Targeting histone deacetyalses in the treatment of B- and T-cell malignancies

HDAC inhibitors (HDACI) are now emerging as one of the most promising new classes of drugs for the treatment of select forms of non-Hodgkin’s lymphoma (NHL). They are particularly active in T-cell lymphomas, possibly hodgkin’s lymphoma and indolent B cell lymphomas. Presently, two of these agents, vorinostat and romidepsin, have been approved in the US for the treatment of relapsed and refractory cutaneous T cell lymphomas (CTCL). Initially, these agents were developed with the idea that they affected transcriptional activation and thus gene expression, by modulating chromatin condensation and decondensation. It is now clear that their effects go beyond chromatin and by affecting the acetylation status of histones and other intra-cellular proteins, they modify gene expression and cellular function via multiple pathways. Gene expression profiles and functional genetic analysis has led to further understanding of the various molecular pathways that are affected by these agents including cell cycle regulation, pathways of cellular proliferation, apoptosis and angiogenesis all important in lymphomagenesis. There is also increasing data to support the effects of these agents on T cell receptor and immune function which may explain the high level of activity of these agents in T cell lymphomas and hodgkin’s lymphoma. There is ample evidence of epigenetic dysregulation in lymphomas which may underlie the mechanisms of action of these agents but how these agents work is still not clear. Current HDAC inhibitors can be divided into at least four classes based on their chemical structure. At present several of these HDAC inhibitors are in clinical trials both as single agents and in combination with chemotherapy or other biological agents. They are easy to administer and are generally well tolerated with minimal side effects. Different dosing levels and schedules and the use of isospecific HDAC inhibitors are some of the strategies that are being employed to increase the therapeutic effect of these agents in the treatment of lymphomas. There may also be class differences that translate into specific activity against different lymphoma. HDAC inhibitors will likely be incorporated into combinations of targeted therapies both in the upfront and relapsed setting for lymphomas

Green synthesis of polysaccharides-based gold and silver nanoparticles and their promissory biological activity

Indexación: Web of ScienceThis paper demonstrates a green approach for the synthesis of gold and silver nanoparticles using polysaccharides extracted from macroseaweed as reducing agents. The formation of Au-NPs and Ag-NPs was confirmed by UV-Vis spectroscopy and Transmission Electron Microscopy (TEM). TEM analysis of both polysaccharides-based metallic nanoparticles surprisingly showed that the type of the polysaccharides (alginate or carrageenan) not only influence the morphology and the sizes of the nanostructures but also avoid the aggregation of them. The biological activity of these eco-friendly metallic nanoparticles was tested on two Gram-negative pathogenic organisms such as Pseudomonas aeruginosa and Salmonella Typhimurium, showing similar activity than those ones prepared using the well-known inorganic reducing agent, sodium citrate (SC). Futhermore, hemolytic activity was also tested showing that the polysaccharides-based metallic nanoparticles (Ps-MNPs) were less cytotoxic than the corresponding gold and silver nanoparticles prepared using SC. These results strongly suggest that these Ps-MNPs could be used as antimicrobial agents for the treatment of bacterial infections.http://biointerfaceresearch.com

Epigenetic regulation during fetal femur development: DNA methylation matters

Epigenetic modifications are heritable changes in gene expression without changes in DNA sequence. DNA methylation has been implicated in the control of several cellular processes including differentiation, gene regulation, development, genomic imprinting and X-chromosome inactivation. Methylated cytosine residues at CpG dinucleotides are commonly associated with gene repression; conversely, strategic loss of methylation during development could lead to activation of lineage-specific genes. Evidence is emerging that bone development and growth are programmed; although, interestingly, bone is constantly remodelled throughout life. Using human embryonic stem cells, human fetal bone cells (HFBCs), adult chondrocytes and STRO-1+ marrow stromal cells from human bone marrow, we have examined a spectrum of developmental stages of femur development and the role of DNA methylation therein. Using pyrosequencing methodology we analysed the status of methylation of genes implicated in bone biology; furthermore, we correlated these methylation levels with gene expression levels using qRT-PCR and protein distribution during fetal development evaluated using immunohistochemistry. We found that during fetal femur development DNA methylation inversely correlates with expression of genes including iNOS (NOS2) and COL9A1, but not catabolic genes including MMP13 and IL1B. Furthermore, significant demethylation was evident in the osteocalcin promoter between the fetal and adult developmental stages. Increased TET1 expression and decreased expression of DNA (cytosine-5-)-methyltransferase 1 (DNMT1) in adult chondrocytes compared to HFBCs could contribute to the loss of methylation observed during fetal development. HFBC multipotency confirms these cells to be an ideal developmental system for investigation of DNA methylation regulation. In conclusion, these findings demonstrate the role of epigenetic regulation, specifically DNA methylation, in bone development, informing and opening new possibilities in development of strategies for bone repair/tissue engineering.<br/

