2025
Liver lipid droplet cholesterol content is a key determinant of metabolic dysfunction–associated steatohepatitis
Sakuma I, Gaspar R, Nasiri A, Dufour S, Kahn M, Zheng J, LaMoia T, Guerra M, Taki Y, Kawashima Y, Yimlamai D, Perelis M, Vatner D, Petersen K, Huttasch M, Knebel B, Kahl S, Roden M, Samuel V, Tanaka T, Shulman G. Liver lipid droplet cholesterol content is a key determinant of metabolic dysfunction–associated steatohepatitis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2502978122. PMID: 40310463, DOI: 10.1073/pnas.2502978122.Peer-Reviewed Original ResearchConceptsCholine-deficient l-amino acid-defined high-fat dietBempedoic acidLiver fibrosisLiver diseaseL-amino acid-defined high-fat dietAdvanced liver diseaseCholesterol contentHSD17B13 variantsHigh-fat dietTotal liver cholesterol contentTreated miceActivate signaling pathwaysVariant rs738409Liver cholesterol contentLiver lipidsFibrotic responsePromote inflammationTherapeutic approachesSteatotic liver diseaseDietary cholesterol supplementationFibrosisHuman liver samplesI148MAntisense oligonucleotidesProgressive formCold and hot fibrosis define clinically distinct cardiac pathologies
Miyara S, Adler M, Umansky K, Häußler D, Bassat E, Divinsky Y, Elkahal J, Kain D, Lendengolts D, Flores R, Bueno-Levy H, Golani O, Shalit T, Gershovits M, Weizman E, Genzelinakh A, Kimchi D, Shakked A, Zhang L, Wang J, Baehr A, Petrover Z, Sarig R, Dorn T, Moretti A, Saez-Rodriguez J, Kupatt C, Tanaka E, Medzhitov R, Krüger A, Mayo A, Alon U, Tzahor E. Cold and hot fibrosis define clinically distinct cardiac pathologies. Cell Systems 2025, 16: 101198. PMID: 39970910, PMCID: PMC11922821, DOI: 10.1016/j.cels.2025.101198.Peer-Reviewed Original ResearchConceptsHeart failureMyocardial infarctionAutocrine growth factor loopsUnmet medical needCardiac fibrosisNeutralizing antibodiesReduced fibrosisTreatment strategiesMyofibroblast proliferationAcute MIFibrosis post-MICardiac pathologyFibrosisTherapeutic approachesPost-MIChronic injuryMyofibroblastsMedical needFactor loopsInvestigational gene expression inhibitors for the treatment of idiopathic pulmonary fibrosis
Spagnolo P, Tonelli R, Mura M, Reisman W, Sotiropoulou V, Tzouvelekis A. Investigational gene expression inhibitors for the treatment of idiopathic pulmonary fibrosis. Expert Opinion On Investigational Drugs 2025, 34: 61-80. PMID: 39916340, DOI: 10.1080/13543784.2025.2462592.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisGene therapyPulmonary fibrosisAssociated with tolerability issuesProgressive fibrosing interstitial lung diseaseEfficacy of gene therapyApplication of gene therapyTreatment of idiopathic pulmonary fibrosisLong-term clinical dataFibrosing interstitial lung diseaseFirst-line therapyImproved vector designInterstitial lung diseaseMitigate off-target effectsTolerated treatmentDismal prognosisClinical dataLung diseaseClinical studiesAssociated with poor qualityProfibrotic pathwaysTarget cellsTherapyFibrosisOff-target effectsCollagen Hybridizing Peptide-Based Radiotracers for Molecular Imaging of Collagen Turnover in Pulmonary Fibrosis.
