BACKGROUND The role of macrophages in rheumatoid arthritis(RA)and its mechanism have attracted much attention in RA pathogenesis.Macrophages accumulate in the synoviums of RA,and the proportion of M1 type pro-inflamma...BACKGROUND The role of macrophages in rheumatoid arthritis(RA)and its mechanism have attracted much attention in RA pathogenesis.Macrophages accumulate in the synoviums of RA,and the proportion of M1 type pro-inflammatory macrophages is higher than that of M2 type anti-inflammatory macrophages,leading to the secretion of inflammatory molecules and the aggravation of inflammatory reaction,which has made macrophages a potential target of RA drugs.Iguratimod is a kind of cyclo-oxygenase-2 inhibitor that affects macrophage polarity.It is speculated that its anti-inflammatory and anti-rheumatic effects may be related to the regulation of macrophage M1/M2 ratio.AIM To investigate the effects of Iguratimod on the polarity of mononuclear macrophages in elderly patients with RA.METHODS Elderly patients with RA and joint effusion were selected,including 10 men and 25 women,with an average age of 66.37±4.42 years.Patients were treated with oral administration of 25 mg Iguratimod(Iremod,State Food and Drug Administration Approval No.H20110084)twice daily for 12 wk.Disease Activity Score 28 and Health Assessment Questionnaire score were collected according to the disease severity before and after treatment.Venous blood and joint effusion fluid were collected,mononuclear macrophages were extracted and expression of cell surface markers CD86,CD64,CD163,and CD206 was analyzed by flow cytometry.The concentration of inflammatory factors interleukin(IL)-6,IL-1β,transforming growth factor-β,and IL-4 in the joint effusion fluid was analyzed by enzyme-linked immunosorbent assay.Expression of mononuclear cells inhibitor of nuclear factor-κB(IκB)and phosphorylated IκB in peripheral blood was analyzed by western blotting.RESULTS Disease Activity Score 28 score and Health Assessment Questionnaire score of patients treated with Iguratimod decreased significantly.The percentage of cell surface markers CD86 and CD64 decreased significantly,and the percentage of CD163 and CD206 increased significantly(P<0.05).The inflammatory factors IL-6 and IL-1βdecreased significantly,and transforming growth factor-βand IL-4 increased significantly.Western blot analysis showed that mononuclear cell inhibitor of nuclear factor-κB in peripheral blood was significantly increased after treatment,and its phosphorylation level was significantly decreased(P<0.05).CONCLUSION Iguratimod can promote the transformation of mononuclear macrophages from M1 to M2 in elderly patients with RA by inhibiting the nuclear factor-κB pathway,thus improving symptoms of RA.展开更多
BACKGROUND Primary Sjögren's syndrome(pSS)concomitant with autoimmune hemolytic anemia(AIHA)but without eye and mouth dryness is exceedingly rare.Iguratimod(IGU)has been widely used in the treatment of pSS.Ho...BACKGROUND Primary Sjögren's syndrome(pSS)concomitant with autoimmune hemolytic anemia(AIHA)but without eye and mouth dryness is exceedingly rare.Iguratimod(IGU)has been widely used in the treatment of pSS.However,there are few reports about the application of IGU in pSS concomitant with AIHA.CASE SUMMARY Here,we present the case of a patient with pSS concomitant with AIHA but without eye and mouth dryness.The patient was initially diagnosed with hyperplastic anemia and AIHA while pSS was missed,and was finally diagnosed with pSS concomitant with AIHA.The patient was treated with IGU along with prednisone and hydroxychloroquine,and her hemoglobin,reticulocytes and IgG returned to normal levels.CONCLUSION IGU was effective for and well tolerated by our patient with pSS concomitant with AIHA,and may be a promising therapy for the treatment of this disease.展开更多
