2025
Elevated initial blood kynurenine is associated with increased odds of post-stroke infection Kynurenine and post-stroke infection
Dylla L, Reisz J, Poisson S, Herson P, Sansing L, Monte A. Elevated initial blood kynurenine is associated with increased odds of post-stroke infection Kynurenine and post-stroke infection. Journal Of Stroke And Cerebrovascular Diseases 2025, 34: 108268. PMID: 40015349, DOI: 10.1016/j.jstrokecerebrovasdis.2025.108268.Peer-Reviewed Original ResearchConceptsPost-stroke infectionsAssociated with increased oddsTryptophan metabolitesHistory of diabetes mellitusEnd stage renal diseaseNIH Stroke Scale scoreConcentrations of kynurenineAcute ischemic stroke patientsMultivariate logistic regressionStage renal diseaseStroke Scale scoreCirculating kynurenineIschemic stroke onsetIschemic stroke patientsKynurenine concentrationsConcentrations of tryptophanEmergency department admissionsKynurenic acidDiabetes mellitusMortality of ischemic strokeRenal diseaseTryptophan metabolismOdds ratioQuinolinic acidImmune response
2024
Up-regulated PLA2G10 in cancer impairs T cell infiltration to dampen immunity
Zhang T, Yu W, Cheng X, Yeung J, Ahumada V, Norris P, Pearson M, Yang X, van Deursen W, Halcovich C, Nassar A, Vesely M, Zhang Y, Zhang J, Ji L, Flies D, Liu L, Langermann S, LaRochelle W, Humphrey R, Zhao D, Zhang Q, Zhang J, Gu R, Schalper K, Sanmamed M, Chen L. Up-regulated PLA2G10 in cancer impairs T cell infiltration to dampen immunity. Science Immunology 2024, 9: eadh2334. PMID: 38669316, DOI: 10.1126/sciimmunol.adh2334.Peer-Reviewed Original ResearchConceptsT cell infiltrationT cell exclusionT cellsResistance to anti-PD-1 immunotherapyPoor T-cell infiltrationAnti-PD-1 immunotherapyImmunogenic mouse tumorsT cell mobilizationHuman cancer tissuesTherapeutic immunotherapyCancer immunotherapyMouse tumorsChemokine systemImmunotherapyTumor tissuesImpaired infiltrationTumorLipid metabolitesHuman cancersCancer tissuesInfiltrationA2 groupCancerPLA2G10Up-regulated
2023
Upregulation of Insulin-like Growth Factor-1 Receptor Expression in Pretibial Myxedema: Evidence for a Treatment Target
Walsh H, Shoji M, Gallo R, Mervis J, Maeng M, Elgart G, Kirsner R, Wester S. Upregulation of Insulin-like Growth Factor-1 Receptor Expression in Pretibial Myxedema: Evidence for a Treatment Target. American Journal Of Dermatopathology 2023, 46: 153-154. PMID: 38055967, DOI: 10.1097/dad.0000000000002597.Peer-Reviewed Original ResearchBone marrow sinusoidal endothelial cells are a site of Fgf23 upregulation in a mouse model of iron deficiency anemia
Li X, Lozovatsky L, Tommasini S, Fretz J, Finberg K. Bone marrow sinusoidal endothelial cells are a site of Fgf23 upregulation in a mouse model of iron deficiency anemia. Blood Advances 2023, 7: 5156-5171. PMID: 37417950, PMCID: PMC10480544, DOI: 10.1182/bloodadvances.2022009524.Peer-Reviewed Original ResearchConceptsSinusoidal endothelial cellsEndothelial cellsBone marrowBM sectionsFGF23 upregulationFibroblast growth factor 23Iron deficiencyElevated serum erythropoietinFGF23 promoter activityBM endothelial cellsGrowth factor 23Vitamin D metabolismIron deficiency anemiaSystemic iron deficiencyKnockout mice exhibitBone marrow sinusoidal endothelial cellsNormal iron balanceNonanemic controlsChronic anemiaFactor 23D metabolismEndothelial cell populationErythropoietin treatmentDeficiency anemiaMouse modelHSV-2 triggers upregulation of MALAT1 in CD4+ T cells and promotes HIV latency reversal
