2025
Gene-dose effect of the glutathione biosynthesis gene on ascorbate deficiency in mice
Strand R, Orlicky D, Chen Y. Gene-dose effect of the glutathione biosynthesis gene on ascorbate deficiency in mice. Biochemical And Biophysical Research Communications 2025, 766: 151900. PMID: 40294460, PMCID: PMC12058385, DOI: 10.1016/j.bbrc.2025.151900.Peer-Reviewed Original ResearchConceptsGene-dose effectAscorbate deficiencyTissue GSH levelsDouble-knockoutVitamin CDietary vitamin CAllele dosage effectGlutamate-cysteine ligaseMiceClinical interplayGSH levelsOxidative stressBrain tissueRedox imbalanceGCLMDosage effectBrain functionDeficiencyGlutathione biosynthesis genesIncreased vulnerabilityBrainPhenotypic outcomesModifier subunitRedox balanceGSH biosynthesis
2024
Vitamin C Alleviates the Risk of Gestational Diabetes Mellitus Associated With Exposure to Metals
Wang Y, Wu W, Zhang P, Chen X, Feng Y, Yang H, Jin L, Huang H, Shi X, Wang S, Zhang Y. Vitamin C Alleviates the Risk of Gestational Diabetes Mellitus Associated With Exposure to Metals. Journal Of Diabetes Research 2024, 2024: 1298122. PMID: 39035682, PMCID: PMC11260216, DOI: 10.1155/2024/1298122.Peer-Reviewed Original ResearchConceptsRisk of gestational diabetes mellitusGestational diabetes mellitusVitamin C intakeDietary vitamin C intakeVitamin C supplement useExposure to heavy metalsHeavy metalsC intakeInductively coupled plasma mass spectrometryAssociated with increased risk of GDMGestational diabetes mellitus casesHigher dietary vitamin C intakeUnconditional logistic regression modelsAssociated with increased riskConcentrations of metalsLevels of mercuryExposure to metalsCase-control studyBlood levels of mercuryHigher blood levelsVitamin CVitamin C supplementationAssociated with metalsOxidative stress pathwaysEarly pregnancy
2023
Role of ascorbic acid in cardiac allograft vasculopathy
Chang A, Martin K, Colvin M, Bellumkonda L. Role of ascorbic acid in cardiac allograft vasculopathy. Clinical Transplantation 2023, 37: e15153. PMID: 37792313, DOI: 10.1111/ctr.15153.Peer-Reviewed Original ResearchConceptsCardiac allograft vasculopathySmooth muscle cell apoptosisAllograft vasculopathyDisease processMuscle cell apoptosisSignificant long-term morbidityCell apoptosisProgressive fibroproliferative diseasePost-transplant carePost-transplant managementLong-term morbiditySmall clinical trialsChallenging disease processVascular smooth muscle cell apoptosisHeart transplantationCAV progressionEndothelial dysfunctionRapamycin inhibitorsClinical trialsIntimal thickeningPrevents developmentInterferon γRodent modelsIntimal hyperplasiaMTOR inhibitorsCirculating levels of micronutrients and risk of infections: a Mendelian randomization study
Flatby H, Ravi A, Damås J, Solligård E, Rogne T. Circulating levels of micronutrients and risk of infections: a Mendelian randomization study. BMC Medicine 2023, 21: 84. PMID: 36882828, PMCID: PMC9993583, DOI: 10.1186/s12916-023-02780-3.Peer-Reviewed Original ResearchConceptsRisk of infectionGastrointestinal infectionsBlood levelsMendelian randomizationMendelian randomization studyOdds ratioObservational studyImmune responseIndependent cohortRandomization studySignificant associationInfectionClear associationMR analysisLevels of micronutrientsStatistical significanceConclusionsOur resultsPrevious observational studiesStandard deviation increaseUK BiobankRiskLevels of copperEuropean ancestryAvailable summary statisticsAssociation
2022
