An engineered POSS drug delivery system for copper(II) anticancer metallodrugs in a selective application toward melanoma cells.

In this work, a polyhedral silsesquioxane (POSS) was used as an engineered drug delivery system for two oxindolimine-copper(II) anticancer complexes, [Cu(isaepy)]+ and [Cu(isapn)]+. The interest in hybrid POSS comes from the necessity of developing materials that can act as adjuvants to improve the cytotoxicity of non-soluble metallodrugs. Functionalization of POSS with a triazole ligand (POSS-atzac) permitted the anchorage of such copper complexes, producing hybrid materials with efficient cytotoxic effects. Structural and morphological characterizations of these copper-POSS systems were performed by using different techniques (IR, NMR, thermogravimetric analysis). A combination of continuous-wave (CW) and pulsed EPR (HYSCORE) spectroscopies conducted at the X-band have enabled the complete characterization of the coordination environment of the copper ion in the POSS-atzac matrix. Additionally, the cytotoxic effects of the loaded materials, [Cu(isapn)]@POSS-atzac and [Cu(isaepy)]@POSS-atzac, were assessed toward melanomas (SK-MEL), in comparison to non-tumorigenic cells (fibroblast P4). Evaluation of their nuclease activity or ability to facilitate cleavage of DNA indicated concentrations as low as 0.6 µg mL-1, while complete DNA fragmentation was observed at 25 µg mL-1. By using adequate scavengers, investigations on active intermediates responsible for their cytotoxicity were performed, both in the absence and in the presence of ascorbate as a reducing agent. Based on the observed selective cytotoxicity of these materials toward melanomas, investigations on the reactivity of these complexes and corresponding POSS-materials with melanin, a molecule that contributes to melanoma resistance to chemotherapy, were carried out. Results indicated the main role of the binuclear copper species, formed at the surface of the silica matrix, in the observed reactivity and selectivity of these copper-POSS systems.

Desempenho zootécnico de juvenis de tilápias do nilo (Oreochromis niloticus) alimentados com cepas probióticas e submetidos a desafio sanitário / Zootechnical performance of nile tilapia (Oreochromis niloticus) juvenile fed with probiotic cepas and submetids a health challenge

O surgimento de doenças ocasionadas pelo estresse durante o cultivo de juvenis vem tornando-se comum devido à intensificação dos sistemas de produção, ocorrendo elevada mortalidade e prejuízos econômicos ao produtor. Mediante esse contexto, os probióticos que são um conjunto de micro-organismos vivos, estão sendo utilizados devido à sua capacidade de estabelecer-se e multiplicar-se no intestino do hospedeiro e promover o equilíbrio da microbiota, contribuindo com a sanidade e o desempenho dos peixes principalmente nas primeiras semanas de vida. Objetivou-se avaliar o desempenho de juvenis de tilápias do Nilo alimentados com cepas probióticas e submetidos a desafio sanitário. Foram utilizados 180 juvenis, distribuídos em delineamento inteiramente casualizado, com três tratamentos, quatro repetições e 15 peixes como unidade experimental. Os tratamentos foram: T1 - peixes cultivados em água limpa sem o uso de probiótico; T2 - peixes cultivados em água sob desafio e sem o uso de probiótico e T3 - peixes cultivados em água sob desafio e com o uso de probiótico. Não houve efeito significativo (P>0,05) nos parâmetros de desempenho zootécnico, no consumo de ração e sobrevivência. A utilização de probiótico na ração não mostrou-se hábil para proporcionar melhorias no desempenho, consumo de ração e na sobrevivência de juvenis de tilápias do Nilo no período de 30 dias de cultivo.(AU)

The appearance of diseases caused by stress during the cultivation of juveniles have become rather common due to the intensification of the production systems, causing high mortality and economic loss to the grower. Due to this context, the probiotics (which are a group of live microorganisms) are being employed due to their capacity of establishing and multiplying in the hosts intestine and promote equilibrium to the microbiota contributing with the sanity and performance of fish, especially in the first weeks of life. Thus, this work had as objective to evaluate the development of juvenile of Nile tilapia fed with probiotic strains and subjected to sanitary challenge. 180 juvenile were experimented, distributed in a completely randomized design with three treatments, four replications and 15 fishes as experimental unit. The treatments were: T1 - fish cultivated in clean water without the use of probiotics; T2 - fish cultivated in water under challenge and without the use of probiotics; DP - fish cultivated in water under challenge with the use of probiotics. There was no significant effect (P>0.05) in the parameters of zootechnical performance, feeding consumption and survival rate. The use of probiotics in the feeding was not able provide improvements in the performance, feeding consumption and survival of juvenile Nile tilapia in the period of 30 days of cultivation.(AU)

Desempenho zootécnico de juvenis de tilápias do nilo (Oreochromis niloticus) alimentados com cepas probióticas e submetidos a desafio sanitário / Zootechnical performance of nile tilapia (Oreochromis niloticus) juvenile fed with probiotic cepas and submetids a health challenge

O surgimento de doenças ocasionadas pelo estresse durante o cultivo de juvenis vem tornando-se comum devido à intensificação dos sistemas de produção, ocorrendo elevada mortalidade e prejuízos econômicos ao produtor. Mediante esse contexto, os probióticos que são um conjunto de micro-organismos vivos, estão sendo utilizados devido à sua capacidade de estabelecer-se e multiplicar-se no intestino do hospedeiro e promover o equilíbrio da microbiota, contribuindo com a sanidade e o desempenho dos peixes principalmente nas primeiras semanas de vida. Objetivou-se avaliar o desempenho de juvenis de tilápias do Nilo alimentados com cepas probióticas e submetidos a desafio sanitário. Foram utilizados 180 juvenis, distribuídos em delineamento inteiramente casualizado, com três tratamentos, quatro repetições e 15 peixes como unidade experimental. Os tratamentos foram: T1 - peixes cultivados em água limpa sem o uso de probiótico; T2 - peixes cultivados em água sob desafio e sem o uso de probiótico e T3 - peixes cultivados em água sob desafio e com o uso de probiótico. Não houve efeito significativo (P>0,05) nos parâmetros de desempenho zootécnico, no consumo de ração e sobrevivência. A utilização de probiótico na ração não mostrou-se hábil para proporcionar melhorias no desempenho, consumo de ração e na sobrevivência de juvenis de tilápias do Nilo no período de 30 dias de cultivo.

The appearance of diseases caused by stress during the cultivation of juveniles have become rather common due to the intensification of the production systems, causing high mortality and economic loss to the grower. Due to this context, the probiotics (which are a group of live microorganisms) are being employed due to their capacity of establishing and multiplying in the host’s intestine and promote equilibrium to the microbiota contributing with the sanity and performance of fish, especially in the first weeks of life. Thus, this work had as objective to evaluate the development of juvenile of Nile tilapia fed with probiotic strains and subjected to sanitary challenge. 180 juvenile were experimented, distributed in a completely randomized design with three treatments, four replications and 15 fishes as experimental unit. The treatments were: T1 - fish cultivated in clean water without the use of probiotics; T2 - fish cultivated in water under challenge and without the use of probiotics; DP - fish cultivated in water under challenge with the use of probiotics. There was no significant effect (P>0.05) in the parameters of zootechnical performance, feeding consumption and survival rate. The use of probiotics in the feeding was not able provide improvements in the performance, feeding consumption and survival of juvenile Nile tilapia in the period of 30 days of cultivation.