Extracellular stimuli may influence the M1/M2 phenotypic polarization of macrophages. We examined M1/M2 biomarkers, phagocytic activity, and tumoricidal activity in RAW 264.7 mouse macrophages. Macrophages were treated with conditioned media (CM) from 4T1 breast cancer cells, curcumin, 22-oxacalcitriol, LPS, or a combination of the previously listed. Arginase activity, a M2 phenotypic biomarker, was upregulated by the treatment of macrophages with conditioned media. Curcumin, 22- oxacalcitriol, and LPS partially inhibited RAW 264.7 arginase activity in the presence of 4T1 breast cancer media. 22-oxacalcitriol increased the phagocytic ability of RAW 264.7 macrophages in the presence of M2 polarizing substances produced by the 4T1 breast cancer cells. Also, LPS increased RAW 264.7 phagocytic ability in the presence of 4T1 breast cancer CM. This study looked at the potential substances that would possibly reverse the M2 tumor promoting macrophage phenotype seen in the breast cancer tumor environment. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2017. / FAU Electronic Theses and Dissertations Collection

Thesis (Ph.D.)--University of Alberta, 2009. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy, Department of Biochemistry. Title from pdf file main screen (viewed on August 11, 2009). Includes bibliographical references.

The use of modifiers in supercritical fluid chromatography and extraction has become quite common due to the inability of pure carbon dioxide alone to solvate many of the compounds of interest. The effects of modifiers in supercritical fluid chromatography have been more thoroughly studied than the effects of modifier in supercritical fluid extraction. The effects of modifier on trapping efficiencies for off-line supercritical fluid extraction have been evaluated in this work. Sorbent and solid phase traps were investigated with pure carbon dioxide in order to determine the effect of stationary phase identity, pretreatment, and rinse solvent on the recoveries of a test mixture of compounds of varying vapor pressure and molecular weight. The solid phase traps, which were polyethylene frits, performed as well as the sorbent traps in most cases, and significantly better than the sorbent traps in many cases. The ability to cool these traps to -20°C allowed for efficient trapping of volatile compounds without the benefit of sorptive interactions. Sorbent and solid phase traps were then studied with the addition of 1%, 2%, 4%, and 8% methanol to the mobile phase. The sorbent trap explored consisted of 40 µm ODS packing material, while the solid phase trap consisted of 100 yum stainless steel beads. In this work trap temperatures ranged from 5-80°C. It was found that trap temperature, modifier concentration, and trap type influenced recoveries of the test mixture components. Applications of these solid phase and sorbent traps explored were the extraction of polychlorinated biphenyls from river sediment and the extraction of the active components from a drug formulation. The separation of some compounds of pharmaceutical interest was also explored, where the addition of modifier, and in some cases an additive, was required to elute compounds from the chromatographic column. / Ph. D.

Yes / This mini-review highlights the latest advances in the chemistry and biology of Pluronic® triblock copolymers. We focus on their applications in medicine, as drug delivery carriers, biological response modifiers, and pharmaceutical ingredients. Examples of drug delivery systems and formulations currently in clinical use, clinical trials or preclinical development are highlighted. We also discuss the role that Pluronic® copolymers may play in the innovative design of new nanomedicines in the near future. / We thank the Leverhulme Trust (Early Career Fellowship no. ECF-2013-414 to NPEB), the University of Warwick (Grant no. RDF 2013-14 to NPEB) and EPSRC (EP/G004897/1 to APB) for support.

