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Item type:Item, Hydrogel-based zinc ion sensor on optical fiber with high resolution and application to neural cells(2020-08-15) ;Tsai, May-Jywan ;Cheng, Henrich ;Ho, Hsin-Hsien ;Lin, Peng-WeiLiou, Dann-YingSolid-state zinc ion sensor is developed with high enough resolution and reproducibility for the potential application in brain injury monitoring. An optical diffuser is incorporated into the zinc ion sensor based on optical fiber and hydrogel doped with the fluorescent zinc ion probe molecule meso-2,6-Dichlomphenyltripyrrinone (TPN-Cl-2). The diffuser transforms the high-peak-intensity excitation light near the fiber end into a broad light with moderate local intensity to reduce the degradation of the probe molecule. Reversible detection can be reached for 1, 2, and 5 mu m (10(-6) Molar), with slopes 0.3, 0.6, and 0.8 respectively. This is the pathophysiological concentration range after brain injury. The sensor is applied to neuron-glial cultures and macrophage under the stimulation of lipopolysaccharide (LPS), KCl and oxygen/glucose deprivation (OGD) that reflect inflammation, depolarization and ischemia respectively, mimicking events after brain injury. The zinc ion level is raised to 4-5 mu m after LPS treatment, and then reduced to <3 mu m after the co-treatment with the herbal drug silymarin. The results suggest the conditions of the neural cells under stress can be monitored.Item type:Item, Development of an inflammatory tissue-selective chimeric TNF receptor(2019-01-01) ;Lee, Chia-Jung ;Wang, Chao-Ching ;Chen, Michael ;Chuang, Kuo-HsiangCheng, Tian-LuBackground: Inhibiting TNF-alpha is an effective therapy for inflammatory diseases such as rheumatoid arthritis. However, systemic, nondiscriminatory neutralization of TNF-alpha is associated with considerable adverse effects. Methods: Here, we developed a trimeric chimeric TNF receptor by linking an N-terminal mouse Acrp30 trimerization domain and an MMP-2/9 substrate sequence to the mouse extracellular domain of TNF receptor 2 followed by a C-terminal mouse tetranectin coiled-coil domain (mouse Acrp-MMP-TNFR-Tn). Results: Here, we show that the Acrp30 trimerization domain inhibited the binding activity of TNFR, possibly by closing the binding site of the trimeric receptor. Cleavage of the substrate sequence by MMP-9, an enzyme highly expressed in inflammatory sites, restored the binding activity of the mouse TNF receptor. We also constructed a recombinant human chimeric TNF receptor (human Acrp-MMP-TNFR-Tn) in which an MMP-13 substrate sequence was used to link the human Acrp and the human TNF receptor 2. Human Acrp-MMP-TNFR-Tn showed reduced binding activity, and MMP-13 digestion recovered its binding activity with TNF-alpha. Conclusion: Acrp-masked chimeric TNF receptors may be able to be used for inflammatory tissue-selective neutralization of TNF-alpha to reduce the adverse effects associated with systemic neutralization of TNF-alpha.Item type:Item, Interleukin-17 enhances cardiac ventricular remodeling via activating MAPK pathway in ischemic heart failure(2018-09-01) ;Chang, Shih-Lin ;Hsiao, Ya-Wen ;Tsai, Yung-Nan ;Lin, Shien-FongLiu, Shuen-HsinBackground: We aimed to investigate the impact of interleukin (IL)-17 on ventricular remodeling and the genesis of ventricular arrhythmia (VA) in an ischemic heart failure (HF) model. The expression of the proinflammatory cytokine IL-17 is upregulated during myocardial ischemia and plays a fundamental role in post-infarct inflammation. However, the influence of IL-17 on the genesis of VA has not yet been studied. Methods and results: The level of inflammation and Th17 cell (CD4(+)IL-17(+)) expression in the rabbit model of ischemic HF were studied by flow cytometry, quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay (ELISA). The effect of IL-17 on VA induction following acute and chronic administration of IL-17 was determined using electrophysiological techniques and optical mapping. The expression of IL-17 target genes and related cytokines and chemokines in vivo and in vitro were measured using qPCR, ELISA, and immunoblotting. Th17 cells were markedly increased in the ischemic HF rabbit model. IL-17 directly induced VA in vivo and in vitro in a dose-dependent manner. IL-17 decreased conduction velocity, lengthened action potential duration, and