A predictive model for premature atherosclerosis in systemic lupus erythematosus based on clinical characteristics.

OBJECTIVE: Systemic lupus erythematosus (SLE) is associated with a significant risk of atherosclerotic cardiovascular disease, especially in the development of premature atherosclerosis. Specific prediction models for premature atherosclerosis in SLE patients are still limited. The objective of this study was to establish a predictive model for premature atherosclerosis in SLE. METHOD: The study collected clinical and laboratory data from 148 SLE patients under the age of 55, between January 2021 and June 2023. The least absolute shrinkage and selection operator logistic regression model was utilized to identify potentially relevant features. Subsequently, a nomogram was developed using multivariable logistic analysis. The performance of the nomogram was evaluated through a receiver-operating characteristic curve, calibration curve, and decision curve analysis (DCA). RESULTS: A total of 148 SLE patients who fulfilled the inclusion criteria were enrolled in the study, of whom 53 patients (35.81%) met the definition of premature atherosclerosis. Hypertension, antiphospholipid syndrome, azathioprine use, duration of glucocorticoid, and age of patients were included in the multivariable regression. The nomogram, based on the non-overfitting multivariable model, was internally validated and demonstrated sufficient clinical utility for assessing the risk of premature atherosclerosis (area under curve: 0.867). CONCLUSIONS: The comprehensive nomogram constructed in this study serves as a useful and convenient tool for evaluating the risk of premature atherosclerosis in SLE patients. It is helpful for clinicians to early identify SLE patients with premature atherosclerosis and facilitates the implementation of more effective preventive measures. Key Points • SLE patients are at a significantly higher risk of developing premature atherosclerosis compared to the general population, and this risk persists even in cases with low disease activity. Traditional models used to evaluate and predict premature atherosclerosis in SLE patients often underestimate the risk. • This study establishes a comprehensive and visually orientated predictive model of premature atherosclerosis in SLE patients, based on clinical characteristics. • The scoring system allows for convenient and effective prediction of individual incidence of premature atherosclerosis, and could provide valuable information for identification and making further intervention decision.

Elevated expression of hsa_circ_0000479 in neutrophils correlates with features of systemic lupus erythematosus.

OBJECTIVE: Accumulating evidence suggests that differentially expressed circular RNAs (circRNAs) play critical roles in immune cells of systemic lupus erythematosus (SLE) patients. Hsa_circ_0000479 has been studied in the field of cancer and infection, whereas seldom studied in autoimmune diseases. The aim of this study was to investigate the role and clinical value of neutrophil hsa_circ_0000479 in SLE. METHODS: The expression levels of hsa_circ_0000479 in both healthy individuals and SLE patients' neutrophils were detected by qPCR and compared with those in peripheral blood mononuclear cells (PBMCs) . In addition, the correlation of hsa_circ_0000479 levels in neutrophils with the clinical and immunological features of SLE patients was also analysed. RESULTS: The expression levels of hsa_circ_0000479 in the patients with SLE were significantly higher in neutrophils than that of PBMCs, and also significantly higher than that in healthy controls (HCs). Moreover, the expression levels of hsa_circ_0000479 in neutrophils were negatively associated with absolute neutrophil count and complement 3 (C3), whereas positively correlated with anti-dsDNA and anti-nucleosome antibodies in SLE. In addition, SLE patients with higher levels of hsa_circ_0000479 demonstrated more several clinical manifestations, including Raynaud's phenomenon, alopecia and leucopenia. CONCLUSIONS: Hsa_circ_0000479 is up-regulated in neutrophils of SLE patients, and is also associated with several important laboratory indicators and clinical manifestations, suggesting that hsa_circ_0000479 in neutrophils was one of probable factors involved in the pathogenesis of SLE with potential clinical value.

Hsa_circ_0000479 was expressed in neutrophils and was considerably higher than that of PBMCs in SLE patients.The neutrophil hsa_circ_0000479 was correlated with laboratory parameters, including NEUT, C3, anti-dsDNA antibodies and AnuA, in addition to being associated with Raynaud's phenomenon, alopecia, and leucopenia in patients with SLE.Hsa_circ_0000479 in neutrophils may play an influential role in SLE patients and will be important to understand the pathogenesis, stratification and treatment in SLE.

Tyro3 receptor tyrosine kinase contributes to pathogenic phenotypes of fibroblast-like synoviocytes in rheumatoid arthritis and disturbs immune cell balance in experimental arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by synovitis and joint damage, the underlying causes of which remain unclear. Our prior investigations revealed a notable correlation between the expression of Tyro3 Protein Tyrosine Kinase (Tyro3TK) and the progression of RA. To further elucidate the pathogenic role of Tyro3TK in RA, we analyzed the influence of Tyro3TK on pathogenic phenotypes of RA fibroblast like synoviocyte (FLS) in vitro and compared disease severity, joint damages and immunological parameters of K/BxN serum transfer arthritis (STA) in Tyro3TK-/- deficient mice and wild type controls. Our findings underscored the remarkable effectiveness of Tyro3TK blockade, as evidenced by diminished secretion of inflammatory cytokines and matrix metalloproteinases (MMPs), curtailed migration and invasiveness of RAFLS, and attenuated differentiation of pathogenic helper T cell subsets mediated by RAFLS. Correspondingly, our in vivo investigations illuminated the more favorable outcomes in Tyro3TK-deficient mice, characterized by reduced joint pathology, tempered synovial inflammation, and restored immune cell equilibrium. These data suggested that Tyro3TK might contribute to aggravated autoimmune arthritis and immunological pathology and act as a potential therapeutic target for RA.

Pinocembrin Promotes OPC Differentiation and Remyelination via the mTOR Signaling Pathway.

The exacerbation of progressive multiple sclerosis (MS) is closely associated with obstruction of the differentiation of oligodendrocyte progenitor cells (OPCs). To discover novel therapeutic compounds for enhancing remyelination by endogenous OPCs, we screened for myelin basic protein expression using cultured rat OPCs and a library of small-molecule compounds. One of the most effective drugs was pinocembrin, which remarkably promoted OPC differentiation and maturation without affecting cell proliferation and survival. Based on these in vitro effects, we further assessed the therapeutic effects of pinocembrin in animal models of demyelinating diseases. We demonstrated that pinocembrin significantly ameliorated the progression of experimental autoimmune encephalomyelitis (EAE) and enhanced the repair of demyelination in lysolectin-induced lesions. Further studies indicated that pinocembrin increased the phosphorylation level of mammalian target of rapamycin (mTOR). Taken together, our results demonstrated that pinocembrin promotes OPC differentiation and remyelination through the phosphorylated mTOR pathway, and suggest a novel therapeutic prospect for this natural flavonoid product in treating demyelinating diseases.