Co-exposure of the organic nanomaterial fullerene C60 with benzo[a]pyrene in Danio rerio (zebrafish) hepatocytes: Evidence of toxicological interactions

Compounds from the nanotechnology industry, such as carbon-based nanomaterials, are strong candidates to contaminate aquatic environments because their production and disposal have exponentially grown in a few years. Previous evidence shows that fullerene C60, a carbon nanomaterial, can facilitate the intake of metals or PAHs both in vivo and in vitro, potentially amplifying the deleterious effects of these toxicants in organisms. The present work aimed to investigate the effects of fullerene C60 in a Danio rerio (zebrafish) hepatocyte cell lineage exposed to benzo[a]pyrene (BaP) in terms of cell viability, oxidative stress parameters and BaP intracellular accumulation. Additionally, a computational docking was performed to investigate the interaction of the fullerene C60 molecule with the detoxificatory and antioxidant enzyme πGST. Fullerene C60 provoked a significant (p 0.05) alter the enzyme activity when added to GST purified extracts from the zebrafish hepatocyte cells. These results show that fullerene C60 can increase the intake of BaP into the cells, decreasing cell viability and impairing the detoxificatory response by phase II enzymes, such as GST, and this latter effect should be occurring at the transcriptional level.Fil: Ribas Ferreira, Josencler L.. Universidade Federal do Rio Grande do Sul; BrasilFil: Lonné, María Noelia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: França, Thiago A.. Universidade Federal do Rio Grande do Sul; BrasilFil: Maximilla, Naiana R.. Universidade Federal do Rio Grande do Sul; BrasilFil: Lugokenski, Thiago H.. Universidade Federal de Santa Maria. Departamento de Química; BrasilFil: Costa, Patrícia G.. Universidade Federal do Rio Grande do Sul; BrasilFil: Fillmann, Gilberto. Universidade Federal do Rio Grande do Sul; BrasilFil: Soares, Félix A.. Universidade Federal de Santa Maria. Departamento de Química; BrasilFil: de la Torre, Fernando Roman. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Luján. Departamento de Ciencias Básicas; ArgentinaFil: Monserrat, José María. Universidade Federal do Rio Grande do Sul; Brasil. Instituto Nacional de Ciência e Tecnologia de Nanomateriais de Carbono; Brasi

A Pyranoxanthone as a potent antimitotic and sensitizer of cancer cells to low doses of Paclitaxel

Microtubule-targeting agents (MTAs) remain a gold standard for the treatment of several cancer types. By interfering with microtubules dynamic, MTAs induce a mitotic arrest followed by cell death. This antimitotic activity of MTAs is dependent on the spindle assembly checkpoint (SAC), which monitors the integrity of the mitotic spindle and proper chromosome attachments to microtubules in order to ensure accurate chromosome segregation and timely anaphase onset. However, the cytotoxic activity of MTAs is restrained by drug resistance and/or toxicities, and had motivated the search for new compounds and/or alternative therapeutic strategies. Here, we describe the synthesis and mechanism of action of the xanthone derivative pyranoxanthone 2 that exhibits a potent anti-growth activity against cancer cells. We found that cancer cells treated with the pyranoxanthone 2 exhibited persistent defects in chromosome congression during mitosis that were not corrected over time, which induced a prolonged SAC-dependent mitotic arrest followed by massive apoptosis. Importantly, pyranoxanthone 2 was able to potentiate apoptosis of cancer cells treated with nanomolar concentrations of paclitaxel. Our data identified the potential of the pyranoxanthone 2 as a new potent antimitotic with promising antitumor potential, either alone or in combination regimens.Portugal 2020: PTDC/SAU-PUB/28736/2017 (POCI-01-0145-FEDER-028736; FCT: SFRH/BD/116167/2016/ SFRH/BD/140844/2018/ PD/00016/2012info:eu-repo/semantics/publishedVersio

