2021

Nous avons le plaisir d'accueillir de nouveaux arrivants au sein de l'équipe de recherche :

- Jérémie Gouyon, MCU, Thématique de recherche : Caractérisation de nanoparticules et développement de méthodes analytiques

- Franceline REYNAUD, ATER en Pharmacie galénique, Thématique de recherche : Complexation de particules lipidiques avec l'ADN

- Diego Mauricio RAMOS, ATER en pharmacie galénique, Thématique de recherche : Emulsions lipidiques

 

Nous leur souhaitons la bienvenue.

Un article intitulé "Rubella epidemiology in the Central African Republic, 2015-2016 and molecular characterization of virus strains from 2008-2016" vient de paraître dans "International Journal of Infectious Diseases".

Auteurs : M. S. Pagonendji, I.Gouandkika-Vasilache, E. Charpentier, A. Sausy, A. Le Faou, R.E. Duval, J. M. Hübschen

Int J Infect Dis. 2021 Aug 24;S1201-9712(21)00684-6. doi: 10.1016/j.ijid.2021.08.050.

Abstract :

Objectives: Rubella cases in the Central African Republic (CAF) are currently identified during measles surveillance. This study aimed to investigate rubella epidemiology between 2015 and 2016 and to provide baseline genotype data for monitoring future rubella control efforts.

Methods: 831 measles IgM negative or equivocal sera from 2015/2016 were tested for rubella IgM antibodies and 350 rubella IgM positive sera collected between 2008 and 2016 were selected for PCR and sequencing.

Results: 411 of the 831 sera (49.5%) were rubella IgM positive and most cases (n=391, 95.1%) occurred between January and April. Most patients were between 5 and 9 years old (50.2%) and more than half of the rubella cases (56.7%) originated from the capital Bangui. Genotype information was obtained for 37 of the 350 selected rubella IgM-positive specimens, with the majority of the patients originating from Bangui (n=24, 64.9%) and sequences covering all years except 2009. Phylogenetic analysis identified genotypes 1E (n=12), 1G (n=5) and 2B (n=20), with 2B being detected from 2014 onwards.

Conclusions: Our study confirmed the important role of rubella as rash and fever disease in CAF and provided comprehensive data on rubella epidemiology and first information on rubella genotypes in the country.

Un article intitulé "Targeting the Angiotensin II Type 1 Receptor in Cerebrovascular Diseases: Biased Signaling Raises New Hopes" vient d'être publié dans l'issue spéciale "Molecular Vascular Physiology" du journal "International Journal of Molecular Sciences".

Auteurs : Céline Delaitre, Michel Boisbrun, Sandra Lecat, François Dupuis

Int. J. Mol. Sci. 2021, 22(13), 6738; https://doi.org/10.3390/ijms22136738

 

Abstract :

The physiological and pathophysiological relevance of the angiotensin II type 1 (AT1) G protein-coupled receptor no longer needs to be proven in the cardiovascular system. The renin–angiotensin system and the AT1 receptor are the targets of several classes of therapeutics (such as angiotensin converting enzyme inhibitors or angiotensin receptor blockers, ARBs) used as first-line treatments in cardiovascular diseases. The importance of AT1 in the regulation of the cerebrovascular system is also acknowledged. However, despite numerous beneficial effects in preclinical experiments, ARBs do not induce satisfactory curative results in clinical stroke studies. A better understanding of AT1 signaling and the development of biased AT1 agonists, able to selectively activate the β-arrestin transduction pathway rather than the Gq pathway, have led to new therapeutic strategies to target detrimental effects of AT1 activation. In this paper, we review the involvement of AT1 in cerebrovascular diseases as well as recent advances in the understanding of its molecular dynamics and biased or non-biased signaling. We also describe why these alternative signaling pathways induced by β-arrestin biased AT1 agonists could be considered as new therapeutic avenues for cerebrovascular diseases.

Un article intitulé " Electrically Switchable Nanolever Technology for the Screening of Metal-Chelating Peptides in Hydrolysates" vient d'être publié dans "Journal of Agricultural and Food Chemistry".

