This paper presents a comprehensive review of European Union (EU) legislation addressing the safety of chemical substances, and possibilities within each piece of legislation for applying grouping ...and read-across approaches for the assessment of nanomaterials (NMs). Hence, this review considers both the overarching regulation of chemical substances under REACH (Regulation (EC) No 1907/2006 on registration, evaluation, authorization, and restriction of chemicals) and CLP (Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures) and the sector-specific pieces of legislation for cosmetic, plant protection and biocidal products, and legislation addressing food, novel food, and food contact materials. The relevant supporting documents (e.g. guidance documents) regarding each piece of legislation were identified and reviewed, considering the relevant technical and scientific literature. Prospective regulatory needs for implementing grouping in the assessment of NMs were identified, and the question whether each particular piece of legislation permits the use of grouping and read-across to address information gaps was answered.
•UNCD and DLC films were modified by UV/O3 treatments, O2 or NH3-containing plasmas.•Surface composition, wettability and surface energy change upon modifications.•Higher efficiency of UNCD ...modifications was observed.•Cell attachment and growth were influenced by the surface termination and roughness.
Diamond and diamond-like carbon (DLC) films possess a set of excellent physical and chemical properties which together with a high biocompatibility make them attractive candidates for a number of medical and biotechnological applications. In the current work thin ultrananocrystalline diamond (UNCD) and DLC films were comparatively investigated with respect to cell attachment and proliferation after different surface modifications. The UNCD films were prepared by microwave plasma enhanced chemical vapor deposition, the DLC films by pulsed laser deposition (PLD). The films were comprehensively characterized with respect to their basic properties, e.g. crystallinity, morphology, chemical bonding nature, etc. Afterwards the UNCD and DLC films were modified applying O2 or NH3/N2 plasmas and UV/O3 treatments to alter their surface termination. The surface composition of as-grown and modified samples was studied by X-ray photoelectron spectroscopy (XPS). Furthermore the films were characterized by contact angle measurements with water, formamide, 1-decanol and diiodomethane; from the results obtained the surface energy with its dispersive and polar components was calculated. The adhesion and proliferation of MG63 osteosarcoma cells on the different UNCD and DLC samples were assessed by measurement of the cell attachment efficiency and MTT assays. The determined cell densities were compared and correlated with the surface properties of as-deposited and modified UNCD and DLC films.
Nanotechnology is a key enabling technology with billions of euros in global investment from public funding, which include large collaborative projects that have investigated environmental and health ...safety aspects of nanomaterials, but the reuse of accumulated data is clearly lagging behind. Here we summarize challenges and provide recommendations for the efficient reuse of nanosafety data, in line with the recently established FAIR (findable, accessible, interoperable and reusable) guiding principles. We describe the FAIR-aligned Nanosafety Data Interface, with an aggregated findability, accessibility and interoperability across physicochemical, bio-nano interaction, human toxicity, omics, ecotoxicological and exposure data. Overall, we illustrate a much-needed path towards standards for the optimized use of existing data, which avoids duplication of efforts, and provides a multitude of options to promote safe and sustainable nanotechnology.
A defective induction of epithelial autophagy may have a role in the pathogenesis of inflammatory bowel diseases. This process is regulated mainly by extracellular factors such as nutrients and ...growth factors and is highly induced by diverse situations of stress. We hypothesized that epithelial autophagy is regulated by the immune response that in turn is modulated by local hypoxia and inflammatory signals present in the inflamed mucosa. Our results reveal that HIF-1α and Wnt1 were co-localized with CD68 in cells of the mucosa of IBD patients. We have observed increased protein levels of β-catenin, phosphorylated mTOR, and p62 and decreased expression of LC3II in colonic epithelial crypts from damaged mucosa in which β-catenin positively correlated with phosphorylated mTOR and negatively correlated with autophagic protein markers. In cultured macrophages, HIF-1 mediated the increase in Wnt1 expression induced by hypoxia, which enhanced protein levels of β-catenin, activated mTOR, and decreased autophagy in epithelial cells in co-culture. Our results demonstrate a HIF-1-dependent induction of Wnt1 in hypoxic macrophages that undermines autophagy in epithelial cells and suggest a role for Wnt signaling and mTOR pathways in the impaired epithelial autophagy observed in the mucosa of IBD patients.
