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 effectsA 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 analysisTRPM7 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 4
2023
Targeting 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 functionCartilageCollagenPharmacokinetic similarity study comparing the biosimilar candidate, LY05008, with its reference product dulaglutide in healthy Chinese male subjects
Zhang Q, Sun C, Wu J, Wu J, Zhang X, Liu Y, Dou C, Qin H, Zhang Q, Zhou R, Hu W. Pharmacokinetic similarity study comparing the biosimilar candidate, LY05008, with its reference product dulaglutide in healthy Chinese male subjects. Expert Opinion On Biological Therapy 2023, 23: 727-735. PMID: 36880118, DOI: 10.1080/14712598.2023.2189009.Peer-Reviewed Original ResearchConceptsHealthy Chinese male subjectsChinese male subjectsGeometric mean ratiosMale subjectsImmunogenicity profilePK parametersGlucagon-like peptide-1 receptor agonistsPeptide-1 receptor agonistsChinese Clinical Trial RegistryCardiovascular adverse eventsParallel-group studyPrimary study endpointClinical Trials RegistryMaximum serum concentrationLast quantifiable concentrationBiosimilar candidateConfidence intervalsConcentration-time curvePK similarityAdverse eventsGlycemic controlStudy endpointTrials RegistryImmunogenicity dataComparable safetySafety and Tolerability of Tecarfarin (ATI-5923) in Healthy Chinese Volunteers: Multiple Oral Dose-Escalation Phase I Trial
Zhou Q, Wang Z, Wang H, Chen Z, Li X, Dai X, Zhang Y, Yu X, Zhou R, Hu W. Safety and Tolerability of Tecarfarin (ATI-5923) in Healthy Chinese Volunteers: Multiple Oral Dose-Escalation Phase I Trial. American Journal Of Cardiovascular Drugs 2023, 23: 101-112. PMID: 36622539, DOI: 10.1007/s40256-022-00562-5.Peer-Reviewed Original ResearchConceptsHealthy Chinese volunteersMultiple ascending dosesChinese volunteersDose titrationAdverse eventsPharmacodynamic profileSequential cohortsDose-escalation phase I trialTarget international normalized ratioTreatment-related adverse eventsSerious adverse eventsPhase I trialInternational normalized ratioTarget rangeHealthy Chinese populationAscending dosesI trialNormalized ratioStable anticoagulationTecarfarinCohortChinese populationTolerabilityEarly withdrawalVolunteers
2022
LC–MS/MS determination of HY072808, a novel candidate for treating atopic dermatitis, and its active metabolite: Application to a first‐in‐human pharmacokinetic study
Wu J, Zheng L, Zhang Q, Zhang Q, Qin H, Zhou R, Chu Z, He G, Wang L, Hu W. LC–MS/MS determination of HY072808, a novel candidate for treating atopic dermatitis, and its active metabolite: Application to a first‐in‐human pharmacokinetic study. Biomedical Chromatography 2022, 37: e5542. PMID: 36330676, DOI: 10.1002/bmc.5542.Peer-Reviewed Original ResearchConceptsAtopic dermatitisClinical developmentActive metabolitePhosphodiesterase 4 inhibitorNovel phosphodiesterase 4 inhibitorClinical trialsSimple liquid-liquid extraction methodTopical administrationHealthy humansSensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) methodHuman pharmacokinetic studiesPg/Liquid chromatography-tandem mass spectrometry methodChromatography-tandem mass spectrometry methodPositive ion modeLiquid chromatographic separationPharmacokinetic studyPlasma samplesMultiple reaction monitoringLiquid-liquid extraction methodMass spectrometry methodLC-MS/MS determinationDermatitisMS/MS quantificationIon modeModulators of ASIC1a and its potential as a therapeutic target for age-related diseases
Zhou R, Liang H, Hu W, Ding J, Li S, Chen Y, Zhao Y, Lu C, Chen F, Hu W. Modulators of ASIC1a and its potential as a therapeutic target for age-related diseases. Ageing Research Reviews 2022, 83: 101785. PMID: 36371015, DOI: 10.1016/j.arr.2022.101785.Peer-Reviewed Original ResearchConceptsAcid-sensing ion channel 1aAge-related diseasesTherapeutic targetPotential therapeutic targetMost age-related diseasesIon channel 1aNovel drug targetsEffective drugsMultiple organsPathophysiological processesChannel 1aDiseaseChannel family membersPharmacological propertiesImproved treatmentSuch diseasesTissue degenerationCellular apoptosisTreatmentDrug targetsFamily membersPhysiological functionsUrgent needWorldwide populationIschemiaCalcium-Permeable Channels Cooperation for Rheumatoid Arthritis: Therapeutic Opportunities
