2025
Uric Acid Stroke Cerebroprotection Transcended Sex, Age, and Comorbidities in a Multicenter Preclinical Trial
Patel R, Kumskova M, Kodali H, Budnik I, Kuznetsov V, Jain A, Jha A, Thedens D, Dhanesha N, Sutariya B, Nagarkatti K, Lamb J, Kamat P, Shi Y, Avery B, Imai T, Jin X, Chauhan A, Boisserand L, Khan M, Dhandapani K, Sanganahalli B, Sansing L, Hess D, Koehler R, McCullough L, Aronowski J, Ayata C, Diniz M, Lyden P, Planas A, Chamorro A, Chauhan A, Leira E, Investigators O. Uric Acid Stroke Cerebroprotection Transcended Sex, Age, and Comorbidities in a Multicenter Preclinical Trial. Stroke 2025, 56: 965-973. PMID: 40091742, PMCID: PMC11932773, DOI: 10.1161/strokeaha.124.048748.Peer-Reviewed Original ResearchConceptsUA-treated animalsPrimary functional outcomeFunctional outcomesMiddle cerebral artery filament occlusionModified intention-to-treat populationIntention-to-treat populationUric acidHuman clinical trialsImprove functional outcomesStudy drugIntravenous salineEffects of UARelevant to patientsClinical trialsPrimary outcomeSaline controlsSecondary outcomesPreclinical trialsDay 2Survival rateDay 7Filament occlusionGroups of animalsComorbiditiesDiverse comorbidities
2023
Does This Child With High Blood Pressure Have Secondary Hypertension?
Nugent J, Jiang K, Funaro M, Saran I, Young C, Ghazi L, Bakhoum C, Wilson F, Greenberg J. Does This Child With High Blood Pressure Have Secondary Hypertension? JAMA 2023, 329: 1012-1021. PMID: 36976276, DOI: 10.1001/jama.2023.3184.Peer-Reviewed Original ResearchConceptsBlood pressure loadAmbulatory blood pressure monitoringSecondary hypertensionBlood pressure monitoringPrimary hypertensionFamily historyBlood pressurePressure monitoringDiastolic blood pressure loadSystolic blood pressure loadSerum uric acid concentrationAmbulatory blood pressureHigh blood pressureHistory of prematurityPrimary care clinicsRisk of biasNumber of patientsDatabases of MEDLINEDiagnostic Accuracy Studies toolLower body weightRandom-effects modelingUric acid concentrationWeb of ScienceLikelihood ratioAsymptomatic presentation
2022
Ethnic and gender differences in hepatic lipid content and related cardiometabolic parameters in lean individuals
Petersen KF, Dufour S, Li F, Rothman DL, Shulman GI. Ethnic and gender differences in hepatic lipid content and related cardiometabolic parameters in lean individuals. JCI Insight 2022, 7 PMID: 35167495, PMCID: PMC9057590, DOI: 10.1172/jci.insight.157906.Peer-Reviewed Original ResearchConceptsCardiometabolic risk factorsInsulin resistanceRisk factorsHDL cholesterolLDL cholesterolTotal cholesterolLean individualsMatsuda insulin sensitivity indexAI menCardiovascular risk factorsHomeostatic model assessmentHepatic triglyceride contentInsulin sensitivity indexType 2 diabetesHepatic lipid contentNovo Nordisk FoundationUric acid concentrationCardiometabolic parametersCardiovascular riskPremenopausal womenFatty liverPlasma insulinInsulin sensitivityPlasma concentrationsModel assessment
2021
Could Sodium/Glucose Co-Transporter-2 Inhibitors Have Antiarrhythmic Potential in Atrial Fibrillation? Literature Review and Future Considerations
Vrachatis DA, Papathanasiou KA, Iliodromitis KE, Giotaki SG, Kossyvakis C, Raisakis K, Kaoukis A, Lambadiari V, Avramides D, Reimers B, Stefanini GG, Cleman M, Giannopoulos G, Lansky A, Deftereos SG. Could Sodium/Glucose Co-Transporter-2 Inhibitors Have Antiarrhythmic Potential in Atrial Fibrillation? Literature Review and Future Considerations. Drugs 2021, 81: 1381-1395. PMID: 34297330, DOI: 10.1007/s40265-021-01565-3.Peer-Reviewed Original ResearchConceptsAtrial fibrillationSGLT2 inhibitorsCardiorenal protectionAntiarrhythmic effectsClinical dataSodium/glucose co-transporter-2 inhibitorClinical data implyDate available evidenceGlucose-lowering medicationsEffective therapeutic optionPotential pathophysiological linkLarge clinical trialsPre-specified endpointsType 2 diabetesPossible beneficial effectsPost Hoc AnalysisNormoglycemic adultsAF burdenAF preventionPathophysiologic mechanismsPathophysiological linkSGLT2 inhibitionAntiarrhythmic potentialSodium glucoseTherapeutic options