In the present study, we have compared the effects of ultrananocrystalline diamond/amorphous carbon composite films (UNCD/a-C) and nanocrystalline diamond (NCD) containing hydrogels to support the ...osteogenesis of endothelial progenitor cells (EPCs)
. The course of EPCs osteogenic differentiation was followed 21
days and assayed by measuring cell-associated alkaline phosphatase activity, calcium deposition, and expression of fibronectin. We found that EPCs were capable to adhere to both surfaces in flattened and elongated morphology. The attachment and spreading on the UNCD/a-C films were faster as compared to the hydrogels containing NCDs (by day 7), and this was connected with the release and adsorption of fibronectin to the surfaces. During the process of EPCs differentiation, the release of fibronectin was favored by hydrogels
+
NCD (day 21). The formation of calcium nodules, characteristic of osteoblastic mineralization, was detected by Alizarin Red S staining. Differentiation-induced calcium nodules were detected in EPCs growing on both surfaces. The EPCs cultured on hydrogels containing NCD deposited more extracellular calcium in comparison with those on UNCD/a-C films on day 21. These results were consistent with the data about the alkaline phosphatase activity on the same day and verified that an active EPC transformation to osteoblast phenotype occurred on both substrates. Our results could have direct implications in the use of biomaterials in tissue engineering strategies, and this work might be useful for the improvement of the methodologies for substrate preparation (including scaffolds). Thus both surfaces studied could be used for modification of bone implants (bone-anchoring parts of joint prostheses or bone replacements) in order to improve their integration with the surrounding bone tissue, for which improved cell–substrate adhesion is also needed.
► Nanodiamond containing hydrogels and coatings for acceleration of osteogenesis. ► Support of osteogenic differentiation of endothelial progenitor cells. ► Nanodiamonds as biomaterials in tissue engineering strategies.
Abstract Copper has gained increased interest because of its important role in metabolism and antimicrobial activity. In this study, composite target material of Ti and Cu was used to deposit TiO 2 ...coatings doped with copper on Ti6Al4V alloy. The aim was to examine the influence of the applied bias during the deposition of Cu-doped TiO 2 coating by sputtering in a glow-discharge in a pure O 2 atmosphere for a deposition time of 240 min. Different substrate values, selected from 0 to -150 V, were used in the process. The increase in bias voltage from -50 to - 150 V decreased the thickness of the oxide coatings and improved their adhesion to the substrate while increasing the Cu 2 O phase at the expense of a CuO phase decrease. Simultaneously, the increase in bias voltage decreased Cu content from about 32 wt% for the -50 V biased down to around 11 wt% for the -150 V biased specimens. The antimicrobial efficacy against E. coli estimated by direct contact experiments on the top of the uncoated (control) and coated Ti6Al4V alloy revealed about 94% inhibition for the -50V biased down to around 37% for the -150 V biased coatings as opposed to the control.
Copper has gained increased interest because of its important role in metabolism and antimicrobial activity. In this study, composite target material of Ti and Cu was used to deposit TiO2 coatings ...doped with copper on Ti6Al4V alloy. The aim was to examine the influence of the applied bias during the deposition of Cu-doped TiO2 coating by sputtering in a glow-discharge in a pure O2 atmosphere for a deposition time of 240 min. Different substrate values, selected from 0 to -150 V, were used in the process. The increase in bias voltage from -50 to - 150 V decreased the thickness of the oxide coatings and improved their adhesion to the substrate while increasing the Cu2O phase at the expense of a CuO phase decrease. Simultaneously, the increase in bias voltage decreased Cu content from about 32 wt% for the -50 V biased down to around 11 wt% for the -150 V biased specimens. The antimicrobial efficacy against E. coli estimated by direct contact experiments on the top of the uncoated (control) and coated Ti6Al4V alloy revealed about 94% inhibition for the -50V biased down to around 37% for the -150 V biased coatings as opposed to the control.
