Colon cancer is the third most common cancer in the United States. However, evidence indicates that a proper diet abundant in fruits and vegetables may be protective against colon cancer development. Bioactive compounds in fruits and vegetables, such as flavonoids and limonoids, have been shown to possess anti-proliferative and antitumorigenic effects in various in vitro and in vivo models of cancer. Since there are few animal studies involving flavonoids and limonoids and colon cancer, this experiment investigated the potentially protective effects of four citrus flavonoids and one limonoid mixture against the promotion stage of chemically-induced colon cancer in rats. Male SD rats (n =60; 10 rats/group) were assigned to receive diets containing 0.1% apigenin, 0.02% naringenin, 0.1% hesperidin, 0.01% nobiletin, 0.035% limonin glucoside/obacunone glucoside mixture, or a control diet (0% flavonoid/limonoid). Rats received the diets for 10 wk and were injected with azoxymethane (15 mg/kg) at wk 3 and 4. The excised colons were evaluated for aberrant crypt foci (ACF) formation, cell proliferation (PCNA assay), apoptosis (TUNEL assay), and iNOS and COX-2 expression. When compared to the control diet, apigenin lowered the number of high multiplicity ACF (> 4 AC/focus) by 57% (P<0.05) and tended to lower the proliferative index (28%; P=0.07), while naringenin lowered both the number of high multiplicity ACF by 51% (P<0.05) and the proliferative index by 32% (P<0.05). Both apigenin and naringenin increased apoptosis of surface colon cells (78% and 97%, respectively; P<0.05) when compared to control diet. Hesperidin, nobiletin, and the limoninglucoside/obacunone glucoside mixture did not have any effects on the above variables measured in this model of colon carcinogenesis. The colonic mucosal protein levels of iNOS or COX-2 were not different among the six diet groups. Evidence suggests that high multiplicity ACF are indicative of future tumor development in both humans and rats. Furthermore, dysregulated proliferation and apoptosis may also lead to tumorigenesis. Therefore, the ability of dietary apigenin and naringenin to reduce high multiplicity ACF, lower proliferation, and increase apoptosis may contribute toward colon cancer prevention. However, their protection is not due to their influence on iNOS and COX-2 protein levels.

Yes / Apigenin (4′,5,7-trihydroxyflavone, APG) has many potential therapeutic benefits; however, its poor aqueous solubility has limited its clinical applications. In this work, a large scale cocrystal screening has been conducted, aiming to discover potential APG cocrystals for enhancement of its solubility and dissolution rate. In order to reduce the number of the experimental screening tests, three computational prescreening tools, i.e., molecular complementarity (MC), hydrogen bond propensity (HBP), and hydrogen bond energy (HBE), were used to provide an initial selection of 47 coformer candidates, leading to the discovery of seven APG cocrystals. Among them, six APG cocrystal structures have been determined by successful growth of single crystals, i.e., apigenin-carbamazepine hydrate 1:1:1 cocrystal, apigenin-1,2-di(pyridin-4-yl)ethane hydrate 1:1:1 cocrystal, apigenin-valerolactam 1:2 cocrystal, apigenin-(dl) proline 1:2 cocrystal, apigenin-(d) proline/(l) proline 1:1 cocrystal. All of the APG cocrystals showed improved dissolution performances with the potential to be formulated into drug products.

