2023
Absence of either Ripk3 or Mlkl reduces incidence of hepatocellular carcinoma independent of liver fibrosis
Mohammed S, Thadathil N, Ohene-Marfo P, Tran A, Van Der Veldt M, Georgescu C, Oh S, Nicklas E, Wang D, Haritha N, Luo W, Janknecht R, Miller B, Wren J, Freeman W, Deepa S. Absence of either Ripk3 or Mlkl reduces incidence of hepatocellular carcinoma independent of liver fibrosis. Molecular Cancer Research 2023, 21: 933-946. PMID: 37204757, PMCID: PMC10472095, DOI: 10.1158/1541-7786.mcr-22-0820.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseProgression of NAFLDHepatocellular carcinomaChronic inflammationLiver fibrosisMale miceMouse modelCholine-deficient high-fat dietFemale wild-type miceOncogenic pathwaysFatty liver diseaseMarkers of inflammationHigh-fat dietLow-fat dietDevelopment of inflammationValid therapeutic targetWild-type miceHepatic inflammationInflammation contributesLiver diseaseWT miceFemale miceSex-specific differencesInflammationTherapeutic target
2022
17α-estradiol, a lifespan-extending compound, attenuates liver fibrosis by modulating collagen turnover rates in male mice
Ali Mondal S, Sathiaseelan R, Mann S, Kamal M, Luo W, Saccon T, Isola J, Peelor F, Li T, Freeman W, Miller B, Stout M. 17α-estradiol, a lifespan-extending compound, attenuates liver fibrosis by modulating collagen turnover rates in male mice. AJP Endocrinology And Metabolism 2022, 324: e120-e134. PMID: 36516471, PMCID: PMC9902223, DOI: 10.1152/ajpendo.00256.2022.Peer-Reviewed Original ResearchConceptsLiver fibrosisMale miceCombination hormone replacement therapyMatrix metalloproteinase-2 activityHepatic stellate cell activationChronic liver diseaseHormone replacement therapySubset of womenMetalloproteinase-2 activityStellate cell activationGrowth factor-β1Proinflammatory macrophage activationFibrotic burdenCollagen synthesis ratesChronic treatmentLiver diseaseReplacement therapyCytokine expressionMacrophage contentImmune cellsTGF-β1Estrogen signalingHSC activationFactor-β1Macrophage activationSenolytic treatment reduces cell senescence and necroptosis in Sod1 knockout mice that is associated with reduced inflammation and hepatocellular carcinoma
Thadathil N, Selvarani R, Mohammed S, Nicklas E, Tran A, Kamal M, Luo W, Brown J, Lawrence M, Borowik A, Miller B, Van Remmen H, Richardson A, Deepa S. Senolytic treatment reduces cell senescence and necroptosis in Sod1 knockout mice that is associated with reduced inflammation and hepatocellular carcinoma. Aging Cell 2022, 21: e13676. PMID: 35869934, PMCID: PMC9381894, DOI: 10.1111/acel.13676.Peer-Reviewed Original ResearchConceptsSod1KO miceHepatocellular carcinomaQ treatmentCellular senescenceSenescence-associated secretory phenotype factorsMarkers of necroptosisSod1 knockout miceChronic liver diseaseMarkers of inflammationMonths of ageExpression of p16WT levelsSenolytic treatmentLiver diseaseReduced inflammationCu/Zn-superoxide dismutaseMacrophage levelsLiver fibrosisPhenotype factorsLiver cancerNecrostatin-1sKnockout miceAge-associated pathologiesMice nullInflammation