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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Papel imunorregulador da Hsp70 de Mycobacterium tuberculosis, murina e humana

Lopes, Rafael Lisboa 16 March 2016 (has links)
Submitted by Setor de Tratamento da Informa??o - BC/PUCRS (tede2@pucrs.br) on 2016-08-03T18:08:58Z No. of bitstreams: 1 DIS_RAFAEL_LISBOA_LOPES_COMPLETO.pdf: 9085477 bytes, checksum: b4223f63e2f669559a5830cd87644a78 (MD5) / Made available in DSpace on 2016-08-03T18:08:58Z (GMT). No. of bitstreams: 1 DIS_RAFAEL_LISBOA_LOPES_COMPLETO.pdf: 9085477 bytes, checksum: b4223f63e2f669559a5830cd87644a78 (MD5) Previous issue date: 2016-03-16 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Hsp70 (Heat shock protein 70 kDa) is a chaperone protein which has intra- and extracellular functions. In the early studies, only intracellular functions were operated, as to aid in folding, prevent aggregation and protein refolding. In 80?s a study has shown that this protein can be exported into the extracellular environment exerting effects on other cells, such as the immune system. Our group are exploring the role of this protein in key immune response cells such as macrophages and dendritic cells. Present study noted that the Hsp70 of Mycobacterium tuberculosis can polarize macrophages to a M2 phenotype and this response is dependent on IL-10. Peritoneal and bone marrow derived macrophages were treated with DnaK (Hsp70 prokaryotic homolog) from M. tuberculosis for 24 hours. After this period there was an increase of M2 classic phenotype markers, such as FIZZ1, YM1, CD206, IL-10 and Arg1. On the other hand, there was a decrease in expression of IL-6, MCP-1, TNF-?, NO, MHC class II and CD86 (M1 markers), and these cells are able to promote tumor growth in allogeneic model. It was also observed with KO cells or blocking IL-10R that this modulation is dependent on IL-10. In addition, this cellular modulation is not restricted to macrophages; such protein acting on dendritic cells by modulating them with an immature phenotype, as has been shown in prior works of our group (Borges et al, 2010;. Motta et al., 2007 ). However, it is not yet known what specific region of the protein is essential for that purpose and whether it is restricted to that homologues, DnaK from M. tuberculosis. Therefore, another objective was to express and purify in the same system their counterparts Hspa1a (murine Hsp70) and HSPA1A (human Hsp70) and subsequently testing them in parallel in immunological experimental models. Work is currently in progress with regard to purification of Hspa1a and initial dendritic cells activation state tests were conducted. It is believed that whether there is an effect with DnaK homologues, this effect is less obvious, according to previous results. / A Hsp70 (Heat shock protein 70 kDa) ? uma prote?na de choque t?rmico de 70 kDa que possui fun??es intra e extracelulares. Nos estudos iniciais, somente as fun??es intracelulares eram exploradas, como o aux?lio no dobramento, impedir a agrega??o e o redobramento prot?ico H? d?cadas mostrou-se que essa prote?na pode ser exportada para o ambiente extracelular e exercer efeitos sobre outras c?lulas, como as do sistema imune. O nosso grupo v?m explorando o papel dessa prote?na em c?lulas chave da resposta imune, como macr?fagos e c?lulas dendr?ticas. O presente trabalho observou que a Hsp70 de Mycobacterium tuberculosis pode polarizar macr?fagos a um fen?tipo M2 e que essa resposta ? dependente de IL-10. Macr?fagos peritoneais e derivados de medula ?ssea foram tratados com DnaK (hom?logo procari?tico da Hsp70) de Mycobacterium tuberculosis por 24h. Ap?s esse per?odo observou-se o aumento de marcadores cl?ssicos de fen?tipo M2, como: FIZZ1, YM1, CD206, IL-10, Arg1. Por outro lado, houve uma diminui??o na express?o de IL-6, MCP-1, TNF-?, NO, MHC de classe II e CD86, al?m de essas c?lulas serem capazes de promover o crescimento tumoral em modelo alog?nico. Observou-se tamb?m, com c?lulas KO ou bloqueando o IL-10R que essa modula??o ? dependente de IL-10. Al?m disso, essa modula??o celular n?o ? restrita aos macr?fagos, podendo essa prote?na agir sobre c?lulas dendr?ticas, modulando-as a um fen?tipo imaturo, como j? mostrado em trabalho anteriores do grupo (1,2). Por?m, n?o se sabe ainda qual regi?o espec?fica da prote?na ? essencial para esse efeito e se ele ? restrito a esse hom?lo, DnaK de M. tuberculosis. Portanto, outro objetivo do trabalho foi expressar e purificar no mesmo sistema os seus hom?logos Hspa1a (Hsp70 murina) e HSPA1A (Hsp70 humana) e posteriormente, test?-las em paralelo em modelos experimentais imunol?gicos. O trabalho est? em andamento atualmente em rela??o a purifica??o da Hspa1a e os primeiros testes de estado de ativa??o de c?lulas dendr?ticas foram realizados. Acredita-se que se h? um efeito dos hom?logos de DnaK, esse efeito ? menos evidente, segundo resultados pr?vios.
