2024
Versatility of 14-3-3 proteins and their roles in bone and joint-related diseases
Zhou R, Hu W, Ma P, Liu C. Versatility of 14-3-3 proteins and their roles in bone and joint-related diseases. Bone Research 2024, 12: 58. PMID: 39406741, PMCID: PMC11480210, DOI: 10.1038/s41413-024-00370-4.Peer-Reviewed Original ResearchSafety, tolerability, pharmacokinetics and pharmacodynamics of a single intravenous dose of SHR-1707 in healthy adult subjects: two randomized, double-blind, single-ascending-dose, phase 1 studies
Yang Y, Qiu H, Fan Y, Zhang Q, Qin H, Wu J, Zhang X, Liu Y, Zhou R, Zhang Q, Ye Z, Ma J, Xu Y, Feng S, Fei Y, Li N, Cui X, Dong F, Wang Q, Shen K, Shakib S, Williams J, Hu W. Safety, tolerability, pharmacokinetics and pharmacodynamics of a single intravenous dose of SHR-1707 in healthy adult subjects: two randomized, double-blind, single-ascending-dose, phase 1 studies. Alzheimer's Research & Therapy 2024, 16: 218. PMID: 39390616, PMCID: PMC11465679, DOI: 10.1186/s13195-024-01584-8.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsPhase 1 studySingle-ascending-doseIntravenous doseHealthy adult subjectsDouble-blindElderly subjectsHealthy young adultsAdult subjectsTransient laboratory abnormalitiesPD profilesDose-proportional mannerSingle intravenous dosesYoung adultsDose-dependent increaseIgG1 monoclonal antibodyDose cohortsPlacebo groupLaboratory abnormalitiesPreclinical studiesAdverse eventsClinical developmentDose levelsNo ethnic differencesTransgenic miceMacrophage membrane-camouflaged biomimetic nanoparticles for rheumatoid arthritis treatment via modulating macrophage polarization
Zhou R, Xue S, Cheng Y, Chen Y, Wang Y, Xing J, Liu H, Xu Y, Lin Y, Pei Z, Wei X, Ding J, Li S, Wang K, Yao F, Zhao Y, Ding C, Hu W. Macrophage membrane-camouflaged biomimetic nanoparticles for rheumatoid arthritis treatment via modulating macrophage polarization. Journal Of Nanobiotechnology 2024, 22: 578. PMID: 39300463, PMCID: PMC11414146, DOI: 10.1186/s12951-024-02822-9.Peer-Reviewed Original ResearchConceptsCollagen-induced arthritisNanotherapeutic systemInflamed jointsRheumatoid arthritisMacrophage polarizationModulating macrophage polarizationDelay disease progressionDebilitating autoimmune diseaseChronic joint inflammationComprehensive in vitroAnti-inflammatory M2 phenotypeReduced synovial inflammationEnhanced cellular uptakeIntra-articular injectionRheumatoid arthritis treatmentPro-inflammatory M1Treatment optionsAutoimmune diseasesRepolarize macrophagesBiomimetic nanoparticlesDisease progressionMouse modelNanoparticlesTherapeutic strategiesSide effectsIon channels in osteoarthritis: emerging roles and potential targets
Zhou R, Fu W, Vasylyev D, Waxman S, Liu C. Ion channels in osteoarthritis: emerging roles and potential targets. Nature Reviews Rheumatology 2024, 20: 545-564. PMID: 39122910, DOI: 10.1038/s41584-024-01146-0.Peer-Reviewed Original ResearchIon channelsVoltage-dependent calcium channelsAcid-sensing ion channelsTransient receptor potential channelsVoltage-gated sodium channelsIon channel modulatorsFunction of ion channelsPotential clinical applicationsCalcium channelsPreclinical studiesClinical impactSymptomatic reliefPotassium channelsChloride channelsDisease-modifying treatmentsClinical trialsSodium channelsBone hyperplasiaChannel modulationIon channel biologySynovial inflammationClinical applicationPiezo channelsModel of OAPotential targetA Randomized, Double-Blind, Parallel-Group Phase I Study Comparing the Pharmacokinetics, Safety, and Immunogenicity of CMAB015, a Candidate Secukinumab Biosimilar, with Its Reference Product Cosentyx® in Healthy Chinese Male Subjects