Maspin (Mammary Serine Protease Inhibitor) was first reported in 1994 as a serpin with tumor suppressive properties. Maspin was initially isolated through subtractive hybridization and differential display analysis as a 42kDa protein that is expressed in normal mammary epithelial cells but reduced or absent in breast carcinomas. Further research led to maspin's characterization as a class II tumor suppressor based on its ability to inhibit cell invasion, promote apoptosis and inhibit angiogenesis. Since then, efforts have been made to characterize maspin's tumor suppressive mechanisms. In particular, researchers have studied maspin localization, the regulation of maspin expression, and more recently, maspin protein interactions. We employed a maspin-baited yeast two-hybrid system and subsequently identified Interferon Regulatory Factor 6 (IRF6) as a maspin-binding protein. Whereas many of the IRF family members have been well characterized, IRF6 remains poorly understood. In this dissertation, we elucidate some of the complex mechanisms involved in maspin activity, specifically relating to IRF6 regulation and function. We have examined the expression of IRF6 in breast cancer cells and we show that, similar to maspin, IRF6 is reduced or absent in breast carcinomas. We further show that the re-expression of IRF6 in breast cancer cells results in genotypic and phenotypic changes which can be abrogated in the presence of maspin. We identify ERK1/2 as a kinase involved in IRF6 phosphorylation, and we demonstrate a possible role for toll-like receptor signaling in the activation of IRF6. We also evaluate the differential expression of maspin and IRF6 during murine mammary gland development and we show that both maspin and IRF6 are maximally expressed during lactation. These studies have increased our understanding of the complex, pleiotropic nature of maspin and provide an avenue to develop maspin's potential as a diagnostic marker for cancer progression and as a potentially powerful therapeutic agent in the fight against breast cancer.

No description available.

No description available.

Os extratos vegetais, em função de sua rica composição e propriedades medicinais têm tido grande interesse na área cosmética. Contudo, muitas vezes, o grande número de componentes químicos pode causar instabilidade às formulações, assim, a indústria cosmética também utiliza seus principais componentes isolados. Dentre esses extratos podemos destacar o de camomila, o qual vem sendo comumente utilizado em cosméticos. Este possui uma rica composição de flavonóides, terpenos, polissacarídeos, dentre outros, o que lhe confere propriedades anti-inflamatória, antioxidante e emoliente, as quais foram bastante estudadas quanto às suas aplicações farmacológicas em geral, porém pouco estudadas quanto a sua aplicação tópica. O objetivo deste trabalho foi o desenvolvimento de formulações cosméticas estáveis contendo extrato glicólico de camomila (Matricaria chamomilla L.), ou os seus componentes isolados, alfa-bisabolol e apigenina, bem como a avaliação da eficácia clínica destas formulações na hidratação e proteção da pele. Visando avaliar potencial antioxidante in vitro do extrato de camomila e do seu componente isolado, apigenina, foram realizados estudos de quimioluminescência. Foram desenvolvidas cinco formulações à base de blend autoemulsificante, de copolímero de ácido sulfônico acriloildimetiltaurato e vinilpirrolidona (ASAV), blend autoemulsificante de polímero de celulose, copolímero de ASAV e polímero de poliacrilamida. Estas formulações foram acrescidas ou não (veículo) de 0,5% de alfa-bisabolol e de 5% de extrato de camomila. Realizou-se estudos preliminares de estabilidade e estudos de estabilidade física por determinação do comportamento reológico, bem como uma análise sensorial. A formulação composta copolímero ASAV apresentou melhor estabilidade e melhor sensorial e, assim, foi utilizada como veículo na avaliação da eficácia clínica a curto (efeitos imediatos) e longo prazo. Para a avaliação dos efeitos imediatos, analisou-se a hidratação, a perda transepidérmica de água, as propriedades viscoelásticas e o microrelevo da pele da região interna dos antebraços e da face, antes e após 2 horas da aplicação das formulações: veículo (F1), veículo + alfa-bisabolol (F2), veículo + extrato de camomila (F3) e veículo + apigenina (F4). Para analisar os efeitos a longo prazo, as voluntárias aplicaram as formulações duas vezes ao dia nos antebraços e na face sendo que, após 15 e 30 dias de aplicação, foram realizadas medidas dos parâmetros acima mencionados e das propriedades mecânicas da pele por determinação de suas características anisotrópicas. Os resultados