Moxibustion of Zusanli (ST36) and Shenshu (BL23) alleviates the inflammation of rheumatoid arthritis in rats through regulating macrophage migration inhibitory factor/glucocorticoids signaling.

OBJECTIVE: To test the hypothesis that moxibustion may inhibit rheumatoid arthritis (RA) synovial inflammation by regulating the expression of macrophage migration inhibitory factor (MIF)/glucocorticoids (GCs). METHODS: Fifty male Sprague-Dawley rats were randomly divided into five groups (n = 10 each): blank Control (CON) group, RA Model (RA) group, Moxibustion (MOX) group, MIF inhibitor (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) group, and Moxibustion + MIF inhibitor ISO-1 (MOX + ISO-1) group. Rats in the ISO-1 group and ISO-1 + MOX group were intraperitoneally injected with the inhibitor ISO-1. The rats in the RA group, ISO-1 group, MOX group, and ISO-1 + MOX group were injected with Freund's complete adjuvant (FCA) in the right hind footpad to establish an experimental RA rat model. In the MOX group and MOX + ISO-1 group, rats were treated with Moxa. The thickness of the footpads of the rats in each group was measured at three-time points before, after modeling and after moxibustion treatment. The contents of serum MIF, corticosterone (CORT), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were detected by enzyme-linked immunosorbent assay; and the contents of synovial MIF were detected by Western blot. Hematoxylin-eosin (HE) staining method was used to observe the pathological changes of synovial tissue under a section light microscope, and pathological scoring was performed according to the grading standard of the degree of synovial tissue disease. RESULTS: Moxibustion was found to reduce the level of MIF and alleviate inflammation in RA rats in this study. In addition, after inhibiting the expression of MIF, the level of CORT increased, and the level of TNF-α decreased. Treating RA rats with inhibited MIF by moxibustion, the level of CORT was almost unchanged, but the level of TNF-α further decreased. The correlation analysis data suggested that MIF was positively related to the expression of TNF-α and negatively correlated with the expression of CORT. CONCLUSION: Reducing MIF to increase CORT and decrease TNF-α by moxibustion treatment in RA. MIF may be a factor for moxibustion to regulate the expression of CORT, but the expression of TNF-α is due to the incomplete regulation of the MIF. This study added to the body of evidence pointing to moxibustion's anti-inflammatory mechanism in the treatment of RA.

Astragalus polysaccharide improves diabetic ulcers by promoting M2-polarization of macrophages to reduce excessive inflammation via the ß-catenin/ NF-κB axis at the late phase of wound-healing.

Ethnopharmacological relevance: Astragalus polysaccharide (APS), the most biologically active ingredient of Astragali Radix, is used to treat diabetes mellitus (DM)-related chronic wounds in traditional Chinese medicine for several decades. This herb possesses an anti-inflammatory effect. Our study proved that APS can reduce excessive inflammation at the late phase of wound-healing in diabetic ulcers. Aim of the study: To clarify the molecular mechanism of APS in promoting wound-healing via reducing excessive inflammation in diabetic ulcers during the late stages of wound-healing. Methods and materials: The rat model of the diabetic ulcers was established via intraperitoneal injection of streptozocin (60 mg/kg). We detected the regulation of APS on diabetic ulcers by measuring wound-healing rates. Bioinformatics was used to predict the target genes of APS, and autodocking was used to predict the combination of APS and target genes. Immunohistochemistry, Enzyme-linked immunosorbent assay, Western blot, immunofluorescence staining, flow cytometry, and flow cytometric sorting were investigated. Results: The results demonstrated that APS promoted wound-healing and inhibited excessive inflammation at the late phase of wound-healing in diabetic rats. Mechanistic findings showed that APS promoted the expression of ß-catenin and Rspo3 while inhibiting the expression of NF-KB and GSK-3ß, which leads to the transformation of M1-type macrophages into M2-type macrophages and thus reducing excessive inflammation at the late phase of wound-healing in diabetic ulcers. Conclusion: We found an interesting finding that APS promoted the polarization of macrophages towards M2-type through the ß-catenin/NF-κB axis to reduce excessive inflammation at the late phase of wound-healing. Therefore, APS may be a promising drug for treating diabetic ulcers in clinic.

Efficacy of Moxa-burning heat stimulating Zusanli (ST36) and Shenshu (BL23) on expressions of macrophage migration inhibitory factor and macrophage apoptosis in rabbits with adjuvant-induced arthritis.

