2024
The effect of a fermented soy beverage among patients with localized prostate cancer prior to radical prostatectomy
Lokeshwar S, Ali A, Weiss T, Reynolds J, Shuch B, Ferencz T, Kyriakides T, Mehal W, Brito J, Renzulli J, Leapman M. The effect of a fermented soy beverage among patients with localized prostate cancer prior to radical prostatectomy. BMC Urology 2024, 24: 102. PMID: 38702664, PMCID: PMC11067086, DOI: 10.1186/s12894-024-01483-y.Peer-Reviewed Original ResearchConceptsEnd-of-studyProstate cancerRadical prostatectomyTreatment armsDouble-blind randomized trialProstate cancer characteristicsSurgical margin statusLocalized prostate cancerFACT-P scoresBaseline to end-of-studySerum PSACAPRA scoreGleason scorePSA levelsPlacebo-controlledMedium-chain triglyceridesPrimary endpointIntermediate riskClinical stageMargin statusSerum testosteroneRandomization armFACT-PRisk strataITT analysisLetter to the Editor: Concerns regarding the use of fatty liver index in studies of lean NAFLD
Zahrawi F, Mehal W. Letter to the Editor: Concerns regarding the use of fatty liver index in studies of lean NAFLD. Hepatology 2024, 79: e129-e129. PMID: 38214551, DOI: 10.1097/hep.0000000000000754.Peer-Reviewed Original Research
2023
Bioactive signalling lipids as drivers of chronic liver diseases
Kaffe E, Tisi A, Magkrioti C, Aidinis V, Mehal W, Flavell R, Maccarrone M. Bioactive signalling lipids as drivers of chronic liver diseases. Journal Of Hepatology 2023, 80: 140-154. PMID: 37741346, DOI: 10.1016/j.jhep.2023.08.029.Peer-Reviewed Original ResearchConceptsChronic liver diseaseLiver diseasePrevalent chronic liver diseaseBioactive lipidsPotential therapeutic targetG protein-coupled receptorsProtein-coupled receptorsTherapeutic targetPoly-unsaturated fatty acidsMalignant transformationPotent modulatorEnergy homeostasisDiseaseCell proliferationSignaling lipidsTissue repairReceptorsFatty acidsMultiple cellular functionsLipidsBioactive roleBioactive signaling lipidsInflammationProgressionHumanized mouse liver reveals endothelial control of essential hepatic metabolic functions
Kaffe E, Roulis M, Zhao J, Qu R, Sefik E, Mirza H, Zhou J, Zheng Y, Charkoftaki G, Vasiliou V, Vatner D, Mehal W, AlcHepNet, Kluger Y, Flavell R. Humanized mouse liver reveals endothelial control of essential hepatic metabolic functions. Cell 2023, 186: 3793-3809.e26. PMID: 37562401, PMCID: PMC10544749, DOI: 10.1016/j.cell.2023.07.017.Peer-Reviewed Original ResearchConceptsMetabolic functionsSpecies-specific interactionsKey metabolic functionsCell-autonomous mechanismsNon-alcoholic fatty liver diseaseMajor metabolic hubNon-parenchymal cellsMetabolic hubHuman hepatocytesMicroenvironmental regulationHuman diseasesHuman-specific aspectsHuman pathologiesHomeostatic processesSpecies mismatchCholesterol uptakeFatty liver diseaseParacrine mannerHuman immuneBile acid conjugationSinusoidal endothelial cellsHepatic metabolic functionMouse liverEndothelial cellsCellsMitochondrial 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
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
Incorporating Weight Loss Medications Into Hepatology Practice for Nonalcoholic Steatohepatitis
Do A, Kuszewski EJ, Langberg K, Mehal W. Incorporating Weight Loss Medications Into Hepatology Practice for Nonalcoholic Steatohepatitis. Hepatology 2019, 70: 1443-1456. PMID: 30991446, PMCID: PMC6783325, DOI: 10.1002/hep.30658.Peer-Reviewed Original ResearchConceptsTotal body weight lossWeight loss medicationsNonalcoholic steatohepatitisHepatology clinicStaging of NASHPartial histological responseBody weight lossHepatology practiceNASH histologyLiver histologyClinical profileLiver diseaseLiver triglyceridesNew medicationsClinical trialsHistological responseLifestyle changesPatientsMedicationsUncommonly resultsNatural historyClinical interventionsWeight lossSteatohepatitisHepatologists
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 responseActivation
2015
Antifibrotic Therapies in the Liver
Mehal W, Schuppan D. Antifibrotic Therapies in the Liver. Seminars In Liver Disease 2015, 35: 184-198. PMID: 25974903, PMCID: PMC5743222, DOI: 10.1055/s-0035-1550055.Peer-Reviewed Original ResearchConceptsAntifibrotic therapyIdeal patient populationRegression of fibrosisBest noninvasive methodFibrolytic propertiesDose titrationClinical outcomesFibrosis regressionPulmonary fibrosisPatient populationCombination therapyLiver fibrosisIndividualized therapyEncouraging dataFibrotic responseTherapeutic targetDrug AdministrationFibrosisTherapyNoninvasive methodInterindividual heterogeneityCell populationsAntifibroticsLiverFibrolysis