Auteurs : Sarah El Hajj, Cindy Tatiana Sepúlveda Rincón, Jean-Michel Girardet, Céline Cakir-Kiefer, Loic Stefan, José Edgar Zapata Montoya, Sandrine Boschi-Muller, Caroline Gaucher, Laetitia Canabady-Rochelle

J Agric Food Chem. 2021 Aug 11;69(31):8819-8827. doi: 10.1021/acs.jafc.1c02199.

 

Abstract

Metal-chelating peptides (MCP) are considered as indirect antioxidants due to their capacity to inhibit radical chain reaction and oxidation. Here, we propose a new proof of concept for the screening of MCPs present in protein hydrolysates for valorizing their antioxidant properties by using the emerging time-resolved molecular dynamics technology, switchSENSE. This method unveils possible interactions between MCPs and immobilized nickel ions using fluorescence and electro-switchable DNA chips. The switchSENSE method was first set up on synthetic peptides known for their metal-chelating properties. Then, it was applied to soy and tilapia viscera protein hydrolysates. Their Cu2+-chelation capacity was, in addition, determined by UV-visible spectrophotometry as a reference method. The switchSENSE method has displayed a high sensitivity to evidence the presence of MCPs in both hydrolysates. Hence, we demonstrate for the first time that this newly introduced technology is a convenient methodology to screen protein hydrolysates in order to determine the presence of MCPs before launching time-consuming separations.

Un article intitulé « Pourquoi faire ses cosmétiques soi-même est une fausse bonne idée », rédigé par Marianne Parent, a été publié sur The Conversation.

Il est accessible en cliquant ici.

 

 

 

La revue ci-dessous, fruit de la collaboration internationale et co-tutelle de thèse de Justine Bonetti avec l'Université de Pise vient d'être acceptée :
Bonetti J., Corti A., Lerouge L., Pompella A., Gaucher C. Phenotypic modulation of macrophages and vascular smooth muscle cells in atherosclerosis – Nitro-redox interconnections. Antioxidants 2021, 10(4), 516; https://doi.org/10.3390/antiox10040516 (registering DOI)
 

 

Abstract

 

Monocytes/macrophages and vascular smooth muscle cells (vSMCs) are the main cells types implicated in atherosclerosis development, and unlike other mature cell types both retain a remarkable plasticity. In mature vessels, differentiated vSMCs control the vascular tone and the blood pressure. In response to vascular injury and modifications of local environment (inflammation, oxidative stress), vSMCs switch from a contractile to a secretory phenotype and also display macrophagic markers expression and a macrophagic behaviour.. Endothelial dysfunction promotes adhesion to endothelium of monocytes, which infiltrate the sub-endothelium and differentiate into macrophages. The latter become polarised into M1 (pro-inflammatory), M2 (anti-inflammatory) or Mox macrophages (oxidative stress phenotype). Both monocyte-derived macrophages and macrophage-like vSMCs are able to internalise and accumulate oxLDL, leading to formation of ‘foam cells’ within atherosclerotic plaques. Variations in the levels of nitric oxide (NO) can affect several of the molecular pathways implicated in the described phenomena. Elucidation of underlying mechanisms could help to identify novel specific therapeutic targets, but to date much remains to be explored. The present article is an overview of the different factors and signaling pathways implicated in plaque formation and of the effects of NO on molecular steps of the phenotypic switch of macrophages and vSMCs.

Un nouvel article intitulé "Multifunctional hybrid nanoplatform based on Fe3O4@Ag NPs for nitric oxide delivery: development, characterization, therapeutic efficacy, and hemocompatibility" vient d'être publié.

Claudio Pieretti J, Chue Gonçalves M, Nakazato G, Carolina Santos de Souza A, Boudier A, Barozzi Seabra A;

J MATER SCI-MATER M; 2021;32(3):23;

PMID: 33675446; DOI: 10.1007/s10856-021-06494-x

Abstract :

The combination of Fe3O4@Ag superparamagnetic hybrid nanoparticles and nitric oxide (NO) represents an innovative strategy for a localized NO delivery with a simultaneous antibacterial and antitumoral actions. Here, we report the design of Fe3O4@Ag hybrid nanoparticles, coated with a modified and nitrosated chitosan polymer, able to release NO in a biological medium. After their synthesis, physicochemical characterization confirmed the obtention of small NO-functionalized superparamagnetic Fe3O4@Ag NPs. Antibacterial assays demonstrated enhanced effects compared to control. Bacteriostatic effect against Gram-positive strains and bactericidal effect against E. coli were demonstrated. Moreover, NO-functionalized Fe3O4@Ag NPs demonstrated improved ability to reduce cancer cells viability and less cytotoxicity against non-tumoral cells compared to Fe3O4@Ag NPs. These effects were associated to the ability of these NPs act simultaneous as cytotoxic (necrosis inductors) and cytostatic compounds inducing S-phase cell cycle arrest. NPs also demonstrated low hemolysis ratio (<10%) at ideal work range, evidencing their potential for biomedical applications.

