Suchergebnisse

We investigated the role of the gold nanoparticles functionalized with polyvinylpyrrolidone (PVP–AuNPs) on the innate immune response against an acute infection caused by Vibrio anguillarum in an in vitro immunological nonmammalian next-generation model, the sea urchin Paracentrotus lividus. To profile the immunomodulatory function of PVP–AuNPs (0.1 μg mL) in sea urchin immune cells stimulated by Vibrio (10 μg mL) for 3 h, we focused on the baseline immunological state of the donor, and we analysed the topography, cellular metabolism, and expression of human cell surface antigens of the exposed cells, as well as the signalling leading the interaction between PVP–AuNPs and the Vibrio-stimulated cells. PVP–AuNPs are not able to silence the inflammatory signalling (TLR4/p38MAPK/NF-κB signalling) that involves the whole population of P. lividus immune cells exposed to Vibrio. However, our findings emphasise the ability of PVP–AuNPs to stimulate a subset of rare cells (defined here as Group 3) that express CD45 and CD14 antigens on their surface, which are known to be involved in immune cell maturation and macrophage activation in humans. Our evidence on how PVP–AuNPs may stimulate sea urchin immune cells represents an important starting point for planning new research work on the topic. ; This project has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement (No. 671881).

ACS AuthorChoice - This is an open access article published under an ACS AuthorChoice License.-- et al. ; We report the fine-tuning of the localized surface plasmon resonances (LSPRs) from ultraviolet to near-infrared by nanoengineering the metal nanoparticle morphologies from solid Ag nanocubes to hollow AuAg nanoboxes and AuAg nanoframes. Spatially resolved mapping of plasmon resonances by electron energy loss spectroscopy (EELS) revealed a homogeneous distribution of highly intense plasmon resonances around the hollow nanostructures and the interaction, that is, hybridization, of inner and outer plasmon fields for the nanoframe. Experimental findings are accurately correlated with the boundary element method (BEM) simulations demonstrating that the homogeneous distribution of the plasmon resonances is the key factor for their improved plasmonic properties. As a proof of concept for these enhanced plasmonic properties, we show the effective label free sensing of bovine serum albumin (BSA) of single-walled AuAg nanoboxes in comparison with solid Au nanoparticles, demonstrating their excellent performance for future biomedical applications. ; J.A. and A.G. acknowledge the funding from Generalitat de Catalunya 2014 SGR 1638 and Spanish MICINN Project eATOM (MAT2014-51480-ERC). A.G. acknowledges the Turkish Ministry of National Education for the Ph.D. scholarship. J.P., N.G.B., and V.P. acknowledge financial support from the Generalitat de Catalunya 2014-SGR-612, Spanish MICINN (MAT2012-33330), and European Community (EU-FP7) through the FutureNanoNeeds project. N.G.B. thanks the Spanish MICINN for the financial support through the Juan de la Cierva program and European Commission for the Career Integration Grant (CIG)-Marie Curie Action. Some of the research leading to these results has received funding from the European Union Seventh Framework Program under Grant Agreement 312483 - ESTEEM2 (Integrated Infrastructure Initiative − I3). ; Peer Reviewed

The effects of adding zero-valent iron nanoparticles (nZVI) on the physicochemical, biological and biochemical responses of a semi-continuous anaerobic digestion of sewage sludge have been assessed. Two sets of consecutive experiments of 103 and 116 days, respectively, were carried out in triplicate. nZVI were magnetically retained in the reactors, and the effect of punctual doses (from 0.27 to 4.33 g L) over time was studied. Among the different parameters monitored, only methane content in the biogas was significantly higher when nZVI was added. However, this effect was progressively lost after the addition, and in 5–7 days, the methane content returned to initial values. The increase in the oxidation state of nanoparticles seems to be related to the loss of effect over time. Higher dose (4.33 g L) sustained positive effects for a longer time along with higher methane content, but this fact seems to be related to microbiome acclimation. Changes in microbial community structure could also play a role in the mechanisms involved in methane enhancement. In this sense, the microbial consortium analysis reported a shift in the balance among acetogenic eubacterial communities, and a marked increase in the relative abundance of members assigned to Methanothrix genus, recognized as acetoclastic species showing high affinity for acetate, which explain the rise in methane content in the biogas. This research demonstrates that biogas methane enrichment in semicontinuous anaerobic digesters can be achieved by using nZVI nanoparticles, thus increasing energy production or reducing costs of a later biogas upgrading process. ; Raquel Barrena is grateful to TECNIOspring fellowship programme (TECSPR15-1-0051) co-financed by the European Union through the Marie Curie Actions and ACCIÓ (Generalitat de Catalunya).

