42 research outputs found

    Cobalt protoporphyrin IX increases endogenous G-CSF and mobilizes HSC and granulocytes to the blood

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    Granulocyte colony-stimulating factor (G-CSF) is used in clinical practice to mobilize cells from the bone marrow to the blood; however, it is not always effective. We show that cobalt protoporphyrin IX (CoPP) increases plasma concentrations of G-CSF, IL-6, and MCP-1 in mice, triggering the mobilization of granulocytes and hematopoietic stem and progenitor cells (HSPC). Compared with recombinant G-CSF, CoPP mobilizes higher number of HSPC and mature granulocytes. In contrast to G-CSF, CoPP does not increase the number of circulating T cells. Transplantation of CoPP-mobilized peripheral blood mononuclear cells (PBMC) results in higher chimerism and faster hematopoietic reconstitution than transplantation of PBMC mobilized by G-CSF. Although CoPP is used to activate Nrf2/HO-1 axis, the observed effects are Nrf2/HO- 1 independent. Concluding, CoPP increases expression of mobilization- related cytokines and has superior mobilizing efficiency compared with recombinant G-CSF. This observation could lead to the development of new strategies for the treatment of neutropenia and HSPC transplantation

    Evolution of glassy carbon under heat treatment : correlation structure-mechanical properties

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    In order to accommodate an increasing demand for glassy carbon products with tailored characteristics, one has to understand the origin of their structure-related properties. In this work, through the use of high-resolution transmission electron microscopy, Raman spectroscopy, and electron energy loss spectroscopy it has been demonstrated that the structure of glassy carbon at different stages of the carbonization process resembles the curvature observed in fragments of nanotubes, fullerenes, or nanoonions. The measured nanoindentation hardness and reduced Young’s modulus change as a function of the pyrolysis temperature from the range of 600–2500 °C and reach maximum values for carbon pyrolyzed at around 1000 °C. Essentially, the highest values of the mechanical parameters for glassy carbon manufactured at that temperature can be related to the greatest amount of non-planar sp2-hybridized carbon atoms involved in the formation of curved graphene-like layers. Such complex labyrinth- like structure with sp2-type bonding would be rigid and hard to break that explains the glassy carbon high strength and hardness

    Iron chelators and exogenic photosensitizers. Synergy through oxidative stress gene expression

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    In non-invasive anticancer photodynamic therapy (PDT), a nontoxic photosensitizer (PS), which is activated by visible light, is used as a magic bullet that selectively destroys cancer cells. Recently, we described the combined therapy of 5-aminolevulinic acid (ALA-PDT) with thiosemicarbazone (TSC), i.e. an iron-chelating agent. This resulted in a strong synergistic effect. Herein, we investigated a novel strategy using a combination of PDT consist of the xenobiotic-porphyrin type PS with TSC. We observed a synergistic effect for all of the pairs of TSC-PS. This approach can be rationalized by the fact that both chlorin and TSC can affect the generation of reactive oxygen species (ROS). In order to elucidate the plausible mechanism of action, we also combined the investigated PSs with DFO, which forms complexes that are redox inactive. We detected a slight antagonism or additivity for this combination. This may suggest that the ability of an iron chelator (IC) to participate in the production of ROS and the generation of oxidative stress is important

    Synthesis of New Styrylquinoline Cellular Dyes, Fluorescent Properties, Cellular Localization and Cytotoxic Behavior

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    New styrylquinoline derivatives with their photophysical constants are described. The synthesis was achieved via Sonogashira coupling using the newly developed heterogeneous nano-Pd/Cu catalyst system, which provides an efficient synthesis of high purity products. The compounds were tested in preliminary fluorescent microscopy studies to in order to identify their preferable cellular localization, which appeared to be in the lipid cellular organelles. The spectroscopic properties of the compounds were measured and theoretical TD- DFT calculations were performed. A biological analysis of the quinolines that were tested consisted of cytotoxicity assays against normal human fibroblasts and colon adenocarcinoma cells. All of the compounds that were studied appeared to be safe and indifferent to cells in a high concentration range. The presented results suggest that the quinoline compounds that were investigated in this study may be valuable structures for development as fluorescent dyes that could have biological applications

    Exploring the Anti-Cancer Activity of Novel Thiosemicarbazones Generated through the Combination of Retro-Fragments: Dissection of Critical Structure-Activity Relationships