Vitamin C epigenetically controls osteogenesis and bone mineralization
Thaler R, Khani F, Sturmlechner I, Dehghani SS, Denbeigh JM, Zhou X, Pichurin O, Dudakovic A, Jerez SS, Zhong J, Lee JH, Natarajan R, Kalajzic I, Jiang YH, Deyle DR, Paschalis EP, Misof BM, Ordog T, van Wijnen AJ. Vitamin C epigenetically controls osteogenesis and bone mineralization. Nature Communications 2022, 13: 5883. PMID: 36202795, PMCID: PMC9537512, DOI: 10.1038/s41467-022-32915-8.Peer-Reviewed Original ResearchConceptsSevere skeletal defectsBone-specific genesEpigenetic functionsChromatin accessibilityHistone demethylationDNA hydroxymethylationTranscriptional activityPro-osteogenic genesCell differentiationOsteogenic cell differentiationOsteogenic differentiationGenesSkeletal defectsBone phenotypeMurine boneOsteoblastogenesisDifferentiationKnockout miceGulo knockout miceVitamin C deficiencyTET1Collagen maturationPromoterDemethylationVitamin C
2021
Regeneration of infarcted mouse hearts by cardiovascular tissue formed via the direct reprogramming of mouse fibroblasts
Cho J, Kim S, Lee H, Rah W, Cho HC, Kim NK, Bae S, Shin DH, Lee MG, Park IH, Tanaka Y, Shin E, Yi H, Han JW, Hwang PTJ, Jun HW, Park HJ, Cho K, Lee SW, Jung JK, Levit RD, Sussman MA, Harvey RP, Yoon YS. Regeneration of infarcted mouse hearts by cardiovascular tissue formed via the direct reprogramming of mouse fibroblasts. Nature Biomedical Engineering 2021, 5: 880-896. PMID: 34426676, PMCID: PMC8809198, DOI: 10.1038/s41551-021-00783-0.Peer-Reviewed Original ResearchConceptsDirect reprogrammingMouse tail-tip fibroblastsBone morphogenetic protein 4Smooth muscle cellsTail-tip fibroblastsMuscle cellsSomatic cellsEndothelial cellsReprogrammingCell typesTissue-like structuresMouse fibroblastsProtein 4Gap junctionsCardiovascular tissuesVessel formationDisease modellingDrug discoveryImmature characteristicsFibroblastsCellsMouse heartsCardiomyocytesTissueHost cardiomyocytesCharacterization of Macroporous Polycaprolactone/Silk Fibroin/Gelatin/Ascorbic Acid Composite Scaffolds and In Vivo Results in a Rabbit Model for Meniscus Cartilage Repair
Abpeikar Z, Moradi L, Javdani M, Kargozar S, Soleimannejad M, Hasanzadeh E, Mirzaei S, Asadpour S. Characterization of Macroporous Polycaprolactone/Silk Fibroin/Gelatin/Ascorbic Acid Composite Scaffolds and In Vivo Results in a Rabbit Model for Meniscus Cartilage Repair. Cartilage 2021, 13: 1583s-1601s. PMID: 34340598, PMCID: PMC8804732, DOI: 10.1177/19476035211035418.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAscorbic AcidFibroinsGelatinMeniscusPolyestersRabbitsTissue EngineeringTissue ScaffoldsConceptsComposite scaffoldsSuitable mechanical propertiesSelf-healing capacityMechanical propertiesMechanical testsElectron microscopeInner avascular zoneAllogeneic adipose-derived mesenchymal stem cellsAdipose-derived mesenchymal stem cellsGood biocompatibilityMeniscus cartilageScaffoldsCarbodiimide hydrochlorideCartilage repairAntioxidant capacityNew Zealand rabbitsTotal antioxidant capacityBiocompatibilityMicroneedling as an adjuvant to topical therapies for melasma: A systematic review and meta-analysis
Bailey AJM, Li HO, Tan MG, Cheng W, Dover JS. Microneedling as an adjuvant to topical therapies for melasma: A systematic review and meta-analysis. Journal Of The American Academy Of Dermatology 2021, 86: 797-810. PMID: 33857549, DOI: 10.1016/j.jaad.2021.03.116.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, CutaneousAscorbic AcidHumansMelanosisProspective StudiesTranexamic AcidTreatment OutcomeConceptsTreatment of melasmaTopical therapyMelasma severitySystematic reviewSerious adverse eventsTopical tranexamic acidEfficacy of microneedlingPlatelet-rich plasmaAdverse eventsTopical interventionsTopical medicationsTranexamic acidProspective studyEligible studiesRadiofrequency microneedlingPRISMA guidelinesTherapyMicroneedlingMelasmaStudy designVitamin CAdjuvantWeeksDepigmenting agentTreatmentEffect of Vitamin C, Thiamine, and Hydrocortisone on Ventilator- and Vasopressor-Free Days in Patients With Sepsis
Sevransky J, Rothman R, Hager D, Bernard G, Brown S, Buchman T, Busse L, Coopersmith C, DeWilde C, Ely E, Eyzaguirre L, Fowler A, Gaieski D, Gong M, Hall A, Hinson J, Hooper M, Kelen G, Khan A, Levine M, Lewis R, Lindsell C, Marlin J, McGlothlin A, Moore B, Nugent K, Nwosu S, Polito C, Rice T, Ricketts E, Rudolph C, Sanfilippo F, Viele K, Martin G, Wright D, Nugent K, Spainhour C, Polito C, Moore B, Negrin L, Khan A, Kea B, Krol O, Haq E, Pinkert V, Nguyen K, Brown S, Bledsoe J, Peltan I, Applegate D, Armbruster B, Montgomery Q, Brown K, Daw A, Gong M, Aboodi M, Chen J, Hope A, Gummadi S, Lopez B, Hinson J, Hager D, Ricketts E, Clements C, Gajic O, Kashyap R, Vanmeter D, Busse L, McBride M, Ginde A, Moss M, Finck L, Howell M, McKeehan J, Higgins C, Clare J, McBryde B, Barksdale A, Kalin D, Kruse D, Hilz K, Qadir N, Chang S, Beutler R, Tam A, Harris E, Youngquist S, Middleton E, Davidov E, Plante A, Belsky J, Siner J, Wira C, Brokowski C, Steingrub J, Smithline H, Thornton-Thompson S, Fowler A, Miller S, Narron K, Puskarich M, Prekker M, Hendrickson A, Quinn J, Wilson J, Levitt J, Mann R, Visweswaran A, Gentile N, Marchetti N, Reimer H, Guirgis F, Jones L, Black L, Henson M, Meyer N, Greenwood J, Ittner C, Rivers E, Jayaprakash N, Gardner-Gray J, Hurst G, Pflaum J, Jaehne A, Gill J, Cook A, Janz D, Vonderhaar D, Romaine C, Wilkerson R, McCurdy M, Beach D, Lasko K, Gill R, Price K, Dickson L, Duggal A, Mace S, Hite R, Hastings A, Haukoos J, Douglas I, Trent S, Lyle C, Cupelo A, Gravitz S, Hiller T, Oakes J, LoVecchio F, Quiroga P, Danley S, Mulrow M, Encinas A, Goodwin A, Hall G, Grady A, Exline M, Terndrup T, Pannu S, Robart E, Karow S, Files D, Smith L, Gibbs K, Flores L, Pastores S, Shaz D, Kostelecky N, Case C, Wilkins E, Gaieski D, Baram M, Schwegler D, Renzi N, Mosier J, Hypes C, Campbell E, Hooper M, Sill J, Mitchell K, Hudock K, Lyons M, Gorder K, Ahmad Y, Studer A, Davis J, Barrett M, Nomura J, Knox J, Park P, Co I, McSparron J, Hyzy R, McDonough K, Hanna S, Self W, Semler M, Hays M, Bartz R, Limkakeng A, Sweeney K, Woodburn R, Goyal M, Zaaqoq A, Moriarty T, Oropello J, Zhang Z. Effect of Vitamin C, Thiamine, and Hydrocortisone on Ventilator- and Vasopressor-Free Days in Patients With Sepsis. JAMA 2021, 325: 742-750. PMID: 33620405, PMCID: PMC7903252, DOI: 10.1001/jama.2020.24505.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnti-Inflammatory AgentsAscorbic AcidCritical IllnessDouble-Blind MethodDrug Therapy, CombinationEarly Termination of Clinical TrialsFemaleHumansHydrocortisoneLength of StayMaleMiddle AgedOrgan Dysfunction ScoresRespiration, ArtificialRespiratory InsufficiencySepsisThiamineTreatment OutcomeVasoconstrictor AgentsVitaminsConceptsVasopressor-free daysIntensive care unitVitamin CPlacebo groupCare unitIntervention groupDays of randomizationIntravenous vitamin CPlacebo-controlled trialThirty-day mortalityTotal daily doseKey secondary outcomesAdult patientsSecondary outcomesDaily doseIll patientsPrimary outcomeSubstantial morbidityCardiovascular dysfunctionEmergency departmentCommon syndromeMAIN OUTCOMESepsisPlaceboPatientsAn IDH1-vitamin C crosstalk drives human erythroid development by inhibiting pro-oxidant mitochondrial metabolism
Gonzalez-Menendez P, Romano M, Yan H, Deshmukh R, Papoin J, Oburoglu L, Daumur M, Dumé AS, Phadke I, Mongellaz C, Qu X, Bories PN, Fontenay M, An X, Dardalhon V, Sitbon M, Zimmermann VS, Gallagher PG, Tardito S, Blanc L, Mohandas N, Taylor N, Kinet S. An IDH1-vitamin C crosstalk drives human erythroid development by inhibiting pro-oxidant mitochondrial metabolism. Cell Reports 2021, 34: 108723. PMID: 33535038, PMCID: PMC9169698, DOI: 10.1016/j.celrep.2021.108723.Peer-Reviewed Original ResearchMeSH KeywordsAscorbic AcidCell DifferentiationErythropoiesisHumansIsocitrate DehydrogenaseMitochondriaConceptsIsocitrate dehydrogenase 1Oxidative phosphorylationMitochondrial metabolismReactive oxygen speciesHuman erythroid differentiationHuman erythroid developmentMitochondrial oxidative phosphorylationVitamin C homeostasisHSPC developmentIDH1 knockdownErythroid developmentStepwise differentiationErythroid differentiationLate-stage erythropoiesisTerminal stepCritical regulatorHematopoietic stemMitochondrial superoxideMitochondrial oxidationProgenitor cellsDehydrogenase 1Oxygen speciesCongenital dyserythropoietic anemiaCentral roleDyserythropoietic anemia
2018
Engineering tyrosine residues into hemoglobin enhances heme reduction, decreases oxidative stress and increases vascular retention of a hemoglobin based blood substitute
Cooper C, Silkstone G, Simons M, Rajagopal B, Syrett N, Shaik T, Gretton S, Welbourn E, Bülow L, Eriksson N, Ronda L, Mozzarelli A, Eke A, Mathe D, Reeder B. Engineering tyrosine residues into hemoglobin enhances heme reduction, decreases oxidative stress and increases vascular retention of a hemoglobin based blood substitute. Free Radical Biology And Medicine 2018, 134: 106-118. PMID: 30594736, PMCID: PMC6597946, DOI: 10.1016/j.freeradbiomed.2018.12.030.Peer-Reviewed Original ResearchConceptsTyrosine residuesΒ-subunitSingle tyrosine mutationsFerryl heme speciesOxidative stressExtracellular proteinsTyrosine mutationWild typePromising mutantsHEK cellsProtein surfaceHeme speciesMutationsMembrane damageRedox-active tyrosine residueHeme reductionOxidative toxicityFerryl speciesFerric HbSubunitsHb additionHeme lossSpeciesProteinFerric formA review of micronutrients in sepsis: the role of thiamine, l-carnitine, vitamin C, selenium and vitamin D
Belsky JB, Wira CR, Jacob V, Sather JE, Lee PJ. A review of micronutrients in sepsis: the role of thiamine, l-carnitine, vitamin C, selenium and vitamin D. Nutrition Research Reviews 2018, 31: 281-290. PMID: 29984680, DOI: 10.1017/s0954422418000124.Peer-Reviewed Original ResearchConceptsVitamin CLife-threatening organ dysfunctionRole of micronutrientsCurrent available dataSeptic patientsOrgan dysfunctionSeptic shockVitamin DVitamin D.Clinical trialsRole of thiamineThiamine deficiencySepsisHuman studiesHost responseConclusion statementsCellular dysfunctionNormal physiologyMetabolic demandsCarnitinePotential roleDysfunctionPresent reviewCellular turnoverPivotal role
2017
Acute Effects of Vitamin C Exposure On Colonic Crypts: Direct Modulation of pH Regulation
Aldajani MM, Vanicek CN, Alhazzaa N, Lysyy T, Agarwal R, Geibel JP. Acute Effects of Vitamin C Exposure On Colonic Crypts: Direct Modulation of pH Regulation. Cellular Physiology And Biochemistry 2017, 44: 377-387. PMID: 29132138, DOI: 10.1159/000484914.Peer-Reviewed Original ResearchConceptsVitamin CColonic cryptsAcute effectsDependent intracellular pH recoveryTumor formationIntracellular pH recoveryNew therapeutic agentsMM vitamin CColorectal cancerDistal colonLeading causeTranscellular passive diffusionBasolateral membraneAcute additionNormal colonic cryptsC exposureNutraceutical agentTherapeutic agentsPH recoveryIntracellular pH changesCancer cellsVitamin C.CryptsLow intracellularTight junctionsVascular smooth muscle cells derived from inbred swine induced pluripotent stem cells for vascular tissue engineering
Luo J, Qin L, Kural MH, Schwan J, Li X, Bartulos O, Cong XQ, Ren Y, Gui L, Li G, Ellis MW, Li P, Kotton DN, Dardik A, Pober JS, Tellides G, Rolle M, Campbell S, Hawley RJ, Sachs DH, Niklason LE, Qyang Y. Vascular smooth muscle cells derived from inbred swine induced pluripotent stem cells for vascular tissue engineering. Biomaterials 2017, 147: 116-132. PMID: 28942128, PMCID: PMC5638652, DOI: 10.1016/j.biomaterials.2017.09.019.Peer-Reviewed Original ResearchConceptsVascular smooth muscle cellsSmooth muscle cellsPluripotent stem cellsFunctional vascular smooth muscle cellsMassachusetts General Hospital miniature swineMuscle cellsSelf-assembly approachBiodegradable polyglycolic acid (PGA) scaffoldsPrimary vascular smooth muscle cellsSmooth muscle myosin heavy chainMuscle myosin heavy chainVascular tissue engineeringStem cellsTissue engineeringPolyglycolic acid scaffoldsReprogramming factorsVascular diseaseContractile functionVascular constructsImmunodeficient miceOrgan transplantsMiniature swinePreclinical investigationsGreat potentialMyosin heavy chain
2016
Dietary antioxidant vitamins intake and mortality: A report from two cohort studies of Chinese adults in Shanghai
Zhao L, Shu X, Li H, Zhang W, Gao J, Sun J, Zheng W, Xiang Y. Dietary antioxidant vitamins intake and mortality: A report from two cohort studies of Chinese adults in Shanghai. Journal Of Epidemiology 2016, 27: 89-97. PMID: 28142039, PMCID: PMC5363781, DOI: 10.1016/j.je.2016.10.002.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntioxidantsAscorbic AcidAsian PeopleCardiovascular DiseasesCarotenoidsCause of DeathChinaCohort StudiesDietDietary SupplementsDose-Response Relationship, DrugFemaleHumansMaleNeoplasmsProportional Hazards ModelsProspective StudiesRisk FactorsSocioeconomic FactorsSurveys and QuestionnairesVitamin EVitaminsConceptsDietary antioxidant vitamin intakeAntioxidant vitamin intakeRisk of mortalityHealth StudyCohort study of middle-agedChinese adultsCohort study of Chinese adultsShanghai Men's Health StudyShanghai Women's Health StudyRisk of cardiovascular disease mortalityStudy of middle-agedCohort studyHazard ratioMiddle-agedWomen's Health StudyCardiovascular disease mortalityConfidence intervalsElderly Chinese adultsMen's Health StudyVitamin intakeCardiovascular diseaseCox proportional hazards regression modelsProportional hazards regression modelsVitamin C intakeHazards regression models
2013
Antioxidant Supplementation Ameliorates Molecular Deficits in Smith-Lemli-Opitz Syndrome
