Moxibustion regulates the polarization of macrophages through the IL-4/STAT6 pathway in rheumatoid arthritis.

OBJECTIVE: To observe the effects of moxibustion on "Shenshu" and "Zusanli" on macrophage polarization and IL-4/STAT6 signaling pathway in rats with rheumatoid arthritis (RA). To further explore the possible anti-inflammatory mechanism of moxibustion in the treatment of RA. METHODS: The rats' right hind paws were injected with freund's complete adjuvant (FCA) to establish the model of RA. Seven days after the injection of FCA, moxibustion therapy was performed on the acupoints of Shenshu (BL23) and Zusanli (ST36) once a day for three weeks. The researchers measured the thickness of the foot pad. ELISA and Histological Analysis were performed to observe the anti-inflammatory effect of moxibustion. Then researchers detected the expression of macrophage phenotype and the expression of IL-4/STAT6 signaling pathway related molecules. RESULTS: It was observed that after the injection of FCA, the rats' feet showed obvious symptoms of redness and swelling. But the symptoms were significantly improved when moxibustion was employed. The study found lower IL-23 and higher IL-4 level in the serum of FCA-injected rats after moxibustion treatment. HE staining showed that the synovium of the RA group was hyperemia and edema, with a large number of inflammatory cells infiltration and vascular dilatation. In the moxibustion group, the degree of synovial hyperemia and edema was improved, and the infiltration of inflammatory cells and vascular dilation were reduced. The study also found that there wer differences among the expressions of macrophage phenotypes in RA, and this was shown by the high expression of CD86 and low expression of CD206. However, the polarization of macrophages in the moxibustion group changed, and that was manifested by enhanced M2-polarized Mφs and inhibited M1-polarized Mφs. Meanwhile, moxibustion suppressed the activation of JAK1, JAK3 and STAT6 in the IL-4/STAT6 signaling pathway, which contributed to the polarization of M2 . CONCLUSION: The results demonstrate that moxibustion not only suppresses the polarization of M1, but also promotes the polarization of M1. The anti-inflammatory effect of moxibustion may be related to the regulation of macrophage polarization through IL-4/STAT6 signaling pathway.

Effect of Moxibustion on Inflammatory Cytokines in Animals with Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.

BACKGROUND: This study aims to systematically evaluate the effect of moxibustion on the level of inflammatory cytokines in animal models with rheumatoid arthritis (RA) and to provide evidence for the clinical application of moxibustion to the treatment of RA and related basic researches. METHODS: The databases employed in this study include PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), SinoMed, and Wanfang Data Information Site. The retrieval time was from the establishment of these databases to March 2020. The reviewers made use of the CAMARADES 10-item checklist to evaluate the quality of each included study. The inflammatory cytokines were considered as the outcome measure. The Revman 5.3 software was used to conduct meta-analysis on the outcome indicators of the studies included. RESULTS: A total of 648 articles were retrieved and 18 animal experiments were included in this study. The quality scores of the studies ranged from two to eight with a mean of 5.8. Compared with the effect of the control group, moxibustion reduced the expression of TNF-α (SMD 2.95, 95% CI: 1.99-3.92, P < 0.00001), IL-1ß (SMD 4.10, 95% CI: 2.37-5.84, P < 0.00001), IFN-γ (MD 25, 95% CI: 16.17-33.82, P < 0.00001), IL-6 (MD 11.83, 95% CI: 6.22-17.44, P < 0.0001), and IL-17 (MD 99.3, 95% CI: 86.83-111.76, P < 0.00001). At the same time, the level of IL-2 (SMD 8.89, 95% CI: 0.93-16.86, P=0.03), IL-4 (MD 1.79, 95% CI: 0.26-3.32, P=0.02), and IL-10 (MD 5.93, 95% CI: 1.37-10.49, P=0.01) increased after moxibustion treatment. Asymmetric funnel plots indicated that there was publication bias. CONCLUSION: The findings of the present review indicate that moxibustion can protect the synovium of joint in animal models with RA by upregulation of the level of anti-inflammatory cytokines and downregulation of the level of proinflammatory cytokines. Moxibustion has the potential to relieve inflammation of RA.

