Tubson-2 decoction ameliorates rheumatoid arthritis complicated with osteoporosis in CIA rats involving isochlorogenic acid A regulating IL-17/MAPK pathway.

BACKGROUND: Osteoporosis (OP) is considered as one of the major comorbidities of rheumatoid arthritis (RA), and is responsible for fragility fracture. However, there is currently no effective treatment for RA complicated with OP. Tubson-2 decoction (TBD), a Mongolian medicine also known as Erwei Duzhong Decoction, has been shown to exert a preventive effect on post-menopausal osteoporosis (PMOP). The preventive effects of TBD on RA-induced OP, as well as the bioactive compound responsible and the underlying mechanisms, remain to be elucidated. OBJECTIVE: To explore the effects of TBD on RA-induced OP in vivo, and to elucidate the mechanism of isochlorogenic acid A (ICA), the effective component of TBD, in vitro. METHODS: To evaluate the anti-arthritic and anti-osteoporotic effects of TBD, we conducted H&E straining and safranine O/fast green, TEM, immunohistochemistry (IHC), bone histomorphometry, micro-CT imaging, and biomechanical testing in collagen induced arthritis (CIA) rats. The active ingredient in TBD was identified using network pharmacology and molecular docking. The identification was supported by in vivo IHC assay, and further confirmed using qRT-PCR, Western blot, and SEM analysis in TNF-α-treated MH7A cells and/or in LPS-exposed RAW264.7 cells. RESULTS: Oral administration of TBD attenuated the severity of arthritis and osteopenia as well as poor bone quality, in CIA rats. Additionally, TBD and the positive control, tripterygium glycosides (TG), exhibited similar effects in reducing inflammation in both the synovium and ankle joint. They also were both effective in improving bone loss, microarchitecture, and overall bone quality. TBD reduced the expression of MMP13, IL-17, and p-JNK protein in the synovium of CIA rats. ICA, which was screened, suppressed TNF-α or LPS-triggered inflammatory responses via down-regulating IL-17 signaling, involving in MMP13, IL-1ß, IL-23, and IL-17, and the MAPK pathway including p-ERK, p-JNK, and p-P38, both in MH7A cells and in RAW264.7 cells. Furthermore, ICA prevented osteoclasts from differentiating and bone resoprtion in a dose-dependent manner in vitro. CONCLUSION: This study provides the first evidence that TBD exerts intervening effects on RA-induced OP, possibly through the downregulation of the IL-17/MAPK signaling pathway by ICA. The findings of our study provides valuable insights for further research in this area.

The relationship between optimism and job satisfaction for Chinese specialist nurses: A serial-multiple mediation model.

AIM: This study aimed to examine the relationship between optimism, core self-evaluations, positive coping strategies, and job satisfaction for Chinese specialist nurses. METHODS: A cross-sectional design was used. Two hundred and seventy-eight Chinese specialist nurses answered the Chinese Minnesota Satisfaction Questionnaire, the Chinese Revised Life Orientation Test, the Chinese Core Self-Evaluations Scale, and the Chinese Simplified Coping Style Scale. Descriptive analysis, independent-sample T-tests, one-way analysis of variance, Pearson correlation analyses, and bootstrap method were conducted to analyze data. RESULTS: Total effect (c = 0.860, SE = 0.143, 95% CI 0.579-1.142) of optimism on job satisfaction was significant. The path through single mediation of core self-evaluations (point estimate = 0.165; 95% CI 0.041-0.318), the path through the single mediation of positive coping (point estimate = 0.124; 95% CI 0.042-0.254), and the path through both mediators (point estimate = 0.033; 95% CI 0.005-0.085) were all statistically significant. The total indirect effect was also statistically significant (point estimate = 0.322; 95% CI 0.151-0.535). CONCLUSIONS: This study concluded that optimism was first sequentially associated with core self-evaluations and then associated with positive coping strategies, which was in turn related to job satisfaction of Chinese specialist nurses. Clinical nursing administrators should take measures that focus on improving specialist nurse job satisfaction to further improve their retention rates.