ObjectiveTo explore whether platelet activation is associated with systemic inflammatory responses. MethodsWe conducted a cross-sectional study to enroll all aortic dissection (AD) patients (AD group) from January 1, 2015 to June 30, 2015 in the Emergency Department. According to the characteristics of AD patients, we matched hypertension (hypertension group) and health participants (health group) with AD patients at a proportion of 1:1:1. Blood samples were collected on admission for blood routine test [mean platelet volume (MPV)/platelet (PLT)] and inflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-6] analysis. We compared all parameters among the three groups and performed bivariate correlation analyses. ResultsExpressions of TNF-α and IL-6 in the AD group [(20.9±4.5), (168.8±75.1) pg/mL] were significantly higher than those in the hypertension group [(4.3±1.9), (8.4±2.9) pg/mL] and healthy group [(5.4±1.6), (8.7±3.8) pg/mL] (P＜0.05). MPV/PLT in the AD group was significantly higher than that in the hypertension group and healthy group (0.106±0.035 vs 0.049±0.010, P＜0.05; 0.106±0.035 vs 0.054±0.019, P＜0.05). There were positive correlations between MPV/PLT and TNF-α (r=0.516, P=0.002), and between MPV/PLT and IL-6 (r=0.633, P＜0.001) in the AD group. ConclusionIn summary, our study shows that platelets of AD patients can be activated, and the degree of activation is associated with systemic inflammatory responses.
Objective To investigate the effects of 4-methylcatechol (4MC) on the migration and inflammatory response in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS), as well as its underlying mechanisms of action. Methods RA-FLS was isolated from synovial tissue donated by RA patients, and the optimal concentration of 4MC was determined by cell counting kit 8 method for subsequent experiments, and the effect of 4MC on the migratory ability of RA-FLS was evaluated via a cell scratch assay. An inflammation model of RA-FLS was induced by tumor necrosis factor α (TNF-α). Real-time fluorescence quantitative PCR and ELISA were employed to detect the gene and protein expression levels of interleukin-1β (IL-1β) and IL-6 in RA-FLS and their culture supernatants, respectively, thereby investigating the anti-inflammatory effects of 4MC. Western blot was used to examine the expression of nuclear factor κB (NF-κB) signaling pathway-related proteins, including inhibitor of NF-κB-α (IKBα), phosphorylated (P)-IκBα, NF-κB-inducing kinase α (IKKα), P-IKKαβ, P-p65, and p65. Cellular immunofluorescence was utilized to detect the expression and localization of p65 in RA-FLS, exploring whether 4MC exerts its anti-inflammatory effects by regulating the NF-κB signaling pathway. Finally, a collagen-induced arthritis (CIA) mouse model was established. The anti-RA effect of 4MC in vivo was evaluated by gross observation and histological examination. Results 4MC inhibited RA-FLS migration in a concentration-dependent manner. In the TNF-α-induced RA-FLS inflammation model, 4MC significantly decreased the gene and protein expression levels of IL-1β and IL-6. Furthermore, 4MC markedly reduced the ratios of P-IΚBα/IΚBα, P-IKKαβ/IKKα, and P-p65/p65, thereby blocking the transcriptional activity of p65 by inhibiting its nuclear translocation. This mechanism effectively suppressed the activation of the TNF-α-mediated NF-κB signaling pathway. Animal studies demonstrated that 4MC [10 mg/(kg·day)] significantly lowered serum levels of IL-1β, IL-6, and TNF-α, and alleviated arthritis severity and bone destruction in CIA mice. Conclusion 4MC not only inhibits the migration of RA-FLS but also mitigates their inflammatory response by suppressing the NF-κB signaling pathway, thereby effectively exerting its anti-RA effects.