Islet transplantations have been successful in restoring glucose homeostasis in patients with diabetes; however, the limited number of donor organs limits the success of this treatment. The lineage reprograming of different cell sources to beta cells potentially provides an unlimited supply of insulin-producing cells for regenerative therapy for patients with diabetes. The aim of this study was to investigate the ability to transdifferentiate two cell lines into an endocrine lineage. Insulin production in pancreatic beta cells can be increased using a small molecule, 3,5-disubstituted isoxazole, N-cyclopropyl-t-(thiophen-2-yl)isoxazole-3-carboxamide (isoxazole) but its effect on other cell types has not been reported. Here, we investigated the lineage reprogramming of PANC-1 pancreatic ductal cells to insulin producing cells by isoxazole treatment. Gene expression was performed using RT-PCR and qPCR for approximately 30 genes critical to beta cell development and function. In addition, quantitative proteomic profiling was performed using LC-MS by monitoring protein abundance in isoxazole-treated PANC-1 cells compared to time-matched controls. Isoxazole treatment stimulated PANC-1 cells to aggregate into islet-like clusters and gene expression analysis revealed induction of important developmental beta cell markers including NGN3, NEUROD1 and INSULIN. In addition, beta cell surface markers were also upregulated such as CD200, GPR50, TROP-2, GLUT2 and SLC30A8. Using LC-MS a catalogue of approximately 2400 identified proteins was generated; 257 proteins were differentially expressed in isoxazole-treated cells compared to DMSO-vehicle controls at p < 0.05. Amongst the proteins upregulated were molecules that regulate metabolic processes and cytoskeletal reorganisation. The expression of the majority of these proteins has not been previously reported or studied in the context of beta cell differentiation. Functional analysis of the relative protein changes was determined using Ingenuity Pathway Analysis, IPA, and gene ontology, GO, software, which revealed the regulation of several cellular canonical pathways including metabolic pathways, cell adhesion, remodelling of epithelial adherens junctions and actin cytoskeleton signalling. The effects of isoxazole were further studied in the A549 lung cancer cell line. Similar effects were observed, such as the induction of pro-endocrine markers NGN3 and NEUROD1 and endocrine-specific hormones INS and GCG. These results indicate that isoxazole has the capacity to transdifferentiate pancreatic and non-pancreatic cell origins into an endocrine lineage. This study reveals the powerful induction capacity of isoxazole in inducing cellular reprogramming events.

No description available.

Pomegranate extract (PE) is a standardized whole fruit extract of pomegranate (Punica granatum L.), a fruit with known anti inflammatory and anti cancer properties. In the present study, the effects of PE on two different cell lines of human pancreatic cancer cells, AsPC-1 and PANC-1 were examined. Both cell lines are epithelial cancers but differ morphologically and in their response to treatment with PE. PE inhibited proliferation of both cancer cell lines in a dose dependent and time dependent manner. The reason for this was the potency of PE to cause significant cell cycle arrest in the pancreatic cancer cells, which was noted to be cell specific. AsPC-1 was arrested in G₂ phase while PANC-1 was arrested in G₀/G₁phase of the cell cycle. PE also checked the viability of confluent cancer cells in a concentration dependent manner. In case of AsPC-1 this was due to the action of PE to induce apoptosis, as demonstrated by the Annexin-V assay. In case of PANC-1, a highly invading cancer greatly affected by the presence of surface stem cell markers CD44⁺/CD24⁺, PE was capable of modifying the stem cell markers and induce an increase in the non tumorigenic sub population of cells. A study was also conducted to look at the action of PE in causing inhibition of pancreatic cancer cell proliferation, in comparison to a clinically used chemotherapeutic agent, Paclitaxel. The results indicated that the effect of PE, at clinically feasible doses was superior to that of clinically used doses of Paclitaxel. This data suggests that PE, which is proven to be a safe dietary supplement, looks promising in the prevention and treatment of human pancreatic cancer cells without the side effects of standard drug therapy and could possibly have a role in controlling stem cancer cell population / text

