2024
Ferroptosis in Osteoarthritis: Towards Novel Therapeutic Strategy
Zhang Y, Li J, Liu J, Gao Y, Li K, Zhao X, Liu Y, Wang D, Hu X, Wang Z. Ferroptosis in Osteoarthritis: Towards Novel Therapeutic Strategy. Cell Proliferation 2024, 58: e13779. PMID: 39624950, PMCID: PMC11882765, DOI: 10.1111/cpr.13779.Peer-Reviewed Original ResearchArticular cartilageTherapeutic strategiesChondrocyte viabilityCell deathMechanical stressNovel therapeutic strategiesOA cartilagePotential therapeutic strategyIron-dependent formPersistent painRegulated cell deathAutophagic cell deathIron overloadPathogenetic mechanismsExtracellular matrix integrityInflammatory responseContrast‐enhanced computed tomography for ex vivo assessment of human kidneys: A proof‐of‐concept study
Feizi A, DiRito J, Richfield O, Stendahl J, Harris M, Spindler S, Edwards C, Lysyy T, Lee S, Boutagy N, Feher A, Yoo P, Hosgood S, Mulligan D, Nicholson M, Sinusas A, Haakinson D, Tietjen G. Contrast‐enhanced computed tomography for ex vivo assessment of human kidneys: A proof‐of‐concept study. Artificial Organs 2024, 48: 1536-1548. PMID: 39189738, DOI: 10.1111/aor.14840.Peer-Reviewed Original ResearchContrast-enhanced computed tomographyNormothermic perfusionComputed tomographyHuman kidneyLocal informationAnalysis of biopsiesAssess organ functionNovel therapeutic strategiesEx vivo assessmentWhole organ perfusionProof-of-concept studyEx vivo perfusionInfusion scansAnatomical structuresOrgan perfusion
2023
Circulating Mitochondrial DNA Is Associated With High Levels of Fatigue in Two Independent Sarcoidosis Cohorts
Fiorini V, Hu B, Sun Y, Yu S, McGovern J, Gandhi S, Woo S, Turcotte-Foster S, Pivarnik T, Khan Z, Adams T, Herzog E, Kaminski N, Gulati M, Ryu C. Circulating Mitochondrial DNA Is Associated With High Levels of Fatigue in Two Independent Sarcoidosis Cohorts. CHEST Journal 2023, 165: 1174-1185. PMID: 37977267, PMCID: PMC11110677, DOI: 10.1016/j.chest.2023.11.020.Peer-Reviewed Original ResearchPatient-related outcome measuresToll-like receptor 9Fatigue Assessment ScalePlasma mtDNA concentrationsTLR9 activationSarcoidosis patientsMtDNA concentrationsMulti-organ sarcoidosisCommon chief complaintInnate immune activationNovel therapeutic strategiesDomains of fatigueSevere clinical phenotypePsychobiologic mechanismsSarcoidosis cohortScadding stageCorticosteroid useCytokine levelsExtrapulmonary diseaseProspective cohortFAS scoresPulmonary fibrosisChief complaintImmune activationPatient populationTLR9 ligand sequestration by chemokine CXCL4 negatively affects central B cell tolerance
Çakan E, Kioon M, Garcia-Carmona Y, Glauzy S, Oliver D, Yamakawa N, Loza A, Du Y, Schickel J, Boeckers J, Yang C, Baldo A, Ivashkiv L, Young R, Staudt L, Moody K, Nündel K, Marshak-Rothstein A, van der Made C, Hoischen A, Hayward A, Rossato M, Radstake T, Cunningham-Rundles C, Ryu C, Herzog E, Barrat F, Meffre E. TLR9 ligand sequestration by chemokine CXCL4 negatively affects central B cell tolerance. Journal Of Experimental Medicine 2023, 220: e20230944. PMID: 37773045, PMCID: PMC10541333, DOI: 10.1084/jem.20230944.Peer-Reviewed Original ResearchConceptsCentral B cell toleranceB cell toleranceCell toleranceB cellsSystemic sclerosisTLR9 functionNovel therapeutic strategiesTLR9/MyD88Immature B cellsB cell receptorTolerogenic functionSSc patientsTLR9 expressionHumanized miceTLR9 responsesAutoreactive clonesTherapeutic strategiesChemokine CXCL4Cell receptorCXCL4Vivo productionTLR9MyD88ReceptorsCellsLoss of ZNF148 enhances insulin secretion in human pancreatic β cells
