sincalide and Arthritis--Rheumatoid

Rheumatoid arthritis (RA) is a systemic autoimmune disease, which has been reported closely associated with the dysfunction of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. This study aims to explore the potential therapeutic effect of Tofacitinib, a putative JAK/STAT inhibitor, in RA. Tofacitinib suppressed proliferation and accelerated apoptosis of rheumatoid arthritis synovial fibroblasts (RA-FLS) as confirmed by CCK-8, EdU and Western blot assays. Tofacitinib significantly inhibited expression of pro-inflammatory factors including tumor necrosis factor-α (TNF-α), vascular endothelial growth factor A, matrix metalloproteinase 1, matrix metalloproteinase 3, interleukin-6 and interferon gamma in RA-FLS cells. mechanistically, tofacitinib decreased signal transducer and activator of transcription 6 (STAT6), which transcriptionally activates miR-425-5p, and thus increased insulin like growth factor 1 (IGF1) expression, a target of miR-425-5p in RA-FLS. Overexpression of STAT6 restored the expression of pro-inflammatory factors and proliferation inhibited by Tofacitinib in RA-FLS. Overall, Tofacitinib exerted inhibitory effect on proliferation and inflammation of RA-FLS through modulating STAT6/miR-425-5p/IGF1 signal axis. These findings shed light on the novel strategies for improving RA.

Topics: Arthritis, Rheumatoid; Cell Proliferation; Cells, Cultured; Fibroblasts; Humans; Inflammation; Insulin-Like Growth Factor I; Interferon-gamma; Interleukin-6; Janus Kinases; Matrix Metalloproteinase 1; MicroRNAs; Piperidines; Pyrimidines; Sincalide; STAT6 Transcription Factor; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

To observe the analgesic effect of acupuncture and to explore its central analgesic mechanism in rheumatoid arthritis rabbits.
 Methods: A total of 60 flap-eared white rabbits were randomly assigned into a normal control group (n=6), a model group (n=6), a body-acupuncture group (n=24), and a buccal acupuncture group (n=24). The later 2 groups were further randomly assigned into 0, 0.5, 1, and 2 h subgroups, with 6 cases in each group. The rheumatoid arthritis model was established by induction of egg-albumin. In the body acupuncture group, bilateral "Xiyan" and "Zusanli" were punctured for 15 s while in the buccal acupuncture group, acupuncture was applied to "Xi" for 15 s, with the needle retaining for 30 min. The pain threshold was detected with PL-200, taking struggle movements of rabbits as a measurement index, response latency from irradiation to struggling movements as the rabbit's pain threshold. The contents of β-endorplhin (β-EP) and cholecystokinin-8 (CCK-8) in cerebrospinal fluid were examined by radioimmunoassay.
 Results: Compared with the control group, pain threshold and CCK-8 levels decreased significantly (P<0.01) and the concentration of β-EP significantly increased (P<0.05) in the model group. The pain threshold in the body-acupuncture group and the buccal acupuncture group at 0 and 
1 h (P<0.05 or P<0.01) increased significantly, while the β-EP and CCK-8 contents in the body-acupuncture group and the buccal acupuncture group were significantly higher than those in the model group (P<0.01 or P<0.05). Both β-EP and CCK-8 contents in the buccal acupuncture group at 0 h were significantly higher than those in the body-acupuncture group (P<0.05).
 Conclusion: The analgesic effect of buccal acupuncture is superior to that of body-acupuncture. Both buccal acupuncture and body-acupuncture can effectively raise the pain threshold in acute arthritis rabbits, which is closely associated with their effects in the up-regulation of β-EP and CCK-8 contents in cerebrospinal fluid.. 目的：探究针刺对患有类风湿性关节炎大耳白兔的镇痛时效及其中枢作用机制。方法：将60只大耳白兔随机分为正常组(n=6)、模型组(n=6)、体针组(n=24)和颊针组(n=24)，再将后两组分为针后即时(0 h)、针后0.5，1，2 h 4个亚组，每组各6只。白兔类风湿性关节炎模型采用卵蛋白诱导建立。体针组针刺双侧“膝眼”和“足三里”
1次，颊针组双侧颊针针刺“膝”1次，行针15 s，留针30 min。采用PL-200热刺痛仪检测痛阈，以兔出现缩耳挣扎动作为疼痛反应指标，自照射开始至兔出现反应的潜伏期时间作为该兔的痛阈值；使用放射免疫法检测兔脑脊液中β-内啡肽(β-endorplhin，β-EP)及八肽胆囊收缩素(cholecystokinin-8，CCK-8)含量。结果：与正常组相比，模型组痛阈和CCK-8含量显著降低(P<0.01)，β-EP含量显著升高(P<0.05)；与模型组相比，体针组和颊针组的痛阈在0和1 h(P<0.05或P<0.01)显著升高；体针组和颊针组兔脑脊液中CCK-8和β-EP含量均显著高于模型组(P<0.01或P<0.05)；颊针组的即时(0 h)CCK-8和β-EP含量显著高于体针组(P<0.05)，其他时间无明显变化。结论：针刺治疗可以有效缓解类风湿性关节炎的疼痛，颊针疗法的即时镇痛效应优于体针治疗，且这种即时镇痛效应与脑脊液中β-EP和CCK-8含量变化相关。.

Topics: Acupuncture Analgesia; Acupuncture Points; Animals; Arthritis, Rheumatoid; beta-Endorphin; Mouth; Movement; Pain Threshold; Rabbits; Random Allocation; Sincalide; Time Factors