Search

International audience; HypothesisPrecise modulation of immuno-inflammatory response is crucial to control periodontal diseases and related systemic comorbidities. The present nanosystem with the controlled-release and cell-penetrating manner enhances the inflammation modulation effects of baicalein in human gingival epithelial cells (hGECs) for better oral healthcare.ExperimentsWe constructed a red-emissive mesoporous silica nanoparticle-based nanosystem with cell-penetrating poly(disulfide) (CPD) capping, through a facile in-situ polymerization approach. It was featured with a glutathione-responsive manner and instant cellular internalization capacity for precisely delivering baicalein intracellularly. Laboratory experiments assessed whether and how the nanosystem per se with the delivered baicalein could modulate immuno-inflammatory responses in hGECs.FindingsThe in-situ polymerized CPD layer capped the nanoparticles and yet controlled the release of baicalein in a glutathione-responsive manner. The CPD coating could facilitate cellular internalization of the nanosystem via endocytosis and thiol-mediated approaches. Notably, the intracellularly released baicalein effectively downregulated the expression of pro-inflammatory cytokines through inhibiting the NF-κB signaling pathway. The nanosystem per se could modulate immuno-inflammatory responses by passivating the cellular response to interlukin-1β. This study highlights that the as-synthesized nanosystem may serve as a novel multi-functional vehicle to modulate innate host response via targeting the NF-κB pathway for precision healthcare.

Introduction: in a context where lung cancer is underreported as occupational diseases, the aim was to study the validity of an application based on silica and asbestos job-exposure matrices in screening occupational exposure. Methods: between november 2016 and september 2017, fifty patients hospitalized with primitive lung cancer or mesothelioma, in a university hospital center in the Hauts-de-Seine department of France, were included in this retrospective diagnostic study. The job history was collected for each patient, from which data was entered single-blindly intothe job-exposure matrices and a questionnaire (Q-SPLF) was completed by a resident in occupational medicine. The patients also had a consultation with a chief resident in occupational medicine considered the gold standard. The exposure probabilities given by the matrices and the consultation were divided into two categories: exposed (if > 0% for the matrix, and >30% for the consultation) or not exposed and then compared. The main outcome was the diagnostic performance of the matrices. Results: the matrices had sensitivities of 100%, specificities of 76,1% and 87,8%, the positive likelihood ratios were at 4,19 [2,5-5,6] and 8,17 [3,9-10,8], the negative likelihood ratios were at 0 and the areas under the ROC curve were at 0,90 and 0,98 respectively for the asbestos and silica matrices. The kappa coefficients were at 0,34 [0,08-0,60] for the asbestos matrix and 0,22 [-0,14-0,59] for the silica matrix. Discussion: the application has a great diagnostic performance which is well adapted for a use as a screening tool. Further large-scale studies will be useful to confirm these results.; Introduction : dans un contexte de sous-déclaration des cancers pulmonaires en maladie professionnelle, l’objectif a été d’évaluer la validité d’une application basée sur des matrices emplois-expositions silice et amiante comme outil de dépistage des expositions professionnelles.Méthodes : entre novembre 2016 et septembre 2017, 50 patients hospitalisés pour cancer pulmonaire primitif ou mésothéliome dans un Centre Hospitalo-Universitaire des Hauts-de-Seine ont été inclus dans cette étude diagnostique rétrospective. Ils ont eu un curriculum laboris dont les données ont été saisies en simple aveugle dans les matrices, un questionnaire (Q-SPLF), leurs réponses étant recueillies par une interne en médecine du travail et une consultation par un chef de clinique de pathologie professionnelle, constituant la méthode de référence. Les probabilités d’exposition recueillies ont été divisées en deux catégories, exposé (si >0% pour la matrice, >30% pour la consultation)/non-exposé, puis comparées. Le critère de jugement principal était la performance diagnostique des matrices. Résultats : les sensibilités étaient de 100%, les spécificités de 76,1% et 87,8%, les rapports de vraisemblance positifs de 4,19 [2,5-5,6] et 8,17 [3,9-10,8], les rapports de vraisemblance négatifs de 0 et les aires sous la courbe ROC de 0,90 et 0,98 pour respectivement les matrices amiante et silice. Les coefficients de concordance kappa étaient à 0,34 [0,08-0,60] pour la matrice amiante et 0,22 [-0,14-0,59] pour la matrice silice. Discussion : l’application a une bonne performance diagnostique adaptée à son utilisation comme outil de dépistage. D’autres études à plus grande échelle seront nécessaires pour confirmer ces résultats.

