72 research outputs found

    Zeolite development from fly ASH and utilization in lignite mine-water treatment

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    The synthetic zeolitic materials were tested comparatively, showing that the more intense the zeolitic presence in the synthetic materials, the greater the uptake rates for certain groups of trace elements

    Targeting the CoREST complex with dual histone deacetylase and demethylase inhibitors

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    Here we report corin, a synthetic hybrid agent derived from the class I HDAC inhibitor (entinostat) and an LSD1 inhibitor (tranylcypromine analog). Enzymologic analysis reveals that corin potently targets the CoREST complex and shows more sustained inhibition of CoREST complex HDAC activity compared with entinostat. Cell-based experiments demonstrate that corin exhibits a superior anti-proliferative profile against several melanoma lines and cutaneous squamous cell carcinoma lines compared to its parent monofunctional inhibitors but is less toxic to melanocytes and keratinocytes. CoREST knockdown, gene expression, and ChIP studies suggest that corin's favorable pharmacologic effects may rely on an intact CoREST complex. Corin was also effective in slowing tumor growth in a melanoma mouse xenograft model. These studies highlight the promise of a new class of two-pronged hybrid agents that may show preferential targeting of particular epigenetic regulatory complexes and offer unique therapeutic opportunities

    Epigenetic re-wiring of breast cancer by pharmacological targeting of C-terminal binding protein

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    The C-terminal binding protein (CtBP) is an NADH-dependent dimeric family of nuclear proteins that scaffold interactions between transcriptional regulators and chromatin-modifying complexes. Its association with poor survival in several cancers implicates CtBP as a promising target for pharmacological intervention. We employed computer-assisted drug design to search for CtBP inhibitors, using quantitative structure-activity relationship (QSAR) modeling and docking. Functional screening of these drugs identified 4 compounds with low toxicity and high water solubility. Micro molar concentrations of these CtBP inhibitors produces significant de-repression of epigenetically silenced pro-epithelial genes, preferentially in the triple-negative breast cancer cell line MDA-MB-231. This epigenetic reprogramming occurs through eviction of CtBP from gene promoters; disrupted recruitment of chromatin-modifying protein complexes containing LSD1, and HDAC1; and re-wiring of activating histone marks at targeted genes. In functional assays, CtBP inhibition disrupts CtBP dimerization, decreases cell migration, abolishes cellular invasion, and improves DNA repair. Combinatorial use of CtBP inhibitors with the LSD1 inhibitor pargyline has synergistic influence. Finally, integrated correlation of gene expression in breast cancer patients with nuclear levels of CtBP1 and LSD1, reveals new potential therapeutic vulnerabilities. These findings implicate a broad role for this class of compounds in strategies for epigenetically targeted therapeutic intervention

    KDM1A microenvironment, its oncogenic potential, and therapeutic significance

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    The lysine-specific histone demethylase 1A (KDM1A) was the first demethylase to challenge the concept of the irreversible nature of methylation marks. KDM1A, containing a flavin adenine dinucleotide (FAD)-dependent amine oxidase domain, demethylates histone 3 lysine 4 and histone 3 lysine 9 (H3K4me1/2 and H3K9me1/2). It has emerged as an epigenetic developmental regulator and was shown to be involved in carcinogenesis. The functional diversity of KDM1A originates from its complex structure and interactions with transcription factors, promoters, enhancers, oncoproteins, and tumor-associated genes (tumor suppressors and activators). In this review, we discuss the microenvironment of KDM1A in cancer progression that enables this protein to activate or repress target gene expression, thus making it an important epigenetic modifier that regulates the growth and differentiation potential of cells. A detailed analysis of the mechanisms underlying the interactions between KDM1A and the associated complexes will help to improve our understanding of epigenetic regulation, which may enable the discovery of more effective anticancer drugs