mostraram que o extrato de camomila possui potencial antioxidante e que as formulações estudadas apresentaram efeitos hidratantes no estudo a curto prazo, porém somente as que continham extrato de camomila proporciono tal efeitos no estudo a longo prazo. Finalizando, de acordo com os resultados obtidos, pôde-se concluir que a formulação contendo extrato de camomila foi estável e apresentou propriedade hidratante, efeito esse evidenciado na avaliação da percepção da eficácia da referida formulação. Assim, o extrato de camomila pode ser sugerido para a aplicação em produtos cosméticos, visando a obtenção de efeitos hidratantes pronunciado e manutenção do equilíbrio fisiológico da pele. / Botanical extracts due to its rich composition and medicinal properties have attracted great interest in the cosmetic area. However, the large amount of chemicals compounds present in those extracts could cause instability to the formulations; thus, the cosmetic industry also uses its isolated major compounds. Among these extracts we can mention the Matricaria chamomilla L. extract, which has been commonly used in cosmetics. This extract has a rich composition in flavonoids, terpenes, polysaccharides, among others, which confers anti-inflammatory, antioxidant and emollient properties. M. chamomilla L. extract has had its use recognized and, in general, in terms of pharmacological applications, it has being well studied on its therapeutic properties. Although, there are only a few studies about its topical application. The aim of this study was to development of stable cosmetic formulations containing glycolic extract, or its isolated compounds, alpha-bisabolol and apigenin, as well as to evaluate the clinical efficacy of those formulations on skin hydration and skin protection. In order, to evaluate the in vitro antioxidant activity of the M. chamomilla L. and apigenin was applied the chemiluminescence assay. Five formulations were developed based on sclerotium gum, ammonium acryloyldimethyltaurate/ vinylpyrrolidone copolymer (A/VPC), hydroxietylcelulose, acrylate polymer and C13-14 Laureth-7 acrylamide polymer. Those formulations were supplemented or not (vehicle) with 0.5% of alpha-bisabolol and 5% of M. chamomilla L. extract. Afterwards, further studies were carried out to determine the formulations physical stability by analyzing the rheological behavior and also a sensorial analysis. The formulation containing A/VPC copolymer demonstrated the best physical stability and the best sensorial characteristics and thus it was used as the vehicle to evaluate the clinical efficacy in the immediate and long term effects. In order to evaluate the immediate effects, it was analyzed the skin hydration, transepidermal water loss, the viscoelastic properties and the skin microrelief on the region of the volunteers forearms and face, before and after 2 hours of the following formulations application: vehicle (F1), vehicle + alpha-bisabolol (F2), vehicle + M. chamomilla L. extract (F3) and vehicle + apigenin (F4). For the long-term study, the volunteers applied the formulations twice a day in the forearms and face; after 15 and 30 day-period of application, the parameters above mentioned were measured and the skin mechanical properties was also evaluated, by determining skin anisotropic characteristics. The results showed that M. chamomilla L.extract has antioxidant activity and the formulations studied demonstrated immediate moisturizing effects, but only the formulation containing M. chamomilla L. extract provides such effects in long-term study. Finally, according to the obtained results, it can be concluded that the formulation containing M. chamomilla L. extract was stable and showed moisturizing properties, it also was demonstrated by the efficacy perception assessment. Thus, M. chamomilla L. extract can be suggested for application in cosmetic product, in order to obtain pronounced hydration effect and keeping physiological balance of the skin.

As propriedades dos extratos vegetais vêm sendo cada vez mais investigadas, suscitando o interesse em aliar o potencial destes para minimizar efeitos do fotoenvelhecimento da pele decorrentes da ação dos radicais livres à fotoproteção proporcionada pelos filtros solares. Apesar do uso difundido de vários extratos vegetais, alguns deles, como a Matricaria chamomilla, ainda carecem de estudos acerca de suas propriedades e efeitos biológicos na pele, especialmente quando este é veiculado em formulações dermocosméticas. Assim, esse trabalho teve por objetivo a avaliação da estabilidade e da eficácia pré-clínica de formulações fotoprotetoras contendo o extrato de Matricaria chamomilla ou dos componentes isolados do vegetal, a-bisabolol