Background: Respirable crystalline silica is a highly prevalent occupational exposure and a recognized lung carcinogen. Most previous studies have focused on selected high-exposure occupational groups. This study examines the relationship between occupational exposure to silica and lung cancer in an occupationally diverse male population. Methods: Two large population-based case-control studies of lung cancer were conducted in Montreal, one in 1979-1986 (857 cases, 533 population controls, 1,349 cancer controls) and the second in 1996-2001 (738 cases and 899 controls). Interviews provided descriptive lifetime job histories, smoking histories, and other information. Industrial hygienists translated job histories into histories of exposure to a host of occupational substances, including silica. Relative risk was estimated, adjusting for several potential confounders, including smoking. Results: The odds ratio for substantial exposure to silica was 1.67 (95% confidence interval, 1.21-2.31) and for any exposure was 1.31 (95% confidence interval, 1.08-1.59). Joint effects between silica and smoking were between additive and multiplicative, perhaps closer to the latter. In this population, it is estimated that approximately 3% of lung cancers were attributable to substantial silica exposure. Conclusions: The carcinogenicity of inhaled crystalline silica was observed in a population with a wide variety of exposure circumstances. Impact: The finding of carcinogenicity across a wide range of occupations complements prior studies of specific high-exposure occupations. This suggests that the burden of cancer induced by silica may be much greater than previously thought. Cancer Epidemiol Biomarkers Prev; 19(6); 1602–11. ©2010 AACR.

International audience; Obtaining high-throughput electrophysiological recordings is an ongoing challenge in ion channel biophysics and drug discovery. One particular area of development is the replacement of glass pipettes with planar devices in order to increase throughput. However, successful patch-clamp recordings depend on a surface coating which ideally should promote and stabilize giga-seal formation. Here, we present data supporting the use of a structured SiO(2) coating to improve the ability of cells to form a "seal" with a planar patch-clamp substrate. The method is based on a correlation study taking into account structure and size of the pores, surface roughness and chip capacitance. The influence of these parameters on the quality of the seal was assessed. Plasma-enhanced chemical vapour deposition (PECVD) of SiO(2) led to an hourglass structure of the pore and a tighter seal than that offered by a flat, thermal SiO(2) surface. The performance of PECVD chips was validated by recording recombinant potassium channels, BK(Ca), expressed in stable HEK-293 cell lines and in inducible CHO cell lines and low conductance IRK1, and endogenous cationic currents from CHO cells. This multiparametric investigation led to the production of improved chips for planar patch-clamp applications which allow electrophysiological recordings from a wide range of cell lines.

International audience; A hot melt dispersion method was used to prepare new sustained release ibuprofen composite microparticles of a solid lipid at ambient temperature, cetyl alcohol. The dispersion of colloidal silicon dioxide nanoparticles (hydrophilic Aerosil 200 or hydrophobic Aerosil R974) either in the oily phase or in the aqueous phase led to the preparation of large (about 400 μm diameter) surfactant free free-flowing particles. Mapping-scanning electronic microscopy using silicon probe revealed that silicon was in the oily core in all cases. The nature of silica nanoparticles and the way used for their dispersion influenced the internal structure of the composite microparticles and the aggregation of nanoparticles in the core of the microparticles. Hydrophobic Aerosil R974 allowed the formation of homogeneous microparticles. Although silica nanoparticles had no influence on thermic profile, crystalline state of ibuprofen and lipid, they had an influence on the kinetics drug release related to the increase of the size of the composite solid lipid microparticles prepared.

