Tesis: "Immunoregulatory properties and inflammation"

1

Alder, Louise B. A. "Immunoregulatory properties of polyclonal immunoglobulin for therapeutic use". Thesis, University of Newcastle Upon Tyne, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.361937.

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2

Wongjindanon, Nuttapong. "Immunoregulatory properties of MPO and pathophysiology of its autoantibodies". Thesis, University of Cambridge, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.621380.

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3

Khademi, Mohsen. "Characterization and modulation of immunoregulatory molecules in neuroinflammation /". Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-006-0/.

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4

Matsubara, Yasushi. "Delineation of immunoregulatory properties of adult T cell leukemia cells". Kyoto University, 2007. http://hdl.handle.net/2433/135653.

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5

Schneider, Enja [Verfasser]. "The immunoregulatory role of T cell-derived CD73 in the context of inflammation / Enja Schneider". Hamburg : Staats- und Universitätsbibliothek Hamburg Carl von Ossietzky, 2020. http://d-nb.info/1229387374/34.

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6

Van, Oers Nicolai S. C. (Nicolai Stanislas Cyrille). "Biochemical and immunoregulatory properties of a distincte murine alpha-fetoprotein isoform". Thesis, McGill University, 1990. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=74568.

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Alpha-fetoprotein (AFP) is a tumor-associated embryonic serum glycoprotein, existing in the circulation as a heterogeneous population of closely related molecular variants. The biological function(s) of AFP is not known, but the precisely regulated expression of AFP molecules during ontogenetic development and in certain diseases is consistent with an immunoregulatory function.
The present thesis examines the functional significance of murine AFP microheterogeneity. In the initial phase of this study, seven individual AFP isoforms were purified with a novel separation protocol developed on Mono Q anion-exchange columns linked to an FPLC system. All seven subspecies were further characterized by isoelectric focusing gels, immunoblot analysis, molecular weight determination, and sialic acid composition studies. When all seven variants were tested in several AFP sensitive immune assays, we determined that all the immunosuppressive activity of native AFP was localized to a single distinct molecular variant. This isoform, AFP-1, exhibited an isoelectric point of pH = 5.1, contained 1 mol of sialic acid/mol of protein, and represented approximately 6% of the total population of naturally occurring AFP isoforms isolated from the amniotic fluid at days 15-19 of murine gestation. Further studies indicated that sialic acid expression on the carbohydrate portion of the AFP molecules was unlikely to be involved in the suppressor function.
Since it has been reported that the polyunsaturated fatty acids arachidonic acid and docosahexaenoic acid complexed to AFP molecules may be necessary for the expression of AFP-mediated immunoregulatory activity, we also examined the potential contribution of these polyunsaturated fatty acids to the immunoregulative function of the active isoform. Gas liquid chromatographic analyses, delipidation procedures and fatty acid reassociation experiments indicated that these fatty acids are unlikely to contribute to AFP-mediated immunosuppressive activity. We also determined that MAF-derived AFP from different gestational time points including days 10.5, 12.5, 14.5, 16.5, and 18.5 exhibits immunosuppressive activity in vitro. All the above results are the first direct demonstration that individual molecular variants of murine AFP have distinct immunoregulatory properties. This should facilitate a better comprehension of the relationship of molecular structure to biological function of AFP molecules during fetal development.

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7

Kaur, Komal Amandeep. "The Immunoregulatory Role of Natural Killer (NK) Cell Derived IL-10 During Microbial Infections". Thesis, Université d'Ottawa / University of Ottawa, 2014. http://hdl.handle.net/10393/31353.

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Natural Killer (NK) cells, lymphocytes of the innate immune response, play a vital role in controlling infections and in tumor surveillance. NK cells provide protection by direct cytolysis of infected cells and by the production of pro-inflammatory cytokines such as, IFN-γ and TNF-α. Notably, NK cells have recently been identified to regulate the immune response by producing the anti-inflammatory cytokine IL-10. Several other cells can produce IL-10 during infections, however NK cell derived IL-10 can be critical in regulating immune response during early phases of infection and therefore protecting the host from excessive immunopathology. Although the regulatory role of NK cells seems to be plausible, the physiological relevance of NK cell mediated immune regulation during infections has not been demonstrated in detail. To investigate the immunoregulatory function of NK cells, I used Murine Cytomegalovirus (MCMV) infection induced by a high dose challenge and demonstrated that NK cells are a major IL-10 producer during acute stage of the infection. To elucidate the role of NK cell derived IL-10 during infections, I generated NK cell specific IL-10 knockout, NKp46iCre  Il-10flox/flox mice (NK-Il-10-/-) by crossing Il-10flox/flox mice with mice expressing Cre recombinase exclusively under the NK cell specific promoter, NKp46 (NKp46iCre knock-in mice). My results indicated that Cre mediated Il-10 genomic deletion occurred predominantly in NK cells but not in NKT, T and B cells. Enriched NK cells from NK-Il-10-/- mice failed to produce IL-10 upon ex vivo IL-2/IL-12 stimulation. Furthermore, histological analysis of the colon indicated that NK-Il-10-/- mice are free from aberrant inflammation. During sustained MCMV infection, significantly higher production of IFN-γ by CD8+ T cells of NK-Il-10-/- mice in salivary glands indicates that NK cell derived IL-10 contributes to the establishment of the immune suppressive environment in the organ. NK-Il-10-/- mice also demonstrated increased susceptibility to acute Listeria monocytogenes (LM) infection based on enhanced body weight loss. Taken together, I have successfully generated NK-Il-10-/- mice that lack the Il-10 gene exclusively in NK cells. The NK-Il-10-/- mouse can be used as an ideal model to dissect the immunoregulatory role of NK cells during various microbial infections and tumorogenesis.

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Lin, Jiaying [Verfasser]. "Immunoregulatory properties of cancer stem-like cells derived from carcinoma cell lines of the cervix uteri / Jiaying Lin". Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2014. http://d-nb.info/1052530338/34.

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9

Amarakoon, A. M. T. "Studies on the antioxidant activity and immunomodulatory properties of black tea". Thesis, University of Southampton, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241795.

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10

Hotchkiss, Kelly M. "Engineering Surface Properties to Modulate Inflammation and Stem Cell Recruitment through Macrophage Activation". VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5492.

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Biomaterials are becoming the most commonly used therapeutic method for treatment of lost or damaged tissue in the body. Metallic materials are chosen for high strength orthopaedic and dental applications. Titanium (Ti) implants are highly successful in young, healthy patients with the ability to fully integrate to surrounding tissue. However the main population requiring these corrective treatments will not be healthy or young, therefore further research into material modifications have been started to improve outcomes in compromised patients. The body’s immune system will generate a response to any implanted material, and control the final outcome. Among the first and most influential, cells to interact with the implant will be macrophages. Throughout this study we have 1) established the ability of macrophages to recognize and differentially activate in response to material surface properties, 2) investigated the role of integrin binding in macrophage activation to material properties, and 3) confirmed the importance of macrophage activation in vivo following Ti implant placement. The generation of a hydrophilic implant surface promoted the greatest anti-inflammatory and pro-regenerative macrophage activation. Surface wettability will control protein adsorption which can activated different integrin binding on macrophages and may be responsible for changes in activation. When integrin β3 subunit binding was prevented hydrophilic surfaces no longer promoted an anti-inflammatory macrophage activation. Additionally, when macrophage levels were reduced using two separate ablation models, MaFIA mice and clodronate liposomes, hydrophilic surfaces no longer promoted anti-inflammatory T-cell populations and cytokine profiles. There were also fewer stem cells adhered to implant surfaces at 1, 3, and 7 days when macrophage populations were compromised.

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11

Shen, Qiwen. "Identification of Anti-inflammatory and Antioxidant Properties of MangostinXanthones in Adipocyte Reporter Assays". The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1366099986.

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12

Yu, Jie. "Immunomoduatory properties of host defence peptide LL-37 during infection and inflammation in human blood cells". Thesis, University of British Columbia, 2006. http://hdl.handle.net/2429/31500.

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The human cathelicidin, LL-37, is a cationic host defence peptide and serves as an essential component of innate immunity. In addition to its modest antimicrobial activity, LL-37 has been demonstrated to be a multifunctional modulator of innate immune responses, although the mechanism(s) of which have not been elucidated. The present study demonstrated that LL-37 could synergistically enhance IL-1β-induced production of cytokines (IL-6, IL-10) and chemokines (MCP-3) in primary human PBMCs. In contrast to the neutralization of LPS-induced secretion of pro-inflammatory cytokines, LL-37 dramatically augmented LPS-stimulated MCP-3 production. LL-37 by itself induced transient phosphorylation of IkB-α. and the subsequent nuclear translocation of NF - kB subunits p50 and p65, which could be further enhanced in the presence of IL-1β. Similar effects of LL-37 and I L-1β were also observed oh activation of Akt and CREB. Therefore, we propose that, in addition to its well-known anti-inflammatory activity, the human host defence peptide LL-37 also plays an important role in boosting the innate immune responses in combination with inflammatory mediator (IL-1β), which provides a new mechanism for LL-37 in modulating the inflammatory responses in innate immunity.
Science, Faculty of
Microbiology and Immunology, Department of
Graduate

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13

Riester, Karin Dorota [Verfasser]. "The effect of peripheral inflammation on in vivo functional properties of cortical networks / Karin Dorota Riester". Tübingen : Universitätsbibliothek Tübingen, 2020. http://d-nb.info/1217249265/34.

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14

Schröder, Oliver. "Studies on molecular properties and functional regulation of terminal leukotriene C₄ synthases and cysteinyl-leukotriene receptor signalling in human endothelium /". Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-146-3/.

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15

Dai, Jin. "PREPARATION AND CHARACTERIZATION OF BLACKBERRY EXTRACTS AND THEIR ANTICANCER AND ANTI-INFLAMMATORY PROPERTIES". UKnowledge, 2009. http://uknowledge.uky.edu/gradschool_diss/739.

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Blackberries are rich in polyphenols including anthocyanins. Polyphenols are hypothesized to have biological activities that impact positively on human health. The purpose of these studies was to develop phenolic extracts from selected cultivars of blackberries currently grown in Kentucky as potential Botanical Drug Products for the treatment and prevention of cancer and inflammatory diseases. An ultrasound-assisted ethanol extraction method was employed to obtain anthocyanin-containing extracts (ACEs) from puree or powder (lyophilized puree) of blackberries. ACEs were analyzed for total anthocyanin and phenolics content, polymeric color, and total antioxidant capacity (TAC). The influence of water content in the extraction system was evaluated. A 90 day stability study of the extract and a 48 h stability study of the extract in biologically relevant buffers were completed. HPLC-MS results showed the anthocyanins in ACE were mainly cyanidin-based. As compared to powder-derived ACEs, puree-derived ACEs contained similar amounts of anthocyanins, but greater levels of phenolics and increased TAC. The in vitro antiproliferative effects of ACEs were evaluated in human leukemia (HL- 60), colon (HT-29), and breast (MCF-7) cancer cells. The anticancer mechanism involving reactive oxygen species (ROS) generation was investigated. It was found puree-derived ACEs significantly enhanced production of H2O2 and cytotoxicity in all cell lines as compared to powder-derived ACEs. Cyanidin 3-glucoside exerted anticancer effect by acting synergistically or additively with other active components in the extracts. Furthermore, the phenolic-enriched fractions were separated from non-phenolic fractions in ACEs and found to have potent antioxidant and antiproliferative activities. Pureederived ACE and corresponding phenolic-enriched methanol fraction (MF) induced cell death through ROS-independent caspase 3 pathway whereas the cytotoxicity induced by powder-derived ACE and corresponding MF is related to ROS mechanisms. The in vitro anti-inflammatory studies showed ACEs inhibited Lipid A-induced Interleukin-12 (IL-12) release from mouse dendritic cells, and modulated lipopolysaccharide (LPS)-induced secretion of tumor necrosis factor-α (TNF-α) and Interleukin-6 (IL-6) from murine macrophages. These studies have important implications for the potential use of blackberry extracts for the treatment and prevention of cancer and inflammation diseases and provide essential information for the development of Botanical Drug Products from extracts derived from blackberries and other fruits.