Un article intitulé "Analytical strategy for studying the formation and stability of multilayered films containing gold nanoparticles" vient d'être publié dans "Analytical and Bioanalytical Chemistry".

Auteurs : Pallotta A, Clarot I, Beurton J, Creusot B, Chaigneau T, Tu A, Lavalle P & Boudier A

ANAL BIOANAL CHEM; 2021; PMID: 33495848, DOI: 10.1007/s00216-020-03113-6

 

Abstract

The design of layer-by-layer (LbL) polyelectrolyte films including nanoparticles is a growing field of innovation in a wide range of biomedical applications. Gold nanoparticles (AuNPs) are very attractive for further biomolecule coupling to induce a pharmacological effect. Nanostructured LbL films coupled with such metallic species show properties that depend on the conditions of construction, i.e. the polymer nature and dissolution buffer. Tripartite LbL films (polycation, AuNP, and polyanion) were evaluated using two different polycationic polymers (poly(allylamine hydrochloride) (PAH), poly(ethylene imine) (PEI)) and various medium conditions (salts, i.e. phosphate, Tris or Tris-NaCl buffers, and concentration). AuNP incorporation and film stability were analysed by visible spectrophotometry, capillary zone electrophoresis, a quartz crystal microbalance, and high-performance liquid chromatography. The ideal compromise between AuNP loading and film stability was obtained using PAH prepared in Tris-NaCl buffer (0.01-0.15 M). This condition allowed the formation of a LbL film that was more stable than the film with PEI and provided an AuNP quantity that was 4.8 times greater than that of the PAH-PBS-built film. In conclusion, this work presents an analytical strategy for the characterization of nanostructured multilayer films and optimization of LbL films enriched with AuNPs to design biomedical device coatings.

Frédéric Bier (technicien) vient de rejoindre l'équipe pour un CDD d'1 an (projet industriel confidentiel)

Un article intitulé "Investigation of Nanoparticle Metallic Core Antibacterial Activity: Gold and Silver Nanoparticles against Escherichia coli and Staphylococcus aureus" vient d'être publié dans "International Journal of Molecular Sciences".

Auteurs : Jimmy Gouyau, Raphaël E. Duval, Ariane Boudier, Emmanuel Lamouroux

Int. J. Mol. Sci. 2021, 22(4), 1905

Le texte intégral en Open Access est disponible ici.

 

Abstract

Multidrug-resistant (MDR) bacteria constitute a global health issue. Over the past ten years, interest in nanoparticles, particularly metallic ones, has grown as potential antibacterial candidates. However, as there is no consensus about the procedure to characterize the metallic nanoparticles (MNPs; i.e., metallic aggregates) and evaluate their antibacterial activity, it is impossible to conclude about their real effectiveness as a new antibacterial agent. To give part of the answer to this question, 12 nm gold and silver nanoparticles have been prepared by a chemical approach. After their characterization by transmission electronic microscopy (TEM), Dynamic Light Scattering (DLS), and UltraViolet-visible (UV-vis) spectroscopy, their surface accessibility was tested through the catalytic reduction of the 4-nitrophenol, and their stability in bacterial culture medium was studied. Finally, the antibacterial activities of 12 nm gold and silver nanoparticles facing Staphylococcus aureus and Escherichia coli have been evaluated using the broth microdilution method. The results show that gold nanoparticles have a weak antibacterial activity (i.e., slight inhibition of bacterial growth) against the two bacteria tested. In contrast, silver nanoparticles have no activity on S. aureus but demonstrate a high antibacterial activity against Escherichia coli, with a minimum inhibitory concentration of 128 µmol/L. This high antibacterial activity is also maintained against two MDR-E. coli strains.