International audience; Prins cyclization between a homoallylic alcohol and an aldehyde, promoted by trimethylsilyl halide, afforded 4-halo-tetrahydropyrans with good to excellent yields. Thanks to the absence of the solvent and metal, the THP thus obtained have been implicated without purification in several other reactions, in a sequential way, affording in particular new indole derivatives.

International audience; Supramolecular self-assembly is an attractive pathway for bottom-up synthesis of novel nanomaterials. In particular, this approach allows the spontaneous formation of structures of well-defined shapes and monodisperse characteristic sizes. Because nanotechnology mainly relies on size-dependent physical phenomena, the control of monodispersity is required, but the possibility of tuning the size is also essential. For self-assembling systems, shape, size, and monodispersity are mainly settled by the chemical structure of the building block. Attempts to change the size notably by chemical modification usually end up with the loss of self-assembly. Here, we generated a library of 17 peptides forming nanotubes of monodisperse diameter ranging from 10 to 36 nm. A structural model taking into account close contacts explains how a modification of a few Å of a single aromatic residue induces a fourfold increase in nanotube diameter. The application of such a strategy is demonstrated by the formation of silica nanotubes of various diameters.

Different lanthanide chelates have been simultaneously embedded in a silica matrix yielding bright dual-mode lanthanide doped nanospheres which are uniform in size distribution, tunable, photostable, and leakage free. Depending on the chelate combination, two color emission with a single light source or tunable emission with multiple sources is obtained. © 2010 The Royal Society of Chemistry.

Bacterial pesticide degraders are generally heterogeneously distributed in soils, leaving soil volumes devoid of degradation potential. This is expected to have an impact on degradation rates because the degradation of pollutant molecules in such zones will be contingent either on degraders colonizing these zones or on pollutant mass transfer to neighboring zones containing degraders. In a model system, we quantified the role exerted by water on mineralization rate in the context of a heterogeneously distributed degradation potential. Alginate beads colonized by Pseudomonas putida KT2440 were inserted at prescribed locations in sand microcosms so that the initial spatial distribution of the mineralization potential was controlled. The mineralization rate was strongly affected by the matric potential (decreasing rate with decreasing matric potential) and by the initial distribution of the degraders (more aggregated distributions being associated with lower rates). The mineralization was diffusion-limited, as confirmed with a mathematical model. In wet conditions, extensive cell dispersal was observed for the flagellated wild type and, albeit to a lesser extent, for a nonflagellated mutant, partially relieving the diffusion limitation. Dry conditions, however, sustained low mineralization rates through the combined effects of low pollutant diffusivity and limited degrader dispersal.

International audience; The authors examined associations between exposure to aluminum or silica from drinking water and risk of cognitive decline, dementia, and Alzheimer's disease among elderly subjects followed for 15 years (1988-2003). They actively searched for incident cases of dementia among persons aged 65 years or over living in 91 civil drinking-water areas in southern France. Two measures of exposure to aluminum were assessed: geographic exposure and individual exposure, taking into account daily consumption of tap water and bottled water. A total of 1,925 subjects who were free of dementia at baseline and had reliable water assessment data were analyzed. Using random-effects models, the authors found that cognitive decline with time was greater in subjects with a higher daily intake of aluminum from drinking water (>or=0.1 mg/day, P=0.005) or higher geographic exposure to aluminum. Using a Cox model, a high daily intake of aluminum was significantly associated with increased risk of dementia. Conversely, an increase of 10 mg/day in silica intake was associated with a reduced risk of dementia (adjusted relative risk =0.89, P=0.036). However, geographic exposure to aluminum or silica from tap water was not associated with dementia. High consumption of aluminum from drinking water may be a risk factor for Alzheimer's disease.

International audience; Functionalisation of MSN with mannose for PDT applications dramatically improved the efficiency of PDT on breast cancer cells.