Yao F, Wang C, Ding J, Zhang Q, Zheng L, Zhang Q, Yang T, Zhang X, Shan Y, Hou S, Wang H, Zhou R, Hu W. A Randomized, Double-Blind, Parallel-Group Phase I Study Comparing the Pharmacokinetics, Safety, and Immunogenicity of CMAB015, a Candidate Secukinumab Biosimilar, with Its Reference Product Cosentyx® in Healthy Chinese Male Subjects. Drug Design Development And Therapy 2024, 18: 3891-3901. PMID: 39224901, PMCID: PMC11368109, DOI: 10.2147/dddt.s470619.Peer-Reviewed Original ResearchConceptsHealthy Chinese male subjectsChinese male subjectsGeometric mean ratiosAnti-drug antibodiesDouble-blindMale subjectsRates of anti-drug antibodiesPK parametersNon-radiographic axial spondyloarthritisIncidence of TEAEsPhase I studyPrimary study endpointInterleukin (IL)-17AArea under the curveEnthesitis-related arthritisTreatment of psoriasisConfidence intervalsSafety profileSingle doseHidradenitis suppurativaSecukinumabStudy endpointAdverse eventsAxial spondyloarthritisImmunogenicity analysisNS8593 inhibits chondrocyte ferroptosis and alleviates cartilage injury in rat adjuvant arthritis through TRPM7 / HO-1 pathway
Hao W, Zhu R, Zhang H, Chen Y, Li S, Zhou F, Hu W, Zhou R. NS8593 inhibits chondrocyte ferroptosis and alleviates cartilage injury in rat adjuvant arthritis through TRPM7 / HO-1 pathway. The International Journal Of Biochemistry & Cell Biology 2024, 174: 106618. PMID: 39053766, DOI: 10.1016/j.biocel.2024.106618.Peer-Reviewed Original ResearchTransient receptor potential melastatin 7Inhibit TRPM7 channelsHeme oxygenase-1TRPM7 channelsTRPM7 inhibitorRheumatoid arthritisHeme oxygenase-1 pathwayRat adjuvant arthritisExpression of heme oxygenase-1Treatment of RAChondrocyte ferroptosisFerroptosis inducer erastinIn vitro modelCartilage destructionAA ratsNS8593Oxidative stress injuryRestoring redox balanceArticular cartilage damageAdjuvant arthritisPotential novel drugOxygenase-1Restored cell viabilityArticular cartilage destructionReduced cytotoxicityEfferocytosis: Unveiling its potential in autoimmune disease and treatment strategies
Xing J, Wang K, Xu Y, Pei Z, Yu Q, Liu X, Dong Y, Li S, Chen Y, Zhao Y, Yao F, Ding J, Hu W, Zhou R. Efferocytosis: Unveiling its potential in autoimmune disease and treatment strategies. Autoimmunity Reviews 2024, 23: 103578. PMID: 39004157, DOI: 10.1016/j.autrev.2024.103578.Peer-Reviewed Original ResearchClearance of apoptotic cellsApoptotic cellsDegradation of apoptotic cellsPhagocyte surface receptorsAutoimmune diseasesInternalize apoptotic cellsEfficient clearance of apoptotic cellsSelf-antigensRelease of self-antigensSystemic lupus erythematosusTreat autoimmune diseasesSignaling pathwayType 1 diabetesSurface receptorsImmunosuppressive signalsImmune toleranceLupus erythematosusImmune homeostasisTreatment strategiesEfferocytosis processEfficient clearanceInadequate clearanceTherapeutic strategiesImmune responsePhagocytesNS8593 inhibits sodium nitroprusside-induced chondrocyte apoptosis by mediating the STING signaling pathway
Zhu R, Hao W, Li S, Chen Y, Zhou F, Zhou R, Hu W. NS8593 inhibits sodium nitroprusside-induced chondrocyte apoptosis by mediating the STING signaling pathway. Heliyon 2024, 10: e31375. PMID: 38831839, PMCID: PMC11145487, DOI: 10.1016/j.heliyon.2024.e31375.Peer-Reviewed Original ResearchTransient receptor potential cation channel subfamily M member 7STING signaling pathwayCyclic GMP-AMP synthase (cGAS)-stimulatorSNP-induced decreaseAtrial fibrillation therapyPhosphorylation levelsSignaling pathwayApoptosis in vitroCell viabilityNS8593Atrial fibrillationDose-dependentlyImprove atrial fibrillationInterferon genesSNP-induced chondrocyte apoptosisArticular cartilage damageApoptosisChondrocyte apoptosisFeatures of osteoarthritisChondrocyte apoptosis in vitroArticular cartilage destructionCartilage destructionCartilage damageStingsTreatmentSafety, tolerability, and pharmacokinetics of the novel RdRp inhibitor SHEN26 against SARS-CoV-2: a randomized, placebo-controlled, double-blind Phase I study in healthy subjects