Made available in DSpace on 2014-12-17T14:06:48Z (GMT). No. of bitstreams: 1 HaroldoRAM.pdf: 1140599 bytes, checksum: 95a046b646a7cfa0d6cf0153f138783f (MD5) Previous issue date: 2008-08-20 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Titanium is a biomaterial widely employed in biomedical applications (implants, prostheses, valves, stents). Several heat treatments are usually used in order to obtain physical properties required to different applications. This work studied the influence of the heat treatment on microstructure of commercial pure titanium, and their consequences in growth and proliferation of MC3T3-E1 cells. Discs of titanium were treated in different temperatures, and characterized by optical microscopy, image analysis, wettabillity, roughness, hardness and X-ray diffraction. After the heat treatment, significant modifications in these properties were observed. Pattern images of titanium, before and after the cell culture, were compared by overlapping to analyze the influence of microstructure in microstructure and preferences guidance cells. However, in general, titanium discs that showed a higher residual strength also presented an increase of cells numbers on surface / O tit?nio como biomaterial ? amplamente utilizado em dispositivos biom?dicos (implantes, pr?teses, v?lvulas, stents entre outros). Diversos tratamentos t?rmicos s?o usualmente utilizados na obten??o das propriedades necess?rias para as diferentes aplica??es. Este trabalho estudou a influ?ncia desses tratamentos na microestrutura do tit?nio comercialmente puro e suas conseq??ncias no crescimento, forma e prolifera??o de c?lulas pr?-osteobl?stica. Para tanto foram utilizados discos de tit?nio submetidos a diferentes tratamentos e caracterizados por microscopia ?tica, an?lise de imagens, molhabilidade, rugosidade, dureza e difra??o de raios-X. Ap?s os tratamentos t?rmicos foram verificado modifica??es significantes nestas propriedades. Padr?es de imagens de superf?cies do tit?nio antes e ap?s a cultura de c?lula foram comparados atrav?s de sobreposi??o para analisar a influ?ncia da microestrutura na resposta biol?gica, n?o sendo verificadas correla??es entre a microestrutura e as prefer?ncias orientacionais das c?lulas. Entretanto de um modo geral verificou-se que os discos que presentaram maior estado de tens?o residual apresentaram tamb?m maior n?mero de c?lulas em sua superf?cie

Made available in DSpace on 2014-12-17T14:07:09Z (GMT). No. of bitstreams: 1 HaroldoRAM_TESE.pdf: 4102900 bytes, checksum: e74f8a9122bb5cd84cbeadae3a476ce1 (MD5) Previous issue date: 2012-02-03 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / The titanium and titanium alloys are widely used as biomaterial in biomedical device and so research have been developed aiming to improve and/or better to understand interaction biomaterial/biological environment. The process for manufacturing of this titanium implants usually involves a series of thermal and mechanical processes which have consequence on the final product. The heat treatments are usually used to obtain different properties for each application. In order to understand the influence of these treatments on the biological response of the surface, it was done, in this work, different heat treatments in titanium and analyzed their influence on the morphology, adhesion and proliferation of the pre-osteoblastic cells (MC3T3-E1). For such heat-treated titanium disks were characterized by optical microscopy, contact angle, surface energy, roughness, microhardness, X-ray diffraction and scanning through the techniques (BSE, EDS and EBSD). For the analysis of biological response were tested by MTT proliferation, adhesion by crystal violet and β1 integrin expression by flow cytometry. It was found that the presence of a microstructure very orderly, defined by a chemical attack, cells tend to stretch in the same direction of orientation of the material microstructure. When this order does not happen, the most important factor influencing cell proliferation is the residual stress, indicated by the hardness of the material. This way the disks with the highest level state of residual stress also showed increased cell proliferation / O tit?nio e suas ligas s?o amplamente utilizados como biomaterial em dispositivos biom?dicos e devido a isso pesquisas t?m sido desenvolvidas visando aperfei?oar e/ou compreender melhor a intera??o biomaterial/meio biol?gico. O processo de fabrica??o desses dispositivos de tit?nio geralmente envolve uma s?rie de processos t?rmicos e mec?nicos e que t?m consequ?ncias no produto final. Os tratamentos t?rmicos s?o usualmente utilizados para obten??o de propriedades diferenciadas para cada aplica??o. Com o intuito de entender a influ?ncia desses tratamentos sobre a resposta biol?gica da superf?cie, foram realizados, no presente trabalho, diferentes tratamentos t?rmicos em tit?nio e analisadas suas influ?ncias na morfologia, ades?o e prolifera??o de c?lulas pr?