Antidiabetic effect and mode of action of cytopiloyne

Cytopiloyne was identified as a novel polyacetylenic compound. However, its antidiabetic properties are poorly understood. The aim of the present study was to investigate the anti-diabetic effect and mode of action of cytopiloyne on type 2 diabetes (T2D). We first evaluated the therapeutic effect of cytopiloyne on T2D in db/db mice. We found that one dose of cytopiloyne reduced postprandial glucose levels while increasing blood insulin levels. Accordingly, long-term treatment with cytopiloyne reduced postprandial blood glucose levels, increased blood insulin, improved glucose tolerance, suppressed the level of glycosylated hemoglobin A1c (HbA1c), and protected pancreatic islets in db/db mice. Next, we studied the anti-diabetic mechanism of action of cytopiloyne. We showed that cytopiloyne failed to decrease blood glucose in streptozocin- (STZ-)treated mice whose β cells were already destroyed. Additionally, cytopiloyne dose dependently increased insulin secretion and expression in β cells. The increase of insulin secretion/expression of cytopiloyne was regulated by protein kinase C α (PKC α ) and its activators, calcium, and diacylglycerol (DAG). Overall, our data suggest that cytopiloyne treats T2D via regulation of insulin production involving the calcium/DAG/PKC α cascade in β cells. These data thus identify the molecular mechanism of action of cytopiloyne and prove its therapeutic potential in T2D

Testing Variation in Esports Spectators’ Motivations in Relation to Consumption Behaviour

This study aims to examine firstly the motivations of esports spectators driving them to engage in consumption behaviour, and secondly, two spectator groups (League of Legends, LOL; Hearthstone) to compare the findings of the independence model and the competing model. In recent decades, the concept of esports has emerged as a major component of the sports industry and, therefore, of the global economy. However, the basic functioning of this new sector is relatively poorly understood. This study considers consumer motivations as they relate to esports and aims to assess how selected motivations interact. The motivations chosen in five categories were adopted from the Uses and Gratifications Theory. The independence model (based on Uses and Gratifications Theory (UGT)) and competing model (based on multiple theoretical perspectives) were applied to the LOL and Hearthstone spectator groups. Data (n = 574) were collected via online surveys with cross-validation measured and established between the two groups. The findings showed that social integrative motivations positively impacted consumption behaviour across game genres. Affective motivation partially mediated the relationship between social integrative motivation and consumption behaviour in LOL, and cognitive and personal integrative motivations positively influenced consumption behaviour in Hearthstone. The tension-release motivation had no significant association with consumption behaviour for spectators of either game. The findings can help the commercial interests of different esports game genres to predict why people consume particular esports and thus aid effective marketing strategies

JNK suppression is essential for 17β-Estradiol inhibits prostaglandin E2-Induced uPA and MMP-9 expressions and cell migration in human LoVo colon cancer cells

<p>Abstract</p> <p>Background</p> <p>Epidemiological studies demonstrate that the incidence and mortality rates of colorectal cancer in women are lower than in men. However, it is unknown if 17β-estradiol treatment is sufficient to inhibit prostaglandin E2 (PGE2)-induced cellular motility in human colon cancer cells.</p> <p>Methods</p> <p>We analyzed the protein expression of urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA), matrix metallopeptidases (MMPs), plasminogen activator inhibitor-1 (PAI-1) and tissue inhibitor of metalloproteinases (TIMPs), and the cellular motility in PGE2-stimulated human LoVo cells. 17β-Estradiol and the inhibitors including LY294002 (Akt activation inhibitor), U0126 (ERK1/2 inhibitor), SB203580 (p38 MAPK inhibitor), SP600125 (JNK1/2 inhibitor), QNZ (NFκB inhibitor) and ICI 182 780 were further used to explore the inhibitory effects of 17β-estradiol on PGE2-induced LoVo cell motility. Student's t-test was used to analyze the difference between the two groups.</p> <p>Results</p> <p>Upregulation of urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA) and matrix metallopeptidases (MMPs) is reported to associate with the development of cancer cell mobility, metastasis, and subsequent malignant tumor. After administration of inhibitors including LY294002, U0126, SB203580, SP600125 or QNZ, we found that PGE2 treatment up-regulated uPA and MMP-9 expression via JNK1/2 signaling pathway, thus promoting cellular motility in human LoVo cancer cells. However, PGE2 treatment showed no effects on regulating expression of tPA, MMP-2, plasminogen activator inhibitor-1 (PAI-1), tissue inhibitor of metalloproteinase-1, -2, -3 and -4 (TIMP-1, -2, -3 and -4). We further observed that 17β-estradiol treatment inhibited PGE2-induced uPA, MMP-9 and cellular motility by suppressing activation of JNK1/2 in human LoVo cancer cells.</p> <p>Conclusions</p> <p>Collectively, these results suggest that 17β-estradiol treatment significantly inhibits PGE2-induced motility of human LoVo colon cancer cells.</p

