Untersuchungen zum Einfluss eines erhöhten Omega-3 Fettsäure Gehaltes auf das Lipidmediatorenprofil und zum anti-inflammatorischen Potential der murinen 15-Lipoxygenase, 17-Hydroxydocosapentaensäure und 10,17-Dihydroxydocosapentaensäure

Long-chain polyunsaturated omega-3 (n-3 PUFA) and omega-6 fatty acids are precursors of highly potent lipid mediators and metabolites, which are synthesized via cyclooxygenases, lipoxygenases (LOX), cytochrome P450 (CYP-450) or via autooxidation processes, and their synthesis can be modulated. The lipid mediator profile, especially of monohydroxy lipid metabolites hydroxyeicosatetraenoic acids, hydroxyeicosapentaenoic acids (HEPE) and hydroxydocosahexaenoic acids, and their modifications due to elevated n-3 PUFA levels was characterized in different organs in healthy mice. Furthermore the role of murine 15-lipoxygenase as well as omega-6 docosapentaenoic acid-derived 17-hydroxydocosapentaenoic acid (17-HDPAn-6) and 10,17-dihydroxydocosapentaenoic acid (10,17-HDPAn-6) in experimental colitis was investigated. In the first study, the profile of monohydroxy lipid metabolites in heart, lung, liver, colon, kidney, spleen and skeletal muscle of healthy wildtype mice were characterized using liquid chromatography–mass spectrometry. We found distinct characteristic lipid metabolite patterns in different organs. Elevated n-3 PUFA levels in transgenic fat-1 mice lead to increased formation of n-3 PUFA derived metabolites. Eicosapentaenoic acid – even though levels were low - was strongly utilized for formation of 12-HEPE in the lung as well as spleen and 9-HEPE and 18-HEPE in the other organs. The second study showed that higher n-3 PUFA levels could be achieved through dietary intervention with a diet enriched with n-3 PUFA compared to the fat-1 mouse model. This was reflected by increased levels of n-3 PUFA derived lipid metabolites. In plasma of mice fed with an enriched n-3 PUFA diet the lipid metabolite profile was dominated by metabolites derived from the LOX and CYP450 pathways. The anti-inflammatory effect of 17-HDPAn-6 and 10,17-HDPAn-6 in dextran sodium sulfate (DSS)-induced colitis was examined in the third study. Intraperitoneal injection of 17-HDPAn-6 or 10,17-HDPAn-6 alleviated DSS-colitis, epithelial damage and macrophage infiltration. Furthermore 17-HDPAn-6 and 10,17-HDPAn-6 increased phagocytosis activity in macrophage cell line RAW 264.7. The role of murine 15-lipoxgenase (Alox15) in DSS-colitis was explored in the fourth study. Alox 15 expression was augmented in wildtype C57BL/6 mice with DSS-colitis. Furthermore, systemic inactivation of the Alox15 gene (Alox15−/−) was associated with less severe colitis signs and preserved function of the intestinal barrier. Lower 12-hydroxyeicosatetraenoic acid (12-HETE) levels were detected in Alox15−/− mice with DSS-colitis. 12-HETE impaired intestinal epithelial barrier function in vitro in CaCo-2 cells. The results indicate a protective effect of systemic Alox15 inactivation, which might be related to reduced formation of 12-HETE, as well as of the lipid mediators 17-HDPAn-6 and 10,17-HDPAn-6 in the context of DSS-colitis.Langkettige mehrfach ungesättigte Omega-3 und Omega-6 Fettsäuren stellen Vorläufer für bioaktive Lipidmediatoren und – metabolite dar, welche enzymatisch über Cyclooxygenasen, Lipoxygenasen (LOX), Cytochrome P450 (CYP-450) sowie Autooxidationsprozessen synthetisiert werden, und können in ihrer Bildung pharmakologisch beeinflusst werden. In den dieser Arbeit zugrundeliegenden Publikationen wurde der Einfluss von erhöhten Omega-3 Fettsäurespiegeln auf die Zusammensetzung des Lipidmediatorenprofils, insbesondere der einfach hydroxylierten Metabolite Hydroxyeicosatetraensäuren, Hydroxyeicosapentaensäuren (HEPE) sowie Hydroxydocosahexaensäuren, in verschiedenen Organen der Maus untersucht. Weiterhin wurde die Rolle der murinen 15-Lipoxygenase sowie der von Omega-6 Docosapentaensäure stämmigen Lipidmetabolite 17-Hydroxydocosapentaensäure (17-HDPAn-6) und 10,17-Dihydroxydocosapentaensäure (10,17-HDPAn-6) im Kontext eines experimentellen Kolitismodells untersucht. In der ersten Studie wurde mittels Flüssigchromatographie mit Massenspektrometrie-Kopplung die Zusammensetzung von Monohydroxy-Lipidmetaboliten in Herz, Lunge, Leber, Kolon, Nieren, Milz und Skelettmuskel der Maus charakterisiert. Es fand sich eine organ- und gewebespezifische Verteilung der untersuchten Monohydroxy-Lipidmetabolite. Ein erhöhter Omega-3 Fettsäurespiegel in der transgenen fat-1 Maus führte zu einem organ- und gewebespezifischen Anstieg der Omega-3 Fettsäure stämmigen Lipidmetabolite. Eicosapentaensäure wurde trotz geringer Mengen hocheffizient zu hauptsächlich 12-HEPE in der Lunge sowie Milz und 9-HEPE und 18-HEPE in den anderen Organen verstoffwechselt. In der zweiten Studie konnte gezeigt werden, dass durch diätetische Intervention mittels Omega-3 Fettsäure angereichertem Futter ein höherer Omega-3 Fettsäurespiegel im Vergleich zum transgenen fat-1 Mausmodell erzielt wurde. Es fanden sich entsprechend erhöhte Spiegel der von Omega-3 Fettsäuren abgeleiteten Lipidmetabolite. Im Plasma von Mäusen auf Omega-3 Fettsäurereichem Futter wurde das Lipidmetabolitenprofil von LOX und CYP-450 Enzymen synthetisierten Lipidmetaboliten dominiert. Der anti-inflammatorische Effekt von 17-HDPAn-6 und 10,17-HDPAn-6 wurde in der dritten Studie im Dextran Natriumsulfat (DSS)-induzierten Kolitismodell in wildtyp C57BL/6 Mäusen untersucht. Eine intraperitoneale Behandlung mit 17-HDPAn-6 oder 10,17-HDPAn-6 milderte die DSS-Kolitis, den epithelialen Schaden sowie die Makrophageninfiltration. Weiterhin erhöhte 17-HDPAn-6 sowie 10,17-HDPAn-6 in der Makrophagen-Zelllinie RAW 264.7 die Phagozytoseaktivität. Die Rolle der murinen 15-Lipoxygenase (Alox15) wurde in der vierten Studie im DSS-Kolitismodell untersucht. Unsere Ergebnisse zeigen eine erhöhte Alox15 Expression in wildtyp Mäusen mit DSS-Kolitis. Eine systemische Inaktivierung des Alox15 Genes (Alox15−/−) war mit einer signifikant milderen Kolitisaktivität und einer erhaltenen Funktion der intestinalen Barriere assoziiert. In Alox15−/− Mäusen mit DSS-Kolitis wurden verminderte 12-Hydroxyeicosatetraensäure (12-HETE) Spiegel gemessen. In vitro Experimente konnten zeigen, dass 12-HETE die epitheliale Barriere in CaCo-2 Zellen stört. Die Ergebnisse weisen auf einen protektiven Effekt der systemischen Alox15 Inaktivierung, möglicherweise bedingt durch eine verminderte Synthese von 12-HETE, sowie der Lipidmediatoren 17-HDPAn-6 und 10,17-HDPAn-6 im DSS-Kolitismodell hin