2014
Lactate Reduces Liver and Pancreatic Injury in Toll-Like Receptor– and Inflammasome-Mediated Inflammation via GPR81-Mediated Suppression of Innate Immunity
Hoque R, Farooq A, Ghani A, Gorelick F, Mehal WZ. Lactate Reduces Liver and Pancreatic Injury in Toll-Like Receptor– and Inflammasome-Mediated Inflammation via GPR81-Mediated Suppression of Innate Immunity. Gastroenterology 2014, 146: 1763-1774. PMID: 24657625, PMCID: PMC4104305, DOI: 10.1053/j.gastro.2014.03.014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Inflammatory AgentsArrestinsBeta-Arrestin 2Beta-ArrestinsCarrier ProteinsCell LineCeruletideChemical and Drug Induced Liver InjuryCytoprotectionDisease Models, AnimalDose-Response Relationship, DrugDown-RegulationGalactosamineHumansImmunity, InnateInflammasomesInjections, IntraperitonealInterleukin-1betaLipopolysaccharidesLiverMacrophagesMaleMiceMice, Inbred C57BLMonocytesNF-kappa BNLR Family, Pyrin Domain-Containing 3 ProteinPancreasPancreatitisReceptors, G-Protein-CoupledRNA InterferenceRNA, Small InterferingSignal TransductionSodium LactateToll-Like Receptor 4Toll-Like ReceptorsTransfectionConceptsToll-like receptorsRelease of IL1βAdministration of lipopolysaccharideOrgan injuryNF-κBCaspase-1TLR inductionAcute pancreatitisPyrin domain-containing protein 3Administration of lactatePromising immunomodulatory therapyAcute liver injuryAcute organ injuryMacrophages of miceDomain-containing protein 3Production of IL1βRAW 264.7 cellsConcentration of lactateAcute hepatitisImmunomodulatory therapyImmune hepatitisPancreatic injuryLactate receptorLiver injuryNLRP3 inflammasome
2013
The Gordian Knot of dysbiosis, obesity and NAFLD
Mehal WZ. The Gordian Knot of dysbiosis, obesity and NAFLD. Nature Reviews Gastroenterology & Hepatology 2013, 10: 637-644. PMID: 23958600, DOI: 10.1038/nrgastro.2013.146.Peer-Reviewed Original Research
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 receptors
2010
Cell Death and Fibrogenesis
Mehal W, Imaeda A. Cell Death and Fibrogenesis. Seminars In Liver Disease 2010, 30: 226-231. PMID: 20665375, PMCID: PMC3219753, DOI: 10.1055/s-0030-1255352.BooksConceptsHepatic stellate cellsQuiescent hepatic stellate cellsChronic liver injuryNatural killer cellsCell deathHIV infectionLiver injuryNK cellsKiller cellsAntifibrotic effectsImmune suppressionImmune cellsProfibrotic effectsStellate cellsHepatocyte deathHSC apoptosisDeathCellular deathFibrosisCellular debrisMatrix depositionHSC deathSurvival signalsApoptotic bodiesProapoptotic signals
2009
Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome
Imaeda AB, Watanabe A, Sohail MA, Mahmood S, Mohamadnejad M, Sutterwala FS, Flavell RA, Mehal WZ. Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome. Journal Of Clinical Investigation 2009, 119: 305-314. PMID: 19164858, PMCID: PMC2631294, DOI: 10.1172/jci35958.Peer-Reviewed Original ResearchMeSH KeywordsAcetaminophenAnalgesics, Non-NarcoticAnimalsApoptosisAspirinCarrier ProteinsCaspase InhibitorsCell LineCyclooxygenase InhibitorsDose-Response Relationship, DrugHumansImmunity, InnateInflammationInterleukin-18Interleukin-1betaLiverMiceMice, Inbred C57BLNLR Family, Pyrin Domain-Containing 3 ProteinSignal TransductionToll-Like Receptor 9ConceptsLiver injuryIL-1betaNALP3 inflammasomeHepatocyte deathAcetaminophen-induced liver injuryCaspase-1Proinflammatory cytokine activationInnate immune activationSterile inflammatory responseType of injuryCOX-1 inhibitionMature IL-1betaPotential therapeutic approachSinusoidal endothelial cellsOverall tissue injuryIL-18Immune activationProinflammatory cytokinesTLR9 antagonistInitial insultInflammatory responseTissue injuryProtective effectCytokine activationTherapeutic approaches
2001
Immunology of the healthy liver: Old questions and new insights
Mehal W, Azzaroli F, Crispe I. Immunology of the healthy liver: Old questions and new insights. Gastroenterology 2001, 120: 250-260. PMID: 11208734, DOI: 10.1053/gast.2001.20947.Peer-Reviewed Original Research
2000
The liver as a site of T‐cell apoptosis: graveyard, or killing field?