Combined Phytochemistry and Chemotaxis Assays for Identification and Mechanistic Analysis of Anti-Inflammatory Phytochemicals in Fallopia japonica

Plants provide a rich source of lead compounds for a variety of diseases. A novel approach combining phytochemistry and chemotaxis assays was developed and used to identify and study the mechanisms of action of the active compounds in F. japonica, a medicinal herb traditionally used to treat inflammation. Based on a bioactivity-guided purification strategy, two anthranoids, emodin and physcion, were identified from F. japonica. Spectroscopic techniques were used to characterize its crude extract, fractions and phytochemicals. The crude extract, chloroform fraction, and anthranoids of F. japonica significantly inhibited CXCR4-mediated chemotaxis. Mechanistic studies showed that emodin and physcion inhibited chemotaxis via inactivating the MEK/ERK pathway. Moreover, the crude extract and emodin could prevent or treat type 1 diabetes in non-obese diabetic (NOD) mice. This study illustrates the applicability of a combinational approach for the study of anti-inflammatory medicine and shows the potential of F. japonica and its anthranoids for anti-inflammatory therapy

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

Treating VX2 Tumor in Liver by Percutaneous

經皮注射酒精是目前常用於治療小型肝癌(小於直徑3.0cm)的治療方法，但是由於酒精會造成肝細胞的毒性，所以併用一些中國傳統草藥萃取出來的純物質─黃酮類(Flavonoid)化合物作為肝癌治療藥物，期望能有酒精殺滅腫瘤細胞的能力並且能夠有發揮保護肝細胞的功能。在體外實驗部分，以人類的肝癌細胞株(HepG2 及 Chang liver cell line )作為實驗材料，並將AP-1(Activator Protein-1)結合序列/報導基因(Luciferase)重組到肝癌細胞形成HepG2/AP-1 及 Chang liver/AP-1 重組細胞。以常用的腫瘤促進劑TPA(12-o-teradecanoylphorbol- 13-acetate)處理重組細胞後，用MTT(3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)來判斷細胞經過24種黃酮類化合物處理後之細胞存活率及計算藥物的半致死劑量，並測量細胞裡的AP-1活性(Luciferase assay)，最後選取可有效抑制肝癌重組細胞生長的黃酮類化合物(Quercetin)進行肝癌動物模式之實驗。實驗動物模式方面，選用兔子之VX2肝癌模式，將VX2細胞接種於兔子肝臟，兩週後使用電腦斷層掃描(CT)監測腫瘤之大小，待肝臟腫瘤直徑約2.0-3.0cm時，再經CT引導在腫瘤原位注射酒精併用Quercetin、酒精併用Daunorubicin及無水酒精進行治療，之後以CT追蹤並評估療效。 結果顯示，本實驗使用之24種黃酮類藥物中，抑制肝癌重組細胞株之AP-1表現方面，以Flavonols類(Quercetin)最為明顯。動物實驗方面。酒精併用Quercetin及無水酒精可以使得腫瘤細胞壞死而達到抑制腫瘤生長的效果，而酒精併用Daunorubicin並不能有效的殺滅腫瘤細胞及抑制腫瘤生長。酒精併用Quercetin療法運用在兔肝癌實驗上能有效抑制腫瘤生長並且可能有保護肝細胞的功能，期望未來能夠運用在人類肝癌的治療。