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16

Lynch, Patrick Michael. "Analysis of the barrier properties of the initial lymphatics and the toxicity of lymph fluid during inflammation". Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2007. http://wwwlib.umi.com/cr/ucsd/fullcit?p3249655.

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Thesis (Ph. D.)--University of California, San Diego, 2007.
Title from first page of PDF file (viewed March 23, 2007). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 96-102).

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17

Love, Heather. "The effects of surfactant phospholipids on the diophysical properties of spuum, inflammation, and repair in cystic fibrosis". Thesis, Queen's University Belfast, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.534693.

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18

Singh, Shalini. "Amphiphilic Peptide Interactions with Complex Biological Membranes : Effect of peptide properties on antimicrobial and anti-inflammatory effects". Doctoral thesis, Uppsala universitet, Institutionen för farmaci, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-282781.

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With increasing problem of resistance development in bacteria against conventional antibiotics, as well as problems associated with diseases either triggered or enhanced by infection, there is an urgent need to identify new types of effective therapeutics for the treatment of infectious diseases and its consequences. Antimicrobial and anti-inflammatory peptides have attracted considerable interest as potential new antibiotics in this context. While antimicrobial function of such peptides is being increasingly understood demonstrated to be due to bacterial membrane disruption, the mechanisms of their anti-inflammatory function are poorly understood. Since bacterial membrane component lipopolysaccharide triggers inflammation, this thesis aims at clarifying importance of lipopolysaccharide (LPS)-peptide interactions while investigating possible modes of action of peptides exhibiting anti-inflammatory effect. Furthermore, effect of poly(ethylene)glycol (PEG)-conjugation was investigated to increase performance of such peptides. Results presented in this thesis demonstrate that peptide-induced LPS- and lipid A binding/scavenging is necessary but not sufficient criterium for anti-inflammatory effects of peptides. Furthermore, preferential binding to LPS over lipid membrane, as well as higher binding affinity to the lipid A moiety within LPS, are seen for these peptides. In addition, results demonstrate that apart from direct LPS scavenging, membrane-localized peptide-induced LPS scavenging seem to contribute partially to anti-inflammatory effect. Furthermore, fragmentation and densification of LPS aggregates, in turn dependent on the peptide secondary structure on LPS binding, as well as aromatic packing interactions, correlate to the anti-inflammatory effect, thus promoting peptide-induced packing transition in LPS aggregates as key for anti-inflammatory functionality. Thus, peptide-induced LPS aggregate disruption together with reduction of the negative charge of LPS suggests the importance of phagocytosis as an alternative to the inflammatory pathway, which needs to be further investigated. Furthermore, PEG conjugation of peptide results in strongly reduced toxicity at a cost of reduced antimicrobial activity but markedly retained anti-inflammatory effect. Taken together, the results obtained in this work have demonstrated several key issues which need to be taken into consideration in the development of effective and selective anti-inflammatory peptide therapeutics for the treatment of severe Gram-negative bacterial infections.

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19

Gerard, Claire. "Développement d’une stratégie thérapeutique immunosuppressive dérivée de cellules myéloïdes dans la maladie du greffon contre l’hôte". Thesis, Bourgogne Franche-Comté, 2020. https://nuxeo.u-bourgogne.fr/nuxeo/site/esupversions/a02d57d7-6368-477d-8e8d-0badac13bda0.

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Résumé :Notre équipe a développé une thérapie cellulaire originale dérivant de la lignée monocytaire. Cette sous-population de cellules humaines suppressives d’origine myéloide, appelée Human Monocyte-derived Suppressor Cells (HuMoSC, cellules CD33+), est capable d’inhiber la prolifération des lymphocytes T effecteurs et d’induire des CD4 et CD8 Treg. De plus, les HuMoSC préviennent l’apparition de la maladie du greffon contre l’hôte (GvHD).Dans un premier temps, nous avons montré qu’un environnement inflammatoire ou la présence d’immunosuppresseurs ne diminuaient pas la capacité des HuMoSC à inhiber la prolifération lymphocytaire et à favoriser l’induction de CD4 et CD8 Treg. Enfin, nous avons montré que l’effet graft-versus-leukemia (GvL) est préservé en présence des HuMoSC. Toutes ces données confirment l’intérêt des HuMoSC dans la prévention de la GvHD.Cependant, en raison d’un faible rendement de génération des HuMoSC et d’un problème de disponibilité de billes de tri CD33+ GMP, nous avons aussi modifié notre protocole pour isoler les cellules CD14+, appelées CD14-HuMoSC. Ainsi, dans un second temps, nous nous sommes intéressés aux propriétés des surnageants des HuMoSC et des CD14- HuMoSC. Ces modifications du protocole ont permis d’obtenir un grand nombre de cellules CD14-HuMoSC et de grandes quantités de surnageant produit en conditions GMP. Nous avons montré que les deux surnageants diminuaient l’activation et la prolifération des LT, diminuaient la réponse Th1 au profit de la réponse Th2, favorisaient l’induction des Treg et diminuaient la capacité des cellules dendritiques à induire la prolifération des LT. In vivo, les surnageants préviennent le développement de la GvHD dans un modèle murin de GvHD xénogénique. Enfin, pour montrer que ces deux surnageants seront efficace chez les patients, nous avons montré qu’un environnement inflammatoire ou que la présence d’immunosuppresseurs n’altéraient pas l’effet immunosuppressif des surnageants. Ces résultats confirment leur intérêt thérapeutique. L’étude proteomique de ces deux surnageants a permis d’identifier des protéines immunosuppressives qui pourraient être responsables de leurs capacités immunosuppressives.En conclusion, les HuMoSC et les surnageants des cellules dérivées des HuMoSC représentent un arsenal thérapeutique prometteur dans la prévention de la GvHD mais aussi dans les maladies inflammatoires
Abstract :Our team has developed an original cell therapy derived from monocytes. This sub-population of human suppressor cells of myeloid origin, called Human Monocyte-Derived Suppressor Cells (HuMoSC, CD33+ cells) is able to inhibit effector T cell proliferation and to induce CD4 and CD8 Treg. It has been demonstrated that HuMoSC prevent from graft-versus-host disease (GvHD).In a first time, we showed that an inflammatory environment or the presence of immunosuppressive drugs did not decrease HuMoSC abilities to inhibit T cell proliferation and to promote CD4 and CD8 Treg induction. Finally, we showed that graft-versus-leukemia (GvL) effect is preserved in presence of HuMoSC. Taken together, those data confirm the interest of HuMoSC in GvHD prevention.Nevertheless, due to a low yield of HuMoSC generation with this protocol and problem with avaibility of CD33 GMP beads, we also modified our protocol to isolate CD14+ cells, called CD14-HuMoSC. This is why in a second time, we took interest in HuMoSC and CD14-HuMoSC supernatant properties. These protocol modifications allow us to obtain large number of CD14-HuMoSC cells and large quantities of supernatant produced under GMP conditions. We showed that both supernatants decrease T cell activation and proliferation, decrease Th1 response in favor of Th2 response, promote Treg induction and decrease capacity of dendritic cells to induce T cell proliferation. In vivo, supernatants prevent from GvHD in a murine model of xenogenic GvHD. Finally, in order to assess that these supernatants will be efficient in patient, we showed that an inflammatory environment or presence of immunosuppressive drugs did not alter both supernatant immunosuppressive effects. These results confirm their therapeutic interest. Proteomic analysis allowed us to identify immunosuppressive proteins which could be responsible for supernatants immunosuppressive capacities.In conclusion, HuMoSC and supernatant derived from HuMoSC represent a promising therapeutic arsenal for GvHD prevention but also in inflammatory diseases

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FUMAGALLI, MARCO. "STRAWBERRY (FRAGARIA X ANANASSA DUCH.) TANNINS AS INGREDIENTS OF NUTRACEUTICALS WITH POTENTIAL ANTI-GASTRITIS PROPERTIES". Doctoral thesis, Università degli Studi di Milano, 2018. http://hdl.handle.net/2434/606032.

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Gastritis is an inflammatory-based disease, involving millions of people in the world. Helicobacter pylori (H. pylori) is the main cause of inflammation at the gastric level, inducing the expression and release of different pro-inflammatory cytokines (ex. IL-8 and IL-6) by gastric epithelial cells. The presence of H. pylori results also in reactive oxygen species (ROS) production by the gastric mucosa; gastric epithelial cells contribute to the production of ROS, thus exacerbating oxidative stress in this district. Strawberry is one of the most commonly consumed fruits in the world and it is an important source of sugars, vitamins, fibers, micronutrients and polyphenols, including anthocyanosides (i.e. pelargonidin and cyanidin glycosides) and tannins. Condensed (procyanidins) and hydrolysable tannins (especially ellagitannins, such as agrimoniin) are among the most abundant polyphenols. Although tannins are important components of strawberries, until now the activity of these strawberry compounds, on gastric inflammation, is unknown. In the present study, the chemical profile and the biological properties of tannin-enriched extracts from strawberries were analyzed in cell models of gastric inflammation, considering also the chemical and biological features of strawberry tannins after in vitro simulated gastric digestion. The anti-inflammatory activities of pure strawberry tannins were assayed to get mechanistic insights. Tannin-enriched extracts from strawberries inhibit IL-8 secretion in TNFα-treated human tumour gastric epithelial cells (AGS) by dampening the NF-κB signaling. In vitro simulated gastric digestion slightly affects the chemical composition and the biological properties of strawberry tannins. By using pure compounds, I found that casuarictin may act as a pure NF-B inhibitor while agrimoniin inhibits IL-8 secretion also acting on other biological targets; in our system procyanidin B1 prevents the TNFα-induced effects without interfering with the NF-κB pathway. The effects of strawberry tannins are maintained in normal gastric epithelial cells (GES-1) showing an inhibitory effect on NF-κB activity and the expression and release of some pro-inflammatory mediators (like IL-8, IL-6 and MMP-9). Comparing the IC50s between AGS and GES-1 cells, the activity of strawberry tannins appear slightly higher in AGS cells than in GES-1 cells. Compounds from strawberry are able to counteract H. pylori-induced IL-8 release in both GES-1 and AGS cells, although the effect appears at higher concentrations than in TNFα-treated cells. Concentrations showing efficacy are easily reachable in vivo after with a moderate consumption of the fruit. Agrimoniin and casuarictin are able to exert an antioxidant activity in a cell-free system and to suppress basal Nrf2 activation. Taken together these results suggest that strawberry tannins, even after in vitro simulated gastric digestion, exert anti-inflammatory activities at nutritionally relevant concentrations.

