A robust predictive model was developed using 136 novel peroxisome proliferator-activated receptor delta (PPARδ) agonists, a distinct subtype of lipid-activated transcription factors of the nuclear ...receptor superfamily that regulate target genes by binding to characteristic sequences of DNA bases. The model employs various structural descriptors and docking calculations and provides predictions of the biological activity of PPARδ agonists, following the criteria of the Organization for Economic Co-operation and Development (OECD) for the development and validation of quantitative structure-activity relationship (QSAR) models. Specifically focused on small molecules, the model facilitates the identification of highly potent and selective PPARδ agonists and offers a read-across concept by providing the chemical neighbours of the compound under study. The model development process was conducted on Isalos Analytics Software (v. 0.1.17) which provides an intuitive environment for machine-learning applications. The final model was released as a user-friendly web tool and can be accessed through the Enalos Cloud platform's graphical user interface (GUI).
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Over the last decade the existence of “the corona,” a natural interface between nanomaterials and living matter in biological milieu, evolved from a vague concept into broadly recognized fact. This ...robust shell arises (to some extent) on the surface of all nanoparticles (NPs), even the ones designed to avoid its formation upon contact with biological fluids and confers a biological identity to the nanomaterials such that they can engage with cellular machinery. The NP corona consists of those proteins (and other biomolecules such as lipids and sugars) residing on the NP surface for a sufficient timescale to influence the NP’s properties and interactions with living systems. This chapter aims to provide simple protocols, as well as notes on potential pitfalls, to help researchers to perform basic experiments in this field as the basis for a more mechanistic approach to study and understand NP–protein corona complexes. This work has been supported by INSPIRE (Integrated NanoScience Platform for Ireland) funded by the Irish Government’s Programme for Research in Third Level Institutions, Cycle 4, National Development Plan 2007–2013, and 3MICRON (NMP-2009-LA-245572), NAMDIATREAM (NMP4-LA-2010-246479) and QualityNano (INFRA-2010-262163) funded by the European Commission 7th Framework Programme.
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FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In the context of global concerns about plastics, this paper sets out and exemplifies a research agenda for articulating children’s encounters with plastics. The paper analyses data co-produced with ...11–15 year-olds through interviews, app-based research and experimental/arts-led workshops. It moves beyond scholarship in health and environmental sciences, and in environmental education research, to outline a far richer range of ways to conceptualise children’s encounters with plastics, based in children’s everyday, embodied and emotive interactions with plastics.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
(1) Background: Despite the encouraging indications regarding the suitability (biocompatibility) of iron carbide nanoparticles (ICNPs) in various biomedical applications, the published evidence of ...their biosafety is dispersed and relatively sparse. The present review synthesizes the existing nanotoxicological data from in vitro studies relevant to the diagnosis and treatment of cancer. (2) Methods: A systematic review was performed in electronic databases (PubMed, Scopus, and Wiley Online Library) on December 2023, searching for toxicity assessments of ICNPs of different sizes, coatings, and surface modifications investigated in immortalized human and murine cell lines. The risk of bias in the studies was assessed using the ToxRTool for in vitro studies. (3) Results: Among the selected studies (
= 22), cell viability emerged as the most frequently assessed cellular-level toxicity endpoint. The results of the meta-analysis showed that cell models treated with ICNPs had a reduced cell viability (SMD = -2.531; 95% CI: -2.959 to -2.109) compared to untreated samples. A subgroup analysis was performed due to the high magnitude of heterogeneity (I
= 77.1%), revealing that ICNP concentration and conjugated ligands are the factors that largely influence toxicity (
< 0.001). (4) Conclusions: A dose-dependent cytotoxicity of ICNP exposure was observed, regardless of the health status of the cell, tested organism, and NP size. Inconsistent reporting of ICNP physicochemical properties was noted, which hinders comparability among the studies. A comprehensive exploration of the available in vivo studies is required in future research to assess the safety of ICNPs' use in bioimaging and cancer treatment.
For nanotechnology to meet its potential as a game-changing and sustainable technology, it is important to ensure that the engineered nanomaterials and nanoenabled products that gain entry to the ...marketplace are safe and effective. Tools and methods are needed for regulatory purposes to allow rapid material categorization according to human health and environmental risk potential, so that materials of high concern can be targeted for additional scrutiny, while material categories that pose the least risk can receive expedited review. Using carbon nanotubes as an example, we discuss how data from alternative testing strategies can be used to facilitate engineered nanomaterial categorization according to risk potential and how such an approach could facilitate regulatory decision-making in the future.