Sun C, Liu H, Ouyang Z, Ding J, Zhang Q, Ma H, Xu D, Zhang Q, Zhou R, Yang M, Hu W. Safety, tolerability, and pharmacokinetics of the novel RdRp inhibitor SHEN26 against SARS-CoV-2: a randomized, placebo-controlled, double-blind Phase I study in healthy subjects. Expert Opinion On Investigational Drugs 2024, 33: 533-542. PMID: 38662639, DOI: 10.1080/13543784.2024.2347302.Peer-Reviewed Original ResearchArea under the curveAscending-dose studyFood effect studyHealthy subjectsPlacebo-controlled phase I studySARS-CoV-2Increased approximately dose-proportionallyPlasma concentrationsTreatment-related adverse eventsApproximately dose-proportionallyPhase I studyHigh-fat mealBroad-spectrum antiviral drugsPreclinical activityDose proportionalityDouble-blindPlacebo-controlledReport safetyDose groupSafety profileStandard mealAdverse eventsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2TRPM7 facilitates fibroblast-like synoviocyte proliferation, metastasis and inflammation through increasing IL-6 stability via the PKCα-HuR axis in rheumatoid arthritis
Lin Y, Chen Y, Hu W, Liu X, Hao W, Xing J, Ding J, Xu Y, Yao F, Zhao Y, Wang K, Li S, Yu Q, Hu W, Zhou R. TRPM7 facilitates fibroblast-like synoviocyte proliferation, metastasis and inflammation through increasing IL-6 stability via the PKCα-HuR axis in rheumatoid arthritis. International Immunopharmacology 2024, 132: 111933. PMID: 38581988, DOI: 10.1016/j.intimp.2024.111933.Peer-Reviewed Original ResearchConceptsTransient receptor potential melastatin 7Rheumatoid arthritisInhibition of transient receptor potential melastatin 7Human RA patientsSynovial hyperplasiaAdjuvant-induced arthritis ratsIncreased TRPM7 expressionIL-6 mRNATreatment of RAPathogenesis of RAFibroblast-like synoviocytesTRPM7 silencingProgression of rheumatoid arthritisTRPM7 expressionChannel inhibitionCation channelsRA patientsMetastasisPharmacological inhibitionArthritis ratsInflammationNuclear translocationSynoviocyte proliferationHyperplasiaProliferationExtracellular CIRP induces abnormal activation of fibroblast-like synoviocytes from patients with RA via the TLR4-mediated HDAC3 pathways
Yao F, Zhao Y, Yu Q, Hu W, Lin Y, Chen Y, Li L, Sun C, Li S, Wang K, Yang M, Zhou R, Hu W. Extracellular CIRP induces abnormal activation of fibroblast-like synoviocytes from patients with RA via the TLR4-mediated HDAC3 pathways. International Immunopharmacology 2024, 128: 111525. PMID: 38218010, DOI: 10.1016/j.intimp.2024.111525.Peer-Reviewed Original ResearchConceptsExtracellular cold-inducible RNA-binding proteinCold-inducible RNA-binding proteinToll-like receptor 4Histone deacetylase 3Endogenous proinflammatory moleculesRheumatoid arthritisActivity of RA-FLSAA ratsAbnormal activationProinflammatory moleculesEffect of cold-inducible RNA-binding proteinHistone deacetylase 3 knockdownRelease of IL-1bSeverity of arthritisFibroblast-like synoviocytesDevelopment of rheumatoid arthritisRA-FLSActivation of fibroblast-like synoviocytesIL-33Expression of N-cadherinProinflammatory effectsArthritis severityIL-1BInflammatory diseasesReceptor 4IUPHAR ECR review: The cGAS-STING pathway: Novel functions beyond innate immune and emerging therapeutic opportunities
He X, Wedn A, Wang J, Gu Y, Liu H, Zhang J, Lin Z, Zhou R, Pang X, Cui Y. IUPHAR ECR review: The cGAS-STING pathway: Novel functions beyond innate immune and emerging therapeutic opportunities. Pharmacological Research 2024, 201: 107063. PMID: 38216006, DOI: 10.1016/j.phrs.2024.107063.Peer-Reviewed Original ResearchStimulator of interferon genesAdaptor protein complex 1Function of STINGRegulation of cellular metabolismRegulatory functionsRegulation of stimulator of interferon genesInnate immune signaling pathwaysImmune signaling pathwaysInnate immune regulationInnate immune sensorsCellular physiologyCGAS-STING pathwayDNA repairNegative regulatorComplex regulationCellular metabolismCytosolic DNAStimulator of interferon genes agonistsCell deathAP-1Stimulators of interferon genes signallingSignaling pathwayMolecular mechanismsImmune regulatory drugImmune sensorsSafety and Pharmacokinetics of HRS-2261, a P2X3 Receptor Antagonist, in Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled Phase 1 Study
