Comparative Analysis of the Toxicity Profile of Eleven Consumer-Relevant Nanomaterials in Human Intestinal and Placental Barrier Cells

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.This research was funded by the project NanoBioBarriers, grant number PTDC/MED‐TOX/31162/2017, co-financed by the Operational Program for Competitiveness and Internationalization (POCI) through European Regional Development Funds (FEDER/FNR) and the Foundation for Science and Technology (FCT/MCTES). This work is financed by national funds through FCT – Foundation for Science and Technology within the scope of projects UIDB/04750/2020 and LA/P/0064/2020.info:eu-repo/semantics/publishedVersio

Cell Model of Depression: Reduction of Cell Stress with Mirtazapine

This article belongs to the Special Issue Blood-Brain Barrier in CNS Injury and Repair 2022Depression is a very prevalent and complex disease. This condition is associated with a high rate of relapse, making its treatment a challenge. Thus, an intensive investigation of this disease and its treatment is necessary. In this work, through cell viability assays (MTT and neutral red assays) and alkaline comet assays, we aimed to test the induction of stress in human SH-SY5Y cells through the application of hydrocortisone and hydrogen peroxide and to test the reversal or attenuation of this stress through the application of mirtazapine to the cells. Our results demonstrated that hydrogen peroxide, and not hydrocortisone, can induce cellular stress, as evidenced by DNA damage and a global cellular viability reduction, which were alleviated by the antidepressant mirtazapine. The establishment of a cellular model of depression through stress induction is important to study new possibilities of treatment of this disease using cell cultures.This research was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operational Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through Fundação para a Ciência e a Tecnologia (FCT) in the framework of the project IF/00092/2014/CP1255/CT0004 and CHAIR in Onco-Innovation.info:eu-repo/semantics/publishedVersio

Histórias com sentidos nas Artes

Dissertação de Mestrado em Educação Artística apresentada na Escola Superior de Educação do Instituto Politécnico de Viana do CasteloEste estudo surgiu da necessidade de se verificar, os hábitos de leitura no âmbito da Literatura para a Infância e o recurso às Artes Visuais e à Música na idade pré-escolar (dos 3 aos 6 anos), após se constatar que, atualmente, as crianças nestas idades, cada vez menos recorrem à Área Infantil da Biblioteca Municipal, preferindo utilizar o telemóvel dos pais, ou as tablets, nos seus tempos livres. Neste sentido desenvolveu-se uma investigação de enfoque qualitativo, baseada na metodologia de investigação-ação, centrada nas práticas das implementações que decorreram na Biblioteca Municipal Tomaz de Figueiredo e no Centro Interpretativo do Barroco em Arcos de Valdevez, que envolveram a investigadora, as crianças participantes, os respetivos pais e também a Diretora da Biblioteca. A intervenção curricular envolveu a planificação de atividades, seleção de recursos visuais e sonoros com o propósito de incentivar o gosto e o hábito da leitura, e a exploração de diversas técnicas e estratégias interdisciplinares convencionais e não convencionais. A recolha de dados no decorrer das implementações, envolveu a observação participativa da investigadora, o diário reflexivo, registos fotográficos e de vídeo, questionários aos pais e às crianças e uma entrevista à Diretora da Biblioteca. Os dados permitiram verificar o lugar da Literatura para a Infância, tendo todos os participantes adultos vivenciado o impacto positivo, que tal experiência exerce sobre as crianças, havendo cada vez mais um enorme campo a explorar no domínio da leitura partilhada, da abordagem interdisciplinar e do desenvolvimento sensorial. Conclui-se que os pais devem contribuir para que os seus filhos se sintam motivados pela leitura de literatura para a infância, como uma forma de arte, uma forma de comunicação, que valoriza as emoções, as sensações, a criatividade e a formação integral das crianças. Estimular tais contactos com os livros, e atividades lúdicas, pedagógicas, de diversão à volta de leitura, irá possivelmente contribuir para canalizar mais a atenção das crianças para o seu imaginário de fantasia e reduzir o seu interesse pelos tablets. Todos podem contribuir, pois como dizia Al Gore: “Para se criar uma criança, não basta uma família… É preciso uma aldeia inteira!”This study arose from the need to verify, the reading habits shared in the scope of Literature for Children and the use of Visual Arts and Music in pre-school age (from 3 to 6 years old), after verifying that, currently, children of these ages are increasingly less likely to use the Children's Area of the Municipal Library, preferring to use their parents' cell phones, or tablets, in their spare time. In this sense, a qualitative investigation was developed, based on the action-research methodology, centered on the implementation practices that took place at the Municipal Library Tomaz de Figueiredo and at the Baroque Interpretative Center in Arcos de Valdevez, which involved the researcher, the children participants, their parents and also the Library Director. A The curricular intervention involved the planning of activities, selection of visual and sound resources in order to encourage the taste and habit of reading, and the exploration of various conventional and unconventional interdisciplinary techniques and strategies. The collection of data during the implementations involved participatory observation by the researcher, the reflective diary, photographic and video records, questionnaires to parents and children and an interview with the Director of the Library. The data made it possible to verify the place of literature for childhood, with all adult participants evidencing the positive impact that such an experience has on children, with an increasing field to explore in the field of shared reading, interdisciplinary approach and development. sensory. It is concluded that parents should contribute so that their children feel motivated by reading literature for childhood, as an art form., a form of communication that values the emotions, sensations, creativity, and integral education of children. Stimulating such contacts with books, and ludic, pedagogical, fun activities around reading, will possibly contribute to channeling children's attention more to their fantasy imagination and reducing their interest in tablets. Everyone can contribute, because as Al Gore said: “To raise a child, a family is not enough ... An entire village is needed!