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21

Yadav, Rashmi. "An investigation into the anti-inflammatory properties of the anti-thrombotic drug abciximab using rat models of inflammation". Thesis, Imperial College London, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.524671.

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22

Saha, Chaitrali. "Unravelling the therapeutic intervention of inflammation and cancer by Viscum album : understanding its anti-inflammatory and immunostimulatory properties". Thesis, Compiègne, 2015. http://www.theses.fr/2015COMP2210/document.

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Les préparations de Viscum album (VA), connu sous le nom vernaculaire de gui européen, sont fréquemment utilisées en support des traitements anticancéreux, principalement pour améliorer la qualité de vie des malades et réduire la croissance des tumeurs. Elles sont connues pour exercer des effets anti-tumoraux. Il existe de plus en plus de données scientifiques faisant état de liens étroits entre cancer et inflammation. Étant donné que la prostaglandine E2 (PGE2) induite par la cyclo-oxygénase 2 (COX-2) joue un rôle clef dans l’inflammation, j’ai exploré la régulation du système COX-2-PGE2 par VA et ses mécanismes sous-jacents. J’ai montré que VA exerce ses effets anti-inflammatoires en inhibant sélectivement l’expression de COX-2 et en diminuant la production de PGE2 qui en découle, par le biais d’une déstabilisation de l’ARNm de COX-2. En plus de leurs propriétés cytotoxiques, il a été montré que les préparations de VA ont également des effets immunostimulants. Les différentes préparations de VA sont hautement hétérogènes du fait de leurs compositions biochimiques qui varient selon la récolte, l’espèce de l’arbre hôte et les méthodes de préparation qui peuvent influer sur leur efficacité clinique. De ce fait, j’ai réalisé une étude comparative sur cinq préparations de VA dans le but d’analyser leurs capacités de maturation et d’activation des cellules dendritiques (DC) qui peuvent à leur tour présenter une réponse immunitaire anti-tumorale. Les résultats ont montré que parmi les cinq préparations,VA Qu Spez induit de manière significative l’activation des DC et la sécrétion de cytokines pro-inflammatoires telle que l’IL-6, l’IL-8 et le TNF-α qui induisent la production d’IFN-γ,orientant de ce fait la réponse immunitaire vers une réponse Th1. L’orchestration de la11fonction des cellules myélomonocytiques est un élément central à l’interface entre inflammation et cancer. Il constitue un paradigme expliquant la plasticité et la fonction des macrophages. Mon étude met en évidence l’influence de VA Qu Spez sur la polarisation des macrophages qui passent d’un état alternatif (M2) à un état dit classique (ou M1). Les macrophages M2 sont connus pour polariser les réponses immunitaires Th2, pour participer à l’élimination des parasites, pour diminuer l’inflammation, pour promouvoir le remodelage tissulaire et la progression des tumeurs et pour avoir des fonctions immunorégulatrices. Les macrophages M1 sont impliqués dans la réponse Th1, favorisent la résistance aux pathogènes intracellulaires et aux tumeurs et promeuvent des réactions de désagrégation tissulaires. L’ensemble de ces résultats permet de comprendre les propriétés anti-inflammatoires et immunostimulantes des préparations de VA. Des recherches complémentaires permettront d’améliorer les stratégies d’utilisation thérapeutique de VA et son utilisation dans les soins de support aux traitements anticancéreux
Viscum album (VA) preparations, commonly known as European mistletoe, are frequentlyused as complementary therapy in cancer, mainly to improve quality of life of the patients andto reduce the tumor growth. They are known to exert anti-tumoral effects. There is increasing evidence of the convoluted connection of cancer and inflammation. As cyclooxygenase-2(COX-2)-induced prostaglandin E2 (PGE2) plays a key role in the inflammation, I explored the regulation of COX-2-PGE2 axis by VA and underlying mechanisms. I found that VA exerts anti-inflammatory effects by selectively inhibiting COX-2 expression and ensuing PGE2 production. Inhibition of COX-2 expression implicates COX-2 mRNA destabilisation. In addition to their cytotoxic properties, they have also been shown to have immunostimulatory properties. Each VA preparations are highly heterogeneous because oftheir chemical composition which varies depending on the time of harvest, species of host treeand manufacturing methods, together which might influence clinical efficacy of VA.Therefore I performed a comparative study involving five different preparations of VA concerning maturation and activation of dendritic cells (DCs) which in turn may manifestanti-tumoral immune response. Results showed that among all five preparations, VA Qu Spez significantly induces DC activation, secretion of pro-inflammatory cytokines such as IL-6, Il-8 and TNF-α, enhancing IFN-γ production hence promoting Th1 immune response. The orchestration of myelomonocytic cell function is a key element that links inflammation and cancer and provides a paradigm for macrophage plasticity and function. My study reveals the effect of VA Qu Spez in switching the M2 macrophages which are known to participate inpolarizing Th2 responses, help with parasite clearance, dampen inflammation, promote tissue remodelling and tumor progression and have immunoregulatory functions, towards classicallyactivated M1 macrophages which are part of a polarized Th1 response and mediate resistance13to intracellular pathogens and tumors and elicit tissue-disruptive reactions. These results together should assist in understanding the anti-inflammatory and immunostimulatory properties of VA preparations and further research is warranted to improve the therapeutic strategies of use of VA and their role as complimentary therapy in cancer

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Chong, Wai-po y 莊偉波. "Tolerogenic and inflammatory properties of natural killer cells after interacting with apoptotic cells and immunoglobulin G opsonizedapoptotic cells". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B40203633.

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24

Chong, Wai-po. "Tolerogenic and inflammatory properties of natural killer cells after interacting with apoptotic cells and immunoglobulin G opsonized apoptotic cells". Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/hkuto/record/b40203633.

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25

BUSA', Rosalia. "Evaluation of antitumor and immunomodulatory properties of Indicaxanthin from Opuntia Ficus Indica (L. Mill) fruit". Doctoral thesis, Università degli Studi di Palermo, 2020. http://hdl.handle.net/10447/395264.

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Cancer is a growing health problem around the world and according to estimates from the International Agency for Research on Cancer (IARC), 14.1 million new cancer cases and 8.2 million cancer deaths worldwide have been reported in 2012 (Ferlay et al., 2015). By 2030, the global burden is expected to grow to 21.7 million new cancer cases and 13 million cancer deaths simply due to the growth and aging of the population. Indicaxanthin ((2S)-2,3-dihydro-4-[2-[(2S)-2a-carboxypyrrolidin-1- yl]ethenyl]pyridine-2a,6-dicarboxylic acid), a betalain pigment from cactus pear fruit, has been the object of sound experimental work over the latest years. As many phytochemicals, indicaxanthin is a redox-active compound and has been shown to act as antioxidant in a number of in vitro studies (Allegra et al., 2005; Turco Liveri et al., 2009). Interestingly, thanks to its charged portions, ionizable groups and lipophilic moieties, it is amphiphilic at physiological pH (Turco Liveri et al., 2009) and has been demonstrated to interact with cell membranes (Tesoriere et al., 2006; Turco Liveri et al., 2009). This feature is critical to allow bioactive compounds to interact with cells and to initiate signaling events. In this regard, indicaxanthin has been showed to modulate specific redox-dependent signaling pathways involved in macrophage activation and apoptosis, epithelial and endothelial dysfunction in vitro (Allegra et al., 2014; Tesoriere et al., 2015). Remarkably, and in contrast with the majority of dietary phytochemicals, indicaxanthin is highly bioavailable (Tesoriere et al., 2004). The molecule has been shown to cross unaltered intestinal epithelial cell in vitro being absorbed through paracellular junctions (Tesoriere et al., 2013). In line with that, indicaxanthin has been found in human plasma at a 7 μM peak concentration 3 h after the ingestion of four cactus pear fruits containing 28 mg of the pigment (Tesoriere et al., 2004). Moreover, its amphiphilicity allows it to cross the blood-brain-barrier and localize within the CNS (Allegra et al., 2015). Finally, thanks to its bioavailability and redox-modulating properties, indicaxanthin exerts significant pharmacological effects in vivo. Indeed, oral administration of the PhC at nutritionally-relevant doses (2 μmol/kg) generates, in rats, a plasma peak concentration of 0.2 μM able to exert strong anti-inflammatory effects in an in vivo model of acute inflammation (Allegra et al., 2014). The causative link between inflammation and melanoma has accurately been explored in the recent years (Bald et al., 2014; Meyer et al., 2011; Reinhardt et al., 2017; Soudja et al., 2010). Experiments in mice revealed that UV-induced skin inflammatory responses can cause the reactive proliferation and migration of melanocytes (Zaidi et al., 2011). More recently, it has been shown that reciprocal interactions between melanoma and immune cells in a pro-inflammatory microenvironment provide a source of phenotypic heterogeneity that drives therapy resistance and metastasis (Bald et al., 2014; Landsberg et al., 2012). In keeping this perspective, we decided to investigate the effects of Indicaxanthin against human melanoma cell proliferation and in a model of cutaneous melanoma. We here demonstrate that indicaxanthin induces apoptosis of human melanoma cells through the inhibition of the NF-κB pathway and the downstream anti-apoptotic signaling events in vitro and these effects were paralleled in vivo in a murine model of melanoma. Finally, preliminary data on six healthy volunteers, showed that indicaxanthin is able to modulate TNF- and Il-6 production in a whole blood ex vivo model. Furthermore, the phytochemical induces an increase in the phagocytosis of 5 different Gram-negative pathogens on whole blood assay, without exerting antimicrobial effects on them. Interestingly, preliminary data on 4 of the 6 volunteers showed that the observed effects maybe attributed to the modulation of LTB4 levels, strictly correlated to the activation of immune cells.

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26

Almeida, Sarah Raquel Matos. "Uncovering the binding and functional properties of S4D-SRCRB and Spα". Master's thesis, Universidade de Aveiro, 2015. http://hdl.handle.net/10773/15466.

