No abstract

Vascular risk factors have been linked to cognitive decline and dementia in the elderly. Microvascular inflammation, especially of the endothelium, may contribute to the progression of neurodegenerative events in Alzheimer's disease (AD). Memantine, an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, is a licensed drug used for the treatment of moderate to severe AD. However, little information is available regarding its anti-inflammatory effects on the endothelium. In this study, we investigated the effects of memantine on human brain microvascular endothelial dysfunction induced by the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α). Our results show that memantine prevents the attachment of monocyte THP-1 cells to human brain microvascular endothelial cells (HBMVEs). An in vitro BBB model experiment displayed that memantine could rescue TNF-α-induced disruption of the in vitro BBB model. In addition, memantine also interferes with monocyte transmigration across the BBB model. Our results indicate that TNF-α significantly increased the expression of cell adhesion molecules, such as ICAM-1, VCAM-1, and E-selectin, which was prevented by pretreatment with memantine. Mechanistically, memantine reversed activation of the transcription factor NF-κB by preventing the phosphorylation and degradation of its inhibitor IκBα. Our data is the first to describe a novel anti-inflammatory mechanism driven by the endothelial cell-mediated neuroprotective effects of memantine.

In a mouse model of ulcerative colitis (UC), C. butyricum exerted a protective effect on the epithelial barrier by regulating microflora, maintaining the expression of TJ proteins and exerting immunoregulatory effects.

Purpose: To investigate the levels of systemic heparanase, inflammatory markers, and coagulation factor activities in patients with retinal vein occlusion (RVO). Methods: This prospective study included 18 patients with central RVO, 22 patients with branch RVO, and 40 patients with age-related cataract as the control group. Serum heparanase protein levels and activities were measured by ELISA and a heparan degrading enzyme assay kit, respectively. Serum levels of MMP-2, MMP-9, TLR-2, and TLR-4 were measured by ELISA kits. The activities of coagulation factors (V, VII, VIII, and IX) were determined with an autoanalyzer. The Mann–Whitney U test was used to compare the above parameters between patients with RVO and control subjects. The relationship between two of the above parameters was analyzed by Spearman's correlation. Results: Patients with RVO had higher levels of systemic heparanase protein, heparanase activities, coagulation factors' (V, VIII, and IX) activities, MMP-2, MMP-9, TLR-2, and TLR-4 compared with the control group. Systemic heparanase levels were correlated with serum levels of MMP-2, MMP-9, TLR-2, TLR-4, and activities of coagulation factors VIII and IX. Conclusion: Increase of systemic heparanase in RVO is associated with activation of systemic inflammation and blood hypercoagulability.

Objective:Optimal duration of dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation remains controversial. The present study is an assessment of efficacy and safety of short-term (≤6 months) DAPT after DES implantation in patients with coronary artery disease, especially in important subgroups.Methods:PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched for randomized, controlled trials comparing short-term and long-term (>6 months) DAPT after DES implantation. Primary efficacy outcome was stent thrombosis (ST). Primary safety outcome was major bleeding. Pooled relative risks (RRs) with 95% confidence interval (CI) were calculated using random- or fixed-effects models as appropriate.Results:Total of 7 trials involving 15870 patients were included in the study. Short-term DAPT significantly reduced major bleeding by 49% compared with long-term DAPT (RR 0.51; 95% CI 0.32–0.80; p=0.003) without increasing risk of ST (RR 1.28; 95% CI 0.83–1.97; p=0.266). In addition, no differences were observed in all-cause mortality, myocardial infarction (MI), cardiac mortality, or cerebrovascular accidents. Moreover, no significant difference in composite of cardiovascular events, bleeding, and mortality was found in important clinical subgroups.Conclusion:Short-term DAPT is associated with lower bleeding risk compared with long-term DAPT. Number of ST and MI was higher with short-term DAPT without reaching statistical significance. Comprehensive clinical judgment is necessary to weigh benefits and risks in the individual patient.