-osteobl?stica (MC3T3-E1). Para tanto os discos de tit?nio tratados termicamente foram caracterizados por microscopia ?tica, ?ngulo de contato, energia de superf?cie, rugosidade, microdureza Vickers, difra??o de raios-X e microscopia eletr?nica de varredura atrav?s das t?cnicas de EBS, EDS e EBSD. Para an?lise da resposta biol?gica foram realizados teste de prolifera??o por MTT, ades?o por cristal violeta e express?o da integrina β1 por citometria de fluxo. Foi verificado que na presen?a de uma microestrutura muito ordenada, definida atrav?s de um ataque qu?mico, as c?lulas tendem a se alongar no mesmo sentido da orienta??o microestrutural do material. Quando essa ordem n?o acontece, o fator mais importante a influenciar na prolifera??o celular ? a tens?o residual, indicada pela dureza do material. Deste modo os discos que apresentaram maior estado de tens?o residual apresentaram tamb?m maior prolifera??o celular

The interferon (IFN) response is a crucial component of cellular innate immunity, vital for controlling virus infections. Dysregulation of the IFN response however can lead to serious medical conditions including autoimmune disorders. Modulators of IFN induction and signalling could be used to treat these diseases and as tools to further understand the IFN response and viral infections. We have developed cell-based assays to identify modulators of IFN induction and signalling, based on A549 cell lines where a GFP gene is under the control of the IFN-β promoter (A549/pr(IFN-β).GFP) and the ISRE containing MxA promoter (A549/pr(ISRE).GFP) respectively. The assays were optimized, miniaturized and validated as suitable for HTS by achieving Z' Factor scores >0.6. A diversity screen of 15,667 compounds using the IFN induction reporter assay identified 2 hit compounds (StA-IFN-1 and StA-IFN-4) that were validated as specifically inhibiting IFNβ induction. Characterisation of these molecules demonstrated that StA-IFN-4 potently acts at, or upstream, of IRF3 phosphorylation. We successfully expanded this HTS platform to target viral interferon antagonists acting upon IFN-signalling. An additional assay was developed where the A549/pr(ISRE).GFP.RBV-P reporter cell line constitutively expresses the Rabies virus phosphoprotein. A compound inhibiting viral protein function will restore GFP expression. The assay was successfully optimized for HTS and used in an in-house screen. We further expanded this assay by placing the expression of RBV-P under the control of an inducible promoter. This demonstrates a convenient approach for assay development and potentiates the targeting of a variety of viral IFN antagonists for the identification of compounds with the potential to develop a novel class of antiviral drugs.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / The world population has been showing more concern for the food and its constituents, encouraging the food industry to invest in healthy products and in functional foods. Among those considered functional foods is the flaxseed (Linum usitatissimum L.), a small grain of ovate shape with high nutritional value by being a good source of fiber, essential fatty acids and protein. The aim of this study was observe the flaxseed functional properties in different processing conditions and use in food, through the determination of the grain chemical composition, biological response in rats and the fatty acids profile. The chemical determination was found that flaxseed used in this study is rich in lipid (37,04 g%), in protein (16,69% g) and in fiber (32,9 g%). In the biological trial, 32 male Wistar rats received four diet types (P: diet standard as AIN; LC: diet with 16% of raw flaxseed; LA: diet with 16% of roast flaxseed; and OL: diet with flaxseed oil), it was found that the use of raw flaxseed, roast flaxseed and flaxseed oil resulted positively in vivo. There was a decrease in biochemical blood glucose, triglyceride and total cholesterol levels, and increase the fecal excretion and lipid excretion, no change in the growth of rats in treatments with flaxseed. The more positive data were detected in animals feed with the raw grain. By gas chromatography analysis was carried out of the grain and flaxseed oil lipid profile subjected to different processes involving high temperatures: raw grain (LC); grain baked in electric oven to 150ºC for 40 minutes (L150); grain baked in electric oven to 180ºC for 40 minutes (L180); grain heated in microwave oven (LM); flaxseed oil (OL) and flaxseed oil