2020
Gout Treatment in the USA from 2009 to 2016: A Repeated Cross-sectional Analysis
Chock YP, Ross JS, Suter LG, Rhee TG. Gout Treatment in the USA from 2009 to 2016: A Repeated Cross-sectional Analysis. Journal Of General Internal Medicine 2020, 36: 1134-1136. PMID: 32524250, PMCID: PMC8041910, DOI: 10.1007/s11606-020-05942-8.Peer-Reviewed Original Research
2019
P2X7 Receptor Stimulation Is Not Required for Oxalate Crystal-Induced Kidney Injury
Luz H, Reichel M, Unwin R, Mutig K, Najenson A, Tonner L, Eckardt K, Tam F, Knauf F. P2X7 Receptor Stimulation Is Not Required for Oxalate Crystal-Induced Kidney Injury. Scientific Reports 2019, 9: 20086. PMID: 31882798, PMCID: PMC6934555, DOI: 10.1038/s41598-019-56560-2.Peer-Reviewed Original ResearchConceptsIL-1ß releaseDendritic cellsKidney failureP2X7 receptorBone marrowNLRP3/CASPP2X7 receptor signalingProgressive kidney diseaseSuitable therapeutic targetProgressive kidney failureMonosodium urate crystalsHuman peripheral bloodKidney injuryRenal inflammationRenal injuryTubular damageWT miceIL-1ßKidney diseasePeripheral bloodCytokine releasePlasma creatinineMurine bone marrowInterleukin-1betaInflammasome activation
2017
β-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares
Goldberg EL, Asher JL, Molony RD, Shaw AC, Zeiss CJ, Wang C, Morozova-Roche LA, Herzog RI, Iwasaki A, Dixit VD. β-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares. Cell Reports 2017, 18: 2077-2087. PMID: 28249154, PMCID: PMC5527297, DOI: 10.1016/j.celrep.2017.02.004.Peer-Reviewed Original ResearchConceptsKetogenic dietGouty flaresΒ-hydroxybutyrateMajor risk factorAnti-inflammatory moleculesNLRP3-dependent mannerAlternate metabolic fuelsGout flaresJoint destructionIL-1βIntense painInterleukin-1βNLRP3 inflammasomeRisk factorsInflammatory neutrophilsBacterial infectionsNeutrophilsNLRP3Immune defenseGoutMetabolic fuelsBHBS100A9 fibrilsDietPain
2016
Diagnosis of Acute Gout: A Clinical Practice Guideline From the American College of Physicians.
Qaseem A, McLean R, Starkey M, Forciea M, Denberg T, Barry M, Boyd C, Chow R, Fitterman N, Humphrey L, Kansagara D, Manaker S, Vijan S, Wilt T. Diagnosis of Acute Gout: A Clinical Practice Guideline From the American College of Physicians. Annals Of Internal Medicine 2016, 166: 52-57. PMID: 27802479, DOI: 10.7326/m16-0569.Peer-Reviewed Original ResearchConceptsAcute goutPatient populationAmerican CollegeShort-term clinical outcomesClinical practice guidelinesSynovial fluid analysisTarget patient populationDiagnosis of goutJoint swellingJoint inflammationClinical outcomesDatabase inceptionClinical recommendationsPractice guidelinesGout diagnosisEvaluated outcomesClinical judgmentGRADE methodsSystematic reviewClinical decisionDiagnostic testingGrading systemFluid analysisIntermediate outcomesAdverse effectsUricase Inhibits Nitrogen Dioxide–Promoted Allergic Sensitization to Inhaled Ovalbumin Independent of Uric Acid Catabolism
Ather JL, Burgess EJ, Hoyt LR, Randall MJ, Mandal MK, Matthews DE, Boyson JE, Poynter ME. Uricase Inhibits Nitrogen Dioxide–Promoted Allergic Sensitization to Inhaled Ovalbumin Independent of Uric Acid Catabolism. The Journal Of Immunology 2016, 197: 1720-1732. PMID: 27465529, PMCID: PMC4992621, DOI: 10.4049/jimmunol.1600336.Peer-Reviewed Original ResearchConceptsAllergic airway diseaseAllergic sensitizationAirway diseaseUric acidDevelopment of OVAOVA-specific responsesAirways of miceUric acid levelsAdaptive immune responsesOVA-specific AbT cell proliferationPowerful inhibitory effectEnvironmental air pollutantsImmune deviationOVA challengeOVA uptakeDendritic cellsCytokine productionAdjuvant activityImmune responseRespiratory diseaseMouse modelUric acid formationInhibitory effectAcid levels