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IJS, KILJ, NUK, PNG, UL, UM
There is increasing recognition that environmental nano-biological interactions in model species, and the resulting effects on progeny, are of paramount importance for nanomaterial (NM) risk ...assessment. In this work, Daphnia magna F0 mothers were exposed to a range of silver and titanium dioxide NMs. The key biological life history traits (survival, growth and reproduction) of the F1 intergenerations, at the first (F1B1), third (F1B3) and fifth (F1B5) broods, were investigated. Furthermore, the F1 germlines of each of the three broods were investigated over 3 more generations (up to 25 days each) in continuous or removed-from NM exposure, to identify how the length of maternal exposure affects the resulting clonal broods. Our results show how daphnids respond to NM-induced stress, and how the maternal effects show trade-offs between growth, reproduction and survivorship. The F1B1 (and following germline) had the shortest F0 maternal exposure times to the NMs, and thus were the most sensitive showing reduced size and reproductive output. The F1B3 generation had a sub-chronic maternal exposure, whereas the F1B5 generation suffered chronic maternal exposure where (in most cases) the most compensatory adaptive effects were displayed in response to the prolonged NM exposure, including enhanced neonate output and reduced gene expression. Transgenerational responses of multiple germlines showed a direct link with maternal exposure time to 'sub-lethal' effect concentrations of NMs (identified from standard OECDs acute toxicity tests which chronically presented as lethal) including increased survival and production of males in the F1B3 and G1B5 germlines. This information may help to fine-tune environmental risk assessments of NMs and prediction of their impacts on environmental ecology.
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Nanosilver is one of the most commonly used engineered nanomaterials (ENMs). In our study we focused on assessing the size-dependence of the toxicity of nanosilver (Ag ENMs), utilising materials of ...three sizes (50, 80 and 200 nm) synthesized by the same method, with the same chemical composition, charge and coating.
Uptake and localisation (by Transmission Electron Microscopy), cell proliferation (Relative growth activity) and cytotoxic effects (Plating efficiency), inflammatory response (induction of IL-8 and MCP-1 by Enzyme linked immune sorbent assay), DNA damage (strand breaks and oxidised DNA lesions by the Comet assay) were all assessed in human lung carcinoma epithelial cells (A549), and the mutagenic potential of ENMs (Mammalian hprt gene mutation test) was assessed in V79-4 cells as per the OECD protocol. Detailed physico-chemical characterization of the ENMs was performed in water and in biological media as a prerequisite to assessment of their impacts on cells. To study the relationship between the surface area of the ENMs and the number of ENMs with the biological response observed, Ag ENMs concentrations were recalculated from μg/cm2 to ENMs cm2/cm2 and ENMs/cm2.
Studied Ag ENMs are cytotoxic and cytostatic, and induced strand breaks, DNA oxidation, inflammation and gene mutations. Results expressed in mass unit μg/cm2 suggested that the toxicity of Ag ENMs is size dependent with 50 nm being most toxic. However, re-calculation of Ag ENMs concentrations from mass unit to surface area and number of ENMs per cm2 highlighted that 200 nm Ag ENMs, are the most toxic. Results from hprt gene mutation assay showed that Ag ENMs 200 nm are the most mutagenic irrespective of the concentration unit expressed.
We found that the toxicity of Ag ENMs is not always size dependent. Strong cytotoxic and genotoxic effects were observed in cells exposed to Ag ENMs 50 nm, but Ag ENMs 200 nm had the most mutagenic potential. Additionally, we showed that expression of concentrations of ENMs in mass units is not representative. Number of ENMs or surface area of ENMs (per cm2) seem more precise units with which to compare the toxicity of different ENMs.
Toxicogenomics (TGx) approaches are increasingly applied to gain insight into the possible toxicity mechanisms of engineered nanomaterials (ENMs). Omics data can be valuable to elucidate the ...mechanism of action of chemicals and to develop predictive models in toxicology. While vast amounts of transcriptomics data from ENM exposures have already been accumulated, a unified, easily accessible and reusable collection of transcriptomics data for ENMs is currently lacking. In an attempt to improve the FAIRness of already existing transcriptomics data for ENMs, we curated a collection of homogenized transcriptomics data from human, mouse and rat ENM exposures in vitro and in vivo including the physicochemical characteristics of the ENMs used in each study.
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•Intranasal exposure to ZnO NPs induced accumulation of Zn in liver of rat.•No accumulation of Zn in liver was found in ZnSO4 treatment.•Persistence of NPs in liver 7 days post ...exposure was revealed by XAFS.•More and distinct metabolites in liver were altered by ZnO NPs than by ZnSO4.•ZnO NPs induced particle-specific effects revealed by metabolomics.
Toxicity of ZnO nanoparticles (NPs) are often related to the release of Zn2+ ions due to their dissolution. Studies also suggest that the toxicity of ZnO NPs cannot be solely explained by the release of Zn2+ ions; however, there is a lack of direct evidence of ZnO particulate effects. This study compared the acute toxicity of ZnO NPs and ZnSO4 following intranasal exposure using a combination of metallomics and metabolomics approaches. Significant accumulation of Zn in the liver was only found in the ZnO NP treatment, with 29% of the newly accumulated Zn in the form of ZnO as revealed by X-ray fine structure spectroscopy (XAFS). This is the first direct evidence suggesting the persistence of ZnO NPs in liver upon intranasal exposure. Although both ZnO NPs and ZnSO4 altered the metabolite profiles, with some overlaps and considerable specificity, of both liver and plasma samples, more and distinct metabolites in the liver and opposite effects in the plasma were altered by ZnO NPs compared with ZnSO4, consistent with no accumulation of Zn detected in liver from ZnSO4. Specifically, a large number of antioxidant-related compounds and energetic substrates were exclusively elevated in the liver of ZnO NP-treated animals. These findings provided direct evidence that persistence of ZnO NPs induced particle-specific effects on the antioxidant systems and energy metabolism pathways.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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