Medication-Related Osteonecrosis of the Jaw: New Insights into Molecular Mechanisms and Cellular Therapeutic Approaches

peer reviewedIn recent years, medication-related osteonecrosis of the jaw (MRONJ) became an arising disease due to the important antiresorptive drug prescriptions to treat oncologic and osteoporotic patients, as well as the use of new antiangiogenic drugs such as VEGF antagonist. So far, MRONJ physiopathogenesis still remains unclear. Aiming to better understand MRONJ physiopathology, the first objective of this review would be to highlight major molecular mechanisms that are known to be involved in bone formation and remodeling. Recent development in MRONJ pharmacological treatments showed good results; however, those treatments are not curative and could have major side effects. In parallel to pharmacological treatments, MSC grafts appeared to be beneficial in the treatment of MRONJ, in multiple aspects: (1) recruitment and stimulation of local or regional endogenous cells to differentiate into osteoblasts and thus bone formation, (2) beneficial impact on bone remodeling, and (3) immune-modulatory properties that decrease inflammation. In this context, the second objective of this manuscript would be to summarize the molecular regulatory events controlling osteogenic differentiation, bone remodeling, and osteoimmunology and potential beneficial effects of MSC related to those aspects, in order to apprehend MRONJ and to develop new therapeutic approaches

Modes de Kovásznay dans la stabilité d'écoulements d'ablation en fusion par confinement inertiel

Une approche possible pour l'étude de la stabilité d'écoulements d'ablation en fusion par confinement inertiel consiste à considérer les solutions exactes autosemblables de l'hydrodynamique avec conduction thermique non linéaire pour des gaz parfaits en milieu semi-infini. Ces solutions autosemblables et leurs perturbations sont calculées à l'aide d'une méthode spectrale de Tchebyshev multidomaine avec adaptation dynamique de maillage. Pour des non-uniformités du flux laser, nous obtenons les évolutions spatio-temporelles des perturbations de l'écoulement pour une large gamme de nombres d'onde. Ici nous poursuivons cette approche en analysant les perturbations à l'aide des modes de Kov\'asznay. Ainsi, dans un premier temps, l'équation exacte de propagation des perturbations acoustiques a été établie, puis des équations de propagation approchées pour chaque zone de l'écoulement sont obtenues après une analyse des termes sources

Glioma Stem Cells in Pediatric High-Grade Gliomas: From Current Knowledge to Future Perspectives.

In children, high-grade gliomas (HGG) and diffuse midline gliomas (DMG) account for a high proportion of death due to cancer. Glioma stem cells (GSCs) are tumor cells in a specific state defined by a tumor-initiating capacity following serial transplantation, self-renewal, and an ability to recapitulate tumor heterogeneity. Their presence was demonstrated several decades ago in adult glioblastoma (GBM), and more recently in pediatric HGG and DMG. In adults, we and others have previously suggested that GSCs nest into the subventricular zone (SVZ), a neurogenic niche, where, among others, they find shelter from therapy. Both bench and bedside evidence strongly indicate a role for the GSCs and the SVZ in GBM progression, fostering the development of innovative targeting treatments. Such new therapeutic approaches are of particular interest in infants, in whom standard therapies are often limited due to the risk of late effects. The aim of this review is to describe current knowledge about GSCs in pediatric HGG and DMG, i.e., their characterization, the models that apply to their development and maintenance, the specific signaling pathways that may underlie their activity, and their specific interactions with neurogenic niches. Finally, we will discuss the clinical relevance of these observations and the therapeutic advantages of targeting the SVZ and/or the GSCs in infants

L'étude du récepteur ACKR3/CXCR7 dans le glioblastome

After validation of ACKR3 staining by using U87-ACKR3 cell line, we showed that ACKR3 expression was very low in patients GBM stem-like cells. However we detect the receptor on GBM patient tissue, where it appears distributed in various cell subtypes. Both public transcriptomic datasets of GBM and results that we have obtained have revealed that ACKR3 is expressed in tumor cells in situ, but also in cells from the surrounding tumor microenvironment. Morever, ACKR3 expression pattern varies in different regions of a tumor, and between different patients. The role of ACKR3 in GBM growth might be more subtle than expected, and likely involves malignant GBM cells as well as their microenvironment. The role of CXCR4 together with ACKR3 also deserves deep investigation

Comprehensive profiling of stem-like features in pediatric glioma cell cultures and their relation to the subventricular zone

peer reviewe

Patient-Oriented Perspective on Chemokine Receptor Expression and Function in Glioma.