2

An?lise do comportamento das linhagens celulares SCC-25, SAS e HSC-3 frente ? presen?a dos exossomos derivados dos macr?fagos (TAMs) dos subtipos M1 e M2

Demeda, Clarissa Favero 17 February 2016 (has links)
Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-10-11T22:29:37Z No. of bitstreams: 1 ClarissaFaveroDemeda_TESE.pdf: 3254557 bytes, checksum: 71f116b43b1323319edbd07fa141e478 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-10-17T23:03:20Z (GMT) No. of bitstreams: 1 ClarissaFaveroDemeda_TESE.pdf: 3254557 bytes, checksum: 71f116b43b1323319edbd07fa141e478 (MD5) / Made available in DSpace on 2016-10-17T23:03:20Z (GMT). No. of bitstreams: 1 ClarissaFaveroDemeda_TESE.pdf: 3254557 bytes, checksum: 71f116b43b1323319edbd07fa141e478 (MD5) Previous issue date: 2016-02-17 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq) / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / Os exossomos s?o respons?veis pela comunica??o c?lula-c?lula e podem influenciar na progress?o tumoral, met?stase e efic?cia terap?utica. Dentre as c?lulas capazes de secretar exossomos est?o as c?lulas tumorais e as c?lulas imunes. Sabe-se que a presen?a das c?lulas imunes ? importante para erradicar os tumores. No entanto, achados recentes demonstram que a inflama??o pode promover o crescimento tumoral. Os macr?fagos associados a tumores (TAMs) s?o conhecidos por apresentarem diferentes subtipos, M1 e M2, capazes de secretarem exossomos. O presente estudo se prop?s a observar o comportamento dos exossomos derivados dos TAMs, dos subtipos 1 e 2, frente a cultura de c?lulas humanas SCC-25, HSC-3 e SAS derivadas de CE de l?ngua, por meio da an?lise da capacidade de invas?o, prolifera??o e viabilidade das c?lulas tumorais na presen?a dos exossomos. Observou-se que as microves?culas derivadas dos TAMs apresentam positividade para CD63, caracterizando-as como exossomos. Os exossomos dos TAMs do subtipo M2 foram os ?nicos a apresentarem marca??o para TGF-?, quando em compara??o com os exossomos M1, THP1 e das linhagens celulares de CE, sugerindo que os exossomos M2 podem ser respons?veis pela express?o de TGF-? nas c?lulas tumorais, uma vez que s?o internalizados. Nos ensaios de migra??o, observou-se que as c?lulas SCC-25 em presen?a de meio de cultura DMEM F/12, apresentaram maior capacidade de invas?o frente aos exossomos M2 (p?0,001), para concentra??o de 0,1 ?g/ml. Para as c?lulas HSC-3 e SAS, n?o foi observada rela??o estatisticamente significante entre a presen?a de exossomos cultivados juntamente com as c?lulas tumorais e a capacidade de invas?o celular (p>0,05). Quando os exossomos foram colocados no compartimento inferior do transwell, as c?lulas HSC-3 em presen?a dos exossomos M2 (1,0 ?g/ml) apresentaram maior capacidade de invas?o (p?0,001). O teste de viabilidade demonstrou que as c?lulas HSC-3 tornam-se mais vi?veis frente ? presen?a dos exossomos M2 (p?0,001) na concentra??o de 50 ?g/ml. Para as c?lulas SCC-25, o resultado foi o mesmo (p?0,05). A imunofluoresc?ncia demonstrou a internaliza??o dos exossomos nas linhagens celulares estudadas. Os achados sugerem que a presen?a de exossomos M2, frente ?s culturas de c?lulas de CE de l?ngua, pode ser um campo de pesquisa importante para futuros estudos com terapias-alvo. / Squamous cell carcinoma (SCC) of the oral tongue is one of the most common malignant lesions in the oral cavity and is characterized by presenting a locally invasive and aggressive behavior. The exosomes are responsible for cell-cell communication and may influence tumor progression, metastasis and therapeutic efficacy. Among the cells that can secrete exosomes are tumor cells and immune cells. It is known that the presence of immune cells is important to eradicate tumors. However, recent findings suggest that inflammation may promote tumor growth. The tumor associated macrophages (TAMs) are known to have subtypes, M1 and M2, that secrete exosomes. This study?s goal was to observe the behavior of derivatives TAMs exosomes, subtypes 1 and 2, against human cell culture SCC-25, HSC-3 and SAS derived from SCC of oral tongue, through the analysis of invasiveness, proliferation and viability of tumor cells in the presence of exosomes. It was observed that the microvesicles derived from TAMs are positive for CD63, characterizing them as exosomes. The exosomes of the M2 subtype TAMs were the only ones to present TGF-? marking, as compared with M1 exosomes, THP1 and SCC cell lines, suggesting that M2 exosomes may be responsible for TGF-? expression in tumor cells. In the migration tests, it was found that the SCC-25 cells in the presence of culture medium DMEM F / 12 showed higher invasion capacity in the presence of M2 exosomes (p?0,001) to a concentration of 0.1 ?g/ml. For HSC-3 and SAS cells, there was no significant statistical relationship between the presence of exosomes and invasiveness (p> 0.05) for the exosomes derived from TAMs. When the exosomes were placed in the lower compartment of the transwell, the HSC-3 cells in the presence of M2 exosomes (1.0 ?g/ml) had higher invasiveness (p?0,001). The viability test showed that HSC-3 cells became more viable in the presence of M2 exosomes (p?0.001) at a concentration of 50 ?g/ml. For SCC-25 cells, the result was the same (p?0.05). Immunofluorescence showed the internalization of exosomes in the cell lines studied. These findings suggest that the presence of M2 exosomes in the SCC of the oral tongue cell cultures may be an important research field for future studies of targeted therapies.
