Rheumatoid arthritis (RA) is a systemic autoimmune disease (AD) caused by the aberrant attack of the immune system on its own joint tissues. Genetic and environmental factors are the main reasons of immune system impairment and high incidence of RA. Although there are medications on the market that lessen disease activity, there is no known cure for RA, and patients are at risk in varying degrees of systemic immunosuppression. By transporting (encapsulating or surface binding) RA-related self-antigens, nucleic acids, immunomodulators, or cytokines, tolerogenic nanoparticles—also known as immunomodulatory nano-preparations—have the potential to gently regulate local immune responses and ultimately induce antigen-specific immune tolerance. We review the recent advances in immunomodulatory nano-preparations for delivering self-antigen or self-antigen plus immunomodulator, simulating apoptotic cell avatars in vivo , acting as artificial antigen-presenting cells, and based on scaffolds and gels, to provide a reference for developing new immunotherapies for RA.
Aims: To explore angiopoietin-1 (Ang-1) involved in cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (aSAH) through effected on endoplasmic reticulum stress (ERS) and apoptosis of vascular endothelial cells (VECs). Background: CVS accounts for high morbidity and mortality of aSAH. Abnormal cellular physiological processes of VECs play a critical rale in aSAH induced CVS. In addition, Ang-1 involve in the regulation of vascular structure and function. Objective: To study the role of Ang-1 played in CVS and the underlying mechanism. Methods: Blood samples of 130 aSAH patients were collected from 2016 to 2020 in West China Hospital of Sichuan University. Two-hemorrhage rodent model was employed to structured aSAH-induced CVS rat model. And oxyHb was used to treat VECs to constructed CVS cell model in vitro. ELISA was used to measure the level of Ang-1. HE staining was used to assess basilar arteries of rat. CCK-8 was used to detect cell viability ability. Flow cytometry was used to test the cell apoptosis rate. Western blotting was used to determine the expression level of ERS marker and apoptosis-related proteins. Results: There was an abnormally low expression of Ang-1 in CVS patients and CVS rats; besides, oxyHb treatment decreased Ang-1 in VECs in a concentration-dependent manner. Ang-1 treatment led to the basilar artery wall thinner and lumen circumference larger in CVS rat; moreover, in oxyHb treated VECs, Ang-1 treatment inhibited ERS and apoptosis. In addition, the expression of p-PI3K and p-Akt in the CVS group decreased, while the expression of p53 in the CVS group increased. The expression of p-PI3K and p-Akt in 8 CVS rat have negative correlation with expression of Ang-1, but the correlation between p53 and Ang-1 was positive. Furthermore, the results suggested that Ang-1 suppressed ERS and apoptosis of VECs through regulated PI3K/Akt/p53 pathway. Conclusion: Elevated Ang-1 inhibited p53 mediated ERS and apoptosis of VECs by activated PI3K/Akt pathway, Ang-1 might be an attractive treatment strategy for CVS.
AimsPrevious studies suggested a significant relationship between four surrogate indexes of insulin resistance and subsequent type 2 diabetes mellitus (T2DM). But the association of longitudinal changes (denoted as -D) in CVAI (Chinese visceral adiposity index), LAP (lipid accumulation product), TyG (triglyceride-glucose), and TG/HDL-C (triglyceride/ high-density lipoprotein cholesterol) indexes with the risk of T2DM remained uncertain. We aimed to compare the changes in those four surrogate indexes for predicting T2DM in middle-aged and elderly Chinese.MethodsWe extracted data from the China Health and Retirement Longitudinal Study (CHARLS). Multivariate logistic regression models were used to estimate odds ratio (OR) with 95% confidence interval (CI) of incident T2DM with four surrogate indexes. The restricted cubic spline analysis was used to examine potential non-linear correlation and visualize the dose-response relationship between four indexes and T2DM. The receiver operator characteristic curve was used to compare the performance of the four indexes to predict T2DM.ResultsWe enrolled 4,596 participants in total, including 504 (10.97%) with T2DM. Analysis results showed that four surrogate indexes were associated with T2DM, and the multivariate-adjusted ORs (95% CIs) of T2DM were 1.08 (1.00–1.16), 1.47 (1.32-1.63), 1.12 (1.00–1.25), and 2.45 (2.12–2.83) for each IQR (interquartile range) increment in CVAI-D, LAP-D, TG/HDLC-D, and TyG-D, respectively. Restricted cubic spline regression showed a non-linear correlation between four surrogate indexes and the risk of T2DM (p for non-linear < 0.001). From the ROC (receiver operating characteristic) curve, TyG-D had the highest AUC (area under curve), and its AUC values were significantly different from other three indexes both in male and female (all P < 0.001).ConclusionCompared with other indexes, TyG-D was a better predictor in the clinical setting for identifying middle-aged and elderly Chinese with T2DM. Monitoring long-term changes in TyG might help in the early identification of individuals at high risk of T2DM.
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