In vitro genotoxicity assessment of a dextrin-based hydrogel for biomedical applications

[Excerpt] Hydrogels are three dimensional, crosslinked networks of hydrophilic polymers swollen with a large amount of water or biological fluids. Dextrin, a low-molecularweight carbohydrate composed by glucose residues, has been used to develop a novel fully resorbable and injectable hydrogel for biomedical applications. Dextrin was firstly oxidized (ODEX) to introduce aldehyde groups which then reticulate with adipic acid dihydrazide (ADH), forming the dextrin-based hydrogel (HG) [1]. The cross-linked ODEX is an in situ forming hydrogel, which displays a three-dimensional network with inter-connective pores, and is able to incorporate nanogels, cells and biomolecules for biomedical applications [1-3]. [...]Isabel Pereira was supported by the grant SFRH/BD/ 90066/2012 from FCT. We thank FEDER and NORTE 2020 through the project nº 003262 titled “iBONE therapies: advanced solutions for bone regeneration”. We also thank the funding from FCT (UID/BIO/044469/2013) and from FEDER through COMPETE 2020 (POCI-01-0145-FEDER-006684).info:eu-repo/semantics/publishedVersio

Dataset on ammonia, nitrous oxide, methane, and carbon dioxide fluxes from two soils fertilized amended with treated and non-treated cattle slurry

Data Articleinfo:eu-repo/semantics/publishedVersio

Multiparametric in vitro genotoxicity assessment of different variants of amorphous silica nanomaterials in rat alveolar epithelial cells