    Mineralogical and chemical properties of FGD gypsum from Florina, Greece

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    Bagkground: The aim of this work is to define the chemical and mineralogical composition of the fuel gas desulphurization (FGD) gypsum produced from the Meliti thermal power plant in the region of Florina in North West Greece, in order to investigate potential uses in the cement industry. Mineralogical and microprobe analyses were carried out on FGD gypsum samples collected from the Meliti 330 MW lignite-fired power plant. Results: Results show that the main component of the FGD gypsum is pure mineral gypsum (CaSO4.2H2O). The particle size of the gypsum ranges from 5 to 50 μm and the crystals are mainly of rhomboid shape. Microprobe analysis shows that the concentration of CaO and SO3, which are the main components, range from 31.9%-32.5% and from 45.90-46.40%, respectively. Conclusion: This FGD gypsum can easily substitute the natural gypsum used in the production of cement. © 2007 Society of Chemical Industry

    Fossilized bacteria in Fe-Mn-mineralization: Evidence from the Legrena valley, W. Lavrion mine (Greece)

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    The primary mineralization in the famous Lavrion mine in the Lavreotiki area, Attica (Greece), associated with a granodiorite intrusion of Upper Miocene age and composed of massive sulphide Pb-Zn-Ag ores [sphalerite, pyrite and galena (B.P.G)], has been extensively studied. The present study is focused on thin, hard, dark brown to black Fe-Mn crusts (a few mm to cm in thickness) in the Legrena valley, SW Lavreotiki, aiming to provide new insights on that type of Fe-Mn-mineralization. The scanning electron microscope (SEM)/energy dispersive spectroscopy (EDS) data presented revealed the presence of fine rounded fragments, resembling nodules (up to 200 μm) and fossilized bacteriomorphic Fe-Mn-oxides/hydroxides, within brecciated and foliated zones of carbonate rocks. They exhibit unusual features when compared to the common massive Fe-Mn mineralization with regards the following: (a) the extensive occurrence of bacteriomorphic Fe-oxides/hydroxides and their micro-textures; and (b) the minor elements (K, Na, P, S, Ca, As and Cl). The occurrence of abundant bacteriomophic Fe-Mn-oxides/hydroxides in the samples from the Legrena valley may reflect their catalytic role in the redox reactions during ore-forming processes. The characteristic features of that type of Fe-Mn mineralization seems to be the result of multistage supergene processes superimposed over initial hydrothermal stages. Such a multistage remobilization and precipitation of metals along open space surfaces on karstified carbonates during a subsequent stage of their initial precipitation may be widespread in the Attica region, Greece. © 2018 by the authors. Licensee MDPI, Basel, Switzerland

    Factors controlling the heterogeneous distribution of Cr(VI) in soil, plants and groundwater: Evidence from the Assopos basin, Greece

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    The effective influence of industry or ultramafic rocks by natural processes to soil, plants and groundwater contamination by chromium, which is often a subject of debate, was investigated for the case of the Assopos basin, Greece. The Neogene Assopos basin, is mainly composed by Tertiary and Quaternary sediments of more than 400. m thick and is characterized by brittle type deformation (fault zones, faults). Chromium in soil, ranging from 67 to 204. ppm, is mostly hosted in chromite, Fe-chromite, Cr-bearing goethite and silicates. Special attention was given to the plants, which are a major source of organic matter that serves as the driving force for Cr(VI) reduction. The increase of the Fe, Mn and Ni contents, with the increasing Cr content in the plant-roots, in particular at the external parts of roots and those of bulb-type plants, suggest reduction and immobilization of Cr(VI) and that redox reactions play a significant role to the translocation processes from root to shoot. Groundwater samples from the Assopos aquifer showed a wide spatial variability, ranging from <2 to 180ppb Crtotal content [almost same to the Cr(VI)-values] despite their spatial association. The presence of Cr(VI)-contaminated groundwater at depths >200m is attributed to a direct injection of Cr(VI)-rich industrial wastes at depth rather than that Cr(VI) is derived from the Assopos river or by the interaction between water and Cr-bearing rocks. The heterogeneous distribution of Cr in groundwater may be related with the intense neotectonic deformation, as is exemplified by several sharp tectonic contacts between sediment types, while the Cr content in soil is mostly depend on the transported chromite grains. © 2011 Elsevier GmbH
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