المؤلفون: Gulinigaer Anwaier, Guan Lian, Gui-Zhi Ma, Wan-Li Shen, Chih-I Lee, Pei-Ling Lee, Zhan-Ying Chang, Yun-Xia Wang, Xiao-Yu Tian, Xiao-Li Gao, Jeng-Jiann Chiu, Rong Qi

المصدر: Frontiers in Cell and Developmental Biology, Vol 9 (2021)

مصطلحات موضوعية: pomegranate, punicalagin, oscillatory shear stress, atherosclerosis, endothelial cell, Smads, Biology (General), QH301-705.5

الوصف: BackgroundPathophysiological vascular remodeling in response to disturbed flow with low and oscillatory shear stress (OSS) plays important roles in atherosclerosis progression. Pomegranate extraction (PE) was reported having anti-atherogenic effects. However, whether it can exert a beneficial effect against disturbed flow-induced pathophysiological vascular remodeling to inhibit atherosclerosis remains unclear. The present study aims at investigating the anti-atherogenic effects of pomegranate peel polyphenols (PPP) extraction and its purified compound punicalagin (PU), as well as their protective effects on disturbed flow-induced vascular dysfunction and their underlying molecular mechanisms.MethodsThe anti-atherogenic effects of PPP/PU were examined on low-density lipoprotein receptor knockout mice fed with a high fat diet. The vaso-protective effects of PPP/PU were examined in rat aortas using myograph assay. A combination of in vivo experiments on rats and in vitro flow system with human endothelial cells (ECs) was used to investigate the pharmacological actions of PPP/PU on EC dysfunction induced by disturbed flow. In addition, the effects of PPP/PU on vascular smooth muscle cell (VSMC) dysfunction were also examined.ResultsPU is the effective component in PPP against atherosclerosis. PPP/PU evoked endothelium-dependent relaxation in rat aortas. PPP/PU inhibited the activation of Smad1/5 in the EC layers at post-stenotic regions of rat aortas exposed to disturbed flow with OSS. PPP/PU suppressed OSS-induced expression of cell cycle regulatory and pro-inflammatory genes in ECs. Moreover, PPP/PU inhibited inflammation-induced VSMC dysfunction.ConclusionPPP/PU protect against OSS-induced vascular remodeling through inhibiting force-specific activation of Smad1/5 in ECs and this mechanism contributes to their anti-atherogenic effects.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fcell.2021.697539/fullTest; https://doaj.org/toc/2296-634XTest

الوصول الحر: https://doaj.org/article/3d54a532fe2b48fa875b4dd09c1d1380Test

المؤلفون: Wei-Li Wang, Li-Jing Chen, Shu-Yi Wei, Yu-Tsung Shih, Yi-Hsuan Huang, Pei-Lin Lee, Chih-I Lee, Mei-Cun Wang, Ding-Yu Lee, Shu Chien, Jeng-Jiann Chiu

المصدر: Frontiers in Cell and Developmental Biology, Vol 9 (2021)

مصطلحات موضوعية: disturbed flow, endothelium, MicroRNA, shear stress, Smad, Biology (General), QH301-705.5

الوصف: MicroRNAs (miRs) and bone morphogenetic protein receptor–specific Smads are mechano-responsive molecules that play vital roles in modulating endothelial cell (EC) functions in response to blood flow. However, the roles of interplay between these molecules in modulating EC functions under flows remain unclear. We elucidated the regulatory roles of the interplay between miR-487a and Smad5 in EC proliferation in response to different flow patterns. Microarray and quantitative RT-PCR showed that disturbed flow with low and oscillatory shear stress (OS, 0.5 ± 4 dynes/cm2) upregulates EC miR-487a in comparison to static controls and pulsatile shear stress (12 ± 4 dynes/cm2). MiR-487a expression was higher in ECs in the inner curvature (OS region) than the outer curvature of the rat aortic arch and thoracic aorta and also elevated in diseased human coronary arteries. MiR-487a expression was promoted by nuclear phospho-Smad5, which bound to primary-miR-487a to facilitate miR-487a processing. Algorithm prediction and luciferase reporter and argonaute 2-immunoprecipitation assays demonstrated that miR-487a binds to 3′UTR of CREB binding protein (CBP) and p53. Knockdown and overexpression of miR-487a decreased and increased, respectively, phospho-Rb and cyclin A expressions through CBP and p53. A BrdU incorporation assay showed that miR-487a enhanced EC proliferation under OS in vitro and in disturbed flow regions of experimentally stenosed rat abdominal aorta in vivo. These results demonstrate that disturbed flow with OS induces EC expression of miR-487a through its enhanced processing by activated-Smad5. MiR-487 inhibits its direct targets CBP and p53 to induce EC cycle progression and proliferation. Our findings suggest that EC miR-487 may serve as an important molecular target for intervention against disturbed flow–associated vascular disorders resulting from atherosclerosis.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fcell.2021.647714/fullTest; https://doaj.org/toc/2296-634XTest