Liang H, Yin H, Li S, Chen Y, Zhao Y, Hu W, Zhou R. Calcium-Permeable Channels Cooperation for Rheumatoid Arthritis: Therapeutic Opportunities. Biomolecules 2022, 12: 1383. PMID: 36291594, PMCID: PMC9599458, DOI: 10.3390/biom12101383.Peer-Reviewed Original ResearchConceptsPathogenesis of RARheumatoid arthritisCalcium-permeable channelsIntra-articular inflammationCommon autoimmune diseaseTreatment of RAEntry of CaDrug targetsSynovial invasionPatients' qualityAutoimmune diseasesNovel drug targetsCartilage damageArthritisTherapeutic opportunitiesPathological processesCalcium signalingInflammationPathogenesisSpecific roleRAHuman cellsTargetCell membraneDisease
2021
A randomized, double-blind, parallel-group phase I study comparing the pharmacokinetics, safety, and immunogenicity of LY01008, a candidate bevacizumab biosimilar, with its reference product Avastin® in healthy Chinese male subjects
Zhou R, Yang J, Liu Y, Zhang Q, Lu C, Tang K, Li X, Tang W, Gao E, Wu C, Dou C, Hu W. A randomized, double-blind, parallel-group phase I study comparing the pharmacokinetics, safety, and immunogenicity of LY01008, a candidate bevacizumab biosimilar, with its reference product Avastin® in healthy Chinese male subjects. Expert Opinion On Biological Therapy 2021, 22: 263-269. PMID: 34913787, DOI: 10.1080/14712598.2022.2019703.Peer-Reviewed Original ResearchConceptsHealthy Chinese male subjectsChinese male subjectsStudy endpointBevacizumab biosimilarPK parametersMale subjectsGMRs of AUCParallel-group studyPrimary study endpointSecondary study endpointsMaximum serum concentrationLast quantifiable concentrationFurther clinical evaluationConcentration-time curveHealthy Chinese malesInhibitors of angiogenesisAnti-cancer therapyImmunogenicity profileComparable safetySimilar immunogenicitySerum concentrationsClinical evaluationBioequivalence marginTime zeroHealthy subjectsSystemic pharmacological verification of Baixianfeng decoction regulating TNF-PI3K-Akt-NF-κB pathway in treating rheumatoid arthritis
Wei X, Zhou R, Chen Y, Ma G, Yang Y, Lu C, Xu W, Hu W. Systemic pharmacological verification of Baixianfeng decoction regulating TNF-PI3K-Akt-NF-κB pathway in treating rheumatoid arthritis. Bioorganic Chemistry 2021, 119: 105519. PMID: 34864624, DOI: 10.1016/j.bioorg.2021.105519.Peer-Reviewed Original ResearchConceptsAdjuvant arthritis ratsRheumatoid arthritisArthritis ratsIL-1βIL-6Akt-NFSystemic pharmacologyAdjuvant arthritis rat modelAnimal experimentsPathological phenotypesProtein expressionArthritis rat modelP-p65 proteinP-PI3KPathway protein expressionTraditional Chinese medicinePharmacological verificationInflammatory factorsSystemic diseaseRat modelΚB pathwayDegradation of collagenP-AktTNFSerum contentImmunomodulatory functions of TRPM7 and its implications in autoimmune diseases
Liang H, Chen Y, Wei X, Ma G, Ding J, Lu C, Zhou R, Hu W. Immunomodulatory functions of TRPM7 and its implications in autoimmune diseases. Immunology 2021, 165: 3-21. PMID: 34558663, DOI: 10.1111/imm.13420.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoimmune DiseasesAutoimmunityBiomarkersDisease SusceptibilityDrug DevelopmentGene Expression RegulationHumansImmune SystemImmunomodulationIon Channel GatingOrgan SpecificityProtein Kinase InhibitorsProtein Serine-Threonine KinasesSignal TransductionStructure-Activity RelationshipTRPM Cation ChannelsConceptsAutoimmune diseasesRole of TRPM7New treatment targetsPotential therapeutic targetReceptor ion channelsImmune toleranceRheumatoid arthritisMultiple sclerosisSystemic disordersBody of evidenceImmune cellsCytokine secretionImmunoreactive substancesFunctional damageImmunomodulatory functionsTherapeutic targetTreatment targetsDiseaseEffective interventionsPharmacological propertiesOne-tissueTRPM7Physiologic conditionsInappropriate responsesCell migrationBioequivalence and Pharmacokinetic Evaluation of Two Oral Formulations of Regorafenib: An Open-Label, Randomised, Single-Dose, Two-Period, Two-Way Crossover Clinical Trial in Healthy Chinese Volunteers Under Fasting and Fed Conditions