e apigenina, na proteção de danos causados pela radiação ultravioleta (UV). Para tal, verificou-se a estabilidade dos ativos veiculados em formulação com FPS previamente determinado, bem como outras formulações de protetor solar foram desenvolvidas e a estas adicionadas extrato de camomila ou alfa-bisabolol, sendo testados por centrifugação, pH e análise visual. A estabilidade física das formulações mais estáveis foi analisada por estudos reológicos. A estabilidade química de formulações contendo extrato de camomila, apigenina e bisabolol foi determinada por Cromatografia Líquida de Alta Eficiência (HPLC). Estas formulações acrescidas de apigenina, extrato de camomila, ou alfa-bisabolol finalmente foram avaliadas no que tange à eficácia pré-clínica. Neste estudo, camundongos foram submetidos à radiação UV e o efeito protetor das formulações foi avaliado através de técnicas de biofísica nãoinvasiva e análise de imagem, que forneceram medidas de eritema, o teor de água do estrato córneo, a perda de água transepidérmica, ecogenicidade e espessura da derme. Os resultados permitiram selecionar as formulações fisicamente estáveisl para ambas as combinações de filtros UV associados contendo as substâncias ativas em estudo. No estudo de estabilidade química, a apigenina foi mais estável quando comparada às outras substâncias ativas em estudo e o bisabolol mostrou estabilidade química baixa. Todas as formulações foram eficazes na redução da perda de água transepidérmica. Os efeitos destas formulações na pele foram muito positivos, pois todas elas levaram a aumentos ecogenicidade e valores menores de espessura quando comparada às regiões irradiadas. Esses resultados mostraram efeitos significativos na melhoria do processo inflamatório causado pela radiação. Finalmente, as formulações desenvolvidas foram estáveis e eficazes na proteção da pele. Além disso, quando o extrato de camomila ou apigenina esteve presente na formulação fotoprotetora os efeitos foram mais pronunciados. / Particular plant extracts are being increasingly studied for their properties, in order to combine their potential to minimize skin photoaging effects from the action of free radicals with photoprotection provided by sunscreens. Despite of the widespread use of various plant extracts, some of them as it is the case of Matricaria chamomilla still need mored detailed studies especially on their properties and biological effects on skin, especially in dermocosmetic formulations. The aim of the present study was to assess the stability and the preclinical efficacy of sunscreen formulations containing M. chamomilla extract or its isolated components, alpha-bisabolol and apigenin, in the protection from damage caused by ultraviolet radiation. For this purpose, the physical stability in a pre-determined SPF formulation added of the active substances under study was determinated. Other sunscreen formulations were developed and supplemented with chamomile extract or alpha-bisabolol, and these were tested for centrifugation stability, pH and visual analysis. Physical stability of the most stable formulations was estimated by rheological measurements. The chemical stability of the formulations containing chamomile extract, apigenin, and bisabolol was determinated by High Efficiency Liquid Chromatography (HPLC). These formulations with chamomile extract, apigenin or alpha-bisabolol were finally evaluated in terms of preclinical efficacy. In this study, hairless mice were submitted to UV radiation and the protective effect of the formulations was evaluated using noninvasive biophysics techniques and image analysis, in which we obtained measures of erythema, the water content of stratum corneum, transepidermal water loss, the echogenicity and the thickness of the dermis. The results allowed selecting physicallystable formulations for both the combinations of UV-filters associated containing the actives substances under study. In the chemical stability study, the apigenin present in the extract was more stable when compared to the other active substances under study and the bisabolol showed a low chemical stabilitity. All the formulations were effective in the transepidermic water-loss reduction. The effects of these formulations on skin were very positive since all of them led to ecogenicity increases and lower thickness values when compared to irradiated regions. These results showed significant effects in the improvement of the inflammatory process caused by radiation. Finally, the formulations developed were stable and effective in the skin protection. In addition, when the chamomile extract or apigenin was present in the formulation the photoprotective effects were more pronounced.