Le diabète de type 1 (DT1) est une maladie chronique multifactorielle. Les infections entérovirales, en particulier à Coxsackievirus du groupe B (CVB), et notamment CVB4, transmises par voie digestive, constituent le facteur de risque le plus souvent évoqué dans la littérature. Plusieurs mécanismes physiopathologiques sont proposés pour expliquer cette relation entre CVB4 et diabète de type 1. Il s’agit, entre autres, du tropisme préférentiel de CVB4 pour les ilots et les cellules &#946; pancréatiques et l’inflammation qui s’ensuit, de la persistance du virus au niveau des cellules infectées qui pourrait constituer un facteur déterminant dans le processus d’altération des cellules endocrines, de l’exacerbation possible de l’infection par des d’anticorps facilitateurs ou encore du mimétisme moléculaire entre les auto-antigènes et les antigènes viraux. Par ailleurs des auteurs ont montré que la cause de la déplétion des cellules &#946; chez des souris infectées par la souche diabétogénique CVB4E2 est un défaut de régénération plutôt qu’une destruction directe de ces cellules par le virus. La présence de constituants entéroviraux dans les cellules ductales du pancréas de patients diabétiques a été observée. Le diabète de type 1, qui serait l’expression finale d’un long processus, survient généralement chez des sujets jeunes, c’est pourquoi l’hypothèse que le tissu pancréatique jeune serait plus permissif aux infections à CVB4 n’est pas exclue. La prévention des infections virales reste le meilleur moyen de protéger les individus contre les maladies qu’elles provoquent. Un intérêt particulier est aujourd’hui accordé à la mise en évidences et à la caractérisation d’inhibiteurs antiviraux à large spectre. L’absence d’allaitement maternel est associé à un risque plus élevé de diabète de type 1, mais la nature du ou des facteurs du lait conférant une protection est mal connue, et l’activité anti-CVB4 du lait maternel n’a pas été étudiée jusqu’à présent. Objectifs : Nous avons émis l’hypothèse que CVB4 pouvait infecter des cellules humaines précurseurs de cellules endocrines, impliquées dans la régénération des îlots. L’infection de ces cellules par CVB4E2 et ses conséquences ont été étudiées ; nous avons utilisé des cellules humaines précurseurs canalaires primitives et la lignée continue de cellules Panc-1, dont la différenciation in vitro est possible. La permissivité au CVB4 du tissu pancréatique selon l’âge a été étudiée ex vivo chez le rat et l’existence d’inhibiteurs antiviraux à large spectre est notamment explorée dans l’intestin de souris. L’activité anti-CVB4 du lait maternel susceptible de protéger, à un âge critique, le jeune enfant vis-à-vis d’un virus diabétogène a été étudiée in vitro et l’hypothèse que le lait humain pourrait prévenir le déclenchement du DT1 chez la souris NOD a également été évaluée in vivo. / Type 1 diabetes (T1D) is a chronic multifactorial disease. Enteroviral infections, especially those with group B coxsackieviruses, and in particular the B4 serotype (CVB4), mainly transmitted by the fecal-oral route, are among the environmental factors most able to be involved in the pathogenesis of the disease. Several pathophysiological mechanisms have been proposed to explain this relationship between CVB4 and T1D. Among these mechanisms, the preferential tropism of CVB4 for islets and pancreatic &#946; cells and the resulted inflammation; virus persistence in infected cells which can constitute an important factor in the process leading to endocrine cells alteration; the possible worsening of the infection by enhancing antibodies or molecular mimicry between self-antigens and viral antigens. Moreover, some studies have demonstrated that &#946;-cell depletion in mice infected with the diabetogenic strain CVB4E2 is due to lack of regeneration rather than direct destruction of these cells by the virus. Enteroviral constituents have been detected in pancreatic ductal cells of T1D patients. Type 1 diabetes is a final expression of a long process usually occurring in young children. Therefore, the hypothesis that the pancreatic tissue of young subjects is more permissive to CVB4 infection can not be excluded. Prevention of viral infections is the best way to protect people against diseases they cause. Thus, identification and characterization of broad-spectrum antiviral inhibitors are of particular interest. A lower risk of T1D is associated with breastfeeding, however, the support of the breast milk protective effect has not been clarified, and the neutralizing activity of breast milk in vitro against CVB4 has not been studied so far.

