Merozoite surface antigens can induce protective immune responses and may becandidate antigens for malaria vaccine.Four hybridoma cell lines secreting monoclonalantibodies against Plasmodium falciparum Fcc7801/HN were...Merozoite surface antigens can induce protective immune responses and may becandidate antigens for malaria vaccine.Four hybridoma cell lines secreting monoclonalantibodies against Plasmodium falciparum Fcc7801/HN were produced.Antibodies fromthree of the four lines showed significant growth-inhibiting effect on P.falciparum invitro.One monoclonal antibody,known as C6,conjugated the antigen located exclusivelyon the merozoite surface and distributed evenly over the entire surface,as wasdemonstrated by immunoelectron microscopy.C6 also precipitated a single protein of Mr71000.展开更多
Background:Clinically amyopathic dermatomyositis(CADM)is a unique sub-type of idiopathic inflammatory myopathies with a high prevalence of interstitial lung disease(ILD).Poor prognosis of the patients was strongly ass...Background:Clinically amyopathic dermatomyositis(CADM)is a unique sub-type of idiopathic inflammatory myopathies with a high prevalence of interstitial lung disease(ILD).Poor prognosis of the patients was strongly associated with rapid progressive ILD.The aim of this study was to identify risk factors for prediction of different types of ILD in CADM.Methods:In this study,data of 108 inpatients with CADM were collected,including 87 with ILD.The baseline clinical data and laboratory parameters,including myositis-specific and associated antibodies and tumor-associated antigens were analyzed to identify risk factors for acute or subacute interstitial pneumonitis(A/SIP)and chronic interstitial pneumonitis(CIP).Results:In 87 patients with CADM-ILD,39(36.1%)were A/SIP,and 48(44.4%)were CIP.There were 22(20.4%)patients with asymptomatic ILD who were detected by routine high resolution computed tomography.Cytokeratin-19 fragment(CYFRA21-1)was significantly higher in CADM-ILD than that in CADM patients without ILD;carcinoembryonic antigen and neuron-specific enolase were significantly elevated in A/SIP than that in CIP.Patients with A/SIP had a higher positive rate of anti-melanoma differentiation-associated gene 5(MDA5),while patients with CIP had a higher positive rate of anti PL-12 and anti-Ro-52.Logistic regression analysis indicated that elevation of CYFRA21-1 was a risk factor for ILD,higher titer of anti-MDA5 indicated increased likelihood for A/SIP,and higher titer of anti-Ro-52 was also clearly associated with CIP.Conclusions:This study indicated that the prevalence of ILD was high in CADM.Asymptomatic ILD has been previously underestimated.Anti-MDA5 was a risk factor for the presence of A/SIP,and CYFRA21-1 was a risk factor for ILD.展开更多
Introduction:Thrombocytopenia,a common noncriteria manifestation of antiphospholipid syndrome(APS),is severe in approximately one-third of patients with APS.However,there are no guidelines for treating such thrombocyt...Introduction:Thrombocytopenia,a common noncriteria manifestation of antiphospholipid syndrome(APS),is severe in approximately one-third of patients with APS.However,there are no guidelines for treating such thrombocytopenia.B-cell-targeting therapy may be an option in refractory cases;however,its efficacy has not been firmly established.Here,we report on two patients with refractory antiphospholipid antibodies(aPLs)-associated thrombocytopenia treated with telitacicept.Case Description:Case 1,a 39-year-old woman,presented with systemic lupus erythematosus(SLE)and APS with diffuse alveolar hemorrhage,persistent thrombocytopenia,and recurrent miscarriages.The thrombocytopenia had been refractory to multiple lines of treatments,the most recent being mycophenolate mofetil and prednisone(5 mg/day).After receiving telitacicept(160 mg/week)for 3 months,she had presented with decreased titers of aPLs and a slight increase in platelet counts(14×10^(9)to 35×10^(9)/L).Case 2,a 51-year-old woman,presented with SLE and APS with refractory thrombocytopenia.She had been diagnosed with pulmonary tuberculosis 4.5 years ago and received antituberculosis therapy for 2 years.She had also undergone pulmonary lobectomy 4 years ago for lung adenocarcinoma.Her thrombocytopenia relapsed(lowest 14×10^(9)/L)when prednisone was tapered to<10mg/day.After adding telitacicept(160 mg/week)to cyclosporin A(150 mg/day)and hydroxychloroquine(400 mg/day)for 5 months,aPLs decreased and platelet counts increased(78×10^(9)to 183×10^(9)/L),enabling halving of her dose of prednisone from 15 to 7.5 mg/day.Neither patient had any adverse effects.Conclusion:Telitacicept can safely reduce aPLs titers and improve refractory thrombocytopenia in patients with secondary APS.Randomized-controlled trials to assess its effectiveness are urgently required.展开更多
