2024
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
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 proliferationHyperplasiaProliferation
2023
Pharmacokinetic 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 safety
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 subjectsBioequivalence 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 parametersCurcumin ameliorates IL‐1β‐induced apoptosis by activating autophagy and inhibiting the NF‐κB signaling pathway in rat primary articular chondrocytes
Chen T, Zhou R, Chen Y, Fu W, Wei X, Ma G, Hu W, Lu C. Curcumin ameliorates IL‐1β‐induced apoptosis by activating autophagy and inhibiting the NF‐κB signaling pathway in rat primary articular chondrocytes. Cell Biology International 2021, 45: 976-988. PMID: 33377585, DOI: 10.1002/cbin.11541.Peer-Reviewed Original ResearchConceptsIL-1βChondrocyte apoptosisProtective effectNF-κBPrimary articular chondrocytesNF-κB inhibitor pyrrolidine dithiocarbamatePhosphorylation levelsArticular chondrocytesCurcumin-mediated protectionWnt/β-catenin inhibitorInhibitor pyrrolidine dithiocarbamateIL-1β stimulationArticular chondrocyte apoptosisArticular cartilage damageΒ-catenin inhibitorMechanism of curcuminArticular cartilage diseaseSynthase kinase-3βCurcumin pretreatmentRheumatoid arthritisΚB p65Chondrocyte injuryInterleukin-1βCartilage damageXAV-939
2020
Acid‐sensing ion channel 1a mediates acid‐induced pyroptosis through calpain‐2/calcineurin pathway in rat articular chondrocytes
Zu S, Feng Y, Zhu C, Wu X, Zhou R, Li G, Dai B, Wang Z, Xie Y, Li Y, Ge J, Chen F. Acid‐sensing ion channel 1a mediates acid‐induced pyroptosis through calpain‐2/calcineurin pathway in rat articular chondrocytes. Cell Biology International 2020, 44: 2140-2152. PMID: 32678496, DOI: 10.1002/cbin.11422.Peer-Reviewed Original ResearchConceptsAcid-sensing ion channel 1aAcid-sensing ion channelsRat articular chondrocytesIon channel 1aChondrocyte pyroptosisTime-dependent mannerCalpain-2Activation of ASICsChannel 1aExtracellular acidosisInhibition of ASIC1aProtein expressionInterleukin-1β levelsArticular chondrocytesSystemic autoimmune diseasePrimary rat articular chondrocytesApoptosis-associated speck-like proteinNLRP3 inflammasome proteinsCalcineurin pathwaySpeck-like proteinCation channel familyRheumatoid arthritisAutoimmune diseasesDegenerative articular cartilageInflammasome proteins17β-estradiol attenuates rat articular chondrocyte injury by targeting ASIC1a-mediated apoptosis
Song S, Tao J, Li S, Qian X, Niu R, Wang C, Zhang Y, Chen Y, Wang K, Zhu F, Zhu C, Ma G, Yang-Yang, Peng X, Zhou R, Chen F. 17β-estradiol attenuates rat articular chondrocyte injury by targeting ASIC1a-mediated apoptosis. Molecular And Cellular Endocrinology 2020, 505: 110742. PMID: 32006608, DOI: 10.1016/j.mce.2020.110742.Peer-Reviewed Original ResearchConceptsAcid-sensing ion channel 1aRheumatoid arthritisChondrocyte injuryTreatment of RAEstradiol replacement therapyProtein levelsAcid-induced damageIon channel 1aAutophagy-lysosomal pathwayJoint swellingCartilage destructionLocal inflammationOvariectomized modelReplacement therapyEstrogen metabolismArticular damageEpidemiological evidenceASIC1a proteinProtective roleAcid-induced apoptosisChannel 1aSodium-permeable channelsInjuryERα receptorMitochondrial function
2019
Effects of autophagy on apoptosis of articular chondrocytes in adjuvant arthritis rats