Fan Y, Zhang X, Zhang Q, Zheng L, Zhou R, Sun C, Wang X, Song K, He Z, Wang H, Zhang Q, Hu W. Safety and Pharmacokinetics of HRS-2261, a P2X3 Receptor Antagonist, in Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled Phase 1 Study. Clinical Pharmacokinetics 2024, 63: 293-302. PMID: 38198010, DOI: 10.1007/s40262-023-01330-7.Peer-Reviewed Original ResearchP2X3 receptor antagonistAdverse eventsReceptor antagonistHealthy subjectsChronic coughPlacebo-controlled phase 1 trialModerate adverse eventsMost adverse eventsTwice-daily dosingSelective P2X3 receptor antagonistPhase 1 studyPhase 1 trialUnexplained chronic coughSingle oral doseStudy phaseMedian tmaxPrimary endpointGood tolerabilityOral doseTherapeutic optionsResultsA totalDrug exposureMean t1/2Lower incidenceFood intakeNav1.7 as a chondrocyte regulator and therapeutic target for osteoarthritis
Fu W, Vasylyev D, Bi Y, Zhang M, Sun G, Khleborodova A, Huang G, Zhao L, Zhou R, Li Y, Liu S, Cai X, He W, Cui M, Zhao X, Hettinghouse A, Good J, Kim E, Strauss E, Leucht P, Schwarzkopf R, Guo E, Samuels J, Hu W, Attur M, Waxman S, Liu C. Nav1.7 as a chondrocyte regulator and therapeutic target for osteoarthritis. Nature 2024, 625: 557-565. PMID: 38172636, PMCID: PMC10794151, DOI: 10.1038/s41586-023-06888-7.Peer-Reviewed Original ResearchVoltage-gated sodium channelsOA progressionDorsal root ganglion neuronsStructural joint damagePain relief treatmentHuman OA chondrocytesCommon joint diseaseMultiple mouse modelsNav1.7 blockersPain behaviorGanglion neuronsPharmacological blockadeJoint damageJoint degenerationChannel blockersJoint diseaseOA chondrocytesMouse modelTherapeutic targetOsteoarthritisIntracellular Ca2Nav1.7Nav1.7 channelsGenetic ablationLimited evidence
2023
Safety, tolerability, pharmacokinetics and pharmacodynamics of a single intravenous dose of SHR‐1707 in healthy adult subjects: two randomized, double‐blind, phase 1 studies
Hu W, Shakib S, Williams J, Fan Y, Zhang Q, Qin H, Wu J, Zhang X, Liu Y, Zhou R, Yang Y, Zhang Q, Ye Z, Qiu H, Ma J, Zhu M, Feng S, Fei Y, Li N, Cui X, Dong F, Wang T. Safety, tolerability, pharmacokinetics and pharmacodynamics of a single intravenous dose of SHR‐1707 in healthy adult subjects: two randomized, double‐blind, phase 1 studies. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.074758.Peer-Reviewed Original ResearchPhase 1 studySingle intravenous doseHealthy young adultsPK/PD profilesHealthy adult subjectsIntravenous doseElderly subjectsYoung adultsDose levelsPD profilesAdult subjectsDose-proportional mannerPK/pharmacodynamicsFurther clinical developmentDose-dependent increaseSame dose levelIgG1 monoclonal antibodyPlacebo groupLaboratory abnormalitiesMicroglial phagocytosisAβ plaquesPreclinical studiesSHRClinical developmentAβ42 concentrationsSafety, pharmacokinetics and pharmacodynamics of HRS‐7535, a novel oral small molecule glucagon‐like peptide‐1 receptor agonist, in healthy participants: A phase 1, randomized, double‐blind, placebo‐controlled, single‐ and multiple‐ascending dose, and food effect trial