الوصول الحر: https://doaj.org/article/f48be3cc57df40fcb55804f6801d6cd7Test

المؤلفون: Jong-Tar Kuo, Hsiao-En Tsai, Ching-Ting Lin, Chih-I Lee, Pei-Ling Lee, Yu-Rong Ruan, Jeng-Jiann Chiu, Ding-Yu Lee

المصدر: Cardiology Research and Practice, Vol 2021 (2021)

مصطلحات موضوعية: Diseases of the circulatory (Cardiovascular) system, RC666-701

الوصف: Background. MicroRNA-10a (miR-10a) inhibits transcriptional factor GATA6 to repress inflammatory GATA6/VCAM-1 signaling, which is regulated by blood flow to affect endothelial function/dysfunction. This study aimed to identify the expression patterns of miR-10a/GATA6/VCAM-1 in vivo and study their implications in the pathophysiology of human coronary artery disease (CAD), i.e., atherosclerosis. Methods. Human atherosclerotic coronary arteries and nondiseased arteries were used to detect the expressions of miR-10a/GATA6/VCAM-1 in pathogenic vs. normal conditions. In addition, sera from CAD patients and healthy subjects were collected to detect the level of circulating miR-10a. Results. The comparison of human atherosclerotic coronary arteries with nondiseased arteries demonstrated that lower levels of endothelial miR-10a are related to human atherogenesis. Moreover, GATA6/VCAM-1 (a downstream target of miR-10a) was highly expressed in the endothelium, accompanied by the reduced levels of miR-10a during the development of human atherosclerosis. In addition, CAD patients had a significantly lower concentration of miR-10a in their serum compared to healthy subjects. Conclusions. Our findings suggest that low miR-10a and high GATA6/VCAM-1 in the cardiovascular endothelium correlates to the development of human atherosclerotic lesions, suggesting that miR-10a signaling has the potential to be developed as a biomarker for human atherosclerosis.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2090-8016Test; https://doaj.org/toc/2090-0597Test

الوصول الحر: https://doaj.org/article/445b780eb1e54066b7cbb526718d06f8Test

المؤلفون: Tung-Lin Yang, Pei-Ling Lee, Ding-Yu Lee, Wei-Li Wang, Shu-Yi Wei, Chih-I Lee, Jeng-Jiann Chiu

المصدر: Journal of Biomedical Science, Vol 25, Iss 1, Pp 1-13 (2018)

مصطلحات موضوعية: Endothelial cell, Extracellular matrix, Integrin, Shear stress, Transforming growth factor receptor, Medicine

الوصف: Abstract Background Atherosclerosis occurs in arterial curvatures and branches, where the flow is disturbed with low and oscillatory shear stress (OSS). The remodeling and alterations of extracellular matrices (ECMs) and their composition is the critical step in atherogenesis. In this study, we investigated the effects of different ECM proteins on the regulation of mechanotransduction in vascular endothelial cells (ECs) in response to OSS. Methods Through the experiments ranging from in vitro cell culture studies on effects of OSS on molecular signaling to in vivo examinations on clinical specimens from patients with coronary artery disease (CAD), we elucidated the roles of integrins and different ECMs, i.e., fibronectin (FN) and laminin (LM), in transforming growth factor (TGF)-β receptor (TβR)-mediated Smad2 activation and nuclear factor-κB (NF-κB) signaling in ECs in response to OSS and hence atherogenesis. Results OSS at 0.5±12 dynes/cm2 induces sustained increases in the association of types I and II TβRs with β1 and β3 integrins in ECs grown on FN, but it only transient increases in ECs grown on LM. OSS induces a sustained activation of Smad2 in ECs on FN, but only a transient activation of Smad2 in ECs on LM. OSS-activation of Smad2 in ECs on FN regulates downstream NF-κB signaling and pro-inflammatory gene expression through the activation of β1 integrin and its association with TβRs. In contrast, OSS induces transient activations of β1 and β3 integrins in ECs on LM, which associate with type I TβR to regulate Smad2 phosphorylation, resulting in transient induction of NF-κB and pro-inflammatory gene expression. In vivo investigations on diseased human coronary arteries from CAD patients revealed that Smad2 is highly activated in ECs of atherosclerotic lesions, which is accompanied by the concomitant increase of FN rather than LM in the EC layer and neointimal region of atherosclerotic lesions. Conclusions Our findings provide new insights into the mechanisms of how OSS regulates Smad2 signaling and pro-inflammatory genes through the complex signaling networks of integrins, TβRs, and ECMs, thus illustrating the molecular basis of regional pro-inflammatory activation within disturbed flow regions in the arterial tree.