Ahmad A, Ghim M, Kukreja G, Neishabouri A, Zhang Z, Li J, Salarian M, Toczek J, Gona K, Hedayatyanfard K, Morrison T, Zhang J, Huang Y, Liu C, Yu S, Sadeghi M. Collagen Hybridizing Peptide-Based Radiotracers for Molecular Imaging of Collagen Turnover in Pulmonary Fibrosis. Journal Of Nuclear Medicine 2025, 66: 425-433. PMID: 39915119, PMCID: PMC11876730, DOI: 10.2967/jnumed.124.268832.Peer-Reviewed Original ResearchConceptsPulmonary fibrosisTracer uptakeLung uptakeMurine model of pulmonary fibrosisModel of pulmonary fibrosisMice 3 wkEffect of antifibrotic therapyCollagen turnoverInterstitial lung diseaseClinical diagnostic methodsSPECT/CT imagingHybrid tracersLung histologyAntifibrotic therapyControl miceDisease activityMurine modelLung diseaseMice 8Tissue fibrosisPatient managementLiver uptakeSPECT/CTFibrosisSPECT imagesNeural network analysis as a novel skin outcome in a trial of belumosudil in patients with systemic sclerosis
Gunes I, Bernstein E, Cowper S, Panse G, Pradhan N, Camacho L, Page N, Bundschuh E, Williams A, Carns M, Aren K, Fantus S, Volkmann E, Bukiri H, Correia C, Kolachalama V, Wilson F, Mawe S, Mahoney J, Hinchcliff M. Neural network analysis as a novel skin outcome in a trial of belumosudil in patients with systemic sclerosis. Arthritis Research & Therapy 2025, 27: 85. PMID: 40217251, DOI: 10.1186/s13075-025-03508-9.Peer-Reviewed Original ResearchConceptsModified Rodnan skin scoreSystemic sclerosisFibrosis scoreHistological parametersDiffuse cutaneous systemic sclerosisInterquartile rangeSystemic sclerosis skin biopsiesRodnan skin scoreCutaneous systemic sclerosisOpen-label trialSkin scorePathological parametersSkin biopsiesBiopsySkin outcomesStudy terminationFibrosisHistological analysisBlinded dermatopathologistStained sectionsSpearman correlationBelumosudilPatientsSkin featuresScores
2024
Portal Fibrosis and the Ductular Reaction: Pathophysiological Role in the Progression of Liver Disease and Translational Opportunities
Gupta V, Sehrawat T, Pinzani M, Strazzabosco M. Portal Fibrosis and the Ductular Reaction: Pathophysiological Role in the Progression of Liver Disease and Translational Opportunities. Gastroenterology 2024, 168: 675-690. PMID: 39251168, PMCID: PMC11885590, DOI: 10.1053/j.gastro.2024.07.044.Peer-Reviewed Original ResearchLiver diseasePortal fibrosisDuctular reactionPathological repairProgression of liver diseaseCholestatic liver diseaseTranslational opportunitiesChronic liver diseaseProgression of fibrosisCell typesChronic human liver diseaseHuman liver diseaseTumor microenvironmentTherapeutic advancesImmune modulationHistological abnormalitiesVascular changesLiver repairPathophysiological roleFibrosisTreatment prospectsPortal spacesMesenchymal cellsVascular cellsComplex crosstalkCasRx-based Wnt activation promotes alveolar regeneration while ameliorating pulmonary fibrosis in a mouse model of lung injury
Shen S, Wang P, Wu P, Huang P, Chi T, Xu W, Xi Y. CasRx-based Wnt activation promotes alveolar regeneration while ameliorating pulmonary fibrosis in a mouse model of lung injury. Molecular Therapy 2024, 32: 3974-3989. PMID: 39245939, PMCID: PMC11573616, DOI: 10.1016/j.ymthe.2024.09.008.Peer-Reviewed Original ResearchWnt/b-catenin signalingStem cell activityLung epitheliumAlveolar regenerationPulmonary fibrosisLung fibrosisWnt signalingCell activationMouse models of lung injuryModel of lung injuryWnt activityAlveolar type II cell proliferationBleomycin-induced injuryAmeliorated pulmonary fibrosisActivation of Wnt signalingType II cell proliferationInhibit lung fibrosisRegenerative medicineAnti-fibrotic effectsTreating pulmonary fibrosisActivated Wnt signalingLung injuryMouse modelFibrosisWnt/b-catenin219 CFTR dysfunction shapes airway immune cell compositions contributing to lung pathogenesis in children with cystic fibrosis
