2023
Generation and Characterization of SORT1-Targeted Antibody–Drug Conjugate for the Treatment of SORT1-Positive Breast Tumor
Zhuang W, Zhang W, Xie L, Wang L, Li Y, Wang Z, Zhang A, Qiu H, Feng J, Zhang B, Hu Y. Generation and Characterization of SORT1-Targeted Antibody–Drug Conjugate for the Treatment of SORT1-Positive Breast Tumor. International Journal Of Molecular Sciences 2023, 24: 17631. PMID: 38139459, PMCID: PMC10743877, DOI: 10.3390/ijms242417631.Peer-Reviewed Original ResearchConceptsAntibody-drug conjugatesSortilin 1Breast tumorsTumor antigen heterogeneityAdvanced breast tumorsSuperior safety profileAnti-tumor activityBreast tumor cell linesSafety profileADC targetBreast cancerCell cytotoxicityBystander killingTumor cell linesDrug resistanceAntigen heterogeneityTumorsPromising targetNew targetsTreatmentCell linesHER2Effective cytotoxicityTumor suppressionLysosomal traffickingRNA m6A methylation in psychiatric disorders.
Mao Q, Luo J, Luo X, Zhu X, Wang K, Zuo L, Zhang Y, Luo X. RNA m6A methylation in psychiatric disorders. EC Psychology And Psychiatry 2023, 12 PMID: 38145106, PMCID: PMC10745284.Peer-Reviewed Original ResearchMajor psychiatric disordersPsychiatric disordersM6A modificationM6A methyltransferase METTL3Synaptic protein synthesisInflammatory infiltrationImmune infiltrationRNA m6A methylationTherapeutic targetM6A regulatorsAlzheimer's diseaseNeuropsychiatric disordersMethyltransferase METTL3Subtype classificationPromising targetDiseaseDisordersM6A methylationInfiltrationCritical roleProtein synthesisReviewPathogenesisComprehensive reviewPreventionTargeting PGLYRP1 promotes antitumor immunity while inhibiting autoimmune neuroinflammation
Schnell A, Huang L, Regan B, Singh V, Vonficht D, Bollhagen A, Wang M, Hou Y, Bod L, Sobel R, Chihara N, Madi A, Anderson A, Regev A, Kuchroo V. Targeting PGLYRP1 promotes antitumor immunity while inhibiting autoimmune neuroinflammation. Nature Immunology 2023, 24: 1908-1920. PMID: 37828379, PMCID: PMC10864036, DOI: 10.1038/s41590-023-01645-4.Peer-Reviewed Original ResearchConceptsPeptidoglycan recognition protein 1T cellsMyeloid cellsGenetic deletionPotent antitumor immune responsesCo-inhibitory moleculesExperimental autoimmune encephalomyelitisAntitumor immune responseImmune checkpoint blockadePromising targetSuccessful treatment optionT cell functionCentral nervous systemT cell activationMultiple human cancersAutoimmune neuroinflammationAntitumor immunityAutoimmune encephalomyelitisCheckpoint blockadeCheckpoint moleculesEffector phenotypeAutoimmune diseasesProinflammatory moleculesTissue inflammationTreatment optionsTTD: Therapeutic Target Database describing target druggability information
Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F. TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Research 2023, 52: d1465-d1477. PMID: 37713619, PMCID: PMC10767903, DOI: 10.1093/nar/gkad751.Peer-Reviewed Original ResearchScreening for small molecule inhibitors of SAH nucleosidase using an SAH riboswitch
Sadeeshkumar H, Balaji A, Sutherland A, Mootien S, Anthony K, Breaker R. Screening for small molecule inhibitors of SAH nucleosidase using an SAH riboswitch. Analytical Biochemistry 2023, 666: 115047. PMID: 36682579, PMCID: PMC11149561, DOI: 10.1016/j.ab.2023.115047.Peer-Reviewed Original ResearchConceptsHigh-throughput screenAutoinducer-2Reporter geneBacterial processesEssential bacterial processesGram-negative bacterial cellsQuorum sensing signalsΒ-galactosidase reporter geneSmall molecule inhibitorsAntibiotic drug discoveryNatural riboswitchesAntimicrobial drug developmentRNA elementsPhysiological signalingRiboswitchBacterial cellsMolecule inhibitorsS-adenosylmethionineEscherichia coliCritical functionsNew targetsGenesDrug discoverySmall moleculesPromising targetTargeting ATAD3A-PINK1-mitophagy axis overcomes chemoimmunotherapy resistance by redirecting PD-L1 to mitochondria
