Cellular mechanisms triggered by the cotreatment of resveratrol and doxorubicin in breast cancer: A translational in vitro–In silico model

Doxorubicin (Doxo) is the most effective chemotherapeutic agent for the treatment of breast cancer. However, resistance to Doxo is common. Adjuvant compounds capable of modulating mechanisms involved in Doxo resistance may potentiate the effectiveness of the drug. Resveratrol (Rsv) has been tested as an adjuvant in mammary malignancies. However, the cellular and molecular mechanisms underlying the effects of cotreatment with Doxo and Rsv in breast cancer are poorly understood. Here, we combined in vitro and in silico analysis to characterize these mechanisms. In vitro, we employed a clinically relevant experimental design consisting of acute (24 h) treatment followed by 15 days of analysis. Acute Rsv potentiated the long-lasting effect of Doxo through the induction of apoptosis and senescence. Cells that survived to the cotreatment triggered high levels of autophagy. Autophagy inhibition during its peak of activation but not concomitant with Doxo+Rsv increased the long-term toxicity of the cotreatment. To uncover key proteins potentially associated with in vitro effects, an in silico multistep strategy was implemented. Chemical-protein networks were predicted based on constitutive gene expression of MCF7 cells and interatomic data from breast cancer. Topological analysis, KM survival analysis, and a quantitative model based on the connectivity between apoptosis, senescence, and autophagy were performed. We found seven putative genes predicted to be modulated by Rsv in the context of Doxo treatment: CCND1, CDH1, ESR1, HSP90AA1, MAPK3, PTPN11, and RPS6KB1. Six out of these seven genes have been experimentally proven to be modulated by Rsv in cancer cells, with 4 of the 6 genes in MCF7 cells. In conclusion, acute Rsv potentiated the long-term toxicity of Doxo in breast cancer potentially through the modulation of genes and mechanisms involved in Doxo resistance. Rational autophagy inhibition potentiated the effects of Rsv+Doxo, a strategy that should be further tested in animal models

Efeito do treinamento físico sobre a resistência óssea

A intensão deste estudo foi analisar os efeitos do treinamento físico sobre a resistência meânica óssea a esforços deformantes em tíbia de ratos. O processo de treinamento físico consitiu de natação 1 h por dia com carga de 5% do peso corporal por 30 dias. Foram realizados as seguintes análises: glicogênio muscular (gastrocnêmio), resistência máxima, flexa de ruptura e rigidez média. Verificamos que o tipo de atividade física realizada nesse estudo provocou aumento no glicogênio muscular e elevou a resistência e a rigidez óssea após 30 dias de treinamento

Plant-antivenom: Database of anti-venom medicinal plants

Plant-antivenom is a computational Websystem about medicinal plants with anti-venom properties. The system consists of a database of these plants, including scientific publications on this subject and amino acid sequences of active principles from venomous animals. The system relates these data allowing their integration through different search applications. For the development of the system, the first surveys were conducted in scientific literature, allowing the creation of a publication database in a library for reading and user interaction. Then, classes of categories were created, allowing the use of tags and the organization of content. This database on medicinal plants has information such as family, species, isolated compounds, activity, inhibited animal venoms, among others. Provision is made for submission of new information by registered users, by the use of wiki tools. Content submitted is released in accordance to permission rules defined by the system. The database on biological venom protein amino acid sequences was structured from the essential information from National Center for Biotechnology Information (NCBI). Plant-antivenom's interface is simple, contributing to a fast and functional access to the system and the integration of different data registered on it. Plant-antivenom system is available on the Internet at http://gbi.fmrp.usp.br/plantantivenom

Transcriptome signature of the adult mouse choroid plexus

<p>Abstract</p> <p>Background</p> <p>Although the gene expression profile of several tissues in humans and in rodent animal models has been explored, analysis of the complete choroid plexus (CP) transcriptome is still lacking. A better characterization of the CP transcriptome can provide key insights into its functions as one of the barriers that separate the brain from the periphery and in the production of cerebrospinal fluid.</p> <p>Methods</p> <p>This work extends further what is known about the mouse CP transcriptome through a microarray analysis of CP tissue from normal mice under physiological conditions.</p> <p>Results</p> <p>We found that the genes most highly expressed are those implicated in energy metabolism (oxidative phosphorylation, glycolysis/gluconeogenesis) and in ribosomal function, which is in agreement with the secretory nature of the CP. On the other hand, genes encoding for immune mediators are among those with lower expression in basal conditions. In addition, we found genes known to be relevant during brain development, and not previously identified to be expressed in the CP, including those encoding for various axonal guidance and angiogenesis molecules and for growth factors. Some of these are known to influence the neural stem cell niche in the subventricular zone, highlighting the involvement of the CP as a likely modulator of neurogenesis. Interestingly, our observations confirm that the CP transcriptome is unique, displaying low homology with that of other tissues. Of note, we describe here that the closest similarity is with the transcriptome of the endothelial cells of the blood-brain barrier.</p> <p>Conclusions</p> <p>Based on the data presented here, it will now be possible to further explore the function of particular proteins of the CP secretome in health and in disease.</p