Kizilirmak T, Yin H, Garrison A, Browne J, Bruscia E, Egan M, Britto C. 219 CFTR dysfunction shapes airway immune cell compositions contributing to lung pathogenesis in children with cystic fibrosis. Journal Of Cystic Fibrosis 2024, 23: s119. DOI: 10.1016/s1569-1993(24)01059-2.Peer-Reviewed Original ResearchRetraction: Chitinase 1 regulates pulmonary fibrosis by modulating TGF-β/SMAD7 pathway via TGFBRAP1 and FOXO3
Lee C, He C, Park J, Lee J, Kamle S, Ma B, Akosman B, Cortez R, Chen E, Zhou Y, Herzog E, Ryu C, Peng X, Rosas I, Poli S, Bostwick C, Choi A, Elias J, Lee C. Retraction: Chitinase 1 regulates pulmonary fibrosis by modulating TGF-β/SMAD7 pathway via TGFBRAP1 and FOXO3. Life Science Alliance 2024, 7: e202402987. PMID: 39209538, PMCID: PMC11361373, DOI: 10.26508/lsa.202402987.Peer-Reviewed Original ResearchGlycolysis in hepatic stellate cells coordinates fibrogenic extracellular vesicle release spatially to amplify liver fibrosis
Khanal S, Liu Y, Bamidele A, Wixom A, Washington A, Jalan-Sakrikar N, Cooper S, Vuckovic I, Zhang S, Zhong J, Johnson K, Charlesworth M, Kim I, Yeon Y, Yoon S, Noh Y, Meroueh C, Timbilla A, Yaqoob U, Gao J, Kim Y, Lucien F, Huebert R, Hay N, Simons M, Shah V, Kostallari E. Glycolysis in hepatic stellate cells coordinates fibrogenic extracellular vesicle release spatially to amplify liver fibrosis. Science Advances 2024, 10: eadn5228. PMID: 38941469, PMCID: PMC11212729, DOI: 10.1126/sciadv.adn5228.Peer-Reviewed Original ResearchConceptsHepatic stellate cellsLiver fibrosisExtracellular vesiclesEV releaseHistone 3 lysine 9 acetylationExtracellular vesicle releaseIncreased EV releaseFibrotic gene expressionNanosized extracellular vesiclesPromoter regionVesicle releasePotential therapeutic targetGene expressionGenetic inhibitionSpatial transcriptomicsStellate cellsGlycolysisUp-regulatedFibrosisTherapeutic targetPericentral zoneLiverPathwayAmplificationExpressionNoninvasive assessment of the lung inflammation-fibrosis axis by targeted imaging of CMKLR1
Mannes P, Adams T, Farsijani S, Barnes C, Latoche J, Day K, Nedrow J, Ahangari F, Kaminski N, Lee J, Tavakoli S. Noninvasive assessment of the lung inflammation-fibrosis axis by targeted imaging of CMKLR1. Science Advances 2024, 10: eadm9817. PMID: 38896611, PMCID: PMC11186491, DOI: 10.1126/sciadv.adm9817.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisFibrotic lung diseaseRisk stratificationMurine modelLung fibrosisLung diseaseModel of bleomycin-induced lung fibrosisBleomycin-induced lung fibrosisImaging biomarkersMurine model of bleomycin-induced lung fibrosisBronchoalveolar lavage cellsMonocyte-derived macrophagesPositron emission tomographyInflammatory endotypesPulmonary fibrosisLavage cellsPoor survivalNoninvasive assessmentTherapeutic monitoringEmission tomographyCMKLR1FibrosisClinical trajectoryLungLung regions292-OR: Coenzyme A Synthase Knockdown Alleviates Metabolic Dysfunction–Associated Steatohepatitis via Decreasing Cholesterol in Liver Lipid Droplets
