Macrophage scavenger receptor 1 mediates lipid-induced inflammation in non-alcoholic fatty liver disease

Background & Aims: Obesity-associated inflammation is a key player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the role of macrophage scavenger receptor 1 (MSR1, CD204) remains incompletely understood. Methods: A total of 170 NAFLD liver biopsies were processed for transcriptomic analysis and correlated with clinicopathological features. Msr1(-/-) and wild-type mice were subjected to a 16-week high-fat and high-cholesterol diet. Mice and ex vivo human liver slices were treated with a monoclonal antibody against MSR1. Genetic susceptibility was assessed using genome-wide association study data from 1,483 patients with NAFLD and 430,101 participants of the UK Biobank. Results: MSR1 expression was associated with the occurrence of hepatic lipid-laden foamy macrophages and correlated with the degree of steatosis and steatohepatitis in patients with NAFLD. Mice lacking Msr1 were protected against diet-induced metabolic disorder, showing fewer hepatic foamy macrophages, less hepatic inflammation, improved dyslipidaemia and glucose tolerance, and altered hepatic lipid metabolism. Upon induction by saturated fatty acids, MSR1 induced a pro-inflammatory response via the JNK signalling pathway. In vitro blockade of the receptor prevented the accumulation of lipids in primary macrophages which inhibited the switch towards a proinflammatory phenotype and the release of cytokines such as TNF-alpha Targeting MSR1 using monoclonal antibody therapy in an obesity-associated NAFLD mouse model and human liver slices resulted in the prevention of foamy macrophage formation and inflammation. Moreover, we identified that rs41505344, a polymorphism in the upstream transcriptional region of MSR1, was associated with altered serum triglycerides and aspartate aminotransferase levels in a cohort of over 400,000 patients. Conclusions: Taken together, our data suggest that MSR1 plays a critical role in lipid-induced inflammation and could thus be a potential therapeutic target for the treatment of NAFLD. Lay summary: Non-alcoholic fatty liver disease (NAFLD) is a chronic disease primarily caused by excessive consumption of fat and sugar combined with a lack of exercise or a sedentary lifestyle. Herein, we show that the macrophage scavenger receptor MSR1, an innate immune receptor, mediates lipid uptake and accumulation in Kupffer cells, resulting in liver inflammation and thereby promoting the progression of NAFLD in humans and mice. (C) 2021 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.Peer reviewe

Genomic aberrations associated with outcome in anaplastic oligodendroglial tumors treated within the EORTC phase III trial 26951

Despite similar morphological aspects, anaplastic oligodendroglial tumors (AOTs) form a heterogeneous clinical subgroup of gliomas. The chromosome arms 1p/19q codeletion has been shown to be a relevant biomarker in AOTs and to be perfectly exclusive from EGFR amplification in gliomas. To identify new genomic regions associated with prognosis, 60 AOTs from the EORTC trial 26951 were analyzed retrospectively using BAC-array-based comparative genomic hybridization. The data were processed using a binary tree method. Thirty-three BACs with prognostic value were identified distinguishing four genomic subgroups of AOTs with different prognosis (p < 0.0001). Type I tumors (25%) were characterized by: (1) an EGFR amplification, (2) a poor prognosis, (3) a higher rate of necrosis, and (4) an older age of patients. Type II tumors (21.7%) had: (1) loss of prognostic BACs located on 1p tightly associated with 19q deletion, (2) a longer survival, (3) an oligodendroglioma phenotype, and (4) a frontal location in brain. Type III AOTs (11.7%) exhibited: (1) a deletion of prognostic BACs located on 21q, and (2) a short survival. Finally, type IV tumors (41.7%) had different genomic patterns and prognosis than type I, II and III AOTs. Multivariate analysis showed that genomic type provides additional prognostic data to clinical, imaging and pathological features. Similar results were obtained in the cohort of 45 centrally reviewed–validated cases of AOTs. Whole genome analysis appears useful to screen the numerous genomic abnormalities observed in AOTs and to propose new biomarkers particularly in the non-1p/19q codeleted AOTs

The complete genome sequence of Corynebacterium pseudotuberculosis FRC41 isolated from a 12-year-old girl with necrotizing lymphadenitis reveals insights into gene-regulatory networks contributing to virulence