The hazard posed to human health by inhaled amorphous silica nanomaterials (aSiO2 NM) remains uncertain. Herein, we assessed the cyto- and genotoxicity of aSiO2 NM variants covering different sizes (7, 15, and 40 nm) and surface modifications (unmodified, phosphonate-, amino- and trimethylsilyl-modified) on rat alveolar epithelial (RLE-6TN) cells. Cytotoxicity was evaluated at 24 h after exposure to the aSiO2 NM variants by the lactate dehydrogenase (LDH) release and WST-1 reduction assays, while genotoxicity was assessed using different endpoints: DNA damage (single- and double-strand breaks [SSB and DSB]) by the comet assay for all aSiO2 NM variants; cell cycle progression and γ-H2AX levels (DSB) by flow cytometry for those variants that presented higher cytotoxic and DNA damaging potential. The variants with higher surface area demonstrated a higher cytotoxic potential (SiO2_7, SiO2_15_Unmod, SiO2_15_Amino, and SiO2_15_Phospho). SiO2_40 was the only variant that induced significant DNA damage on RLE-6TN cells. On the other hand, all tested variants (SiO2_7, SiO2_15_Unmod, SiO2_15_Amino, and SiO2_40) significantly increased total γ-H2AX levels. At high concentrations (28 µg/cm2), a decrease in G0/G1 subpopulation was accompanied by a significant increase in S and G2/M sub-populations after exposure to all tested materials except for SiO2_40 which did not affect cell cycle progression. Based on the obtained data, the tested variants can be ranked for its genotoxic DNA damage potential as follows: SiO2_7 = SiO2_40 = SiO2_15_Unmod > SiO2_15_Amino. Our study supports the usefulness of multiparametric approaches to improve the understanding on NM mechanisms of action and hazard prediction.This work was supported by the Portuguese Foundation for Science and Technology (FCT) through ERA-NET SIINN project NanoToxClass (SIINN/0001/2013). This work was also supported by the NanoBioBarriers project (POCI-01-0145-FEDER-031162), co-financed by the Operational Program for Competitiveness and Internationalization (POCI) through European Regional Development Funds (FEDER/FNR); and by the Spanish Ministry of Science and Innovation: MCIN/AEI/10.13039/501100011033 (Grant PID2020-114908GA-I00); and the Ministry of Education, Culture and Sport BEAGAL18/00142 to V. Valdiglesias. F. Brandão (SFRH/BD/101060/2014) and M.J. Bessa (SFRH/BD/12046/2016) are recipients of FCT PhD scholarships. The Doctoral Program in Biomedical Sciences of the ICBAS – University of Porto offered additional funds. S. Fraga thanks FCT for funding through program DL 57/2016 – Norma transitória (Ref. DL-57/INSA-06/2018). Thanks are also due to FCT/MCTES for the financial support to EPIUnit (UIDB/04750/2020) and ITR (LA/P/0064/2020).info:eu-repo/semantics/publishedVersio

Biocompatible and biodegradable functional coatings with natural occurring materials for the corrosion protection of Mg alloys

Magnesium alloys are amidst the most innovative materials for biomedical applications, as they show a set of unique properties, namely appropriate mechanical properties and biodegradability, when compared to other alloys. Although these properties make them suitable for medical implants, the main challenge is the uncontrolled corrosion. Mg degradation is fast, inhomogeneous, localized and often accompanied by hydrogen formation which can lead to complications in vivo. Here, we propose the development of a functional coating, containing natural-based capsules for the controlled release of biocompatible corrosion inhibitors and well known pharmaceutical agents. Empty and loaded capsules toxicity tests were performed as a first step for materials selection. Subsequently, they were incorporated into polyetherimide (PEI) coatings and tested using electrochemical impedance spectroscopy (EIS) under aggressive conditions. The obtained results showed a successful synthesis of natural-based microcapsules, constituting a fast, simple and environmentally friendly method. Additionally, the high cell proliferation observed in the presence of the aforementioned materials demonstrates their low toxicity. Preliminary results carried out with capsule-modified coatings show that the incorporation of Ca2+-loaded gelatin capsules in PEI coatings leads to barrier and active corrosion protection properties improvement and that anti-inflammatory agent ibuprofen may have a role in active corrosion protection as well.publishe

Assessing the in vitro toxicity of airborne (nano)particles to the human respiratory system: from basic to advanced models