Zhou R, Zhu F, Wu X, Song S, Chen Y, Zhu C, Dai B, Qian X, Wang K, Hu W, Chen F. Effects of autophagy on apoptosis of articular chondrocytes in adjuvant arthritis rats. Journal Of Cellular And Molecular Medicine 2019, 23: 7879-7884. PMID: 31508906, PMCID: PMC6815768, DOI: 10.1111/jcmm.14629.Peer-Reviewed Original ResearchConceptsRheumatoid arthritisEffect of autophagyChondrocyte apoptosisAdjuvant arthritisDevelopment of RATreatment of RASystemic autoimmune diseaseAdjuvant arthritis ratsArticular chondrocyte apoptosisAutophagy activator rapamycinArticular cartilage injuryArticular chondrocytesRat articular cartilageArthritis ratsJoint deformityAutoimmune diseasesAA ratsCartilage injuryJoint functionChondrocyte autophagyAutophagy inhibitorPotential targetArthritisApoptosisRatsβ-Estradiol Protects Against Acidosis-Mediated and Ischemic Neuronal Injury by Promoting ASIC1a (Acid-Sensing Ion Channel 1a) Protein Degradation
Zhou R, Leng T, Yang T, Chen F, Hu W, Xiong Z. β-Estradiol Protects Against Acidosis-Mediated and Ischemic Neuronal Injury by Promoting ASIC1a (Acid-Sensing Ion Channel 1a) Protein Degradation. Stroke 2019, 50: 2902-2911. PMID: 31412757, PMCID: PMC6756944, DOI: 10.1161/strokeaha.119.025940.Peer-Reviewed Original ResearchConceptsIschemic neuronal injuryIschemic brain injuryΒ-estradiol treatmentASIC1a protein expressionNeuronal injuryASIC currentsBrain injuryProtein expressionΒ-estradiolWhole-cell patch-clamp techniqueIntracellular CaAcidosis-induced cytotoxicityAcidosis-mediated injuryActivation of ASIC1aDegree of neuroprotectionOutcome of strokeSeverity of strokeMiddle cerebral arteryTransient focal ischemiaOnline visual overviewAcid-induced elevationEstrogen receptor αReal-time polymerase chain reactionQuantitative real-time polymerase chain reactionPatch-clamp technique
2018
The role of Ca2+ in acid-sensing ion channel 1a-mediated chondrocyte pyroptosis in rat adjuvant arthritis
Wu X, Ren G, Zhou R, Ge J, Chen F. The role of Ca2+ in acid-sensing ion channel 1a-mediated chondrocyte pyroptosis in rat adjuvant arthritis. Laboratory Investigation 2018, 99: 499-513. PMID: 30487596, DOI: 10.1038/s41374-018-0135-3.Peer-Reviewed Original ResearchConceptsAcid-sensitive ion channelsChondrocyte pyroptosisCaspase-1Rheumatoid arthritisIL-18Role of Ca2Autoimmune diseasesIL-1βAdjuvant arthritis rat modelExpression of ASIC1aMain pathogenic featureRat adjuvant arthritisJoints of ratsArthritis rat modelApoptosis-associated speck-like proteinProinflammatory cytokines interleukinExpression of COL2ASpeck-like proteinASIC-1asAdjuvant arthritisPoor prognosisCytokines interleukinNLRP3 inflammasomeAA ratsRat modelNecrostatin-1 ameliorates adjuvant arthritis rat articular chondrocyte injury via inhibiting ASIC1a-mediated necroptosis
Chen Y, Zhu C, Zhu F, Dai B, Song S, Wang Z, Feng Y, Ge J, Zhou R, Chen F. Necrostatin-1 ameliorates adjuvant arthritis rat articular chondrocyte injury via inhibiting ASIC1a-mediated necroptosis. Biochemical And Biophysical Research Communications 2018, 504: 843-850. PMID: 30219231, DOI: 10.1016/j.bbrc.2018.09.031.Peer-Reviewed Original ResearchConceptsRat articular cartilageRheumatoid arthritisNec-1Necrostatin-1Potential therapeutic strategyAcid-induced increaseChannel inhibitor amilorideArticular cartilage damageReceptor interacting protein 1Articular cartilageRIP1/RIP3Chondrocyte injuryAA ratsCartilage damageTherapeutic strategiesRA treatmentCartilage injuryPathophysiological processesPsalmotoxin-1Inhibitor necrostatin-1Expression of RIP1Inhibitor amilorideRIP1 inhibitor necrostatin-1Interacting protein 1ASIC1a
2017
Effects of autophagy on acid-sensing ion channel 1a-mediated apoptosis in rat articular chondrocytes