OBJECTIVE: To evaluate the effects of moxa-burning heat stimulating acupoints Zusanli (ST36) and Shenshu (BL23) on macrophage migration inhibitory factor (MIF) and its related molecules which can provide scientific experimental basis for the clinical application of moxibustion treatment of rheumatoid arthritis (RA). METHODS: Thirty rabbits were randomly assigned to control group, RA model (established by injecting Freund's Complete Adjuvant) group (RA group) and RA model with moxibustion group [Moxa group, Zusanli (ST36) and Shenshu (BL23), 5 moxa pillars/day, 6 d × 3]. The expressions of MIF mRNA were evaluated with reverse transcription polymerase chain reaction; the apoptosis rates of macrophages were detected by erminal deoxynucleotidyl transferase-mediated dTUP nick end labeling; the expressions of related signal molecules were detected with immunohistochemical S-P method and the levels of IL-2 were detected with enzyme-linked immunosorbent assay. RESULTS: The expressions of MIF mRNA, extracellular regulated protein kinases 2, p38 mitogen-activated protein kinase and nuclear factor-κ-gene binding p65 in synovial tissue of RA group were significantly increased when compared with control group, which were lower remarkably in moxa group than those in RA group. The apoptosis rates of macrophages in RA group were significantly down-regulated as compared with the control group, which were up-regulated in moxa group compared with the RA group. The levels of IL-2 in synovial fluid from the RA group were elevated significantly as compared with that from control group, but those of the moxa group were reduced when compared with those from RA group. CONCLUSIONS: Moxibustion may simultaneously regulate the expressions of MIF and its related signaling pathways molecules, the apoptosis rate of macrophages in synovial tissue, as well as the level of inflammatory factors in synovial fluid. The results suggest that the anti-inflammatory effect of moxibustion on RA may be related to inhibit the expression of MIF in synovial tissue, the molecules of some related signaling pathways and promote the apoptosis of macrophage.

Expression of serum nuclear factor-κB, nonocyte chemotactic protein-1 and renal protective mechanism of pioglitazone in early type 2 diabetic nephropathy / 中国综合临床

Objective:To observe the expression of serum nuclear factor-κB (NF-κB) and monocyte chemotactic protein-1 (MCP-1) in patients with early diabetic nephropathy (EDN) and the effect of pioglitazone on the expression of inflammatory factors and renal protective mechanism.Methods:A retrospective case-control study was conducted.From January 2019 to December 2019, the patients were divided into pioglitazone group ( n=35) and glimepiride group ( n=34). At the same time, 30 healthy people in the physical examination center of our hospital were selected as the control group.The levels of serum NF-κB and MCP-1 were detected by immunohistochemistry.The changes of fasting glucose, Hemoglobin A1C (HbA1c), renal function, urinary albumin excretion rate (UAER), and hypersensitive C-reactive protein(hsCRP), interleukin-6(IL-6), homeostasis model insulin Resistance index (HOMA-IR) were detected and compared among the three groups before treatment, pioglitazone group and glimepiride treatment group after treatment.To observe the effect of pioglitazone on serum NF-kB and MCP-1 expression in patients with early type 2 diabetic nephropathy. Results:Serum NF-κB, MCP-1, UAER, fasting blood glucose, HbA1c, HOMA-IR, hsCRP, IL-6 were significantly higher in the diabetic nephropathy group than those in the control group before treatment ( t values were 9.16, 7.61, 16.99, 17.01, 17.05, 12.01, 8.69, 6.28, all P<0.01). After 12 weeks of treatment, the levels of NF- κB, MCP-1, HOMA-IR, hsCRP, IL-6 and UAER in pioglitazone group were lower than those in glimepiide group ( t values were -5.03, -4.63, -2.35, -8.03, -3.06, -2.10, P<0.05 or P<0.01). After treatment, there were no statistically significant differences in fasting blood glucose and HbA1c between the pioglitazone group and the glimepiide group (all P>0.05). Serum NF-κB, MCP-1, HbA1c, HOMA-IR and UAER in EDN group were significantly positively correlated ( R values were 0.568, 0.532, 0.521, 0.466, all P<0.05). Conclusion:The expression of NF - κ B and MCP-1 in serum of EDN patients was increased, which indicated that there was chronic inflammation in patients.Pioglitazone could down regulate the expression of NF - κ B and MCP-1, so as to play an anti-inflammatory and renal protective role.

The Impact of Severity of Psoriasis on Quality of Life in Psoriatic Patients / 中华皮肤科杂志

Objective To investigate the impact of severity of psoriasis on quality of life in patients with psoriasis vulgaris.Methods A questionnaire interview was carried out to the outpatients with psoriasis vulgaris(n=504)from Dec.2000to Sept.2001.All the patients were more than18years old.The content of questionnaire included daily life and activities,work and school performance,social activities and personal relationships,and psychologic status.Disease severity was assessed with psoriasis area and severity index(PASI).498patients were included for the final analysis.Statistical analysis was performed with SPSS software package.Results63.3%patients were restricted in their food selection.40.2%had bad sleep,59.0%could not dress short clothes in the summer.26.5%were restricted in use of public traffic and services.15.1%were rejected in haircut and cosmetic service.31.2%had decreased income along with severity of the disease.58.8%felt uncomfortable in social activities and public places.25.8%avoided handshaking with others.43.3%were reluctant in social intercourse.29.0%were not willing to take part in social activities,especially for moderate and severe cases.54.9%felt that their self-esteem was injured.26.6%thought that other peoples always avoided to meet them.64.4%felt anxiety for their disease.83.1%often worried about relapse or exacerbation of psoriasis.15.9%showed a tendency to commit suicide.Conclusions The more severe the disease is the more impact it may have on the daily life,work and school performance,social activities and personal relationship,and psychologic status in patients with psoriasis vulgaris.It is reccommended that besides the conventional treatment bio-psychic and social medical management be given to the patients especially for moderate and severe cases.