Octyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways

The presence of heterogeneity in responses to oncolytic virotherapy poses a barrier to clinical effectiveness, as resistance to this treatment can occur through the inhibition of viral spread within the tumor, potentially leading to treatment failures. Here we show that 4-octyl itaconate (4-OI), a chemical derivative of the Krebs cycle-derived metabolite itaconate, enhances oncolytic virotherapy with VSVΔ51 in various models including human and murine resistant cancer cell lines, three-dimensional (3D) patient-derived colon tumoroids and organotypic brain tumor slices. Furthermore, 4-OI in combination with VSVΔ51 improves therapeutic outcomes in a resistant murine colon tumor model. Mechanistically, we find that 4-OI suppresses antiviral immunity in cancer cells through the modification of cysteine residues in MAVS and IKKβ independently of the NRF2/KEAP1 axis. We propose that the combination of a metabolite-derived drug with an oncolytic virus agent can greatly improve anticancer therapeutic outcomes by direct interference with the type I IFN and NF-κB-mediated antiviral responses.</p

Octyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways

The presence of heterogeneity in responses to oncolytic virotherapy poses a barrier to clinical effectiveness, as resistance to this treatment can occur through the inhibition of viral spread within the tumor, potentially leading to treatment failures. Here we show that 4-octyl itaconate (4-OI), a chemical derivative of the Krebs cycle-derived metabolite itaconate, enhances oncolytic virotherapy with VSVΔ51 in various models including human and murine resistant cancer cell lines, three-dimensional (3D) patient-derived colon tumoroids and organotypic brain tumor slices. Furthermore, 4-OI in combination with VSVΔ51 improves therapeutic outcomes in a resistant murine colon tumor model. Mechanistically, we find that 4-OI suppresses antiviral immunity in cancer cells through the modification of cysteine residues in MAVS and IKKβ independently of the NRF2/KEAP1 axis. We propose that the combination of a metabolite-derived drug with an oncolytic virus agent can greatly improve anticancer therapeutic outcomes by direct interference with the type I IFN and NF-κB-mediated antiviral responses.</p

Contribution à une méthodologie d'analyse de la cohérence entre les objectifs de conception et d'exploitation d'un système de production

L'objectif du présent mémoire est d'apporter une contribution à l'analyse de la cohérence entre les objectifs de conception d'un système de production et les objectifs d'exploitation qui lui seront assignés ultérieurement. Pour ce faire, nous proposons, dans un premier temps, un modèle de référence pour l'expression de la performance associée aux choix de conception. Dans un deuxième temps, en utilisant le concept de Processus Générique, nous construisons un modèle GRAI qui permet de traduire les performances de conception en performances opérationnelles. L'un des critères choisis est la flexibilité décisionnelle. Enfin, à partir des concepts présentés, nous élaborons une démarche d'analyse de la cohérence entre objectifs de conception et objectifs d'exploitation, démarche qui s'inscrit plus largement dans GRAI Evolution Methodology, méthode dédiée à la gestion de l'évolution du système de production.BORDEAUX1-BU Sciences-Talence (335222101) / SudocSudocFranceF

Big data and predictive analytics in neurocritical care

To describe predictive data and workflow in the intensive care unit when managing neurologically ill patients. In the era of Big Data in medicine, intensive critical care units are data-rich environments. Neurocritical care adds another layer of data with advanced multimodal monitoring to prevent secondary brain injury from ischemia, tissue hypoxia, and a cascade of ongoing metabolic events. A step closer toward personalized medicine is the application of multimodal monitoring of cerebral hemodynamics, bran oxygenation, brain metabolism, and electrophysiologic indices, all of which have complex and dynamic interactions. These data are acquired and visualized using different tools and monitors facing multiple challenges toward the goal of the optimal decision support system. In this review, we highlight some of the predictive data used to diagnose, treat, and prognosticate the neurologically ill patients. We describe information management in neurocritical care units including data acquisition, wrangling, analysis, and visualization

Contribution à la définition d'une démarche de conception de multimatériaux (application à la mise en oeuvre d'un réservoir permettant le déconfinement de matières énergétiques)

Cette étude contribue à la définition d'une démarche de conception de multimatériaux d'une part en s'inspirant des méthodes de conception de produits manufacturés, et d'autre part en confrontant la démarche à une étude de cas. Le travail a consisté en une étude bibliographique des méthodes de conception les plus répandues pour en dégager des principes généraux applicables à une démarche de conception de multimatériaux. L'application de certains aspects de ces principes au cas d'un réservoir permettant le déconfinement de matières énergétiques a conduit à la conception d'une paroi multicouche renforcée par un filet de fibres de polyéthylène. Des essais de traction et de fluage à diverses températures ont permis la caractérisation thermomécanique des constituants nécessaire au dimensionnement et à la simulation du comportement de la structure. Enfin, la dernière étape a résidé dans la fabrication d'un réservoir cylindrique adapté à la vérification expérimentale de ses fonctions.BORDEAUX1-BU Sciences-Talence (335222101) / SudocSudocFranceF

Cell and tissue manipulation with ultrashort infrared laser pulses in light-sheet microscopy

Three-dimensional live imaging has become an indispensable technique in the fields of cell, developmental and neural biology. Precise spatio-temporal manipulation of biological entities is often required for a deeper functional understanding of the underlying biological process. Here we present a home-built integrated framework and optical design that combines three-dimensional light-sheet imaging over time with precise spatio-temporal optical manipulations induced by short infrared laser pulses. We demonstrate their potential for sub-cellular ablation of neurons and nuclei, tissue cauterization and optogenetics by using the Drosophila melanogaster and zebrafish model systems

Cell and tissue manipulation with ultrashort infrared laser pulses in light-sheet microscopy

International audienceThree-dimensional live imaging has become an indispensable technique in the fields of cell, developmental and neural biology. Precise spatio-temporal manipulation of biological entities is often required for a deeper functional understanding of the underlying biological process. Here we present a home-built integrated framework and optical design that combines three-dimensional light-sheet imaging over time with precise spatio-temporal optical manipulations induced by short infrared laser pulses. We demonstrate their potential for sub-cellular ablation of neurons and nuclei, tissue cauterization and optogenetics by using the Drosophila melanogaster and zebrafish model systems