Rheumatoid arthritis(RA)is an autoimmune disease characterized by severe synovial inflammation and cartilage damage.Despite great progress in RA therapy,there still lacks the drugs to completely cure RA patients.Herei...Rheumatoid arthritis(RA)is an autoimmune disease characterized by severe synovial inflammation and cartilage damage.Despite great progress in RA therapy,there still lacks the drugs to completely cure RA patients.Herein,we propose a reprogrammed neutrophil cytopharmaceuticals loading with TNFα-targeting-siRNA(siTNFα)as an alternative anti-inflammatory approach for RA treatment.The loaded siTNFαact as not only the gene therapeutics to inhibit TNFαproduction by macrophages in inflamed synovium,but also the editors to reprogram neutrophils to anti-inflammatory phenotypes.Leveraging the active tendency of neutrophils to inflammation,the reprogrammed siTNFα/neutrophil cytopharmaceuticals(siTNFα/TP/NEs)can rapidly migrate to the inflamed synovium,transfer the loaded siTNFαto macrophages followed by the significant reduction of TNFαexpression,and circumvent the pro-inflammatory activity of neutrophils,thus leading to the alleviated synovial inflammation and improved cartilage protection.Our work provides a promising cytopharmaceutical for RA treatment,and puts forward a living neutrophil-based gene delivery platform.展开更多
目的:探讨补肾活血汤对肾虚血瘀型膝骨性关节炎(KOA)患者的临床疗效及对血清炎症因子的影响。方法:选取2019年3月~2020年9月梧州市红十字会医院收治的80例KOA患者,随机数字表法分为两组,对照组(n=40)接受止痛消炎软膏治疗,观察组(n=40)...目的:探讨补肾活血汤对肾虚血瘀型膝骨性关节炎(KOA)患者的临床疗效及对血清炎症因子的影响。方法:选取2019年3月~2020年9月梧州市红十字会医院收治的80例KOA患者,随机数字表法分为两组,对照组(n=40)接受止痛消炎软膏治疗,观察组(n=40)接受补肾活血汤联合止痛消炎软膏治疗,比较两组患者临床疗效和治疗后中医症状积分、KOA严重程度及血清转化生长因子β1(TGF-β1)、胰岛素样生长因子-1(IGF-1)、成纤维细胞生长因子-2(FGF-2)、白介素-1(IL-1β)、IL-6、肿瘤坏死因子-α(TNF-α)水平和不良反应发生情况。结果:观察组临床治疗总有效率明显高于对照组(P<0.05);治疗后观察组中医症状积分、西安大略和麦克马斯特大学(Western Ontario and McMaster Universities,WOMAC)骨关节炎评分指数和血清IL-1β、IL-6、TNF-α水平明显低于对照组,血清TGF-β1、IGF-1、FGF-2水平明显高于对照组(P<0.05);两组患者均未出现明显不良反应。结论:补肾活血汤联合止痛消炎软膏治疗肾虚血瘀型KOA疗效显著,可有效缓解关节疼痛,改善活动受限,促进软骨修复,抑制炎症因子表达,且安全性高,值得推广。展开更多
基金supported by the National Natural Science Foundation of China(81930099,82073785,82130102,92159304,81773664)the Natural Science Foundation of Jiangsu Province(BK20212011,China)+3 种基金“Double First-Class”University project(CPU2018GY47,China)111 Project from the Ministry of Education of Chinathe State Administration of Foreign Expert Affairs of China(No.111-2-07,B17047,China)the Open Project of State Key Laboratory of Natural Medicines(No.SKLNMZZ202223,China)。
文摘Rheumatoid arthritis(RA)is an autoimmune disease characterized by severe synovial inflammation and cartilage damage.Despite great progress in RA therapy,there still lacks the drugs to completely cure RA patients.Herein,we propose a reprogrammed neutrophil cytopharmaceuticals loading with TNFα-targeting-siRNA(siTNFα)as an alternative anti-inflammatory approach for RA treatment.The loaded siTNFαact as not only the gene therapeutics to inhibit TNFαproduction by macrophages in inflamed synovium,but also the editors to reprogram neutrophils to anti-inflammatory phenotypes.Leveraging the active tendency of neutrophils to inflammation,the reprogrammed siTNFα/neutrophil cytopharmaceuticals(siTNFα/TP/NEs)can rapidly migrate to the inflamed synovium,transfer the loaded siTNFαto macrophages followed by the significant reduction of TNFαexpression,and circumvent the pro-inflammatory activity of neutrophils,thus leading to the alleviated synovial inflammation and improved cartilage protection.Our work provides a promising cytopharmaceutical for RA treatment,and puts forward a living neutrophil-based gene delivery platform.
文摘目的:探讨补肾活血汤对肾虚血瘀型膝骨性关节炎(KOA)患者的临床疗效及对血清炎症因子的影响。方法:选取2019年3月~2020年9月梧州市红十字会医院收治的80例KOA患者,随机数字表法分为两组,对照组(n=40)接受止痛消炎软膏治疗,观察组(n=40)接受补肾活血汤联合止痛消炎软膏治疗,比较两组患者临床疗效和治疗后中医症状积分、KOA严重程度及血清转化生长因子β1(TGF-β1)、胰岛素样生长因子-1(IGF-1)、成纤维细胞生长因子-2(FGF-2)、白介素-1(IL-1β)、IL-6、肿瘤坏死因子-α(TNF-α)水平和不良反应发生情况。结果:观察组临床治疗总有效率明显高于对照组(P<0.05);治疗后观察组中医症状积分、西安大略和麦克马斯特大学(Western Ontario and McMaster Universities,WOMAC)骨关节炎评分指数和血清IL-1β、IL-6、TNF-α水平明显低于对照组,血清TGF-β1、IGF-1、FGF-2水平明显高于对照组(P<0.05);两组患者均未出现明显不良反应。结论:补肾活血汤联合止痛消炎软膏治疗肾虚血瘀型KOA疗效显著,可有效缓解关节疼痛,改善活动受限,促进软骨修复,抑制炎症因子表达,且安全性高,值得推广。