increased the slope of the left ventricle (LV) restitution curve. IL-17 treatment led to fibrosis, collagen production and apoptosis in the LV. Furthermore, increased IL-17 signaling activated mitogen-activated protein kinase and increased the expression of downstream target genes, IL-6, TNF, CCL20, and CXCL1. An anti IL -17 neutralizing antibody abolished the effects of IL-17. Conclusions: The expression of IL-17 and its downstream target genes may play fundamental roles in inducing VA in ischemic HF.Item type:Item, 5-Demethyltangeretin is more potent than tangeretin in inhibiting dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin tumorigenesis(2014-11-01) ;Ma, Nianhan ;Lai, Ching-Shu ;Chung, Chih-Han ;Yang, Jinn-MoonHsu, Kai-Cheng5-Demethyltangeretin (5-DTAN), an autohydrolysis product of tangeretin (TAN) found in citrus peel, exhibited more potent anti-proliferative activity in human cancer cells than TAN itself. In this study, we investigated the anti-tumor promoting effect and underlying molecular mechanism of 5-DTAN on 7,12-dimethyl-benz(a)anthracene (DMBA)-induced and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin carcinogenesis. Application of 5-DTAN prior to each TPA-treatment was more effective than that of TAN on reducing the number, incidence and size of papillomas in DMBA-initiated mouse skin. Moreover, 5-DTAN suppressed cyclooxygenase-2 (COX-2) protein expression more strongly than TAN through interfering with phosphatidylinositiol 3-kinase (PI3K)/Akt signaling and further activation of transcription factor NF-kappa B. Taken together, these results revealed for the first time the in vivo chemopreventive efficacy of 5-DTAN on inhibition of skin carcinogenesis through promoting apoptosis and molecular interactions with residues of PI3K, COX-2, and AKT that may potentially serve as a novel functional agent capable of preventing inflammation-associated tumorigenesis. (C) 2014 Elsevier Ltd. All rights reserved.Item type:Item, 胰磷脂質水解酵素A2和其受體在調控發炎反應上的機理(1998) ;袁俊傑 ;CHIUN-JYEYUAN交通大學生物科技研究所Item type:Item, Peripheral neuropathology of the upper airway in obstructive sleep apnea syndrome(2013-04-01) ;Tsai, Yi-Ju ;Ramar, Kannan ;Liang, Yao-Jen ;Chiu, Po-HanPowell, NelsonObstructive sleep apnea syndrome (OSAS) is a common sleep disorder that leads to significant morbidity and mortality without adequate treatment. Though much emphasis on the pathogenesis of OSAS has been placed on a narrow upper airway space and associated muscular factors, possible neuropathy of the upper airway has not been fully elucidated. Increasing peer reviewed evidence suggests involvement of neurologic lesions of the upper airway in OSAS patients. In this article, we review the etiology and pathophysiology of OSAS, the evidence and possible mechanisms leading to upper airway neuropathy, and the relationship between upper airway neuropathy and OSAS. Further studies should focus on the long term effects of the upper airway neuropathy as related to the duration and severity of snoring and or apnea, and also on the potential methods of prevention and management of the neuropathy in sleep disordered breathing. (C) 2012 Elsevier Ltd. All rights reserved.Item type:Item, Characterizing the polymeric status of Helicobacter pylori heat shock protein 60(2009-10-16) ;Lin, Ching-Yi ;Huang, Yu-Shan ;Li, Chi-Han ;Hsieh, Yuan-TingTsai, Nu-ManHelicobacter pylori heat shock protein 60 (HpHsp60) was first identified as an adhesion molecule associated with H. pylori infection. Here we have analyzed the structure of HpHsp60 via amino acid BLAST, circular dichroism, and electrophoresis and the results indicate that most recombinant HpHsp60 molecules exist as dimers or tetramers, which is quite different from Escherichia coli Hsp60. Treatment of human monocytic cells THP-1 with HpHsp60 was found to up-regulate a panel of cytokines including IL-1 alpha, IL-8, IL-10, IFN-gamma, TNF-alpha, TGF-beta, GRO, and RANTES. Carboxymethylated HpHsp60 molecules with a switched oligomeric status were able to further enhance NF-kappa B-mediated IL-8 and TNF-alpha secretion in THP-1 cells compared to unmodified HpHsp60 molecules. These results indicated that the oligomeric status of HpHsp60s might have an important role in regulating host inflammation and thus help facilitate H. pylori persistent infection. (C) 2009 Elsevier Inc. All rights reserved.