In vivo efficacy and toxicity of curcumin nanoparticles in breast cancer treatment : a systematic review

Breast cancer is one of the most prevalent types of malignant tumors in the world, resulting in a high incidence of death. The development of new molecules and technologies aiming to apply more effective and safer therapy strategies has been intensively explored to overcome this situation. The association of nanoparticles with known antitumor compounds (including plant-derived molecules such as curcumin) has been considered an effective approach to enhance tumor growth suppression and reduce adverse effects. Therefore, the objective of this systematic review was to summarize published data regarding evaluations about efficacy and toxicity of curcumin nanoparticles (Cur-NPs) in in vivo models of breast cancer. The search was carried out in the databases: CINAHL, Cochrane, LILACS, Embase, FSTA, MEDLINE, ProQuest, BSV regional portal, PubMed, ScienceDirect, Scopus, and Web of Science. Studies that evaluated tumor growth in in vivo models of breast cancer and showed outcomes related to Cur-NP treatment (without association with other antitumor molecules) were included. Of the 528 initially gathered studies, 26 met the inclusion criteria. These studies showed that a wide variety of NP platforms have been used to deliver curcumin (e.g., micelles, polymeric, lipid-based, metallic). Attachment of poly(ethylene glycol) chains (PEG) and active targeting moieties were also evaluated. Cur-NPs significantly reduced tumor volume/weight, inhibited cancer cell proliferation, and increased tumor apoptosis and necrosis. Decreases in cancer stem cell population and angiogenesis were also reported. All the studies that evaluated toxicity considered Cur-NP treatment to be safe regarding hematological/biochemical markers, damage to major organs, and/or weight loss. These effects were observed in different in vivo models of breast cancer (e.g., estrogen receptor-positive, triple-negative, chemically induced) showing better outcomes when compared to treatments with free curcumin or negative controls. This systematic review supports the proposal that Cur-NP is an effective and safe therapeutic approach in in vivo models of breast cancer, reinforcing the currently available evidence that it should be further analyzed in clinical trials for breast cancer treatments

A Computational Approach Applied to the Study of Potential Allosteric Inhibitors Protease NS2B/NS3 from Dengue Virus

Dengue virus (DENV) is a danger to more than 400 million people in the world, and there is no specific treatment. Thus, there is an urgent need to develop an effective method to combat this pathology. NS2B/NS3 protease is an important biological target due it being necessary for viral replication and the fact that it promotes the spread of the infection. Thus, this study aimed to design DENV NS2B/NS3pro allosteric inhibitors from a matrix compound. The search was conducted using the Swiss Similarity tool. The compounds were subjected to molecular docking calculations, molecular dynamics simulations (MD) and free energy calculations. The molecular docking results showed that two compounds, ZINC000001680989 and ZINC000001679427, were promising and performed important hydrogen interactions with the Asn152, Leu149 and Ala164 residues, showing the same interactions obtained in the literature. In the MD, the results indicated that five residues, Lys74, Leu76, Asn152, Leu149 and Ala166, contribute to the stability of the ligand at the allosteric site for all of the simulated systems. Hydrophobic, electrostatic and van der Waals interactions had significant effects on binding affinity. Physicochemical properties, lipophilicity, water solubility, pharmacokinetics, druglikeness and medicinal chemistry were evaluated for four compounds that were more promising, showed negative indices for the potential penetration of the Blood Brain Barrier and expressed high human intestinal absorption, indicating a low risk of central nervous system depression or drowsiness as the the side effects. The compound ZINC000006694490 exhibited an alert with a plausible level of toxicity for the purine base chemical moiety, indicating hepatotoxicity and chromosome damage in vivo in mouse, rat and human organisms. All of the compounds selected in this study showed a synthetic accessibility (SA) score lower than 4, suggesting the ease of new syntheses. The results corroborate with other studies in the literature, and the computational approach used here can contribute to the discovery of new and potent anti-dengue agents

Inclusão tecnológica e direito à cultura : movimentos rumo à sociedade democrática do conhecimento

