Taipei Veterans General Hospital

About: Taipei Veterans General Hospital is a healthcare organization based out in Taipei, Taiwan. It is known for research contribution in the topics: Population & Cancer. The organization has 11878 authors who have published 16478 publications receiving 363424 citations. The organization is also known as: Táiběi Róngmín Zǒngyī Yuàn.

A novel mechanism of coenzyme Q10 protects against human endothelial cells from oxidative stress-induced injury by modulating NO-related pathways

Abstract: Background Atherosclerosis is a chronic inflammatory disease of the vessel wall associated with oxidized low-density lipoprotein (oxLDL)-induced apoptosis of endothelial cells. Coenzyme Q10 (CoQ10), a potent antioxidant and a critical intermediate of the electron transport chain, has been reported to inhibit LDL oxidation and thus the progression of atherosclerosis. However, its molecular mechanisms on endothelial cells remain still unclarified. Methods In this study, primary human umbilical vein endothelial cell cultures treated with oxLDL were used to explore the protective effects of CoQ10. Results Our results showed that CoQ10 attenuated the oxLDL-induced generation of reactive oxygen species and improved the antioxidant capacity. CoQ10 also attenuated the oxLDL-mediated down-regulation of endothelial nitric oxide synthase (eNOS) and up-regulation of inducible nitric oxide synthase (iNOS). In addition, CoQ10 suppressed oxLDL-activated NF-κB and downstream inflammatory mediators, including expression of adhesion molecules, release of proinflammatory cytokines and the adherence of monocytic THP-1 cells. Moreover, CoQ10 attenuated oxLDL-altered proapoptotic responses. The inhibitor of eNOS ( l -NIO 10 μM) and iNOS (1400W 10 μM) as well as NO enhancer (SNP 10 μM) were used to clean up the mechanism. Conclusion These results provide new insight into the possible molecular mechanisms by which CoQ10 protects against atherogenesis by NO-related pathways.

Heme oxygenase-1 gene promotor microsatellite polymorphism is associated with angiographic restenosis after coronary stenting

Abstract: Aims Heme oxygenase-1 (HO-1) is a rate-limiting enzyme in heme degradation, leading to the generation of free iron, biliverdin, and carbon monoxide (CO). CO exerts potent antiproliferative and anti-inflammatory effects in the vascular walls, thereby influencing neointimal formation after vascular injury. A dinucleotide GT repeat in the promotor region of human HO-1 gene shows a length polymorphism that modulates the level of gene transcription. This study aimed to assess the association of the length of (GT)n repeats in HO-1 gene promotor with restenosis and adverse cardiac events after coronary stenting. Methods and results Quantitative coronary angiography was evaluated before, immediately after and 6 months after stent implantation in 323 consecutive patients with successful coronary stenting. In each patient, the allele frequency of (GT)n repeats in HO-1 gene promotor was examined. Compared with those with shorter (S, <26) GT repeats, patients with longer (L, ≥26) GT repeats on either allele had more frequent angiographic restenosis with an adjusted odds ratio (OR) of 3.74 (95% confidence interval, 1.61 to 8.70, P=0.002). Such association was even more prominant in patients with small coronary arteries or complex lesions before stenting. Besides, carriers of L/L genotype had an increased risk (adjusted OR, 3.26; 95% confidence interval, 1.58 to 6.72, P=0.001) for adverse cardiac events during follow-up. Conclusions The length polymorphism of GT repeat in HO-1 gene promoter is an independent risk factor for angiographic restenosis as well as adverse cardiac events after coronary stenting. These findings suggest the genetic contribution to stent restenosis and support the notion that the long dinucleotide GT repeat in promotor region may interfere with HO-1 gene transcription, leading to decreased vascular protection upon injury. © 2003 Published by Elsevier Ltd on behalf of The European Society of Cardiology.

Immediate gain is long-term loss: Are there foresighted decision makers in the Iowa Gambling Task?

Abstract: The Somatic Marker Hypothesis suggests that normal subjects are "foreseeable" and ventromedial prefrontal patients are "myopic" in making decisions, as the behavior shown in the Iowa Gambling Task. The present study questions previous findings because of the existing confounding between long-term outcome (expected value, EV) and gain-loss frequency variables in the Iowa Gambling Task (IGT). A newly and symmetrically designed gamble, namely the Soochow Gambling Task (SGT), with a high-contrast EV between bad (A, B) and good (C, D) decks, is conducted to clarify the issue about IGT confounding. Based on the prediction of EV (a basic assumption of IGT), participants should prefer to choose good decks C and D rather than bad decks A and B in SGT. In contrast, according to the prediction of gain-loss frequency, subjects should prefer the decks A and B because they possessed relatively the high-frequency gain. The present experiment was performed by 48 participants (24 males and 24 females). Most subjects are college students recruited from different schools. Each subject played the computer version SGT first and completed a questionnaire for identifying their final preference. The IGT experimental procedure was mostly followed to assure a similar condition of decision uncertainty. The SGT experiment demonstrated that the prediction of gain-loss frequency is confirmed. Most subjects preferred to choose the bad decks A and B than good decks C and D. The learning curve and questionnaire data indicate that subjects can not "hunch" the EV throughout the game. Further analysis of the effect of previous choice demonstrated that immediate gain increases the probability to stay at the same deck. SGT provides a balanced structure to clarify the confounding inside IGT and demonstrates that gain-loss frequency rather than EV guides decision makers in these high-ambiguity gambles. Additionally, the choice behavior is mostly following the "gain-stay, lose-randomize" strategy to cope with the uncertain situation. As demonstrated in SGT, immediate gain can bring about a long-term loss under uncertainty. This empirical result may explain some shortsighted behaviors in real life.

Elimination of head and neck cancer initiating cells through targeting glucose regulated protein78 signaling

Abstract: Head and neck squamous cell carcinoma (HNSCC) is a highly lethal cancer that contains cellular and functional heterogeneity. Previously, we enriched a subpopulation of highly tumorigenic head and neck cancer initiating cells (HN-CICs) from HNSCC. However, the molecular mechanisms by which to govern the characteristics of HN-CICs remain unclear. GRP78, a stress-inducible endoplasmic reticulum chaperone, has been reported to play a crucial role in the maintenance of embryonic stem cells, but the role of GRP78 in CICs has not been elucidated. Initially, we recognized GRP78 as a putative candidate on mediating the stemness and tumorigenic properties of HN-CICs by differential systemic analyses. Subsequently, cells with GRP78 anchored at the plasma membrane (memGRP78+) exerted cancer stemness properties of self-renewal, differentiation and radioresistance. Of note, xenotransplantation assay indicated merely 100 memGRP78+ HNSCCs resulted in tumor growth. Moreover, knockdown of GRP78 significantly reduced the self-renewal ability, side population cells and expression of stemness genes, but inversely promoted cell differentiation and apoptosis in HN-CICs. Targeting GRP78 also lessened tumorigenicity of HN-CICs both in vitro and in vivo. Clinically, co-expression of GRP78 and Nanog predicted the worse survival prognosis of HNSCC patients by immunohistochemical analyses. Finally, depletion of GRP78 in HN-CICs induced the expression of Bax, Caspase 3, and PTEN. In summary, memGRP78 should be a novel surface marker for isolation of HN-CICs, and targeting GRP78 signaling might be a potential therapeutic strategy for HNSCC through eliminating HN-CICs.