3

Purifica??o, caracteriza??o e efeitos imunomodulat?rio e antiproliferativo de uma lectina do fungo Clavaria cristata (Holmsk.) Pers

Cunha, Dayse Caroline Severiano da 08 October 2010 (has links)
Made available in DSpace on 2014-12-17T14:03:34Z (GMT). No. of bitstreams: 1 DayseCSC_DISSERT.pdf: 507696 bytes, checksum: 782930a6c60b8e6d0073baa1386c82e5 (MD5) Previous issue date: 2010-10-08 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / A 140,0 kDa lectin was purified and characterized from the mushroom Clavaria cristata. The purification procedures from the crude extract of the mushroom comprised gel filtration chromatography on Sephacryl s200 and ion exchange on Resource Q column. The purified lectin agglutinated all types of human erythrocytes with preference for trypsinized type O erythrocytes. The haemagglutinating activity is dependent of Ca 2+ ions and was strongly inhibited by the glycoprotein bovine submaxillary mucin (BSM) up to the concentration of 0, 125 mg/mL. The C. cristata lectin (CcL) was stable in the pH range of 2,5-11,5 and termostable up to 80 ?C. CcL molecular mass determined by gel filtration on a Superose 6 10 300 column was approximately 140,3 kDa. SDS polyacrilamide gel electrophoresis revealed a single band with a molecular mass of approximately 14,5 kDa, when the lectin was heated at 100 ?C in the presence or absence of ?-mercaptoethanol. CcL induced activation of murine peritoneal macrophages in vitro resulting in the release of nitric oxide (NO), reaching the maximum production at 24 h. In experimental paw oedema model in mice, CcL showed proinflammatory activity being able to induce oedema formation. Cell viability of HepG2, MDA 435 e 3T3 cell lines was examined after 72 h of incubation with CcL in different concentrations (0,5-50 ?g/mL). CcL inhibited HepG2 cells growth with an IC50 value of 50 ?g/mL. In the present work, the observed immunomodulatory and antiproliferative effects indicate CcL as a possible immunomodulator compound, interfering in the macrophages immune response, taking possible anti-parasitic, anti-tumoral effects or diagnostic and/or therapeutic / Uma lectina de 140,0 kDa foi purificada e caracterizada a partir do extrato prot?ico do fungo Clavaria cristata. O processo de purifica??o a partir do extrato bruto do fungo compreendeu uma cromatografia de gel filtra??o SEPHACRYL S200 e uma cromatografia de troca i?nica Resource Q em sistema FPLC-AKTA (Fast Protein Liquid Chromatography). A lectina de C. cristata (CcL) aglutinou todos os tipos de eritr?citos humanos com prefer?ncia pelos do tipo O tratados com tripsina. A atividade hemaglutinante de CcL se mostrou dependente do ?on c?lcio e foi fortemente inibida pela glicoprote?na mucina bovina (BSM) at? a concentra??o m?nima de 0,125 mg/mL. CcL foi est?vel numa ampla faixa de pH, que variou entre 2,5-11,5 e termoest?vel at? 80?C por uma hora. A massa molecular da CcL, determ inada por cromatografia de gel filtra??o Superose 6 10 300 GL em sistema de FPLC-AKTA foi de aproximadamente 140,3 kDa e uma eletroforese SDS-PAGE revelou uma ?nica banda com massa molecular de aproximadamente 14,5 kDa quando a lectina foi aquecida ? temperatura de 100 ?C. CcL induziu a ativa??o de macr?fagos murinos in vitro com conseq?ente libera??o de ?xido n?trico atingindo a m?xima produ??o de ?xido n?trico no tempo de 24 h. Em modelo experimental de edema de pata em camundongos, a lectina do fungo apresentou atividade pr?-inflamat?ria sendo capaz de induzir a forma??o do edema. A viabilidade celular das linhagens celulares HepG2, MDA 435 e 3T3 foi analisada ap?s incuba??o por 72 h com concentra??es de CcL (0,5-50 ?g/mL). O valor do IC50 foi obtido com a concentra??o de CcL de 50 ?g/mL para linhagem de c?lulas HepG2. No presente trabalho, os efeitos imunomodulat?rios e antiproliferativos foram observados apontando a CcL como um poss?vel imunomodulador, interferindo na resposta imune de macr?fagos levando a poss?veis efeitos anti-parasit?rios, anti-tumorais ou agente diagn?stico e/ou terap?utico
4

Efeito imunomodulador e atividade antimicrobiana de heterofucanas de Sargassum filipendula