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s12929-017-0402-4Test; https://doaj.org/toc/1423-0127Test

الوصول الحر: https://doaj.org/article/c3cb75c2dc3947b5beb4e404c29a0470Test

المؤلفون: Yuan-Pin Hung, Hsiao-Ju Lin, Tai-Chieh Wu, Hsiu-Chuan Liu, Jen-Chieh Lee, Chih-I Lee, Yi-Hui Wu, Lei Wan, Pei-Jane Tsai, Wen-Chien Ko

المصدر: PLoS ONE, Vol 8, Iss 7, p e69577 (2013)

مصطلحات موضوعية: Medicine, Science

الوصف: BACKGROUND: This study is to investigate the significance and risk factors of fecal toxigenic (tCdC) or non-toxigenic Clostridium difficile colonization (ntCdC) among hospitalized patients. METHODS: Adults admitted to medical wards in a district hospital between January 2011 and June 2012 were enrolled, and those with a history of colectomy, C. difficile fecal colonization or infection or receipt of either metronidazole or oral vancomycin within 3 months, were excluded. Stools collected within 48 hours after admission and every week during hospitalization were cultured for C. difficile. FINDINGS: Among the 441 enrolled patients, 84 (20.0%) had CdC at initial screening, including 58 (13.2%) with tCdC and 26 (6.8%) with ntCdC. Among patients with initial negative fecal screening for CdC, it took an average of 70.6 days or 66.5 days to develop tCdC or ntCdC during the study period. Finally 78 (17.7%) had tCdC and 34 (7.7%) had ntCdC. During the follow-up period, the patients with tCdC had a higher risk of CDAD (11/79, 14.1%) than those without CdC (3/328, 0.9%) and those with ntCdC (0/34, 0%) (P

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC3723847?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/b83a1bf36e5b4dda94347496389856c9Test

المؤلفون: Yuan-Pin Hung, Pei-Jane Tsai, Kuei-Hsiang Hung, Hsiu-Chuan Liu, Chih-I Lee, Hsiao-Ju Lin, Yi-Hui Wu, Jiunn-Jong Wu, Wen-Chien Ko

المصدر: PLoS ONE, Vol 7, Iss 8, p e42415 (2012)

مصطلحات موضوعية: Medicine, Science

الوصف: BACKGROUND: The impact of toxigenic Clostridium difficile colonization (tCDC) in hospitalized patients is not clear. AIM: To study the significance of tCDC in hospitalized patients. METHODS: A prospective study in the medical wards of a regional hospital was performed from January to June 2011. Fecal samples collected from patients at the time of admission were tested for tcdB by real-time polymerase chain reaction (PCR) and cultured for C. difficile. The patients were followed up weekly or when they developed diarrhea during hospitalization. If C. difficile was isolated, tcdA and tcdB would be tested by multiplex PCR. The primary outcome was the development of C. difficile-associated diarrhea (CDAD). FINDINGS: Of 168 patients enrolled, females predominated (87, 51.8%), and the mean patient age was 75.4 years old. Approximately 70% of the patients were nursing home residents, and one third had a recent hospitalization within the prior three months. Twenty-eight (16.7%) patients had tCDC, including 16 (9.5%) patients with tCDC at the time of admission and 12 (7.2%) with tCDC during the follow-up period. With regard to the medications taken during hospitalization, the patients were more likely to have tCDC if they had received more than one class of antibiotics than if they had received monotherapy (odds ratio [OR] 6.67, 95% confidence interval [CI] 1.41-31.56, P = 0.01), particularly if they received a glycopeptide in combination with a cephalosporin or penicillin or a cephalosporin and a carbapenem. More patients with tCDC developed CDAD than those without tCDC (17.9%, 5/28 vs. 1.4%, 2/140, P = 0.002). Overall 7 (4.2%) of the 168 patients developed CDAD, and crude mortality rate of those with and without tCDC was similar (21.4%, 6/28 vs. 19.4%, 27/140, P = 0.79). CONCLUSION: Recent use of glycopeptides and β-lactam antibiotics is associated with toxigenic C. difficile colonization, which is a risk factor for developing C. difficile-associated diarrhea.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC3411658?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/483f8b829529459782d4397348e6f5fdTest

