2022
Stimulating TAM-mediated anti-tumor immunity with mannose-decorated nanoparticles in ovarian cancer
Glass E, Hoover A, Bullock K, Madden M, Reinfeld B, Harris W, Parker D, Hufnagel D, Crispens M, Khabele D, Rathmell W, Rathmell J, Wilson A, Giorgio T, Yull F. Stimulating TAM-mediated anti-tumor immunity with mannose-decorated nanoparticles in ovarian cancer. BMC Cancer 2022, 22: 497. PMID: 35513776, PMCID: PMC9074180, DOI: 10.1186/s12885-022-09612-2.Peer-Reviewed Original ResearchConceptsTumor-associated macrophagesAnti-tumor immunityOvarian cancerConsecutive days' treatmentTumor burdenMouse modelSolid tumorsImmunosuppressive tumor-associated macrophagesAnti-tumor phenotypeLate-stage diseaseClear therapeutic effectImmune cell compositionImmunosuppressive tumor microenvironmentM1 macrophage polarizationStrong translational potentialOvarian cancer modelFuture clinical studiesNF-κB alphaOvarian cancer progressionHigh response rateNF-κB activityEvidence of toxicityNuclear factor-kappaBInducible transgenic miceID8 modelSingle cell transcriptomic landscape of diabetic foot ulcers
Theocharidis G, Thomas BE, Sarkar D, Mumme HL, Pilcher WJR, Dwivedi B, Sandoval-Schaefer T, Sîrbulescu RF, Kafanas A, Mezghani I, Wang P, Lobao A, Vlachos IS, Dash B, Hsia HC, Horsley V, Bhasin SS, Veves A, Bhasin M. Single cell transcriptomic landscape of diabetic foot ulcers. Nature Communications 2022, 13: 181. PMID: 35013299, PMCID: PMC8748704, DOI: 10.1038/s41467-021-27801-8.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkersCell Adhesion MoleculesChitinase-3-Like Protein 1Diabetes MellitusDiabetic FootEndothelial CellsExome SequencingFibroblastsGene Expression RegulationHigh-Throughput Nucleotide SequencingHumansHypoxia-Inducible Factor 1, alpha SubunitKeratinocytesLeukocytesMacrophagesMatrix Metalloproteinase 1Matrix Metalloproteinase 11Matrix Metalloproteinase 3Single-Cell AnalysisSkinTranscriptomeWound HealingConceptsDiabetic foot ulcerationSpatial transcriptomicsSingle-cell transcriptomic landscapeSingle-cell RNA sequencingPeripheral blood mononuclear cellsBlood mononuclear cellsDiabetic foot ulcersM1 macrophage polarizationNovel therapeutic approachesTranscriptomic landscapeWound healing microenvironmentRNA sequencingDFU patientsDevastating complicationFoot ulcerationDFU healingFoot ulcersDFU treatmentMononuclear cellsM1 macrophagesM2 macrophagesMacrophage polarizationTherapeutic approachesSame patientHigh abundancePenfluridol targets acid sphingomyelinase to inhibit TNF signaling and is therapeutic against inflammatory autoimmune diseases
Chen Y, Liu R, Cui Y, Hettinghouse A, Fu W, Zhang L, Zhang C, Liu C. Penfluridol targets acid sphingomyelinase to inhibit TNF signaling and is therapeutic against inflammatory autoimmune diseases. Arthritis Research & Therapy 2022, 24: 27. PMID: 35045889, PMCID: PMC8767691, DOI: 10.1186/s13075-021-02713-6.Peer-Reviewed Original ResearchConceptsInflammatory autoimmune diseaseAnti-TNF activityNF-κB activationInflammatory arthritisAutoimmune diseasesAcid sphingomyelinase activityTherapeutic effectTumor necrosis factor αInhibitory effectTNFα-transgenic miceCollagen-induced arthritisSeverity of arthritisInflammatory cytokine productionM1 macrophage polarizationBone marrow-derived macrophagesNecrosis factor αNF-κB activitySphingomyelinase activitySmall molecule drug libraryRAW 264.7 macrophage cell lineMarrow-derived macrophagesAcid sphingomyelinaseDrug affinity responsive target stabilityCytokine productionChronic schizophrenia
2016
IRF5 and IRF5 Disease-Risk Variants Increase Glycolysis and Human M1 Macrophage Polarization by Regulating Proximal Signaling and Akt2 Activation
Hedl M, Yan J, Abraham C. IRF5 and IRF5 Disease-Risk Variants Increase Glycolysis and Human M1 Macrophage Polarization by Regulating Proximal Signaling and Akt2 Activation. Cell Reports 2016, 16: 2442-2455. PMID: 27545875, PMCID: PMC5165654, DOI: 10.1016/j.celrep.2016.07.060.Peer-Reviewed Original ResearchMeSH KeywordsAcetylmuramyl-Alanyl-IsoglutamineAdjuvants, ImmunologicAnimalsCell DifferentiationGene Expression RegulationGlycolysisHumansHypoxia-Inducible Factor 1, alpha SubunitInterferon Regulatory FactorsInterleukin-1 Receptor-Associated KinasesIntracellular Signaling Peptides and ProteinsMacrophagesMiceMice, Inbred C57BLMice, KnockoutMutationNod2 Signaling Adaptor ProteinPrimary Cell CultureProtein BindingProto-Oncogene Proteins c-aktReceptor-Interacting Protein Serine-Threonine Kinase 2Signal TransductionTNF Receptor-Associated Factor 6ConceptsInterferon regulatory factor 5Akt2 activationPro-inflammatory cytokinesM1 macrophage polarizationGlycolytic pathway genesHuman macrophagesDisease-associated polymorphismsM1 polarizationMacrophage polarizationInflammatory M1 macrophage polarizationPathway genesProximal signalingOligomerization domainRegulatory factor 5Glycolytic pathwayEnhanced glycolysisGenetic variantsGlycolysisMetabolic outcomesIRF5 expressionM1 macrophagesCentral mediatorFactor 5CytokinesMacrophages
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