ReviewSeveral studies have been conducted to address the potential adverse health risks attributed to exposure to nanoscale materials. While in vivo studies are fundamental for identifying the relation-ship between dose and occurrence of adverse effects, in vitro model systems provide important information regarding the mechanism(s) of action at the molecular level. With a special focus on exposure to inhaled (nano)particulate material toxicity assessment, this review provides an over-view of the available human respiratory models and exposure systems for in vitro testing, advan-tages, limitations, and existing investigations using models of different complexity. A brief overview of the human respiratory system, pathway and fate of inhaled (nano)particles is also presented.The work was supported by the Fundação para a Ciência e a Tecnologia [POCI-01-0145-FEDER-029651, SFRH/BPD/122112/2016,PTDC/MED‐TOX/31162/2017, DL-57/INSA06/2018,SFRH/BD/101060/2014,SFRH/BD/120646/2016, SIINN/0004/2014,UIDB/04750/2020, LA/P/0064/2020]; Spanish Ministry of Education, Culture and Sport [BEAGAL18/00142]; Spanish Ministry of Science and Innovation [PID2020-114908GA-I00].info:eu-repo/semantics/publishedVersio

In vivo biocompatibility and safety asessment of a dextrin-based hydrogel for biomedical applications

[Excerpt] Hydrogels are three dimensional, crosslinked networks of hydrophilic polymers swollen with a large amount of water or biological fluids. They can be combined with granules of ceramic-based synthetic bone substitutes (SBSs) aiming to stabilize them into bone defects and to obtain injectable formulations. Our research group has been characterizing a fully resorbable and injectable dextrin-based hydrogel (HG) which was intended to perform as a multifunctional platform, enabling the combination with stem cells and other bioactive agents, during clinical procedures [1-3]. In a subcutaneous assay, the HG was able to incorporate and stabilize ceramic granules (250-500 um) in the implant site, demonstrating its potential as an injectable carrier and stabilizer of SBSs [3]. [...]Isabel Pereira was supported by the grant SFRH/BD/ 90066/2012 from FCT. We thank FEDER and NORTE 2020 through the project nº 003262 titled iBONE therapies: advanced solutions for bone regeneration and NORTE-01-0145-FEDER-000012. We also thank the funding from FCT (UID/BIO/044469/2013 and UID/BIM/04293/2013) and from FEDER through COMPETE 2020 (POCI-01-0145-FEDER-006684).info:eu-repo/semantics/publishedVersio

In vitro genotoxicity assessment of an oxidized dextrin-based hydrogel for biomedical applications

Hydrogels are threedimensional, crosslinked networks of hydrophilic polymers swollen with a large amount of water or biological fluids, without dissolving. Dextrin, a lowmolecularweight carbohydrate composed by glucose residues, has been used to develop an injectable hydrogel for biomedical applications. Dextrin was first oxidized to introduce aldehyde groups, which then reticulate with adipic acid dihydrazide, forming the dextrinbased hydrogel (HG). The HG and its components were tested for cyto and genotoxicity according to the International Standard ISO 109933 on the biological evaluation of medical devices. To assess genotoxicity, a battery of in vitro genotoxicity tests employing both eukaryotic and prokaryotic models was performed: comet assay, cytokinesisblock micronucleus assay and Ames test. Our data revealed that the HG (IC50 = 2.8 mg/mL) and oxidized dextrin by itself (IC50 = 1.2 mg/mL) caused a concentrationdependent decrease in cellular viability of human lymphoblastoid TK6 cells after 24 hours of exposure to the test agents. However, these concentrations are unlikely to be reached in vivo. In addition, no significant increase in the DNA and chromosomal damage of TK6 cells exposed to noncytotoxic concentrations of the HG and its isolated components was detected. Furthermore, neither the HG nor its metabolites exerted a mutagenic effect in different of Salmonella typhimurium strains and in an Escherichia coli mix. Our data demonstrated the genocompatibility of the HG (up to 3.5 mg/mL) for biomedical applications. To our best acknowledge, this is the first report with a detailed genotoxicity assessment of an aldehydemodified polysaccharide/adipic acid dihydrazide hydrogel.FEDER ‐ Fundo Europeu de Desenvolvimento Regional. Grant Numbers: NORTE‐01‐0145‐FEDER‐000004, NORTE‐01‐0247‐FEDER‐003262 Fundação para a Ciência e a Tecnologia. Grant Numbers: PTDC/CTM‐BIO/2170/2014, SFRH/BD/ 90066/2012info:eu-repo/semantics/publishedVersio