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5 results on '"LUNAM Université, F-49933 Angers, France"'

1. Circulating PCSK9 levels are not associated with the severity of hepatic steatosis and NASH in a high-risk population

Author

Bertrand Cariou, Odile Blanchet, Matthieu Wargny, Sarra Smati, L. Arnaud, Matthieu Pichelin, Benjamin Bouillet, Luc Van Gaal, Sven Francque, Philippe Lefebvre, Jean-Michel Petit, Jérôme Boursier, Pierre-Henri Ducluzeau, Cédric Le May, Bart Staels, Adrien Lannes, Bruno Vergès, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Endocrinologie (CHRU Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Bourgogne Franche-Comté [COMUE] (UBFC), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Service d'Endocrinologie, Diabétologie et Maladies Métaboliques (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Département d'hépatologie (CHU Angers), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre de Ressources Biologiques [CHU d'Angers] (CRB CHU d'Angers BB-0033-00038), Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Gastroenterology and Hepatology (Antwerp University Hospital), Antwerp University Hospital [Edegem] (UZA), Department of Endocrinology, Diabetology and Metabolism (Antwerp University Hospital), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), LUNAM Université, F-49933 Angers, France, Plateforme PACeM (Plateforme d'Analyse Cellulaire et Moléculaire), SFR ICAT4208, F-49933 Angers, France., PACeM Angers, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Unité de recherche de l'institut du thorax (ITX-lab), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Plateforme d'Analyse Cellulaire et Moléculaire [SFR ICAT - UA] (PACEM), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Université d'Angers (UA)-Université d'Angers (UA), ANR-16-RHUS-0007,CHOPIN,CHOPIN(2016), and Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, Male, Biopsy, Liver steatosis, Type 2 diabetes, 030204 cardiovascular system & hematology, Gastroenterology, Severity of Illness Index, PCSK9, 0302 clinical medicine, Fibrosis, Non-alcoholic Fatty Liver Disease, LDL-cholesterol, ComputingMilieux_MISCELLANEOUS, education.field_of_study, medicine.diagnostic_test, Middle Aged, Liver biopsy, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Magnetic Resonance Imaging, 3. Good health, Liver, Female, France, Proprotein Convertase 9, Cardiology and Cardiovascular Medicine, MRI, Adult, Risk, medicine.medical_specialty, Population, Liver fibrosis, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, education, Aged, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatology, medicine.disease, Fatty Liver, 030104 developmental biology, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Linear Models, Human medicine, Steatosis, Steatohepatitis, business
Abstract

Background and aims: Some studies suggested that proprotein convertase subtilisin kexin type 9 (PCSK9) is linked to liver steatosis severity and non-alcoholic steatohepatitis (NASH). We aimed to assess whether circulating PCSK9 levels are associated with either liver fat content (LFC) or histological markers of NASH in high-risk patients. Methods: We present results from three cross-sectional studies from two French Hospitals: Dijon and Numevox (departments of Endocrinology) and Angers (department of Hepatology). Only patients without lipid-lowering therapy were included. All 132 patients had type 2 diabetes in Dijon, compared to 55/224 in Numevox (25%) and 39/122 in Angers (32%). LFC was assessed on MRI (Dijon and Numevox), and NASH lesion on liver biopsy (Angers). Additionally, we included mRNA results from 138 overweight patients of a Belgian Hospital (Antwerp). Results: While circulating levels of PCSK9 were positively correlated with total cholesterol, LDL-C, triglycerides and non-HDL-C in all 3 cohorts, no significant association was found between PCSK9 and transaminases. Furthermore, no association was found between plasma PCSK9 levels and LFC in both Numevox (beta(adjusted) = 0.71 +/- 1.33, p = 0.60) and Dijon (beta(adjusted) = 1.03 +/- 0.90, p = 0.25). There was no correlation between circulating PCSK9 and histological liver lesions: steatosis severity (beta(adjusted) = -3.95 +/- 2.75, p = 0.15), NASH activity score (beta(adjusted) = -0.31 +/- 0.17, p = 0.082), lobular (beta = -0.067 +/- 0.055, p = 0.22) or portal inflammation (beta = -0.088 +/- 0.079, p = 0.27), ballooning (beta = -0.025 +/- 0.065, p = 0.70) and fibrosis (beta = -0.17 +/- 0.11, p = 0.12). Finally, hepatic PCSK9 mRNA levels were not correlated with NASH histological severity. Conclusions: Circulating PCSK9 concentrations are not associated with the severity of liver steatosis or histological markers of NASH. These data are reassuring regarding the clinical use of PCSK9 inhibitors in cardiovascular diseases.