[Effects of moxibustion on serum cytokines in experimental animals with rheumatoid arthritis: a systematic review and meta-analysis].

OBJECTIVE: To systematically review the effects of moxibustion on serum cytokines in experimental animals with rheumatoid arthritis. METHODS: PubMed, Embase, Web of Science, The Cochrane Library, CNKI, VIP, Wanfang Data, and CBM were searched for animal experiments on moxibustion intervention for rheumatoid arthritis. Related data were extracted, and RevMan 5.3 was used to perform a meta-analysis of outcome measures, including serum tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), interleukin-17 (IL-17), interleukin-2 (IL-2), interferon-γ (IFN-γ), receptor activator of nuclear factor-kappa B ligand (RANKL), transforming growth factor-ß (TGF-ß), and degree of swelling of diseased joint. RESULTS: A total of 18 studies were included. The detection methods included radioimmunoassay and ELISA and the experimental animal species included rats and rabbits. The studies on serum TNF-α and degree of swelling of diseased joint had publication bias. Meta-analysis showed that the moxibustion group had significant reductions in the serum levels of TNF-α, IL-1, IL-2, IL-6, VEGF, IL-17, and RANKL, significant increases in the serum levels of TGF-ß and IFN-γ, and a significant reduction in the degree of swelling of diseased joints in model animals. CONCLUSION: Moxibustion can effectively regulate levels of the serum cytokines in experimental animals of rheumatoid arthritis and thus reduce inflammatory response and alleviate the swelling of diseased joints.

[Mechanism on moxibustion for rheumatoid arthritis based on PD-1/PD-L1 signaling pathway].

OBJECTIVE: To explore the mechanism of moxibustion on the treatment of rheumatoid arthritis (RA) in the perspective of programmed cell death-1 and its ligand 1 (PD-1/PD-L1). METHODS: A total of 30 Japanese big ear white rabbits were randomly divided into a control group, a model group and a moxibustion group, 10 rabbits in each one. In the model group and the moxibustion group, RA model was prepared by the injection of Freund's complete adjuvant (FCA) into the hind knee joint cavities of each rabbit. In the control group, 0.9% sodium chloride solution of the same dose was injected. On the 8th day of experiment, in the moxibustion group, moxibustion was applied to "Shenshu" (BL 23) and "Zusanli" (ST 36), 5 cones at each acupoint, on the bilateral sides alternatively, once a day, 6 treatments as one course, with an interval of 1 days between the treatment courses. Totally, 3 courses of treatment were required. On the 1st, 7th, 14th, 21st and 28th days of experiment, successively, the circumference of the bilateral knee joints was measured with the tape. On the 28th day of experiment, H.E. staining was adopted to observe the histopathological morphology and to evaluate the score of knee synovial tissue. ELISA was used to determined the concentrations of soluble PD-1 (sPD-1) and its ligand 1 (sPD-L1), the interleukin 2 (IL-2) and IL-17 in knee synovial fluid and the concentrations of sPD-1 and sPD-L1 in serum. The histochemistry method was used to determine the expressions of membrane PD-1 (mPD-1) and its ligand 1 (mPD-L1) in spleen tissue. RESULTS: On the 14th, 21st and 28th days of experiment, the circumference of both knee joints was increased in each of the rabbits in the model group as compared with the control group (P<0.01), and it was reduced significantly in the moxibustion group as compared with the model group (P<0.01). Compared with the control group, the hyperplasia of synovial tissue and fibrous tissue, as well as inflammatory cell infiltration were increased obviously in the model group (P<0.01), and they were reduced significantly in the moxibustion group as compared with the model group (P<0.01, P<0.05). Compared with the control group, the concentrations of IL-2 and IL-17 in knee synovial fluid were increased in the rabbits of the model group (P<0.01). Compared with the model group, after the intervention with moxibustion, the concentrations of IL-2 and IL-17 in knee synovial fluid were reduced in the rabbits of the moxibustion group (P<0.05). Compared with the control group, the concentrations of sPD-1 and sPD-L1 in knee synovial fluid and serum in the rabbits of the model group were all increased (P<0.05). Compared with the model group, the concentration of sPD-1 in the knee synovial fluid and serum were reduced in the rabbits of moxibustion group (P<0.05). Compared with the control group, the expressions of mPD-1 and mPD-L1 in spleen tissue were increased obviously in the rabbits of the model group (P<0.05). Compared with the model group, the expression of mPD-L1 in spleen tissue was up-regulated in the rabbits of the moxibustion group (P<0.05). CONCLUSION: Moxibustion could inhibit the over-activation of T cells by enhancing the negative regulation of PD-1/PD-L1 signaling pathway so as to play its effect in treatment of RA.