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Mestrado em Biologia Molecular e Celular
The scavenger receptor cysteine-rich (SRCR) superfamily is characterized by proteins containing scavenger domains composed of about 100 amino acids with cysteine residues placed in a highly conserved manner among species. It is divided into two groups, A and B. The proteins of this superfamily can be expressed in diverse types of cells and be secreted or cell surface-bound, mediating protein-protein interactions and binding to (a) ligand(s). There is no special feature that unifies these proteins, except for the structural properties of the highly conserved domains. SRCR B proteins are involved in diverse functions such as pathogen recognition, modulation of immune response, epithelial homeostasis and tumor development among others. Spα and S4DSRCRB belong to this group. Spα is being associated to inflammatory conditions, like metabolic disorders (atherosclerosis and obesity), liver and lung cancer, being a pattern recognition receptor for diverse bacteria and fungi. Although structurally similar to Spα, very little is known about the expression pattern and localization of S4D-SRCRB. The characterization of both Spα and S4D-SRCRB proteins is important to understand what kind of roles they have in the homeostasis of the immune system. While the role(s) of S4D-SRCRB remain largely unknown, the importance of Spα as a pattern recognition receptor (PRR) and its involvement in inflammation was already observed. Nonetheless, numerous mechanisms associated with these proteins remain unexplored. The goal of this work was therefore to study the role of these proteins in inflammation. For that, different detection techniques were used for the characterization of the expression of the two proteins, at the tissue and cellular levels in a resting state. Then the variation of these proteins expression depending on inflammatory and anti-inflammatory stimuli given to epithelial or hematopoietic-origin cells was also analyzed. In this work new localizations of these two proteins are reported and their expression was shown to be different in response to inflammatory/antiinflammatory conditions, suggesting that they may have a role in different cellular locations and a function in the inflammatory modulation of both innate and adaptive immunity. Through the purification of the recombinant Spα, it was possible to identify cells that express ligand(s) for this protein, an important step to understand its function.
A superfamília de recetores scavenger ricos em cisteína é caracterizada por proteínas contendo domínios scavenger compostos por 100 aminoácidos com resíduos de cisteínas dispostos de uma forma bem conservada entre espécies. A superfamília encontra-se dividida em dois grupos, A e B, podendo as proteínas ser expressas em diversos tipos de células e serem secretadas ou estarem associadas à superfície celular mediando interações com outras proteínas e ligandos. Não há uma característica específica que unifique estas proteínas, exceto as propriedades estruturais dos domínios altamente conservados que apresentam. As proteínas pertencentes ao grupo SRCR B estão envolvidas em diversas funções como reconhecimento de patogénios, modulação da resposta imune, homeostasia do epitélio e desenvolvimento de tumores entre outros. Spα e S4D-SRCRB pertencem a este grupo. A proteína Spα tem sido associada a condições inflamatórias, como doenças metabólicas (aterosclerose e obesidade), cancro do pulmão e fígado, sendo também considerado um recetor de reconhecimento de patogénios para diversas bactérias e fungos. Apesar de estruturalmente semelhante ao Spα, pouco se sabe acerca do padrão de expressão da proteína S4D-SRCRB. As características de ambas proteínas Spα e S4D-SRCRB são importantes para a compreensão do tipo de papéis que estas proteínas têm na homeostasia do sistema imunitário. Enquanto que o papel de S4D-SRCRB permanece desconhecido, a importância de Spα como recetor de reconhecimento a patogénios e o seu envolvimento na inflamação foram já observados. No entanto, inúmeros mecanismos associados a estas proteínas permanecem desconhecidos. O objetivo deste trabalho foi, por conseguinte, estudar o papel destas proteínas na inflamação. Para tal, diferentes técnicas foram utilizadas para a caracterização da expressão destas duas proteínas, a nível tecidular e celular num estado de repouso. Após isto, foi analisado também a variação da expressão destas proteínas após estímulos inflamatórios e anti-inflamatórios dados a células de origem epitelial ou hematopoiética. Neste trabalho são reportadas novas localizações destas duas proteínas e demonstrado que a sua expressão parece ser diferente em resposta a condições de inflamação/anti-inflamação, sugerindo que possam ter um papel em diferentes localizações celulares e uma função na modulação da inflamação tanto na imunidade inata como adaptativa. Pela purificação da proteína recombinante Spα foi possível identificar células que expressam ligando(s) para esta proteína, um passo importante para entender a sua função.

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27

Gau, Jana, Paul-Georg Furtmüller, Christian Obinger, Jürgen Arnhold y Jörg Flemmig. "Enhancing hypothiocyanite production by lactoperoxidase – mechanism and chemical properties of promotors". Universitätsbibliothek Leipzig, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-206322.

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Background: The heme enzyme lactoperoxidase is found in body secretions where it significantly contributes to the humoral immune response against pathogens. After activation the peroxidase oxidizes thiocyanate to hypothiocyanite which is known for its microbicidal properties. Yet several pathologies are accompanied by a disturbed hypothiocyanite production which results in a reduced immune defense. Methods: The results were obtained by measuring enzyme-kinetic parameters using UV–vis spectroscopy and a standardized enzyme-kinetic test system as well as by the determination of second order rate constants using stopped-flow spectroscopy. Results: In this study we systematically tested thirty aromatic substrates for their efficiency to promote the lactoperoxidase-mediated hypothiocyanite production by restoring the native ferric enzyme state. Thereby hydrophobic compounds with a 3,4-dihydroxyphenyl partial structure such ashydroxytyrosol and selected flavonoids emerged as highly efficient promotors of the (pseudo-)halogenating lactoperoxidase activity. Conclusions: This study discusses important structure-function relationships of efficient aromatic LPO substrates and may contribute to the development of new agents to promote lactoperoxidase activity in secretory fluids of patients. Significance: This study may contribute to a better understanding of the (patho-)physiological importance of the (pseudo-)halogenating lactoperoxidase activity. The presented results may in future lead to the development of new therapeutic strategies which, by reactivating lactoperoxidase-derived hypothiocyanite production, promote the immunological activity of this enzyme.

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28

Keet, Lana. "Development of in vitro models to investigate the anti-inflammatory properties of Cyclopia Maculata and other South African herbal teas : a comparative study". Thesis, Stellenbosch : Stellenbosch University, 2015. http://hdl.handle.net/10019.1/97030.

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Thesis (MSc)--Stellenbosch University, 2015.
ENGLISH ABSTRACT: Chronic inflammation is suggested to contribute to cancer development and therefore a potential target for chemoprevention. In the skin, keratinocytes and macrophages play an integral part in acute and chronic inflammation, with interleukin 1-α (IL-1α) and tumor necrosis factor α (TNF-α) as key cytokines governing this process. Green tea (Camellia sinensis) and the South African herbal teas, rooibos (Aspalathus linearis) and honeybush (Cyclopia spp.) displayed antiinflammatory effects in mouse and human skin. To further investigate the antiinflammatory properties of green tea and the herbal teas, rooibos and honeybush (C. subternata and C. maculata) herbal teas, suitable cell culture models were developed and validated utilising human keratinocytes (HaCaT) and monocyte (THP- 1) derived macrophages. Aqueous extracts of the green tea and unfermented herbal teas were prepared and their chemical composition determined by high performance liquid chromatography (HPLC) and the antioxidant activity characterised utilising different antioxidant assays. Green tea and rooibos exhibited similar antioxidant activities while C. maculata displayed the lowest overall antioxidant activity of all the extracts, despite possessing the highest mangiferin level, the major polyphenol in honeybush. The modulation of cytokine release was studied in (i) an UVB-induced pre-exposure HaCaT model monitoring the accumulation of IL-1α and (ii) a LPS stimulated THP-1 macrophage model monitoring the TNF-α release, utilising both a pre-exposure and co-exposure extract regimens. In the pre-exposure HaCaT inflammatory model the UVB-induced IL-1α was decreased by the green tea extract while a far weaker response was obtained with the rooibos extract. Both the honeybush extracts displayed a significant effect in the reduction of IL-1α with C. subternata exhibiting a slight increased protection at a lower extract concentration. In the pre-exposure THP-1 derived macrophage model, green tea and the herbal tea extracts inhibited TNF-α release in a dose dependent manner in the absence of an overt loss in cell viability and apoptosis at lower extract concentrations, suggesting a typical anti-inflammatory effect. In the co-exposure model, the different extracts also exhibited an anti-inflammatory effect at the lowest concentrations in the absence of apoptosis while at higher extract concentrations the effect was masked by a decrease in cell viability and increased apoptosis. C. maculata exhibit differential effects when considering the inhibition of cytokine production and, depending on the cell model, either exhibited a weaker or stronger effect when compared to C. subternata and rooibos. Phenolic diversity of the different teas is likely to explain the differential effects in the antioxidant assays and cell culture models with respect to the regulation of the production of the inflammatory markers. Proposed mechanism for the anti-inflammatory effects include the modulation of oxidative stress via various pathways and the subsequent down regulation of nuclear factor kappa β (NFκB) and activated protein-1 (AP-1) which are key regulators of cytokine production governing the inflammatory response.
AFRIKAANSE OPSOMMING: Kroniese inflammasie van die vel kan bydra tot die ontwikkeling van kanker en is dus ’n potensiële area om te teiken in die voorkoming van velkanker. Keratinosiete en makrofage speel ’n integrale rol in akute en chroniese inflammasie van die vel en TNF-α en IL-1α is die belangrikste sitokiene wat hierdie proses inisieer. Dit is bekend dat ekstrakte van groen tee (Camellia sinensis) en die Suid-Afrikaanse kruietees, rooibos (Aspalathus linearis) en heuningbos (Cyclopia spp.) ‘n anti-inflammatoriese effek op die vel van muise en mense het. Om die anti-inflammatoriese aktiwitieit van groen tee, rooibos en 2 heuningbos kruietees (C. subternata en C. maculata) verder te ondersoek en te definieer is geskikte selkultuurmodelle ontwikkel en gevalideer deur gebruik te maak van menslike keratinosiete (HaCaT) en monosiet (THP-1) afgeleide makrofage. Water ekstrakte van groen tee en ongefermenteerde kruietees is voorberei en die chemiese samestelling deur hoë druk vloeistof chromatografie (HDLC) bepaal. ‘n Verskeidenheid van antioksidant bepalingstoetse is gebruik om die antioksidant aktiwiteit van die ekstrakte te meet. Groen tee en rooibos het soortgelyke antioksidant aktiwiteite getoon, terwyl C. maculata die swakste algehele aktiwiteit getooon het, ten spyte van die teenwoordigheid van hoёr vlakke van mangiferin, die belangrikste polifenoliese verbinding in heuningbos. Modulasie van sitokiene is verder bestudeer in (i) ’n UVB-geïnduseerde vooraf-blootstelling HaCaT model, waartydens akkumulering van IL-1α gemonitor is en (ii) ‘n lipopolisakkaried (LPS)-gestimuleerde THP-1 makrofaag model, waar die vrystelling van TNF-α gemonitor is. Vir die THP-1 model is beide die voor en gelyktydige blootstelling benaderings vir die ekstrakte met LPS gebruik. In die keratinosiet model, waar die selle aan ekstrakte blootgestel is voor UVB bestraing, is IL-1α beduidend verlaag deur die groen tee ekstrak, terwyl ’n swakker reaksie gesien is met rooibos. Beide heuningbos ekstrakte het ’n beduidende invloed in die vermindering van IL-1α getoon, waar C. subternata ’n effense verhoogde beskerming teen selsterfte by ‘n laer ekstrakkonsentrasie toon. Blootstelling van die makrofage aan al vier ekstrakte voor LPS stimulasie (vooraf-blootstelling), het gelei tot inhibisie van TNF-α vrystelling op ’n dosis afhanklike wyse en die afwesigheid van apoptose en selsterftes by lae ekstrak konsentrasievlakke. Hierdie waarnemings dui op ’n tipiese antiinflammatoriese effek. In die gelyktydige-blootstelling model verlaag al die ekstrakte TNF-α vrystelling teen die laagste ekstrak konsentrasievlakke, in die afwesigheid van apoptose en met geen effek op seldood nie. Hoёr ekstrak konsentrasievlakke het sitotoksisiteit en verhoogde apoptose getoon, dus was die anti-inflammatoriese effek gemaskeer. C. maculata toon ‘n variërende effek met betrekking tot antioksidant aktiwiteit en die bekamping van sitokien produksie, afhangend van die model wat bestudeer is. Die verskeidenheid fenoliese verbindings teenwoordig in die verskillende tee ekstrakte is waarskynlik die rede vir die effekte wat waargeneem is tydens antioksidant toetsing en selkultuurmodelle. Die anti-inflammatoriese meganismes wat deur hierdie studie voorgestel word sluit die modulasie van oksidatiewe stres via verskeie metaboliese paaie in. Modulasie van oksidatiewe stres lei tot af-regulering van kernfaktor-kappaB (NF-κB) en aktiveerderproteïen- 1(AP-1), wat sleutel reguleerders van sitokien produksie tydens inflammatoriese respons is.