SAKUMA I, GASPAR R, NASIRI A, KAHN M, GUERRA M, YIMLAMAI D, MURRAY S, PERELIS M, BARNES W, VATNER D, PETERSEN K, SAMUEL V, SHULMAN G. 292-OR: Coenzyme A Synthase Knockdown Alleviates Metabolic Dysfunction–Associated Steatohepatitis via Decreasing Cholesterol in Liver Lipid Droplets. Diabetes 2024, 73 DOI: 10.2337/db24-292-or.Peer-Reviewed Original ResearchCholine-deficient l-amino acid-defined high-fat dietAccumulation of cholesterolMRNA expressionPlasma ALTL-amino acid-defined high-fat dietProtective effectLiver lipid dropletsType 2 diabetesPotential therapeutic approachHigh-fat dietDecreased plasma ALTFibrosis markersFree cholesterol accumulationLipid dropletsLiver inflammationDay 1Macrophage markersHepatic inflammationMouse modelMarker expressionTherapeutic approachesDay 2Day 3Day 7FibrosisThe protective role of GATA6+ pericardial macrophages in pericardial inflammation
Hughes D, Won T, Talor M, Kalinoski H, Jurčová I, Szárszoi O, Stříž I, Čurnová L, Bracamonte-Baran W, Melenovský V, Čiháková D. The protective role of GATA6+ pericardial macrophages in pericardial inflammation. IScience 2024, 27: 110244. PMID: 39040070, PMCID: PMC11260870, DOI: 10.1016/j.isci.2024.110244.Peer-Reviewed Original ResearchMyocardial infarctionMyocardial inflammationPericardial inflammationTrafficking of inflammatory monocytesCoxsackievirus B3-induced myocarditisUpregulation of inflammatory markersPreventing interstitial fibrosisCardiac function post-MIStimulated in vitroFunction post-MIInduced pericarditisInflammatory monocytesInflammatory markersBone marrowInterstitial fibrosisCardiac fibrosisAttenuated traffickingPost-MIInflammationInduced upregulationFibrosisMacrophagesGATA6Pericardial cavityCoxsackievirus B3Free-breathing 3D cardiac extracellular volume (ECV) mapping using a linear tangent space alignment (LTSA) model
Lee W, Han P, Marin T, Mounime I, Eslahi S, Djebra Y, Chi D, Fakhri G, Ma C. Free-breathing 3D cardiac extracellular volume (ECV) mapping using a linear tangent space alignment (LTSA) model. Proceedings Of The International Society For Magnetic Resonance In Medicine ... Scientific Meeting And Exhibition. 2024 DOI: 10.58530/2024/1493.Peer-Reviewed Original ResearchAberrant Alveolar Epithelial Cells Alter the Alveolar Mesenchyme to Promote Fibrosis in a Clinical Sftpc Mutation Model of Lung Fibrosis
Hoffman E, Roque Barboza W, Rodriguez L, Murthy A, Dherwani R, Bennett A, Tomer Y, Raredon M, Beers M, Katzen J. Aberrant Alveolar Epithelial Cells Alter the Alveolar Mesenchyme to Promote Fibrosis in a Clinical Sftpc Mutation Model of Lung Fibrosis. 2024, a5197-a5197. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a5197.Peer-Reviewed Original ResearchA Monocyte-specific Gene-signature Predicts Outcomes in Patients With Idiopathic Pulmonary Fibrosis and Is Reproducible in Peripheral Blood, Bronchoalveolar Lavage, and Lung Tissue
Karampitsakos T, Tourki B, Juan-Guardela B, Perrot C, Marlin K, Arsenault A, Binder H, Wuyts W, Rottoli P, Prasse A, Tzouvelekis A, Restrepo Jaramillo R, Qureshi M, Patel K, Bandyopadhyay D, Kaminski N, Herazo-Maya J. A Monocyte-specific Gene-signature Predicts Outcomes in Patients With Idiopathic Pulmonary Fibrosis and Is Reproducible in Peripheral Blood, Bronchoalveolar Lavage, and Lung Tissue. 2024, a2860-a2860. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a2860.Peer-Reviewed Original ResearchA Patient With Oral Discomfort and Reduced Oral Aperture