Trost E, Ott L, Schneider J, et al. The complete genome sequence of Corynebacterium pseudotuberculosis FRC41 isolated from a 12-year-old girl with necrotizing lymphadenitis reveals insights into gene-regulatory networks contributing to virulence. BMC Genomics. 2010;11(1): 728

Landmarking the nerves of the deep regions of the face : surgical, radiological and physiological applications

L’Anatomie (sous-section 42-01 du Conseil National des Universités) est à la fois la plus vieille discipline scientifique et médicale, celle selon certains « où plus aucun progrès n’est à attendre », mais aussi une Science actuelle répondant aux besoins d’une médecine moderne toujours plus exigeante. Les nerfs des régions profondes de la tête illustrent bien cette thématique. Que ce soit en chirurgie maxillo-faciale et ORL, en neurologie pour l’exploration électrophysiologique des branches sensitives du nerf mandibulaire (dont l’intérêt médico-légal est réel, en particulier en stomatologie pour des interventions aussi banales que l’extraction des dents de sagesse), ou encore en imagerie, une parfaite connaissance de ces structures est indispensable aux développements qui feront l’avenir de nos disciplines cliniques. Plusieurs travaux anatomiques et anatomo-cliniques ont été réalisés autour de cette thématique, démontrant l’actualité et la vitalité de notre discipline.Anatomy (section 42-01 of the National University Council) is both the oldest scientific and medical discipline (from whom “nothing is yet to expect” according to some of our collegues), and an up-to-date science directely connected to the clinical pratice. The nerves of the deep regions of the head illustrate this theme very well. In the field of oral and maxillofacial surgery, of electrophysiological exploration of the sensitory branches of the mandibular nerve (for example in the follow-up of lingual nerve injury during wisdom teeth extraction, the first cause of juridic litigation in France for oral surgeons and dentists), or in medical imaging, an accurate knowledge of these structures is mandatory for the developments of our clinical practices. Some anatomical and anatomo-clinical studies have been designed in this field, demonstrating the actuality and vitality of our discipline

Ostéosynthèse des fractures sous-condyliennes basses mandibulaires par plaque TCP® (à propos de 20 cas)

DIJON-BU Médecine Pharmacie (212312103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Atlas de techniques chirurgicales en traumatologie maxillo-faciale

DIJON-BU Médecine Pharmacie (212312103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Prise en charge et rééducation des fractures du condyle mandibulaire de l adulte (revue bibliographique)

Les fractures du condyle mandibulaire représentent un tiers des fractures de la mandibule. Leur physiopathologie est désormais bien connue mais leur prise en charge reste sujette à discussion. L'objectif de ce travail est de présenter les différents traitements chirurgicaux et orthopédiques et de faire le point, grâce à une revue de bibliographie, sur les techniques de rééducation après fracture du condyle. L'anatomie et la physiologie de l'articulation temporo-mandibulaire sont fondamentales. Elles permettent de comprendre les signes et le retentissement des fractures du condyle. L'essentiel de la prise en charge des fractures du condyle est de savoir si le traitement doit être chirurgical ou fonctionnel pur, en sachant que plus le trait de fracture est haut, plus le traitement choisi est fonctionnel. Le traitement chirurgical est encore en plein essor avec le développement de techniques, comme l'endoscopie, qui permettent de traiter chirurgicalement des fractures, avant laissées telles quelles et/ou rééduquées. Malgré cela, la rééducation garde une place très importante dans la prise en charge des fractures du condyle. Que ce soit après un traitement chirurgical ou en traitement exclusif, les techniques de rééducation sont précises et nécessitent du personnel entrainé. L'objectif étant de retrouver des mouvements mandibulaires symétriques et sans douleur. La difficulté actuelle est le manque d'uniformisation de ces techniques qui sont propres à chaque service de chirurgie maxillo-faciale en fonction de leur formation originelle et il est donc impossible de comparer les prises en charge, tant sur le plan des techniques chirurgicales que sur les protocoles de rééducation.ROUEN-BU Médecine-Pharmacie (765402102) / SudocSudocFranceF

Comments about the article “A Crouzon syndrome from the classic period of Maya civilization?” The art historian’s point of view

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Management of patients with inherited bleeding disorders in oral surgery: A 13-year experience

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