المؤلفون: CHIH-I LEE, 李芷怡

مرشدي الرسالة: Po-Chin Wu, 吳博欽

الوصف: 106
This study mainly carries out two modifications based on the three-factor model proposed by Fama-French (1993) (market factor, size factor, and book /market factor). First, we add the term of price-cost margin that represents market monopoly power into the Fama-French model as another factor to form a linear four-factor model. The price-cost margins are similar to the market monopoly indicators - Lerner index and Bain index. The larger the price set by the firm deviates from the marginal cost or average cost, the higher the firm''s monopoly power would be. Second, we apply the panel smooth transition regression (PSTR) model and rewrite the linear four-factor model as a four-factor PSTR framework. In the four-factor PSTR model, the deposit spread is used as the transition variable to estimate stock returns and four risk premiums (market, size, book-to-market, and monopoly power) that vary with companies and time. Empirically, a panel data set of 28 listed financial stocks in Taiwan during March 2008 to June 2017 is used. Thus, there are 1064 observations. Empirical results are summarized as follows: First, for the financial industry, the growth stocks have higher excess returns than value stocks; the big size stocks have higher excess returns than small size stocks. Second, the four risk premiums all vary with the deposit spreads of individual financial companies in different periods, which is quite different from the constant risk premiums obtained from the traditional Fama-French three-factor model and linear four-factor model. Third, when considering deposit spreads, the traditional linear model underestimates the positive impact of market factors on the stock returns. In addition, a high deposit spread would increase the contribution of market factors to stock prices, while a moderate deposit spread would minimize the contribution. Fourth, the impact of size factor on stock returns is significant, but the sign is ambiguous. In the case of moderate deposit spreads, there may be an increase in the non-performing loans, resulting in a decrease in the size premium. Fifth, the contribution of book-to-market ratio to share prices is insignificant and ambiguous. The value premium is maximum when the deposit spreads are high. Sixth, the effect of market monopoly power on stock returns is negative but not significant. However, the effect in the linear four-factor model is positive and insignificant. In other words, simply considering the factor of market monopoly power and ignoring different level of deposit spreads will misestimate its impact on the stock returns.

وصف الملف: 59

الإتاحة: http://ndltd.ncl.edu.tw/handle/vu2g2sTest

المؤلفون: Chih-I Lee, 李芝儀

مرشدي الرسالة: Ben-Chang Shia, 謝邦昌

الوصف: 92
This main purpose of the study is finding the development of business model “Customer Relationship Management” on power industry liberalization in Taiwan. It is divided into five parts including an introduction, literature review, research method, findings, and conclusions and suggestions. Two statistical analysis methods — Logistic Regression and Chi-Square Automatic Interaction Detector in the study are used to analyze the situation of changing power companies and the satisfaction of Taiwan Power Company. The study has the following findings: (1). Customers in different areas have different attitudes toward changing power companies. (2). Customers in different areas have different satisfaction of Taiwan Power Company.

وصف الملف: 110

الإتاحة: http://ndltd.ncl.edu.tw/handle/57116636528358381344Test

المؤلفون: Chih-I Lee, Shu Yi Wei, Hsin-Yi Wu, Pei Ling Lee, Shu Chien, Wei-Li Wang, Chia-Yu Lin, Jeng-Jiann Chiu, Yu-Ju Chen, Yu-Tsung Shih

المصدر: Circulation research. 129(12)

مصطلحات موضوعية: Male, Physiology, Cell Line, Rats, Sprague-Dawley, Mice, Animals, Humans, Phosphorylation, Casein Kinase II, YY1 Transcription Factor, Binding Sites, Chemistry, Endothelial Cells, Proto-Oncogene Proteins c-mdm2, Zinc Fingers, Atherosclerosis, YIN-YANG-1, Cell biology, Rats, Endothelial stem cell, Mice, Inbred C57BL, Flow (mathematics), Blood Circulation, Disturbed flow, Casein kinase 1, Endothelium, Vascular, Tetrabromocinnamic acid, Cardiology and Cardiovascular Medicine, Protein Binding

