α-Lactosylceramide Protects Against iNKT-Mediated Murine Airway Hyperreactivity and Liver Injury Through Competitive Inhibition of Cd1d Binding.

Invariant natural killer T (iNKT) cells, which are activated by T cell receptor (TCR)-dependent recognition of lipid-based antigens presented by the CD1d molecule, have been shown to participate in the pathogenesis of many diseases, including asthma and liver injury. Previous studies have shown the inhibition of iNKT cell activation using lipid antagonists can attenuate iNKT cell-induced disease pathogenesis. Hence, the development of iNKT cell-targeted glycolipids can facilitate the discovery of new therapeutics. In this study, we synthesized and evaluated α-lactosylceramide (α-LacCer), an α-galactosylceramide (α-GalCer) analog with lactose substitution for the galactose head and a shortened acyl chain in the ceramide tail, toward iNKT cell activation. We demonstrated that α-LacCer was a weak inducer for both mouse and human iNKT cell activation and cytokine production, and the iNKT induction by α-LacCer was CD1d-dependent. However, when co-administered with α-GalCer, α-LacCer inhibited α-GalCer-induced IL-4 and IFN-γ production from iNKT cells. Consequently, α-LacCer also ameliorated both α-GalCer and GSL-1-induced airway hyperreactivity and α-GalCer-induced neutrophilia when co-administered in vivo. Furthermore, we were able to inhibit the increases of ConA-induced AST, ALT and IFN-γ serum levels through α-LacCer pre-treatment, suggesting α-LacCer could protect against ConA-induced liver injury. Mechanistically, we discerned that α-LacCer suppressed α-GalCer-stimulated cytokine production through competing for CD1d binding. Since iNKT cells play a critical role in the development of AHR and liver injury, the inhibition of iNKT cell activation by α-LacCer present a possible new approach in treating iNKT cell-mediated diseases

Mechanisms of enterococcus faecalis-mediated Immunomodulation

Enterococci are a major cause of hospital-acquired infections with Enterococcus faecalis and Enterococcus faecium frequently found as a component of chronic, polymicrobial infections alongside other bacteria. This study explores interactions between innate immune cells and E. faecalis, with a focus on identifying both effective responses deployed by these cells to eliminate the bacteria, as well as specific immunomodulating mechanisms utilized by E. faecalis to evade clearance. E. faecalis induced large amount of reactive oxygen species (ROS) production in neutrophils. When co-infection with potent NET-inducer S. aureus, E. faecalis both reduced S. aureus-induced NETosis and promoted S. aureus survival. This points to the possible collaboration mechanisms underpinning the persistence of chronic, polymicrobial infection with these two bacterial strains. E. faecalis was reported to suppress LPS-induced NF-κB activation, so a transposon library screening was conducted to identify the mutants that failed to reach a similar level of activity reduction. This screen identified that shikimic acid pathway promoted E. faecalis-driven cytotoxicity in macrophages, likely by inducing apoptosis and thus reduced the overall immune activity such as cytokine production. Collectively, these findings provide clues behind the high correlation of E. faecalis with S. aureus in persistent polymicrobial infections. It furthermore illustrated key mechanisms utilized by E. faecalis to subvert the antimicrobial mechanisms of both murine neutrophils and macrophages directly. These findings have important implications for our understanding of E. faecalis host-pathogen interactions, most importantly through the identification of potential targets which may serve to interrupt E. faecalis immune evasion.Doctor of Philosoph

Cost-effectiveness of Drug-eluting Stents in Patients With Stable Coronary Artery Disease

Drug-eluting stents (DESs) have been shown to reduce in-stent restenosis and target vessel revascularization (TVR) in large clinical trials. We conducted this study to elucidate the differences in the cost and clinical outcome of DESs and bare metal stents (BMSs). Methods: We retrospectively analyzed the clinical data and costs of patients with stable angina treated with coronary stents from September 2003 to January 2005 at the National Taiwan University Hospital, Taipei, Taiwan. Results: We enrolled 186 patients treated with DESs and 194 patients treated with BMSs. The use of DESs is associated with a lower rate of TVR compared with that with BMSs (12% vs. 22%, p = 0.011). Compared with the BMS group, the overall costs were significantly higher in the DES group (NT$352,495 ± 140,408 vs. NT$298,947 ± 131,289, p<0.001). The incremental cost to avoid one TVR at 2 years was NT$546,444 (95$151,071-2,565,793). Conclusion: The use of DESs reduces the rate of TVR at 2 years after intervention, but is probably not cost-effective compared with BMSs in patients with stable coronary artery disease