de Klerk E, Xiao Y, Emfinger C, Keller M, Berrios D, Loconte V, Ekman A, White K, Cardone R, Kibbey R, Attie A, Hebrok M. Loss of ZNF148 enhances insulin secretion in human pancreatic β cells. JCI Insight 2023, 8: e157572. PMID: 37288664, PMCID: PMC10393241, DOI: 10.1172/jci.insight.157572.Peer-Reviewed Original ResearchConceptsPancreatic β-cellsΒ-cellsSC-β cellsHuman pancreatic β-cellsInsulin secretionHuman β-cellsVesicle traffickingGenetic regulatorsStem cell-derived β cellsDirect repressionS100 genesCells identifiesZNF148Annexin A2Tetrameric complexCell membraneNovel therapeutic targetNovel therapeutic strategiesHuman isletsRegulatorTherapeutic targetCellsS100A16 expressionGlucose homeostasisTherapeutic strategiesInterrogating the Etiology of Sporadic Alzheimer’s Disease Using Aging Rhesus Macaques: Cellular, Molecular, and Cortical Circuitry Perspectives
Datta D. Interrogating the Etiology of Sporadic Alzheimer’s Disease Using Aging Rhesus Macaques: Cellular, Molecular, and Cortical Circuitry Perspectives. The Journals Of Gerontology Series A 2023, 78: 1523-1534. PMID: 37279946, PMCID: PMC10460555, DOI: 10.1093/gerona/glad134.Peer-Reviewed Original ResearchConceptsPrimate dorsolateral prefrontal cortexSporadic Alzheimer's diseaseAlzheimer's diseaseDorsolateral prefrontal cortexRhesus macaquesPrefrontal cortexSignificant risk factorsHuman Alzheimer's diseaseAspartic acid (NMDA) receptorsNonhuman primate modelNovel therapeutic strategiesCalcium-buffering proteinsPattern of pathologyInflammatory cascadeTau pathologyNeuropathological cascadeSynaptic dysfunctionRisk factorsPrimate modelNeurofibrillary tanglesAmyloid plaquesDendritic spinesTherapeutic strategiesGenetic predispositionAnimal modelsArtemis inhibition as a therapeutic strategy for acute lymphoblastic leukemia
Ogana H, Hurwitz S, Hsieh C, Geng H, Müschen M, Bhojwani D, Wolf M, Larocque J, Lieber M, Kim Y. Artemis inhibition as a therapeutic strategy for acute lymphoblastic leukemia. Frontiers In Cell And Developmental Biology 2023, 11: 1134121. PMID: 37082620, PMCID: PMC10111164, DOI: 10.3389/fcell.2023.1134121.Peer-Reviewed Original ResearchMature B cell lineB-cell acute lymphoblastic leukemiaB cell linesDNA double-strand break repairChromosome breaksDouble-strand break repairDNA-PKcs complexDNA-PK inhibitorGene expression analysisCell linesAcute lymphoblastic leukemiaKey endonucleaseDNA-PKcsBreak repairNonhomologous endExpression analysisLymphoblastic leukemiaTherapeutic strategiesRefractory B-cell acute lymphoblastic leukemiaHigh-risk prePharmacological inhibitionNovel therapeutic strategiesIndirect suppressionDirect inhibitionProliferationTolerance Induction in Vascularized Composite Allotransplantation—A Brief Review of Preclinical Models
Huelsboemer L, Kauke-Navarro M, Reuter S, Stoegner V, Feldmann J, Hirsch T, Kueckelhaus M, Dermietzel A. Tolerance Induction in Vascularized Composite Allotransplantation—A Brief Review of Preclinical Models. Transplant International 2023, 36: 10955. PMID: 36846605, PMCID: PMC9946984, DOI: 10.3389/ti.2023.10955.Peer-Reviewed Original ResearchConceptsTolerance inductionLong-term effectsAnimal modelsImmune systemDonor-specific toleranceLong-term outcomesRecipient's immune systemPreclinical animal modelsNovel therapeutic strategiesPre-clinical studiesVascularized Composite AllotransplantationChronic rejectionImmunosuppressive protocolsTransplant recipientsAllograft rejectionOrgan dysfunctionPreclinical modelsComposite allograftsTherapeutic strategiesComposite allotransplantationClinical practiceIS protocolClinical translationInductionReview articleThe age of bone marrow dictates the clonality of smooth muscle-derived cells in atherosclerotic plaques
