Application of gold nanoparticles as radiosensitizer for metastatic prostate cancer cell lines

More than 50% of all prostate cancer (PCa) patients are treated by radiotherapy (RT). Radioresistance and cancer recurrence are two consequences of the therapy and are related to dose heterogeneity and non-selectivity between normal and tumoral cells. Gold nanoparticles (AuNPs) could be used as potential radiosensitizers to overcome these therapeutic limitations of RT. This study assessed the biological interaction of different morphologies of AuNPs with ionizing radiation (IR) in PCa cells. To achieve that aim, three different amine-pegylated AuNPs were synthesized with distinct sizes and shapes (spherical, AuNPsp-PEG, star, AuNPst-PEG, and rods, AuNPr-PEG) and viability, injury and colony assays were used to analyze their biological effect on PCa cells (PC3, DU145, and LNCaP) when submitted to the accumulative fraction of RT. The combinatory effect of AuNPs with IR decreased cell viability and increased apoptosis compared to cells treated only with IR or untreated cells. Additionally, our results showed an increase in the sensitization enhancement ratio by cells treated with AuNPs and IR, and this effect is cell line dependent. Our findings support that the design of AuNPs modulated their cellular behavior and suggested that AuNPs could improve the RT efficacy in PCa cells.The author is grateful for the financial support of Foundation for Science and Technology (grant reference: SFRH/BD/138271/2018).info:eu-repo/semantics/publishedVersio

Constraining New Physics with the CDF Measurement of CP Violation in B→ψKSB \to \psi K_S

Recently, the CDF collaboration has reported a measurement of the CP asymmetry in the $B\to\psi K_S$ decay: $a_{\psi K_S}=0.79^{+0.41}_{-0.44}$. We analyze the constraints that follow from this measurement on the size and the phase of contributions from new physics to B-\barB mixing. Defining the relative phase between the full $M_{12}$ amplitude and the Standard Model contribution to be $2\theta_d$, we find a new bound: \sin2\theta_d\gsim-0.6 (-0.87) at one sigma (95% CL). Further implications for the CP asymmetry in semileptonic B decays are discussed.Comment: 13 pages, harvmac, 3 figures; v2: a discussion of new physics effects on tree level decays added; references added; accepted for publication in Physical Review Letter

Evaluation of the indicators of inflammation in the diagnosis of ovine mastitis

O objetivo do presente trabalho foi avaliar diferentes indicadores inflamatórios no diagnóstico da mamite em ovinos da raça Santa Inês. Após a realização do exame físico das mamas e a prova de fundo escuro, foram coletadas e analisadas 390 amostras de leite, sendo as metades mamárias divididas de acordo com o exame bacteriológico e a prova de fundo escuro, resultando em 290 amostras negativas em ambos os exames, 90 amostras negativas à prova de fundo escuro e positivas na cultura bacteriológica, 5 amostras positivas à prova de fundo escuro e negativas ao exame bacteriológico e 3 amostras positivas em ambos os testes. Nestas amostras foram realizadas a contagem automática de células somáticas (CCS), o California Mastitis Test (CMT), a determinação da concentração hidrogeniônica (pH) e dos teores de cloreto e lactose, e ainda a avaliação do índice de cloreto-lactose. Os maiores valores preditivos foram observados para a CCS, CMT e teor de cloreto; o pH, o teor de lactose e o índice cloreto-lactose apresentaram-se como marcadores inflamatórios menos sensíveis, onde se considerou o resultado da cultura bacteriológica como padrão ouro. O exame físico não se mostrou como método diagnóstico seguro quando utilizado isoladamente, exaltando a importância da associação de outros meios diagnósticos indiretosThe aim of this trial was to evaluate distinct indictors of inflammation in the diagnosis of mastitis in Santa Ines ewes. The physical examination and the dark bottom cup test were performed. Afterwards, the bacteriologic samples of 390 milk samples were analyzed. The samples were divided according to the bacteriological examination and the dark cup bottom test, resulting in 290 samples negative in both tests, 90 samples positive in the bacteriological examination and negative in the dark cup bottom test, 5 samples positive in the dark cup bottom test and negative in bacteriological culture, and 3 samples positive in both tests. The automatic somatic cell count (SSC), the California mastitis test (CMT), the pH, the chloride and lactose content, and the chloride-lactose number were established. Then, their predictive value as a indicator of inflammation was calculated assuming the bacteriologic examination as the gold standard test. The CCS, CMT and chloride content proved to be the best predictors, while the pH, the lactose content and chloride-lactose number were the least sensitive tests. The physical examination was revealed to be a nonsensitive diagnostic procedure when used as the only procedure to detect the disease, showing that other diagnostics tests are requiredFAPESPCNP

ECOSSISTEMA DE INOVAÇÃO PEDAGÓGICA DIGITAL

Resumo: A partir da constatação de que os elementos vida, conhecimento e cultura vem sofrendo marcantes alterações cabendo ao elemento “escola” buscar uma ressignificação de seus currículos, sob pena de não mais se comunicar eficientemente com a sociedade. O professor que se reconhece como o protagonista de sua prática e utiliza as tecnologias educacionais de modo crítico e criativo, coloca-se em sintonia com as linguagens e símbolos que fazem parte deste novo mundo do aluno, além de conferir a este maior autonomia e reponsabilidade sob seu processo de aprendizagem. O objetivo geral deste projeto foi de estruturar um conjunto de ações que despertassem e capacitassem professores e alunos a atuarem mediados por tecnologias educacionais de modo crítico e criativo, colocando-os em sintonia com as linguagens e símbolos que fazem parte deste novo mundo digital e interconectado

Identification of Thioredoxin Glutathione Reductase Inhibitors That Kill Cestode and Trematode Parasites

Parasitic flatworms are responsible for serious infectious diseases that affect humans as well as livestock animals in vast regions of the world. Yet, the drug armamentarium available for treatment of these infections is limited: praziquantel is the single drug currently available for 200 million people infected with Schistosoma spp. and there is justified concern about emergence of drug resistance. Thioredoxin glutathione reductase (TGR) is an essential core enzyme for redox homeostasis in flatworm parasites. In this work, we searched for flatworm TGR inhibitors testing compounds belonging to various families known to inhibit thioredoxin reductase or TGR and also additional electrophilic compounds. Several furoxans and one thiadiazole potently inhibited TGRs from both classes of parasitic flatworms: cestoda (tapeworms) and trematoda (flukes), while several benzofuroxans and a quinoxaline moderately inhibited TGRs. Remarkably, five active compounds from diverse families possessed a phenylsulfonyl group, strongly suggesting that this moiety is a new pharmacophore. The most active inhibitors were further characterized and displayed slow and nearly irreversible binding to TGR. These compounds efficiently killed Echinococcus granulosus larval worms and Fasciola hepatica newly excysted juveniles in vitro at a 20 µM concentration. Our results support the concept that the redox metabolism of flatworm parasites is precarious and particularly susceptible to destabilization, show that furoxans can be used to target both flukes and tapeworms, and identified phenylsulfonyl as a new drug-hit moiety for both classes of flatworm parasites