[Background and aims]: The occurrence of endothelial alterations in the liver and in the splanchnic vasculature of cirrhotic patients and experimental models of liver diseases has been demonstrated. However, the pathological role of the portal vein endothelium in this clinical context is scarcely studied and, therefore, deserves attention. In this context, we aimed to investigate whether pathological endothelial activation occurs in the portal vein of cirrhotic rats. ; [Methods]: Cirrhosis was induced in wistar rats by CCl4 inhalation. We generated immortalized endothelial cells from the portal vein of control (CT-iPVEC) and cirrhotic rats (CH-iPVEC) by retroviral transduction of the SV40 T antigen. We assessed differential gene expression and intracellular reactive oxygen species (ROS) levels in iPVECs and in portal veins of control and cirrhotic rats. Finally, we assessed the therapeutic effectiveness of cerium oxide nanoparticles (CeO2NP) on reversing PVEC activation and macrophage polarization. ; [Results]: CH-iPVECs overexpressed collagen-I, endothelin-1, TIMP-1, TIMP-2, IL-6 and PlGF genes. These results were consistent with the differential expression showed by whole portal veins from cirrhotic rats. In addition, CH-iPVECs showed a significant increase in intracellular ROS and the capacity of potentiating M1 polarization in macrophages. The treatment of CH-iPVECs with CeO2NPs blocked intracellular ROS formation and IL-6 and TIMP-2 gene overexpression. In agreement with the in vitro results, the chronic treatment of cirrhotic rats with CeO2NPs also resulted in the blockade of both ROS formation and IL-6 gene overexpression in whole portal veins. ; [Conclusions]: Endothelial cells from portal vein of cirrhotic rats depicted an abnormal phenotype characterized by a differential gene expression and the induction of M1 polarization in macrophages. We identified the excess of intracellular reactive oxygen species (ROS) as a major contributor to this altered phenotype. In addition, we demonstrated the utility of the nanomaterial cerium oxide as an effective antioxidant capable of reverse some of these pathological features associated with the portal vein in the cirrhosis condition. ; Supported by grants from the Ministerio de Economia y Competitividad (SAF 2015-64126-R to WJ, PI15-00077 to GC and SAF2016-75358-R to MM-R), co-financed by FEDER, European Union, a way of making Europe, Fundacio La Marato de TV3 (Marato 120930), Spanish MINECO (MAT2015-70725-R) and the Catalan Agència de Gestio d'Ajuts Universitaris i de Recerca (AGAUR) (2017-SGR-143 to VP and 2016-BP-00301 to EC). JR-V is the recipient of a BIOTRACK Postdoctoral Fellowship supported by the European Community's Seventh Framework Programme and the MINECO (Contract 229673). CIBERehd is financed by the Instituto de Salud Carlos III. ; Peer reviewed