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29

Gau, Jana, Paul-Georg Furtmüller, Christian Obinger, Jürgen Arnhold y Jörg Flemmig. "Enhancing hypothiocyanite production by lactoperoxidase – mechanism and chemical properties of promotors". Elsevier, 2015. https://ul.qucosa.de/id/qucosa%3A14827.

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Background: The heme enzyme lactoperoxidase is found in body secretions where it significantly contributes to the humoral immune response against pathogens. After activation the peroxidase oxidizes thiocyanate to hypothiocyanite which is known for its microbicidal properties. Yet several pathologies are accompanied by a disturbed hypothiocyanite production which results in a reduced immune defense. Methods: The results were obtained by measuring enzyme-kinetic parameters using UV–vis spectroscopy and a standardized enzyme-kinetic test system as well as by the determination of second order rate constants using stopped-flow spectroscopy. Results: In this study we systematically tested thirty aromatic substrates for their efficiency to promote the lactoperoxidase-mediated hypothiocyanite production by restoring the native ferric enzyme state. Thereby hydrophobic compounds with a 3,4-dihydroxyphenyl partial structure such ashydroxytyrosol and selected flavonoids emerged as highly efficient promotors of the (pseudo-)halogenating lactoperoxidase activity. Conclusions: This study discusses important structure-function relationships of efficient aromatic LPO substrates and may contribute to the development of new agents to promote lactoperoxidase activity in secretory fluids of patients. Significance: This study may contribute to a better understanding of the (patho-)physiological importance of the (pseudo-)halogenating lactoperoxidase activity. The presented results may in future lead to the development of new therapeutic strategies which, by reactivating lactoperoxidase-derived hypothiocyanite production, promote the immunological activity of this enzyme.

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30

MENEGUZZO, DAIANE T. "Fototerapia com laser em baixa intensidade em processo inflamatorio agudo induzido por carragenina em pata de camundongos - estudos de dosimetria". reponame:Repositório Institucional do IPEN, 2010. http://repositorio.ipen.br:8080/xmlui/handle/123456789/9605.

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Made available in DSpace on 2014-10-09T12:28:33Z (GMT). No. of bitstreams: 0
Made available in DSpace on 2014-10-09T13:56:00Z (GMT). No. of bitstreams: 0
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Tese (Doutoramento)
IPEN/T
Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP
FAPESP:08/00723-4

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31

Abdou, Bouba Armand. "Contribution à l’étude du développement d’un aliment fonctionnel à base d’épices du Cameroun : caractérisation physico-chimique et fonctionnelle". Thesis, Vandoeuvre-les-Nancy, INPL, 2009. http://www.theses.fr/2009INPL006N/document.

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La recrudescence des maladies dégénératives ces dernières décennies dans le monde a amené plusieurs chercheurs et médecins à médiatiser les antioxydants à cause des vertus qu’on leur prête: de la protection contre les maladies cardiovasculaires à la prévention de certains cancers. Le présent travail a été mené avec pour objectif principal d’évaluer le pouvoir antioxydant des épices entrant dans la préparation de la sauce en vue du développement d’un complément alimentaire nutraceutique. Pour ce faire, vingt épices largement consommées ont été choisies sur la base d’une enquête exploratoire menée au Cameroun. Les différentes épices réduites en poudres ont été analysées pour leurs teneurs en composition nutritionnelle. Le pouvoir antiradicalaire in vitro des extraits méthanoliques des différentes épices a été déterminé ainsi que le pouvoir anti-inflammatoire et antistress sur des rats adultes à stress induit. Les résultats obtenus ont montré des variations très significatives de la composition des épices. L’activité antioxydante utilisant la méthode au N’ N-diphényl-N’-picrylhydrazyl (DPPH), au « trolox equivalent antioxidant capacity » (TEAC) et le pouvoir réducteur total (PRT) ont révélé que Z. leprieurii et D. glomerata présentent les activités particulièrement élevées. Les extraits de ces deux épices ont servi de base à la préparation de mélange dont l’effet a été testé sur des rats mâles à inflammation induite. Les résultats obtenus ont montré que les épices individuelles et leur mélange à des doses de 100 mg/kg et 150 mg/kg présentent une activité anti-inflammatoire importante comparable à ceux commerciaux: inodméthacine, déxaméthasone et célécoxib. La variation de la teneur en malonaldéhyde (marqueur de l’oxydantion lipidique) a révélée l’action antioxydante in vivo des extraits, démontrant ainsi leur potentiel dans le développement de compléments alimentaires à effet antistress
Increasing evidences from current research point to the fact that certain disease conditions can be prevented through the consumption of antioxidant rich foods. The present work was carried out to evaluate the antioxidant potentials of twenty Cameroonian spices commonly used in some Cameroonian cuisine. The nutritional properties of spices, the in vitro antioxidant potential of their methanolic extracts as well as the in vivo antioxidant potential of the methanolic extracts of some selected samples were determined. The antioxidant activity brought about by N’ N-diphenyl-N’-picrylhydrazyl (DPPH), «trolox antioxidant equivalent capacity» (TEAC) and the total reduction power (PRT) methods have revealed that Z. leprieurii and D. glomerata presented the highest activities. The extracts of the two spices were used to prepare a mixture whose effect was tested on male rats with induced inflammation. The results obtained indicate that the individual spices and their mixture at 100 mg/kg and 150 mg/kg present an important anti-inflammatory activity comparable to that of commercial anti-inflammatory like indomethacin, dexamethasone and celecoxib. The variation of malondialdehyde content (a lipidic oxidant marquer) revealed the in vivo antioxidant action of extracts, thus demonstrating their potential for the development of functional foods with anti-stress effect

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32

Harris, James Patrick. "The Glia-Neuronal Response to Cortical Electrodes: Interactions with Substrate Stiffness and Electrophysiology". Case Western Reserve University School of Graduate Studies / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1320950439.

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33

Costa, Maria Alexandra Barata de Vasconcelos Nunes. "Regulation of the inducible L-arginine-nitric oxide pathway by oxidative stress and statins". Thesis, University of Hertfordshire, 2010. http://hdl.handle.net/2299/4323.

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Oxidative stress (OS) plays a critical role in the pathogenesis of atherosclerosis potentially through interaction with nitric oxide (NO) generated by the inducible nitric oxide synthase (iNOS) pathway. Although considerable literature supports a pro-atherogenic role for iNOS-induced NO, recent evidence suggest an anti-atherogenic property for this enzyme where iNOS-induced NO attenuates atherosclerotic lesions after immune injury, enhancing endothelial integrity, survival, protecting against OS-induced apoptosis and necrosis. We therefore hypothesize that iNOS may have a cardio-protective role in the atherosclerotic vessel and that under conditions of OS, expression and function of this enzyme may be impaired, thus contributing to the deleterious consequences of OS. Experiments have therefore been conducted to establish whether pro-oxidants regulate iNOS expression/function in rat cultured aortic smooth muscle cells (RASMCs). These cells were induced for 24 hours with LPS and IFN-γ to mimic inflammatory conditions. Oxidative stress inducers may modulate iNOS-induced NO production through alteration of the expression and/or function of the inducible L-arginine-NO pathway. We examined the effects of hydrogen peroxide (H2O2), antimycin A and diethyl maleate (DEM) on this pathway in vascular smooth muscle cells. H2O2 had little effect on NO production or L-arginine transport while antimycin A and DEM independently caused a concentration dependent inhibition of both processes. Only DEM induced hemeoxygenase-1 (HO-1) expression, monitored by western blotting as a marker of OS. The effects of statins on NO synthesis and L-arginine transport in the presence and absence of OS were also investigated. The benefits of statins therapy in cardiovascular medicine are ascribed in part to their lipid-lowering effect by inhibiting 3-hydroxy-3-methoxyglutaryl coenzyme A (HMG-CoA) reductase, the rate limiting enzyme for cholesterol synthesis. However, statins may possess anti-inflammatory properties and are able to improve endothelial function, stabilize atherosclerotic plaque, and inhibit platelet aggregation, vascular smooth muscle cells proliferation and vessel wall inflammation. These effects may be exerted through novel actions of statins that include interaction with specific signalling pathways in cells which may be associated with the induction of iNOS and/or cationic amino acid transporters (CATs). Thus, we have extended our investigations to include an examination of the effects of statins on both iNOS and CAT function and expression under control conditions and following exposure of cells to OS. Atorvastatin caused a bell shaped response on NO production and iNOS expression and also enhanced L-arginine transport but in a non-concentration dependent manner. Simvastatin only affected NO synthesis without altering transporter activity. Pravastatin was without effect on either system. Further studies demonstrated that that atorvastatin was able to reverse the effects of antimycin A and DEM but only on NO production. These findings confirm that the inducible L-arginine-NO pathway can be downregulated by pro-oxidants. This mechanism may therefore contribute to the deleterious effects observed in disease states associated with OS. Moreover, statins (in particular atorvastatin) appear to be effective in reversing the inhibition of NO production caused by inducers of OS. This, together with the fact that atorvastatin and simvastatin can potentiate iNOS-induced NO production and indeed L-arginine transport (with atorvastatin), highlights a potential novel mechanism through which the cardio-protective actions of these compounds could be mediated.

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34

Billaud, Yann. "Modélisation hybride stochastique-déterministe des incendies de forêts". Thesis, Aix-Marseille 1, 2011. http://www.theses.fr/2011AIX10100/document.

