Neutrophil extracellular traps: Potential targets for the treatment of rheumatoid arthritis with traditional Chinese medicine and natural products.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Abnormal formation of neutrophil extracellular traps (NETs) at the synovial membrane leads to the release of many inflammatory cytokines, including IL-1ß, IL-6, and TNF-α. Elastase, histone H3, and myeloperoxidase, which are carried by NETs, damage the soft tissues of the joints and aggravate the progression of RA. The balance of NET formation coordinates the pro-inflammatory and anti-inflammatory effects and plays a key role in the development of RA. Therefore, when NETs are used as effector targets, highly targeted drugs with fewer side effects can be developed to treat RA without damaging the host immune system. Currently, an increasing number of studies have shown that traditional Chinese medicines and natural products can regulate the formation of NETs through multiple pathways to counteract RA, which shows great potential for the treatment of RA and has a promising future for clinical application. In this article, we review the latest biological progress in understanding NET formation, the mechanism of NETs in RA, and the potential targets or pathways related to the modulation of NET formation by Chinese medicines and natural products. This review provides a relevant basis for the use of Chinese medicines and natural products as natural adjuvants in the treatment of RA.

Exosomes and exosomal miRNAs: A new avenue for the future treatment of rheumatoid arthritis.

Rheumatoid arthritis is a chronic systemic autoimmune disease that involves mainly synovitis and joint injury and is one of the main causes of disability. The pathogenesis of rheumatoid arthritis is complicated, and the treatment cycle is long. The traditional methods of inhibiting inflammation and immunosuppression are no longer sufficient for treatment of the disease, so there is an urgent need to seek new treatments. The exocrine microenvironment is a kind of microvesicle with a lipid bilayer membrane structure that can be secreted by most cells in the body. This structure contains cell-specific proteins, lipids and nucleic acids that can transmit this information from one cell to another. To achieve cell-to-cell communication. Exocrine microRNAs can be contained in exocrine cells and can be selectively transferred to target receptor cells via exocrine signaling, thus regulating the physiological function of target cells. This article focuses on the pathological changes that occur during the development of rheumatoid arthritis and the biological regulation of exocrine and exocrine microRNAs in rheumatoid joints. Research on the roles of exocrine and exocrine microRNAs in regulating the inflammatory response, cell proliferation/apoptosis, autophagy, effects on fibroblast-like synoviocytes and immune regulation in rheumatoid arthritis was reviewed. In addition, the challenges faced by this new treatment are discussed.

Development and validation of a predictive model assessing the risk of sarcopenia in rheumatoid arthritis patients.

Background: Sarcopenia is linked to an unfavorable prognosis in individuals with rheumatoid arthritis (RA). Early identification and treatment of sarcopenia are clinically significant. This study aimed to create and validate a nomogram for predicting sarcopenia risk in RA patients, providing clinicians with a reliable tool for the early identification of high-risk patients. Methods: Patients with RA diagnosed between August 2022 and January 2024 were included and randomized into training and validation sets in a 7:3 ratio. Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis and multifactorial logistic regression analysis were used to screen the risk variables for RA-associated muscle loss and to create an RA sarcopenia risk score. The predictive performance and clinical utility of the risk model were evaluated by plotting the receiver operating characteristic curve and calculating the area under the curve (AUC), along with the calibration curve and clinical decision curve (DCA). Results: A total of 480 patients with RA were included in the study (90% female, with the largest number in the 45-59 age group, about 50%). In this study, four variables (body mass index, disease duration, hemoglobin, and grip strength) were included to construct a nomogram for predicting RA sarcopenia. The training and validation set AUCs were 0.915 (95% CI: 0.8795-0.9498) and 0.907 (95% CI: 0.8552-0.9597), respectively, proving that the predictive model was well discriminated. The calibration curve showed that the predicted values of the model were basically in line with the actual values, demonstrating good calibration. The DCA indicated that almost the entire range of patients with RA can benefit from this novel prediction model, suggesting good clinical utility. Conclusion: This study developed and validated a nomogram prediction model to predict the risk of sarcopenia in RA patients. The model can assist clinicians in enhancing their ability to screen for RA sarcopenia, assess patient prognosis, make early decisions, and improve the quality of life for RA patients.

Structural Modification and Optimisation of Hyperoside Oriented to Inhibit TGF-ß-Induced EMT Activity in Alveolar Epithelial Cells.

Pulmonary fibrosis (PF) is a disease characterised by diffuse nonspecific alveolar inflammation with interstitial fibrosis, which clinically manifests as dyspnoea and a significant decline in lung function. Many studies have shown that the epithelial-mesenchymal transition (EMT) plays a pivotal role in the pathogenesis of pulmonary fibrosis. Based on our previous findings, hypericin (Hyp) can effectively inhibit the process of the EMT to attenuate lung fibrosis. Therefore, a series of hyperoside derivatives were synthesised via modifying the structure of hyperoside, and subsequently evaluated for A549 cytotoxicity. Among these, the pre-screening of eight derivatives inhibits the EMT. In this study, we evaluated the efficacy of Z6, the most promising hyperoside derivative, in reversing TGF-ß1-induced EMTs and inhibiting the EMT-associated migration of A549 cells. After the treatment of A549 cells with Z6 for 48 h, RT-qPCR and Western blot results showed that Z6 inhibited TGF-ß1-induced EMTs in epithelial cells by supressing morphological changes in A549 cells, up-regulating E-cadherin (p < 0.01, p < 0.001), and down-regulating Vimentin (p < 0.01, p < 0.001). This treatment significantly reduced the mobility of transforming growth factor ß1 (TGF-ß1)-stimulated cells (p < 0.001) as assessed by wound closure, while increasing the adhesion rate of A549 cells (p < 0.001). In conclusion, our results suggest that hyperoside derivatives, especially compound Z6, are promising as potential lead compounds for treating pulmonary fibrosis, and therefore deserve further investigation.