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Browsing by Issue Date, starting with "2023-04-21"

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  • Comparative Analysis of the Toxicity Profile of Eleven Consumer-Relevant Nanomaterials in Human Intestinal and Placental Barrier Cells
    Publication . Pires, Joana; Moreira, Luciana; Teixeira, João Paulo; Fraga, Sónia
    Background: The growing number of items incorporating nanomaterials (NM) has prompted considerable concerns about human health and safety [1]. Metal nanoparticles, inorganic non-metallic, and carbon-based NM are among the types with the highest market volume [2]. Objective: The purpose of this study was to determine the effect of chemical composition [Ag, Au, TiO2, SiO2, and graphene oxide (nano_GO)], primary size (10, 30 and 60 nm AgNP and AuNP), crystal structure (TiO2NP rutile/anatase and anatase), and surface coating (citrate and PEGylated AuNP) on potential toxicity to human intestinal (Caco-2) and placental (BeWo b30) epithelial cells. Methods: Changes in cell morphology, metabolic activity, plasma membrane integrity, intracellular ROS and ATP levels, and DNA integrity were assessed to investigate their potential toxicity at 24 h after exposure. Results: In both barrier models, the toxicity profile was similar, however placentalwere more sensitive than intestinal epithelial cells. Overall, NM may be ranked for cytotoxicity as AgNP > nano_GO > AuNP ~ TiO2NP ~ SiO2NP, with the effects becoming more evident at greater concentrations. The influence of size was more pronounced for AgNP than for AuNP, with the smaller nanoparticles producing higher cytotoxic effects. The cytotoxicity of AuNP was prevented by PEG capping. AgNP and nano_GO exposure markedly raised the levels of ROS, indicating that oxidative stress may play a role in their cytotoxicity. Except for 10 nm AuNP, every NM tested markedly increased intracellular ATP levels. One interesting finding was that a higher cytotoxic potential did not necessarily equate to a higher genotoxic potential, since only AgNP (classified as positive) and anatase TiO2NP (classified as equivocal) caused DNA damage. Conclusions: Our findings alert to the potential risks associated with human barriers exposure to NM, where the physicochemical properties are important determinants of their toxicity. Additional research is needed for a deeper understanding of NM impact on human barriers.
    2023-04-21Conference object Open access Show more
  • Neurological Disease Modeling Using Pluripotent and Multipotent Stem Cells: A Key Step towards Understanding and Treating Mucopolysaccharidoses
    Publication . Carvalho, Sofia; Santos, Juliana Inês; Moreira, Luciana; Gonçalves, Mariana; David, Hugo; Matos, Liliana; Encarnação, Marisa; Alves, Sandra; Coutinho, Maria Francisca
    Despite extensive research, the links between the accumulation of glycosaminoglycans (GAGs) and the clinical features seen in patients suffering from various forms of mucopolysaccharidoses (MPSs) have yet to be further elucidated. This is particularly true for the neuropathology of these disorders; the neurological symptoms are currently incurable, even in the cases where a disease-specific therapeutic approach does exist. One of the best ways to get insights on the molecular mechanisms driving that pathogenesis is the analysis of patient-derived cells. Yet, not every patient-derived cell recapitulates relevant disease features. For the neuronopathic forms of MPSs, for example, this is particularly evident because of the obvious inability to access live neurons. This scenario changed significantly with the advent of induced pluripotent stem cell (iPSC) technologies. From then on, a series of differentiation protocols to generate neurons from iPSC was developed and extensively used for disease modeling. Currently, human iPSC and iPSC-derived cell models have been generated for several MPSs and numerous lessons were learnt from their analysis. Here we review most of those studies, not only listing the currently available MPS iPSC lines and their derived models, but also summarizing how they were generated and the major information different groups have gathered from their analyses. Finally, and taking into account that iPSC generation is a laborious/expensive protocol that holds significant limitations, we also hypothesize on a tempting alternative to establish MPS patient-derived neuronal cells in a much more expedite way, by taking advantage of the existence of a population of multipotent stem cells in human dental pulp to establish mixed neuronal and glial cultures.
    2023-04-21Journal article Open access Show more