Published
2018
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2. Effects of mesenchymal stem cell therapy, in association with pharmacologically active microcarriers releasing VEGF, in an ischaemic stroke model in the rat

Author

Jérôme Cayon, Didier Divoux, Simon Roussel, Omar Touzani, Léna Marteau, Myriam Lecocq, Jérôme Toutain, Claudia N. Montero-Menei, Marie-Sophie Quittet, Fabien Fillesoye, Laurence Sindji, Myriam Bernaudin, Hypoxie, physiopathologies cérébrovasculaire et tumorale (CERVOxy), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Micro et Nanomédecines Biomimétiques (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL), Plateforme d'Analyse Cellulaire et Moléculaire [SFR ICAT - UA] (PACEM), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Université d'Angers (UA)-Université d'Angers (UA), LUNAM Université, F-49933 Angers, France, Plateforme PACeM (Plateforme d'Analyse Cellulaire et Moléculaire), SFR ICAT4208, F-49933 Angers, France., and PACeM Angers

Subjects
Doublecortin Domain Proteins, Male, Vascular Endothelial Growth Factor A, Angiogenesis, [SDV]Life Sciences [q-bio], Biochemistry, Brain Ischemia, Rats, Sprague-Dawley, chemistry.chemical_compound, 0302 clinical medicine, Medicine, Stroke, 0303 health sciences, Drug Carriers, Behavior, Animal, Infarction, Middle Cerebral Artery, General Medicine, VEGF, Magnetic Resonance Imaging, Vascular endothelial growth factor, Pharmacologically active microcarriers, Treatment Outcome, medicine.symptom, Microtubule-Associated Proteins, Biotechnology, medicine.medical_specialty, Biomedical Engineering, Context (language use), Brain damage, Mesenchymal Stem Cell Transplantation, Biomaterials, 03 medical and health sciences, In vivo, parasitic diseases, Animals, Molecular Biology, 030304 developmental biology, business.industry, Mesenchymal stem cell, Neuropeptides, Mesenchymal Stem Cells, Recovery of Function, Hypoxia (medical), medicine.disease, Surgery, Disease Models, Animal, chemistry, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Cancer research, Blood Vessels, Laminin, business, 030217 neurology & neurosurgery
Abstract

CERVOXY; International audience; Few effective therapeutic interventions are available to limit brain damage and functional deficits after ischaemic stroke. Within this context, mesenchymal stem cell (MSC) therapy carries minimal risks while remaining efficacious through the secretion of trophic, protective, neurogenic and angiogenic factors. The limited survival rate of MSCs restricts their beneficial effects. The usefulness of a three-dimensional support, such as a pharmacologically active microcarrier (PAM), on the survival of MSCs during hypoxia has been shown in vitro, especially when the PAMs were loaded with vascular endothelial growth factor (VEGF). In the present study, the effect of MSCs attached to laminin-PAMs (LM-PAMs), releasing VEGF or not, was evaluated in vivo in a model of transient stroke. The parameters assessed were infarct volume, functional recovery and endogenous cellular reactions. LM-PAMs induced the expression of neuronal markers by MSCs both in vitro and in vivo. Moreover, the prolonged release of VEGF increased angiogenesis around the site of implantation of the LM-PAMs and facilitated the migration of immature neurons towards the ischaemic tissue. Nonetheless, MSCs/LM-PAMs-VEGF failed to improve sensorimotor functions. The use of LM-PAMs to convey MSCs and to deliver growth factors could be an effective strategy to repair the brain damage caused by a stroke.

Published
2014
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3. Demonstration of the interactions between aromatic compound-loaded lipid nanocapsules and Acinetobacter baumannii bacterial membrane.

Author

Montagu A, Joly-Guillou ML, Guillet C, Bejaud J, Rossines E, and Saulnier P

Subjects
Acinetobacter Infections drug therapy, Acrolein administration & dosage, Acrolein pharmacology, Anti-Bacterial Agents administration & dosage, Anti-Bacterial Agents pharmacology, Carbonyl Cyanide m-Chlorophenyl Hydrazone metabolism, Cymenes, Lipids chemistry, Monoterpenes pharmacology, Nanocapsules, Acinetobacter baumannii drug effects, Acrolein analogs & derivatives, Carbocyanines chemistry, Monoterpenes administration & dosage
Abstract