Nas cidades de São José do Barreiro e Areias, no Vale do Paraíba Paulista é possível encontrar dentro do centro urbano características associadas à ruralidade, como o cultivo de hortaliças e frutas nos quintais, além da presença de detentores de um conhecimento botânico sobre plantas alimentícias. Os quintais, as plantas e os saberes são considerados patrimônio, apresentando a contextualização para a construção de uma definição integradora, tendo em vista os saberes etnobotânicos e suas peculiaridades dentro da população estudada. Dessa forma, o presente trabalho teve como objetivo caracterizar o uso de dessas plantas alimentícias nesses quintais, com vistas a identificar as vulnerabilidades nas quais plantas e os saberes a elas associados estão sujeitos. Foram entrevistados 67 residentes dos dois municípios, e encontradas 172 espécies e variedades alimentícias, das quais 31 são consideradas espontâneas. Nos quintais, foram listadas ainda 20 espécies que possuem potencial na alimentação, mas não foram citadas. O conhecimento de plantas alimentícias da população é notável, contudo, diversos processos podem comprometer a transmissão desses saberes. Esses patrimônios estão sujeitos ao desaparecimento, de forma que os saberes botânicos detidos por parte da população também estão em risco. / In the cities of São José do Barreiro and Areias, in the Vale do Paraíba Paulista, it is possible to find in the urban center, characteristics associated with rurality, such as the cultivation of vegetables and fruits in the homegardens, besides the presence of holders of a botanical knowledge about edible plants. The homegardens, the plants and the knowledge are considered heritage, presenting the contextualization for the construction of an integrative definition, in the perspective of ethnobotanical knowledge and its peculiarities in that population. Thus, the present work aimed to characterize the use of these food plants in these homegardens, in order to identify the vulnerabilities in which plants and the associated knowledge are associated. We interviewed 67 residents in the two municipalities, and are found 172 edible species and varieties of plants, of which 31 are considered spontaneous. In the homegardens, 20 species have potential for humans consumption, but were not mentioned. The knowledge of food plants in the population is remarkable, however, several processes can compromise the transmission of these knowledge. These heritage is subject to disappearance, so that the botanical knowledge held by the population is also at risk.