A presente obra coletiva apresenta uma reflexão sobre Sociedade Informacional no que se refere à Inclusão Tecnológica e Direito à Cultura, tudo para a construção de um pensamento jurídico adequado às necessidades da nossa sociedade contemporânea. O conjunto de artigos foi estruturado em dois eixos principais: (i) Sociedade Informacional e Inclusão Tecnológica; e, (ii) Sociedade Democrática do Conhecimento e Direito à Cultura. Aqui consignamos o esforço de todos os professores e alunos do nosso PPGD/UFSC, como também, dos Programas de Mestrado e Doutorado da PUCPR, UniBrasil e UniSantos que desenvolveram pesquisas dentro do PROCAD. Também cabe ressaltar o apoio do Ministério da Cultura e os recursos recebidos da CAPES Coordenação de Aperfeiçoamento de Pesssoal de Nível Superior.Sumário. Prefácio / Noemi Olivera Universidade Nacional de La Plata/Argentina 9. Parte I: Sociedade Informacional e Inclusão Tecnológica. Movimentos rumo a Sociedade Democrática do Conhecimento / Marcos Wachowicz e Carol Proner 15. Questões Criticas do Direito da Internet / José de Oliveira Ascensão 39. Sociedade da Informação e Darknets / Cinthia O. de A. Freitas 69. Os Conhecimentos Tradicionais e a Biodiversidade: a Necessidade de um Regime Próprio de Proteção / Antonio César Mateo 91. Órgãos, Domínio e Licenças Públicas / Christiano Lacorte 111. O Abuso do Direito Autoral nas Relações Contratuais / Carlos Affonso Pereira de Souza 123. Direito das Minorias e Inclusão Digital: Análise do Caso da Rede nacional de quilombos digitais (RNQD) / Eduardo Biacchi Gomes, Laura Garbini Both 161. Parte II Sociedade Democrática do Conhecimento e Direito à Cultura. Sociedade de Consumo e o Direito à Informação / Fernanda Mara Gibran Antônio Carlos Efing 185. A internet e a participação Política: acesso a informaçao com equidade / Gabriela Grosselli 201. Democracia, Desenvolvimento e Formas de Inclusão Social Tecnológica: o direito de autor a partir da concepção de commons / Larissa Alcântara Pereira 221. A Proposta do Marco Civil da Internet no tocante à Promoção da Cultura e Desenvolvimento Tecnológico pelo Poder Público / Rangel Oliveira Trindade 247. Da obra sem autorao autor sem obra: cultura e inclusão tecnológica na recomposição do direito de autor / Rosalice Fidalgo Pinheiro 261. Cultura e Preservação da Memória e Patrimônio Histórico do Poder Judiciário no contexto da tecnologia / Andréia Regina de Moraes Benedtti e Vladmir Passos de Freitas 283. Diversidade Cultural na Sociedade Informacional promessas e desafios: Por uma visão dialética sobre o tema / Marcos Wachowicz e Luiza Landerdahl Chistmann 309. Sobre os Autores 339

Evaluation of milled pearl millet in the feeding of growing rabbits

Two experiments were carried out in order to estimate the nutritional value and the performance of growing rabbits fed different levels of pearl millet (ADR 7010). In the digestibility trial, nutritional values of pearl millet were determined in 22 45-day-old New Zealand White rabbits, allotted in a completely randomized design, subjected to two treatments - a reference diet and a test diet with 70% of its volume composed of reference diet and 30% of pearl millet - and 11 replications. The apparent digestibility values of dry matter, crude protein, neutral detergent fiber and gross energy of the pearl millet were 88.7, 85.4, 24.4 and 75.0%, respectively. In the performance trial, 120 32-day-old New Zealand White rabbits were used. Rabbits were allotted in a completely randomized design and subjected to six treatments, with 10 replications and two animals for each experimental unit. The diets were formulated with increasing levels of pearl millet (20, 40, 60, 80 and 100%), substituting the corn in the reference diet, according to the digestible energy. No differences were observed in daily feed intake, daily weight gain, feed conversion, carcass traits and feed cost per kilogram of rabbit. Regardless of the amount of corn substituted, pearl can replace corn in diets for growing rabbits