Telles, Cinthia Beatrice da Silva 26 June 2015 (has links)
Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-05-30T20:01:31Z No. of bitstreams: 1 CinthiaBeatriceDaSilvaTelles_TESE.pdf: 1798517 bytes, checksum: 1ec7c34c6f828ce70bd877620c9ebb47 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-05-31T22:29:14Z (GMT) No. of bitstreams: 1 CinthiaBeatriceDaSilvaTelles_TESE.pdf: 1798517 bytes, checksum: 1ec7c34c6f828ce70bd877620c9ebb47 (MD5) / Made available in DSpace on 2016-05-31T22:29:14Z (GMT). No. of bitstreams: 1 CinthiaBeatriceDaSilvaTelles_TESE.pdf: 1798517 bytes, checksum: 1ec7c34c6f828ce70bd877620c9ebb47 (MD5) Previous issue date: 2015-06-26 / Macroalgas marinhas constituem uma fonte extremamente rica de compostos bioativos, dentre eles, polissacar?deos sulfatados. Sargassum filipendula (SF), alga pertencente ? ordem Phaeophycea, ? fonte de heterofucanas conhecidas pela capacidade de modular uma s?rie de fun??es biol?gicas. Considerando a necessidade de encontrar f?rmacos mais eficientes no combate a infec??es microbianas, as heterofucanas de SF foram avaliadas como agentes imunomoduladores e antimicrobianos. As heterofucanas SF0.5V, SF0.7V e SF1.0V apresentaram uma forte atividade imunomoduladora intensificando a libera??o de ?xido n?trico (NO) por macr?fagos murinos (RAW 264.7), bem como, por macr?fagos originados de mon?citos prim?rios humanos. Al?m disso, quando macr?fagos humanos foram infectados por Leishmania infantum e tratados com SF0.5V, SF0.7V e SF1.0V ocorreu um aumento significativo na libera??o extracelular de NO. Como a citotoxicidadede de macrof?gos contra a forma intracelular de leishmanias ? mediada pela produ??o de NO, avaliamos a atividade leishmanicida sobre a forma amastigota intracelular de L. infantum e observamos que macr?fagos infectados e tratados com SF0.5V, SF0.7V e SF1.0V se tornaram menos suscept?veis ? infec??o. As heterofucanas que se mostraram com capacidade de induzir a atividade anti-leishmania tamb?m apresentaram melhor taxa de produ??o de NO, por?m os dados de correla??o levaram a observa??o que este n?o ? o principal mecanismo de a??o das fucanas de SF no combate a esse protozo?rio. A heterofucana SF0.5V tamb?m apresentou atividade inibit?ria da forma??o de biofilme (~ 50%) frente a bact?ria Staphylococcus epidermidis. J? SF0.7V e 1.0V inibiram quase que totalmente a replica??o do protozo?rio Trichomonas vaginalis. Resultados como esse refletem o espectro de a??o desses polissacar?deos sulfatados obtidos de SF e mostram o seu potencial como agentes imunomoduladores e microbicidas. / Fucans, sulphated polysaccharides that contain L-fucose in its constitution, obtained from species of Phaeophyceae of the Sargassum kind, display several biological activities. Heterofucans from Sargassum filipendula are bioactive molecules that contain strong antiproliferative and antioxidant activity. However, their immunomodulatory and antimicrobial activities have not yet been examined. In this context, the aim of this research was to evaluate the heterofucans as for their immunomodulatory capacity and antimicrobial action against Leishmania infantum, Trichomonas vaginalis, Staphylococcus epidermidis and Klebsiella pneumonia (KPC). The five heterofucans obtained from S. filipendula show activities that are distant as stimulants of the immune system and microbial agent. The SF0.5V, SF0.7V amd SF1.0V heterofucans were capable of acting in the activation of murine and human macrophages. In addition to that, SF0.5V has shown antibiofilm activity of S. epidermides and SF0.7V and 1.0V almost completely inhibited the survival of the protozoan T. vaginalis. Results such as this one, reflect the broad range of action of the sulphated polysaccharides obtained from seaweeds, especially from the species S.filipendula
5

Propriedades anti-inflamat?rias e antioxidantes dos extratos aquosos das folhas de Turnera subulata Sm. E Anacardium occidentale L. / Anti-inflammatory and antioxidant properties of aqueous extracts of Turnera subulata Sm. and Anacardium occidentale L.

