2023
Mitochondrial DNA and the STING pathway are required for hepatic stellate cell activation
Arumugam S, Li B, Boodapati S, Nathanson M, Sun B, Ouyang X, Mehal W. Mitochondrial DNA and the STING pathway are required for hepatic stellate cell activation. Hepatology 2023, 78: 1448-1461. PMID: 37013923, PMCID: PMC10804318, DOI: 10.1097/hep.0000000000000388.Peer-Reviewed Original ResearchConceptsVoltage-dependent anion channelBioenergetic capacityMitochondrial DNATranscriptional upregulationCyclic GMP-AMP synthaseGMP-AMP synthaseTranscriptional regulationBioenergetic organellesFunctional mitochondriaMitochondrial membraneExternal mitochondrial membraneAnabolic pathwaysMitochondrial massAnion channelInterferon genesHSC transdifferentiationSubsequent activationCGAS-STINGTransdifferentiationIRF3 pathwayPathwaySTING pathwayGenesMitochondriaQuiescent HSCsNew uses for an old remedy: Digoxin as a potential treatment for steatohepatitis and other disorders
Jamshed F, Dashti F, Ouyang X, Mehal W, Banini B. New uses for an old remedy: Digoxin as a potential treatment for steatohepatitis and other disorders. World Journal Of Gastroenterology 2023, 29: 1824-1837. PMID: 37032732, PMCID: PMC10080697, DOI: 10.3748/wjg.v29.i12.1824.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
2018
Digoxin Suppresses Pyruvate Kinase M2-Promoted HIF-1α Transactivation in Steatohepatitis
Ouyang X, Han SN, Zhang JY, Dioletis E, Nemeth BT, Pacher P, Feng D, Bataller R, Cabezas J, Stärkel P, Caballeria J, Pongratz RL, Cai SY, Schnabl B, Hoque R, Chen Y, Yang WH, Garcia-Martinez I, Wang FS, Gao B, Torok NJ, Kibbey RG, Mehal WZ. Digoxin Suppresses Pyruvate Kinase M2-Promoted HIF-1α Transactivation in Steatohepatitis. Cell Metabolism 2018, 27: 339-350.e3. PMID: 29414684, PMCID: PMC5806149, DOI: 10.1016/j.cmet.2018.01.007.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCell NucleusChromatinDigoxinDisease Models, AnimalEndotoxinsHistonesHumansHypoxia-Inducible Factor 1, alpha SubunitInflammationLiverNon-alcoholic Fatty Liver DiseaseOxidation-ReductionProtein BindingPyruvate KinaseTHP-1 CellsTranscription, GeneticTranscriptional ActivationConceptsHIF-1α transactivationSterile inflammationHIF-1α pathway activationNon-alcoholic steatohepatitisKinase M2Major clinical consequencesAbility of digoxinLiver inflammationLiver diseasePyruvate kinase M2Clinical consequencesTherapeutic targetInflammationTissue damageHIF-1αPathway activationDigoxinOxidative stressCardiac glycosidesSteatohepatitisDigoxin bindsNovel roleLiverUbiquitous responseActivation894 - Digoxin Protects from Alcoholic Hepatitis and Inhibits TGF-B Induced Fibrotic Response
Ouyang X, Mehal W. 894 - Digoxin Protects from Alcoholic Hepatitis and Inhibits TGF-B Induced Fibrotic Response. Gastroenterology 2018, 154: s-1109. DOI: 10.1016/s0016-5085(18)33689-8.Peer-Reviewed Original Research
2013
Adenosine is required for sustained inflammasome activation via the A2A receptor and the HIF-1α pathway