Percutaneous ethanol injection (PEI) is a common treatment of small hepatocellular carcinoma (HCC) where the diameter of the tumor is 3 cm or less. However, PEI may cause cytotoxic effects to normal liver cells. In this study, we used ethanol combined with flavonoid compounds extracted from Chinese herb to treat the liver cancer. In the in vitro studies, we selected 24 flavonoids to pre-treat HepG2/AP-1 and Chang liver/AP-1 recombinant cells before the cells were exposed to TPA (12-o-teradecanoylphorbol-13- acetate), a tumor promoter. MTT (3-(4,5-dimethy lthiazol -2-yl)-2,5- diphenyltetrazolium bromide) assay was used to define the survival rate of the recombinant cells after flavonoid treatment and the 50% lethal dose (LD50) of flavonoid were calculated. The flavonoid with the best protective effect to the recombinant cancer cells was then subjected further to the developed VX2 animal model study. In the animal model, VX2 cells were implanted into the left liver of rabbit.and computed tomography (CT) was used to monitor the tumor growth until the tumor was two to three cm in diameter. CT was also used to guide intratumoral injections of ethanol, Quercetin with ethanol and Daunorubicin with ethanol as well as, to evaluate the treatment effects. The results indicated that the Flavonols can inhibit Ap-1 upregulation in the hepatoma recombinant cells. Ethanol alone and Quercetin with ethanol can induce tumor cell necrosis and inhibit tumor growth in the animal model while Daunorubcin with ethanol can not. We conclude that the combination of Quercetin and ethanol is inhibitive to VX2 tumor cells with potential protective effects to normal liver cells.目錄 目錄 I 圖次 III 表次 IV 中文摘要 V 英文摘要 VI 第一章 前言 1 第二章 文獻探討 第一節 肝癌的重要性 2 第二節 肝癌的診斷方法與治療方法 2 第三節 肝臟的解剖生理 10 第四節 肝癌的動物模式(以兔VX2為animal model) 12 第五節 人類肝癌細胞株Hep/G2與Chang liver 及Active protein-1(AP-1) 13 第六節 黃酮類化合物 15 第三章 材料與方法 體外試驗部分(In Vitro) 17 動物實驗部分(In Vivo) 18 第四章 結果 體外試驗部分(In Vitro) 黃酮類可調控AP-1的活性 28 黃酮類化合物(Quercetin)與臨床抗腫瘤藥物( Daunorubicin)對肝癌細胞之作用 29 動物實驗部分(In Vivo) 預備實驗的結果 30 正式實驗結果 31 血液學分析 36 病理學結果 37 第五章 討論 第一節 肝臟VX2腫瘤的誘導 45 第二節 經皮電腦斷層掃描引導腫瘤內注射藥物 46 第三節 療效分析 48 第六章 結論 50 第七章 參考文獻 5