Xie X, Yang Y, Wang Q, Liu H, Fang X, Li C, Jiang Y, Wang S, Zhao H, Miao J, Ding S, Liu X, Yao X, Yang W, Jiang J, Shao Z, Jin G, Bian X. Targeting ATAD3A-PINK1-mitophagy axis overcomes chemoimmunotherapy resistance by redirecting PD-L1 to mitochondria. Cell Research 2023, 33: 215-228. PMID: 36627348, PMCID: PMC9977947, DOI: 10.1038/s41422-022-00766-z.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsPD-L1Combination therapyTherapeutic responsePD-1/PD-L1 signalingShorter progression-free survivalBreast cancer benefitProgression-free survivalPD-L1 signalingCheckpoint inhibitorsNab-paclitaxelCancer benefitImmunotherapy cohortImmune microenvironmentPreclinical resultsTumor cell membranesTumor samplesPaclitaxelHigh expressionPromising targetPatientsTherapyTumorsResistant factorATAD3A expression
2022
Targeting ferroptosis to treat colorectal cancer
Yan H, Talty R, Johnson C. Targeting ferroptosis to treat colorectal cancer. Trends In Cell Biology 2022, 33: 185-188. PMID: 36473802, DOI: 10.1016/j.tcb.2022.11.003.Peer-Reviewed Original ResearchConceptsProtein kinase BArachidonic acidColorectal cancer treatmentProtein kinaseKinase BMammalian targetKey pathwaysGlutathione metabolismFerroptosis inductionEnergy metabolismCRC treatmentColorectal cancerCRC pathogenesisFerroptosisCancer treatmentPromising targetNew conceptual avenuesMetabolismTreatmentHippoKinasePrimary strategyRapamycinTargetConceptual avenuesIn the face of change: Which coping strategies predict better psychosocial outcomes in face transplant recipients?
Nizzi M, Pomahac B. In the face of change: Which coping strategies predict better psychosocial outcomes in face transplant recipients? Frontiers In Psychology 2022, 13: 995222. PMID: 36467137, PMCID: PMC9712221, DOI: 10.3389/fpsyg.2022.995222.Peer-Reviewed Original ResearchBetter mental healthPsychosocial outcomesMental healthLong-term psychosocial outcomesPre-transplant assessmentPost-transplant phasePost-transplant dataTerm psychosocial outcomesQuality of lifePoor mental healthMental health trajectoriesBetter psychosocial outcomesFace transplant recipientsTransplant recipientsTransplant candidatesMeasures of depressionPatients' qualityCoping strategiesPatientsPsychosocial functioningHealth trajectoriesMonthsOptimal outcomesPromising targetOutcomesHigh-resolution crystal structure and chemical screening reveal pantothenate kinase as a new target for antifungal development
Gihaz S, Gareiss P, Choi JY, Renard I, Pal AC, Surovsteva Y, Chiu JE, Thekkiniath J, Plummer M, Hungerford W, Montgomery ML, Hosford A, Adams EM, Lightfoot JD, Fox D, Ojo KK, Staker BL, Fuller K, Ben Mamoun C. High-resolution crystal structure and chemical screening reveal pantothenate kinase as a new target for antifungal development. Structure 2022, 30: 1494-1507.e6. PMID: 36167065, PMCID: PMC10042587, DOI: 10.1016/j.str.2022.09.001.Peer-Reviewed Original ResearchConceptsCrystal structureHigh-throughput chemical screenHigh-resolution crystal structuresAntifungal drug developmentHigh-affinity inhibitorsEukaryotic pathogensChemical screenNew compoundsSingle chemotypeFunctional analysisLigand bindingAntifungal developmentPantothenate phosphorylationFungal isolatesPantothenate kinaseNew targetsFungiPanKPromising targetEnzymeDrug developmentNew mechanismCatalysisBiosynthesisKinaseTRPM7 channel inhibition attenuates rheumatoid arthritis articular chondrocyte ferroptosis by suppression of the PKCα-NOX4 axis