Background:Fibroblast-like synoviocytes(FLSs),resident mesenchymal cells of synovial joints,play an important role in the pathogenesis of rheumatoid arthritis(RA).Dickkopf-1(DKK-1)has been proposed to be a master regu...Background:Fibroblast-like synoviocytes(FLSs),resident mesenchymal cells of synovial joints,play an important role in the pathogenesis of rheumatoid arthritis(RA).Dickkopf-1(DKK-1)has been proposed to be a master regulator of bone remodeling in inflammatory arthritis.Here,potential impairation on the activity of FLSs derived from RA to small interfering RNAs(siRNAs)targeting DKK-1 was investigated.Methods:siRNAs targeting DKK-1 were transfected into FLSs of patients with RA.Interleukin(IL)-1β,IL-6,IL-8,matrix metalloproteinase(MMP)2,MMP3,MMP9,transforming growth factor(TGF)-pi,TGF-β2 and monocyte chemoattractant protein(MCP)-1 levels in the cell culture supernatant were detected by enzyme-linked immunosorbent assay(ELISA).Invasion assay and 3H incorporation assay were utilized to investigate the effects of siRNAs targeting DKK-1 on FLSs invasion and cell proliferation,respectively.Western blotting was performed to analyze the expression of nuclear factor(NF)-kB,interleukin-1 receptor-associared kinase(IRAK)1,extracellular regulated protein kinases(ERK)1,Jun N-terminal kinase(JNK)and p-catenin in FLSs.Results:DKK-1 targeting siRNAs inhibited the expression of DKK-1 in FLSs(P<0.01).siRNAs induced a significant reduction of the levels of IL-6,IL-8,MMP2,MMP3 and MMP9 in FLSs compared to the control group(P<0.05).DKK-1 targeting siRNAs inhibited the proliferation and invasion of FLSs(P<0.05).Important molecules of pro-inflammatory signaling in FLSs,including IRAKI and ERK1,were decreased by the inhibition of DKK-1 in FLSs.In contrast,β-catenin,a pivotal downstream molecule of the Wnt signaling pathway was increased.Conclusions:By inhibiting DKK-1,we were able to inhibit the proliferation,invasion and pro-inflammatory cytokine secretion of FLSs derived from RA,which was mediated by the ERK or the IRAK-1 signaling pathway.These data indicate the application of DKK-1 silencing could be a potential therapeutic approach to RA.展开更多
Transforming growth factor-β1(TGF-β1)acts as a tumor promoter in advanced prostate cancer(PCa).We speculated that microRNAs(miRNAs)that are inhibited by TGF-β1 might exert anti-tumor effects.To assess this,we ident...Transforming growth factor-β1(TGF-β1)acts as a tumor promoter in advanced prostate cancer(PCa).We speculated that microRNAs(miRNAs)that are inhibited by TGF-β1 might exert anti-tumor effects.To assess this,we identified several miRNAs downregulated by TGF-β1 in PCa cell lines and selected miR-3691-3p for detailed analysis as a candidate anti-oncogene miRNA.miR-3691-3p was expressed at significantly lower levels in human PCa tissue compared with paired benign prostatic hyperplasia tissue,and its expression level correlated inversely with aggressive clinical pathological features.Overexpression of miR-3691-3p in PCa cell lines inhibited proliferation,migration,and invasion,and promoted apoptosis.The miR-3691-3p target genes E2F transcription factor 3(E2F3)and PR domain containing 1,with ZNF domain(PRDM1)were upregulated in miR-3691-3p-overexpressing PCa cells,and silencing of E2F3 or PRDM1 suppressed PCa cell proliferation,migration,and invasion.Treatment of mice bearing PCa xenografts with a miR-3691-3p agomir inhibited tumor growth and promoted tumor cell apoptosis.Consistent with the negative regulation of E2F3 and PRDM1 by miR-3691-3p,both proteins were overexpressed in clinical PCa specimens compared with noncancerous prostate tissue.Our results indicate that TGF-β1-regulated miR-3691-3p acts as an anti-oncogene in PCa by downregulating E2F3 and PRDM1.These results provide novel insights into the mechanisms by which TGF-β1 contributes to the progression of PCa.展开更多
基金The project was supported by the National Natural Science Foundation of China,No 3860869
文摘Merozoite surface antigens can induce protective immune responses and may becandidate antigens for malaria vaccine.Four hybridoma cell lines secreting monoclonalantibodies against Plasmodium falciparum Fcc7801/HN were produced.Antibodies fromthree of the four lines showed significant growth-inhibiting effect on P.falciparum invitro.One monoclonal antibody,known as C6,conjugated the antigen located exclusivelyon the merozoite surface and distributed evenly over the entire surface,as wasdemonstrated by immunoelectron microscopy.C6 also precipitated a single protein of Mr71000.