Souza, Nat?lia Cabral 25 August 2017 (has links)
Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-11-01T23:16:15Z No. of bitstreams: 1 NataliaCabralSouza_DISSERT.pdf: 6162949 bytes, checksum: a617efb8abda58ca56a363d6c5f97c62 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-11-16T21:48:54Z (GMT) No. of bitstreams: 1 NataliaCabralSouza_DISSERT.pdf: 6162949 bytes, checksum: a617efb8abda58ca56a363d6c5f97c62 (MD5) / Made available in DSpace on 2017-11-16T21:48:54Z (GMT). No. of bitstreams: 1 NataliaCabralSouza_DISSERT.pdf: 6162949 bytes, checksum: a617efb8abda58ca56a363d6c5f97c62 (MD5) Previous issue date: 2017-08-25 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / Extratos vegetais s?o aplicados amplamente na medicina popular, principalmente na regi?o Nordeste do Brasil. O extrato das folhas de Turnera subulata e Anacardium occidentale, por exemplo, ? aplicado como alternativa no tratamento de diversas doen?as como diabetes, hipertens?o, dor cr?nica, c?ncer e inflama??es. Entretanto, apesar do seu amplo uso, os efeitos desses compostos ainda n?o est?o bem descritos. Deste modo, buscamos avaliar as propriedades antioxidantes e anti-inflamat?rias dos extratos das folhas de T. subulata e A. occidentale em um modelo de inflama??o in vitro, usando o lipopolissac?rideo como estimulo em macr?fagos da linhagem RAW 264.7. Para tanto, fizemos a quantifica??o de marcadores de resposta inflamat?ria na linhagem, assim como a sua capacidade de modula??o das prote?nas cinases ativadas por mit?geno (p38, ERK? e JNK). Adicionalmente, foram realizados ensaios de viabilidade pela rea??o com o brometo de 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetraz?lio e da sulforhodamina B, avalia??o da modula??o em fator de necrose tumoral alfa e interleucina-1?, al?m de ensaios espec?ficos para a avalia??o antioxidante como o de oxida??o de diclorofluoresce?na em tempo real, quantifica??o das esp?cies reativas do ?cido tiobarbit?rico, prote?nas tiol e carbonila??o de prote?nas. Os extratos apresentaram atividades antioxidantes e anti-inflamat?rias, por ser poss?vel observar que o co-tratamento com o extrato das folhas de T. subulata foi capaz de reduzir o estresse oxidativo nas c?lulas, produzido pela resposta inflamat?ria, tal como, possuiu a capacidade de modular diretamente a resposta inflamat?ria, modulando a atividade dos membros das vias prote?nas cinases ativadas por mit?geno. No extrato das folhas de A. occidentale, os resultados tamb?m demostraram atividade antioxidante, que foi observado a partir da diminui??o do dano oxidativo em macr?fagos tratados com as dosagens de 0,5 e 5 ?g/mL do extrato. Al?m disso, esse extrato reverteu os danos oxidativos e os par?metros inflamat?rios induzidos por lipopolissac?rideo nas c?lulas testadas, sendo capaz de inibir a libera??o do fator de necrose tumoral alfa e interleucina-1?. Marcadores inflamat?rios como receptor toll-like 4, receptor para produtos de glica??o avan?ada e CD40, que s?o induzidos por lipopolissac?rideo tamb?m foram modulados. Posteriormente avaliamos as vias de sinaliza??o envolvidas na resposta inflamat?ria mediada por lipopolissac?rideo. O extrato de A. occidentale bloqueou os efeitos do lipopolissac?rideo na fosforila??o de ERK?, SAPK/JNK e P38. Dessa forma, nossos resultados indicam os poss?veis efeitos antioxidantes e anti-inflamat?rios dos extratos aquosos de T. subulata e A. occidentale e demonstram os poss?veis mecanismos biol?gicos respons?veis por esses efeitos. / Plant extracts are widely applied in popular medicine, mainly in the Northeastern Brazil. The leaf extracts of Turnera subulata and Anacardium occidentale, for example, are applied as an alternative in the treatment of lots diseases such diabetes, hypertension, chronic pain, cancer and inflammation. Despite their wide use, the effects of these are still not well described. Thus, we to evaluate the antioxidant and anti-inflammatory properties of leaf extracts of T. subulata and A. occidentale in an in vitro inflammation model of using lipopolysaccharide macrophage RAW 264.7 cells. Therefore, we quantified the inflammatory