Exploiting Mitochondrial Dysfunction for Effective Elimination of Imatinib-Resistant Leukemic Cells

Challenges today concern chronic myeloid leukemia (CML) patients resistant to imatinib. There is growing evidence that imatinib-resistant leukemic cells present abnormal glucose metabolism but the impact on mitochondria has been neglected. Our work aimed to better understand and exploit the metabolic alterations of imatinib-resistant leukemic cells. Imatinib-resistant cells presented high glycolysis as compared to sensitive cells. Consistently, expression of key glycolytic enzymes, at least partly mediated by HIF-1α, was modified in imatinib-resistant cells suggesting that imatinib-resistant cells uncouple glycolytic flux from pyruvate oxidation. Interestingly, mitochondria of imatinib-resistant cells exhibited accumulation of TCA cycle intermediates, increased NADH and low oxygen consumption. These mitochondrial alterations due to the partial failure of ETC were further confirmed in leukemic cells isolated from some imatinib-resistant CML patients. As a consequence, mitochondria generated more ROS than those of imatinib-sensitive cells. This, in turn, resulted in increased death of imatinib-resistant leukemic cells following in vitro or in vivo treatment with the pro-oxidants, PEITC and Trisenox, in a syngeneic mouse tumor model. Conversely, inhibition of glycolysis caused derepression of respiration leading to lower cellular ROS. In conclusion, these findings indicate that imatinib-resistant leukemic cells have an unexpected mitochondrial dysfunction that could be exploited for selective therapeutic intervention

Photochemical Degradation of the Anticancer Drug Bortezomib by V–UV/UV (185/254 nm) Investigated by 1 H NMR Fingerprinting: A Way to Follow Aromaticity Evolution

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Evaluation of chloride contamination in concrete using electromagnetic non-destructive testing methods

We present the results of the sensitivity of some electromagnetic non-destructive testing (NDT) methods to chloride contamination. The NDT methods are resistivity, using a quadripole probe, capacitive technique, with few sets of electrodes, and radar technique, using different bistatic configurations. A laboratory study was carried out involving three different concretes with different water to cement ratios. The concretes were conditioned with different degrees of NaCl saturation by means of three solutions containing 0 g/L, 30 g/l or 120 g/l. The solution was homogenized in the concrete by using a specific procedure. Results show that the EM techniques are very sensitive to the chloride content and saturation rate and, on a second level, to the porosity. Multi- linear regression processing was performed to estimate the level of sensitivity of the NDT measurements to the three indicators. Values of ten ND observables are presented and discussed. At last, the uncertainties of the regression models are studied on a real structure in a tidal zone

Corrosion de béton armé (développement d'un essai accéléré par carbonatation et couplage galvanique)

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Significance of macrocell corrosion of reinforcing steel in partially carbonated concrete: numerical and experimental investigation

WOS:000347554900015International audienceConcrete carbonation is usually assumed to induce microcell corrosion of reinforcing steel by uniform depassivation. However, the carbonation front evolves continuously as a slow, time-dependent process and concrete carbonation is often non-uniform in real concrete structures. Hence some areas of the steel reinforcement network in concrete are likely to be depassivated before others and, consequently, the theoretical conditions of macrocell corrosion appear to occur quite frequently in real concrete structures. This paper therefore focuses on steel corrosion phenomenology in partly carbonated concrete structures. The conclusions are supported by an experimental and numerical study based on accelerated macrocell corrosion tests, carried out on partly carbonated concrete specimens with embedded active and passive steel bars. The specimen design allowed for electrically connecting one active bar with one or several passive bars in order to form macrocell corrosion systems with various cathode-to-anode (C/A) surface ratios. Despite the high resistivity of the carbonated concrete layer, direct measurements of galvanic current revealed high macrocell corrosion rates, even in cases of low C/A ratio. The significance of galvanic coupling in carbonation-induced corrosion was thus confirmed experimentally. In addition to experiments, a synthetic, but comprehensive, theoretical description of macrocell corrosion is proposed and finite element simulations of experiments are reported. The agreement between numerical and experimental results is demonstrated regarding both potential field and C/A influence on macrocell current intensity. This consistency highlights the relevance of the modeling and simulation approach

Contrôle qualité de compléments alimentaires à base de berbérine par analyses RMN haut champ et bas champ

International audienc

Chemometric Analysis of Low-field 1H NMR Spectra for Unveiling Adulteration of Slimming Dietary Supplements by Pharmaceutical Compounds

International audienc

High-Field and Low-Field proton NMR spectroscopy for the analysis of cinnamon samples marketed as food or dietary supplements

International audienc

A toolbox to explore NMR metabolomic data sets using the R environment

International audienc