Zhou R, Chen Y, Li S, Wei X, Hu W, Tang S, Ding J, Fu W, Zhang H, Chen F, Hao W, Lin Y, Zhu R, Wang K, Dong L, Zhao Y, Feng X, Chen F, Ding C, Hu W. TRPM7 channel inhibition attenuates rheumatoid arthritis articular chondrocyte ferroptosis by suppression of the PKCα-NOX4 axis. Redox Biology 2022, 55: 102411. PMID: 35917680, PMCID: PMC9344030, DOI: 10.1016/j.redox.2022.102411.Peer-Reviewed Original ResearchArticular cartilage destructionRheumatoid arthritisCartilage destructionChannel inhibitionPharmacological inhibitionTreatment of RAHuman RA patientsAdjuvant arthritis ratsExpression of TRPM7Primary rat articular chondrocytesArticular cartilage damageArticular chondrocytesRat articular chondrocytesRA patientsArthritis ratsTRPM7 channel activityAA ratsCartilage damageIntracellular CaVirus 9Human chondrocytesPromising targetFerroptosis inducersFerroptosisTRPM7Sarcomere protein modulation: The new frontier in cardiovascular medicine and beyond
Morelli C, Ingrasciotta G, Jacoby D, Masri A, Olivotto I. Sarcomere protein modulation: The new frontier in cardiovascular medicine and beyond. European Journal Of Internal Medicine 2022, 102: 1-7. PMID: 35534374, DOI: 10.1016/j.ejim.2022.04.020.Peer-Reviewed Original ResearchConceptsHeart failureCardiovascular medicineVentricular outflow obstructionHeart muscle diseaseDegenerative neuromuscular diseaseSpecific disease mechanismsCardiovascular deathOutflow obstructionSystolic functionRandomized trialsUnderlying pathophysiologyCardiac patientsOmecamtiv mecarbilHypertrophic cardiomyopathyFunctional capacityNeuromuscular diseaseMuscle diseaseAvailable evidenceContractile proteinsSkeletal muscleTranslational researchPromising targetDiseaseDisease mechanismsFailureIntegrating human brain proteomes with genome-wide association data implicates novel proteins in post-traumatic stress disorder
Wingo TS, Gerasimov ES, Liu Y, Duong DM, Vattathil SM, Lori A, Gockley J, Breen MS, Maihofer AX, Nievergelt CM, Koenen KC, Levey DF, Gelernter J, Stein MB, Ressler KJ, Bennett DA, Levey AI, Seyfried NT, Wingo AP. Integrating human brain proteomes with genome-wide association data implicates novel proteins in post-traumatic stress disorder. Molecular Psychiatry 2022, 27: 3075-3084. PMID: 35449297, PMCID: PMC9233006, DOI: 10.1038/s41380-022-01544-4.Peer-Reviewed Original ResearchConceptsProteome-wide association studyTranscriptome-wide association studyGenome-wide association studiesBrain protein abundanceHuman brain proteomeBrain proteomeAssociation studiesProtein abundanceGenome-wide association dataHuman brain transcriptomePost-traumatic stress disorderGWAS resultsNovel proteinBrain transcriptomeRisk lociProteomeGenesAssociation dataPrecursor cellsPTSD pathogenesisBrain mRNA levelsMRNA levelsOligodendrocyte precursor cellsPromising targetNew insightsLCOR mediates interferon-independent tumor immunogenicity and responsiveness to immune-checkpoint blockade in triple-negative breast cancer
Pérez-Núñez I, Rozalén C, Palomeque JÁ, Sangrador I, Dalmau M, Comerma L, Hernández-Prat A, Casadevall D, Menendez S, Liu DD, Shen M, Berenguer J, Ruiz IR, Peña R, Montañés JC, Albà MM, Bonnin S, Ponomarenko J, Gomis RR, Cejalvo JM, Servitja S, Marzese DM, Morey L, Voorwerk L, Arribas J, Bermejo B, Kok M, Pusztai L, Kang Y, Albanell J, Celià-Terrassa T. LCOR mediates interferon-independent tumor immunogenicity and responsiveness to immune-checkpoint blockade in triple-negative breast cancer. Nature Cancer 2022, 3: 355-370. PMID: 35301507, DOI: 10.1038/s43018-022-00339-4.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerCancer stem cellsLigand-dependent corepressorTumor immunogenicityBreast cancerImmune checkpoint blockadeBreast cancer metastasisICB efficacyICB resistanceLCoR expressionClinical responsePresentation machineryImmune escapeAPM genesPreclinical modelsTherapy resistanceCancer metastasisPromising targetOvercame resistanceIFNRNA therapyCancerImmunogenicitySignaling-independent mannerStem cells8 Mechanisms of Damage After Cerebral Hemorrhage