Although MT is detected as a cytoplasmic protein in hepatocytes of adult liver, it can be localized in the hepatocyte nuclei in human fetal liver bound to zinc and copper. Both nuclear and ...cytoplasmic localization of MT have been observed in several human tumours, especially in regions of high proliferation. Transient co-localization of zinc and MT has been shown in differentiating myoblast and 3T3-L1 fibroblasts, and during the G1-/S-phase progression in cell cycle. Several mechanisms have been proposed for the import and retention of MT in the nucleus, including signal transduction pathways. The high levels of MT in the nucleus of cells under certain conditions may be related to the increased requirement for zinc for several metallo-enzymes and transcription factors during rapid growth. The function of nuclear MT may be to protect the cell from DNA damage and apoptosis, and also to regulate gene expression during certain stages of cell cycle.
The process of identifying suitable genome-wide association (GWA) studies and formatting the data to calculate multiple polygenic risk scores on a single genome can be laborious. Here, we present a ...centralized polygenic risk score calculator currently containing over 250,000 genetic variant associations from the NHGRI-EBI GWAS Catalog for users to easily calculate sample-specific polygenic risk scores with comparable results to other available tools. Polygenic risk scores are calculated either online through the Polygenic Risk Score Knowledge Base (PRSKB; https://prs.byu.edu ) or via a command-line interface. We report study-specific polygenic risk scores across the UK Biobank, 1000 Genomes, and the Alzheimer's Disease Neuroimaging Initiative (ADNI), contextualize computed scores, and identify potentially confounding genetic risk factors in ADNI. We introduce a streamlined analysis tool and web interface to calculate and contextualize polygenic risk scores across various studies, which we anticipate will facilitate a wider adaptation of polygenic risk scores in future disease research.
Alteration of endothelins (ET) and/or their receptors may be important in mediating vascular dysfunction in diabetes. We investigated mechanisms regulating ET-1 expression in human umbilical vein ...endothelial cells (HUVEC) in response to glucose and the functional significance of these mechanisms. Permeability across HUVEC, grown in medium containing either low (5 mmol/l) or high (25 mmol/l) D-glucose were investigated. L-glucose was used as a control. ET-1, ET(A), and ET(B) mRNA were assessed by semiquantitative RT-PCR. ET-1 immunoreactivity and F-actin microfilament assembly were investigated using confocal microscopy. Increased transendothelial permeability was noted in cells cultured in high glucose or when the cells grown in low (physiologic) glucose were incubated with ET-1, vascular endothelial growth factor (VEGF), or N (G) -nitro-L-arginine methyl ester but not when they were incubated with ET-3, N(G)-nitro-D-arginine methyl ester, or L-glucose. Increased permeability was associated with increased ET-1, ET(A), and ET(B) mRNA expression and augmented ET-1 immunoreactivity. High glucose induced increased permeability, increased ET-1, ET(A), and ET(B) mRNA expression. ET-1 immunoreactivity was blocked by the protein kinase C (PKC) inhibitor chelerythrine, the specific PKC isoform inhibitor 379196, VEGF-neutralizing antibody, or the ET(A) blocker TBC11251, but was not blocked by the specific ET(B) blocker BQ788 or by a VEGF-non-neutralizing antibody. Increased permeability was also associated with deranged F-actin assembly in the endothelial cells and by derangement of endothelial cell junctions as assessed by electron microscopy. Data from this study suggest that high glucose-induced increased permeability may be induced through increased ET-1 expression and disorganization of F-actin assembly. ET-1 expression and increased permeability may occur secondary to PKC isoform activation and may be modulated by VEGF and nitric oxide.
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