Chung Hwa University of Medical Technology
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A study on the topgraphical correlations of the Jiang clean in Zhuwei with Lutaoyang and others during of the Ta-pa-ni Incident slaughter story
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Studing the signal transduction pathway of thymic stromal lymphopoietin in TGF-beta 1induced renal and lung cellular fibrosis
No full text[[abstract]]糖尿病與肺炎是國人十大死因第四名與第六名，病程中分別會發展成腎纖維化與肺纖維化。許多研究指出生長因子間的表現失衡正是造成糖尿病腎纖維化與肺纖維化的主因。目前研究發現胸腺基質淋巴生成素（TSLP）與發炎疾病有著直接關聯。然而，沒有文獻指出TSLP所誘導的發炎反應是跟纖維化有關。因此，我們研究TSLP在NRK（腎臟纖維母細胞）與HFL-1（肺臟纖維母細胞）中的角色。然而，第一型乙型轉型生長因子（TGF-beta 1）是多功能性的細胞激素並且扮演引起腎纖維化與肺纖維化的重要角色。因此，本研究以第一型乙型轉型生長因子刺激腎臟纖維母細胞（NRK-49F）與肺臟纖維母細胞（HFL-1）進行體外培養，模擬腎細胞與肺細胞纖維化。接著，我們以酵素連結免疫吸附分析法與西方墨點法在TGF-beta 1（0.1、1或10 ng/mL）劑量和時間點下，發現NRK-49F 和HFL-1細胞外與細胞內中的TSLP隨著TGF-beta 1 劑量增加而上升。此外，加入外源性的TSLP（1、10 或100 ng/mL）劑量刺激下，會誘導NRK-49F 和HFL-1中纖維蛋白的增加。因此，我們以單獨（TGF-beta 1,TSLP）及協同的方式探討TGF-beta 1 與受器結合後Smad蛋白與其磷酸化程度的改變，發現在NRK-49F中不影響Smad蛋白（Smad2/3、pSmad2/3與Smad4）的表現，但會影響MAPK路徑（Raf-1、ERK-1與MEK-1）的表現。在HFL-1中，外源性的TSLP（1、10 或100 ng/mL）劑量刺激下，會影響Smad蛋白（Smad2/3、pSmad2/3與Smad4）的表現。另外，並探討施以抗發炎因子（如TSLP shRNA）對纖維化抑制的可行性。因此本研究主要探討TGF-beta 1 誘導的腎細胞纖維化與肺細胞纖維化的過程與TSLP的關係並且以TSLP shRNA抗纖維化作用機轉。
Diabetes and Pulmonary is the 4th and 6th leading causes of death in Taiwan. Many studies have demonstrated that dysregulation of growth factors might be the maincauses underlying the mechanism of diabetic renal fibrosis and Pulmonary fibrosis. The cytokine thymic stromal lymphopoietin (TSLP) has been linked to inflammatory diseases. None literature indicate TSLP induced the expression of inflammation response to correlate of fibrosis. Thus, we investigated the role of TSLP in NRK-49F cells (rat fibroblasts) and HFL-1 cells (lung fibroblasts).
Transforming growth factor (TGF)-beta 1 is a multifunctional cytokine which also plays an important role in progressive renal and lung fibrosis. In this study, we used TGF-beta 1 induces renal and lung cellular fibrosis expression of TSLP. Moreover, exogenous TSLP significantly induce the expression of fibronectin in NRK-49F and HFL-1 cells.
After inducing renal and lung cellular fibrosis by TGF-beta 1 and post-receptor signaling molecules (Smads and MAPK pathway) will be systemically investigated to elucidate the interactions between TSLP, renal and lung fibrosis. In addition, We show here TSLP expression was increased in the renal and lung fibroblast. Moreover, the feasibility using dual strategies by anti-inflammatory factor (i.e. TSLP shRNA) to control renal and lung fibrosis will also be examined in this project
Characterization of mutation UGT1A4 in Taiwan colorectal cancer patients
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研究生口試委員會審定書 i
博碩士論文電子檔案上網授權書 ii
中文摘要 iii
英文摘要 v
誌謝 vii
目錄 viii
第一章 文獻回顧 1
第一節 大腸癌簡介 1
第二節 致癌物質與代謝酵素之簡介 6
第三節UDP glucuronosyl transferase簡介 8
第四節Tamoxifen(TAM)之相關研究 11
第二章 研究目的 16
第三章 材料與方法 18
第一節 檢體收集 18
第二節 UDP glucuronosyl transferase 1A4 基因多型性分析 18
第三節 UGT1A4基因的選殖 28
第四節 HPLC 分析 46
第五節 統計方法 50
第四章 結果 51
第五章 討論 55
第六章 結論 58
參考文獻 60
表與圖 72
圖表目錄
Table 1. 2008 the leading causes of death for cancer in Taiwan…….…………….72
Table 2. Anticancer and carcinogenic substrates of UGT1A isozymes……………..73
Table 3. UGT1A4 mutation primer sequence………...............................................74
.
Table 4. Difference in distribution of UGT1A4 SNP in patients…..………...........75
Table 5. UGT1A4 exon1(wild type) primer sequence…..…………………...........76
Table 6. Kinetic analysis of UGT1A4-induced glucuronidation of 4-hydroxytamoxifen…..……………….………………………..…...........77
Fig 1.Xenobiotic chemicals mechanism of UGTs isozymes…………………………78
Fig 2. Schematic of the UGT1A gene complex………………………………………79
Fig 3.Structures of TAMs…………………………………………………….………80
Fig 4. Structures of HO-TAM…………………………………….…………….……81
Fig 5. Western blot analysis of UGT1A4 protein from UGT1A4-overexpress-
ing cell lines.…………………………………………………………………………82
Fig 6. p3xflag-cmv10 vector map……………………………….…………..………83
Fig 7. UGT1A4 Site-directed mutagenesis Sequencing ( Reverse )…………………84
Fig 8. HPLC analysis of propranol standard cure (0.625、1.25、2.5、3.75、5µg/mL)…………………………………………………………………………....…85
Fig 9. HPLC analysis of 4-hydroxytamoxifen HPLC analysis of 4-hydroxytamoxifen glucuronides formed by cell microsomes , internal propranolol only………..………86
Fig 10. HPLC analysis of 4-hydroxytamoxifen standard cure (0、0.65、12.5、25、37.5、50mM)…………………………….…….………………………………….…87
Fig 11. HPLC analysis of 4-hydroxytamoxifen HPLC analysis of 4-hydroxytamoxifen glucuronides formed by cell microsomes , internal 4-OH-TAM only..………………88
Fig 12. HPLC analysis of 4-hydroxytamoxifen HPLC analysis of 4-hydroxytamoxifen glucuronides formed by cell microsomes , internal 4-OH-TAM and standard (propranolol) ………………………………………………………………….….…89
Fig 13. HPLC analysis of 4-hydroxytamoxifen HPLC analysis of 4-hydroxytamoxifen glucuronides formed by cell microsomes , internal protein …………………..….…90
Fig 14. HPLC analysis of 4-hydroxytamoxifen HPLC analysis of 4-hydroxytamoxifen glucuronides formed by cell microsomes , internal 4-OH-TAM and standard (propranolol), UGT1A4 Wild type overexpressing cell protein ……………….……91
Fig 15. HPLC analysis of 4-hydroxytamoxifen HPLC analysis of 4-hydroxytamoxifen glucuronides formed by cell microsomes , internal 4-OH-TAM and standard (propranolol), UGT1A4 UGT1A4 128G>A overexpressing cell protein……………92
Fig 16. HPLC analysis of 4-hydroxytamoxifen HPLC analysis of 4-hydroxytamoxifen glucuronides formed by cell microsomes , internal 4-OH-TAM and standard (propranolol), UGT1A4 UGT1A4 134G>A overexpressing cell protein……………93