peer reviewedGliomas are severe brain malignancies, with glioblastoma (GBM) being the most aggressive one. Despite continuous efforts for improvement of existing therapies, overall survival remains poor. Over the last years, the implication of chemokines and their receptors in GBM development and progression has become more evident. Recently, large amounts of clinical data have been made available, prompting us to investigate chemokine receptors in GBM from a still-unexplored patient-oriented perspective. This study aims to highlight and discuss the involvement of chemokine receptors-CCR1, CCR5, CCR6, CCR10, CX3CR1, CXCR2, CXCR4, ACKR1, ACKR2, and ACKR3-most abundantly expressed in glioma patients based on the analysis of publicly available clinical datasets. Given the strong intratumoral heterogeneity characterizing gliomas and especially GBM, receptor expression was investigated by glioma molecular groups, by brain region distribution, emphasizing tissue-specific receptor functions, and by cell type enrichment. Our study constitutes a clinically relevant and patient-oriented guide that recapitulates the expression profile and the complex roles of chemokine receptors within the highly diversified glioma landscape. Additionally, it strengthens the importance of patient-derived material for development and precise amelioration of chemokine receptor-targeting therapies

Machine learning techniques to characterize functional traits of plankton from image data

Plankton imaging systems supported by automated classification and analysis have improved ecologists' ability to observe aquatic ecosystems. Today, we are on the cusp of reliably tracking plankton populations with a suite of lab-based and in situ tools, collecting imaging data at unprecedentedly fine spatial and temporal scales. But these data have potential well beyond examining the abundances of different taxa; the individual images themselves contain a wealth of information on functional traits. Here, we outline traits that could be measured from image data, suggest machine learning and computer vision approaches to extract functional trait information from the images, and discuss promising avenues for novel studies. The approaches we discuss are data agnostic and are broadly applicable to imagery of other aquatic or terrestrial organisms

Modes de Kovásznay pour l'étude de la stabilité linéaire d'écoulements d'ablation autosemblables

Une approche possible pour l étude de la stabilité d écoulements d ablation en fusion par confinement inertiel consiste à considérer les solutions autosemblables de l hydrodynamique avec conduction thermique non linéaire pour des gaz parfaits en milieu semi-infini. Ces solutions et leurs perturbations sont calculées à l aide de méthodes spectrales multidomaines avec adaptation dynamique de maillage. Pour des non-uniformités du flux laser, il est montré que le maximum d amplitude des perturbations dépend fortement de la compressibilité. Des couplages entre les modes de Kovásznay sont identifiés et des équations d évolution sont déterminées pour chaque zone de l écoulement d ablation. Une comparaison avec des résultats expérimentaux d écoulements soumis à des perturbations de type rugosité est ensuite amorcéePARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

How do “Young-old” Adults Project their Self? A Study of Self-defining Future Projections in Normal Ageing

International audienceBackground: Self-defining future projections (SDFP) are mental representations of plausible and highly significant future events that provide core information of one’s understanding of self. Objective: We explored SDFPs in a large sample of older adults and aimed to target the interrelations between the main dimensions of SDFPs. Moreover, correlations between these dimensions and clinical and cognitive variables were examined. Methods: We recruited 87 young-old adults (60-75 years) with normal cognitive functioning who were asked to generate three SDFPs. Results: We found integrative meaning as a salient dimension and older individuals preferentially generated projections containing leisure or relationship events. Anxiety and self-esteem were correlated with integrative meaning and high executive functioning was found to be protective towards the simulation of future events containing dependence and death or end-of-life events. Conclusion: This study will contribute to the understanding of personal goals and identity in normal ageing

Exploring Characteristics of Self-Defining Memories in Older Adults

International audienceThe aim of this descriptive study was to investigate the Self-Defining Memories (SDMs) in a large sample of 181 older adults (65–90 years; mean age = 73.0 years) and to target the relationships between their different dimensions. The sampling method was nonprobabilistic, based on voluntary participation. Participants were asked to recall three SDMs. They also completed the Mini-Mental State Examination, the Hospital Anxiety and Depression Scale, and a Self-esteem Scale. Almost half of the SDMs were specific and more than a quarter were integrated. Specificity, tension, redemption, contamination sequences, and affective response varied regarding thematic content. Specificity was positively correlated to tension whereas autobiographical reasoning was positively correlated to redemption and negatively linked to emotional response and depression. This research highlighted that identity is constituted by the main types of events that make up a life: interpersonal relationships, life-threatening events, achievement, and leisure