As propriedades dos extratos vegetais vêm sendo cada vez mais investigadas, suscitando o interesse em aliar o potencial destes para minimizar efeitos do fotoenvelhecimento da pele decorrentes da ação dos radicais livres à fotoproteção proporcionada pelos filtros solares. Apesar do uso difundido de vários extratos vegetais, alguns deles, como a Matricaria chamomilla, ainda carecem de estudos acerca de suas propriedades e efeitos biológicos na pele, especialmente quando este é veiculado em formulações dermocosméticas. Assim, esse trabalho teve por objetivo a avaliação da estabilidade e da eficácia pré-clínica de formulações fotoprotetoras contendo o extrato de Matricaria chamomilla ou dos componentes isolados do vegetal, a-bisabolol e apigenina, na proteção de danos causados pela radiação ultravioleta (UV). Para tal, verificou-se a estabilidade dos ativos veiculados em formulação com FPS previamente determinado, bem como outras formulações de protetor solar foram desenvolvidas e a estas adicionadas extrato de camomila ou alfa-bisabolol, sendo testados por centrifugação, pH e análise visual. A estabilidade física das formulações mais estáveis foi analisada por estudos reológicos. A estabilidade química de formulações contendo extrato de camomila, apigenina e bisabolol foi determinada por Cromatografia Líquida de Alta Eficiência (HPLC). Estas formulações acrescidas de apigenina, extrato de camomila, ou alfa-bisabolol finalmente foram avaliadas no que tange à eficácia pré-clínica. Neste estudo, camundongos foram submetidos à radiação UV e o efeito protetor das formulações foi avaliado através de técnicas de biofísica nãoinvasiva e análise de imagem, que forneceram medidas de eritema, o teor de água do estrato córneo, a perda de água transepidérmica, ecogenicidade e espessura da derme. Os resultados permitiram selecionar as formulações fisicamente estáveisl para ambas as combinações de filtros UV associados contendo as substâncias ativas em estudo. No estudo de estabilidade química, a apigenina foi mais estável quando comparada às outras substâncias ativas em estudo e o bisabolol mostrou estabilidade química baixa. Todas as formulações foram eficazes na redução da perda de água transepidérmica. Os efeitos destas formulações na pele foram muito positivos, pois todas elas levaram a aumentos ecogenicidade e valores menores de espessura quando comparada às regiões irradiadas. Esses resultados mostraram efeitos significativos na melhoria do processo inflamatório causado pela radiação. Finalmente, as formulações desenvolvidas foram estáveis e eficazes na proteção da pele. Além disso, quando o extrato de camomila ou apigenina esteve presente na formulação fotoprotetora os efeitos foram mais pronunciados. / Particular plant extracts are being increasingly studied for their properties, in order to combine their potential to minimize skin photoaging effects from the action of free radicals with photoprotection provided by sunscreens. Despite of the widespread use of various plant extracts, some of them as it is the case of Matricaria chamomilla still need mored detailed studies especially on their properties and biological effects on skin, especially in dermocosmetic formulations. The aim of the present study was to assess the stability and the preclinical efficacy of sunscreen formulations containing M. chamomilla extract or its isolated components, alpha-bisabolol and apigenin, in the protection from damage caused by ultraviolet radiation. For this purpose, the physical stability in a pre-determined SPF formulation added of the active substances under study was determinated. Other sunscreen formulations were developed and supplemented with chamomile extract or alpha-bisabolol, and these were tested for centrifugation stability, pH and visual analysis. Physical stability of the most stable formulations was estimated by rheological measurements. The chemical stability of the formulations containing chamomile extract, apigenin, and bisabolol was determinated by High Efficiency Liquid Chromatography (HPLC). These formulations with chamomile extract, apigenin or alpha-bisabolol were finally evaluated in terms of preclinical efficacy. In this study, hairless mice were submitted to UV radiation and the protective effect of the formulations was evaluated using noninvasive biophysics techniques and image analysis, in which we obtained measures of erythema, the water content of stratum corneum, transepidermal water loss, the echogenicity and the thickness of the dermis. The results allowed selecting physicallystable formulations for both the combinations of UV-filters associated containing the actives substances under study. In the chemical stability study, the apigenin present in the extract was more stable when compared to the other active substances under study and the bisabolol showed a low chemical stabilitity. All the formulations were effective in the transepidermic water-loss reduction. The effects of these formulations on skin were very positive since all of them led to ecogenicity increases and lower thickness values when compared to irradiated regions. These results showed significant effects in the improvement of the inflammatory process caused by radiation. Finally, the formulations developed were stable and effective in the skin protection. In addition, when the chamomile extract or apigenin was present in the formulation the photoprotective effects were more pronounced.