The Emergence of the Legitimacy of Religious Healing Knowledge in Taiwan

This dissertation investigates how religious healing knowledge has been defined and used by scholars, physicians, and New Agers and how religious healing knowledge emerged as a legitimate area of knowledge in Taiwan. The key position of religious healing knowledge within the entanglement between religion and spirituality is also examined. After the martial law was lifted in 1987, Taiwan’s society had rapidly diversified, and its religions were at the transition point between the old and the new. Meanwhile, the new spirituality culture was introduced into Taiwan in the 1980s and got popular in the 1990s, and it inherited the trend of religious individuality and the orientation of syncretism. Results in this dissertation showed that the concept of “spirituality” had its particularity in the context of Taiwan. Although there was a continuity between religion and spirituality, the concept of “spirituality” was not stabilized in Taiwan, giving actors like scholars, physicians, and New Agers an operating space to do knowledge production and connect differentiated knowledges. They regarded religious healing knowledge as a resource for knowledge translation, which made its legitimacy had gradually emerged. The scholars’ interest was to indigenize academic knowledge, and they mobilized religious healing knowledge to connect foreign and local knowledge; the conceptual distinction between disease and illness was important to them. The physicians’ interest was to find other healing methods to supplement the deficiencies of Western medicine, and they mobilized religious healing knowledge to connect CAM and Western medicine; the conceptual distinction between cure and healing was important to them. New Agers’ interest was to seek spirituality that is different from traditional religions, and they mobilized religious healing knowledge to construct a flexible, hybrid cosmology in order to connect foreign and local healing knowledge; the conceptual distinction between religion and spirituality was important to them. The three concepts of illness, healing, and spirituality were more flexible than concepts of disease, cure, and religion. They provided these actors a space for operation in their knowledge production. The legitimacy of religious healing knowledge was brought out through their knowledge production

In search of Lin Zhao\u27s soul = 尋找林昭的靈魂

Film Director: Hu Jie (胡杰) Film Release Year: 2004https://commons.ln.edu.hk/ccs_worksheet/1001/thumbnail.jp

Umbilic hypersurfaces of constant sigma-k curvature in the Heisenberg group

We study immersed, connected, umbilic hypersurfaces in the Heisenberg group $H_{n}$ with $n$ $\geq$ $2.$ We show that such a hypersurface, if closed, must be rotationally invariant up to a Heisenberg translation. Moreover, we prove that, among others, Pansu spheres are the only such spheres with positive constant sigma-k curvature up to Heisenberg translations.Comment: 28 pages, 6 figure