heated to 180ºC for 30 minutes (OF).Changes in the saturated and unsaturated fatty acids were detected, but the flaxseed and the flaxseed oil remained significant amounts of polyunsaturated fatty acids, mainly of Y- linolenic acid, in all treatments. Despite the minor benefits caused by flaxseed processing (baked grains or as oil), it was noted that part of Y-linolenic acid remains in the food and is absorbed by the organism. In conclusion, it is possible to state that flaxseed is still quite stable when subjected to various processes involving high temperatures and it is an alternative source of Y-linolenic acid. However more studies are needed to provide the appropriate doses for humans, according to the particular individual. / A população mundial vem demonstrando crescente preocupação com a alimentação e seus constituintes, o que incentiva a indústria de alimentos a investir em produtos saudáveis e nos ditos alimentos funcionais. Entre os alimentos considerados funcionais encontra-se a linhaça (Linum usitatissimum L), um pequeno grão de formato oval com grande valor nutritivo por ser fonte de fibras, ácidos graxos essenciais e proteína. O presente trabalho teve como objetivo observar as propriedades funcionais da linhaça em diferentes condições de preparo e de uso em alimentos, o que foi realizado por meio da determinação da composição química do grão, de ensaio biológico em ratos e da análise do perfil de ácidos graxos. Quanto aos resultados, com a determinação da composição química verificou-se que a linhaça utilizada neste estudo é rica em lipídio (37,04g%), em proteína (16,69g%) e em fibras alimentares (32,9g%). No ensaio biológico, momento em que 32 ratos wistar machos recém desmamados receberam quatro tipos de ração (P: ração padrão conforme AIN; LC: ração com 16% de linhaça crua; LA: ração com 16% de linhaça assada a 180ºC por 40 minutos; e OL: ração com óleo de linhaça), constatou-se que a utilização do grão de linhaça cru, do grão assado e do óleo de linhaça resultou positivamente in vivo. Foi observada uma diminuição nos parâmetros bioquímicos glicemia, triglicerídio e colesterol total, aumento da excreção lipídica e da excreção fecal, sem alteração no desenvolvimento ponderal dos ratos nos tratamentos adicionados de linhaça, sendo que os dados mais positivos foram detectados nos animais que receberam o grão in natura. Por meio da cromatografia gasosa, realizou-se a análise do perfil lipídico do grão e do óleo de linhaça submetidos a diferentes processos envolvendo altas temperaturas: grão in natura (LC); grão assado em forno elétrico a 150ºC por 40 minutos (L150); grão assado em forno elétrico a 180ºC por 40 minutos (L180); grão aquecido em forno de microondas (LM); óleo de linhaça in natura (OL); e óleo de linhaça aquecido a 180ºC por 30 minutos (OF). Modificações no perfil de ácidos graxos saturados e insaturados foram detectadas, entretanto o grão e o óleo de linhaça mantiveram quantidades significativas de ácidos graxos poliinsaturados, principalmente de ácido Y-linolênico, em todos os tratamentos. Apesar dos menores benefícios causados pela linhaça processada (grão assado ou como óleo), observou-se que parte do ácido Y-linolênico permanece no alimento e é absorvido pelo organismo. Com tudo isso, é possível afirmar que a linhaça se mantém bastante estável quando submetida a diferentes processamentos envolvendo altas temperaturas, sendo uma fonte alternativa de ácido Y-linolênico. Entretanto mais estudos são necessários para estipular as doses adequadas para humanos, de acordo com as particularidades individuais.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Barley is one of the most economically important winter crops for the farming system in the southern Brazil and it is well-known by its high content of soluble dietary fiber (beta-glucans) which lowers plasmatic cholesterol as well as the glycemic index besides reducing the risk of colon cancer. In what concerns human consumption it has been observed recent interest for this cereal since its dietetic properties can be associated to health benefits. The aim of this research was to determine the chemical composition of barley grains under different processings, covered barley, hulless barley, hulless roasted barley, barley flakes, barley flour as well as relating the effects of the inclusion of processed barley grains as a source of fiber in diet by having Wistar rats as biological model. The grains were analyzed in relation to the dry matter content, ash, crude protein, lipids, total dietary fiber, insoluble and soluble fiber, non-fibrous carbohydrates, beta-glucans and minerals (calcium, phosphorus, magnesium, potassium, zinc, iron, manganese and copper). The bioassay was performed during 42 