2024
Therapeutic landscape of metabolic dysfunction-associated steatohepatitis (MASH)
Do A, Zahrawi F, Mehal W. Therapeutic landscape of metabolic dysfunction-associated steatohepatitis (MASH). Nature Reviews Drug Discovery 2024, 1-19. PMID: 39609545, DOI: 10.1038/s41573-024-01084-2.Peer-Reviewed Original ResearchSide effect profileTrial end pointsCombination of therapeuticsReverse many aspectsFatty acid synthase inhibitorGenetic susceptibility factorsPlacebo responseEffect profileFibrosis reversalTreated patientsClinical studiesLiver inflammationSynthase inhibitorLiver diseaseTherapeutic approachesClinical useEnd pointsSteatotic liver diseaseTherapeutic landscapeMetabolic environmentHepatocyte deathSusceptibility factorsChronic overnutritionGlobal epidemicLiver
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
2007
The Role of Inflammation and Immunity in the Pathogenesis of Liver Fibrosis
Mehal W, Friedman S. The Role of Inflammation and Immunity in the Pathogenesis of Liver Fibrosis. 2007, 111-121. DOI: 10.1007/978-1-59745-518-3_10.Peer-Reviewed Original ResearchHepatic fibrosisChronic liver diseaseRole of inflammationWound healing responseViral hepatitisLiver diseaseFibrosis progressionAutoimmune diseasesChronic injuryLiver fibrosisCellular sourceFibrosisExtracellular matrixDiseaseRealistic expectationsUbiquitous responseMajor advancesTranscriptional eventsHepatitisInflammationPatientsPathophysiologyPathogenesisInjuryLiver
2001
Involvement of CD1 in Peripheral Deletion of T Lymphocytes Is Independent of NK T Cells
Dao T, Exley M, Mehal W, Tahir S, Snapper S, Taniguchi M, Balk S, Crispe I. Involvement of CD1 in Peripheral Deletion of T Lymphocytes Is Independent of NK T Cells. The Journal Of Immunology 2001, 166: 3090-3097. PMID: 11207260, DOI: 10.4049/jimmunol.166.5.3090.Peer-Reviewed Original ResearchConceptsNK T cellsPeripheral T cell deletionT cell deletionT cellsCell deletionCD1-deficient miceBone marrow chimerasExpression of CD1T cell activationMHC-like moleculesNonlymphoid organsLymph nodesPeripheral deletionNormal miceT lymphocytesCell activationMutant mouse linesMouse linesAttenuated accumulationMiceLymphocytesNovel roleCD1Ab resultsLiver
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 Research
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
1996
Strange brew: T cells in the liver
Crispe I, Mehal W. Strange brew: T cells in the liver. Trends In Immunology 1996, 17: 522-525. PMID: 8961629, DOI: 10.1016/s0167-5699(96)80906-6.Peer-Reviewed Original Research