Pierce C, Loh L, Steach H, Cheshenko N, Preston-Hurlburt P, Zhang F, Stransky S, Kravets L, Sidoli S, Philbrick W, Nassar M, Krishnaswamy S, Herold K, Herold B. HSV-2 triggers upregulation of MALAT1 in CD4+ T cells and promotes HIV latency reversal. Journal Of Clinical Investigation 2023, 133: e164317. PMID: 37079384, PMCID: PMC10232005, DOI: 10.1172/jci164317.Peer-Reviewed Original ResearchConceptsHIV-1 reactivationHIV latency reversalT cellsLatency reversalHuman CD4HIV-1 viral loadHIV-1 restriction factorsHSV-2 recurrencesHSV-2 infectionHIV-1 latencyUpregulation of MALAT1Primary human CD4HSV-2 proteinsViral loadHIV replicationPeripheral bloodMALAT1 expressionHSV-2Tissue reservoirsCD4Viral replicationExpression of transcriptsBystander cellsRestriction factorsMALAT1Metabolic reprogramming by immune-responsive gene 1 up-regulation improves donor heart preservation and function
Lei I, Huang W, Noly P, Naik S, Ghali M, Liu L, Pagani F, Abou El Ela A, Pober J, Pitt B, Platt J, Cascalho M, Wang Z, Chen Y, Mortensen R, Tang P. Metabolic reprogramming by immune-responsive gene 1 up-regulation improves donor heart preservation and function. Science Translational Medicine 2023, 15: eade3782. PMID: 36753565, PMCID: PMC10068866, DOI: 10.1126/scitranslmed.ade3782.Peer-Reviewed Original ResearchConceptsImmune response gene 1Primary graft dysfunctionDonor heart preservationValproic acidDonor heartsVPA treatmentHeart preservationHeart functionImmune-responsive gene 1Donor heart functionHistone deacetylase inhibitor valproic acidImproved heart functionAntioxidant protein expressionMetabolic reprogrammingDonor-recipient matchingPromising therapeutic strategyHuman donor heartsInhibitor valproic acidGene 1Graft dysfunctionCardioprotective effectsKetoglutarate solutionTherapeutic strategiesResponse gene-1Nuclear factor
2022
The Prostate Cancer Androgen Receptor Cistrome in African American Men Associates with Upregulation of Lipid Metabolism and Immune Response
Berchuck J, Adib E, Alaiwi S, Dash A, Shin J, Lowder D, McColl C, Castro P, Carelli R, Benedetti E, Deng J, Robertson M, Baca S, Bell C, McClure H, Zarif T, Davidsohn M, Lakshminarayanan G, Rizwan K, Skapura D, Grimm S, Davis C, Ehli E, Kelleher K, Seo J, Mitsiades N, Coarfa C, Pomerantz M, Loda M, Ittmann M, Freedman M, Kaochar S. The Prostate Cancer Androgen Receptor Cistrome in African American Men Associates with Upregulation of Lipid Metabolism and Immune Response. Cancer Research 2022, 82: 2848-2859. PMID: 35731919, PMCID: PMC9379363, DOI: 10.1158/0008-5472.can-21-3552.Peer-Reviewed Original ResearchMeSH KeywordsBlack or African AmericanHumansImmunityLipid MetabolismMaleProstatic NeoplasmsReceptors, AndrogenUp-RegulationConceptsProstate cancerImmune responseProstate tumorsAndrogen receptorAggressiveness of prostate cancerLipid metabolismAA prostate tumorsPrimary prostate tumorsProstate cancer cohortProstate cancer progressionAA prostate cancerIncreased androgen signalingEA prostate cancerLevels of lipid metabolismImmune response genesAR cistromeUpregulation of lipid metabolismAndrogen signalingPoor prognosisClinical developmentLipid metabolism gene expressionMetabolomics dataCancer cohortProstateInhibitors of metabolic enzymesPan-cancer pervasive upregulation of 3′ UTR splicing drives tumourigenesis
Chan J, Zhang B, Chew X, Salhi A, Kwok Z, Lim C, Desi N, Subramaniam N, Siemens A, Kinanti T, Ong S, Sanchez-Mejias A, Ly P, An O, Sundar R, Fan X, Wang S, Siew B, Lee K, Chong C, Lieske B, Cheong W, Goh Y, Fam W, Ooi M, Koh B, Iyer S, Ling W, Chen J, Yoong B, Chanwat R, Bonney G, Goh B, Zhai W, Fullwood M, Wang W, Tan K, Chng W, Dan Y, Pitt J, Roca X, Guccione E, Vardy L, Chen L, Gao X, Chow P, Yang H, Tay Y. Pan-cancer pervasive upregulation of 3′ UTR splicing drives tumourigenesis. Nature Cell Biology 2022, 24: 928-939. PMID: 35618746, PMCID: PMC9203280, DOI: 10.1038/s41556-022-00913-z.Peer-Reviewed Original ResearchMeSH Keywords3' Untranslated RegionsAdenocarcinomaAlternative SplicingAnimalsCarcinogenesisColonic NeoplasmsMammalsUp-RegulationConceptsUntranslated regionProtein-coding alterationsPost-transcriptional regulationAnti-cancer therapeuticsMammalian genesAlternative polyadenylationPan-cancer landscapeSplicing studiesAntisense oligonucleotide-mediated inhibitionUTR variantsDysregulation eventsSplicingOncogenic functionActivated oncogenesOncogene expressionMessenger RNAOncogeneTumor progressionPolyadenylationPoor prognosisHepatocellular carcinomaUpregulationColon adenocarcinomaGenesRNAAlpha-tocotrienol enhances arborization of primary hippocampal neurons via upregulation of Bcl-xL