Acupuncture versus sham acupuncture for simple obesity: a systematic review and meta-analysis.

Obesity is a growing chronic health problem worldwide. Studies about acupuncture for obesity treatment are many. But there are some doubts about the effectiveness of acupuncture versus sham acupuncture in treating obesity due to its lack of medical evidence. Therefore, the aim of this study is to assess the efficacy of acupuncture for obesity treatment and provide clinic evidence. Four English databases (PubMed, EMBASE, Web of Science and Cochrane Central Register of Controlled Trials) and four Chinese databases (China National Knowledge Infrastructure, Chinese BioMedical Database, Chinese Scientific Journal Database and Wan-Fang Data) were searched from their receptions to August 2019. Randomized controlled trials (RCTs) using the comparison between acupuncture and sham acupuncture to treat simple obesity were included. The primary outcome of body mass index (BMI) would be used to measure the effect of acupuncture on obesity. According to the trial data extraction form based on the Cochrane Handbook, two reviewers separately extracted the data. Risk of bias of the RCTs was assessed by the Cochrane Risk of Bias Tool. The study included 8 RCTs with 403 patients. When compared with sham acupuncture, acupuncture showed obviously effect in BMI reduction (MD=1.0kg/m2, 95% CI=0.6 to 1.4, P<0.001). There was also significant reduction in body weight (MD=1.85kg, 95%CI=0.82 to 2.88, p<0.001), WC (MD=0.97cm, 95%CI=0.24 to 1.71, p=0.01) and body fat mass percentage (MD=1.01, 95%CI=0.25 to 1.77, p<0.05). However, WHR (MD=0.01, 95%CI=0 to 0.03, p>0.05) was not statistically and significantly different between the acupuncture and control groups. Adverse effects were reported in 3 studies. The review suggests that acupuncture is an effective therapy for simple obesity rather than a placebo effect. This potential benefit needs to be further evaluated by longer-term and more rigorous RCTs.

Acupuncture vs sham acupuncture for simple obesity: A protocol for systematic review and meta-analysis.

BACKGROUND: Obesity is a growing chronic health problem worldwide. Studies about acupuncture for obesity treatment are many. But there are some doubts about the effectiveness of acupuncture vs sham acupuncture in treating obesity due to its lack of an evidence-based medical proof. Therefore, the aim of this study is to assess the efficacy of acupuncture for obesity treatment and provide clinic evidence. METHODS: This protocol was based on the previous reporting items for systematic review and meta-analysis agreements. Four English databases (PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials) and 4 Chinese databases (China National Knowledge Infrastructure, Chinese BioMedical Database, Chinese Scientific Journal Database, Wan-Fang Data) will be searched from their receptions to August 2019. Randomized controlled trials (RCTs) using acupuncture compared sham acupuncture (or no treatment) to treat simple obesity will be included. The primary outcome of body mass index (BMI) and body weight (BW) will be used to measure the effect of acupuncture on obesity. According to the trial data extraction form based on the Cochrane Handbook, 2 reviewers will separately extract the data. Risk of bias of the RCTs will be assessed by the Cochrane Risk of Bias Tool. Publication bias will be assessed with funnel plots. RESULTS: This study will be to evaluate whether acupuncture is an effective intervention for simple obesity when compared with sham acupuncture. CONCLUSION: The conclusion of this study will help clinicians provide effective treatment options for obese patients. ETHICS AND DISSEMINATION: Ethical approval is not required for systematic review and meta- analysis. The results of this review will be disseminated in a peer-review journal. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019129825.