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic accumulation of lipids. Antisteatotic effects of cerium oxide nanoparticles (CeO2NPs) have recently been shown in animal models of liver disease. However, it is unclear whether the activity of CeO2NPs is related solely to the decrease in oxidative stress or, in addition, they directly decrease liver fatty acid accumulation. To address this question, in this work, we used an in vitro model of hepatocellular steatosis, exposing HepG2 cells to oleic and palmitic acid. Cell uptake of CeO2NPs and their effect on oxidative stress and viability of hepatic cells cultured with H2O2 were also evaluated. Results show that CeO2NPs were uptaken by HepG2 cells and reduced oxidative stress and improved cell viability. Treatment with oleic and palmitic acid increased lipogenesis and the content of different fatty acids. CeO2NPs reduced palmitic and stearic acid and most fatty acids consisting of more than 18 carbon atoms. These effects were associated with significant changes in elongase and desaturase activity. In conclusion, CeO2NPs directly protected HepG2 cells from cell injury in oxidative stress conditions and reduced fatty acid content in steatotic conditions by inducing specific changes in fatty acid metabolism, thus showing potential in the treatment of NAFLD. ; This research was funded by Ministerio de Economía y Competitividad, grant number PI15-00077 to G.C. and SAF2016-75358-R to M.M-R., co-financed by FEDER, European Union, "A way of making Europe".; "Secretaria d'Universitats i Recerca del Departament d'Empresa i Coneixement de la Generalitat de Catalunya, convocatòria d'Indústria del Coneixement modalitat B", grant number 2018_PROD_00187 toW.J, cofinanced by the European Union through the European Regional Development Fund (ERDF), "A way of making Europe".; CIBERehd is financed by the Instituto de Salud Carlos III.; Wuyi University Funding for Hight Talents Introduction, grant number 2018TP010 to E.C. and 2018TP011 to M.Z.; Foundation from Department of Education of Guangdong Province, grant number 2016KCXTD005 and 2017KSYS010, to E.C. and M.Z. The APC was funded by Wuyi University Funding for Hight Talents Introduction, grant number 2018TP010 to E.C. ; Peer reviewed

Progressive expansion of nanomaterials in our everyday life raises concerns about their safety for human health. Although kidneys are the primary organs of xenobiotic elimination, little attention has been paid to the kidneys in terms of nanotoxicological studies up to now. Here we investigate the cytotoxic and genotoxic potential of four solid-core uncoated inorganic nanoparticles (TiO2NPs, SiO2NPs, Fe3O4NPs and AuNPs) using the human renal proximal tubule epithelial TH1 cells. To mimic the in vivo conditions more realistic, TH1 cells were exposed in vitro to inorganic NPs under static as well as dynamic conditions for 3 h and 24 h. The medium throughput alkaline comet assay (12 minigels per slide) was employed to evaluate the impact of these NPs on genome integrity and their capacity to produce oxidative lesions to DNA. The accumulation and localization of studied inorganic NPs inside the cells was monitored by transmission electron microscopy (TEM) and the efficacy of internalization of particular NPs was determined by atomic absorption spectroscopy (AAS) and inductively coupled plasma mass spectrometry (ICP-MS). From all the tested NPs, only Fe3O4NPs induced a slight cytotoxicity in TH1 cells exposed to high concentrations (>700 μg/ml) for 24 h. On the other hand, the inorganic NPs did not increase significantly the level of DNA strand breaks or oxidative DNA damage regardless of the treatment mode (static vs. dynamic conditions). Interestingly, substantial differences were observed in the internalized amount of inorganic NPs in TH1 cells exposed to equivalent (2.2 μg/ml) concentration. Fe3O4NPs were most efficiently taken up while the lowest quantity of particles was determined in TiO2NPs-treated cells. As the particle size and shape of individual inorganic NPs in culture medium was nearly identical, it is reasonable to suppose that the chemical composition may contribute to the differences in the efficacy of NPs uptake. ; This article was created by the realization of the H2020 project HISENTS No. 685817, COST Action CA15132, VEGA grant 2/0056/17, project "Center of excellence of environmental health", ITMS No. 26240120033, based on the support of operational Research and development program financed from the European Regional Development Fund; and the EEA projectSK0020. Filip Razga received support within the SASPRO Programme (Project No. 0057/01/02) co-funded by the European Union and the Slovak Academy of Sciences. ; Peer reviewed

Dendritic cells (DCs) shape immune responses by influencing T-cell activation. Thus, they are considered both an interesting model for studying nano-immune interactions and a promising target for nano-based biomedical applications. However, the accentuated ability of nanoparticles (NPs) to interact with biomolecules may have an impact on DC function that poses an unexpected risk of unbalanced immune reactions. Here, we investigated the potential effects of gold nanoparticles (AuNPs) on DC function and the consequences for effector and memory T-cell responses in the presence of the microbial inflammatory stimulus lipopolysaccharide (LPS). Overall, we found that, in the absence of LPS, none of the tested NPs induced a DC response. However, whereas 4-, 8-, and 11 nm AuNPs did not modulate LPS-dependent immune responses, 26 nm AuNPs shifted the phenotype of LPS-activated DCs toward a tolerogenic state, characterized by downregulation of CD86, IL-12 and IL-27, upregulation of ILT3, and induction of class E compartments. Moreover, this DC phenotype was less proficient in promoting Th1 activation and central memory T-cell proliferation. Taken together, these findings support the perception that AuNPs are safe under homeostatic conditions; however, particular care should be taken in patients experiencing a current infection or disorders of the immune system. ; This work was supported by the European Union's Horizon 2020, Research and Innovation program (European Training Network PANDORA) [grant number 671881] and by the Austrian Science Fund (FWF) [grant number W01213], County of Salzburg, Cancer Cluster Salzburg [grant number 20102-P1601064-FPR01-2017].