Xie Y, Li Y, Zhou R, Dai B, Qian Y, Wu X, Ge J, Hu W, Chen F. Effects of autophagy on acid-sensing ion channel 1a-mediated apoptosis in rat articular chondrocytes. Molecular And Cellular Biochemistry 2017, 443: 181-191. PMID: 29273849, DOI: 10.1007/s11010-017-3223-6.Peer-Reviewed Original ResearchConceptsRat articular chondrocytesRheumatoid arthritisEffect of autophagyPathogenesis of RAArticular chondrocytesProgression of RAInhibition of ASIC1aAcid-sensing ion channel 1aMultiple pathogenic factorsDegenerative joint diseaseArticular chondrocyte apoptosisRat knee jointsIon channel 1aShort hairpin RNAPrecise etiologyJoint diseasePathogenic factorsKnee jointPsalmotoxin-1Chondrocyte apoptosisPrimary articular chondrocytesChannel 1aASIC1aAutophagy fluxBeclin-1ASIC1a Promotes Acid-Induced Autophagy in Rat Articular Chondrocytes through the AMPK/FoxO3a Pathway
Dai B, Zhu F, Chen Y, Zhou R, Wang Z, Xie Y, Wu X, Zu S, Li G, Ge J, Chen F. ASIC1a Promotes Acid-Induced Autophagy in Rat Articular Chondrocytes through the AMPK/FoxO3a Pathway. International Journal Of Molecular Sciences 2017, 18: 2125. PMID: 29019932, PMCID: PMC5666807, DOI: 10.3390/ijms18102125.Peer-Reviewed Original ResearchInterleukin-1β and tumor necrosis factor-α augment acidosis-induced rat articular chondrocyte apoptosis via nuclear factor-kappaB-dependent upregulation of ASIC1a channel
Zhou R, Dai B, Xie Y, Wu X, Wang Z, Li Y, Wang Z, Zu S, Ge J, Chen F. Interleukin-1β and tumor necrosis factor-α augment acidosis-induced rat articular chondrocyte apoptosis via nuclear factor-kappaB-dependent upregulation of ASIC1a channel. Biochimica Et Biophysica Acta (BBA) - Molecular Basis Of Disease 2017, 1864: 162-177. PMID: 28986307, DOI: 10.1016/j.bbadis.2017.10.004.Peer-Reviewed Original ResearchConceptsAcid-sensing ion channel 1aIL-1βRheumatoid arthritisInterleukin-1βNF-κB inhibitor ammonium pyrrolidinedithiocarbamateNF-κB DNA-binding activityPrimary articular chondrocytesProinflammatory cytokine interleukin-1βAcidosis-induced cytotoxicityCytokines interleukin-1βTumor necrosis factorImportant pathological characteristicNF-κB pathwayArticular chondrocyte apoptosisCaspase-3/9 expressionIon channel 1aNuclear factor-kappaBPleiotropic biological effectsArticular chondrocytesAgent BAPTA-AMASIC1a expressionChondrocyte cytotoxicityΚB expressionAdjuvant arthritisPathological characteristics
2015
Interleukin-6 enhances acid-induced apoptosis via upregulating acid-sensing ion channel 1a expression and function in rat articular chondrocytes
Zhou R, Wu X, Wang Z, Ge J, Chen F. Interleukin-6 enhances acid-induced apoptosis via upregulating acid-sensing ion channel 1a expression and function in rat articular chondrocytes. International Immunopharmacology 2015, 29: 748-760. PMID: 26359543, DOI: 10.1016/j.intimp.2015.08.044.Peer-Reviewed Original ResearchMeSH KeywordsAcid Sensing Ion ChannelsAcidsAnimalsAntibodies, Monoclonal, HumanizedApoptosisApoptosis Regulatory ProteinsArthritis, ExperimentalCartilage, ArticularChondrocytesDose-Response Relationship, DrugEnzyme ActivationInterleukin-6L-Lactate DehydrogenaseMalePeptidesRatsRats, Sprague-DawleySpider VenomsUp-RegulationConceptsInflammatory cytokine interleukin-6Acid-sensing ion channelsArticular chondrocyte apoptosisRat articular chondrocytesChondrocyte apoptosisRheumatoid arthritisAcid-induced cell injuryArticular chondrocytesAdjuvant arthritis ratsPrimary rat articular chondrocytesChronic inflammatory diseaseCytokine interleukin-6IL-6 receptorJAK2/STAT3Dose-dependent mannerArthritis ratsInflammatory diseasesInterleukin-6Specific antagonistCell injuryNF-κBAcid-induced apoptosisLDH releaseArthritic cartilageDownregulated expression