基金This work was supported by grants from the National Natural Science Foundation of China(Nos.81801615 and 81871289).
文摘Background:Clinically amyopathic dermatomyositis(CADM)is a unique sub-type of idiopathic inflammatory myopathies with a high prevalence of interstitial lung disease(ILD).Poor prognosis of the patients was strongly associated with rapid progressive ILD.The aim of this study was to identify risk factors for prediction of different types of ILD in CADM.Methods:In this study,data of 108 inpatients with CADM were collected,including 87 with ILD.The baseline clinical data and laboratory parameters,including myositis-specific and associated antibodies and tumor-associated antigens were analyzed to identify risk factors for acute or subacute interstitial pneumonitis(A/SIP)and chronic interstitial pneumonitis(CIP).Results:In 87 patients with CADM-ILD,39(36.1%)were A/SIP,and 48(44.4%)were CIP.There were 22(20.4%)patients with asymptomatic ILD who were detected by routine high resolution computed tomography.Cytokeratin-19 fragment(CYFRA21-1)was significantly higher in CADM-ILD than that in CADM patients without ILD;carcinoembryonic antigen and neuron-specific enolase were significantly elevated in A/SIP than that in CIP.Patients with A/SIP had a higher positive rate of anti-melanoma differentiation-associated gene 5(MDA5),while patients with CIP had a higher positive rate of anti PL-12 and anti-Ro-52.Logistic regression analysis indicated that elevation of CYFRA21-1 was a risk factor for ILD,higher titer of anti-MDA5 indicated increased likelihood for A/SIP,and higher titer of anti-Ro-52 was also clearly associated with CIP.Conclusions:This study indicated that the prevalence of ILD was high in CADM.Asymptomatic ILD has been previously underestimated.Anti-MDA5 was a risk factor for the presence of A/SIP,and CYFRA21-1 was a risk factor for ILD.
基金Peking University People's Hospital Research and Development Funds,Grant/Award Numbers:RDY 2019-04,RDJP2022-12National Natural Science Foundation of China,Grant/Award Numbers:81801615,81871289。
文摘Introduction:Thrombocytopenia,a common noncriteria manifestation of antiphospholipid syndrome(APS),is severe in approximately one-third of patients with APS.However,there are no guidelines for treating such thrombocytopenia.B-cell-targeting therapy may be an option in refractory cases;however,its efficacy has not been firmly established.Here,we report on two patients with refractory antiphospholipid antibodies(aPLs)-associated thrombocytopenia treated with telitacicept.Case Description:Case 1,a 39-year-old woman,presented with systemic lupus erythematosus(SLE)and APS with diffuse alveolar hemorrhage,persistent thrombocytopenia,and recurrent miscarriages.The thrombocytopenia had been refractory to multiple lines of treatments,the most recent being mycophenolate mofetil and prednisone(5 mg/day).After receiving telitacicept(160 mg/week)for 3 months,she had presented with decreased titers of aPLs and a slight increase in platelet counts(14×10^(9)to 35×10^(9)/L).Case 2,a 51-year-old woman,presented with SLE and APS with refractory thrombocytopenia.She had been diagnosed with pulmonary tuberculosis 4.5 years ago and received antituberculosis therapy for 2 years.She had also undergone pulmonary lobectomy 4 years ago for lung adenocarcinoma.Her thrombocytopenia relapsed(lowest 14×10^(9)/L)when prednisone was tapered to<10mg/day.After adding telitacicept(160 mg/week)to cyclosporin A(150 mg/day)and hydroxychloroquine(400 mg/day)for 5 months,aPLs decreased and platelet counts increased(78×10^(9)to 183×10^(9)/L),enabling halving of her dose of prednisone from 15 to 7.5 mg/day.Neither patient had any adverse effects.Conclusion:Telitacicept can safely reduce aPLs titers and improve refractory thrombocytopenia in patients with secondary APS.Randomized-controlled trials to assess its effectiveness are urgently required.
