChaperonesDifferent familiesArabidopsis
2019
SPHK1 deficiency protects mice from acetaminophen-induced ER stress and mitochondrial permeability transition
Li L, Wang H, Zhang J, Sha Y, Wu F, Wen S, He L, Sheng L, You Q, Shi M, Liu L, Zhou H. SPHK1 deficiency protects mice from acetaminophen-induced ER stress and mitochondrial permeability transition. Cell Death & Differentiation 2019, 27: 1924-1937. PMID: 31827236, PMCID: PMC7244772, DOI: 10.1038/s41418-019-0471-x.Peer-Reviewed Original ResearchConceptsActivation of activating transcription factor 6Mitochondrial permeability transitionApoptosis signal-regulating kinase 1SphK1 deficiencyER stressPermeability transitionEndoplasmic reticulumLevels of activating transcription factor 4Inhibit mitochondrial permeability transitionTranscription factor 6Transcription of inflammatory genesGlycogen synthase kinase 3bSignal-regulated kinases 1Transcription factor 4Phosphorylation of JNKAcetylation of p65Levels of histone deacetylaseHistone deacetylasesSphingosine-1-PhosphateImpaired phosphorylationKinase 1Factor 2AFactor 6Exogenous S1PSphK1Sirtuin 6 Attenuates Kaposi's Sarcoma-Associated Herpesvirus Reactivation by Suppressing Ori-Lyt Activity and Expression of RTA
Hu M, Armstrong N, Seto E, Li W, Zhu F, Wang P, Tang Q. Sirtuin 6 Attenuates Kaposi's Sarcoma-Associated Herpesvirus Reactivation by Suppressing Ori-Lyt Activity and Expression of RTA. Journal Of Virology 2019, 93: 10.1128/jvi.02200-18. PMID: 30651359, PMCID: PMC6430549, DOI: 10.1128/jvi.02200-18.Peer-Reviewed Original ResearchMeSH KeywordsCell LineCell Line, TumorDNA ReplicationDNA, ViralGene Expression Regulation, ViralHEK293 CellsHerpesvirus 8, HumanHumansImmediate-Early ProteinsNuclear ProteinsPromoter Regions, GeneticRepressor ProteinsRNA, Small InterferingSarcoma, KaposiSirtuinsTrans-ActivatorsViral ProteinsVirus LatencyVirus ReplicationConceptsKaposi's sarcoma-associated herpesvirusViral DNA replicationReactivation of KSHVSarcoma-associated herpesvirusDNA replicationGene expressionViral gene expressionKSHV promotersHistone deacetylasesPromoter activityKSHV reactivationKaposi's Sarcoma-Associated Herpesvirus ReactivationCell linesDepletion of SIRT6KSHV gene expressionChromatin immunoprecipitation assaysExpression of RTAViral protein productionReduced gene expressionCellular regulatorsImmunoprecipitation assaysOverexpression of SIRT6Multiple promotersKSHV genomeOri-Lyt
2014
Repeated treatment with electroconvulsive seizures induces HDAC2 expression and down-regulation of NMDA receptor-related genes through histone deacetylation in the rat frontal cortex
Park H, Yu H, Park S, Ahn Y, Kim Y, Kim H. Repeated treatment with electroconvulsive seizures induces HDAC2 expression and down-regulation of NMDA receptor-related genes through histone deacetylation in the rat frontal cortex. The International Journal Of Neuropsychopharmacology 2014, 17: 1487-1500. PMID: 24606669, DOI: 10.1017/s1461145714000248.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAnalysis of VarianceAnimalsButyric AcidChromatin ImmunoprecipitationDisease Models, AnimalElectroshockFrontal LobeGene Expression RegulationGlial Fibrillary Acidic ProteinHistamine AntagonistsHistone Deacetylase 2MalePhosphopyruvate HydrataseRatsRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateRNA, MessengerSeizuresSignal TransductionConceptsSignaling-related genesHistone deacetylasesHistone modificationsHistone acetylationCalcium/calmodulin-dependent protein kinase II alphaChromatin immunoprecipitation analysisRat frontal cortexEarly growth response 1Transcriptional repressionReceptor-related genesHistone deacetylationH4 proteinN-methyl-D-aspartate 2ATarget genesFrontal cortexImmunoprecipitation analysisElectroconvulsive seizuresGene expressionResponse 1GenesHDAC2 expressionNeuronal cellsECS treatmentClass I HDACsII alpha
2013
A phase II study of suberoylanilide hydroxamic acid (SAHA) in subjects with locally advanced, recurrent, or metastatic adenoid cystic carcinoma (ACC).