Park HA, Crowe-White KM, Ciesla L, Scott M, Bannerman S, Davis AU, Adhikari B, Burnett G, Broman K, Ferdous KA, Lackey KH, Licznerski P, Jonas EA. Alpha-tocotrienol enhances arborization of primary hippocampal neurons via upregulation of Bcl-xL. Nutrition Research 2022, 101: 31-42. PMID: 35366596, PMCID: PMC9081260, DOI: 10.1016/j.nutres.2022.02.007.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsbcl-X ProteinHippocampusLymphoma, B-CellNeuronsRatsTocotrienolsUp-RegulationConceptsPrimary hippocampal neuronsControl neuronsHippocampal neuronsAlpha-tocotrienolBcl-xLVitamin E familyCerebral ischemiaNeuronal viabilityMature neuronsB cellsNeurite complexityNeuronal functionMitochondrial energy productionBrain developmentCentral mechanismsNeuronsBeneficial effectsOxidative stressBcl-xL upregulationProtein levelsNeurite branchingTreatmentE familyATP levelsNeurite outgrowthOxidative 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 inductionSARS-CoV-2 RNA elements share human sequence identity and upregulate hyaluronan via NamiRNA-enhancer network
Li W, Yang S, Xu P, Zhang D, Tong Y, Chen L, Jia B, Li A, Lian C, Ru D, Zhang B, Liu M, Chen C, Fu W, Yuan S, Gu C, Wang L, Li W, Liang Y, Yang Z, Ren X, Wang S, Zhang X, Song Y, Xie Y, Lu H, Xu J, Wang H, Yu W. SARS-CoV-2 RNA elements share human sequence identity and upregulate hyaluronan via NamiRNA-enhancer network. EBioMedicine 2022, 76: 103861. PMID: 35124429, PMCID: PMC8811534, DOI: 10.1016/j.ebiom.2022.103861.Peer-Reviewed Original ResearchConceptsHuman identical sequencesRNA elementsHuman genomeSARS-CoV-2 genomeHyaluronan synthase 2Chromatin immunoprecipitation assaysDistant genesSequence similarityGenomic fragmentsSequence identityTarget lociGenomic interactionsMiRNA precursorsH3K27ac enrichmentSARS-CoV-2Identical sequencesBioinformatics analysisImmunoprecipitation assaysGenomeGene expressionHEK293TQuantitative RT-PCRShort sequencesGenesHost enhancement
2021
Adjunct Fenofibrate Up‐regulates Bile Acid Glucuronidation and Improves Treatment Response For Patients With Cholestasis
Gallucci GM, Trottier J, Hemme C, Assis DN, Boyer JL, Barbier O, Ghonem NS. Adjunct Fenofibrate Up‐regulates Bile Acid Glucuronidation and Improves Treatment Response For Patients With Cholestasis. Hepatology Communications 2021, 5: 2035-2051. PMID: 34558841, PMCID: PMC8631103, DOI: 10.1002/hep4.1787.Peer-Reviewed Original ResearchConceptsSerum bile acidsSerum alkaline phosphataseBile acidsTreatment responseIncomplete responseTotal serum bile acidsElevated serum alkaline phosphatasePeroxisome proliferator-activated receptor alphaProliferator-activated receptor alphaAlkaline phosphatasePrimary sclerosing cholangitisPrimary biliary cholangitisStandard of careSerum ALP levelsBile acid glucuronidationCytotoxic bile acidsPrimary human hepatocytesBA detoxificationFenofibrate therapySclerosing cholangitisAdult patientsBiliary cholangitisLiver failureCombination therapyImproved outcomesNogoA-expressing astrocytes limit peripheral macrophage infiltration after ischemic brain injury in primates
