Effect of Ni(II), Cd(II) and Al(III) on human fibroblast bioenergetics, a preliminary comparative study

International audienceExposure to Ni, Cd or Al leads to different health issues depending on the dose and the exposure frequency. Their mechanism of action is poorly known, but as metals, they may have some points in common. The aim of this work was to compare the impact on cell bioenergetic of these metals using a common cell model: a normal human dermal fibroblast (NHDF) in primary culture. To study cell bioenergetics which ''concerns energy conservation and conversion processes in a living cell'' as defined by Demirel and Sandler, two technics are combined: oximetry and microcalorimetry. The heat flow measured by microcalorimetry reflects cell metabolism and more generally glucose catabolism (the only nutriment brought to the NHDF). Cell respiration is measured by oximetry and shows the impact on the mitochondria, the energy factory of the cell. Without incubation, Cd inhibits thermogenesis and cell respiration, Ni has no effect, and Al inhibits cell respiration but not thermogenesis. After 24 h of contact at 40 lM, NHDF died with Cd but seemed over-activated with Al and Ni (thermogenesis and cell respiration increased)

Gold nanoparticles prepared by laser ablation in aqueous biocompatible solutions: assessment of safety and biological identity for nanomedicine applications

International audienceGold nanoparticles prepared by laser ablation in aqueous biocompatible solutions: assessment of safety and biological identity for nanomedicine applications Abstract: Due to excellent biocompatibility, chemical stability, and promising optical properties , gold nanoparticles (Au-NPs) are the focus of research and applications in nanomedicine. Au-NPs prepared by laser ablation in aqueous biocompatible solutions present an essentially novel object that is unique in avoiding any residual toxic contaminant. This paper is conceived as the next step in development of laser-ablated Au-NPs for future in vivo applications. The aim of the study was to assess the safety, uptake, and biological behavior of laser-synthesized Au-NPs prepared in water or polymer solutions in human cell lines. Our results showed that laser ablation allows the obtaining of stable and monodisperse Au-NPs in water, polyethylene glycol, and dextran solutions. The three types of Au-NPs were internalized in human cell lines, as shown by transmission electron microscopy. Biocompatibility and safety of Au-NPs were demonstrated by analyzing cell survival and cell morphology. Furthermore, incubation of the three Au-NPs in serum-containing culture medium modified their physicochemical characteristics , such as the size and the charge. The composition of the protein corona adsorbed on Au-NPs was investigated by mass spectrometry. Regarding composition of complement C3 proteins and apolipoproteins, Au-NPs prepared in dextran solution appeared as a promising drug carrier. Altogether, our results revealed the safety of laser-ablated Au-NPs in human cell lines and support their use for theranostic applications

The GenTree Platform: growth traits and tree-level environmental data in 12 European forest tree species

Background: Progress in the field of evolutionary forest ecology has been hampered by the huge challenge of phenotyping trees across their ranges in their natural environments, and the limitation in high-resolution environmental information. Findings: The GenTree Platform contains phenotypic and environmental data from 4,959 trees from 12 ecologically and economically important European forest tree species: Abies alba Mill. (silver fir), Betula pendula Roth. (silver birch), Fagus sylvatica L. (European beech), Picea abies (L.) H. Karst (Norway spruce), Pinus cembra L. (Swiss stone pine), Pinus halepensis Mill. (Aleppo pine), Pinus nigra Arnold (European black pine), Pinus pinaster Aiton (maritime pine), Pinus sylvestris L. (Scots pine), Populus nigra L. (European black poplar), Taxus baccata L. (English yew), and Quercus petraea (Matt.) Liebl. (sessile oak). Phenotypic (height, diameter at breast height, crown size, bark thickness, biomass, straightness, forking, branch angle, fructification), regeneration, environmental in situ measurements (soil depth, vegetation cover, competition indices), and environmental modeling data extracted by using bilinear interpolation accounting for surrounding conditions of each tree (precipitation, temperature, insolation, drought indices) were obtained from trees in 194 sites covering the species’ geographic ranges and reflecting local environmental gradients. Conclusion: The GenTree Platform is a new resource for investigating ecological and evolutionary processes in forest trees. The coherent phenotyping and environmental characterization across 12 species in their European ranges allow for a wide range of analyses from forest ecologists, conservationists, and macro-ecologists. Also, the data here presented can be linked to the GenTree Dendroecological collection, the GenTree Leaf Trait collection, and the GenTree Genomic collection presented elsewhere, which together build the largest evolutionary forest ecology data collection available

