Investigation of gold nanoparticle cytotoxicity and uptake in kidney cells in vitro

https://drive.google.com/file/d/1m0Gud-BcHFal8Ml6JXg6JrjskBmJ533t/view?usp=sharinghttps://drive.google.com/drive/folders/1punMku8fCPDiuxUiVCaW5XYXjgeyQl0o?usp=sharinghttps://drive.google.com/drive/folders/1ft6zgQOr1aZij0cjCXORTNbz65ZXBEzt?usp=sharin

An ancestral molecular response to nanomaterial particulates

The varied transcriptomic response to nanoparticles has hampered the understanding of the mechanism of action. Here, by performing a meta-analysis of a large collection of transcriptomics data from various engineered nanoparticle exposure studies, we identify common patterns of gene regulation that impact the transcriptomic response. Analysis identifies deregulation of immune functions as a prominent response across different exposure studies. Looking at the promoter regions of these genes, a set of binding sites for zinc finger transcription factors C2H2, involved in cell stress responses, protein misfolding and chromatin remodelling and immunomodulation, is identified. The model can be used to explain the outcomes of mechanism of action and is observed across a range of species indicating this is a conserved part of the innate immune system.Peer reviewe

Particle toxicology and health - where are we?

Background Particles and fibres affect human health as a function of their properties such as chemical composition, size and shape but also depending on complex interactions in an organism that occur at various levels between particle uptake and target organ responses. While particulate pollution is one of the leading contributors to the global burden of disease, particles are also increasingly used for medical purposes. Over the past decades we have gained considerable experience in how particle properties and particle-bio interactions are linked to human health. This insight is useful for improved risk management in the case of unwanted health effects but also for developing novel medical therapies. The concepts that help us better understand particles and fibres risks include the fate of particles in the body; exposure, dosimetry and dose-metrics and the 5 Bs: bioavailability, biopersistence, bioprocessing, biomodification and bioclearance of (nano)particles. This includes the role of the biomolecule corona, immunity and systemic responses, non-specific effects in the lungs and other body parts, particle effects and the developing body, and the link from the natural environment to human health. The importance of these different concepts for the human health risk depends not only on the properties of the particles and fibres, but is also strongly influenced by production, use and disposal scenarios. Conclusions Lessons learned from the past can prove helpful for the future of the field, notably for understanding novel particles and fibres and for defining appropriate risk management and governance approaches.(VLID)359668

An ancestral molecular response to nanomaterial particulates

DATA AVAILABILITY : The pre-processed version of the transcriptomic datasets included in the discovery datasets, that is, ENM exposures of human and mouse samples, have been previously deposited at https://zenodo.org/ record/3949890#.YlPUri0RqH0. The original datasets can be accessed at Array Express (https://www.ebi.ac.uk/biostudies/arrayexpress) with the entry code EMTAB6396 and at GEO (https://www.ncbi.nlm.nih. gov/) under accession numbers GSE103101, GSE112780, GSE113088, GSE117056, GSE122197, GSE127773, GSE146708, GSE148705, GSE157266, GSE16727, GSE17676, GSE19487, GSE20692, GSE29042, GSE35193, GSE39330, GSE41041, GSE42066, GSE42067, GSE42068, GSE43515, GSE45322, GSE45598, GSE4567, GSE46998, GSE46999, GSE50176, GSE51186, GSE51417, GSE51421, GSE51636, GSE53700, GSE55286, GSE55349, GSE56324, GSE56325, GSE60797, GSE60798, GSE60799, GSE60800, GSE61366, GSE62253, GSE62769, GSE63552, GSE63806, GSE68036, GSE75429, GSE79766, GSE81564, GSE81565, GSE81566, GSE81567, GSE81568, GSE81569, GSE82062, GSE84982, GSE85711, GSE88786, GSE92563, GSE92900, GSE92987, GSE96720, GSE98236 and GSE99929. Transcriptomic datasets used for the eco-toxicological analysis are freely available at GEO under accession numbers GSE80461, GSE32521, GSE70509, GSE73427, GSE77148, GSE41333 and GSE47662. Transcriptomic datasets of small molecule exposure (Open-TG GATEs) have been downloaded from https://dbarchive.biosciencedbc.jp/en/ open-tggates/download.html in November 2020. Functional data were downloaded from https://www.gsea-msigdb.org/gsea/msigdb/ version 7.2. All the other relevant data and data supporting the findings of this study have been deposited in the online Zenodo repository (https://doi.org/10.5281/zenodo.7674574).CODE AVAILABILITY : All the relevant and custom code supporting the findings of this study has been deposited in the online Zenodo repository (https://DOI. org/10.5281/zenodo.7674574) and on Github at https://github.com/ fhaive/metanalysis_toxicogenomic_data.The varied transcriptomic response to nanoparticles has hampered the understanding of the mechanism of action. Here, by performing a meta-analysis of a large collection of transcriptomics data from various engineered nanoparticle exposure studies, we identify common patterns of gene regulation that impact the transcriptomic response. Analysis identifies deregulation of immune functions as a prominent response across different exposure studies. Looking at the promoter regions of these genes, a set of binding sites for zinc finger transcription factors C2H2, involved in cell stress responses, protein misfolding and chromatin remodelling and immunomodulation, is identified. The model can be used to explain the outcomes of mechanism of action and is observed across a range of species indicating this is a conserved part of the innate immune system.The Academy of Finland project UNICAST NANO; European Research Council (ERC) programme; Consolidator project ARCHIMEDES; EU Horizon 2020 project NanoSolveIT; NanoInformaTIX; the Tampere Institute for Advanced Study; the National Science Center, Poland; European Union’s Horizon 2020 research and innovation programme; and Science Foundation Ireland. Open access funding provided by Tampere University including Tampere University Hospital, Tampere University of Applied Sciences (TUNI).https://www.nature.com/nnano/am2024School of Health Systems and Public Health (SHSPH)SDG-03:Good heatlh and well-bein

Role of Mutagenicity in Asbestos Fiber-Induced Carcinogenicity and Other Diseases

The cellular and molecular mechanisms of how asbestos fibers induce cancers and other diseases are not well understood. Both serpentine and amphibole asbestos fibers have been shown to induce oxidative stress, inflammatory responses, cellular toxicity and tissue injuries, genetic changes, and epigenetic alterations in target cells in vitro and tissues in vivo. Most of these mechanisms are believe to be shared by both fiber-induced cancers and noncancerous diseases. This article summarizes the findings from existing literature with a focus on genetic changes, specifically, mutagenicity of asbestos fibers. Thus far, experimental evidence suggesting the involvement of mutagenesis in asbestos carcinogenicity is more convincing than asbestos-induced fibrotic diseases. The potential contributions of mutagenicity to asbestos-induced diseases, with an emphasis on carcinogenicity, are reviewed from five aspects: (1) whether there is a mutagenic mode of action (MOA) in fiber-induced carcinogenesis; (2) mutagenicity/carcinogenicity at low dose; (3) biological activities that contribute to mutagenicity and impact of target tissue/cell type; (4) health endpoints with or without mutagenicity as a key event; and finally, (5) determinant factors of toxicity in mutagenicity. At the end of this review, a consensus statement of what is known, what is believed to be factual but requires confirmation, and existing data gaps, as well as future research needs and directions, is provided

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

M. Morain, préfet de police [à son bureau de travail] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 104534Appartient à l’ensemble documentaire : Pho20RolImage de press