Boghdadi AG, Spurrier J, Teo L, Li M, Skarica M, Cao B, Kwan WC, Merson TD, Nilsson SK, Sestan N, Strittmatter SM, Bourne JA. NogoA-expressing astrocytes limit peripheral macrophage infiltration after ischemic brain injury in primates. Nature Communications 2021, 12: 6906. PMID: 34824275, PMCID: PMC8617297, DOI: 10.1038/s41467-021-27245-0.Peer-Reviewed Original ResearchConceptsBrain injuryPeripheral macrophage infiltrationIschemic brain injuryAnti-inflammatory responseMajority of astrocytesNeurite outgrowth inhibitory proteinIschemic strokePeripheral macrophagesReactive astrocytesMacrophage infiltrationStroke recoveryAstrocyte clustersMarmoset monkeysVisual cortexAstrocytesNogoASingle-nucleus transcriptomicsInhibitory proteinInjuryStrokeHuman brainInfiltrationCritical rolePrecise functionOligodendrocytesImpairment of human terminal erythroid differentiation by histone deacetylase 5 deficiency
Wang Y, Li W, Schulz VP, Zhao H, Qu X, Qi Q, Cheng Y, Guo X, Zhang S, Wei X, Liu D, Yazdanbakhsh K, Hillyer CD, Mohandas N, Chen L, Gallagher PG, An X. Impairment of human terminal erythroid differentiation by histone deacetylase 5 deficiency. Blood 2021, 138: 1615-1627. PMID: 34036344, PMCID: PMC8554652, DOI: 10.1182/blood.2020007401.Peer-Reviewed Original ResearchConceptsTerminal erythroid differentiationChromatin condensationErythroid differentiationHuman erythroid cellsAcetylation of H4RNA sequencing analysisEnucleation of erythroblastsGroup of enzymesLate-stage erythroblastsErythroid cell culturesHDAC family membersActivation of p53Short hairpin RNAChromatin accessibilityATAC-seqMammalian erythropoiesisH4 deacetylationNonhistone proteinsH4 acetylationDiverse functionsHDAC inhibitor treatmentHuman erythropoiesisKnockdown of HDAC5Erythroid cellsGene expressionHominini-specific regulation of CBLN2 increases prefrontal spinogenesis
Shibata M, Pattabiraman K, Muchnik SK, Kaur N, Morozov YM, Cheng X, Waxman SG, Sestan N. Hominini-specific regulation of CBLN2 increases prefrontal spinogenesis. Nature 2021, 598: 489-494. PMID: 34599306, PMCID: PMC9018127, DOI: 10.1038/s41586-021-03952-y.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalcium-Binding ProteinsDendritesEnhancer Elements, GeneticFemaleHumansIntercellular Signaling Peptides and ProteinsMacacaMental DisordersMiceNerve Tissue ProteinsNervous System DiseasesNeural Cell Adhesion MoleculesPhylogenyPrefrontal CortexPromoter Regions, GeneticSOXD Transcription FactorsTranscriptomeUp-RegulationConceptsCerebellin 2Prefrontal cortexCerebral cortex regionsDendritic spine formationInitiation of synaptogenesisLaminar distributionDendritic spinesNervous systemNeuropsychiatric disordersSpine formationLevel of expressionCortex regionsGenetic humanizationCortical gradientsDisproportionate increaseSpecies differencesNeurexinsSpinogenesisDysfunctionMolecular basisPathogenesisExpressionCortexSynaptogenesisSpineRenalase is a novel tissue and serological biomarker in pancreatic ductal adenocarcinoma
Gao Y, Wang M, Guo X, Hu J, Chen TM, Finn S, Lacy J, Kunstman JW, H. C, Bellin MD, Robert ME, Desir GV, Gorelick FS. Renalase is a novel tissue and serological biomarker in pancreatic ductal adenocarcinoma. PLOS ONE 2021, 16: e0250539. PMID: 34587190, PMCID: PMC8480607, DOI: 10.1371/journal.pone.0250539.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorCarcinoma, Pancreatic DuctalCase-Control StudiesFemaleGene Expression Regulation, NeoplasticHumansMaleMiddle AgedMonoamine OxidaseNeoplasm GradingPancreatic NeoplasmsPrognosisProspective StudiesRetrospective StudiesSurvival AnalysisUp-RegulationYoung AdultConceptsPlasma renalase levelsBorderline resectable PDACRenalase levelsPDAC precursor lesionsOverall survivalPDAC tissuesTumor characteristicsResectable PDACChronic pancreatitisPrecursor lesionsNormal pancreasPancreatic ductal adenocarcinoma growthAdvanced tumor characteristicsVaried clinical stagesWorse tumor characteristicsNode-positive diseasePancreatic ductal adenocarcinomaNormal pancreatic headSpindle-shaped cellsPlasma renalaseRenalase expressionUnderwent resectionAbdominal traumaPancreatic headPositive diseaseSmall extracellular vesicles released by infused mesenchymal stromal cells target M2 macrophages and promote TGF‐β upregulation, microvascular stabilization and functional recovery in a rodent model of severe spinal cord injury
Nakazaki M, Morita T, Lankford KL, Askenase PW, Kocsis JD. Small extracellular vesicles released by infused mesenchymal stromal cells target M2 macrophages and promote TGF‐β upregulation, microvascular stabilization and functional recovery in a rodent model of severe spinal cord injury. Journal Of Extracellular Vesicles 2021, 10: e12137. PMID: 34478241, PMCID: PMC8408371, DOI: 10.1002/jev2.12137.Peer-Reviewed Original ResearchConceptsMarrow-derived mesenchymal stem/stromal cellsSpinal cord injuryBlood-spinal cord barrierSmall extracellular vesiclesFunctional recoveryM2 macrophagesCord injuryInjury siteTherapeutic effectStromal cellsSevere spinal cord injurySingle MSC injectionImproved functional recoveryBone marrow-derived mesenchymal stem/stromal cellsM2 macrophage markersSimilar therapeutic effectsRelease of sEVsMesenchymal stem/stromal cellsExtracellular vesiclesTight junction proteinsStem/stromal cellsMesenchymal stromal cellsTGF-β receptorMSC infusionSCI ratsAnalysis of the Applicability of microRNAs in Peripheral Blood Leukocytes as Biomarkers of Sensitivity and Exposure to Fractionated Radiotherapy towards Breast Cancer
Marczyk M, Polańska J, Wojcik A, Lundholm L. Analysis of the Applicability of microRNAs in Peripheral Blood Leukocytes as Biomarkers of Sensitivity and Exposure to Fractionated Radiotherapy towards Breast Cancer. International Journal Of Molecular Sciences 2021, 22: 8705. PMID: 34445424, PMCID: PMC8395710, DOI: 10.3390/ijms22168705.Peer-Reviewed Original ResearchConceptsBreast cancer patientsExternal beam radiotherapyCourse of radiotherapyPeripheral blood leukocytesBiomarkers of sensitivityLogistic regression modelsMultinomial logistic regression modelsFractionated RadiotherapyInter-individual variabilityCancer patientsUnivariate analysisBreast cancerCombination of miRNAsBeam radiotherapyBlood leukocytesBlood samplesPromising biomarkerTotal doseSensitive biomarkerRadiotherapyPatientsStrong inter-individual variabilityBiomarkersDoseLeukocytesExpression of Foxp3 by T follicular helper cells in end-stage germinal centers
Jacobsen J, Hu W, R Castro T, Solem S, Galante A, Lin Z, Allon S, Mesin L, Bilate A, Schiepers A, Shalek A, Rudensky A, Victora G. Expression of Foxp3 by T follicular helper cells in end-stage germinal centers. Science 2021, 373 PMID: 34437125, PMCID: PMC9007630, DOI: 10.1126/science.abe5146.Peer-Reviewed Original ResearchConceptsFollicular helper cellsGerminal centersHelper cellsFormation of GCsExpression of Foxp3Effective antibody responseTranscription factor Foxp3Acute surgeAntibody responseFactor Foxp3T cellsFoxp3Immunoglobulin somatic hypermutationGC sizeAffinity maturationPotential regulatorCellsEctopic expressionSomatic hypermutationExpressionAntibodiesDeficiency of histone lysine methyltransferase SETDB2 in hematopoietic cells promotes vascular inflammation and accelerates atherosclerosis
Zhang X, Sun J, Canfrán-Duque A, Aryal B, Tellides G, Chang YJ, Suárez Y, Osborne TF, Fernández-Hernando C. Deficiency of histone lysine methyltransferase SETDB2 in hematopoietic cells promotes vascular inflammation and accelerates atherosclerosis. JCI Insight 2021, 6: e147984. PMID: 34003795, PMCID: PMC8262461, DOI: 10.1172/jci.insight.147984.Peer-Reviewed Original ResearchConceptsHematopoietic cellsHistone methylation/acetylationSingle-cell RNA-seq analysisMethylation/acetylationHistone H3 Lys9RNA-seq analysisProgression of atherosclerosisEpigenetic marksLysine methyltransferasesH3 Lys9Epigenetic modificationsDNA methylationNoncoding RNAsCell regulatorsSETDB2Vascular inflammationAtherosclerotic lesionsAtherosclerotic plaquesMyeloid cell recruitmentGenetic deletionLDLR knockout miceEnhanced expressionHepatic lipid metabolismMurine atherosclerotic lesionsGenes
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