Crispe I, Dao T, Klugewitz K, Mehal W, Metz D. The liver as a site of T‐cell apoptosis: graveyard, or killing field? Immunological Reviews 2000, 174: 47-62. PMID: 10807506, DOI: 10.1034/j.1600-0528.2002.017412.x.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAntigensApoptosisCD8-Positive T-LymphocytesCell AdhesionEndothelium, VascularFas ReceptorHepatitis CHumansImmune ToleranceImmunophenotypingIntestinal AbsorptionKiller Cells, NaturalKupffer CellsLiverLiver CirculationLiver TransplantationLymphocyte ActivationLymphocyte SubsetsMiceMice, TransgenicModels, ImmunologicalPortal VeinConceptsT cellsNatural killerT cell trappingNK T cellsPeripheral immune responsePortal vein infusionApoptotic T cellsT cell apoptosisNormal mouse liverPhenomenon of toleranceApoptotic CD8Liver allograftsOral toleranceHepatitis C.Lymphocyte populationsAntigenic cellsImmune responseLiver pathogensVein infusionClearance phaseLiver resultsLiverDirect perfusionMouse liverCell populations
1999
Selective retention of activated CD8+ T cells by the normal liver.
Mehal W, Juedes A, Crispe I. Selective retention of activated CD8+ T cells by the normal liver. The Journal Of Immunology 1999, 163: 3202-10. PMID: 10477588, DOI: 10.4049/jimmunol.163.6.3202.Peer-Reviewed Original ResearchA prognostic rule for elderly patients admitted with community-acquired pneumonia
Conte H, Chen Y, Mehal W, Phil D, Scinto J, Quagliarello V. A prognostic rule for elderly patients admitted with community-acquired pneumonia. The American Journal Of Medicine 1999, 106: 20-28. PMID: 10320113, DOI: 10.1016/s0002-9343(98)00369-6.Peer-Reviewed Original ResearchConceptsCommunity-acquired pneumoniaElderly patientsDerivation cohortValidation cohortStaging systemHeterogeneous adult populationAdult populationHospital mortality ratePrognostic staging systemVital sign abnormalitiesHospital mortalityCreatinine levelsIndependent predictorsMultivariable analysisPrognostic stratificationAdmission characteristicsPneumoniaMortality ratePatientsCohortPrognostic rulesMotor responseMortalityGreater overall accuracyAdmission
1998
IL-18 augments perforin-dependent cytotoxicity of liver NK-T cells.
Dao T, Mehal W, Crispe I. IL-18 augments perforin-dependent cytotoxicity of liver NK-T cells. The Journal Of Immunology 1998, 161: 2217-22. PMID: 9725214, DOI: 10.4049/jimmunol.161.5.2217.Peer-Reviewed Original ResearchMeSH KeywordsAdjuvants, ImmunologicAnimalsCytokinesCytotoxicity, ImmunologicHumansInterferon InducersInterferon-gammaInterleukin-18Jurkat CellsKiller Cells, NaturalLiverLymphoproliferative DisordersMembrane GlycoproteinsMiceMice, Inbred C57BLMice, Inbred StrainsMice, KnockoutPerforinPore Forming Cytotoxic ProteinsT-Lymphocyte SubsetsT-Lymphocytes, CytotoxicTumor Necrosis Factor-alphaConceptsNK T cellsLiver NK T cellsIL-18NK cellsIntrahepatic lymphocyte subpopulationsNK cell activityPerforin-dependent cytotoxicityPerforin-dependent pathwayTNF-alpha productionSoluble TNF-alphaT cell linesLymphocyte subpopulationsCytotoxic cellsTNF-alphaT cellsCell activityExact mechanismNKCell populationsCell linesLiverCytotoxicityCellsCytokinesCTL