RESUMEN
One of the effective therapeutic strategies to treat rheumatoid arthritis (RA)-related bone resorption is to target excessive activation of osteoclasts. We discovered that 6-O-angeloylplenolin (6-OAP), a pseudoguaianolide from Euphorbia thymifolia Linn widely used for the treatment of RA in traditional Chinese medicine, could inhibit RANKL-induced osteoclastogenesis and bone resorption in both RAW264.7 cells and BMMs from 1 µM and protect a collagen-induced arthritis (CIA) mouse model from bone destruction in vivo. The severity of arthritis and bone erosion observed in paw joints and the femurs of the CIA model were attenuated by 6-OAP administered at both dosages (1 or 5 mg/kg, i.g.). BMD, Tb.N and BV/TV were also improved by 6-OAP treatment. Histological analysis and TRAP staining of femurs further confirmed the protective effects of 6-OAP on bone erosion, which is mainly due to reduced osteoclasts. Molecular docking indicated that c-Src might be a target of 6-OAP and phosphorylation of c-Src was suppressed by 6-OAP treatment. CETSA and SPR assay further confirmed the potential interaction between 6-OAP and c-Src. Three signaling molecules downstream of c-Src that are vital to the differentiation and function of osteoclasts, NF-κB, c-Fos and NFATc1, were also suppressed by 6-OAP in vitro. In summary, the results demonstrated that the function of c-Src was disrupted by 6-OAP, which led to the suppression of downstream signaling vital to osteoclast differentiation and function. In conclusion, 6-OAP has the potential to be further developed for the treatment of RA-related bone erosion.
RESUMEN
Myopia has become a global public health concern. However, its mechanism remains unclear. Dopamine and acetylcholine, as important neurotransmitters in retina, play a critical role in the formation and inhibition of experimental myopia by binding to specific receptors respectively. Simultaneously, the mechanisms of related signaling pathways during myopia have attracted much attention. Most studies have identified that dopamine and acetylcholine receptor antagonists could inhibit the development of experimental myopiato some extent. Furthermore, pharmacological experiments have suggested that the two signaling pathways cross and influence each other, and there may be common mediators. In this paper, we briefly reviewed the recent researches on dopaminergic and cholinergic signaling pathways and their association during myopia, to provide references for further insights into pathogenesis as well as the prevention and treatment of myopia.
RESUMEN
AIM: To systematically evaluate the effects of 0.01%, 0.025% and 0.05% ophthalmic atropine on the change of spherical equivalent(SE)degree and axial length(AL)of myopic children. METHODS: PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Database, VIP and CBM were searched for all publications related to 0.01%, 0.025% and 0.05% atropine to control myopia simultaneously. The publication time is from the database construction to May 2022. The Cochrane handbook was used to evaluate the risk of bias and quality of the included literature, STATA12.0 was used to detect publication bias and Revman5.4 software was used for Meta-analysis. RESULTS: A total of 6 literatures(1 239 eyes)were included, with 5 randomized controlled trials and 1 case-control study. Meta-analysis results showed that 0.025% atropine had better inhibitory effect on SE and AL than 0.01% atropine(SE: WMD=-0.15, 95%CI: -0.23--0.06, P<0.001; AL: WMD=0.07, 95%CI: 0.03-0.10, P<0.001). The inhibitory effect of 0.05% atropine on SE and AL was better than 0.01% atropine(SE: WMD=-0.35, 95%CI: -0.44--0.26, P<0.001; AL: WMD=0.16, 95%CI: 0.12-0.20, P<0.001). The inhibitory effect of 0.05% atropine on SE and AL increase was better than 0.025% atropine(SE: WMD=-0.20, 95%CI: -0.28--0.11, P<0.001; AL: WMD=0.09, 95%CI: 0.06-0.12, P<0.001). CONCLUSION: The concentration of 0.05% atropine is superior to 0.01% and 0.025% atropine in the control of SE and AL. However, the side effects of long-term use remain to be observed.