AVALIAÇÃO DA DESORDEM NUTRICIONAL DE PLANTAS DE AMENDOIM CULTIVADAS EM SOLUÇÃO NUTRITIVA SUPRIMIDAS DE MACRONUTRIENTES

Com o objetivo de avaliar o efeito da omissão de macronutrientes no crescimento e no estado nutricional do amendoim (Arachis hypogaea L.), bem como descrever sintomas visuais de deficiência nutricional, foi desenvolvido um experimento em solução nutritiva na FCAV/UNESP. O delineamento experimental foi o inteiramente casualizado, com sete tratamentos, que corresponderam à solução completa e à omissão individual de N, P, K, Ca, Mg e S, com três repetições. As plantas de amendoim cv. Runner IAC 886 foram cultivadas em solução nutritiva de Hoagland & Arnon em vasos contendo 5 dm³. Foram avaliados a altura das plantas, o diâmetro do caule, o número de folhas, o índice SPAD, a massa seca da parte aérea, das raízes e planta inteira, os teores e o acúmulo dos macronutrientes na parte aérea e raízes e a descrição das desordens nutricionais. A omissão de K, Ca, N, P e Mg foram as que mais limitaram o crescimento vegetativo do amendoim, reduzindo consideravelmente a altura, o diâmetro do caule, o número de folhas, assim como a produção da massa seca do amendoim. Foram observados sintomas de deficiência nutricional de cada elemento. Os teores de nutrientes observados nas plantas de amendoim do tratamento completo e da omissão, na parte aérea, foram, respectivamente: N = 19,0 - 12,2; P = 4,7 - 1,1; K = 27,9 - 4,7; Ca = 10,4 - 1,6; Mg = 6,2 - 0,96; S = 1,2 - 0,7 g kg-1

Identification Of Anln As Etv6 Partner Gene In Recurrent T(7;12)(p15;p13): A Possible Role Of Deregulated Anln Expression In Leukemogenesis.

The ETV6 gene encodes an ETS family transcription factor that is involved in a myriad of chromosomal rearrangements found in hematological malignancies and other neoplasms. A recurrent ETV6 translocation, previously described in patients with acute myeloid leukemia (AML) (Genes Chromosomes Cancer 51:328-337,2012, Leuk Res 35:e212-214, 2011), whose partner has not been identified is t(7;12)(p15;p13). We herein report that the t(7;12)(p15;p13) fuses ETV6 to ANLN, a gene not previously implicated in the pathogenesis of hematological malignancies, and we demonstrate that this translocation leads to high expression of the fusion transcript in the myeloid and lymphoid lineages.1419

HOXB7 mRNA is overexpressed in pancreatic ductal adenocarcinomas and its knockdown induces cell cycle arrest and apoptosis

Background\ud Human homeobox genes encode nuclear proteins that act as transcription factors involved in the control of differentiation and proliferation. Currently, the role of these genes in development and tumor progression has been extensively studied. Recently, increased expression of HOXB7 homeobox gene (HOXB7) in pancreatic ductal adenocarcinomas (PDAC) was shown to correlate with an invasive phenotype, lymph node metastasis and worse survival outcomes, but no influence on cell proliferation or viability was detected. In the present study, the effects arising from the knockdown of HOXB7 in PDAC cell lines was investigated.\ud \ud Methods\ud Real time quantitative PCR (qRT-PCR) (Taqman) was employed to assess HOXB7 mRNA expression in 29 PDAC, 6 metastatic tissues, 24 peritumoral tissues and two PDAC cell lines. siRNA was used to knockdown HOXB7 mRNA in the cell lines and its consequences on apoptosis rate and cell proliferation were measured by flow cytometry and MTT assay respectively.\ud \ud Results\ud Overexpression of HOXB7 mRNA was observed in the tumoral tissues and in the cell lines MIA PaCa-2 and Capan-1. HOXB7 knockdown elicited (1) an increase in the expression of the pro-apoptotic proteins BAX and BAD in both cell lines; (2) a decrease in the expression of the anti-apoptotic protein BCL-2 and in cyclin D1 and an increase in the number of apoptotic cells in the MIA PaCa-2 cell line; (3) accumulation of cell in sub-G1 phase in both cell lines; (4) the modulation of several biological processes, especially in MIA PaCa-2, such as proteasomal ubiquitin-dependent catabolic process and cell cycle.\ud \ud Conclusion\ud The present study confirms the overexpression of HOXB7 mRNA expression in PDAC and demonstrates that decreasing its protein level by siRNA could significantly increase apoptosis and modulate several biological processes. HOXB7 might be a promising target for future therapies.This study was supported in part by a FAPESP grant 2010/01421-1