Exendin-4,一種昇糖素類似胜肽-1,改善db/db糖尿病小鼠之李斯特菌感染

糖尿病在人與動物都會產生相似的症狀，伴侶動物發生糖尿病的機率逐漸上升。糖尿病被認為是感染的風險因子且會因為感染而造成死亡。在本研究裡，以糖尿病治療藥物Exendin-4（一種昇糖素類似胜肽-1）處理db/db糖尿病小鼠在李斯特菌感染的影響。在老年的db/db糖尿病小鼠，觀察到有CD11b+巨噬細胞的數量減少及巨噬細胞內有高脂肪含量且吞噬能力降低的現象。Exendin-4可以降低db/db糖尿病小鼠的巨噬細胞內脂肪含量與增強其吞噬作用進而改善db/db小鼠對抗李斯特菌感染。Exendin-4也改善db/db糖尿病小鼠肥胖及高血糖症狀，且在擬體內試驗(ex vivo)中增加巨噬細胞對細菌清除率。在Exendin-4處理的db/db小鼠受到李斯特菌感染後的肝臟呈現較少的膿瘍。在Exendin-4處理過的db/db糖尿病小鼠分離的巨噬細胞上，我們證實了ABCA1(ATP binding cassette transporter 1)一種膽固醇的傳送器，表現量較高。總之，我們的結果指出Exendin-4藉由調控巨噬細胞內的脂肪含量及吞噬作用來減少糖尿病動物感染的風險。This diabetes mellitus has similar characteristics in both humans and animals. The incidence of this disease is increasing among companion animals. Diabetes is frequently identified as an independent risk factor for infections associated with increased mortality. In this study, homozygous diabetic (db/db) mice were infected with Listeria monocytogenes and then treated with the diabetic treatment drug Exendin-4, a glucagon-like peptide 1 analogue. In aged db/db mice, decreased CD11b+ macrophage populations with higher lipid content and lower phagocytic activity were observed. Exendin-4 lowered high lipid levels and enhanced phagocytosis in macrophages from db/db mice infected with L. monocytogenes. Exendin-4 also ameliorated obesity and hyperglycemia, and improved ex vivo bacteria clearance by macrophages in the diabetic animals. Liver histology examined during L. monocytogenes infection indicated that abscess formation was much milder in Exendin-4 treated db/db mice than in the control animals. Moreover, the expression of ATP binding cassette transporter 1, a sterol transporter, in the macrophages isolated from the Exendin-4 treated db/db mice was higher than the untreated group. Overall, our results indicated that Exendin-4 reduces the risk of infection in diabetic animals by modulating the interaction between intracellular lipids and phagocytic ability of macrophages致謝………………………………………………………………… ii 摘要………………………………………………………………… iii Abstract…………………………………………………… iv 目次………………………………………………………………… v 表目次……………………………………………………………… viii 圖目次……………………………………………………………… ix 第一章 前言………………………………………………… 1 第二章 文獻探討………………………………………………… 2 第1節 糖尿病的介紹………………………………… 2 1-1 糖尿病的盛行率………………………………… 2 1-2 第二型糖尿病的症狀………………………… 2 1-3 第二型糖尿病的臨床治療藥物介紹…………3 1-4 db/db糖尿病小鼠之介紹……………………………3 第2節 腸泌素GLP-1類似物Exendin-4之介紹……………4 2-1 腸泌素(incretin)的介紹………………………………4 2-2 腸泌素的功能………………………………………… 5 2-3 腸泌素在治療糖尿病上遭遇的問題與解決方式…… 5 2-4 GLP-1類似物(Exendin-4)的介紹………………… 6 第3節 免疫在糖尿病的環境下造成的影響………………… 7 3-1 糖尿病與免疫之間的相互關係……………………… 7 3-2 糖尿病病患與感染之間的相互關係………………… 8 3-3 糖尿病病患主要常見的感染疾病…………………… 8 3-4 糖尿病病患與李斯特菌感染的相關性……………… 8 第三章 材料與方法……………………………………………… 10 一、藥物、細菌菌株及實驗動物……………………………… 10 二、以流式細胞儀測量老鼠腹腔灌洗細胞(Peritoneal exudate cells；PEC)之CD11b+，及(ATP binding cassette transporter 1；ABCA1的表現及脂肪含量……………………………… 10 三、老鼠Exendin-4給予方式及測量給藥及對照老鼠的血糖值、膽固醇、三酸甘油酯、低密度脂蛋白及高密度脂蛋白……………………………… 11 四、腹腔灌洗細胞來源的巨噬細胞吞噬能力測定……………11 五、老鼠李斯特菌攻毒試驗及病理學檢驗…………………… 12 六、統計分析…………………………………………………… 13 第四章 結果……………………………………………………… 14 一、db/m及db/db小鼠的巨噬細胞數量的差別…………… 14 二、從db/m及db/db小鼠取得腹腔灌洗細胞之脂肪含量比較………………………………………………………… 14 三、從db/m及db/db小鼠取得腹腔灌洗細胞之吞噬能力差 別…………………………………………………… 14 四、經Exendin-4處理過後db/db小鼠巨噬細胞的吞噬能力 及脂肪含量、ABCA1表現與不給藥的對照組比較……… 15 五、以Exendin-4處理過後db/db小鼠血清中之血糖、三酸 甘油脂、總膽固醇、低密度及高密度脂蛋白濃度與不給 藥的對照組比較………………………………………… 15 六、擬體內試驗進行細菌的廓清率比較…………………… 16 七、經Exendin-4或無處理的db/db小鼠感染李斯特菌之病理學檢驗及李斯特菌感染肝臟病灶區的差別……………… 16 第五章 討論……………………………………………………… 24 參考文獻…………………………………………………………… 28 附錄 修業期間發表論文………………………………………… 3