الوصف: Rationale: Disturbed flow occurring in arterial branches and curvatures induces vascular endothelial cell (EC) dysfunction and atherosclerosis. We postulated that disturbed flow plays important role in modulating phosphoprotein expression profiles to regulate endothelial functions and atherogenesis. Objective: The goal of this study is to discover novel site-specific phosphorylation alterations induced by disturbed flow in ECs to contribute to atherosclerosis. Methods and Results: Quantitative phosphoproteomics analysis of ECs exposed to disturbed flow with low and oscillatory shear stress (0.5±4 dynes/cm 2 ) versus pulsatile shear stress (12±4 dynes/cm 2 ) revealed that oscillatory shear stress induces phospho-YY1 S118 (serine [S]118 phosphorylation of Yin Yang 1) in ECs. Elevated phospho-YY1 S118 level in ECs was further confirmed to be present in the disturbed flow regions in experimental animals and human atherosclerotic arteries. This disturbed flow-induced EC phospho-YY1 S118 is mediated by CK2α (casein kinase 2α) through its direct interaction with YY1. Yeast 2-hybrid library screening and in situ proximity ligation assays demonstrate that phospho-YY1 S118 directly binds ZKSCAN4 (zinc finger with KRAB [krüppel-associated box] and SCAN [SRE-ZBP, CTfin51, AW-1 and Number 18 cDNA] domains 4) to induce promoter activity and gene expression of HDM2 (human double minute 2), which consequently induces EC proliferation through downregulation of p53 and p21 CIP1 . Administration of apoE-deficient ( ApoE −/− ) mice with CK2-specific inhibitor tetrabromocinnamic acid or atorvastatin inhibits atherosclerosis formation through downregulations of EC phospho-YY1 S118 and HDM2. Generation of novel transgenic mice bearing EC-specific overexpression of S118-nonphosphorylatable mutant of YY1 in ApoE −/− mice confirms the critical role of phospho-YY1 S118 in promoting atherosclerosis through EC HDM2. Conclusions: Our findings provide new insights into the mechanisms by which disturbed flow induces endothelial phospho-YY1 S118 to promote atherosclerosis, thus indicating phospho-YY1 S118 as a potential molecular target for atherosclerosis treatment.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c363830da4a13783bcaa7a018fa8561eTest
https://pubmed.ncbi.nlm.nih.gov/34747636Test

المؤلفون: Gulinigaer Anwaier (6903299), Guan Lian (6903302), Gui-Zhi Ma (11034732), Wan-Li Shen (11034735), Chih-I Lee (312933), Pei-Ling Lee (11034738), Zhan-Ying Chang (11034741), Yun-Xia Wang (529831), Xiao-Yu Tian (11034744), Xiao-Li Gao (8036024), Jeng-Jiann Chiu (123092), Rong Qi (1647328)

مصطلحات موضوعية: Cell Biology, Marine Biology, Cell Development, Proliferation and Death, Cell Metabolism, Cell Neurochemistry, Cellular Interactions (incl. Adhesion, Matrix, Cell Wall), pomegranate, punicalagin, oscillatory shear stress, atherosclerosis, endothelial cell, Smads

الوصف: Background Pathophysiological vascular remodeling in response to disturbed flow with low and oscillatory shear stress (OSS) plays important roles in atherosclerosis progression. Pomegranate extraction (PE) was reported having anti-atherogenic effects. However, whether it can exert a beneficial effect against disturbed flow-induced pathophysiological vascular remodeling to inhibit atherosclerosis remains unclear. The present study aims at investigating the anti-atherogenic effects of pomegranate peel polyphenols (PPP) extraction and its purified compound punicalagin (PU), as well as their protective effects on disturbed flow-induced vascular dysfunction and their underlying molecular mechanisms. Methods The anti-atherogenic effects of PPP/PU were examined on low-density lipoprotein receptor knockout mice fed with a high fat diet. The vaso-protective effects of PPP/PU were examined in rat aortas using myograph assay. A combination of in vivo experiments on rats and in vitro flow system with human endothelial cells (ECs) was used to investigate the pharmacological actions of PPP/PU on EC dysfunction induced by disturbed flow. In addition, the effects of PPP/PU on vascular smooth muscle cell (VSMC) dysfunction were also examined. Results PU is the effective component in PPP against atherosclerosis. PPP/PU evoked endothelium-dependent relaxation in rat aortas. PPP/PU inhibited the activation of Smad1/5 in the EC layers at post-stenotic regions of rat aortas exposed to disturbed flow with OSS. PPP/PU suppressed OSS-induced expression of cell cycle regulatory and pro-inflammatory genes in ECs. Moreover, PPP/PU inhibited inflammation-induced VSMC dysfunction. Conclusion PPP/PU protect against OSS-induced vascular remodeling through inhibiting force-specific activation of Smad1/5 in ECs and this mechanism contributes to their anti-atherogenic effects.

العلاقة: https://figshare.com/articles/dataset/Table_1_Punicalagin_Attenuates_Disturbed_Flow-Induced_Vascular_Dysfunction_by_Inhibiting_Force-Specific_Activation_of_Smad1_5_DOCX/14864358Test

الإتاحة: https://doi.org/10.3389/fcell.2021.697539.s001Test