Submitted by Jorge Silva (jorgelmsilva@ufrrj.br) on 2017-08-29T18:10:46Z No. of bitstreams: 1 2017 - Renata Oliveira Santos.pdf: 1382777 bytes, checksum: 331bbbcbeb5b7d3a9f1d49008191a5b8 (MD5) / Made available in DSpace on 2017-08-29T18:10:46Z (GMT). No. of bitstreams: 1 2017 - Renata Oliveira Santos.pdf: 1382777 bytes, checksum: 331bbbcbeb5b7d3a9f1d49008191a5b8 (MD5) Previous issue date: 2017-02-14 / CAPES / In the past few years the use of prebiotics in the making of dairy products has been gathering many supports, although the search for low cost raw-material to achieve that it still a big challenge, which highlights the potential to the development in the research for alternatives sources or new processes in order to obtain those ingredients. Besides, the need to reduces the additives in the diet has been mandatory to the consumers who wants a health diet, as a growing tendency in the food industry in the development of products with cleaner labels, which are known as clean label. In this context, the search and/or value of natural ingredients that contributes simultaneously for the improvement in the functional properties, sensory and technological of food products that make them essential. Among the sources of these ingredients, stands out the araruta (Maranta arundinacea L.) as unconventional food plants (PANC?s) from Marantaceas Family, which presents a food potential, nutritional, functional that is neglected. Therefore, the aim of this paper was to evaluate the effect of the adding of araruta flours in the physical Chemical characteristics, rheological and in the growing of probiotic bacteria in the vanilla dairy dessert. In the Chapter I was developed and research in the literature in order to evaluate the sensory aspects and technological of prebiotics flours in the dairy products. In the Chapter II was performed a study of the prebiotic potential in the araruta flour, as well as, the effect of different % of these flours in the reological and technological of the mentioned dessert. It is possible to conclude that the particles size of the flours directed affected the texture of the desserts, once the flours with bigger size contributed to the increase in firmness of the dairy desserts. In addition, regarding the functional aspects, the araruta flour presented high level of resistent starch (29,47%) low IG(41,8), beyond the probiotic potential, which contribute to the increase number on the Lactobacillus Casey counting. Also, it was verified that % flour contribute to the reduction in the syneresis, rheological properties(flow behavior in oscillatory tests), texture (firmness and stickiness) and on the microscopical characteristics in the vanilla dairy dessert. / Nos ?ltimos anos, o uso de prebi?ticos na elabora??o de produtos l?cteos tem sofrido grande incentivo, embora a procura por mat?rias-primas de baixo custo para sua obten??o ainda seja um grande desafio, evidenciando um potencial para desenvolvimento de pesquisas de fontes alternativas ou novos processos de obten??o desses ingredientes. Al?m disso, a necessidade de redu??o de aditivos na dieta tem sido mandat?ria para os consumidores que buscam uma alimenta??o mais saud?vel, assim como, uma tend?ncia crescente da ind?stria de alimentos no desenvolvimento de produtos com r?tulos mais limpos, conhecidos como clean label. Neste contexto, a busca e/ou valoriza??o de ingredientes naturais que contribuam simultaneamente para a melhoria das propriedades funcionais, sensoriais e tecnol?gicas dos produtos aliment?cios se torna fundamental. Dentre as fontes desses ingredientes, destaca-se a araruta (Maranta arundinacea L.) uma planta aliment?cia n?o convencional (PANC) da fam?lia das Marantaceas que apresenta potencial aliment?cio, nutricional, funcional e tecnol?gico negligenciado. Assim, o objetivo geral do presente trabalho foi avaliar o efeito da adi??o de farinha de araruta nas caracter?sticas f?sico-qu?micas, reol?gicas e no crescimento de bact?rias probi?ticas de sobremesa l?ctea sabor baunilha. No Cap?tulo I deste trabalho foi realizada uma revis?o de literatura visando avaliar os aspectos sensoriais e tecnol?gicos do uso de farinhas prebi?ticas em produtos l?cteos. No Cap?tulo II foi realizado o estudo das propriedades f?sicas, funcionais (amido resistente e ?ndice glic?mico) e do potencial prebi?tico da farinha de araruta, bem como, o efeito de diferentes % dessa farinha nas propriedades reol?gicas e tecnol?gicas de uma sobremesa l?ctea sabor baunilha. Pode-se concluir que o tamanho de part?cula das farinhas afetou diretamente a textura das sobremesas, uma vez que, as farinhas com maior tamanho m?dio de part?culas contribu?ram para aumento da firmeza das sobremesas l?cteas. Com rela??o aos aspectos funcionais, a farinha de araruta apresentou elevado teor de amido resistente (29,47%), baixo IG (41,8), al?m de potencial prebi?tico contribuindo para o aumento da contagem de Lactobacillus casei. Foi verificado que % farinha contribui para redu??o da sin?rese, al?m de afetar as propriedades reol?gicas (comportamento de fluxo e ensaios oscilat?rio), na textura (firmeza e adesividade) e nas caracter?sticas microsc?picas da sobremesa l?ctea sabor baunilha.