International audience; This paper describes the rheological properties of silated hydroxypropylmethylcellulose (HPMC-Si) used in biomaterials domain as a three-dimensional synthetic matrix for tissue engineering. The HPMC-Si is an HPMC grafted with 3-glycidoxypropyltrimethoxysilane (GPTMS). HPMC and HPMC-Si were studied. It is shown that although silanization reduces the hydrodynamic volume in dilute solution, it does not affect significantly the rheological behavior of the concentrated solutions. The HPMC-Si viscous solution (pH 12.8) cross-links by decreasing the pH using an acid buffer, since HPMC-Si solution transforms into an elastic state. The kinetics of cross-linking and final elastic properties is influenced by several parameters such as polymer concentration, pH and temperature. pH and temperature play an important role in the silanol condensation, mainly responsible for network formation. The study of the gelation process revealed the dependence of the final concentration of HPMC-Si hydrogel on cross-linking kinetics and viscoelastic properties. The percolation theory was applied to determine gel point and to discuss the dependence of storage (G') and loss (G'') moduli on frequency. Results showed that both G' and G'' exhibit a power-law behavior with an exponent (0.68) which extends over the entire frequency range. This method is the only one to characterize the time where a liquid viscous phase shifts to hydrogel with elastic properties. In this case it was about 23 min for a final pH of 7.4.

Uses of enzymes for therapeutic purpose or for biosensing require a well-controlled nanoenvironnement to avoid degradation by proteolytic agents, pH variations or dilution effects. A solution is encapsulation under undenaturating conditions into a nanometer sized and stable capsule. The nanometer scall decreases recognition by the reticulo-endothelial system recognition and subsequent immune reaction. Liposomes are the method of choice since they allow protein encapsulation under mild conditions. However they lack in stability. In contrast, other type of capsules exhibit strong stability but with conditions required for formation that are incompatible with enzyme integrity. Here we combine different capsule formation techniques and use liposomes as templates for further stabilization. Here we demonstrate two types of multicomposite capsules. The first type is to coat the liposome surface with polyelectrolytes followed by secondary covalent crosslinking of the polyelectrolytes multilayer. In the second type of capsules we used silica to build an inorganic shell around liposome. Both techniques allow the formation of detergent stable nanocapsules which exhibits properties protective against acetylcholinesterase protein degradation, an enzyme of much interest for pesticide detection.

récupéré dans HAL-INSERM; Short-term physico-chemical reactions at the interface between bioactive glass particles and biological fluids are studied for three glasses with different bioactive properties; these glasses are in the SiO(2)-Na(2)O-CaO-P(2)O(5)-K(2)O-Al(2)O(3)-MgO system. Our aim is to show the difference between the mechanisms of their surface reactions. The relation between the composition and the bioactive properties of these glasses is also discussed. The elemental analysis is performed at the submicrometer scale by scanning transmission electron microscopy associated with energy-dispersive X-ray spectroscopy and electron energy loss spectroscopy. After different immersion times (ranging from 0 to 96 h) of bioactive glass particles in a simulated biological solution, results show the formation of different surface layers at the glass periphery in the case of two bioactive glasses (A9 and BVA). For the third glass (BVH) we do not observe any surface layer formation or any modification of the glass composition. For the two other glasses (A9 and BVA), we observe the presence of different layers: an already observed (Si, O, Al) rich layer at the periphery, a previously demonstrated thin (Si, O) layer formed on top of the (Si, O, Al) layer and a (Ca, P) layer. We determine the different steps of the mechanisms of the surface reactions, which appear to be similar in these glasses, and compare the physico-chemical reactions and kinetics using the different immersion times. The A9 glass permits the observation of all important steps of the surface reactions which lead to bioactivity. This study shows the important relationship between composition and bioactivity which can determine the medical applicability of the glass.

International audience; The influence of processing parameters and synthetic strategies in the properties of sol-gel derived silica matrices intended for the release of bioactive compounds was investigated. The time-evolution of the matrix properties during its aging at room temperature in the dry and wet forms was investigated by measuring some of its physical and drug retaining properties. The results indicate that long term gel aging in the wet form is fundamental for the obtainment of dry matrices that are stable upon storage, a fundamental requirement for any practical application. In the case of hybrid matrices obtained by replacing part of the tetraethoxysilane precursor with mono-methyl trimethoxysilane, the order of addition of the reaction component is also important in determining the properties of the final dry gel, probably by influencing the polymer structural properties. This parameter acts synergistically with the matrix composition in determining the release properties of xerogels embedded with bioactive compounds.