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Les grands incendies de forêts sont responsables de la quasi-totalité de la surface brulée et contribuent, par les émissions de particules et de gaz à effet de serre qu’ils génèrent, au réchauffement climatique. Des observations satellitaires ont mis en évidence un comportement fractal que l’on attribue aux hétérogénéités locales (topographie, végétation, conditions météorologiques) rencontrées par ces feux lors de leur propagation. Le présent travail a été consacré au développement et à la validation d’un modèle hybride de propagation d’incendie, capable de reproduire ce comportement. Ce modèle est une extension du modèle original de réseau de « petit monde » où les phénomènes qui se produisent à l’échelle macroscopique, comme le rayonnement du front de flammes et l’inflammation pilotée de la strate végétale sont traités de façon déterministe. Pour décrire le rayonnement, nous avons utilisé un modèle de flamme solide couplé à une méthode de Monte Carlo. La validation a porté sur des configurations simples, mais aussi plus complexes, comme le rayonnement d’un front hétérogène de flammes ou celui d’une flamme d’éthanol. Un modèle d’inflammation a ensuite été élaboré et appliqué à des litières d’aiguilles de pin. Les paramètres du modèle ont été optimisés par un algorithme génétique, conduisant au meilleur accord avec les résultats expérimentaux, en termes de temps d‘inflammation et de perte de masses. Il a été montré que l’oxydation du résidu charbonneux joue un rôle prépondérant sur l’inflammation à bas flux. Le modèle de propagation de petit monde a été validé sur un brûlage dirigé et sur un feu historique, montrant un bon accord en termes de surface brûlée, de vitesse de propagation, de contours de feu, et de propriétés fractales. On a montré qu’il pouvait être utilisé pour le dimensionnement d’ouvrages de défense, comme les coupures de combustible, ou pour expliquer le comportement atypique du feu dans certaines situations (talweg, ruptures de pente, etc.). Son application a également permis d’optimiser le nombre et l’emplacement d’un réseau de capteurs déployés dans la végétation dans le but de localiser précisément et détecter précocement le départ d’un feu
Most of the area burned by forest fires is attributable to the few fires that escape initial attack to become large. As a consequence large-scale fires produce a large amount of green-house gases and particles which contribute to the global warming. Heterogeneous conditions of weather, fuel, and topography are generally encountered during the propagation of large fires. This shapes irregular contours and fractal post-fire patterns, as revealed by satellite maps. Among existing wildfire spread models, stochastic models seem to be good candidates for studying the erratic behavior of large fires, due to the above-mentioned heterogeneous conditions. The model we developed is a variant of the so-called small-world network model. Flame radiation and fuel piloted ignition are taken into account in a deterministic way at the macroscopic scale. The radiative interaction domain of a burning cell is determined from Monte Carlo simulation using the solid flame model. Some cases are studied, ranging from relatively simple to more complex geometries like an irregular flame fronts or an ethanol pool fire. Then, a numerical model is developed to investigate the piloted ignition of litters composed of maritime pine needles. A genetic algorithm is used to locate a set of model parameters that provide optimal agreement between the model predictions and the experimental data in terms of ignition time and mass loss. The model results had shown the importance of char surface oxidation for heat fluxes close to the critical flux for ignition. Finally, the small-world network model was used to simulate fire patterns in heterogeneous landscapes. Model validation was achieved to an acceptable degree in terms of contours, burned area and fractal properties, through comparison of results with data from a small controlled bushfire experiment and a historical Mediterranean fire. Therefore, it has been proven to be a powerful tool in the sizing of fortifications as fuel break areas at the wildland urban interface or in the understanding of atypical behavior in particular configurations (talweg, slope breaking, etc.). It has also been used for the optimization of an in-situ sensor network whose purpose is to detect precociously and to locate precisely small fires, preventing them from spreading and burning out of control. Our objective was to determine the minimum number and placement of sensors deployed in the forest

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35

Boone, Marc. "High-definition optical coherence tomography: Contribution to the non-invasive near infrared optical imaging techniques of the skin". Doctoral thesis, Universite Libre de Bruxelles, 2016. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/232235.

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Background. The development of non-invasive imaging techniques has been stimulated by the shortcomings of histopathology. Currently the only valid diagnostic technique in dermatology is skin biopsy which remains a painful, invasive intervention for the patient. Moreover, this approach is not always convenient for monitoring and follow-up of a skin disease. Optical imaging technologies could solve these shortcomings as they are fast, precise, repeatable and painless. There are four established non-invasive skin imaging techniques used in daily practice: dermoscopy, high-frequency ultrasound, reflectance confocal microscopy (RCM) and conventional optical coherence tomography (C-OCT). In imaging there is a trade-off between resolution and penetration depth. The former permits the visualization of cells, if the resolution is at least 3 µm. The latter enables the recognition of patterns and structures in deeper layers of the skin if the penetration depth is deeper than 150 µm. New non-invasive techniques using infrared light sources have been developed recently. The technique used in this work is a high-definition optical coherence tomography (HD-OCT).Objectives. The overall aims of this thesis were the feasibility of HD-OCT to visualize in/ex vivo, in real time and in 3-D the cellular and structural morphology of the skin, secondly the assessment of the capability of this technology to measure in vivo and real time the cutaneous optical properties, and finally the determination of the contribution of this technique to the non-invasive near-infrared imaging technologies. Five specific objectives have been established: i) could cells be observed in their 3-D microenvironment in normal and diseased skin, ii) could we describe morphologic features of cells and structures in normal and diseased skin (m_HD-OCT), iii) could these morphologic features be quantified by optical property analysis (o_HD-OCT), iv) was it possible to perform accurate thickness measurements in normal and diseased skin, and finally v) what was the diagnostic potential of this technique?Methodology. HD-OCT uses a combination of parallel time-domain interferometry, high power tungsten lamp (with Gaussian filter, very low lateral coherence and ultra-high bandwidth (1300 nm +/- 100 nm)), and last but not least, full field illumination with real time focus tracking. A constant homogeneous resolution of 3 µm resolution in all three dimensions is obtained up to a depth of 570 µm. Hence, the system is capable of capturing real time full 3-D images. Moreover, the in vivo assessment of optical properties of the skin is only applicable to OCT when operating in focus-tracking mode, which is the case for HD-OCT. The means to obtain answers to the five specific questions were the comparison of en face HD-OCT images with RCM and HD-OCT cross-sectional images with histopathology and C-OCT. Results. At least 160 line pares were observed by imaging a high resolution phantom with HD-OCT. This suggested a 3 µm lateral resolution. The presence of cells such as keratinocytes, melanocytes, inflammatory cells, fibroblasts and melanophages in their 3-D cutaneous microenvironment in vivo as well as ex vivo has been demonstrated .A qualitative description of structures and patterns in normal and diseased skin could be performed by HD-OCT. Clear structural changes of the epidermis, dermo-epidermal junction, papillary dermis and reticular dermis related to intrinsic skin ageing could be observed. Lobulated structures, surrounded by stretched stromal fibers and arborizing vessels, could be demonstrated in nodular basal cell carcinoma (BCC). The o_HD-OCT of normal and diseased skin could be assessed in vivo. This approach permitted the quantitative assessment of the OCT signal attenuation profiles of normal healthy skin, actinic keratosis (AK) and squamous cell carcinoma (SCC). Differences in signal attenuation profiles could be demonstrated between these three groups. These differences were also observed between BCC subtypes. The slope of the exponential attenuation of the signal in the upper part of the epidermis was very high in benign nevi. The more malignant the lesion the lower the slope. Thickness measurements of epidermis and papillary dermis could be performed by m_HD-OCT, based on a cross-sectional images and their corresponding en face image. More accurate measurements of epidermal and papillary dermal thickness could be performed based on the optical analysis of a skin volume by o_HD-OCT. The diagnostic potential of HD-OCT in comparison with dermoscopy, RCM and C-OCT could be assessed regarding i) melanoma, ii) BCC differentiation from BCC imitators and BCC sub-differentiation and iii) SCC differentiation from AK. A much higher diagnostic potential could be demonstrated for o_HD-OCT in comparison with m_HD-OCT concerning melanoma detection. The diagnostic potential of HD-OCT to discriminate BCC from clinical BCC imitators was moderate. However, HD-OCT seemed to have high potential in sub-differentiation of BCC subtypes: i) it seemed to be the best technique to include and exclude a superficial BCC, ii) the technique appeared to be the best approach to exclude nodular BCC, and iii) HD-OCT looked to be the best technique to include an infiltrative BCC. Finally, HD-OCT has proven to be a powerful method to discriminate AK from SCC.Conclusions. HD-OCT is able to capture real time 3-D imaging with a sufficiently high optical resolution and penetration depth to allow the visualization of cells in and ex vivo in their micro-architectural context. At the same time, HD-OCT permits the recognition of patterns and structures in a sufficiently large volume of skin (1.5 mm³). HD-OCT closes therefore the gap between RCM with a high resolution but low penetration depth and C-OCT with a low resolution but high penetration depth. Moreover, HD-OCT permits, in contrast to RCM and C-OCT, the real time in vivo analysis of optical properties of the skin. HD-OCT seems to be a promising tool for early diagnosis of melanoma, BCC sub-differentiation and differentiation between SCC and AK.Future perspectives. Multicenter validation studies are needed to determine the diagnostic performance of this promising new technology, especially in other clinical settings combining both morphological and optical property analysis. This combined analysis could be a valuable method not only for diagnosis, monitoring and therapeutic guidance of dermatologic diseases but it could also be helpful in the management of non-dermatologic conditions such as diabetic micro-angiopathy, infantile cystinosis or even osteoporosis.
Doctorat en Sciences médicales (Santé Publique)
info:eu-repo/semantics/nonPublished

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36

Amamou, Asma. "Le récepteur minéralocorticoide : une cible potentielle dans la fibrose intestinale ? Mineralocorticoid receptor antagonisl improves inflammation and fibrosis in chronic DSS colitis mouse model Neutrophil gelatinas-associated lipocalin (NGAL) is a mineralocorticoid receptor target involved in intestinal inflammation and fibrosis Inflammatory bowel diseases and food additives : to add fuel on the flames Dietary salt activates intestinal fibroblasts, thereby contributing to exacerbation of intestinal fibrosis Dietary aryl hydrocarbon receptor ligands have no anti-fibrotic properties in transforming growth factor-β1-stimulated human colonic fibroblasts Effet d'un régime riche en sel sur la fibrose intestinale dans un modèle murin de colite chronique Etude de l'interaction entre des dérivés du tryptophane et le récepteur aryl hydrocarbone dans un modèle in vitro de fibrose intestinale". Thesis, Normandie, 2020. http://www.theses.fr/2020NORMR079.

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Les maladies inflammatoires chroniques de l’intestin (MICI) se développent chez des individus génétiquement prédisposés sous l’influence de facteurs environnementaux. La fibrose intestinale est une complication fréquente de ces MICI sans traitement spécifique, qui se caractérise par une accumulation de matrice extracellulaire synthétisée par les cellules mésenchymateuses. Le récepteur minéralocorticoïde (RM) est l’effecteur terminal du système hormonal rénineangiotensine-aldostérone (SRAA). Le RM et l’ensemble des composants du SRAA sont exprimés dans le tractus gastro-intestinal et leur expression est augmentée dans l’intestin des patients atteints de MICI. L’antagonisme du RM exerce des effets bénéfiques sur la réduction de l’inflammation et de la fibrose extra-intestinales.L’objectif principal de ce travail de thèse était de déterminer si l’antagonisme du RM exerce des effets bénéfiques sur la fibrogenèse intestinale et d’en identifier les mécanismes sous-jacents. Un modèle de colite chronique induite chez la Souris et des modèles cellulaires de fibrose intestinale ont été utilisés. L’antagonisme du RM a été étudiée par des approches pharmacologiques et par invalidation génétique. Nous avons montré que l’inhibition pharmacologique ou génétique du RM diminue l’inflammation et la fibrose intestinales dans le modèle de colite chronique chez la Souris. L’activation du RM par l’aldostérone augmente la prolifération ainsi que l’expression de TGF-β1 des fibroblastes coliques humains et promeut la transition endothélio-mésanchymateuse, des cellules endothéliales vasculaires intestinales humaines. Nous avons également montré que la lipocaline associée à la gélatinase des neutrophiles (NGAL) est une cible du RM au niveau de l’intestin et est responsable des effets pro-fibrotiques médiés par l’activation du RM. L’invalidation génétique de la NGAL inhibe la voie de signalisation du TGF-β1 dépendante des SMAD, qui joue un rôle central dans l’initiation et le développement de la fibrose. En conclusion, nous avons d’une part démontré l’implication du RM dans la fibrose intestinale et d’autre part montré que ses effets étaient dépendants de la NGAL. Ainsi, l’antagonisme du RM pourrait constituer une nouvelle cible thérapeutique dans la fibrose intestinale associée aux MICI et permettrait de repositionner des molécules déjà disponibles dans le contexte des MICI
Inflammatory bowel diseases (IBD) occur in people with a genetic predisposition under the influence of environmental factors. Intestinal fibrosis is a common complication in IBD with no specific therapy which is characterized by an accumulative deposit of extra-cellular matrix produced by mesenchymal cells. Mineralocorticoid receptor (MR) is the final effector of renin-angiotensin-aldosterone system (RAAS). MR and all components of RAAS are expressed in the gastrointestinal tract and are up-regulated in the intestine from IBD patients. MR antagonism exerts beneficial properties in inflammation and fibrosis from extra-intestinal organs. We aimed to investigate whether MR antagonism had beneficial effects in intestinal fibrogenesis using murine chronic colitis and cellular models of intestinal fibrosis. MR antagonism was investigated by a dual approach using pharmacological inhibition and genetic invalidation. In the present study, we have demonstrated that pharmacological or genetic MR antagonism reduced inflammation and intestinal fibrosis in murine DSS chronic chemically-induced colitis. MR activation by aldosterone increased cell proliferation and TGF-β1 production in human colonic fibroblasts and human intestinal endothelial cells. Lipocalin associated with neutrophil gelatinase (NGAL) mediated pro-fibrotic effects via the activation of RM by aldosterone. Genetic invalidation of NGAL also reduced the SMAD-dependent TGF-β1 signaling pathway. In conclusion, we have demonstrated the MR involvement in intestinal fibrosis and these effects are mediated through NGAL. Thus, MR antagonism may represent a novel attractive approach in the treatment of intestinal fibrosis associated with IBD and may allow the repositioning molecules already available in the field of IBD

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37

Hou, Yu-Chen y 侯又禎. "Immunoregulatory effects of glutamine in pulmonary inflammation". Thesis, 2012. http://ndltd.ncl.edu.tw/handle/41319557074244528455.