基金This work was supported by grants from the National Key R&D Program of China(No.2017YFA0105802)National Natural Science Foundation of China(Nos.81771678,81801617)Peking University People's Hospital Research and Development Funds(No.RDH 2017-02&RDX 2019-02).
文摘Background:Fibroblast-like synoviocytes(FLSs),resident mesenchymal cells of synovial joints,play an important role in the pathogenesis of rheumatoid arthritis(RA).Dickkopf-1(DKK-1)has been proposed to be a master regulator of bone remodeling in inflammatory arthritis.Here,potential impairation on the activity of FLSs derived from RA to small interfering RNAs(siRNAs)targeting DKK-1 was investigated.Methods:siRNAs targeting DKK-1 were transfected into FLSs of patients with RA.Interleukin(IL)-1β,IL-6,IL-8,matrix metalloproteinase(MMP)2,MMP3,MMP9,transforming growth factor(TGF)-pi,TGF-β2 and monocyte chemoattractant protein(MCP)-1 levels in the cell culture supernatant were detected by enzyme-linked immunosorbent assay(ELISA).Invasion assay and 3H incorporation assay were utilized to investigate the effects of siRNAs targeting DKK-1 on FLSs invasion and cell proliferation,respectively.Western blotting was performed to analyze the expression of nuclear factor(NF)-kB,interleukin-1 receptor-associared kinase(IRAK)1,extracellular regulated protein kinases(ERK)1,Jun N-terminal kinase(JNK)and p-catenin in FLSs.Results:DKK-1 targeting siRNAs inhibited the expression of DKK-1 in FLSs(P<0.01).siRNAs induced a significant reduction of the levels of IL-6,IL-8,MMP2,MMP3 and MMP9 in FLSs compared to the control group(P<0.05).DKK-1 targeting siRNAs inhibited the proliferation and invasion of FLSs(P<0.05).Important molecules of pro-inflammatory signaling in FLSs,including IRAKI and ERK1,were decreased by the inhibition of DKK-1 in FLSs.In contrast,β-catenin,a pivotal downstream molecule of the Wnt signaling pathway was increased.Conclusions:By inhibiting DKK-1,we were able to inhibit the proliferation,invasion and pro-inflammatory cytokine secretion of FLSs derived from RA,which was mediated by the ERK or the IRAK-1 signaling pathway.These data indicate the application of DKK-1 silencing could be a potential therapeutic approach to RA.
基金This study was supported by Shanghai Changning District Committee of Science and Technology(CNKW2016Y01)Shanghai Tongren Hospital Project(TRYJ201501)+3 种基金Suzhou Science and Technology Development Program(SYS201717)the Second Affiliated Hospital of Soochow University Advance Research Program of the Natural Science Foundation of China Grants(SDFEYGJ1705)Open project of Jiangsu State Key Laboratory of Radiation Medicine and Projection(GJS1963)the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Transforming growth factor-β1(TGF-β1)acts as a tumor promoter in advanced prostate cancer(PCa).We speculated that microRNAs(miRNAs)that are inhibited by TGF-β1 might exert anti-tumor effects.To assess this,we identified several miRNAs downregulated by TGF-β1 in PCa cell lines and selected miR-3691-3p for detailed analysis as a candidate anti-oncogene miRNA.miR-3691-3p was expressed at significantly lower levels in human PCa tissue compared with paired benign prostatic hyperplasia tissue,and its expression level correlated inversely with aggressive clinical pathological features.Overexpression of miR-3691-3p in PCa cell lines inhibited proliferation,migration,and invasion,and promoted apoptosis.The miR-3691-3p target genes E2F transcription factor 3(E2F3)and PR domain containing 1,with ZNF domain(PRDM1)were upregulated in miR-3691-3p-overexpressing PCa cells,and silencing of E2F3 or PRDM1 suppressed PCa cell proliferation,migration,and invasion.Treatment of mice bearing PCa xenografts with a miR-3691-3p agomir inhibited tumor growth and promoted tumor cell apoptosis.Consistent with the negative regulation of E2F3 and PRDM1 by miR-3691-3p,both proteins were overexpressed in clinical PCa specimens compared with noncancerous prostate tissue.Our results indicate that TGF-β1-regulated miR-3691-3p acts as an anti-oncogene in PCa by downregulating E2F3 and PRDM1.These results provide novel insights into the mechanisms by which TGF-β1 contributes to the progression of PCa.