Aronowski J, Sansing L, Xi G, Zhang J. 8 Mechanisms of Damage After Cerebral Hemorrhage. 2022, 92-102.e9. DOI: 10.1016/b978-0-323-69424-7.00008-9.ChaptersIntracerebral hemorrhageBrain damageTreatment of ICHPathogenesis of ICHPre-clinical animal modelsIschemic brain injuryNeurovascular unitCerebral hemorrhageSecondary injuryBrain injuryAnimal modelsTherapeutic interventionsOxidative stressPromising targetHemorrhageInjuryMechanisms of damageNoxious componentsDamageInflammationPathogenesisPathobiologyBlood
2021
IL-27 signalling promotes adipocyte thermogenesis and energy expenditure
Wang Q, Li D, Cao G, Shi Q, Zhu J, Zhang M, Cheng H, Wen Q, Xu H, Zhu L, Zhang H, Perry RJ, Spadaro O, Yang Y, He S, Chen Y, Wang B, Li G, Liu Z, Yang C, Wu X, Zhou L, Zhou Q, Ju Z, Lu H, Xin Y, Yang X, Wang C, Liu Y, Shulman GI, Dixit VD, Lu L, Yang H, Flavell RA, Yin Z. IL-27 signalling promotes adipocyte thermogenesis and energy expenditure. Nature 2021, 600: 314-318. PMID: 34819664, DOI: 10.1038/s41586-021-04127-5.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAnimalsBariatric SurgeryDisease Models, AnimalEnergy MetabolismFemaleHumansInsulin ResistanceInterleukin-27MaleMiceObesityp38 Mitogen-Activated Protein KinasesPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaReceptors, InterleukinSignal TransductionThermogenesisUncoupling Protein 1ConceptsIL-27Beige adipose tissueAdipose tissueSerum IL-27Diet-induced obesityBariatric surgeryMetabolic morbidityImmunological factorsInsulin resistanceObesity showTherapeutic administrationMetabolic disordersMouse modelObesityPromising targetEnergy expenditureSignaling promotesThermogenesisBody temperatureMetabolic programsImportant roleTissueCritical roleImmunotherapyMorbidity
2020
Endocannabinoids Attenuate the Virulence of Certain Enteropathogenic Bacteria
Osman M, Papon N, Weill F. Endocannabinoids Attenuate the Virulence of Certain Enteropathogenic Bacteria. Trends In Microbiology 2020, 29: 185-187. PMID: 33388214, DOI: 10.1016/j.tim.2020.12.008.Peer-Reviewed Original ResearchConceptsEndocannabinoid systemInflammatory bowel diseaseIntestinal bacterial infectionsMammalian endocannabinoid systemBowel diseaseEnteric infectionsIntestinal infectionsLipid hormonesGastrointestinal physiologyBacterial infectionsEnteropathogenic bacteriaInfectionPromising targetPossible benefitsNew findingsDiseaseMiceHormoneImmunityCannabinoidsPPARγ/PGC1α signaling as a potential therapeutic target for mitochondrial biogenesis in neurodegenerative disorders
Jamwal S, Blackburn J, Elsworth JD. PPARγ/PGC1α signaling as a potential therapeutic target for mitochondrial biogenesis in neurodegenerative disorders. Pharmacology & Therapeutics 2020, 219: 107705. PMID: 33039420, PMCID: PMC7887032, DOI: 10.1016/j.pharmthera.2020.107705.Peer-Reviewed Original ResearchConceptsNeurodegenerative disordersParkinson's diseaseAlzheimer's diseaseParaoxonase 2Mitochondrial biogenesisNeurodegenerative diseasesHuntington's diseasePeroxisome proliferator-activated receptorProliferator-activated receptorPotential therapeutic targetDevastating neurological disorderFunction of neuronsPeroxisome proliferator-activated receptor gamma co-activator-1 alphaPharmacological-based therapiesSymptomatic treatmentCurrent therapiesClinical trialsLigand-inducible transcription factorsTherapeutic targetNeurological disordersDiseasePPARγ modulatorsProgressive lossMitochondrial dysfunctionPromising targetInflammasomes and Pyroptosis as Therapeutic Targets for COVID-19