Introduction: The aim of this study was to observe an inhibition of bone resorption and osteoclastogenesis by iguratimod (IGU, T-614), a disease-modifying anti-rheumatic drug, using adjuvant-induced arthritis (AIA) ra...Introduction: The aim of this study was to observe an inhibition of bone resorption and osteoclastogenesis by iguratimod (IGU, T-614), a disease-modifying anti-rheumatic drug, using adjuvant-induced arthritis (AIA) rats and receptor activator of nuclear factor kappa-B ligand (RANKL)-stimulated RAW264.7 cells. Methods: The bone mineral density and 3D morphometric parameters of hind paws in AIA rats were measured using micro computed tomography (μCT) imaging. The activity of osteoclast cells was estimated based on tartrate-resistant acid phosphatase (TRAP) staining in specimens from the rats. In vitro TRAP activity was investigated using RANKL-stimulated RAW264.7 cells. The amount of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) protein was measured by western blot analysis. The expression of Nfatc1, its regulator genes, its upstream factors, and osteoclast-functional genes were investigated. Results: In addition to the suppression of bone resorption and lesions of bone trabeculae of AIA rats, IGU significantly decreased the number of TRAP-positive cells in the calcaneal bones. Moreover, this drug inhibited the differentiation of RANKL-stimulated RAW264.7 cells into osteoclasts, which were identified morphologically and functionally. IGU decreased the amount of NFATc1 protein and improved the altered expression of NFATc1-associated genes and osteoclast-functional genes. Conclusions: IGU suppressed osteoclastogenesis and bone resorption via the RANKL-NFATc1 pathway, suggesting such effect would be expected in clinical use.展开更多
目的探讨来氟米特和艾拉莫德分别联合甲氨蝶呤治疗类风湿关节炎(rheumatoid arthritis,RA)的有效性和药物经济学,为临床药物的合理选择提供参考。方法计算机搜索Pubmed、Medline、知网、万方、维普等数据库,查找来氟米特和艾拉莫德分别...目的探讨来氟米特和艾拉莫德分别联合甲氨蝶呤治疗类风湿关节炎(rheumatoid arthritis,RA)的有效性和药物经济学,为临床药物的合理选择提供参考。方法计算机搜索Pubmed、Medline、知网、万方、维普等数据库,查找来氟米特和艾拉莫德分别联合甲氨蝶呤治疗RA的随机对照试验,查询期限从建库到2023年7月。通过RevMan5.4软件对纳入文献进行meta分析,同时利用TreeAge Pro 2019软件构建决策树模型,对2种药物分别联合甲氨蝶呤治疗RA进行成本-效果分析,并进行敏感性评价。结果Meta分析结果显示,来氟米特联合甲氨蝶呤组治疗RA有效率高于甲氨蝶呤组[OR=2.95,95%CI(1.91-4.56),P<0.01],艾拉莫德联合甲氨蝶呤组治疗RA有效率高于甲氨蝶呤组[OR=3.35,95%CI(1.88-5.97),P<0.01];药物经济性分析发现,艾拉莫德联合甲氨蝶呤组对比来氟米特联合甲氨蝶呤组的增量成本-效果比为196312.5元,即艾拉莫德联合甲氨蝶呤组每增加1例治疗有效较来氟米特联合甲氨蝶呤组需额外花费196312.5元。敏感性分析结果:对研究结果影响最大的是艾拉莫德联合甲氨蝶呤组治疗有效率和来氟米特联合甲氨蝶呤组治疗有效率。结论来氟米特和艾拉莫德分别联合甲氨蝶呤治疗RA的有效性均高于甲氨蝶呤单独治疗,来氟米特联合甲氨蝶呤治疗更具有经济学优势。展开更多
文摘BACKGROUND The role of macrophages in rheumatoid arthritis(RA)and its mechanism have attracted much attention in RA pathogenesis.Macrophages accumulate in the synoviums of RA,and the proportion of M1 type pro-inflammatory macrophages is higher than that of M2 type anti-inflammatory macrophages,leading to the secretion of inflammatory molecules and the aggravation of inflammatory reaction,which has made macrophages a potential target of RA drugs.Iguratimod is a kind of cyclo-oxygenase-2 inhibitor that affects macrophage polarity.It is speculated that its anti-inflammatory and anti-rheumatic effects may be related to the regulation of macrophage M1/M2 ratio.AIM To investigate the effects of Iguratimod on the polarity of mononuclear macrophages in elderly patients with RA.METHODS Elderly patients with RA and joint effusion were selected,including 10 men and 25 women,with an average age of 66.37±4.42 years.Patients were treated with oral administration of 25 mg Iguratimod(Iremod,State Food and Drug Administration Approval No.H20110084)twice daily for 12 wk.Disease Activity Score 28 and Health Assessment Questionnaire score were collected according to the disease severity before and after treatment.Venous blood and joint effusion fluid were collected,mononuclear macrophages were extracted and expression of cell surface markers CD86,CD64,CD163,and CD206 was analyzed by flow cytometry.The concentration of inflammatory factors interleukin(IL)-6,IL-1β,transforming growth factor-β,and IL-4 in the joint effusion fluid was analyzed by enzyme-linked immunosorbent assay.Expression of mononuclear cells inhibitor of nuclear factor-κB(IκB)and phosphorylated IκB in peripheral blood was analyzed by western blotting.RESULTS Disease Activity Score 28 score and Health Assessment Questionnaire score of patients treated with Iguratimod decreased significantly.The percentage of cell surface markers CD86 and CD64 decreased significantly,and the percentage of CD163 and CD206 increased significantly(P<0.05).The inflammatory factors IL-6 and IL-1βdecreased significantly,and transforming growth factor-βand IL-4 increased significantly.Western blot analysis showed that mononuclear cell inhibitor of nuclear factor-κB in peripheral blood was significantly increased after treatment,and its phosphorylation level was significantly decreased(P<0.05).CONCLUSION Iguratimod can promote the transformation of mononuclear macrophages from M1 to M2 in elderly patients with RA by inhibiting the nuclear factor-κB pathway,thus improving symptoms of RA.