Os extratos vegetais, em função de sua rica composição e propriedades medicinais têm tido grande interesse na área cosmética. Contudo, muitas vezes, o grande número de componentes químicos pode causar instabilidade às formulações, assim, a indústria cosmética também utiliza seus principais componentes isolados. Dentre esses extratos podemos destacar o de camomila, o qual vem sendo comumente utilizado em cosméticos. Este possui uma rica composição de flavonóides, terpenos, polissacarídeos, dentre outros, o que lhe confere propriedades anti-inflamatória, antioxidante e emoliente, as quais foram bastante estudadas quanto às suas aplicações farmacológicas em geral, porém pouco estudadas quanto a sua aplicação tópica. O objetivo deste trabalho foi o desenvolvimento de formulações cosméticas estáveis contendo extrato glicólico de camomila (Matricaria chamomilla L.), ou os seus componentes isolados, alfa-bisabolol e apigenina, bem como a avaliação da eficácia clínica destas formulações na hidratação e proteção da pele. Visando avaliar potencial antioxidante in vitro do extrato de camomila e do seu componente isolado, apigenina, foram realizados estudos de quimioluminescência. Foram desenvolvidas cinco formulações à base de blend autoemulsificante, de copolímero de ácido sulfônico acriloildimetiltaurato e vinilpirrolidona (ASAV), blend autoemulsificante de polímero de celulose, copolímero de ASAV e polímero de poliacrilamida. Estas formulações foram acrescidas ou não (veículo) de 0,5% de alfa-bisabolol e de 5% de extrato de camomila. Realizou-se estudos preliminares de estabilidade e estudos de estabilidade física por determinação do comportamento reológico, bem como uma análise sensorial. A formulação composta copolímero ASAV apresentou melhor estabilidade e melhor sensorial e, assim, foi utilizada como veículo na avaliação da eficácia clínica a curto (efeitos imediatos) e longo prazo. Para a avaliação dos efeitos imediatos, analisou-se a hidratação, a perda transepidérmica de água, as propriedades viscoelásticas e o microrelevo da pele da região interna dos antebraços e da face, antes e após 2 horas da aplicação das formulações: veículo (F1), veículo + alfa-bisabolol (F2), veículo + extrato de camomila (F3) e veículo + apigenina (F4). Para analisar os efeitos a longo prazo, as voluntárias aplicaram as formulações duas vezes ao dia nos antebraços e na face sendo que, após 15 e 30 dias de aplicação, foram realizadas medidas dos parâmetros acima mencionados e das propriedades mecânicas da pele por determinação de suas características anisotrópicas. Os resultados mostraram que o extrato de camomila possui potencial antioxidante e que as formulações estudadas apresentaram efeitos hidratantes no estudo a curto prazo, porém somente as que continham extrato de camomila proporciono tal efeitos no estudo a longo prazo. Finalizando, de acordo com os resultados obtidos, pôde-se concluir que a formulação contendo extrato de camomila foi estável e apresentou propriedade hidratante, efeito esse evidenciado na avaliação da percepção da eficácia da referida formulação. Assim, o extrato de camomila pode ser sugerido para a aplicação em produtos cosméticos, visando a obtenção de efeitos hidratantes pronunciado e manutenção do equilíbrio fisiológico da pele. / Botanical extracts due to its rich composition and medicinal properties have attracted great interest in the cosmetic area. However, the large amount of chemicals compounds present in those extracts could cause instability to the formulations; thus, the cosmetic industry also uses its isolated major compounds. Among these extracts we can mention the Matricaria chamomilla L. extract, which has been commonly used in cosmetics. This extract has a rich composition in flavonoids, terpenes, polysaccharides, among others, which confers anti-inflammatory, antioxidant and emollient properties. M. chamomilla L. extract has had its use recognized and, in general, in terms of pharmacological applications, it has being well studied on its therapeutic properties. Although, there are only a few studies about its topical application. The aim of this study was to development of stable cosmetic formulations containing glycolic extract, or its isolated compounds, alpha-bisabolol and apigenin, as well as to evaluate the clinical efficacy of those formulations on skin hydration and skin protection. In order, to evaluate the in vitro antioxidant activity of the M. chamomilla L. and apigenin was applied the chemiluminescence assay. Five formulations were developed