Low mutation percentage of KRAS and BRAF genes in Brazilian anal tumors

Anal cancer is a rare type of digestive tract disease, which has had a crescent incidence in a number of regions. Carcinomas are most frequently found, with squamous cell carcinoma (SCC) comprising similar to 95% of all anal tumors. The major risk factor for development of this type of tumor is human papillomavirus (HPV) infection. However, previous studies have identified patients with anal cancer that are HPV-/p16-and observed that they have a poorer outcome compared with HPV+/p16+ patients. This suggests that molecular profile may drive anal cancer progression. The aim of the present study was to evaluate the mutational status of two important oncogenes, KRAS and BRAF, in a series of anal cancer lesions. Resected tumors of the anal canal (n=43) were evaluated, nine of these were high-grade squamous intra-epithelial lesion cases (HSIL), 11 were adenocarcinomas, and 23 SCCs. Direct sequencing of KRAS proto-oncogene, GTPase (KRAS; codons 12 and 13) and B-Raf proto-oncogene, serine/threonine kinase (BRAF; codon 600) was performed and associated with patient clinicopathological and molecular features. There was a trend of poorer prognosis of adenocarcinoma compared with HSIL and SCC. Analysis indicated one SCC patient (2.3%) exhibited a KRAS p.G13D mutation, and one adenocarcinoma patient (2.3%) exhibited a BRAF p.V600E mutation. It was observed that, these mutations are rare in anal tumors, and certain patients may be at a disadvantage using targeted therapies based on KRAS and BRAF mutational status. As there is a low mutation percentage in SCCs, adenocarcinomas and HSIL, there may exist other underlying molecular alterations that result in anal cancer development, which require further elucidation.The present study was partially supported by the São Paulo Research Foundation (grant no. 2010/16795-4 to Dr Adhemar Longatto-Filho) and the Ministério da Ciência e Tecnologia/Financiadora de Estudos e Projetos (grant no. CT-INFRA-PROINFRA 01/2011). Dr Lucas Tadeu Bidinotto received a São Paulo Research Foundation fellow-ship (grant no. 2011/08523-7).info:eu-repo/semantics/publishedVersio

Estudos paleoambientais interdisciplinares: dinâmica da vegetação, do ambiente marinho e inferências climáticas milenares a atuais na Costa Norte do Espírito Santo, Brasil

Estudos paleoambientais desde ~50.000 anos na costa do Brasil e, em particular, no litoral do Espírito Santo, são ainda insuficientes para servir de base a reconstituições da dinâmica da vegetação, de oscilações do nível relativo do mar e de flutuações climáticas e respectivas influências sobre a ação humana milenar. Para obter essas informações, uma equipe interdisciplinar, financiada por projetos temáticos FAPESP e CNPq, desenvolveu pesquisas correlatas na Reserva Natural Vale (RNV) e região. Para a caracterização da dinâmica da vegetação e marinha, com inferências climáticas, em locais de floresta de tabuleiros e campos naturais da RNV e região desde ~16.000 anos, utilizaram-se isótopos do C (12C, 13C e 14C) da matéria orgânica do solo e sedimentar, além de palinologia em sedimentos lacustres e terrestres. No estudo da dinâmica do ecótono floresta – campo, apresentam-se inferências preliminares sobre a evolução pedogenética dos Espodossolos associados ao campo, com ênfase às suas características físico-químicas, e também dos Argissolos, encontrados sob floresta. Finaliza-se com o estágio inicial de uma coleção de referência de fitólitos, bioindicador de vegetação utilizado em estudos paleoambientais, extraídos de plantas da floresta de tabuleiros da RNV.A equipe agradece todo o empenho dos funcionários e apoio logístico da Reserva Natural Vale, Linhares, Espírito Santo; à FAPESP através do projeto Temático 2011/00995-7 (ProjES); e ao CNPq – Universal 2012-5/470210, pelo aporte financeiro e a colaboração dos técnicos do Laboratório 14C, Liz Mary Bueno de Moraes e Thiago Casemiro Barrios de Campos, na preparação de amostras gasosas para a datação 14C.Peer Reviewe

Genetic diversity in natural populations of Jacaranda decurrens Cham. determined using RAPD and AFLP markers

Jacaranda decurrens (Bignoniaceae) is an endemic species of the Cerrado with validated antitumoral activity. The genetic diversity of six populations of J. decurrens located in the State of São Paulo was determined in this study by using molecular markers for randomly amplified polymorphic DNA (RAPD) and amplified fragment length polymorphism (AFLP). Following optimization of the amplification reaction, 10 selected primers generated 78 reproducible RAPD fragments that were mostly (69.2%) polymorphic. Two hundred and five reproducible AFLP fragments were generated by using four selected primer combinations; 46.3% of these fragments were polymorphic, indicating a considerable level of genetic diversity. Analysis of molecular variance (AMOVA) using these two groups of markers indicated that variability was strongly structured amongst populations. The unweighted pair group method with arithmatic mean (UPGMA) and Pearson's correlation coefficient (RAPD -0.16, p = 0.2082; AFLP 0.37, p = 0.1006) between genetic matrices and geographic distances suggested that the population structure followed an island model in which a single population of infinite size gave rise to the current populations of J. decurrens, independently of their spatial position. The results of this study indicate that RAPD and AFLP markers were similarly efficient in measuring the genetic variability amongst natural populations of J. decurrens. These data may be useful for developing strategies for the preservation of this medicinal species in the Cerrado