days; it was used 35 male Wistar rats at 21 days old, distributed in 5 treatments of 7 animals which received feed AIN-93G with varied source of dietary fiber: CONT treatment (control) with 5% cellulose; treatment CB with 5% of covered barley; treatment HB with 5% of hulless barley; treatment HRB with 5% of hulless roasted barley fiber, and treatment BF with 5% of barley flakes. It was determined: food intake, weight gain, feed conversion (FC), feed efficiency ratio (FER), multivariate bio-nutritional index (BNI), dry and wet fecal output, moisture from feces, gastrointestinal transit time, liver weight, heart weight, epididymal fat weight, kidney weight, small and large intestine weight, full and empty cecal weight as well as the following blood parameters: total proteins, albumin, hemoglobin, glucose, total cholesterol, HDL cholesterol and triglycerides. The results show significant differences among the barley grains under different processing for dry matter, ash, crude protein, dietary fiber, insoluble fiber, nonfibrous carbohydrates, calcium, potassium, magnesium, zinc, iron and manganese. Variations in the chemical composition occurred due to the effect of processing of the grain because of hullessness, stabilization, flocking and milling. The inclusion of dietary fiber of covered barley as well as of the products from its processing (hulless grain, hulless roasted grains and flakes) may be employed as source of fiber in a standard diet of AIN-93 without compromising the development of rats as well as providing less dry fecal weight, more fecal moisture and less gastrointestinal transit time, what may be attributed to more colonic fermentation. / A cevada é uma das culturas de inverno economicamente mais importantes para o sistema de exploração agrícola no sul do Brasil, sendo conhecida pelo seu alto conteúdo de fibra alimentar solúvel (beta-glicanas), a qual diminui o colesterol plasmático bem como o índice glicêmico, além de reduzir o risco de câncer de cólon. Em relação ao consumo humano, tem-se observado recente interesse pelo uso desse cereal em razão de as suas propriedades dietéticas poderem ser associadas a benefícios com a saúde. Objetivou-se com esta pesquisa determinar a composição química de grãos de cevada submetidos a diferentes processamentos, grão de cevada integral, grão de cevada descascado, grão de cevada descascado tostado, cevada em flocos e farinha de cevada, assim como relacionar os efeitos da inclusão de grãos de cevada processados como fonte de fibra na dieta, empregando-se ratos Wistar como modelo biológico. Os grãos foram analisados quanto aos teores de matéria seca, cinzas, proteína bruta, lipídeos, fibra alimentar total, fibra insolúvel, solúvel, carboidratos não fibrosos, beta-glicanas e minerais (cálcio, fósforo, magnésio, potássio, zinco, ferro, manganês e cobre). O ensaio biológico foi conduzido por um período de 42 dias; utilizou-se 35 ratos Wistar machos, com 21 dias de idade, distribuídos em 5 tratamentos de 7 animais que receberam ração AIN-93G, variando a fonte de fibra alimentar: tratamento CONT (controle), com 5% de celulose; tratamento CI, com 5% de grão de cevada integral; tratamento CD, com 5% de grão de cevada na forma descascada; tratamento CDT, com 5% de fibra grão de cevada descascado tostado; e tratamento CFL, com 5% de flocos de cevada. Foram determinados: consumo alimentar, ganho de peso, conversão alimentar (CA), coeficiente de eficiência alimentar (CEA), índice nutricional multivariado biológico (INMB), produção de fezes secas e úmidas, umidade das fezes, tempo de trânsito gastrintestinal, peso do fígado, peso do coração, peso da gordura epididimal, peso dos rins, peso do intestino delgado e grosso, peso do ceco completo e vazio; além dos seguintes parâmetros sanguíneos: proteínas totais, albumina, hemoglobina, glicose, colesterol total, colesterol HDL e triglicerídeos. Os resultados acusaram diferenças significativas entre os grãos de cevada submetidos a diferentes processamentos para matéria seca, cinzas, proteína bruta, fibra alimentar, fibra insolúvel, carboidratos nãofibrosos, cálcio, potássio, magnésio, zinco, ferro e manganês. Variações na composição química ocorreram devido ao efeito de processamento do grão em função do descascamento, estabilização, flocagem e moagem. A inclusão de fibra alimentar de grãos de cevada integral assim como dos produtos resultantes do seu processamento (grão descascado, grão descascado tostado e flocos) pode ser empregada como fonte de fibra em uma dieta padrão da AIN-93, sem comprometer o desenvolvimento dos ratos, bem como proporcionar menor peso fecal seco, maior umidade fecal e menor tempo de trânsito gastrintestinal, o que pode ser atribuído a maior fermentação no colón.