Fig 17. HPLC analysis of 4-hydroxytamoxifen HPLC analysis of 4-hydroxytamoxifen glucuronides formed by cell microsomes , internal 4-OH-TAM and standard (propranolol), UGT1A4 UGT1A4 128 G>A 134G>A overexpressing cell protein…94
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Zheng, Z., Park, J.Y., Guillemette,
Determination of trace elements in Taiwan herbs infusions by flame atomic absorption spectrometry coupled with STAT
No full text第一章 研究背景與目的 - 1 -
第一節 台灣草藥飲用背景 - 1 -
第二節 微量元素之簡介 - 4 -
第三節 原子吸收光譜儀的簡介 - 8 -
第四節 火焰式原子吸收光譜儀儀器及原子捕捉器的簡介 - 10 -
第五節 研究目的 - 13 -
第二章 材料與研究方法 - 14 -
第一節 儀器設備 - 14 -
第二節 試劑 - 15 -
第三節 實驗器皿之清洗 - 15 -
第四節 溶液配製 - 16 -
第五節 中草藥樣品處理 - 21 -
2-5-1 樣品乾燥 - 21 -
2-5-2 青草沖泡液配置 - 21 -
2-5-3 樣品消化 - 22 -
第六節 方法驗證 - 23 -
2-6-1 檢量線 - 23 -
2-6-2 準確度 - 23 -
2-6-3 精密度 - 24 -
2-6-4 偵測極限 - 24 -
2-6-5 定量極限 - 24 -
2-6-6 污染控制 - 24 -
第三章 結果與討論 - 26 -
第一節 樣品前處理 - 26 -
3-1-1青草樣品－微波消化 - 26 -
3-1-2青草沖泡液－乾式加熱消化 - 26 -
第二節 最佳化條件 - 27 -
3-2-1 氣體流速 - 27 -
3-2-2 燃燒頭高度 - 27 -
第三節 分析方法驗證 - 28 -
3-3-1檢量線 - 28 -
3-3-2準確度 - 32 -
3-3-3精密度 - 34 -
3-3-4偵測極限及定量極限 - 36 -
第三節 分析方法應用 - 37 -
3-2-1 青草沖泡液及青草中元素含量測定 - 37 -
3-2-2 應用STAT-FAAS與FAAS測定元素之比較 - 39 -
3-2-3 青草沖泡液與青草中元素含量絕對值比較 - 40 -
第四章 結論 - 42 -
參考文獻 - 43 -
附錄. - 47 -
表一、微波消化系統針對九種草藥之最佳消化條件 - 48 -
表二、火燄式原子吸收光譜儀各元素最佳化條件 - 49 -
表三、肝炎草沖泡消化液添加回收率 - 50 -
表四、艾草沖泡消化液添加回收率 - 52 -
表五、七層塔沖泡消化液添加回收率 - 54 -
表六、肝炎草消化液添加回收率 - 56 -
表七、艾草消化液添加回收率 - 57 -
表八、七層塔消化液添加回收率 - 58 -
表九、以FAAS及STAT-FAAS測定鋅標準品精密度結果 - 59 -
表十、以FAAS及STAT-FAAS測定鎘標準品精密度結果 - 60 -
表十一、以FAAS及STAT-FAAS測定銅標準品精密度結果 - 61 -
表十二、以FAAS及STAT-FAAS測定錳標準品精密度結果 - 62 -
表十三、以FAAS及STAT-FAAS測定鎳標準品精密度結果 - 63 -
表十四、以FAAS及STAT-FAAS測定鐵標準品精密度結果 - 64 -
表十五、以FAAS及STAT-FAAS測定鉛標準品精密度結果 - 65 -
表十六、火燄式原子吸收光譜儀各元素之LOD、LOQ - 66 -
表十七 、火燄式原子吸收光譜儀測定草藥沖泡液元素含量 - 67 -
表十八 、火燄式原子吸收光譜儀測定草藥元素含量 - 68 -
表十九 、使用FAAS與STAT-FAAS測定草藥沖泡液元素含量 - 69 -
表二十 、火燄式原子吸收光譜儀測定草藥沖泡液、草藥消化液元素含量之百分比（％） - 70 -
表二十一、膳食營養素參考攝取量 - 71 -
表二十二、食品中一般常見重金屬含量的容許量 - 72 -
圖一、STAT接合FAAS火焰頭示意圖 - 73 -
圖二、以FAAS測定鋅標準品檢量線結果 - 74 -
圖三、以STAT-FAAS測定鋅標準品檢量線結果 - 75 -
圖四、以FAAS測定鎘標準品檢量線結果 - 76 -
圖五、以STAT-FAAS測定鎘標準品檢量線結果 - 77 -
圖六、以FAAS測定銅標準品檢量線結果 - 78 -
圖七、以STAT-FAAS測定銅標準品檢量線結果 - 79 -
圖八、以FAAS測定錳標準品檢量線結果 - 80 -
圖九、以STAT-FAAS測定錳標準品檢量線結果 - 81 -
圖十、以FAAS測定鎳標準品檢量線結果 - 82 -
圖十一、以STAT-FAAS測定鎳標準品檢量線結果 - 83 -
圖十二、以FAAS測定鐵標準品檢量線結果 - 84 -
圖十三、以STAT-FAAS測定鐵標準品檢量線結果 - 85 -
圖十四、以FAAS測定鉛標準品檢量線結果 - 86 -
圖十五、以FAAS-STAT測定鉛標準品檢量線結果 - 87 -