Le diabète de type 1 (DT1) est une maladie chronique multifactorielle. Les infections entérovirales, en particulier à Coxsackievirus du groupe B (CVB), et notamment CVB4, transmises par voie digestive, constituent le facteur de risque le plus souvent évoqué dans la littérature. Plusieurs mécanismes physiopathologiques sont proposés pour expliquer cette relation entre CVB4 et diabète de type 1. Il s'agit, entre autres, du tropisme préférentiel de CVB4 pour les ilots et les cellules β pancréatiques et l'inflammation qui s'ensuit, de la persistance du virus au niveau des cellules infectées qui pourrait constituer un facteur déterminant dans le processus d'altération des cellules endocrines, de l'exacerbation possible de l'infection par des d'anticorps facilitateurs ou encore du mimétisme moléculaire entre les auto-antigènes et les antigènes viraux. Par ailleurs des auteurs ont montré que la cause de la déplétion des cellules β chez des souris infectées par la souche diabétogénique CVB4E2 est un défaut de régénération plutôt qu'une destruction directe de ces cellules par le virus. La présence de constituants entéroviraux dans les cellules ductales du pancréas de patients diabétiques a été observée. Le diabète de type 1, qui serait l'expression finale d'un long processus, survient généralement chez des sujets jeunes, c'est pourquoi l'hypothèse que le tissu pancréatique jeune serait plus permissif aux infections à CVB4 n'est pas exclue. La prévention des infections virales reste le meilleur moyen de protéger les individus contre les maladies qu'elles provoquent. Un intérêt particulier est aujourd'hui accordé à la mise en évidences et à la caractérisation d'inhibiteurs antiviraux à large spectre. L'absence d'allaitement maternel est associé à un risque plus élevé de diabète de type 1, mais la nature du ou des facteurs du lait conférant une protection est mal connue, et l'activité anti-CVB4 du lait maternel n'a pas été étudiée jusqu'à présent. Objectifs : Nous avons émis l'hypothèse que CVB4 pouvait infecter des cellules humaines précurseurs de cellules endocrines, impliquées dans la régénération des îlots. L'infection de ces cellules par CVB4E2 et ses conséquences ont été étudiées ; nous avons utilisé des cellules humaines précurseurs canalaires primitives et la lignée continue de cellules Panc-1, dont la différenciation in vitro est possible. La permissivité au CVB4 du tissu pancréatique selon l'âge a été étudiée ex vivo chez le rat et l'existence d'inhibiteurs antiviraux à large spectre est notamment explorée dans l'intestin de souris. L'activité anti-CVB4 du lait maternel susceptible de protéger, à un âge critique, le jeune enfant vis-à-vis d'un virus diabétogène a été étudiée in vitro et l'hypothèse que le lait humain pourrait prévenir le déclenchement du DT1 chez la souris NOD a également été évaluée in vivo.

Nas cidades de São José do Barreiro e Areias, no Vale do Paraíba Paulista é possível encontrar dentro do centro urbano características associadas à ruralidade, como o cultivo de hortaliças e frutas nos quintais, além da presença de detentores de um conhecimento botânico sobre plantas alimentícias. Os quintais, as plantas e os saberes são considerados patrimônio, apresentando a contextualização para a construção de uma definição integradora, tendo em vista os saberes etnobotânicos e suas peculiaridades dentro da população estudada. Dessa forma, o presente trabalho teve como objetivo caracterizar o uso de dessas plantas alimentícias nesses quintais, com vistas a identificar as vulnerabilidades nas quais plantas e os saberes a elas associados estão sujeitos. Foram entrevistados 67 residentes dos dois municípios, e encontradas 172 espécies e variedades alimentícias, das quais 31 são consideradas espontâneas. Nos quintais, foram listadas ainda 20 espécies que possuem potencial na alimentação, mas não foram citadas. O conhecimento de plantas alimentícias da população é notável, contudo, diversos processos podem comprometer a transmissão desses saberes. Esses patrimônios estão sujeitos ao desaparecimento, de forma que os saberes botânicos detidos por parte da população também estão em risco. / In the cities of São José do Barreiro and Areias, in the Vale do Paraíba Paulista, it is possible to find in the urban center, characteristics associated with rurality, such as the cultivation of vegetables and fruits in the homegardens, besides the presence of holders of a botanical knowledge about edible plants. The homegardens, the plants and the knowledge are considered heritage, presenting the contextualization for the construction of an integrative definition, in the perspective of ethnobotanical knowledge and its peculiarities in that population. Thus, the present work aimed to characterize the use of these food plants in these homegardens, in order to identify the vulnerabilities in which plants and the associated knowledge are associated. We interviewed 67 residents in the two municipalities, and are found 172 edible species and varieties of plants, of which 31 are considered spontaneous. In the homegardens, 20 species have potential for humans consumption, but were not mentioned. The knowledge of food plants in the population is remarkable, however, several processes can compromise the transmission of these knowledge. These heritage is subject to disappearance, so that the botanical knowledge held by the population is also at risk.

No description available.

No description available.