response markers in the lineage, as well as its ability to modulate the MAPKs (p38, ERK? and JNK). In addition, MTT and SRB viability tests, TNF-? and IL-1? modulation evaluation were performed, as well as specific tests for antioxidant evaluation such as DCFH, TBARS, thiol proteins and carbonylation of proteins. The extracts presented antioxidant and anti-inflammatory activities, and it was possible to observe that co-treatment with the extract of leaf the T. subulata was able to reduce the oxidative stress in the cells, produced by the inflammatory response, the capacity for modulate directly the inflammatory response, altering the activity of MAPK pathway members. In the extract of leaf the A. occidentale the results also showed antioxidant activity, which was observed when the extract decreased the oxidative damage in cells of macrophages treated with the dosages of 0.5 and 5 ?g/mL. In addition, this extract reversed the oxidative damage and inflammatory parameters induced by lipopolysaccharide in the cells tested, being able to inhibit the release of TNF-? and IL-1?. Inflammatory markers such as TLR4, RAGE and CD40 that are induced by LPS were also modulated. Later, we evaluated the signaling pathways involved in the lipopolysaccharide-mediated inflammatory response. The extract of A. occidentale blocked the effects of lipopolysaccharide on the phosphorylation of ERK?, SAPK/ JNK and p38. In this way, our results indicate the possible antioxidant and anti-inflammatory effects of the aqueous extracts of T. subulata and A. occidentale and demonstrate the possible biological mechanisms responsible for these effects.
6

Express?o do fator inibit?rio da migra??o de macr?fagos e do fator de permeabilidade vascular em les?es da c?rvice uterina induzidas pelo papilomav?rus humano

Nobre, Camila Cristina Guimar?es 31 May 2017 (has links)
Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-10-05T19:11:50Z No. of bitstreams: 1 CamilaCristinaGuimaraesNobre_DISSERT.pdf: 3735111 bytes, checksum: 1da00d1e44ef4ca4da5192f63cc4d5e6 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-10-17T21:08:41Z (GMT) No. of bitstreams: 1 CamilaCristinaGuimaraesNobre_DISSERT.pdf: 3735111 bytes, checksum: 1da00d1e44ef4ca4da5192f63cc4d5e6 (MD5) / Made available in DSpace on 2017-10-17T21:08:41Z (GMT). No. of bitstreams: 1 CamilaCristinaGuimaraesNobre_DISSERT.pdf: 3735111 bytes, checksum: 1da00d1e44ef4ca4da5192f63cc4d5e6 (MD5) Previous issue date: 2017-05-31 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / O c?ncer do colo do ?tero ? o terceiro tipo de c?ncer mais frequente em mulheres no Brasil, sendo a sua frequ?ncia menor apenas do que aquelas observadas para o c?ncer de pele n?o-melanoma e c?ncer de mama. O fator inibit?rio da migra??o de macr?fagos (MIF) ? produzido por diferentes tipos de c?lulas e participa de uma cadeia complexa de eventos que favorece o processo de carcinog?nese, sendo poss?vel observar um alto n?vel de express?o em quase todos os tipos de c?ncer humano, entre eles o c?ncer do colo do ?tero. O MIF tamb?m induz um aumento dose dependente na excre??o do fator de crescimento de endot?lio vascular (VEGF), que promove a angiog?nese, o crescimento tumoral e a migra??o dessas c?lulas no c?ncer do colo do ?tero. O objetivo deste estudo foi investigar a express?o de MIF e VEGF em pacientes que apresentam ou n?o les?es do colo do ?tero, no intuito de identificar a exist?ncia de uma rela??o direta entre a presen?a dos marcadores MIF e VEGF com o grau da les?o da paciente, bem como, com a presen?a do papilomav?rus humano (HPV). Foram inclu?das no estudo 45 mulheres que haviam sido encaminhadas para a Maternidade Escola Janu?rio Cicco com suspeita de les?es na c?rvice uterina. As pacientes que aceitaram participar do estudo responderam a um question?rio, para obten??o de dados s?cio-demograficos, seguido de exame cl?nico. Das mulheres que se submeteram a colposcopia, foram coletados dois fragmentos de tecido do colo do ?tero, um para an?lise histopatol?gica e outro para detec??o do HPV por PCR convencional. A express?o dos biomarcadores, MIF e VEGF, foi