Korade Z, Xu L, Harrison FE, Ahsen R, Hart SE, Folkes OM, Mirnics K, Porter NA. Antioxidant Supplementation Ameliorates Molecular Deficits in Smith-Lemli-Opitz Syndrome. Biological Psychiatry 2013, 75: 215-222. PMID: 23896203, PMCID: PMC3874268, DOI: 10.1016/j.biopsych.2013.06.013.Peer-Reviewed Original ResearchConceptsVitamin EPregnant female miceTransgenic mouse modelSLOS patientsPatient cell culturesSmith-LemliOpitz syndromeQuantitative polymerase chain reactionAntioxidant mixturePolymerase chain reactionFemale miceAntioxidant supplementationMouse modelRodent modelsGlial culturesAntioxidant treatmentVitamin AActive oxysterolsMolecular deficitsCoenzyme Q10Liver tissueWestern blotInborn errorsMaternal feedingLiquid chromatography-tandem mass spectrometryIntakes of vitamin C and carotenoids and risk of amyotrophic lateral sclerosis: Pooled results from 5 cohort studies
Fitzgerald KC, O'Reilly ÉJ, Fondell E, Falcone GJ, McCullough ML, Park Y, Kolonel LN, Ascherio A. Intakes of vitamin C and carotenoids and risk of amyotrophic lateral sclerosis: Pooled results from 5 cohort studies. Annals Of Neurology 2013, 73: 236-245. PMID: 23362045, PMCID: PMC3608702, DOI: 10.1002/ana.23820.Peer-Reviewed Original ResearchConceptsRisk of ALSAmyotrophic lateral sclerosisNurses' Health StudyRisk ratioALS deathsVitamin CLateral sclerosisHealth StudyCancer Prevention Study II Nutrition CohortCox proportional hazards regressionMultivariate risk ratiosRetired Persons DietHealth Professionals FollowVitamin C intakeNational Death IndexProportional hazards regressionHigh dietary intakeRandom-effects methodNutrition CohortProfessionals FollowCohort studyProspective cohortC intakeDeath IndexHazards regression
2012
Effect of vitamin C deficiency during postnatal development on adult behavior: functional phenotype of Gulo(−/−) knockout mice
Chen Y, Curran C, Nebert D, Patel K, Williams M, Vorhees C. Effect of vitamin C deficiency during postnatal development on adult behavior: functional phenotype of Gulo(−/−) knockout mice. Genes Brain & Behavior 2012, 11: 269-277. PMID: 22296218, PMCID: PMC3325330, DOI: 10.1111/j.1601-183x.2011.00762.x.Peer-Reviewed Original ResearchConceptsGulo-/- miceBiosynthesis of ascorbateImportant cellular antioxidantAscorbate deficiencyL-gulono-γ-lactone oxidaseAmount of ascorbateGULO geneRate-limiting enzymeReactive oxygen speciesAerobic respirationAbnormal behavioral phenotypesMetabolic processesVitamin CCellular antioxidantsSupplemental vitamin CFunctional phenotypeOxygen speciesVitamin C deficiencyWild-type littermatesMild motor deficitsSpeciesBehavioral phenotypesPhenotypeDopamine agonistsMotor deficits
2011
Enhanced growth and hepatic differentiation of fetal liver epithelial cells through combinational and temporal adjustment of soluble factors
Qian L, Krause DS, Saltzman WM. Enhanced growth and hepatic differentiation of fetal liver epithelial cells through combinational and temporal adjustment of soluble factors. Biotechnology Journal 2011, 7: 440-448. PMID: 21922669, PMCID: PMC3532892, DOI: 10.1002/biot.201100184.Peer-Reviewed Original Research
2009
Improved MAGIC gel for higher sensitivity and elemental tissue equivalent 3D dosimetry
Zhu X, Reese T, Crowley E, Fakhri G. Improved MAGIC gel for higher sensitivity and elemental tissue equivalent 3D dosimetry. Medical Physics 2009, 37: 183-188. PMID: 20175480, PMCID: PMC2801736, DOI: 10.1118/1.3260844.Peer-Reviewed Original ResearchConceptsMAGIC gelTissue equivalentsGel dosimeterRange verificationNuclear reactionsDosimetry applicationsProton beam therapyPhantom materialTime-activity measurementsDosimetry purposesTransverse relaxation rateRelaxation rateBeam therapyDose-response curveSlopes of dose-response curvesGel formulationMAGICDose responseMelting pointSoft tissueDosimetersPhantomTime-activityProtonGlucose
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