2015
Elevated serum uric acid is associated with vascular inflammation but not coronary artery calcification in the healthy octogenarians: the Brazilian study on healthy aging
Malik R, Aneni EC, Shahrayar S, Freitas WM, Ali SS, Veledar E, Latif MA, Aziz M, Ahmed R, Khan SA, Joseph J, Feiz H, Sposito A, Nasir K. Elevated serum uric acid is associated with vascular inflammation but not coronary artery calcification in the healthy octogenarians: the Brazilian study on healthy aging. Aging Clinical And Experimental Research 2015, 28: 359-362. PMID: 26084248, DOI: 10.1007/s40520-015-0395-3.Peer-Reviewed Original ResearchConceptsSerum uric acidElevated hs-CRPCoronary artery calcificationHs-CRPSUA tertilesCardiovascular diseaseCoronary atherosclerosisHealthy octogenariansArtery calcificationVascular inflammationAssociation of SUATertiles of SUAElevated serum uric acidSensitive C-reactive proteinMedian hs-CRPClinical cardiovascular diseaseHigher SUA levelsC-reactive proteinSubclinical cardiovascular diseaseUric acidCAC burdenCAC presenceSUA levelsOverall prevalenceElderly populationSerum uric acid may not be involved in the development of preeclampsia
Chen Q, Lau S, Tong M, Wei J, Shen F, Zhao J, Zhao M. Serum uric acid may not be involved in the development of preeclampsia. Journal Of Human Hypertension 2015, 30: 136-140. PMID: 25994995, DOI: 10.1038/jhh.2015.47.Peer-Reviewed Original ResearchConceptsDevelopment of preeclampsiaSerum levelsSecond trimesterUric acidSeverity of preeclampsiaTime of presentationHigher serum levelsSerum uric acidTime of onsetNormotensive pregnanciesThird trimesterClinical symptomsPregnant womenPreeclampsiaPrediction biomarkersEarly changesRetrospective sampleProspective sampleTrimesterWomenPresentationLess evidenceMeaningful associationsFunctional characterization of NAT/NCS2 proteins of Aspergillus brasiliensis reveals a genuine xanthine–uric acid transporter and an intrinsically misfolded polypeptide
Krypotou E, Scazzocchio C, Diallinas G. Functional characterization of NAT/NCS2 proteins of Aspergillus brasiliensis reveals a genuine xanthine–uric acid transporter and an intrinsically misfolded polypeptide. Fungal Genetics And Biology 2015, 75: 56-63. PMID: 25639910, DOI: 10.1016/j.fgb.2015.01.009.Peer-Reviewed Original ResearchConceptsNucleobase-ascorbate transporterUptake of purinesAcid transportAspergillus nidulansMisfolded polypeptidesER-retainedGFP tagMisfolded proteinsHeterologous expressionEvolutionary implicationsInactive proteinPutative transportersAspergillus brasiliensisFunctional characterizationTurned-overPlasma membranePeptide sequencesIn silicoProteinSubfamilyAspergillusTransport functionLow affinityHigher affinityVacuoles
2013
Transport assays in filamentous fungi: Kinetic characterization of the UapC purine transporter of Aspergillus nidulans
Krypotou E, Diallinas G. Transport assays in filamentous fungi: Kinetic characterization of the UapC purine transporter of Aspergillus nidulans. Fungal Genetics And Biology 2013, 63: 1-8. PMID: 24355588, DOI: 10.1016/j.fgb.2013.12.004.Peer-Reviewed Original ResearchConceptsFilamentous ascomycete Aspergillus nidulansUric acid-xanthine transporterSpecificity profileAscomycete Aspergillus nidulansTransport assaysNucleobase-ascorbate transporter familySubstrate specificity profileMeasured apparent KmGenetic null mutantsAspergillus nidulansA. nidulansNull mutantsFilamentous fungiGerminating conidiosporesTransporter familyKinetic characterizationGenetic backgroundCompetition assaysVmax valuesMaximal expressionApparent KmUapCMorphological stagesAssayKinetic analysisA Role for Uric Acid and the Nalp3 Inflammasome in Antiphospholipid Antibody-Induced IL-1β Production by Human First Trimester Trophoblast