Goncalves P, Kummar S, Siu L, Hansen A, Savvides P, Sukari A, Chao J, Heilbrun L, Pilat M, Smith D, Casetta L, Boerner S, LoRusso P. A phase II study of suberoylanilide hydroxamic acid (SAHA) in subjects with locally advanced, recurrent, or metastatic adenoid cystic carcinoma (ACC). Journal Of Clinical Oncology 2013, 31: 6045-6045. DOI: 10.1200/jco.2013.31.15_suppl.6045.Peer-Reviewed Original ResearchProgression-free survivalAdenoid cystic carcinomaSuberoylanilide hydroxamic acidMetastatic adenoid cystic carcinomaOverall survivalAdverse eventsResponse durationResponse rateEvaluable patientsOnly grade 3 adverse eventGrade 3 adverse eventsMedian progression-free survivalTreatment of ACCAdequate organ functionMedian overall survivalPhase II studyPhase II trialHistone deacetylasesDrug combination studiesChemo-naïveChemotherapy regimensII trialOral painSecondary endpointsThromboembolic events
2010
HOS2 and HDA1 Encode Histone Deacetylases with Opposing Roles in Candida albicans Morphogenesis
Zacchi LF, Schulz WL, Davis DA. HOS2 and HDA1 Encode Histone Deacetylases with Opposing Roles in Candida albicans Morphogenesis. PLOS ONE 2010, 5: e12171. PMID: 20730094, PMCID: PMC2921335, DOI: 10.1371/journal.pone.0012171.Peer-Reviewed Original ResearchConceptsHistone deacetylasesHuman fungal pathogen Candida albicansFungal pathogen Candida albicansHuman pathogen C. albicansVirulence traitsRole of HDACsWhite-opaque switchingC. albicans morphogenesisCandida albicans MorphogenesisPathogen Candida albicansYeast-hyphal transitionCritical virulence attributeDifferent environmental stimuliPathogen C. albicansMorphogenetic transitionEpigenetic mechanismsHyphal formationC. albicansHos2Diverse pathogensMorphogenesisEnvironmental stimuliVirulence attributesHOS1Opposing roles
2005
The POZ/BTB protein NAC1 interacts with two different histone deacetylases in neuronal‐like cultures
Korutla L, Wang P, Mackler S. The POZ/BTB protein NAC1 interacts with two different histone deacetylases in neuronal‐like cultures. Journal Of Neurochemistry 2005, 94: 786-793. PMID: 16033423, DOI: 10.1111/j.1471-4159.2005.03206.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBlotting, WesternButyratesCells, CulturedEnzyme InhibitorsGene Expression RegulationHippocampusHistone DeacetylasesHumansHydroxamic AcidsImmunoprecipitationMiceNerve Tissue ProteinsNeuroblastomaNeuronsPlasmidsProtein BindingProtein IsoformsRatsRepressor ProteinsTranscription, GeneticTransfectionTwo-Hybrid System TechniquesConceptsPOZ/BTB proteinProtein-protein interactionsBTB proteinsHistone deacetylasesPOZ domainTwo-hybridGlutathione S-transferase pulldownRecruit histone deacetylasesDifferent histone deacetylasesTranscriptional repressionGST pulldownSNAC1Histone deacetylase inhibitionCorepressorDeacetylasesRepressionDeacetylase inhibitionProteinPulldownHDAC-3NaC1MSin3ANucleus accumbensCNS regionsCoimmunoprecipitation
1999
Cloning and Characterization of the Murine Histone Deacetylase (HDAC3)
Mahlknecht U, Hoelzer D, Bucala R, Verdin E. Cloning and Characterization of the Murine Histone Deacetylase (HDAC3). Biochemical And Biophysical Research Communications 1999, 263: 482-490. PMID: 10491319, DOI: 10.1006/bbrc.1999.1389.Peer-Reviewed Original ResearchConceptsHistone deacetylasesCore histone proteinsHuman chromosome 5q31Potential tumor suppressor geneHistone acetylation modifiersMalignant myeloid diseasesTumor suppressor geneHistone proteinsTranscriptional complexHistone acetylationDevelopment of cancerHistone deacetylaseSuppressor geneHDAC3Chromosome 5q31Cellular proliferationEnzymatic activityAcetylationMyeloid diseasesImportant insightsOrthologsHistonesCloningDeacetylasesGenes
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