Ouyang X, Ghani A, Malik A, Wilder T, Colegio OR, Flavell RA, Cronstein BN, Mehal WZ. Adenosine is required for sustained inflammasome activation via the A2A receptor and the HIF-1α pathway. Nature Communications 2013, 4: 2909. PMID: 24352507, PMCID: PMC3895487, DOI: 10.1038/ncomms3909.Peer-Reviewed Original ResearchMeSH KeywordsAdenosineAdenosine TriphosphateAnimalsCarrier ProteinsCyclic AMPCyclic AMP Response Element-Binding ProteinCyclic AMP-Dependent Protein KinasesHypoxia-Inducible Factor 1, alpha SubunitInflammasomesInterleukin-1betaLipopolysaccharidesLiverMacrophagesMaleMiceMice, Inbred C57BLNLR Family, Pyrin Domain-Containing 3 ProteinReceptor, Adenosine A2ASignal TransductionConceptsHIF-1α pathwayInflammasome activityInflammasome activationA2A receptorsIL-1β productionIL-1β responseReceptor-mediated signalingLack of responseTolerogenic stateChronic diseasesInflammatory responseInflammasome pathwayPrevious exposureLipopolysaccharideAdenosineReceptorsActivationKey regulatorInitial activationPathwaySignalingResponseInterleukinStimuliDisease
2024
RNA modifications in the progression of liver diseases: from fatty liver to cancer
Li S, Mehal W, Ouyang X. RNA modifications in the progression of liver diseases: from fatty liver to cancer. Science China Life Sciences 2024, 67: 2105-2119. PMID: 38809498, PMCID: PMC11545962, DOI: 10.1007/s11427-023-2494-x.Peer-Reviewed Original ResearchRNA modificationsRNA metabolismRNA speciesNon-alcoholic fatty liver diseaseN1-methyladenosineCellular functionsN6-methyladenosineGene expressionRNANon-alcoholic steatohepatitisFatty liver to non-alcoholic steatohepatitisM6AHepatocellular carcinomaGlobal health concernFatty liver diseaseLiver diseaseM5CHigher risk of metabolic syndromePseudouridineAssociated with higher risk of metabolic syndromePathological conditionsRisk of metabolic syndromeGenes-methyladenosineProgression of liver diseaseComplement protein signatures in patients with alcohol-associated hepatitis
Taiwo M, Huang E, Pathak V, Bellar A, Welch N, Dasarathy J, Streem D, McClain C, Mitchell M, Barton B, Szabo G, Dasarathy S, Consortium A, Schaefer E, Luther J, Day L, Ouyang X, Suyavaran A, Mehal W, Jacobs J, Goodman R, Rotroff D, Nagy L. Complement protein signatures in patients with alcohol-associated hepatitis. JCI Insight 2024, 9: e174127. PMID: 38573776, PMCID: PMC11141929, DOI: 10.1172/jci.insight.174127.Peer-Reviewed Original ResearchAlcohol-associated hepatitisSevere AHAlcohol use disorderAlcoholic cirrhosisHealthy controlsPredicting 90-day mortalityComplement proteinsSerum proteome of patientsEthanol-induced liver injurySerum proteomeDevelopment of effective therapiesProteome of patientsAssociated with pro-inflammatory cytokinesProtein signaturesPro-inflammatory cytokinesCoagulation factors IINon-invasive biomarkersDiagnostic challengeSerine protease 1Murine modelEffective therapyLiver injuryPrognostic biomarkerHepatic inflammationC1q binding protein
2022
Digoxin as an emerging therapy in noncardiac diseases
Dashti F, Jamshed F, Ouyang X, Mehal W, Banini B. Digoxin as an emerging therapy in noncardiac diseases. Trends In Pharmacological Sciences 2022, 44: 199-203. PMID: 36396496, DOI: 10.1016/j.tips.2022.10.002.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
2019
Reduction in Serum Cholesterol in Subjects Consuming the Fermented Soy Beverage Q-CAN® Plus (P06-118-19)