Mulla MJ, Salmon JE, Chamley LW, Brosens JJ, Boeras CM, Kavathas PB, Abrahams VM. A Role for Uric Acid and the Nalp3 Inflammasome in Antiphospholipid Antibody-Induced IL-1β Production by Human First Trimester Trophoblast. PLOS ONE 2013, 8: e65237. PMID: 23762324, PMCID: PMC3675211, DOI: 10.1371/journal.pone.0065237.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, AntiphospholipidAntiphospholipid Syndromebeta 2-Glycoprotein ICARD Signaling Adaptor ProteinsCarrier ProteinsCaspase 1Cell LineCytoskeletal ProteinsFemaleGene Expression RegulationHumansInflammasomesInterleukin-1betaMiceNLR Family, Pyrin Domain-Containing 3 ProteinPregnancyPregnancy Trimester, FirstProtein PrecursorsSignal TransductionToll-Like Receptor 4TrophoblastsUric AcidConceptsIL-1β productionIntrauterine growth restrictionIL-1β secretionAntiphospholipid syndromeIL-1β processingAntiphospholipid antibodiesIL-1βHuman first trimester trophoblast cell lineFirst trimester trophoblast cell lineUric acidNalp3/ASC inflammasomeHuman first trimester trophoblast cellsToll-like receptor 4Human first-trimester trophoblastsFirst trimester trophoblast cellsAnti-β2GPI AbsAdverse pregnancy outcomesAnti-β2GPI antibodiesRecurrent pregnancy lossTLR4-dependent mannerApoptosis-associated speck-like proteinMaternal-fetal interfaceFirst trimester trophoblastsSpeck-like proteinTrophoblast cell line
2012
Sterile Inflammation in the Liver
Kubes P, Mehal WZ. Sterile Inflammation in the Liver. Gastroenterology 2012, 143: 1158-1172. PMID: 22982943, DOI: 10.1053/j.gastro.2012.09.008.Peer-Reviewed Original ResearchMeSH KeywordsAcetaminophenAdenosine TriphosphateCaspase 1Chemical and Drug Induced Liver InjuryChemotaxis, LeukocyteCytokinesFatty LiverFatty Liver, AlcoholicHepatitisHMGB1 ProteinHumansInflammasomesInterleukin-1betaNeutrophilsNon-alcoholic Fatty Liver DiseaseNucleic AcidsReceptors, Pattern RecognitionReperfusion InjurySignal TransductionUric AcidConceptsDamage-associated molecular patternsPattern recognition receptorsImmune cellsSterile inflammationRecognition receptorsCellular pattern recognition receptorsDrug-induced liver injuryEndogenous damage-associated molecular patternsSuch damage-associated molecular patternsMolecular patternsSite of injuryPathogen-associated molecular patternsProtease caspase-1Alcoholic steatohepatitisLiver injuryNonalcoholic steatohepatitisLiver diseaseProinflammatory cytokinesSpecific therapyInterleukin-1βLiver pathologyTissue injuryImmune responseTherapeutic targetActivate receptorsGBP5 Promotes NLRP3 Inflammasome Assembly and Immunity in Mammals
Shenoy AR, Wellington DA, Kumar P, Kassa H, Booth CJ, Cresswell P, MacMicking JD. GBP5 Promotes NLRP3 Inflammasome Assembly and Immunity in Mammals. Science 2012, 336: 481-485. PMID: 22461501, DOI: 10.1126/science.1217141.Peer-Reviewed Original ResearchMeSH KeywordsAlum CompoundsAnimalsApoptosis Regulatory ProteinsCARD Signaling Adaptor ProteinsCarrier ProteinsCaspase 1Cell LineCytoskeletal ProteinsGTP-Binding ProteinsHumansInflammasomesInterferon-gammaInterleukin-1betaLipopolysaccharidesListeria monocytogenesListeriosisMacrophagesMiceNLR Family, Pyrin Domain-Containing 3 ProteinProtein MultimerizationRNA InterferenceSalmonella typhimuriumUric AcidConceptsGuanylate binding protein 5IL-1β/ILImpaired host defensePresence of infectionNLRP3 inflammasome activationCaspase-1 cleavageNLRP3 inflammasome responseNLRP3 inflammasome assemblyInflammasome assemblyBinding protein 5Inflammatory responseInflammasome activationImmune systemTissue damageInflammasome responseHost defenseInflammasome complexCaspase-1Sensory complexProtein 5InflammasomePathogenic bacteriaILInterleukinNLR
2011
Uric acid is a danger signal of increasing risk for osteoarthritis through inflammasome activation
