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Chen PY Hsu WT Jhuo MD Ou CY Cheng TH Shih TC Wu CH Wu RS Hsia TC Chung JG 《In vivo (Athens, Greece)》2011,25(2):219-228
HCV (Hepatitis C virus) that causes chronic liver disease. HCV NS5B RNA-dependent RNA polymerase (RbRp) and NS3 protease are able to affect virtual replication of genes. Computer-aided drug design (CADD) aims at designing new molecules with pharmacological activity. In this study, we used the Discovery Studio 2.0 program and the scoring function to estimate the Dock Score, piecewise linear potential 1 (PLP1), piecewise linear potential 2 (PLP2), and potential of mean force (PMF) score of novel compounds. In this way, novel compounds with "de novo evolution" can be found. Using the the pharmacophore features that are near the receptor pocket and the score functions to calculate scores for the ligand-receptor interaction, the new ligands were selected, developed and virtually placed in the binding site of the receptor. A new compound, EVO12, gave the best score, indicating that it may be an efficient polymerase inhibitor of HCV NS5B. 相似文献
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Shih-Jie Jhuo Tsyh-Jyi Hsieh Wei-Hua Tang Wei-Chung Tsai Kun-Tai Lee Hsueh-Wei Yen Wen-Ter Lai 《Journal of electrocardiology》2018,51(4):645-651
Background
The relationship of epicardial fat and cardiac arrhythmias has been described in many studies. The association of the amounts of epicardial fat and the characteristics of electrocardiogram (ECG) remains unclear. The purpose of this study was to elucidate the association between the amounts of epicardial fat and the characteristics of ECG.Methods
A total of 100 consecutive patients who received multi-detector computer tomography (MDCT) were enrolled. The amounts of epicardial fat, including total heart, total atria, total ventricles, right atrium (RA), right ventricle (RV), left atrium (LA), and left ventricle (LV) regions, were measured. The PR interval in lead II, the P wave duration in lead I, the characteristics of inter-atrial conduction block manifested in ECG, the corrected QT interval (QTc) and the QT dispersion of a 12?lead ECG were measured manually by a computer caliper.Results
The PR interval was correlated with the amounts of epicardial fat including total heart, total atria, total ventricles, RA, RV, LA, and LV (R?=?0.295, p?=?0.003; R?=?0.379, p?<?0.001; R?=?0.284, p?=?0.003; R?=?0.415, p?<?0.001; R?=?0.287, p?<?0.001; R?=?0.33, p?<?0.001; R?=?0.244, p?=?0.014). The P wave duration of lead I was also correlated with the amounts of epicardial fat (R?=?0.202, p?=?0.043; R?=?0.283, p?=?0.004; R?=?0.225, p?=?0.024; R?=?0.365, p?<?0.001; R?=?0.256, p?=?0.001; R?=?0.20, p?=?0.046; R?=?0.199, p?=?0.048) but the QTc interval and the QT dispersion were not. Inter-atrial conduction block was also associated with the amounts of epicardial fat, including total atria, RA and LA in univariate analysis (odds ratio (OR): 1.04, 95% of confidence interval (CI): 1.01–1.06, p?=?0.015; OR: 1.08, 95% CI: 1.02–1.15, p?=?0.011; OR: 1.05, 95% CI: 1.01–1.10, p?=?0.031). In multivariate analysis of linear regression, the amounts of RA epicardial fat was most significantly associated with the PR interval, and the P wave duration (β value: 1.30, 95% CI: 0.59–2.02, p?<?0.001; β value: 0.81, 95% CI: 0.34–1.28, p?=?0.001). In multivariate analysis of logistic regression, inter-atrial conduction block was also significantly associated with the amounts of RA epicardial fat (odds ratio (OR): 1.08, 95% CI: 1.02–1.15, p?=?0.011).Conclusions
The PR interval, P wave duration and inter-atrial conduction block were associated with the amounts of epicardial fat, which might imply an effect for arrhythmogenesis. 相似文献3.
