16 research outputs found

    The glucocorticoid dexamethasone inhibits HIF-1α stabilization and metabolic reprogramming in lipopolysaccharide-stimulated primary macrophages

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    Synthetic glucocorticoids are used to treat many chronic and acute inflammatory conditions. Frequent adverse effects of prolonged exposure toglucocorticoids include disturbances of glucose homeostasis caused by changes in glucose traffic and metabolism in muscle, liver, and adiposetissues. Macrophages are important targets for the anti-inflammatory actions of glucocorticoids. These cells rely on aerobic glycolysis to supportvarious pro-inflammatory and antimicrobial functions. Employing a potent pro-inflammatory stimulus in two commonly used model systems(mouse bone marrow-derived and human monocyte-derived macrophages), we showed that the synthetic glucocorticoid dexamethasone inhib-ited lipopolysaccharide-mediated activation of the hypoxia-inducible transcription factor HIF-1α, a critical driver of glycolysis. In both cell types,dexamethasone-mediated inhibition of HIF-1α reduced the expression of the glucose transporter GLUT1, which imports glucose to fuel aerobicglycolysis. Aside from this conserved response, other metabolic effects of lipopolysaccharide and dexamethasone differed between human andmouse macrophages. These findings suggest that glucocorticoids exert anti-inflammatory effects by impairing HIF-1α-dependent glucose uptakein activated macrophages. Furthermore, harmful and beneficial (anti-inflammatory) effects of glucocorticoids may have a shared mechanisticbasis, depending on the alteration of glucose utilization

    Dexamethasone impairs the expression of antimicrobial mediators in lipopolysaccharide-activated primary macrophages by inhibiting both expression and function of interferon β

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    Glucocorticoids potently inhibit expression of many inflammatory mediators, and have been widely used to treat both acute and chronic inflammatory diseases for more than seventy years. However, they can have several unwanted effects, amongst which immunosuppression is one of the most common. Here we used microarrays and proteomic approaches to characterise the effect of dexamethasone (a synthetic glucocorticoid) on the responses of primary mouse macrophages to a potent pro-inflammatory agonist, lipopolysaccharide (LPS). Gene ontology analysis revealed that dexamethasone strongly impaired the lipopolysaccharide-induced antimicrobial response, which is thought to be driven by an autocrine feedback loop involving the type I interferon IFNβ. Indeed, dexamethasone strongly and dose-dependently inhibited the expression of IFNβ by LPS-activated macrophages. Unbiased proteomic data also revealed an inhibitory effect of dexamethasone on the IFNβ-dependent program of gene expression, with strong down-regulation of several interferon-induced antimicrobial factors. Surprisingly, dexamethasone also inhibited the expression of several antimicrobial genes in response to direct stimulation of macrophages with IFNβ. We tested a number of hypotheses based on previous publications, but found that no single mechanism could account for more than a small fraction of the broad suppressive impact of dexamethasone on macrophage type I interferon signaling, underlining the complexity of this pathway. Preliminary experiments indicated that dexamethasone exerted similar inhibitory effects on primary human monocyte-derived or alveolar macrophages.</p

    Investigation of Li+ cation Coordination and Transportation, by Molecular Modeling and NMR Studies, in a LiNTf2 doped Ionic Liquid-Vinylene Carbonate Mixture

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    To increase the safety and stability of Lithium ion batteries, the development of electrolytes based on ionic liquids gained a lot of attention in recent years. However, with graphite electrodes neat ILs afford weak cycling performance in the absence of organic additives (e.g. vinylene carbonate, VC). The potential formation of a [Li+]-OVC interaction/coordination could have a major influence on the observed electrochemical behavior of Li-ion batteries. On a specific electrolyte, 1-hexyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide [C1C6Im][NTf2] in association with Li[NTf2] (1mol.L-1) and VC, we performed NOESY, {1H-7Li} HOESY correlations, and pulsed field gradient spin-echo NMR measurements, combined with molecular dynamics simulations in order to determine if a such interaction/coordination between VC and Li+ ions is noticeable. {7Li-1 H} HOESY experiment shows the vicinity of VC with [Li+] cation and Strong correlations and association between [Li+]and VC is observed in intense first peaks in radial distribution functions and quantified by the coordination numbers in the first solvation shell between [Li+]and the carbonyl oxygen atom of VC

    National “Bilad as-Sudan” symposium: “Politics and Cultures” (account by Wiesława Bolimowska)

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    Exhibition about Polish People in Africa – Missed Opportunity

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    Investigation of the interface electrode/ionic liquid based electrolyte for lithium ion battery

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    Dans les batteries ion lithium, la présence d’électrolytes organiques volatiles et inflammables engendre des problèmes récurrents de sécurité. Une possible solution consiste à les remplacer par des sels fondus liquides à température ambiante, les liquides ioniques (LI), présentant une tension de vapeur négligeable et sont considérés comme flamme retardant. Leur utilisation avec des électrodes carbone (les plus usitées dans les batteries commerciales) nécessitent la présence d’un additif pour améliorer les performances des batteries.Le but de cette thèse était de déterminer le rôle de cet additif par des méthodes analytiques et de la modélisation. Tout d’abord, l’impact de cet additif sur la solvatation et la diffusion des sels de lithium a été étudié par RMN 2-D [NOE et HOESY {1H-7Li}, {1H-19F}, et la sphère de coordination du cation lithium a été simulée par dynamique moléculaire. Puis des études électrochimiques ont été développées notamment le cyclage galvanostatique à potentiel sélectionné et le cyclage voltamétrique afin de déterminer la capacité de la batterie et d’étudier les étapes d‘insertion du cation lithium au cours de la première étape de réduction. Cette étape a également été analysée par impédance électrochimique. En complément, une analyse par XPS (spectrométrie photoélectronique X) sur les électrodes post-mortem de piles arrêtées aux potentiels déterminés par impédance, a permis de caractériser les composés chimiques formés à la surface des électrodes au cours de la première réduction, mais également après plusieurs cycles de charge/déchargeIn lithium ion batteries, the commercial organic electrolytes induce difficulties in the manufacturing and the use of the battery (volatile and flammable components). There are active research to eliminate these safety problems, one of the approach is the replacement of conventional battery electrolytes with room temperature ionic liquids (RTILs), which exhibit negligible vapor pressure, low flammability, high flash point. The use of ILs based electrolytes for carbon based electrodes requires presence of organic additive for improving the cyclic performance. The aim of this thesis was to determine the exact role of the organic additive through experimental and computer simulation methodologies. Its impact onto the solvation and transportation of lithium cation was investigated through {1H-7Li}, {1H-19F} NOE correlations (HOESY), and pulsed field gradient spin-echo (PGSE) NMR experiences and Molecular Dynamic simulation. The electrochemical studies were developed such as electrochemical window, galvanostatic cycling with potential limitation and cycling voltammetry showing the obtained capacity of the cell and [Li+] insertion stages during the first reduction step. Moreover, the electrochemical impedance spectroscopy (EIS) during the first reduction process, and XPS analysis of post mortem Gr electrodes stopped at chosen potential during the first reduction process, as well as, after the several charge/discharge cycles were use

    Africa in Global Politics After 1960 Reflections of the observer

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    National Conference: “Does Africa Need New Borders? International Relations in Africa in the Context of Separatisms in the Region”

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    Exhibition: “Blue Mirages. The World of the Tuareg”. Adam Rybinski’s Collection

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