Chen G, Roy S, Cohen J. A Patient With Oral Discomfort and Reduced Oral Aperture. JAMA 2024, 331: 1147-1148. PMID: 38436993, DOI: 10.1001/jama.2023.25945.Peer-Reviewed Original ResearchReduced oral apertureHistory of cigarette smokingNo history of cigarette smokingLower labial mucosaOral apertureChewing areca nutBuccal mucosaOral discomfortOral mucosaSubepithelial fibrosisLabial mucosaNo historyCigarette smokingChewing tobaccoMucosaAreca nutPatientsBiopsyPainFibrosisOrallyDiagnosisMAP kinase phosphatase-1 inhibition of p38α within lung myofibroblasts is essential for spontaneous fibrosis resolution
Fortier S, Walker N, Penke L, Baas J, Shen Q, Speth J, Huang S, Zemans R, Bennett A, Peters-Golden M. MAP kinase phosphatase-1 inhibition of p38α within lung myofibroblasts is essential for spontaneous fibrosis resolution. Journal Of Clinical Investigation 2024, 134: e172826. PMID: 38512415, PMCID: PMC11093610, DOI: 10.1172/jci172826.Peer-Reviewed Original ResearchConceptsMAPK phosphatase 1Fibrosis resolutionPulmonary fibrosisSpontaneous resolutionLung fibrosisBleomycin-induced lung fibrosisLung fibroblastsProgressive pulmonary fibrosisFibroblast-specific deletionExperimental lung fibrosisCells to apoptosisLung injuryRegulation of MAPK activityApoptosis-resistant myofibroblastsTransgenic miceResident fibroblastsTissue injuryFibrosisLung myofibroblastsLoss-of-function studiesGain- and loss-of-function studiesLungVX-702MyofibroblastsMAPK activationPulmonary Fibrosis Stakeholder Summit: A Joint NHLBI, Three Lakes Foundation, and Pulmonary Fibrosis Foundation Workshop Report
Montesi S, Gomez C, Beers M, Brown R, Chattopadhyay I, Flaherty K, Garcia C, Gomperts B, Hariri L, Hogaboam C, Jenkins R, Kaminski N, Kim G, Königshoff M, Kolb M, Kotton D, Kropski J, Lasky J, Magin C, Maher T, McCormick M, Moore B, Nickerson-Nutter C, Oldham J, Podolanczuk A, Raghu G, Rosas I, Rowe S, Schmidt W, Schwartz D, Shore J, Spino C, Craig J, Martinez F. Pulmonary Fibrosis Stakeholder Summit: A Joint NHLBI, Three Lakes Foundation, and Pulmonary Fibrosis Foundation Workshop Report. American Journal Of Respiratory And Critical Care Medicine 2024, 209: 362-373. PMID: 38113442, PMCID: PMC10878386, DOI: 10.1164/rccm.202307-1154ws.Peer-Reviewed Original ResearchConceptsSlow lung function declinePulmonary fibrosisLung function declineField of pulmonary fibrosisRisk factorsStudy pulmonary fibrosisProgressive pulmonary fibrosisIdiopathic pulmonary fibrosisPulmonary Fibrosis FoundationIdentification of risk factorsFunctional declineElucidation of disease mechanismsClinical trial designDisease risk factorsFibrosisImprove diagnosisTrial designBiomarker discoveryDisease mechanismsPulmonaryMedicationMorbidityTherapyGene expression meta-analysis reveals aging and cellular senescence signatures in scleroderma-associated interstitial lung disease
Yang M, Lee S, Neely J, Hinchcliff M, Wolters P, Sirota M. Gene expression meta-analysis reveals aging and cellular senescence signatures in scleroderma-associated interstitial lung disease. Frontiers In Immunology 2024, 15: 1326922. PMID: 38348044, PMCID: PMC10859856, DOI: 10.3389/fimmu.2024.1326922.Peer-Reviewed Original ResearchConceptsScleroderma-associated interstitial lung diseaseSSc-ILDInterstitial lung diseaseLung tissueGene expression meta-analysisPulmonary fibrosisLung diseaseSenescence signatureDegree of skin involvementIdiopathic pulmonary fibrosisTelomere lengthType II alveolar cellsCellular senescence signaturesCellular senescenceIndependent of ageSkin involvementSSc skinExpression meta-analysisHealthy controlsAssociated with degreeAlveolar cellsLungMeta-analysisAging genesFibrosis
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