Les cellules stromales mésenchymateuses (CSM) sont des cellules dotées de nombreuses propriétés dont les plus importantes sont leur rôle de soutien de l’hématopoïèse, leur potentiel de différenciation multilignée et leurs pouvoirs immunomodulateurs. Grâce à ces propriétés et à leur facilité d’obtention et d’amplification ex vivo, les CSM sont des candidats prometteurs pour diverses applications thérapeutiques. Au cours de ce travail, nous avons caractérisé ces pouvoirs immunomodulateurs et étudié les mécanismes sous-jacents.<p><p>Nous avons dans un premier temps, évalué la capacité des CSM de la MO à moduler la prolifération des lymphocytes T purifiés à partir de sang périphérique (SP) ou de sang de cordon ombilical (SCO). Quel que soit le stimulus utilisé pour les activer, les lymphocytes T du SP ou du SCO sont modulés par les CSM d’une manière dose dépendante. Le profil d’inhibition des lymphocytes T du SP ou du SCO par les CSM est différent et vraisemblablement lié à leur composition cellulaire (rapport T naïfs vs mémoires).<p><p>Dans le but de comprendre les mécanismes impliqués dans l’immunomodulation et l’influence de l’environnement sur les CSM, nous nous sommes intéressés à l’expression des molécules d’adhésion et de la galectine 1 ainsi qu’à leurs rôles dans l’immunomodulation. Lors des co-cultures avec les lymphocytes T, il y a augmentation de l’expression du CD54, du CD58 et de la sécrétion de la galectine 1 alors qu’en présence d’un environnement inflammatoire ou infectieux, celles-ci sont différemment modulées. Nous avons ensuite pu démontrer que l’inhibition de la réponse lymphocytaire par les CSM impliquait notamment la galectine 1 comme facteur immunorégulateur.<p><p>Le troisième volet de cette thèse, s’est intéressé à l’étude et à la comparaison du pouvoir immunomodulateur des CSM issues du tissu adipeux et la gelée de Wharton, considérés comme des sources potentiellement alternatives à la MO. L’immunomodulation exercée sur les réponses immunes est indépendante de l’origine des CSM. Les CSM du tissu adipeux et de la gelée de Wharton inhibent l’activation des lymphocytes mise en évidence par l’expression du CD38. La réponse allogénique ou mitogénique des lymphocytes est réduite en présence de CSM et les sous populations (CD4+ et CD8+) sont affectées de la même manière par ces effets suppresseurs. Ces effets sont dépendants des concentrations en CSM et sont vraisemblablement liés à l’expression de la PGE2 et du LIF. Durant les co-cultures, les Tregs sont expansés et cela indépendamment des concentrations en CSM. <p><p>En résumé, nous avons caractérisé le pouvoir immunomodulateur des CSM issues de trois sources différentes à savoir la moelle osseuse, la gelée de Wharton et le tissu adipeux. Comme le mettent en évidence nos observations, ce pouvoir est clairement dépendant de la concentration en CSM utilisée et est fortement sensible à l’environnement auquel les CSM sont exposées. Sur le plan mécanistique, nous avons démontré la participation de la galectine 1, de la PGE2 et du LIF aux fonctions immunosuppressives des CSM. Nous rapportons également la capacité des CSM à promouvoir l’expansion des Tregs aussi bien au sein d’une population lymphocytaire que fraîchement purifiés. Nos travaux soulignent l’importance et l’avantage de l’utilisation des CSM issues de ces nouvelles sources dans le cadre des thérapies immunes.<p> / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished