8 research outputs found

    Comparison of spheroids formed by rat glioma stem cells and neural stem cells reveals differences in glucose metabolism and promising therapeutic applications

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    Cancer stem cells (CSCs) are thought to be partially responsible for cancer resistance to current therapies and tumor recurrence. Dichloroacetate (DCA), a compound capable of shifting metabolism from glycolysis to glucose oxidation, via an inhibition of pyruvate dehydrogenase kinase was used. We show that DCA is able to shift the pyruvate metabolism in rat glioma CSCs but has no effect in rat neural stem cells. DCA forces CSCs into oxidative phosphorylation but does not trigger the production of reactive oxygen species and consecutive anti-cancer apoptosis. However, DCA, associated with etoposide or irradiation, induced a Bax-dependent apoptosis in CSCs in vitro and decreased their proliferation in vivo. The former phenomenon is related to DCA-induced Foxo3 and p53 expression, resulting in the overexpression of BH3-only proteins (Bad, Noxa, and Puma), which in turn facilitates Bax-dependent apoptosis. Our results demonstrate that a small drug available for clinical studies potentiates the induction of apoptosis in glioma CSCs

    Intestinal cell targeting of a stable recombinant Cu–Zn SOD from Cucumis melo fused to a gliadin peptide

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    The mRNA encoding full length chloroplastic Cu–Zn SOD (superoxide dismutase) of Cucumis melo (Cantaloupe melon) was cloned. This sequence was then used to generate a mature recombinant SOD by deleting the first 64 codons expected to encode a chloroplastic peptide signal. A second hybrid SOD was created by inserting ten codons to encode a gliadin peptide at the N-terminal end of the mature SOD. Taking account of codon bias, both recombinant proteins were successfully expressed and produced in Escherichia coli. Both recombinant SODs display an enzymatic activity of ∼5000 U mg−1 and were shown to be stable for at least 4 h at 37 °C in biological fluids mimicking the conditions of intestinal transit. These recombinant proteins were capable in vitro, albeit at different levels, of reducing ROS-induced-apoptosis of human epithelial cells. They also stimulated production and release in a time-dependent manner of an autologous SOD activity from cells located into jejunum biopsies. Nevertheless, the fused gliadin peptide enable the recombinant Cu–Zn SOD to maintain a sufficiently sustained interaction with the intestinal cells membrane in vivo rather than being eliminated with the flow. According to these observations, the new hybrid Cu–Zn SOD should show promise in applications for managing inflammatory bowel diseases

    Exploring the chemical space of white wine antioxidant capacity: A combined DPPH, EPR and FT-ICR-MS study.

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    The chemical composition and functionality of molecular fractions associated with dry white wines oxidative stability remain poorly understood. In the present study, DPPH assay, electron paramagnetic resonance spectroscopy (EPR) and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) were used to explore the chemical diversity associated with the antioxidant capacity (AC) of white wines. AC determined using the DPPH assay and EPR were complementary and enabled differentiation of wine samples into groups with low, medium, and high AC. Mass spectra variations associated with global DPPH- and EPR-derived indices enabled identification of 365 molecular markers correlated with samples with high AC, of which 32% were CHO compounds including phenolic and sugar derivatives, 20% were CHOS and 36% were CHONS compounds including cysteine-containing peptides. This study confirmed the importance of CHONS and CHOS compounds in the antioxidant metabolome of dry white wines. Knowledge about these compounds will enable better understanding of the oxidative stability of white wines and therefore aid in achieving optimum shelf life

    Seismogenic characterization of active faults in Colombia for seismic hazard assessment of the city of Bogotá: Formal agreement between the Colombian Geological Survey and the Centro Nacional Instituto Geológico y Minero de España (CSIC)

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    [EN] The recent update of the Colombian seismic hazard model by Dirección de Geoamenzas of the Colombian Geological Survey (CGS), has identified the necessity of considering fault geological data in future successive updates of the hazard map. At the same time, the faultbased seismic hazard studies developed in the Centro Nacional IGME-CSIC have also identified the need of increasing the available knowledge on recent activity and paleoseismology of Spanish active faults in preparation for a future update of the national seismic hazard. In this frame, both CGS and IGME-CSIC, have formally agreed to collaborate in active faults research as well as their modelling for seismic hazard calculations to improve seismic risk provisions. It has been program firstly a pilot study in the transfer zone between the Algeciras and Guaicaramo faults (Colombia) that could also serve to provide the methodological framework for studying other faults in the country.Peer reviewe

    LANGUAGE IN INDIA Strength for Today and Bright Hope for Tomorrow Role of Stylistics in Learning English as a Second Language

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    There are many good poets and writers be they … Galib is said to have unparalleled style of expression. Abstract Stylistics is an area of study that is growing and developing fast. Its central concern is the way cognitive and communicative effects are achieved by means of linguistic choices. It, therefore, covers literary studies and linguistics as well as discourse studies. One of the types of stylistics, Pedagogical Stylistics, has proved to be very fruitful for learners. The present paper focuses on the pragmatic functions of Stylistics, playing a vital role in learning, teaching and acquisition of English as second language. The paper also focuses on the history, functions and aim of Stylistics in L2 and its role in solving the problems faced in learning L2. The paper concludes by stating the role of Stylistics in learning English as a second language and how it is practically helpful in acquiring the same
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