Kabir I, Zhang X, Dave J, Chakraborty R, Qu R, Chandran R, Ntokou A, Gallardo-Vara E, Aryal B, Rotllan N, Garcia-Milian R, Hwa J, Kluger Y, Martin K, Fernández-Hernando C, Greif D. The age of bone marrow dictates the clonality of smooth muscle-derived cells in atherosclerotic plaques. Nature Aging 2023, 3: 64-81. PMID: 36743663, PMCID: PMC9894379, DOI: 10.1038/s43587-022-00342-5.Peer-Reviewed Original ResearchConceptsAtherosclerotic plaquesBone marrowSmooth muscle-derived cellsSMC progenitorsAtherosclerotic plaque cellsSmooth muscle cell progenitorsPredominant risk factorCause of deathNovel therapeutic strategiesTNF receptor 1Muscle-derived cellsAged bone marrowAged BMEffect of agePlaque burdenAged miceRisk factorsTumor necrosisTherapeutic strategiesPlaque cellsMyeloid cellsReceptor 1Integrin β3Cell progenitorsAtherosclerosis
2022
Targeting Krebs-cycle-deficient renal cell carcinoma with Poly ADP-ribose polymerase inhibitors and low-dose alkylating chemotherapy
Ueno D, Vasquez JC, Sule A, Liang J, van Doorn J, Sundaram R, Friedman S, Caliliw R, Ohtake S, Bao X, Li J, Ye H, Boyd K, Huang RR, Dodson J, Boutros P, Bindra RS, Shuch B. Targeting Krebs-cycle-deficient renal cell carcinoma with Poly ADP-ribose polymerase inhibitors and low-dose alkylating chemotherapy. Oncotarget 2022, 13: 1054-1067. PMID: 36128328, PMCID: PMC9477221, DOI: 10.18632/oncotarget.28273.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine Diphosphate RiboseAnimalsCarcinoma, Renal CellCitric Acid CycleDioxygenasesDNAFumarate HydrataseFumaratesHumansJumonji Domain-Containing Histone DemethylasesKidney NeoplasmsLysineMicePoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsSuccinate DehydrogenaseSuccinatesTemozolomideConceptsRenal cell carcinomaPoly ADP-ribose polymerase inhibitorsADP-ribose polymerase inhibitorsCell carcinomaSDH-deficient renal cell carcinomaPolymerase inhibitorsLow-dose temozolomideAggressive renal cell carcinomaHereditary cancer syndromesNovel therapeutic strategiesDeficient murine modelStandard dosingTMZ resultsMurine modelTherapeutic strategiesCombination treatmentCancer syndromesTumor growthHomologous recombination DNA repair pathwayAccumulation of fumarateHR deficiencyPARP inhibitionTemozolomideChemotherapyCarcinomaHuman WDR5 promotes breast cancer growth and metastasis via KMT2-independent translation regulation
Cai WL, Chen JF, Chen H, Wingrove E, Kurley SJ, Chan LH, Zhang M, Arnal-Estape A, Zhao M, Balabaki A, Li W, Yu X, Krop ED, Dou Y, Liu Y, Jin J, Westbrook TF, Nguyen DX, Yan Q. Human WDR5 promotes breast cancer growth and metastasis via KMT2-independent translation regulation. ELife 2022, 11: e78163. PMID: 36043466, PMCID: PMC9584608, DOI: 10.7554/elife.78163.Peer-Reviewed Original ResearchConceptsBreast cancer cellsMetastatic breast cancerBreast cancerRibosomal gene expressionCancer cellsKnockdown of WDR5Vivo genetic screenReversible epigenetic mechanismsGenetic screenTranslation regulationTriple-negative breast cancerEpigenetic regulatorsEpigenetic mechanismsBreast cancer growthCancer-related deathTranslation efficiencyWDR5Novel therapeutic strategiesTranslation rateGene expressionCell growthAdvanced diseaseEffective therapyMetastatic capabilityPotent suppressionEfficacy of FLT3 and IDH1/2 inhibitors in patients with acute myeloid leukemia previously treated with venetoclax
Bewersdorf JP, Shallis RM, Derkach A, Goldberg AD, Stein A, Stein EM, Marcucci G, Zeidan AM, Shimony S, DeAngelo DJ, Stone RM, Aldoss I, Ball BJ, Stahl M. Efficacy of FLT3 and IDH1/2 inhibitors in patients with acute myeloid leukemia previously treated with venetoclax. Leukemia Research 2022, 122: 106942. PMID: 36108424, DOI: 10.1016/j.leukres.2022.106942.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaIDH2 inhibitorsMyeloid leukemiaResponse rateRetrospective cohort studyOverall response rateRAS pathway mutationsNovel therapeutic strategiesMedian OSR AMLCohort studyShorter OSLandmark trialsTargeted agentsFrontline treatmentMutant FLT3Combination therapyTreatment optionsIDH1/2 inhibitorsDisease progressionTherapeutic strategiesPatientsSmall molecule inhibitorsVenetoclaxTherapyTreating ‘Septic’ With Enhanced Antibiotics and ‘Arthritis’ by Mitigation of Excessive Inflammation