Zhang Q, Wang Z, Wu J, Zhou Z, Zhou R, Hu W. Bioequivalence and Pharmacokinetic Evaluation of Two Oral Formulations of Regorafenib: An Open-Label, Randomised, Single-Dose, Two-Period, Two-Way Crossover Clinical Trial in Healthy Chinese Volunteers Under Fasting and Fed Conditions. Drug Design Development And Therapy 2021, 15: 3277-3288. PMID: 34349503, PMCID: PMC8328391, DOI: 10.2147/dddt.s323169.Peer-Reviewed Original ResearchConceptsHealthy Chinese volunteersSingle oral doseChinese volunteersFed conditionsOral doseSafety profileTwo-way crossover clinical trialSimilar favourable safety profileGeometric least-squares meansOral multi-kinase inhibitorPhase 1 trialCrossover clinical trialFavorable safety profileGood safety profileNon-compartmental methodsMulti-kinase inhibitorTwo-periodOpen labelAdverse eventsSingle doseClinical trialsPharmacokinetic evaluationOral formulationRegorafenibPharmacokinetic parametersSystemic pharmacological investigation of the Feng Shi Gu Tong capsule in the treatment of rheumatoid arthritis
Wei X, Fu W, Zhou R, Chen Y, Lu C, Hu W. Systemic pharmacological investigation of the Feng Shi Gu Tong capsule in the treatment of rheumatoid arthritis. Naunyn-Schmiedeberg's Archives Of Pharmacology 2021, 394: 1285-1299. PMID: 33527195, DOI: 10.1007/s00210-021-02048-8.Peer-Reviewed Original ResearchConceptsRheumatoid arthritisTreatment of RAActive rheumatoid arthritisDisease target networkChinese traditional patent medicineTraditional Chinese medicineRA diseaseMolecular mechanismsImmune responsePharmacological effectsPrecise molecular mechanismsClinical practiceSystemic pharmacologyPharmacological investigationsElimination parametersChinese medicinePatent medicinePotential mechanismsDirect targetArthritisTreatmentCandidate compoundsTotalCapsuleProtein-protein interaction network
2020
Network pharmacology-based study on the mechanism of Yiganling capsule in hepatitis B treatment
Lu C, Fu W, Zhou R, Hu W. Network pharmacology-based study on the mechanism of Yiganling capsule in hepatitis B treatment. BMC Complementary Medicine And Therapies 2020, 20: 37. PMID: 32024508, PMCID: PMC7076828, DOI: 10.1186/s12906-020-2815-y.Peer-Reviewed Original ResearchConceptsHepatitis BCompound-target networkNetwork pharmacology-based studyTraditional Chinese medicinal compoundHepatitis B treatmentFavorable treatment effectChinese medicinal compoundsDisease target networkTraditional Chinese medicine preparationChinese medicine preparationEnrichment analysisPharmacological mechanismsMedicine DatabaseConclusionThis studyChinese Medicine DatabaseProtein-protein interaction networkDisease targetsDisease databaseMedicine preparationTreatment effectsActive compoundsB treatmentHB treatmentTreatmentCapsuleNovel insights into ferroptosis: Implications for age-related diseases
Zhou R, Chen Y, Wei X, Yu B, Xiong Z, Lu C, Hu W. Novel insights into ferroptosis: Implications for age-related diseases. Theranostics 2020, 10: 11976-11997. PMID: 33204324, PMCID: PMC7667696, DOI: 10.7150/thno.50663.Peer-Reviewed Original ResearchConceptsAge-related diseasesInhibition of ferroptosisNew treatment strategiesMolecular signaling pathwaysOrgan failureIron-dependent cell deathCardiovascular diseaseTreatment strategiesTherapeutic targetProgressive deteriorationEffective interventionsDiseaseOlder adultsHealthcare systemFerroptosisSignaling pathwaysCell deathNormal developmentIndirect involvementTissueUrgent needNovel insightsRegulatory mechanismsPathogenesis