Mehal W, Dioletis E, Paiva R, Secor E, Weiss T, Fields M, Ouyang X, Ali A. Reduction in Serum Cholesterol in Subjects Consuming the Fermented Soy Beverage Q-CAN® Plus (P06-118-19). Current Developments In Nutrition 2019, 3: nzz031.p06-118-19. PMCID: PMC6576748, DOI: 10.1093/cdn/nzz031.p06-118-19.Peer-Reviewed Original ResearchTotal cholesterol levelsLDL cholesterolCholesterol levelsLipid parametersTotal cholesterolVisit 1Obese individualsPercentage changeTreatment total cholesterolSerum lipid profileMethods Prospective studyLDL cholesterol valuesPost treatmentVisit 7Clinic visitsHDL cholesterolObese subjectsLean subjectsProspective studyVisit 3Hypolipidemic effectsSerum cholesterolLean individualsLipid profileVisit 8Hematology Safety Data for the Fermented Soy Beverage Q-CAN® Plus (P12-033-19)
Mehal W, Suyavaran A, Dioletis E, Paiva R, Secor E, Weiss T, Fields M, Ouyang X, Ali A. Hematology Safety Data for the Fermented Soy Beverage Q-CAN® Plus (P12-033-19). Current Developments In Nutrition 2019, 3: 3013529. PMCID: PMC6574472, DOI: 10.1093/cdn/nzz035.p12-033-19.Peer-Reviewed Original ResearchObese individualsMean corpuscular hemoglobin concentrationMean corpuscular hemoglobinTreatment periodHematological parametersVisit 1Red blood cell distribution widthC-reactive proteinMethods Prospective studyCell distribution widthYale New Haven HealthCorpuscular hemoglobin concentrationVisit 7Clinic visitsProspective studyVisit 3Significant changesWBC countPlatelet volumeVisit 8Safety dataHematology labCorpuscular volumeHemoglobin concentrationBlood indicesReduction in Serum Levels of Inflammatory Cytokines in Subjects Consuming the Fermented Soy Beverage Q-CAN® Plus (P19-010-19)
Mehal W, Suyavaran A, Dioletis E, Paiva R, Weiss T, Fields M, Ouyang X. Reduction in Serum Levels of Inflammatory Cytokines in Subjects Consuming the Fermented Soy Beverage Q-CAN® Plus (P19-010-19). Current Developments In Nutrition 2019, 3: nzz049.p19-010-19. PMCID: PMC6579392, DOI: 10.1093/cdn/nzz049.p19-010-19.Peer-Reviewed Original ResearchObese subjectsSerum levelsInflammatory cytokinesIL-1raVisit 1Obese individualsHuman magnetic LuminexPDGF-AA levelsMethods Prospective studyKey inflammatory cytokinesAB/BBConclusion ConsumptionGMCSF levelsMagnetic LuminexVisit 7Clinic visitsCytokine levelsLean subjectsProspective studyVisit 3Visit 8Healthy subjectsMetabolic disordersTherapeutic phasePDGF-AA
2015
237 Humans and Mice With NASH Have Increased Plasma Levels of TLR9 Ligand, and a TLR7/9 Bifunctional Antagonist Reduces NASH in Mice
Garcia-Martinez I, Santoro N, Chen Y, Ouyang X, Caprio S, Coffman R, Candia A, Mehal W. 237 Humans and Mice With NASH Have Increased Plasma Levels of TLR9 Ligand, and a TLR7/9 Bifunctional Antagonist Reduces NASH in Mice. Gastroenterology 2015, 148: s-974. DOI: 10.1016/s0016-5085(15)33328-x.Peer-Reviewed Original ResearchSu1058 Low Dose Digoxin Protects From NASH and Alcoholic Hepatitis in Mice by Inhibiting Inflammasome Activity and Mitochondrial ROS Production
Ouyang X, Zhang J, Feng D, Cai S, Protiva P, Garcia-Martinez I, Wang F, Gao B, Mehal W. Su1058 Low Dose Digoxin Protects From NASH and Alcoholic Hepatitis in Mice by Inhibiting Inflammasome Activity and Mitochondrial ROS Production. Gastroenterology 2015, 148: s-1052. DOI: 10.1016/s0016-5085(15)33588-5.Peer-Reviewed Original Research
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