Kwon HK, Dussik CM, Kim SH, Kyriakides TR, Oh I, Lee FY. Treating ‘Septic’ With Enhanced Antibiotics and ‘Arthritis’ by Mitigation of Excessive Inflammation. Frontiers In Cellular And Infection Microbiology 2022, 12: 897291. PMID: 35755835, PMCID: PMC9218192, DOI: 10.3389/fcimb.2022.897291.Peer-Reviewed Original ResearchConceptsSeptic arthritisBacterial burdenAntibiotic treatmentMurine modelTherapeutic goalsConcurrent antimicrobial therapyDistinct therapeutic goalsGeneration of inflammationMRSA septic arthritisSeptic knee arthritisInflammatory joint conditionsArticular cartilageMitigation of inflammationPost-antibiotic treatmentNovel therapeutic strategiesSeptic arthritis modelArticular cartilage damageEx vivo modelArticular cartilage integrityInflammatory arthritisInhibitors of ERKInflammatory profileMRSA infectionSynovial tissueExcessive inflammation
2021
RAF1 amplification drives a subset of bladder tumors and confers sensitivity to MAPK-directed therapeutics
Bekele RT, Samant AS, Nassar AH, So J, Garcia EP, Curran CR, Hwang JH, Mayhew DL, Nag A, Thorner AR, Börcsök J, Sztupinszki Z, Pan CX, Bellmunt J, Kwiatkowski DJ, Sonpavde GP, Van Allen EM, Mouw KW. RAF1 amplification drives a subset of bladder tumors and confers sensitivity to MAPK-directed therapeutics. Journal Of Clinical Investigation 2021, 131 PMID: 34554931, PMCID: PMC8592548, DOI: 10.1172/jci147849.Peer-Reviewed Original ResearchConceptsBladder tumorsUrothelial tumorsTherapeutic strategiesNovel therapeutic strategiesRational therapeutic strategiesPatient-derived modelsRaf/MEK/ERKClinical outcomesMEK/ERKTreatment optionsBladder cancerHeterogeneous diseaseMEK inhibitionTumorsUnique subsetFocal amplificationRAF inhibitorsCell linesRAF1Gene expression patternsActivationExpression patternsSignalingSubsetRaf1 activitySTAT6 Deficiency Attenuates Myeloid Fibroblast Activation and Macrophage Polarization in Experimental Folic Acid Nephropathy
Jiao B, An C, Du H, Tran M, Wang P, Zhou D, Wang Y. STAT6 Deficiency Attenuates Myeloid Fibroblast Activation and Macrophage Polarization in Experimental Folic Acid Nephropathy. Cells 2021, 10: 3057. PMID: 34831280, PMCID: PMC8623460, DOI: 10.3390/cells10113057.Peer-Reviewed Original ResearchConceptsFolic acid nephropathySTAT6 knockout miceM2 macrophage polarizationRenal fibrosis developmentMacrophage polarizationKidney diseaseFibroblast activationKnockout miceRenal fibrosisFibrosis developmentMyeloid fibroblastsEnd-stage kidney diseaseChronic kidney diseaseSevere interstitial fibrosisFibrotic kidney diseaseWild-type miceNovel therapeutic strategiesExtracellular matrix protein productionMatrix protein productionKidney functionPathologic featuresInterstitial fibrosisFibroblast accumulationNephropathyMouse modelProteomic Profiles in Patients with Thrombosis Due to COVID-19 Are Distinct from Non-COVID-19 Thrombosis
Madeeva D, Borges K, Shallow M, Juthani P, Wang S, Gupta A, Chun H, Lee A, Pine A. Proteomic Profiles in Patients with Thrombosis Due to COVID-19 Are Distinct from Non-COVID-19 Thrombosis. Blood 2021, 138: 777. PMCID: PMC8701622, DOI: 10.1182/blood-2021-153959.Peer-Reviewed Original ResearchSerum amyloid ACOVID-19 patientsVenous thromboembolismCOVID-19 infectionLipocalin-2Thromboembolic eventsThromboembolic complicationsPentraxin 3Complement factors C2COVID-19Lower extremity Doppler ultrasoundTissue factorComplement activationCell adhesion molecule-1Pathogenesis of thromboembolismInstitutional review board approvalChest CT angiographyAdhesion molecule-1Endothelial cell adhesion molecule-1Novel therapeutic strategiesSodium citrate tubesReview board approvalClassical complement pathwayRadiologic confirmationICU patientsPotency and Preclinical Evidence of Synergy of Oral Azole Drugs and Miltefosine in an Ex Vivo Model of Leishmania (Viannia) panamensis Infection