Wu J, Zhou R, Zhang Q, Zhang Q, Qin H, Ye Z, Xu Y, Feng S, Shu C, Shen Y, Fan Y, Wang Q, Du Y, Hu W. Safety, pharmacokinetics and pharmacodynamics of HRS‐7535, a novel oral small molecule glucagon‐like peptide‐1 receptor agonist, in healthy participants: A phase 1, randomized, double‐blind, placebo‐controlled, single‐ and multiple‐ascending dose, and food effect trial. Diabetes Obesity And Metabolism 2023, 26: 901-910. PMID: 38100147, DOI: 10.1111/dom.15383.Peer-Reviewed Original ResearchGlucagon-like peptide-1 receptor agonistsPeptide-1 receptor agonistsSingle ascending doseMAD partsReceptor agonistGeometric mean tNovel glucagon-like peptide-1 receptor agonistFood effectHealthy participantsMultiple ascending dosePhase 1 trialType 2 diabetesGLP-1RAsPrimary endpointSingle doseDay 29Day 28Mean reductionClinical developmentMean TBody weightPharmacokineticsPlaceboTolerabilityEffect trialASIC1a-CMPK2-mediated M1 macrophage polarization exacerbates chondrocyte senescence in osteoarthritis through IL-18
Dong L, Zhao Y, Sun C, Ou Yang Z, Chen F, Hu W, Zhang H, Wang Y, Zhu R, Cheng Y, Chen Y, Li S, Wang K, Ding C, Zhou R, Hu W. ASIC1a-CMPK2-mediated M1 macrophage polarization exacerbates chondrocyte senescence in osteoarthritis through IL-18. International Immunopharmacology 2023, 124: 110878. PMID: 37660594, DOI: 10.1016/j.intimp.2023.110878.Peer-Reviewed Original ResearchAcid-sensing ion channel 1aM1 macrophage polarizationM1 macrophagesChondrocyte senescenceMacrophage polarizationIL-18OA patientsPcTX-1IL-18 stimulationOA cartilage damageArticular cartilage destructionMouse OA modelIntra-articular administrationPromising treatment targetIon channel 1aMacrophage-associated genesMacrophage-mediated diseasesMechanism of actionASIC1a expressionOA miceCartilage destructionM1 polarizationCartilage damageOA modelSynovial fluidTargeting regulated chondrocyte death in osteoarthritis therapy
Zhu R, Wang Y, Ouyang Z, Hao W, Zhou F, Lin Y, Cheng Y, Zhou R, Hu W. Targeting regulated chondrocyte death in osteoarthritis therapy. Biochemical Pharmacology 2023, 215: 115707. PMID: 37506921, DOI: 10.1016/j.bcp.2023.115707.Peer-Reviewed Original ResearchConceptsChondrocyte deathCartilage degenerationArticular cartilage degenerationBone erosionExtracellular matrix degradationOA preventionOA pathogenesisChondrocyte senescenceCartilage lossOsteoarthritis therapyOA treatmentOsteoarthritisCell death modeDeathMatrix degradationEssential hallmarkTreatment methodsDegenerationForm of deathDeath modeTreatmentPathogenesisTherapyProgressionPreventionCartilage-Related Collagens in Osteoarthritis and Rheumatoid Arthritis: From Pathogenesis to Therapeutics
Ouyang Z, Dong L, Yao F, Wang K, Chen Y, Li S, Zhou R, Zhao Y, Hu W. Cartilage-Related Collagens in Osteoarthritis and Rheumatoid Arthritis: From Pathogenesis to Therapeutics. International Journal Of Molecular Sciences 2023, 24: 9841. PMID: 37372989, PMCID: PMC10298547, DOI: 10.3390/ijms24129841.Peer-Reviewed Original ResearchConceptsRheumatoid arthritisArticular cartilageCourse of osteoarthritisNew biochemical markersDisease progressionPathogenic factorsCartilage damageDegradation of collagenBiochemical markersProgressive destructionClinical diagnosisMechanical injuryConnective tissueDisease statesRole of collagenCollagen productionLow immunogenicityFacilitate drug developmentArthritisDrug developmentOsteoarthritisBiomechanical propertiesMechanical functionCartilageCollagenFunctions of Peroxiredoxins and Their Roles in Autoimmune Diseases
Zhou F, Chen F, Ouyang Z, Zhu R, Zhou R, Hu W, Lu C. Functions of Peroxiredoxins and Their Roles in Autoimmune Diseases. Antioxidants & Redox Signaling 2023, 40: 329-344. PMID: 36738225, DOI: 10.1089/ars.2022.0139.Peer-Reviewed Original ResearchFunction of peroxiredoxinsAutoimmune diseasesCellular redox signalingOxidative stressRedox signalingRedox homeostasisEssential regulatorExcess ROSPeroxiredoxinsBiological processesReactive oxygen species generationProduction of ROSPhysiological roleNew therapeutic targetsOxygen species generationAntioxidant enzymesPotential targetPathophysiological rolePathological situationsEffective treatmentTherapeutic targetSpecies generationDiseaseROSRecent studies