Between but not within species variation in the distribution of fitness effects

New mutations provide the raw material for evolution and adaptation. The distribution of fitness effects (DFE) describes the spectrum of effects of new mutations that can occur along a genome, and is therefore of vital interest in evolutionary biology. Recent work has uncovered striking similarities in the DFE between closely related species, prompting us to ask whether there is variation in the DFE among populations of the same species, or among species with different degrees of divergence, i.e., whether there is variation in the DFE at different levels of evolution. Using exome capture data from six tree species sampled across Europe we characterised the DFE for multiple species, and for each species, multiple populations, and investigated the factors potentially influencing the DFE, such as demography, population divergence and genetic background. We find statistical support for there being variation in the DFE at the species level, even among relatively closely related species. However, we find very little difference at the population level, suggesting that differences in the DFE are primarily driven by deep features of species biology, and that evolutionarily recent events, such as demographic changes and local adaptation, have little impact

Theranostic nanoparticules in oncology : pharmacological evaluation of their safety and efficacy

Les nano-objets ou nanoparticules sont des systèmes de taille nanométrique. Dans le domaine de l’oncologie, ils sont capables de transporter des agents anticancéreux et/ou des macromolécules comme des gènes ou des protéines, de sorte qu’ils s’accumulent préférentiellement dans le tissu tumoral. Ainsi, les nanoparticules ont pour but de diminuer la quantité de principe actif libre dans l’organisme, responsable de toxicités. Elles permettent en clinique d’améliorer la balance bénéfice/risque des agents de chimiothérapies conventionnels. Ce sont de véritables plateformes qui permettent de s’affranchir de certains excipients toxiques contenus dans la formulation du paclitaxel (Cremophor El). Ainsi, au cours de ce travail nous nous sommes intéressés dans un premier temps aux nanoparticules d’or (Au-NP) produites par ablation laser femtoseconde. Nous avons ainsi caractérisé ces Au-NP sur le plan physico-chimique et biologique, et mis en évidence leur internalisation et leur innocuité. Dans un deuxième temps, nous avons évalué l’efficacité pharmacologique de conjugués dendron-paclitaxel sur des cultures cellulaires 2D et 3D et mis en avant la libération prolongée intracellulaire du paclitaxel et son effet retard. Compte-tenu des propriétés observées, ces nanoparticules sont de bons candidats pour un futur développement. En effet, la liaison de ces deux nanostructures entre elles permettra l’obtention d’un nano-objet aux propriétés de théranostiques.Nano-objects or nanoparticles can be readily fabricated with their size being controlled typically in the range of 1–100 nm. In the field of oncology, they can be used for drug delivery, as their composition/structure may be engineered to load anticancer drugs, macromolecules or proteins. Indeed, the delivery of anticancer drugs through a nanoparticle-based platform offers many attractive features. Nanoparticle-based drugs are synthetized to significantly improve the benefit/risk ratio of conventional chemotherapeutics. They allow overcoming some toxic excipients in the formulation of paclitaxel (Cremophor El). In this work, we first studied the physico-chemical and biological properties of Au-NPs synthetized by femtosecond laser ablation and we investigated their safety and cellular uptake. Second, we evaluated the anticancer activity of dendron-paclitaxel conjugates in 2D and 3D cell cultures and showed a delayed effect of this new formulation. Based on these results, the studied nanoparticles are good candidates for future development. By combining the two nano-objects, we will obtain nanoparticles with theranostic properties

Effect of Ni(II), Cd(II) and Al(III) on human fibroblast bioenergetics, a preliminary comparative study

International audienceExposure to Ni, Cd or Al leads to different health issues depending on the dose and the exposure frequency. Their mechanism of action is poorly known, but as metals, they may have some points in common. The aim of this work was to compare the impact on cell bioenergetic of these metals using a common cell model: a normal human dermal fibroblast (NHDF) in primary culture. To study cell bioenergetics which ''concerns energy conservation and conversion processes in a living cell'' as defined by Demirel and Sandler, two technics are combined: oximetry and microcalorimetry. The heat flow measured by microcalorimetry reflects cell metabolism and more generally glucose catabolism (the only nutriment brought to the NHDF). Cell respiration is measured by oximetry and shows the impact on the mitochondria, the energy factory of the cell. Without incubation, Cd inhibits thermogenesis and cell respiration, Ni has no effect, and Al inhibits cell respiration but not thermogenesis. After 24 h of contact at 40 lM, NHDF died with Cd but seemed over-activated with Al and Ni (thermogenesis and cell respiration increased)

Télémédecine et iatrogénie médicamenteuse en Ehpad

International audienc

Visual compatibility of defibrotide with selected drugs during simulated Y-site administration

International audienc

Front Cover: Delaying Anticancer Drug Delivery by Self‐Assembly and Branching Effects of Minimalist Dendron–Drug Conjugates (Chem. Eur. J. 41/2019)

International audienc

Delaying Anticancer Drug Delivery by Self-Assembly and Branching Effects of Minimalist Dendron-Drug Conjugates

International audienc