based on sclerotium gum, ammonium acryloyldimethyltaurate/ vinylpyrrolidone copolymer (A/VPC), hydroxietylcelulose, acrylate polymer and C13-14 Laureth-7 acrylamide polymer. Those formulations were supplemented or not (vehicle) with 0.5% of alpha-bisabolol and 5% of M. chamomilla L. extract. Afterwards, further studies were carried out to determine the formulations physical stability by analyzing the rheological behavior and also a sensorial analysis. The formulation containing A/VPC copolymer demonstrated the best physical stability and the best sensorial characteristics and thus it was used as the vehicle to evaluate the clinical efficacy in the immediate and long term effects. In order to evaluate the immediate effects, it was analyzed the skin hydration, transepidermal water loss, the viscoelastic properties and the skin microrelief on the region of the volunteers forearms and face, before and after 2 hours of the following formulations application: vehicle (F1), vehicle + alpha-bisabolol (F2), vehicle + M. chamomilla L. extract (F3) and vehicle + apigenin (F4). For the long-term study, the volunteers applied the formulations twice a day in the forearms and face; after 15 and 30 day-period of application, the parameters above mentioned were measured and the skin mechanical properties was also evaluated, by determining skin anisotropic characteristics. The results showed that M. chamomilla L.extract has antioxidant activity and the formulations studied demonstrated immediate moisturizing effects, but only the formulation containing M. chamomilla L. extract provides such effects in long-term study. Finally, according to the obtained results, it can be concluded that the formulation containing M. chamomilla L. extract was stable and showed moisturizing properties, it also was demonstrated by the efficacy perception assessment. Thus, M. chamomilla L. extract can be suggested for application in cosmetic product, in order to obtain pronounced hydration effect and keeping physiological balance of the skin.

Pancreatic cancer is one of the deadliest cancers with a five-year survival rate of 6%. Pancreatic cancer is resistant to conventional chemotherapy and is usually diagnosed at late stages. Current treatment options have minimal effects in extending patients' lives beyond 10 months. One significant limitation in developing treatments to combat pancreatic cancer is its immunosuppressive microenvironment. Pancreatic cancer secretes factors that activate immunosuppressive cells, such as regulatory T cells (Tregs). These Tregs suppress effector CD4+ and CD8+ T cell anti-tumor immune responses. Therefore, novel treatment options to reduce Treg-mediated immune suppression and increase the numbers and functions of CD4+ and CD8+ T cells are paramount to enhance anti-tumor immunity in pancreatic cancer tumor-bearing (TB) hosts. The alternatively spliced transcription factor Ikaros is essential for lymphocyte development and is considered a tumor suppressor in T cells. Ikaros' protein stability and function are regulated by its phosphorylation and dephosphorylation by protein kinase CK2 and phosphatase 1 (PP1), respectively. Mutations and functional inactivation of Ikaros have mainly been investigated in T cell leukemias and lymphomas. In this dissertation, we investigated the role of Ikaros in regulating T cell homeostasis in murine pancreatic cancer. In this study, we report that Ikaros proteins are degraded by the ubiquitin-proteasome pathway in response to factors produced by murine pancreatic cancer cells. Our results further suggest that an increase in CK2 activity leads to Ikaros' degradation and disrupts its localization to pericentromeric heterochromatin in our murine pancreatic TB model. This loss of Ikaros expression is accompanied by an imbalance in T cell homeostasis. More specifically, we observe a significant decrease in effector CD4+ and CD8+ T cells but an increase in Treg percentages in TB and spontaneous pancreatic cancer models. T-cell specific defects in Ikaros protein expression were also observed in TB CD3+ T cells. Apigenin, a natural plant flavonoid and CK2 inhibitor, restored expression of some Ikaros isoforms in our TB model. Apigenin also displayed immunological benefits evident by enhanced anti-tumor immunity in TB mice. These data provide mechanistic and functional evidence that pharmacological inhibition of CK2 can regulate Ikaros expression and identifies the possible involvement of Ikaros in regulating T cell immune responses in murine pancreatic cancer.