α-Lactosylceramide Protects Against iNKT-Mediated Murine Airway Hyperreactivity and Liver Injury Through Competitive Inhibition of Cd1d Binding.

Invariant natural killer T (iNKT) cells, which are activated by T cell receptor (TCR)-dependent recognition of lipid-based antigens presented by the CD1d molecule, have been shown to participate in the pathogenesis of many diseases, including asthma and liver injury. Previous studies have shown the inhibition of iNKT cell activation using lipid antagonists can attenuate iNKT cell-induced disease pathogenesis. Hence, the development of iNKT cell-targeted glycolipids can facilitate the discovery of new therapeutics. In this study, we synthesized and evaluated α-lactosylceramide (α-LacCer), an α-galactosylceramide (α-GalCer) analog with lactose substitution for the galactose head and a shortened acyl chain in the ceramide tail, toward iNKT cell activation. We demonstrated that α-LacCer was a weak inducer for both mouse and human iNKT cell activation and cytokine production, and the iNKT induction by α-LacCer was CD1d-dependent. However, when co-administered with α-GalCer, α-LacCer inhibited α-GalCer-induced IL-4 and IFN-γ production from iNKT cells. Consequently, α-LacCer also ameliorated both α-GalCer and GSL-1-induced airway hyperreactivity and α-GalCer-induced neutrophilia when co-administered in vivo. Furthermore, we were able to inhibit the increases of ConA-induced AST, ALT and IFN-γ serum levels through α-LacCer pre-treatment, suggesting α-LacCer could protect against ConA-induced liver injury. Mechanistically, we discerned that α-LacCer suppressed α-GalCer-stimulated cytokine production through competing for CD1d binding. Since iNKT cells play a critical role in the development of AHR and liver injury, the inhibition of iNKT cell activation by α-LacCer present a possible new approach in treating iNKT cell-mediated diseases

Development of a polymer-based antimicrobial coating for efficacious urinary catheter protection

10.1016/j.biotno.2020.12.001Biotechnology Notes21-1

Usefulness of Drug Eluting Stent in Percutaneous Coronary Intervention—A Single Center Experience in Taiwan

Drug eluting stents (DES) have been shown to reduce in-stent restenosis rate and target vessel revascularization in large clinical trials. However, the safety and efficacy of DES use in the Taiwanese population has not been reported. We designed this trial to analyze the clinical results in patients using DES in a single tertiary center. Methods: We retrospectively analyzed the clinical data of all patients treated at National Taiwan University Hospital, Taipei, Taiwan, with sirolimus- or paclitaxel-eluting stents between September 2003 and January 2005. Results: A total of 585 patients (466 men, 119 women; mean age, 64.5 ± 11.2 years) were enrolled. Meanwhile, 205 sirolimus- and 717 paclitaxel-eluting stents were implanted, with a mean of 1.6 stents per patient. Half (50.2%) of the stents were placed in the left anterior descending artery. Among the enrolled patients, 41.8% had diabetes mellitus, 25% had a diagnosis of acute coronary syndrome, and 10.7% was treated with primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Overall 8-month target vessel revascularization, major adverse cardiac event rate, and cardiac death rate were 8.8%, 9.7% and 2.5%, respectively. There was no difference in clinical events between sirolimus- and paclitaxel-eluting stents. The overall subacute stent thrombosis rate was 1.36%, significantly lower than that in patients who presented with acute coronary syndrome (4%). Conclusion: The use of DES in the Taiwanese population yielded comparable results as those in large clinical trials. Subacute stent thrombosis rate was higher in acute coronary syndrome. The safety of DES in these situations should be further clarified