Yap JKY, Moriyama M, Iwasaki A. Inflammasomes and Pyroptosis as Therapeutic Targets for COVID-19. The Journal Of Immunology 2020, 205: ji2000513. PMID: 32493814, PMCID: PMC7343621, DOI: 10.4049/jimmunol.2000513.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAnimalsAntiviral AgentsBetacoronavirusCoronavirus InfectionsCOVID-19COVID-19 Drug TreatmentHumansImmunity, InnateInflammasomesIntercellular Signaling Peptides and ProteinsMacrophages, AlveolarPandemicsPneumonia, ViralPyroptosisSARS-CoV-2Severe acute respiratory syndrome-related coronavirusSignal TransductionConceptsSevere acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infectionSevere acute respiratory syndrome-related coronavirus 2Coronavirus disease 2019 (COVID-19) patientsSevere coronavirus disease 2019Coronavirus 2 infectionAvailable pharmaceutical agentsCoronavirus disease 2019Innate immune pathwaysClinical outcomesCoronavirus 2Inflammatory responseCellular pyroptosisDisease 2019Downstream cytokinesInflammasome activationInflammasome pathwayTherapeutic targetImmune pathwaysPromising targetPharmaceutical agentsCOVID-19PyroptosisPatientsCytokinesInflammasome
2017
Genetic Dissection of the Impact of miR-33a and miR-33b during the Progression of Atherosclerosis
Price NL, Rotllan N, Canfrán-Duque A, Zhang X, Pati P, Arias N, Moen J, Mayr M, Ford DA, Baldán Á, Suárez Y, Fernández-Hernando C. Genetic Dissection of the Impact of miR-33a and miR-33b during the Progression of Atherosclerosis. Cell Reports 2017, 21: 1317-1330. PMID: 29091769, PMCID: PMC5687841, DOI: 10.1016/j.celrep.2017.10.023.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAtherosclerosisATP Binding Cassette Transporter 1Blood GlucoseCells, CulturedCholesterolCholesterol, HDLDisease ProgressionGene Regulatory NetworksMacrophages, PeritonealMaleMiceMice, Inbred C57BLMice, KnockoutMicroRNAsMitochondrial Trifunctional Protein, beta SubunitMyocardiumReceptors, LDLConceptsPlaque burdenMiR-33MiR-33-deficient miceReduced plaque burdenProgression of atherosclerosisPro-atherogenic effectsMacrophage cholesterol effluxDecreases lipid accumulationTreatment of atherosclerosisMacrophage-specific lossMiR-33 deficiencyPromotes obesityHDL levelsInsulin resistancePlaque macrophagesProtective effectHyperlipidemic conditionsCholesterol effluxPlaque developmentLipid metabolismAtherosclerosisLipid accumulationHDL biogenesisPromising targetMacrophagesAltered metabotropic glutamate receptor 5 markers in PTSD: In vivo and postmortem evidence
Holmes SE, Girgenti MJ, Davis MT, Pietrzak RH, DellaGioia N, Nabulsi N, Matuskey D, Southwick S, Duman RS, Carson RE, Krystal JH, Esterlis I, Friedman M, Kowall N, Brady C, McKee A, Stein T, Huber B, Kaloupek D, Alvarez V, Benedek D, Ursano R, Williamson D, Cruz D, Young K, Duman R, Krystal J, Mash D, Hardegree M, Serlin G. Altered metabotropic glutamate receptor 5 markers in PTSD: In vivo and postmortem evidence. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 8390-8395. PMID: 28716937, PMCID: PMC5547601, DOI: 10.1073/pnas.1701749114.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderMGluR5 availabilityPositron emission tomographyGlutamate systemMetabotropic glutamate receptor 5Treatment of PTSDHuman posttraumatic stress disorderGlutamate receptor 5Mechanism-based treatmentsExpression of FKBP5Promising treatment targetHuman postmortem tissueTargeted pharmacological treatmentStress psychopathologyPharmacological treatmentExpression of proteinsReceptor 5MGluR5Treatment targetsPostmortem tissueEmission tomographyStress disorderPostmortem samplesPromising targetDisorders
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