Fernández OL, Rosales-Chilama M, Quintero N, Travi BL, Wetzel DM, Gómez MA, Saravia NG. Potency and Preclinical Evidence of Synergy of Oral Azole Drugs and Miltefosine in an Ex Vivo Model of Leishmania (Viannia) panamensis Infection. Antimicrobial Agents And Chemotherapy 2021, 66: e01425-21. PMID: 34694879, PMCID: PMC8765415, DOI: 10.1128/aac.01425-21.Peer-Reviewed Original ResearchConceptsFractional inhibitory concentration indexPeripheral blood mononuclear cellsL. panamensisHuman peripheral blood mononuclear cellsClinical strainsLeishmania panamensis infectionOral azole drugsOral combination therapyFailure of treatmentBlood mononuclear cellsEfficacy of treatmentNovel therapeutic strategiesEffectiveness of treatmentHigh potencyReduction of infectionEx vivo modelInhibitory concentration indexFree drug concentrationPanamensis infectionPreclinical evidenceCombination therapyMononuclear cellsAntimonial drugsCutaneous leishmaniasisDrug combinationsSelecting the optimal immunotherapy regimen in driver-negative metastatic NSCLC
Grant MJ, Herbst RS, Goldberg SB. Selecting the optimal immunotherapy regimen in driver-negative metastatic NSCLC. Nature Reviews Clinical Oncology 2021, 18: 625-644. PMID: 34168333, DOI: 10.1038/s41571-021-00520-1.Peer-Reviewed Original ResearchConceptsSubset of patientsTreatment landscapeRegimen selectionTumor cell PD-L1 expressionChemotherapy-immunotherapy combinationsImmune checkpoint inhibitorsTreatment-naive patientsFirst-line therapyPD-L1 expressionCurrent treatment landscapeCell lung cancerAbsence of headCurrent treatment paradigmsPivotal clinical trialsLong-term efficacyNovel therapeutic strategiesImmunotherapy regimenMetastatic NSCLCImmunotherapeutic strategiesClinicopathological factorsPD-1PD-L1Durable efficacyHistological subtypesLung cancerCitrullination and PAD Enzyme Biology in Type 1 Diabetes – Regulators of Inflammation, Autoimmunity, and Pathology
Yang ML, Sodré FMC, Mamula MJ, Overbergh L. Citrullination and PAD Enzyme Biology in Type 1 Diabetes – Regulators of Inflammation, Autoimmunity, and Pathology. Frontiers In Immunology 2021, 12: 678953. PMID: 34140951, PMCID: PMC8204103, DOI: 10.3389/fimmu.2021.678953.Peer-Reviewed Original ResearchConceptsRheumatoid arthritisPeptidylarginine deiminaseAutoimmune diseasesNeutrophil extracellular trap formationSystemic lupus erythematosusRole of neutrophilsPathogenesis of T1D.Different autoimmune diseasesType 1 diabetesExtracellular trap formationNovel therapeutic strategiesGenetic susceptibility factorsAmino acid citrullinePAD inhibitionNOD miceLupus erythematosusT1D patientsAutoimmune responseAutoreactive responsesDiabetes developmentMultiple sclerosisPathogenic roleInflammatory stressT cellsNeutrophil biologyJoining Efforts for PTLD: Lessons Learned from Comparing the Approach and Treatment Strategies Across the Pediatric and Adult Age Spectra
Montanari F, Orjuela-Grimm M. Joining Efforts for PTLD: Lessons Learned from Comparing the Approach and Treatment Strategies Across the Pediatric and Adult Age Spectra. Current Hematologic Malignancy Reports 2021, 16: 52-60. PMID: 33544319, PMCID: PMC8117403, DOI: 10.1007/s11899-021-00606-8.Peer-Reviewed Original ResearchConceptsAdult age spectrumCombination of immunochemotherapyRecent FindingsClinical trialsRisk-stratified strategiesTreatment-related toxicityLarge prospective studiesFuture therapeutic approachesNovel therapeutic strategiesNovel target therapiesLymphoproliferative disordersPediatric populationProspective studyRetrospective studyClinical algorithmTreatment paradigmTreatment strategiesTherapeutic approachesTherapeutic strategiesCellular therapyHeterogeneous groupPTLDTherapyDiseaseImmunochemotherapy
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