Soils might be a final sink for Ag2S nanoparticles (NPs). Still, there are limited data on their effects on soil bacterial communities (SBC). To bridge this gap, we investigated the effects of Ag2S NPs (10 mg kg−1 soil) on the structure and function of SBC in a terrestrial indoor mesocosm, using a multi-species design. During 28 days of exposure, the SBC function-related parameters were analysed in terms of enzymatic activity, community level physiological profile, culture of functional bacterial groups [phosphorous-solubilizing bacteria (P-SB) and heterotrophic bacteria (HB)], and SBC structure was analysed by 16S rRNA gene-targeted denaturing gradient gel electrophoresis. ; The SBC exposed to Ag2S NPs showed a significative decrease of functional parameters, such as β-glucosidase activity and L-arginine consumption, and increase of the acid phosphatase activity. At the structural level, significantly lower richness and diversity were detected, but at later exposure times compared to the AgNO3 treatment, likely because of a low dissolution rate of Ag2S NPs. In fact, stronger effects were observed in soils spiked with AgNO3, in both functional and structural parameters. Changes in SBC structure seem to negatively correlate with parameters related to phosphorous (acid phosphatase activity) and carbon cycling (abundance of HB, P-SB, and β-glucosidase activity). Our results indicate a significant effect of Ag2S NPs on SBC, specifically on parameters related to carbon and phosphorous cycling, at doses as low as 10 mg kg-1 soil. These effects were only observed after 28 days, highlighting the importance of long-term exposure experiments for slowly dissolving NPs. ; All the authors were funded by the European Union Horizon 2020 project Nano-FASE (Nanomaterial Fate and Speciation in the Environment; grant no. 646002). SL, IH, SP and ZK received additional financial support from Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior (FCT/MCTES), through national funds, to CESAM (UIDP/50017/2020 + UIDB/50017/2020). Also, this work was supported by FCT through a PhD grant to Sara Peixoto (SFRH/BD/117738/2016). ; Peer reviewed

Despite the obvious advantages of gold nanoparticles for biomedical applications, controversial and incomplete toxicological data hamper their widespread use. Here, we present the results from an in vivo toxicity study using gold nanoparticles coated with polyethylene glycol (PEG-AuNPs). The pharmacokinetics and biodistribution of PEG-AuNPs were examined in the rat's liver, lung, spleen, and kidney after a single i.v. injection (0.7 mg/kg) at different time intervals. PEG-AuNPs had a relatively long blood circulation time and accumulated primarily in the liver and spleen, where they remained for up to 28 days after administration. Increased cytoplasmic vacuolation in hepatocytes 24 h and 7 days after PEG-AuNPs exposure and apoptotic-like cells in white splenic pulp 24 h after administration has been detected, however, 28 days post-exposure were no longer observed. In contrast, at this time point, we identified significant changes in lipid metabolism, altered levels of liver injury markers, and elevated monocyte count, but without marked biological relevance. In blood cells, no DNA damage was present in any of the studied time intervals, with the exception of DNA breakage transiently detected in primary kidney cells 4 h post-injection. Our results indicate that the tissue accumulation of PEG-AuNPs might result in late toxic effects. ; This paper is supported by European Union's Horizon 2020 research and innovation program under grant agreement No. 857381, project VISION (Strategies to strengthen scientific excellence and innovation capacity for early diagnosis of gastrointestinal cancers), project HISENTS No. 685817, VEGA grants 2/0055/20, 2/0121/21.