detectada pela t?cnica de imuno-histoqu?mica. A ?rea positiva de cada biomarcador foi lida e quantificada utilizando o programa ImageJ?, e o resultado foi analisado atrav?s dos programas de estat?stica SPSS? Statistics e GraphPad Prism. Das 45 pacientes inclu?das no estudo, 20% apresentaram resultado do exame dentro dos padr?es da normalidade, enquanto que 80% apresentaram algum tipo de altera??o no exame; sendo 35,55% les?es intraepiteliais de baixo grau (LIEBG) e 44,44% les?es intraepiteliais de alto grau (LIEAG). A taxa de preval?ncia global de infec??o genital pelo HPV foi de 80%, sendo 86,1% em pacientes com les?o. A express?o m?dia do VEGF e do MIF tiveram um aumento gradativo quando comparado entre as pacientes normais, LIEBG e LIEAG, correspondendo respectivamente aos seguintes valores, 19,62, 41,59 e 55,42 para o VEGF e 4,36, 9,44 e 22,86 para MIF. Foi poss?vel verificar uma correla??o positiva entre a express?o de MIF e VEGF (r = 0,523, p = <0,001). Por meio deste trabalho p?de-se concluir que o VEGF e o MIF est?o correlacionados e envolvidos no processo de displasia cervical, aumentando a sua express?o conforme ocorre a progress?o da les?o. No entanto, n?o foi poss?vel encontrar associa??o entre a presen?a do HPV e os n?veis de MIF e VEGF. / The cervical cancer is the third most frequent type of cancer in women in Brazil, and its frequency is only lower than those observed for non-melanoma skin cancer and breast cancer. Macrophage migration inhibitory factor (MIF) is produced by different cell types and participates in a complex chain of events that favors the process of carcinogenesis, being possible to observe a high expression level in almost all types of human cancer, such as in cervical cancer. MIF also induces a dose-dependent increase in the excretion of vascular endothelial growth factor (VEGF), which promotes angiogenesis, tumor growth and migration of these cells in cervical cancer. The objective of this study was to investigate the expression of MIF and VEGF in patients with or without cervical lesions, in order to identify the existence of a direct relationship between the presence of those markers with the degree of the lesion of the patient, as well, as with the presence of human papillomavirus (HPV). The study included 45 women who had been referred to the Maternity School Janu?rio Cicco with suspected lesions of the uterine cervix. Patients who accepted to participate in the study answered a questionnaire to obtain socio-demographic data, followed by clinical examination. Patients who agreed to participate in the study answered a questionnaire to obtain socio-demographic data, followed by clinical examination. Two cervix tissue fragments were collected from the women who underwent colposcopy, one for histopathological analysis and the other for HPV detection by conventional PCR. The expression of the biomarkers, MIF and VEGF, was detected by the immunohistochemical technique. The positive area of each biomarker was read and quantified using the ImageJ? program and the result was analyzed using the statistical program SPSS? Statistics and GraphPad Prism. Of the 45 patients included in the study, 20% showed no lesions, while 80% had some type of alteration in the exam; being 35.55% low-grade squamous intraepithelial lesion (LSIL) type and 44.44% highgrade squamous intraepithelial lesion (HSIL) type. The overall prevalence rate of genital HPV infection was 80%, with 86.1% in patients with lesions. Mean VEGF and MIF expression increased gradually when compared to normal patients, LSIL and HSIL, respectively, corresponding to the following values: 19.62, 41.59 and 55.42 for VEGF and 4.36, 9, 44 and 22.86 for MIF. A positive correlation between MIF and VEGF expression was found (r = 0.523, p = <0.001). Through this work it was concluded that VEGF and MIF are correlated and involved in the cervical dysplasia process, increasing its expression as the lesion progresses. However, it was not possible to find an association between the presence of HPV and the levels of MIF and VEGF.

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