Increasing levels of circulating Th17 cells and interleukin-17 in rheumatoid arthritis patients with an inadequate response to anti-TNF-α therapy

Introduction: The objective of this study was to investigate the effects of tumor necrosis factor (TNF)-alpha inhibitors on circulating T helper-type 17 (Th17) cells and Th17-related cytokines in patients with rheumatoid arthritis (RA). Methods: The frequencies of circulating Th17 cells and serum levels of Th17-related cytokines were determined using flow cytometry analysis and ELISA, respectively, in 48 RA patients both before (baseline) and six months after anti-TNF-alpha therapy. Therapeutic response was evaluated using European League Against Rheumatism (EULAR) response criteria. Results: Significantly higher baseline frequencies of circulating Th17 cells and serum levels of interleukin (IL)-6, IL17, IL-21, IL-23 and TNF-alpha were observed in active RA patients than in 12 healthy controls (all P < 0.001). After anti-TNF-alpha therapy, 36 patients (75%) were EULAR responders (20 good responders and 16 moderate responders) and 12 (25.0%) were non-responders. The mean levels of circulating Th17 cells and IL-17 significantly decreased (1.13% vs. 0.79%; 43.1 pg/ml vs. 27.8 pg/ml; respectively, both P < 0.001) in parallel with clinical remission in responders. Levels of IL-6, IL-21, IL-23 and TNF-alpha were significantly decreased after anti-TNF-alpha therapy in responders. In contrast, the mean levels of circulating Th17 cells and IL-17 significantly increased after anti-TNF-alpha therapy (2.94% vs. 4.23%; 92.1 pg/ml vs. 148.6 pg/ml; respectively, both P < 0.05) in non-responders. Logistic regression analysis identified a high baseline level of IL-17 as a significant predictor of poor therapeutic response. Conclusions: The beneficial effect of anti-TNF-alpha therapy might involve a decrease in Th17-related cytokines in responders, whereas rising levels of circulating Th17-cells and IL-17 were observed in patients with an inadequate response to anti-TNF-alpha therapy

Leaf Extracts of Calocedrus formosana (Florin) Induce G2/M Cell Cycle Arrest and Apoptosis in Human Bladder Cancer Cells

Calocedrus formosana (Florin) bark acetone/ethylacetate extracts are known to exert an antitumor effect on some human cancer cell lines, but the mechanism is yet to be defined. The aim of this study was to determine the effects of Florin leaf methanol extracts on the growth and apoptosis of human bladder cancer cell lines. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay showed that the growth of these bladder cancer cells was potently inhibited by the Florin leaf extracts. The cell cycle of these extract-treated cells (TCCSUP cells) was arrested at the G2/M phase as determined by flow cytometry. Western blot analysis revealed the increases of cyclin B1 and Cdc2 kinase levels, alone with the decrease of phosphorylated Cdc2 kinase, after treating these cells with the extracts. An immunofluorescence assessment of β-tubulin showed decreased levels of polymerized tubulin in treated cells. However, the proteolytic cleavage of poly ADP-ribose polymerase and the activation of caspase-3/-8/-9 were all increased upon treatments of extracts. The concurrent increase of Bax and decrease of Bcl-2 levels indicated that the extracts could induce apoptosis in these treated cells. Taken together, these results suggest that the Florin leaf extracts may be an effective antibladder cancer agent

本校における幼児発達相談室の取り組み(2) : 小集団によるコミュニケーション支援(幼児教室グループ(2))

金沢大学教育学部附属養護学校小学部金沢大学教育学部附属養護学校小学部金沢大学教育学部附属養護学校小学部金沢大学教育学

大学を拠点に保育者志望学生と多世代が交流する新しい子育て支援の実践 : 「そうじゃ子ども大学」の事例から

This study aimed to examine the “Soja Children’s University”, a practice of a new child-rearing support method. This research study organized the implementation structure and the ideal form of coordination between the university and the local community and further examined the way in which the participating students learned. Through analysis of post-event self-examination, classifications of learning were made in areas such as making new discoveries regarding child rearing, children behavior, family diversity, various insights into how child-rearing support should be provided, the value of real experience, and the significance of parent–child play. Based on what was gathered by the university students who participated in this program, it is possible to enhance the students’practical learning regarding the state of families with young children and how to support them

微流體生醫光電異質整合感測晶片應用於螢光免疫分析-子計畫二：微流體生醫光電感測晶片應用於抗體螢光免疫分析及綠色螢光蛋白質偵測之標準實驗流程建立

In this sub-project, we focus on the three biomarkers about human tumor based on the Antibody-linkedimmunofluorescence assay technique. These three biomarkers are HER-2/neu, PSA (prostate-specificantigen), VEGF (vascular endothelial growth factor). It is been defined that HER-2/neu is a highly expressiongene when the tumor is growing in breast, lung, cervix, ovarian, and bladder. Combining the developedminimized biomedical optoelectronic sensing system, we cannot only reduce the buffer solution and thesample, but also simplify the detection standard procedure. After the first mission - define the standardprocedure for micro-sensing chip and confirm the reliability and repeatability, the fluorescence particle on thesecond antigen is replaced by green fluorescence protein. Follow the same flow to define the procedure.Eventually, the GFP can be applied in the field about the transgenic in vivo and in vitro. We hope this fast andlow cost sensing chip and the standard procedure can help the development of Molecular Biotechnology.在本子計畫中，將利用抗體螢光免疫分析法針對三種癌症因子做為研究對象，分別為HER-2/neu、前列腺專一抗原 (prostate-specific antigen, PSA)、血管內皮細胞生長因子( vascular endothelial growth factor，簡稱 VEGF) 等。ErbB2 被定義為一致癌蛋白(oncoprotein)，因在許多人類組織器官所產生的癌細胞發現此基因具有大量表現之特性。例如乳癌、肺癌、子宮頸癌、卵巢癌及膀胱癌；前列腺特殊抗原在有前列腺癌、良性前列腺肥大的病人中，其前列腺特殊抗原在血液中的濃度是較高且與疾病的發展有正相關。血管內皮細胞生長因子可促使血管內皮細胞分裂、增生並增加血管通透性導致新血管生成，許多研究也發現不同之腫瘤疾病， 如腦腫瘤、肺腫瘤、乳腫瘤、消化道及泌尿道腫瘤等都有血管內皮細胞生長因子過度表現的現象。因此搭配本計畫所發展的微小化生醫光學檢測系統中，因為晶片縮小相當多，因此對於緩衝液 (buffer) 使用量與檢體用量的減少有相當助益，甚至進一步可以檢驗精簡步驟。因此一種快速檢測與低成本的檢測系統將可以被實現。本子計劃第一步先確認晶片式檢驗腫瘤抗原專一性之抗體螢光物質之流程步驟，並確認其可信度與重複性；此外沿用本計畫發展之檢測平台做驗證，以相同的方法定下標準檢驗流程步驟也將評估綠色螢光蛋白質(GFP) 應用於體外或體內的轉殖技術發展，希望對於未來分子生物醫學技術的進展，提供好的檢測方法與檢驗流程