Extraction, Purification and Electrical Characterization of Gross Galactomannan and Purified Galactomannan Obtained from Adenanthera pavonina L. Seeds.

Aiming of self-sustainable production, the search for biodegradable and biocompatible materials has brought with it the need to know the physicochemical and dielectric characteristics of polysaccharide-based composite structures, which can be used as important and promising raw materials for biotechnology and electronic industries. Galactomannans are polysaccharides, extracted from seeds and microbiological sources, consisting of mannose and galactose. In this context, this work aimed to extract, purify and characterize by XRD, FTIR and impedance spectroscopy galactomannan obtained from seeds of Adenanthera pavonina L. The purification process was made with ethyl alcohol at concentrations of 70, 80 and 90 %. Polymeric films were prepared by solvent slow evaporation at low temperatures. XRD measurements revealed that Galactomannan from Adenanthera pavonina L., after purification, has a semi-crystalline structure due to the identification of two peaks the first between 5.849° and 6.118° and the second between 20.011° and 20.247°. FTIR spectra showed the functional groups associated with monosaccharides of the galactomannan from Adenanthera pavonina L. seeds, as well as the typical polysaccharide bands and peaks, confirmed by literature data. The impedance results give an increment on the state-of-the-art of this biomaterial by showing the existence of dielectric relaxations, independent of the degree of purification, using the dielectric modulus formalism. The permittivity analysis reveals the presence of water in the structure of the film, whose dipoles contribute to the relatively high value of the dielectric constant. From the results obtained, it can be concluded that purified galactomannan has the potential for possible applications in the electronics industry as a green and eco-friendly dielectric material.

PRAME/EZH2-mediated regulation of TRAIL: a new target for cancer therapy.

The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exerts a cancer cell-specific pro-apoptotic activity. This property made the TRAIL associated pathway one of the most promising strategies aimed at inducing tumor-selective death. In fact, several approaches have been considered to explore this pathway for cancer therapy, such as recombinant TRAIL, agonist antibodies for TRAIL receptors, and adenoviral TRAIL. However, all of these approaches have certain disadvantages that limit their clinical use. Our recent discovery that the complex PRAME/EZH2 is able to repress TRAIL expression, in a cancer-specific manner, suggests an alternative approach for combined cancer therapy. A genetic or pharmacological inhibition of TRAIL repressors in cancer cells could restore endogenous TRAIL expression, thereby overcoming some of the limitations of and/or cooperating with previous approaches.

Apoptosis: a programme of cell death or cell disposal?

Based primarily on morphological features, apoptosis was described as the cell death that occurs during physiological situations, whereas necrosis was observed during acute harmful conditions. Apoptosis was, therefore, associated with a programme of cell death, as opposed to necrosis, considered an accidental, uncontrolled, pathological cell death. The apoptotic machinery was first unravelled in the nematode Caenorhabditis elegans, where a protease called CED-3 was central to the execution of cells destined to die. Inactivation of ced-3 gene prevents developmental cell death in the worm, an observation that reinforces the notion that apoptosis holds the switch between life and death. In mammals, proteins homologous to CED-3, members of the family collectively called caspases, are considered the executioner proteases responsible for generating fundamentally all aspects of apoptosis. However, inhibition of the so-called executioner caspases (i.e. inhibition of apoptosis) does not prevent cell death to occur. Consequently, in mammals, the decision switch between life and death resides upstream of the activation of caspases and the ensuing apoptotic cell death. Therefore, apoptosis is not a programme of cell death but purely a termination step of a cell death programme, responsible for proper disposal of the already-committed, dying cells.

BCR-ABL-mediated upregulation of PRAME is responsible for knocking down TRAIL in CML patients.

Tumor necrosis factor-related apoptosis-inducing ligand-TNFSF10 (TRAIL), a member of the TNF-α family and a death receptor ligand, was shown to selectively kill tumor cells. Not surprisingly, TRAIL is downregulated in a variety of tumor cells, including BCR-ABL-positive leukemia. Although we know much about the molecular basis of TRAIL-mediated cell killing, the mechanism responsible for TRAIL inhibition in tumors remains elusive because (a) TRAIL can be regulated by retinoic acid (RA); (b) the tumor antigen preferentially expressed antigen of melanoma (PRAME) was shown to inhibit transcription of RA receptor target genes through the polycomb protein, enhancer of zeste homolog 2 (EZH2); and (c) we have found that TRAIL is inversely correlated with BCR-ABL in chronic myeloid leukemia (CML) patients. Thus, we decided to investigate the association of PRAME, EZH2 and TRAIL in BCR-ABL-positive leukemia. Here, we demonstrate that PRAME, but not EZH2, is upregulated in BCR-ABL cells and is associated with the progression of disease in CML patients. There is a positive correlation between PRAME and BCR-ABL and an inverse correlation between PRAME and TRAIL in these patients. Importantly, knocking down PRAME or EZH2 by RNA interference in a BCR-ABL-positive cell line restores TRAIL expression. Moreover, there is an enrichment of EZH2 binding on the promoter region of TRAIL in a CML cell line. This binding is lost after PRAME knockdown. Finally, knocking down PRAME or EZH2, and consequently induction of TRAIL expression, enhances Imatinib sensibility. Taken together, our data reveal a novel regulatory mechanism responsible for lowering TRAIL expression and provide the basis of alternative targets for combined therapeutic strategies for CML.