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    <div><p>Thiosemicarbazones (TSCs) are an interesting class of ligands that show a diverse range of biological activity, including anti-fungal, anti-viral and anti-cancer effects. Our previous studies have demonstrated the potent <i>in vivo</i> anti-tumor activity of novel TSCs and their ability to overcome resistance to clinically used chemotherapeutics. In the current study, 35 novel TSCs of 6 different classes were designed using a combination of retro-fragments that appear in other TSCs. Additionally, di-substitution at the terminal N4 atom, which was previously identified to be critical for potent anti-cancer activity, was preserved through the incorporation of an N4-based piperazine or morpholine ring. The anti-proliferative activity of the novel TSCs were examined in a variety of cancer and normal cell-types. In particular, compounds <b>1d</b> and <b>3c</b> demonstrated the greatest promise as anti-cancer agents with potent and selective anti-proliferative activity. Structure-activity relationship studies revealed that the chelators that utilized “soft” donor atoms, such as nitrogen and sulfur, resulted in potent anti-cancer activity. Indeed, the <i>N</i>,<i>N</i>,<i>S</i> donor atom set was crucial for the formation of redox active iron complexes that were able to mediate the oxidation of ascorbate. This further highlights the important role of reactive oxygen species generation in mediating potent anti-cancer activity. Significantly, this study identified the potent and selective anti-cancer activity of <b>1d</b> and <b>3c</b> that warrants further examination.</p></div

    Lessons from chlorophylls : modifications of porphyrinoids towards optimized solar energy conversion

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    Practical applications of photosynthesis-inspired processes depend on a thorough understanding of the structures and physiochemical features of pigment molecules such as chlorophylls and bacteriochlorophylls. Consequently, the major structural features of these pigments have been systematically examined as to how they influence the S_{1} state energy, lifetimes, quantum yields, and pigment photostability. In particular, the effects of the macrocyclic π-electron system, central metal ion (CMI), peripheral substituents, and pigment aggregation, on these critical parameters are discussed. The results obtained confirm that the π-electron system of the chromophore has the greatest influence on the light energy conversion capacity of porphyrinoids. Its modifications lead to changes in molecular symmetry, which determine the energy levels of frontier orbitals and hence affect the S_{1} state properties. In the case of bacteriochlorophylls aggregation can also strongly decrease the S_{1} energy. The CMI may be considered as another influential structural feature which only moderately influences the ground-state properties of bacteriochlorophylls but strongly affects the singlet excited-state. An introduction of CMIs heavier than Mg^{2+} significantly improves pigments' photostabilities, however, at the expense of S_{1} state lifetime. Modifications of the peripheral substituents may also influence the S1 energy, and pigments’ redox potentials, which in turn influence their photostability

    meso-5,10,15,20-Tetrakis(4-hydroxy-3-methoxyphenyl)porphyrin propionic acid monosolvate

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    In the title compound, C48H38N4O8&amp;#183;C3H6O2, the porphyrin molecule is centrosymmetric. The propionic acid solvent molecule is disordered over two sets of sites with equal occupancy factors. The porphyrin central core is almost planar, with an r.m.s. deviation of the fitted atoms of 0.045&amp;#8197;&amp;#197;. The substituent benzene rings make dihedral angles of 70.37&amp;#8197;(4) and 66.95&amp;#8197;(4)&amp;#176; with respect to the porphyrin core plane. The crystal structure is stabilized by an interesting network of hydrogen bonds. Porphyrin molecules are connected by O&amp;#8212;H...O hydrogen bonds creating ribbons running along the [101] direction. Weak C&amp;#8212;H...O hydrogen bonds connect separate molecular ribbons in the [110] direction, creating (-111) layers. Intramolecular N&amp;#8212;H...N hydrogen bonds also occur. The propionic acid molecules are connected by pairs of &amp;#8212;H...O hydrogen bonds, creating dimers

    N,N&#8242;-Bis(2-hydroxyethyl)benzene-1,4-dicarboxamide

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    The molecule of the title compound, C12H16N2O4, is centrosymmetric and the amide group is twisted relative to the benzene ring by 14.40&#8197;(13)&#176;. The molecules are hydrogen bonded into a three-dimensional framework, with the hydroxy O atoms acting as acceptors in N&#8212;H...O hydrogen bonds and as donors in O&#8212;H...O=C interactions
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