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YUEH-LUN, LEE y 李岳倫. "The immunoregulatory mechanism of IL-12 on animal model of airway inflammation". Thesis, 1998. http://ndltd.ncl.edu.tw/handle/37757638090349873085.

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博士
國立臺灣大學
微生物學研究所
87
The incidence of asthma has increased substantially in the last two decades, despite increased variety of therapeutic agents. Existing drugs offer partial relief of symptoms in such disease, but there is a great need to develop more specific agents to suppress the inflammatory response in allergic asthma. In this study, we develop a novel therapeutic approach for Der p 1-induced allergic asthma with IL-12 treatment. First, an animal model of airway inflammation induced by house dust mite Der p 1 allergen was established. Then, the in vivo effects of IL-12 on the murine model of asthma were examined. The data demonstrated that IL-12 treatment during antigen sensitization not only promoted Th1 immune responses but also inhibited airway inflammation after a single inhaled antigen challenge. Moreover, the studies were extended to investigate the effects of IL-12 administration to maintain immune responses after multiple allergen challenge and to redirect immune responses after Th2-dominated conditions. The data demonstrated that IL-12 was useful as a therapeutic agent to abolish eosinophil recruitment, despite Th2-associated responses were existed. However, IL-12 could not prevent allergic asthma to maintain a stable and dominated Th1 responses for a long-term time. Furthermore, to apply IL-12 gene in gene therapy, plasmid expressing vectors, expressing coordinately p35 and p40 subunits or a single-chain IL-12 protein, was constructed and designated as pIL-12 or pscIL-12, respectively. The bioactivity of recombinant IL-12 was analyzed both in vitro and in vivo studies. These data revealed that pscIL-12 could encode functional single-chain IL-12 fusion protein and the free p40 subunits which can behave as IL-12 antagonist were negligible. Thus, such pscIL-12 may provide a more appropriate tool in future application of gene therapy for allergic diseases.

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39

Sekhon-Loodu, Satvir. "Antioxidant, Anti-inflammatory and Hypolipidemic Properties of Apple Flavonols". 2012. http://hdl.handle.net/10222/15469.

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Obesity is considered an underlying risk factor for metabolic disease including cardiovascular disease (CVD) and diabetes. The fractions containing flavonols from apple peel were evaluated for their antioxidant, anti-inflammatory, and hypolipidemic properties using in vitro and in vivo experimental model systems. The fractionated polyphenolics from apple peels showed a strong antioxidant property protecting against heat-induced oxidation of polyunsaturated fatty acids present in fish oil. Apple flavonols (AF), eicosapentaenoic acid (EPA) and the isoquercitrin-EPA ester (QE) significantly reduced serum triacylglycerols and elevated the high density lipoprotein (HDL)-cholesterol compared to the high fat control group. C-reactive protein and interleukin-6 were also reduced compared to the high fat control group and inflammation induced by lipopolysaccharides. Serum adiponectin and interferon-? concentrations were significantly altered by QE treatment. Overall, AF and QE exhibited anti-inflammatory and hypolipidemic effects under in vivo conditions. These beneficial physiological properties and mode of action of AF and QE need to be further investigated.

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40

Maliba, Ricardo J. M. "Regulation of the proinflammatory properties of angiopoietins". Thèse, 2006. http://hdl.handle.net/1866/15503.

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41

Gandy, Justin John. "An evaluation of the anti-allergic properties of potassium humate". Diss., 2007. http://upetd.up.ac.za/thesis/available/etd-04292008-095801.

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Kim, Jin Hee. "Anti-inflammatory Properties of Citrus Limonoids and Their Isolation and Characterization". Thesis, 2011. http://hdl.handle.net/1969.1/ETD-TAMU-2011-12-10693.

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This dissertation investigates the role of limonoids in inflammation to reduce risk of breast cancer and cardiovascular disease. Radical scavenging activity and apoptotic effects of extracts from lemon seeds were investigated in human breast adenocarcinoma (MCF-7) cells and non-malignant breast (MCF-12F) cells. The MeOH:water (80:20) extract showed the highest (29.1%, P < 0.01) inhibition of MCF-7 cells without affecting the non-malignant breast cells. Further, the purified and modified limonoids were screened for their cytotoxicity on estrogen receptor (ER)-positive (MCF-7) or ER-negative (MDA-MB-231) human breast cancer cells. The MCF-7 cell was more susceptible to tested limonoids. Although most of limonoids induced anti-aromatase activity, the inhibition of proliferation was not related to the anti-aromatase activity. On the other hand, the anti-proliferative activity was significantly correlated with the level of caspase-7 activation by limonoids. The next study investigated the mechanism of anti-breast cancer and anti-aromatase activities of obacunone through inhibition of MCF-7 cell proliferation without affecting non-malignant breast cells. Treatment with obacunone resulted in an increased G1 cell cycle arrest and induction of apoptosis. Exposure of MCF-7 breast cancer cells to obacunone down-regulated expression of inflammatory molecules including nuclear factor-kappa B (NF--2 (COX-2). Furthermore, potential of obacunone on inhibition of COX-2 and NF-the p38 mitogen-activated protein (MAP) kinase was also investigated. In the final study, nomilin was the most potent natural inhibitor for p38 MAP kinase activity in human aortic smooth muscle cells indicating that a seven-membered A ring with acetoxy group, present in nomilin, seems to be essential for its inhibitory activity on p38 MAP kinase. The possible mechanism of nomilin for prevention of cardiovascular disease was determined. Pre-treatment with nomilin resulted in significant inhibition of TNF- induced HASMCs proliferation. The anti-proliferative activity of nomilin is due to apoptosis through mitochondrial dependent pathway.

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43

Naude, P. J. W. (Petrus Johan Wichardt). "An evaluation of the anti-inflammatory properties of a brown coal derived potassium humate". Diss., 2007. http://hdl.handle.net/2263/24574.

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Humin substances have been used as folk remedies for the last 3000 years. Recent studies have shown that humates possess anti-inflammatory properties, but the mechanism of how it affects inflammation is still unclear. In this study the anti-inflammatory properties of potassium humate, a water soluble humic acid salt, was investigated on different inflammatory pathways in vitro and in vivo. The effect of potassium humate on human mononuclear lymphocyte proliferation showed that potassium humate stimulated lymphocyte proliferation of resting-, PHA- and PWM-stimulated lymphocytes in vitro from concentrations of 20 to 80 µg/ml, in a dose dependant manner, where a maximum proliferation was observed at 80 µg/ml whereas lymphocyte proliferation decreased at 100 µg/ml. On the contrary potassium humate, at 40 µg/ml, significantly inhibited the supernatant concentrations of the following cytokines; TNF-α, IL-1ß, IL-6 and IL-10 by PHA stimulated lymphocytes. The effect of potassium humate on the alternative as well as the classical complement pathway was investigated in vitro using the haemolytic complement assay. Results indicated that potassium humate inhibits both the alternative and classical complement pathways without affecting the red blood cell membrane stability. Different inflammatory mechanisms were investigated in vivo, using the carrageenan-induced paw oedema model and the delayed type hypersensitivity reaction model. The carrageenan-induced paw oedema model was used to determine the effect of potassium humate on acute inflammation in the hind paw. Carrageenan was injected into the right hind footpad of a rat which caused an increase in paw volume due to oedema, which was measured with a plethysmometer. Potassium humate significantly inhibited the oedema at a dose of 60 mg/kg bodyweight and compared favourably with indomethacin at 10 mg/kg bodyweight. The effect of potassium humate on the delayed type hypersensitivity reaction model was also investigated whereby rats were sensitised with sheep erythrocytes. Potassium humate was administered daily by oral gavage at a dose of 60 mg/kg bodyweight. After 7 days, rats were challenged by injecting sheep erythrocytes into the right hind footpad. The degree of inflammation was determined by measuring the increase of paw volume with a plethysmometer. It was found that potassium humate did not have an anti-inflammatory effect on the delayed type hypersensitivity reaction as opposed to the inhibition caused by dexamethasone at a dose of 30 mg/kg bodyweight. This study showed that potassium humate selectively inhibited the inflammatory pathway of the carrageenan-induced paw oedema as opposed to the delayed type hypersensitivity. The mechanism of the anti-inflammatory property of potassium humate might possibly be due to the inhibition of the complement cascade. This study clearly shows that potassium humate possesses anti-inflammatory properties that can be utilised in the future as a potential treatment for inflammatory disorders associated with the activation of complement. However further investigation in the mechanism by which potassium humate inhibits complement activation needs to be done.
Dissertation (MSc (Pharmacology))--University of Pretoria, 2008.
Pharmacology
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44

Echalar, Barbora. "Vliv opioidů na imunoregulační a migrační vlastnosti mesenchymálních kmenových buněk". Master's thesis, 2020. http://www.nusl.cz/ntk/nusl-436104.

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Opioids are one of the oldest analgesics used to relieve pain. Besides their therapeutic properties, they also have negative side effects, which include impaired tissue regeneration. Therefore, it can be assumed that opioids also have a negative effect on stem cells which are responsible for tissue healing. One of stem cell populations involved in wound regeneration are mesenchymal stem cells (MSCs). MSCs are undifferentiated, multipotent cells that could be find in almost all tissues. They have immunoregulatory properties and they can migrate to the site of inflammation or injury where they contribute to healing of tissues. Therefore, the purpose of this thesis was to evaluate the effect of morphine and methadone on properties and migration of MSCs. Their effect on the metabolic activity of MSCs and also on the production of cytokines and growth factors was measured. The effect of these opioids on the immunoregulatory properties of MSCs acting on both innate and adaptive immune cells in vitro was studied. The effect of morphine on expression of adhesive molecules on MSCs was also examined. Furthermore, the effect of morphine on migration properties of systemically administered exogenous MSCs in vivo was investigated in mouse models. Distribution of MSCs to individual organs and to the site of...