基金Supported by the Lanzhou Science and Technology Plan Project,No.2018-3-48Lanzhou Talent Innovation and Entrepreneurship Project,No.2019-RC-35and 2019 Special Fund for Doctoral Training of Lanzhou University Second Hospital,No.YJS-BD-15.
文摘BACKGROUND Primary Sjögren's syndrome(pSS)concomitant with autoimmune hemolytic anemia(AIHA)but without eye and mouth dryness is exceedingly rare.Iguratimod(IGU)has been widely used in the treatment of pSS.However,there are few reports about the application of IGU in pSS concomitant with AIHA.CASE SUMMARY Here,we present the case of a patient with pSS concomitant with AIHA but without eye and mouth dryness.The patient was initially diagnosed with hyperplastic anemia and AIHA while pSS was missed,and was finally diagnosed with pSS concomitant with AIHA.The patient was treated with IGU along with prednisone and hydroxychloroquine,and her hemoglobin,reticulocytes and IgG returned to normal levels.CONCLUSION IGU was effective for and well tolerated by our patient with pSS concomitant with AIHA,and may be a promising therapy for the treatment of this disease.
文摘Introduction: The aim of this study was to observe an inhibition of bone resorption and osteoclastogenesis by iguratimod (IGU, T-614), a disease-modifying anti-rheumatic drug, using adjuvant-induced arthritis (AIA) rats and receptor activator of nuclear factor kappa-B ligand (RANKL)-stimulated RAW264.7 cells. Methods: The bone mineral density and 3D morphometric parameters of hind paws in AIA rats were measured using micro computed tomography (μCT) imaging. The activity of osteoclast cells was estimated based on tartrate-resistant acid phosphatase (TRAP) staining in specimens from the rats. In vitro TRAP activity was investigated using RANKL-stimulated RAW264.7 cells. The amount of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) protein was measured by western blot analysis. The expression of Nfatc1, its regulator genes, its upstream factors, and osteoclast-functional genes were investigated. Results: In addition to the suppression of bone resorption and lesions of bone trabeculae of AIA rats, IGU significantly decreased the number of TRAP-positive cells in the calcaneal bones. Moreover, this drug inhibited the differentiation of RANKL-stimulated RAW264.7 cells into osteoclasts, which were identified morphologically and functionally. IGU decreased the amount of NFATc1 protein and improved the altered expression of NFATc1-associated genes and osteoclast-functional genes. Conclusions: IGU suppressed osteoclastogenesis and bone resorption via the RANKL-NFATc1 pathway, suggesting such effect would be expected in clinical use.
文摘目的探讨来氟米特和艾拉莫德分别联合甲氨蝶呤治疗类风湿关节炎(rheumatoid arthritis,RA)的有效性和药物经济学,为临床药物的合理选择提供参考。方法计算机搜索Pubmed、Medline、知网、万方、维普等数据库,查找来氟米特和艾拉莫德分别联合甲氨蝶呤治疗RA的随机对照试验,查询期限从建库到2023年7月。通过RevMan5.4软件对纳入文献进行meta分析,同时利用TreeAge Pro 2019软件构建决策树模型,对2种药物分别联合甲氨蝶呤治疗RA进行成本-效果分析,并进行敏感性评价。结果Meta分析结果显示,来氟米特联合甲氨蝶呤组治疗RA有效率高于甲氨蝶呤组[OR=2.95,95%CI(1.91-4.56),P<0.01],艾拉莫德联合甲氨蝶呤组治疗RA有效率高于甲氨蝶呤组[OR=3.35,95%CI(1.88-5.97),P<0.01];药物经济性分析发现,艾拉莫德联合甲氨蝶呤组对比来氟米特联合甲氨蝶呤组的增量成本-效果比为196312.5元,即艾拉莫德联合甲氨蝶呤组每增加1例治疗有效较来氟米特联合甲氨蝶呤组需额外花费196312.5元。敏感性分析结果:对研究结果影响最大的是艾拉莫德联合甲氨蝶呤组治疗有效率和来氟米特联合甲氨蝶呤组治疗有效率。结论来氟米特和艾拉莫德分别联合甲氨蝶呤治疗RA的有效性均高于甲氨蝶呤单独治疗,来氟米特联合甲氨蝶呤治疗更具有经济学优势。