Revisit service classification to construct a customer-oriented integrative service model

[[abstract]]Purpose – The purpose of this paper is to construct a customer-oriented integrative service model based on the generic service process. Business strategies can then be formulated by using the model. Design/methodology/approach – The key classifying dimensions and their respective attributes are identified through literature reviews. Operational dimensions are formed by combining their attributes weighted by manager-determined importance weights (IW). A generalized mathematical model is built to integrate the core services of a firm with customer-based performance weight (PW). The integrative service model is constructed by combining the operational dimensions. Findings – The selected classification model covers knowledge, information and virtual space dimensions that most of the previous service-process based model lack. The developed model is simpler to understand and to use for managers comparing to the other complicated mathematical models. Research limitations/implications – Empirical studies need to be done to test the effectiveness of the model. Experienced managers are needed to decide the IW. Practical implications – Managers can use the developed model to formulate integrated business strategies as well as forecasting competitor's strategies. The developed model is a customer-oriented approach for service strategy formulation. Originality/value – A generalized mathematical model is derived for a firm offering “n” kinds of core services. Computer software can be written based on it to handle the complex cases.[[journaltype]]國

Analysis and Design of Three-Phase LLC Resonant Converter with Matrix Transformers

This study presents the topology of a three-phase LLC resonant converter with matrix transformers. The three-phase LLC resonant converter has the advantages of conventional LLC resonant converters, including zero-voltage switching at the primary side, zero-current switching at the secondary side, high-frequency feasibility, and high efficiency. Moreover, it has additional advantages that differ from conventional LLC, including low output capacitor current ripple, natural current sharing in three resonant currents, and a high power level. As a result of the above mentioned characteristics, LLC topology has been used in many electric vehicle charging systems, server power systems, and other high-power applications. However, as the power level becomes higher and higher, the input voltage is usually too high to reduce conduction loss, and the output current also increases. This situation makes transformer design more difficult. The increasing current means more core and copper loss, and the heat dissipation of the transformer becomes more difficult. Matrix transformer technology can improve this problem directly and simply. By utilizing matrix transformers, which are primary series connected and secondary parallel connected, the primary voltage stress and secondary current stress of the transformers can be reduced, and the output current can be distributed. The analysis of the proposed converter in this study includes a circuit operation introduction, a time-domain analysis, calculation of the transfer ratio curve in the frequency domain, and a loss analysis. The theoretical analysis and performance of the proposed converter are verified. A three-phase LLC resonant converter with matrix transformers prototype is built with a high input voltage of 800-VDC and high output current of 200-A. The output voltage is 100-VDC. The waveform and efficiency data will be shown in the experimental results

Analysis and Design of Three-Phase LLC Resonant Converter with Matrix Transformers

This study presents the topology of a three-phase LLC resonant converter with matrix transformers. The three-phase LLC resonant converter has the advantages of conventional LLC resonant converters, including zero-voltage switching at the primary side, zero-current switching at the secondary side, high-frequency feasibility, and high efficiency. Moreover, it has additional advantages that differ from conventional LLC, including low output capacitor current ripple, natural current sharing in three resonant currents, and a high power level. As a result of the above mentioned characteristics, LLC topology has been used in many electric vehicle charging systems, server power systems, and other high-power applications. However, as the power level becomes higher and higher, the input voltage is usually too high to reduce conduction loss, and the output current also increases. This situation makes transformer design more difficult. The increasing current means more core and copper loss, and the heat dissipation of the transformer becomes more difficult. Matrix transformer technology can improve this problem directly and simply. By utilizing matrix transformers, which are primary series connected and secondary parallel connected, the primary voltage stress and secondary current stress of the transformers can be reduced, and the output current can be distributed. The analysis of the proposed converter in this study includes a circuit operation introduction, a time-domain analysis, calculation of the transfer ratio curve in the frequency domain, and a loss analysis. The theoretical analysis and performance of the proposed converter are verified. A three-phase LLC resonant converter with matrix transformers prototype is built with a high input voltage of 800-VDC and high output current of 200-A. The output voltage is 100-VDC. The waveform and efficiency data will be shown in the experimental results