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40. 國人膳食營養素參考攝取量. 行政院衛生署消費者資訊網, 2006.[[abstract]]在全球各地廣泛的使用有療效性的植物及其製劑（包含冷或熱的沖泡液）。亞洲國家在使用草藥時，通常是在植物自然狀態下使用，像乾燥的花草和根莖。毒性元素會污染這些植物，這牽涉到許多複雜的潛在因素，如品種、收割與處理過程、污染物濃度和暴露的時間、地形、地質及儲存方式。本研究藉由火焰式原子吸收光譜法（Flame Atomic Absortion Spectrophotometry）和原子捕捉器-火焰原子吸收光譜法（Slotted Tube Atom Trap - Flame Atomic Absorption Spectrometry, STAT-FAAS），測定台灣台南市所販售的九種草藥中元素濃度。藉由原子捕捉器提升火焰式原子吸收光譜法的靈敏度。在樣品的處理上使用草藥的沖泡液，以超純硝酸做乾式加熱方法消化。研究中測定7種元素，包含：鐵、銅、鋅、錳、鎘、鎳、鉛。結果顯示在草藥沖泡液中測的銅 0.2－2.475 mg/kg，鐵 4.875－60.45 mg/g，錳0.475－19.8 mg/kg，鋅1.125－18.9 mg/kg。鎘、鎳、鉛其所測得的數值低於本實驗的偵測極限。本實驗之偵測極限分別為：鎳：0.052 ppm，鎘 ：0.010 ppm，鉛：0.081 ppm。本研究中，樣品沖泡液的製備如一般民眾飲用草藥前的處理方法。然而，這些草藥材很容易受到污染，包括種植和加工過程。期望本實驗能夠提供一個快速的檢測方式來測定草藥中的微量元素濃度。
Medicinal herbs and their preparations (hot and cold infusions) are widely used by human beings all over the world. Asian countries use herbal remedies more in their natural states, like dried herbs and roots. The potential contamination of raw herbal products with toxic elements depends on many complex factors like species, cultivation, processing, harvesting time, level and duration of contaminant exposure, topography, geographical origin, storage. The determinations were performed using flame atomic absorption spectrometry (FAAS ) and slotted tube atom trap - flame atomic absorption spectrometry (STAT-FAAS ). Sensitivity enhancement by using atom trapping in flame atomic absorption spectrophotometry was examined for increasing the residence time of the analyte atoms in the light path. The infusion samples were digested by superpure nitric acid. In this present, the following elements were determined in the leaf infusion : Fe, Cu, Zn, Mn, Cd, Ni and Pb. The metal content of infusion samples were ranged from 0.2–2.475 mg/kg for Cu, 4.875 to 60.45 mg/g for Fe, 0.475 to 19.8 mg/kg for Mn, 1.125 to 18.9 mg/kg for Zn. Pb, Ni and Cd were not detected (limit of quantitation of Ni: 0.052 ppm, Cd :0.010 ppm, Pb: 0.081 ppm).For the sake of representing daily average uptake of elements, the infusion samples were prepared normally as tea. However, medicinal herbs may be contaminated easily during growing and processing. It is important to have a good quality control for herbal medicines in order to protect consumers from contamination
IHG-1 and Myb/Dmp1 Play the Novel Roles in the Pathogenesis of Diabetic Nephropathy
No full text研究領域:臨床醫學類, 生物技
Functional Study of Phosphorylation of Human PGC-1 Protein
No full text研究領域:基礎醫學類, 生物科學類
計畫編號:NSC97-2320-B273-002-MY