Denoble AE, Huffman KM, Stabler TV, Kelly SJ, Hershfield MS, McDaniel GE, Coleman RE, Kraus VB. Uric acid is a danger signal of increasing risk for osteoarthritis through inflammasome activation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 2088-2093. PMID: 21245324, PMCID: PMC3033282, DOI: 10.1073/pnas.1012743108.Peer-Reviewed Original ResearchConceptsIL-18OA severityIL-1βUric acidOA progressionSynovial fluid IL-1βCohort of subjectsKnee OA severityInnate immune systemKnee osteoarthritisBone scintigraphyNLRP3 inflammasomeOA pathologyInflammasome activationDanger signalsImmune systemOsteoarthritisRadiographsSeverityPotential involvementInflammasomeProgressionScintigraphyNLRP3CytokinesUric Acid Induces Trophoblast IL‐1β Production Via the Inflammasome: Implications for the Pathogenesis of Preeclampsia
Mulla MJ, Myrtolli K, Potter J, Boeras C, Kavathas PB, Sfakianaki AK, Tadesse S, Norwitz ER, Guller S, Abrahams VM. Uric Acid Induces Trophoblast IL‐1β Production Via the Inflammasome: Implications for the Pathogenesis of Preeclampsia. American Journal Of Reproductive Immunology 2011, 65: 542-548. PMID: 21352397, PMCID: PMC3114103, DOI: 10.1111/j.1600-0897.2010.00960.x.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingApoptosis Regulatory ProteinsCARD Signaling Adaptor ProteinsCarrier ProteinsCaspase 1Cell LineCytoskeletal ProteinsDisease ProgressionEnzyme ActivationFemaleGene Expression Regulation, DevelopmentalHumansHyperuricemiaInflammasomesInterleukin-1betaMaternal-Fetal RelationsNLR Family, Pyrin Domain-Containing 3 ProteinNLR ProteinsPre-EclampsiaPregnancyTrophoblastsUric AcidConceptsIL-1β secretionIL-1β productionMonosodium urateTrophoblast cellsUric acidFirst trimester trophoblast cellsAdverse pregnancy outcomesPathogenesis of preeclampsiaMaternal-fetal interfaceInduction of inflammationActive IL-1βNOD-like receptorsThird trimester trophoblastActive caspase-1Uric acid increasesCaspase-1 activationIL-1β processingPregnancy outcomesInflammatory dysregulationPlacental dysfunctionClinical manifestationsIL-1βInflammasome activationNALP3 inflammasomePreeclampsia
2005
Urinary angiogenic factors cluster hypertensive disorders and identify women with severe preeclampsia
Buhimschi CS, Norwitz ER, Funai E, Richman S, Guller S, Lockwood CJ, Buhimschi IA. Urinary angiogenic factors cluster hypertensive disorders and identify women with severe preeclampsia. American Journal Of Obstetrics And Gynecology 2005, 192: 734-741. PMID: 15746665, DOI: 10.1016/j.ajog.2004.12.052.Peer-Reviewed Original ResearchConceptsVascular endothelial growth factorSevere preeclampsiaHypertensive disordersHypertensive womenUrinary levelsUrinary outputSFlt-1Soluble fms-like tyrosine kinase-1Fms-like tyrosine kinase-1Antiangiogenic factors sFlt-1Growth factorSFlt-1 concentrationsHealthy pregnant controlsPlacental growth factorTime of enrollmentTyrosine kinase-1Urinary protein measurementsEndothelial growth factorClinical preeclampsiaProteinuric womenPlGF levelsNonpregnant womenPlGF ratioPregnant controlsGestational age
2004
Uric acid and the state of the intrarenal renin-angiotensin system in humans
Perlstein TS, Gumieniak O, Hopkins PN, Murphey LJ, Brown NJ, Williams GH, Hollenberg NK, Fisher ND. Uric acid and the state of the intrarenal renin-angiotensin system in humans. Kidney International 2004, 66: 1465-1470. PMID: 15458439, DOI: 10.1111/j.1523-1755.2004.00909.x.Peer-Reviewed Original ResearchConceptsIntrarenal renin-angiotensin systemRenin-angiotensin systemSerum uric acid concentrationBody mass indexHigh-density lipoproteinUric acid concentrationRenal vascular responsePlasma renin activityAng IIRPF responseExperimental hyperuricemiaBlood pressureVascular responsesUric acidRenal plasma flow responsePara-aminohippuric acid clearanceHigh sodium balanceIntrarenal RAS activityRenal vascular responsivenessExogenous angiotensin IISerum high-density lipoproteinSerum uric acidMultivariable regression analysisPlasma flow responseRenin activity
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