Personne : Asselin, Jérémie
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Université Laval. Département de chimie
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- PublicationRestreintCarbonic anhydrase XII in valve interstitial cells promotes the regression of calcific aortic valve stenosis.(Academic Press Inc, Ltd., 2016-03-11) Lachance, Dominic.; Bouchareb, Rihab; Asselin, Jérémie; Boudreau, Denis; Marette, André; Boulanger, Marie-Chloé; Le Quang, Khai; Côté, Nancy.; Bossé, Yohan; Shayhidin, Elnur Elyar; Messaddeq, Younès; El Husseini, Diala; Mahmut, Ablajan; Pibarot, Philippe; Hadji, Fayez; Mathieu, PatrickAims: Calcific aortic valve stenosis (CAVS) is the most common heart valve disease. In the present work we sought to determine the reversibility of mineralization in the aortic valve. Methods and results: By using in vitro analyses we found that valve interstitial cells (VICs) have the ability to resorb minerals. We documented that agonist of P2Y2 receptor (P2Y2R) promoted the expression of carbonic anhydrase XII (CAXII) at the cell membrane of VICs, whereby minerals are resorbed. P2Y2R-mediated mineral resorption was corroborated by using mouse VICs isolated from wild type and P2Y2R-/- mice. Measurements of extracellular pH (pHe) by using core–shell nanosensors revealed that P2Y2R-mediated CAXII export to the cell membrane led to an acidification of extracellular space, whereby minerals are resorbed. In vivo, we next treated LDLR-/-/ApoB100/100/IGF2 mice, which had developed CAVS under a high-fat/high-sucrose diet for 8 months, with 2-thioUTP (a P2Y2R agonist) or saline for the next 2 months. The administration of 2-thioUTP (2 mg/kg/day i.p.) reduced the mineral volume in the aortic valve measured with serial microCT analyses, which improved hemodynamics and reduced left ventricular hypertrophy (LVH). Examination of leaflets at necropsy confirmed a lower level of mineralization and fibrosis along with higher levels of CAXII in mice under 2-thioUTP. In another series of experiment, the administration of acetazolamide (a CA inhibitor) prevented the acidification of leaflets and the regression of CAVS induced by 2-thioUTP in LDLR-/-/ApoB100/100/IGF2 mice. Conclusion: P2Y2R-mediated expression of CAXII by VICs acidifies the extracellular space and promotes the regression of CAVS.
- PublicationRestreintCorrelating metal-enhanced fluorescence and sructural properties in Ag@SiO2 core-shell nanoparticles(Springer Science + Business Media, 2016-03-12) Asselin, Jérémie; Legros, Philippe; Boudreau, Denis; Grégoire, AlexandreMetal@silica concentric nanoparticles capable of metal-enhanced fluorescence (MEF) represent a powerful means to improve the brightness and stability of encapsulated organic fluorophores and are finding numerous applications in biology, analytical chemistry, and medical diagnostics. The rational design of MEF-enabled labels and sensors often involves comparing fluorescence enhancement factors (EF) between nanostructures having different structural properties (e.g., metal core diameter, silica shell thickness, extent of spectral overlap between plasmon band and fluorophore). Accurate determination of EFs requires the measurement of fluorescence emission intensity in the presence and absence of the plasmonic core while minimizing the impact of physical and chemical artifacts (e.g., signal variations due to scattering, adsorption, sedimentation). In this work, Ag@SiO2@SiO2¿+¿x (where x is fluorescein, eosin, or rhodamine B) nanostructures were synthesized with excellent control of core size, silica spacer shell thickness and fluorophore concentration. Using UV-VIS spectrometry, spectrofluorimetry, time-resolved fluorometry, and transmission electron microscopy, we investigated the influence of these key structural factors on fluorescence emission intensity, and the results were used to develop a generalized methodology for the determination of fluorescence enhancement factors in Ag@SiO2 core-shell nanoparticles. This methodology should be of general importance to designing MEF-enabled nanostructures, sensors, and related analytical techniques.
- PublicationAccès libreA ratiometric nanoarchitecture for the simultaneous detection of pH and halide ions using UV plasmon-enhanced fluorescence(Royal Society of Chemistry, 2016-12-15) Asselin, Jérémie; Boudreau, Denis; Fontaine, Nicolas; Lambert, Marie-PierIn this work, we designed a ratiometric core–shell nanoarchitecture composed of an indium UV plasmonic core, an internal reference (rhodamine B), a pH-sensitive probe (fluorescein), and a halide ion sensor (6-methoxyquinolinium). Immobilizing the fluorophores in distinct silica layers at precise distances from the core modulates the plasmon coupling and tunes the linear concentration range of halide ion detection.
- PublicationAccès libreThinking outside the shell : novel sensors designed from plasmon-enhanced fluorescent concentric nanoparticles(Cambridge Royal Society of Chemistry, 2020-08-20) Asselin, Jérémie; Picard-Lafond, Audrey; Boudreau, Denis; Fontaine, NicolasThe alteration of photophysical properties of fluorophores in the vicinity of a metallic nanostructure, a phenomenon termed plasmon- or metal-enhanced fluorescence (MEF), has been investigated extensively and used in a variety of proof-of-concept demonstrations over the years. A particularly active area of development in this regard has been the design of nanostructures where fluorophore and metallic core are held in a stable geometry that imparts improved luminosity and photostability to a plethora of organic fluorophores. This minireview presents an overview of MEF-based concentric core–shell sensors developed in the past few years. These architectures expand the range of applications of nanoparticles (NPs) beyond the uses possible with fluorescent molecules. Design aspects that are being described include the influence of the nanocomposite structure on MEF, notably the dependence of fluorescence intensity and lifetime on the distance to the plasmonic core. The chemical composition of nanocomposites as a design feature is also discussed, taking as an example the use of non-noble plasmonic metals such as indium as core materials to enhance multiple fluorophores throughout the UV-Vis range and tune the sensitivity of halide-sensing fluorophores operating on the principle of collisional quenching. Finally, the paper describes how various solid substrates can be functionalized with MEF-based nanosensors to bestow them with intense and photostable pH-sensitive properties for use in fields such as medical therapy and diagnostics, dentistry, biochemistry and microfluidics.