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45

YEH, SHAN-PEI y 葉珊貝. "Anti-NLRP3 Inflammasome and Anti-inflammation Properties of Ployenylpyrrole Derivative in Neisseria Gonorrhoeae- Infected Macrophages". Thesis, 2019. http://ndltd.ncl.edu.tw/handle/jdk6bu.

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46

Yu-Chih, Liu. "Establishment of the Drug Screening Systems for Evaluating Chemical Compounds Possessing Anti-SARS or Anti-inflammation Properties". 2007. http://www.cetd.com.tw/ec/thesisdetail.aspx?etdun=U0001-1804200715240600.

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47

Liu, Yu-Chih y 劉育志. "Establishment of the Drug Screening Systems for Evaluating Chemical Compounds Possessing Anti-SARS or Anti-inflammation Properties". Thesis, 2007. http://ndltd.ncl.edu.tw/handle/25208553244051530241.

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博士
國立臺灣大學
生物化學暨分子生物學研究所
95
The challenge of the early drug discovery is to identify molecular targets that hold the greatest potential for therapeutic intervention and then to develop an appropriate assay model for screening libraries composed of individual organic or natural molecules. The first step in this early drug discovery pipeline is typically the establishment of high-throughput screen (HTS). And in vitro biochemical and cellular assays have long been used for HTS of large amount of molecules in 96-well and 384-well plate formats. The specific aim of this study is to develop and validate diverse methods in order to demonstrate their suitability for screening in the drug discovery, and perform small-scale screening and find potential hits or leads in an academic research. In the current work, a FRET (fluorescence resonance energy transfer) assay was developed for the evaluation of SARS-CoV 3CL protease activity. And a cell-based assay was validated for detecting the release level of TNF-α (tumor necrosis factor-α) and IL-1β (interleukin-1β) using LPS-stimulating peripheral blood mononuclear cells (PBMC) model. The assay quality parameter, Z’-factor, was employed. The Z’-factor of the FRET assay was 0.81 and the PBMC cell-based assay was 0.72 and 0.76 respectively for TNF-α and IL-1β release. In terms of the value of the Z’-factor, these screening assay qualities were classified with an excellent performance. The SARS-CoV 3CL protease is an essential enzyme for viral proteins processing and regarded as a good drug target to SARS-CoV replication. Here, hundreds of known compounds were examined by using FRET screening assay. Among these drugs, hexachlorophene was identified as the most potent inhibitor of SARS-CoV 3CL protease (Ki = 4 µM). Further characterization revealed that its binding mode was competitive with the substrate-binding site and the inhibitory effect was pre-incubation time dependent. Besides, two other known drugs, triclosan and nelfinavir, were 10-fold less potent (Ki = 40 µM and Ki = 21 µM respectively) than hexachlorophene. Furthermore, to evaluate the specificity of hexachlorophene, over forty protease assays were conducted to screen its inhibitory effects. The results showed that hexachlorophene not only inhibited SARS-CoV 3CL protease but also inhibited some of cysteine and aspartic proteases, which related to tumor progression and metastasis. After identifying hexachlorophene and its analogues as the inhibitors of SARS-CoV 3CL protease using an enzyme assay model, we try to establish a cell-based screening system to find some anti-inflammatory inhibitors and then identify their molecular targets. LPS (lipopolysaccharide), one of exogenous inflammatory agent, stimulates PBMC to synthesize or release pro-inflammatory cytokines. Therefore, our strategy was to screen test compounds using LPS stimulated-PBMC and find whether some of them can inhibit the release of TNF-α and/or IL-1β. Then we can examine this kind of potential anti-inflammatory candidates to understand their inhibitory targets. Among nearly 500 test compounds, we found that MT4 had the suppressive action on the release of TNF-α and IL-1β, with IC50 values of 22 and 44 nM, respectively. After we evaluated the anti-cytokine effect of MT4 in terms of the inhibition of p38 MAPK, JNK and ERK activity using in vitro kinase assay, MT4 inhibited the activity of p38α and p38β in a concentration-dependent manner. It also displayed moderate inhibitory activity on p38γ and δ. The IC50 values were 0.13, 0.55, 5.47 and 8.63 µM for p38α, β, γ and δ respectively. Further characterization of enzyme kinetics showed that the binding mode of MT4 was competitive with the ATP substrate-binding site of p38α MAPK. Beside the cytokine synthesis and release pathway, we also studied MT4 effect on other inflammatory enzymes and found that it could inhibit cycloxygenase-2 to reduce the prostaglandin-2 production. In summary, our studies offer simple and excellent screens to identify anti-SARS and anti-inflammatory inhibitors. These identified small molecules that can serve as chemical starting points or high quality leads for further optimization to provide a good opportunity for developing novel and potent drug candidates.

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Leshwedi, Mopo. "The anti-inflammatory properties of Salacia leptoclada and Warburgia salutaris : their possible role as therapeutic agents in crystalline silica-induced cellular injury". Thesis, 2012. http://hdl.handle.net/10210/6619.

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M.Tech.
The plants Salacia leptoclada and Warburgia salutaris possess antioxidant properties and are commonly used in Southern Africa for the treatment of inflammatory and other diseases. In order to determine their therapeutic use in crystalline silica-induced injury, the extracts of S. leptoclada and W. salutaris were investigated on silica-induced increased levels of (i) TNF-a, IL-113, INF-y, (ii) the activation of the transcription factor NE-KB, and (iii) the induction of DNA damage and lipid peroxidation. Through its antioxidant property, W. salutaris exhibited a protective effect against crystalline silica-induced inflammatory cytokine expression, NF-KB activation and DNA strand breakage. The extracts of W. salutaris also inhibited cellular membrane peroxidation induced by crystalline silica. Similarly, the extracts of S. leptoclada showed protection of cells against crystalline silica-induced membrane peroxidation. However, S. leptoclada proved ineffective in protecting against silica-induced DNA damage, proinflammatory cytokine expression and NF-KB activation. Since crystalline silica-induced inflammation, NE-KB activation, DNA damage and lipid peroxidation are involved in the process of crystalline silica-induced fibrogenecity and carcinogenicity, W. salutaris may be a potential therapeutic agent against crystalline silica-induced cellular injury.

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49

Sayed, Sharfuddin Sakil. "The toxicity, pharmacokinetics, anti-inflammatory and anti-tumour properties of a methotrexate polymer". Diss., 2010. http://hdl.handle.net/2263/24589.

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A major effort to develop anticancer drugs through both empiric screening and rational design of new compounds has been under way for over 30 years (Katzung, 2004). In recent years, research and development in the field of sitespecific drug therapy has progressed significantly. Safe and non-toxic formulations of cytotoxic drugs based on polymers with their improved sitespecific delivery and effective activation to biologically active cytotoxic compounds at the targeted tumours have become a promising approach to cancer therapy. Drug delivery systems based on polymer micelles, coated microand nanoparticles, liposomes and various pro-drug systems including watersoluble polymer–drug conjugates and immunoconjugates have been prepared and extensively studied as novel drug delivery systems designed for cancer chemotherapy. Amongst these drug delivery systems that enable specific drug delivery and release, water-soluble polymer–drug conjugates rank among the most promising, versatile and efficient systems. This dissertation reviews the preclinical testing and pharmacokinetic study of D85, a novel water-soluble macromolecular pro-drug that is a polymer with pHcontrolled methotrexate (MTX) release with potential for treatment of cancer in humans (Ulbrich&Subr, 2004). As MTX is also indicated in low doses for the treatment of chronic inflammatory conditions, the polymer was further tested in an acute inflammatory model to determine whether the polymer would be more effective than MTX in controlling inflammation. The objective of this study was to compare the potency and efficacy of D85 to MTX. D85, a MTX conjugated polymeric lead compound, was designed and synthesised as a potential anti-neoplastic and anti-inflammatory agent. It was initially tested in vitro on three different cancer cell lines where selective toxicity towards the cancer cell cultures compared to primary cell cultures and greater toxicity than MTX was observed. The initial in vitro tests showed very promising results with D85 demonstrating approximately 300 times greater cytotoxicity than MTX against a colon cancer cell line (COLO 320 DM). This high cytotoxic effect warranted further investigation in an in vivo colon cancer tumour model. An induced murine tumour model of COLO 320 DM was successfully developed in nude mice, and the anti-tumour efficacy of D85 tested in this model. The maximum tolerated dose of D85 was established by carrying out an in vivo dose ranging toxicity test in BALB/c mice. The anti-inflammatory effects of D85 were also determined using the carrageenan-induced paw oedema model in rats where carrageenan was injected into a footpad of a rat causing acute oedema, which was measured using a water displacement plethysmometer. D85 was found to exacerbate the inflammatory response. Finally, the pharmacokinetic parameters of MTX and D85 were assessed using a LC/MS/MS method specifically developed and validated to determine low concentrations of MTX in small volumes of plasma. This new method made use of online solid phase extraction and sample cleanup on 2μl injections of diluted plasma allowing an entire pharmacokinetics study to be completed on an individual rat. Fairly similar pharmacokinetics were determined from both compounds. Copyright
Dissertation (MSc)--University of Pretoria, 2010.
Pharmacology
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50

LIN, TSO-CHING y 林作慶. "Improvement Effects of Eucalyptus Essential Oil Aromatherapy on Ergogenic Properties‚ Anti-oxidant and Inflammation Activities in Endurance Swimming Rats". Thesis, 2018. http://ndltd.ncl.edu.tw/handle/psy65r.

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博士
大葉大學
食品暨應用生物科技學系
107
Eucalyptus globulus possesses important pharmacological activities, including antioxidant and anti-inflammatory effects. We investigated the anti-fatigue, antioxidant, and anti-inflammatory effects of eucalyptus essential oil after swimming exercise using an animal model. Male Sprague–Dawley rats were administered eucalyptus oil (200 µL/h) daily via inhalation (15 min), and anti-fatigue effects were assessed following eucalyptus essential oil administration for 2 or 4 weeks when forced to swim until exhaustion while carrying ~5% body weight-equivalent. To assess antioxidant and anti-inflammatory effects, control and oil-treated groups were subjected to swimming, which was intensified from 90 min to 120 min daily over 4 weeks, with non-swimming groups included as controls. The 2- and 4-week-treated rats increased their swimming-to-exhaustion time by 46 s and 111 s, respectively. Additionally, lactate (LA), creatine kinase (CK), and lactate dehydrogenase (LDH) activities increased significantly in the non-treated swimming relative to levels observed in the non-swimming groups (p < 0.05); however, no significant differences in these markers were observed between the treated groups. The anti-fatigue effects were related to LA clearance and reduced LDH and CK concentrations. Moreover, compared to the corresponding levels in the non-swimmers, the non-treated swimmers showed markedly elevated levels of liver malondialdehyde (MDA), xanthine oxidase (XO), and other factors, but significantly decreased (p < 0.05) glutathione (GSH) concentrations. However, compared with that of the non-swimmer group, the treated swimming group showed no significant changes in these levels (p > 0.05), suggesting stable XO and MDA production and maintenance of GSH levels. These results suggested that eucalyptus oil aromatherapy increased rat swimming performance and antioxidant capacity and decreased oxidative damage and inflammatory reactions in tissues, indicating good anti-fatigue, antioxidant, and anti-inflammatory effects after high-intensity endurance exercise.

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Tesis sobre el tema "Immunoregulatory properties and inflammation"

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