This article belongs to the Special Issue Innovative Molecular Target and Therapeutic Approaches in Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis (NAFLD/NASH). ; Cerium oxide nanoparticles (CeO2NPs) possess powerful antioxidant properties, thus emerging as a potential therapeutic tool in non-alcoholic fatty liver disease (NAFLD) progression, which is characterized by a high presence of reactive oxygen species (ROS). The aim of this study was to elucidate whether CeO2NPs can prevent or attenuate oxidant injury in the hepatic human cell line HepG2 and to investigate the mechanisms involved in this phenomenon. The effect of CeO2NPs on cell viability and ROS scavenging was determined, the differential expression of pro-inflammatory and oxidative stress-related genes was analyzed, and a proteomic analysis was performed to assess the impact of CeO2NPs on cell phosphorylation in human hepatic cells under oxidative stress conditions. CeO2NPs did not modify HepG2 cell viability in basal conditions but reduced H2O2- and lipopolysaccharide (LPS)-induced cell death and prevented H2O2-induced overexpression of MPO, PTGS1 and iNOS. Phosphoproteomic analysis showed that CeO2NPs reverted the H2O2-mediated increase in the phosphorylation of peptides related to cellular proliferation, stress response, and gene transcription regulation, and interfered with H2O2 effects on mTOR, MAPK/ERK, CK2A1 and PKACA signaling pathways. In conclusion, CeO2NPs protect HepG2 cells from cell-induced oxidative damage, reducing ROS generation and inflammatory gene expression as well as regulation of kinase-driven cell survival pathways. ; This research was funded by grants to W. Jiménez from Ministerio de Economia y Competitividad [grants, SAF2015-64126-R, RTI2018-094734-B-C21], to M. Morales-Ruiz [grant SAF2016-75358-R] and to G. Casals [grant PI-15/00777]; cofinanced by FEDER, European Union, a way of making Europe, Agència de Gestió d'Ajuts Universitaris i de Recerca [grant SGR 2014/219]; and Fundació La Marató de TV3 [grant Marató 120930];Wuyi University Funding for Hight Talents Introduction, grant number 2018TP010 and Foundation from Department of Education of Guangdong Province, grant number 2016KCXTD005 and 2017KSYS010, to Eudald Casals The Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) is funded by the Instituto de Salud Carlos III. ; Peer reviewed

Some findings of these studies were previously presented at The International Liver Congress (ILC) 2017 Meeting of the European Association for the Study of the Liver (EASL) (19–23 April, 2017; Amsterdam, The Netherlands). ; Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, ranging from steatosis to non-alcoholic steatohepatitis (NASH). Recently, cerium oxide nanoparticles (CeO2NPs) have emerged as a new antioxidant agent with hepatoprotective properties in experimental liver disease. The aim of the current investigation was to elucidate whether CeO2NPs display beneficial effects in an experimental model of NAFLD.Therefore, fifteen Wistar rats were subjected to a methionine and choline deficient diet (MCDD) for 6 weeks and intravenously treated with CeO2NP or vehicle during the weeks three and four of the diet. The effect of CeO2NPs on serum biochemistry, hepatic steatosis, inflammation, fatty acid content and expression of reactive oxygen species (ROS) and lipid metabolism related genes was assessed. MCDD fed rats showed increased inflammation, enhanced hepatic lipid accumulation of both saturated and unsaturated fatty acids (FAs) and overexpression of genes related to fatty liver and ROS metabolism. Treatment with CeO2NPs was able to reduce the size and content of hepatocyte lipid droplets, the hepatic concentration of triglyceride- and cholesterol ester-derived FAs and the expression of several genes involved in cytokine, adipokine and chemokine signaling pathways. These findings suggest that CeO2NPs could be of beneficial value in NAFLD. ; This research was supported by grants to W. Jiménez from Ministerio de Economia y Competitividad [grants SAF2015-64126R, 12-35979, BES-2013-063685, SAFRTI2018-094734-B-C21], to M. Morales-Ruiz [grant SAF2016-75358-R] and to G. Casals [grant P74844I/15/00777]; Cofinanced by FEDER, European Union, a way of making Europe, Agència de Gestió d'Ajuts Universitaris i de Recerca [grant SGR 2014/219]. The Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) is funded by the Instituto de Salud Carlos III. ; Peer reviewed