Hydrophilic polymer changes the water demand in the implementation of a dwarf cashew orchard.

Abstract: Important losses of dwarf cashew seedlings during the establishment of orchards in the Brazilian semiarid are related to the relatively short rainy season. This study aimed to evaluate biochar and hydrophilic polymer as soil amendments to increase water retention and reduce plant death in the first year. An experiment was conducted at the Curu Station, Paraipaba, CE, Brazil, using the clone BRS 226. The experimental design consisted of randomized blocks, with amounts of 0.5, 1.0, 2.0, and 4.0 kg of cashew wood biochar and 20, 40, 60, 80 g of hydrophilic polymer applied per pit, as well as a control treatment (no soil amendment). Seedlings were submitted to an irrigation regime to avoid water stress (5 L water seedling-1 when the tensiometer installed at a depth of 0.15 m reached 60 kPa). The variables of plant development number of leaves, plant height, stem diameter, and canopy diameter were evaluated up to 374 days after transplanting to the field. The analysis of variance showed no treatment effect on plant development. However, minimum water consumption was observed when 29.56 g of hydrophilic polymer was applied per pit, providing 100.0% seedling survival

Dendroecology of Prosopis species in the world: Secular traces of natural and anthropic events and their effects on Prosopis growth

Prosopis genus comprises 44 species which grow in arid and semiarid environments of America, Asia and Africa and in Oceania as introduced species. Of those 44 species, 30 grow in America. Argentina is supposed to be the origin center of the genus Prosopis, and that could explain the fact that this country has the highest species variability. Prosopis species are of great ecological and social value providing goods such as firewood, food, feed for livestock and medicines as well as services acting as watershed stabilizers and nitrogen and carbon sequesters. In this chapter, we address the new insights that dendrochronological studies have provided about Prosopis genus worldwide with main emphasis in Latin America. Many studies provide information about growth dynamics which are later on applied to develop management plans, to quantify the increment in dead and alive biomass throughout time or to estimate growth changes linked to social and political events. Rainfall is the main growth driver of Prosopis throughout the Andes from Peru to central Argentina, whereas in the flat Pampas temperature is the main tree-ring width driver. Climate variables are hard to separate from other factors affecting growth such as geomorphology, anthropogenic impact and groundwater depth. Outside of Latin America, dendrochronology of Prosopis has been used for the analysis of anthropogenic contamination. Fire, the main disturbance factor in arid and semiarid environments, showed a regional dynamic as a result of human activities. Most dendroecological studies on Prosopis species, which allowed determining these species dynamics, concluded that Prosopis do not present an encroaching behavior. This review demonstrates the avant-garde and influential value of Prosopis genus for dendroecological research as it allows reconstructing past disturbances as fire, anthropogenic impact and changes in groundwater depth for the last 50–100 years and up to 356 years in the case of Prosopis caldenia Burkart in the Pampean Region.Fil: Cangiano, Maria Laura. North Carolina State University; Estados UnidosFil: Cendoya, Maria Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro Regional La Pampa-San Luis. Estación Experimental Agropecuaria San Luis; ArgentinaFil: Risio Allione, Lucia Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis; Argentina. Universidad Nacional de San Luis. Facultad de Ingeniería y Ciencias Económico Sociales. Departamento de Ciencias Agropecuarias; ArgentinaFil: Bogino, Stella Marys. Universidad Nacional de San Luis. Facultad de Ingeniería y Ciencias Económico Sociales. Departamento de Ciencias Agropecuarias; Argentin