Acinetobacter baumannii is an important nosocomial pathogen that is resistant to many commonly-used antibiotics. One strategy for treatment is the use of aromatic compounds (carvacrol, cinnamaldehyde) against A. baumannii. The aim of this study was to determine the interactions between bacteria and lipid nanocapsules (LNCs) over time based on the fluorescence of 3,3'-Dioctadecyloxacarbocyanine Perchlorate-LNCs (DiO-LNCs) and the properties of trypan blue to analyse the physicochemical mechanisms occurring at the level of the biological membrane. The results demonstrated the capacity of carvacrol-loaded LNCs to interact with and penetrate the bacterial membrane in comparison with cinnamaldehyde-loaded LNCs and unloaded LNCs. Modifications of carvacrol after substitution of hydroxyl functional groups by fatty acids demonstrated the crucial role of hydroxyl functions in antibacterial activity. Finally, after contact with the efflux pump inhibitor, carbonylcyanide-3-chlorophenyl hydrazine (CCCP), the results indicated the total synergistic antibacterial effect with Car-LNCs, showing that CCCP is associated with the action mechanism of carvacrol, especially at the level of the efflux pump mechanism., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Published
2016
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4. Effects of mesenchymal stem cell therapy, in association with pharmacologically active microcarriers releasing VEGF, in an ischaemic stroke model in the rat.

Author

Quittet MS, Touzani O, Sindji L, Cayon J, Fillesoye F, Toutain J, Divoux D, Marteau L, Lecocq M, Roussel S, Montero-Menei CN, and Bernaudin M

Subjects
Animals, Behavior, Animal, Blood Vessels drug effects, Brain Ischemia physiopathology, Disease Models, Animal, Doublecortin Domain Proteins, Infarction, Middle Cerebral Artery complications, Infarction, Middle Cerebral Artery pathology, Laminin pharmacology, Magnetic Resonance Imaging, Male, Mesenchymal Stem Cells drug effects, Microtubule-Associated Proteins metabolism, Neuropeptides metabolism, Rats, Sprague-Dawley, Recovery of Function drug effects, Stroke physiopathology, Treatment Outcome, Vascular Endothelial Growth Factor A pharmacology, Brain Ischemia complications, Drug Carriers chemistry, Mesenchymal Stem Cell Transplantation, Mesenchymal Stem Cells cytology, Stroke drug therapy, Stroke etiology, Vascular Endothelial Growth Factor A therapeutic use
Abstract

Few effective therapeutic interventions are available to limit brain damage and functional deficits after ischaemic stroke. Within this context, mesenchymal stem cell (MSC) therapy carries minimal risks while remaining efficacious through the secretion of trophic, protective, neurogenic and angiogenic factors. The limited survival rate of MSCs restricts their beneficial effects. The usefulness of a three-dimensional support, such as a pharmacologically active microcarrier (PAM), on the survival of MSCs during hypoxia has been shown in vitro, especially when the PAMs were loaded with vascular endothelial growth factor (VEGF). In the present study, the effect of MSCs attached to laminin-PAMs (LM-PAMs), releasing VEGF or not, was evaluated in vivo in a model of transient stroke. The parameters assessed were infarct volume, functional recovery and endogenous cellular reactions. LM-PAMs induced the expression of neuronal markers by MSCs both in vitro and in vivo. Moreover, the prolonged release of VEGF increased angiogenesis around the site of implantation of the LM-PAMs and facilitated the migration of immature neurons towards the ischaemic tissue. Nonetheless, MSCs/LM-PAMs-VEGF failed to improve sensorimotor functions. The use of LM-PAMs to convey MSCs and to deliver growth factors could be an effective strategy to repair the brain damage caused by a stroke., (Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Published
2015
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5. A review of the current status of siRNA nanomedicines in the treatment of cancer.

Author

Resnier P, Montier T, Mathieu V, Benoit JP, and Passirani C

Subjects
Animals, Genetic Therapy, Humans, Neoplasms genetics, Neoplasms metabolism, RNA Interference, RNA, Small Interfering genetics, Drug Delivery Systems methods, Neoplasms therapy, RNA, Small Interfering administration & dosage, RNA, Small Interfering therapeutic use
Abstract

RNA interference currently offers new opportunities for gene therapy by the specific extinction of targeted gene(s) in cancer diseases. However, the main challenge for nucleic acid delivery still remains its efficacy through intravenous administration. Over the last decade, many delivery systems have been developed and optimized to encapsulate siRNA and to specifically promote their delivery into tumor cells and improve their pharmacokinetics for anti-cancer purposes. This review aims to sum up the potential targets in numerous pathways and the properties of recently optimized siRNA synthetic nanomedicines with their preclinical applications and efficacy. Future perspectives in cancer treatment are discussed including promising concomitant treatment with chemotherapies or other siRNA. The outcomes in human clinical trials are also presented., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Published
2013
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