Wei-Chung Tsai Kun-Tai Lee Hsuan-Fu Kuo Wei-Hua Tang Shih-Jie Jhuo Chih-Sheng Chu Tsung-Hsien Lin Po-Chao Hsu Ming-Yen Lin Feng-Hsien Lin Ho-Ming Su Wen-Chol Voon Wen-Ter Lai Sheng-Hsiung Sheu 《International journal of medical sciences》2013,10(11):1437-1444
Background: The association between increased arterial stiffness and left ventricular diastolic dysfunction (LVDD) may be influenced by left ventricular performance. P wave dispersion is not only a significant determinant of left ventricular performance, but is also correlated with LVDD. This study is designed to compare left ventricular diastolic function among patients divided by brachial-ankle pulse wave velocity (baPWV) and corrected P wave dispersion (PWDC) and assess whether the combination of baPWV and PWDC can predict LVDD more accurately.Methods: This cross-sectional study enrolled 270 patients and classified them into four groups according to the median values of baPWV and PWDC. LVDD was defined as impaired relaxation and pseudonormal/restrictive mitral inflow patterns.Results: The ratio of transmitral E wave velocity to early diastolic mitral annulus velocity (E/Ea) was higher in group with higher baPWV and PWDC than in the other groups (all p <0.001). The prevalence of LVDD was higher in group with higher baPWV and PWDC than in the two groups with lower baPWV (p ≤ 0.001). The baPWV and PWDC were correlated with E/Ea and LVDD in multivariate analysis (p ≤ 0.030). The addition of baPWV and PWDC to a clinical mode could significantly improve the R square in prediction of E/Ea and C statistic and integrated discrimination index in prediction of LVDD (p ≤ 0.010).Conclusions: This study showed increased baPWV and PWDC were correlated with high E/Ea and LVDD. The addition of baPWV and PWDC to a clinical model improved the prediction of high E/Ea and LVDD. Screening patients by means of baPWV and PWDC might help identify the high risk group of elevated left ventricular filling pressure and LVDD. 相似文献
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Wei-Chung Tsai Chung-Yu Chen Hsuan-Fu Kuo Ming-Tsang Wu Wei-Hua Tang Chih-Sheng Chu Tsung-Hsien Lin Ho-Ming Su Po-Chao Hsu Shih-Jie Jhuo Ming-Yen Lin Kun-Tai Lee Sheng-Hsiung Sheu Wen-Ter Lai 《International journal of medical sciences》2013,10(7):804-811
Background: Areca nut chewing is associated with the risk of obesity, metabolic syndrome, hypertension, and cardiovascular mortality. Although a few case reports or case series have suggested the link between areca nut chewing and cardiac arrhythmias, information about the relationship between areca nut chewing and atrial fibrillation (AF) is lacking. Thus, a nationwide ecological study was conducted to investigate this.Methods: Two national datasets, the nationwide population-based 2005 Taiwan National Health Insurance Research dataset (NHIRD) and the 2005 National Health Interview Survey (NHIS), were used for analyses. The clinical characteristics, inhabited area and medical histories for 375,360 eligible males were retrieved from the 2005 NHIRD. Health related behaviors including areca nut chewing, cigarette smoking, infrequent vegetable eating, and exercise habit were collected from the 2005 NHIS. The prevalence of AF and the areca nut chewing rate were evaluated by multivariate analysis.Results: Of the 375,360 males (mean age, 44 years old), 1,326 (0.35%) were diagnosed with AF. The higher areca nut chewing rate, the higher prevalence rate of AF in Taiwan (Spearman correlation coefficient r = 0.558, p = 0.007). After adjusting for other covariates, the current areca nut chewing rate was found to be independently associated with the prevalence of AF. The adjusted odd ratio for areca nut chewing was 1.02 (95% CI = 1.00-1.04) in risk of AF prevalence.Conclusions: Areca nut chewing is independently associated with the prevalence of AF in Taiwanese men. However, further exploration of the underlying mechanisms is necessary. 相似文献
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Tsun-Li Cheng Zi-Yun Lin Keng-Ying Liao Wei-Chi Huang Cian-Fen Jhuo Pin-Ho Pan Chun-Jung Chen Yu-Hsiang Kuan Wen-Ying Chen 《Nutrients》2022,14(1)
Magnesium lithospermate B (MLB) is a primary hydrophilic component of Danshen, the dried root of Salvia miltiorrhiza used in traditional medicine, and its beneficial effects on obesity-associated metabolic abnormalities were reported in our previous study. The present study investigated the anti-muscle atrophy potential of MLB in mice with high-fat diet (HFD)-induced obesity. In addition to metabolic abnormalities, the HFD mice had a net loss of skeletal muscle weight and muscle fibers and high levels of muscle-specific ubiquitin E3 ligases, namely the muscle atrophy F-box (MAFbx) and muscle RING finger protein 1 (MuRF-1). MLB supplementation alleviated those health concerns. Parallel changes were revealed in high circulating tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), skeletal TNF receptor I (TNFRI), nuclear factor-kappa light chain enhancer of activated B cells (NF-κB), p65 phosphorylation, and Forkhead box protein O1 (FoxO1) as well as low skeletal phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) phosphorylation. The study revealed that MLB prevented obesity-associated skeletal muscle atrophy, likely through the inhibition of MAFbx/MuRF-1-mediated muscular degradation. The activation of the PI3K-Akt-FoxO1 pathway and inhibition of the TNF-α/TNFRI/NF-κB pathway were assumed to be beneficial effects of MLB. 相似文献
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The prevalence and incidence of Parkinson’s disease (PD), an age-related neurodegenerative disease, are higher among elderly people. Independent of etiology, dysfunction and loss of dopaminergic neurons are common pathophysiological changes in PD patients with impaired motor and non-motor function. Currently, preventive or therapeutic treatment for combating PD is limited. The ghrelin axis and ghrelin receptor have been implicated in the preservation of dopaminergic neurons and have potential implications in PD treatment. Teaghrelin, a compound originating from Chin-Shin Oolong tea, exhibits ghrelin agonist activity. In this study, the neuroprotective potential of teaghrelin against PD was explored in a cell model in which human neuroblastoma SH-SY5Y cells were treated with the mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP+). Upon MPP+ exposure, SH-SY5Y cells exhibited decreased mitochondrial complex I activity and apoptotic cell death. Teaghrelin activated AMP-activated protein kinase (AMPK)/sirtuin 1(SIRT1)/peroxisome proliferator-activated receptor gamma (PPARγ) coactivator-1α (PGC-1α) and extracellular signal–regulated kinases 1 and 2 (ERK1/2) pathways to antagonize MPP+-induced cell death. Herein, we propose that teaghrelin is a potential candidate for the therapeutic treatment of PD. 相似文献
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