Cerium Oxide Nanoparticles Protect against Oxidant Injury and Interfere with Oxidative Mediated Kinase Signaling in Human-Derived Hepatocytes

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

Bespoken Nanoceria : An Effective Treatment in Experimental Hepatocellular Carcinoma

Despite the availability of new-generation drugs, hepatocellular carcinoma (HCC) is still the third most frequent cause of cancer-related deaths worldwide. Cerium oxide nanoparticles (CeONPs) have emerged as an antioxidant agent in experimental liver disease because of their antioxidant, anti-inflammatory, and antisteatotic properties. In the present study, we aimed to elucidate the potential of CeONPs as therapeutic agents in HCC. HCC was induced in 110 Wistar rats by intraperitoneal administration of diethylnitrosamine for 16 weeks. Animals were treated with vehicle or CeONPs at weeks 16 and 17. At the eighteenth week, nanoceria biodistribution was assessed by mass spectrometry (MS). The effect of CeONPs on tumor progression and animal survival was investigated. Hepatic tissue MS-based phosphoproteomics as well as analysis of principal lipid components were performed. The intracellular uptake of CeONPs by human ex vivo perfused livers and human hepatocytes was analyzed. Nanoceria was mainly accumulated in the liver, where it reduced macrophage infiltration and inflammatory gene expression. Nanoceria treatment increased liver apoptotic activity, while proliferation was attenuated. Phosphoproteomic analysis revealed that CeONPs affected the phosphorylation of proteins mainly related to cell adhesion and RNA splicing. CeONPs decreased phosphatidylcholine-derived arachidonic acid and reverted the HCC-induced increase of linoleic acid in several lipid components. Furthermore, CeONPs reduced serum alpha-protein levels and improved the survival of HCC rats. Nanoceria uptake by ex vivo perfused human livers and in vitro human hepatocytes was also demonstrated. These data indicate that CeONPs partially revert the cellular mechanisms involved in tumor progression and significantly increase survival in HCC rats, suggesting that they could be effective in patients with HCC

Dynamic and wear study of an extremely bidisperse magnetorheological fluid

Acceso a la versión publicada en Smart Mater. Struct. 24(12) 127001 (http://iopscience.iop.org/0964-1726/24/12/127001)"This is an author-created, un-copyedited version of an article accepted for publication/published in Smart Materials and Structures. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at http://dx.doi.org/10.1088/0964-1726/24/12/127001."In this work the friction and wear properties of five magnetorheologicalfluids (MRFs)with varying compositions are investigated. Considering that many of the proposed applications for these fluids involve lubricated contact between mobile metal –metal or polymer– metal parts, the relationship between MR response and wear behavior appears to be of fundamental importance. One of the fluids(MR#1)contains only the iron microparticles and base oil; the second and third ones(MR#2 and MR#3) contain an anti-wear additive as well. The fourth one(MR#4)is a well known commercial MRF. Finally, MR#5 is stabilized by dispersing the iron particles in a magnetite ferrofluid. The MR response of the latter fluid is better(higher yield stress and post-yield viscosity)than that of the others. More importantly, it remains(and even improves)after the wear test: the pressure applied in the four-ball apparatus produces a compaction of the magnetite layer around the iron microparticles. Additionally, the friction coefficient is larger, which seems paradoxical in principle, but can be explained by considering the stability of MR#5 in comparison to the other four MRs, which appear to undergo partial phase separation during the test. In fact, electron and optical microscope observations confirm a milder wear effect of MR#5, with almost complete absence of scars from the steel test spheres and homogeneous and shallow grooves on them. Comparatively, MR#2, MR#3 and, particularly, MR#1 produce a much more significant wear.MINECO Ramón y Cajal Programme (RYC-2014-16901)MINECO FIS 2013-07666-C3-1-RCEI Biotic BS27.2015Junta de Andalucía, PE2012-FQM-069

Bespoken nanoceria: A new effective treatment in experimental hepatocellular carcinoma

Background and aims: Despite the availability of new-generation drugs, hepatocellular carcinoma (HCC) is still the third most frequent cause of cancer-related deaths worldwide. Cerium oxide nanoparticles (CeO2 NPs) have emerged as an antioxidant agent in experimental liver disease because of their antioxidant, anti-inflammatory, and antisteatotic properties. In the present study, we aimed to elucidate the potential of CeO2 NPs as therapeutic agents in HCC. Approach and results: HCC was induced in 110 Wistar rats by intraperitoneal administration of diethylnitrosamine for 16 weeks. Animals were treated with vehicle or CeO2 NPs at weeks 16 and 17. At the eighteenth week, nanoceria biodistribution was assessed by mass spectrometry (MS). The effect of CeO2 NPs on tumor progression and animal survival was investigated. Hepatic tissue MS-based phosphoproteomics as well as analysis of principal lipid components were performed. The intracellular uptake of CeO2 NPs by human ex vivo perfused livers and human hepatocytes was analyzed. Nanoceria was mainly accumulated in the liver, where it reduced macrophage infiltration and inflammatory gene expression. Nanoceria treatment increased liver apoptotic activity, while proliferation was attenuated. Phosphoproteomic analysis revealed that CeO2 NPs affected the phosphorylation of proteins mainly related to cell adhesion and RNA splicing. CeO2 NPs decreased phosphatidylcholine-derived arachidonic acid and reverted the HCC-induced increase of linoleic acid in several lipid components. Furthermore, CeO2 NPs reduced serum alpha-protein levels and improved the survival of HCC rats. Nanoceria uptake by ex vivo perfused human livers and in vitro human hepatocytes was also demonstrated. Conclusions: These data indicate that CeO2 NPs partially revert the cellular mechanisms involved in tumor progression and significantly increase survival in HCC rats, suggesting that they could be effective in patients with HCC. © 2020 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of American Association for the Study of Liver Diseases

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Predictive factors for flea occurrence in red foxes (Vulpes vulpes) from semi-arid Mediterranean environments

© 2022 Wiley-VCH GmbH. This document is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is accepted version of a published Work that appeared in final form in Medical and Veterinary Entomology. To access the final edited and published work see https://doi.org/10.1111/tbed.14393The role of red fox as host for a wide range of parasites, particularly fleas and other arthropods causing vector-borne diseases, in combination with its capability to adapt to anthropized environments, makes this wild canid an epidemiologically remarkable species at the wildlife–domestic–human interface, especially in the present time of rise of emerging and re-emerging diseases. This study evaluated the prevalence and parasite intensity of fleas in 88 foxes from Murcia Region (Southeastern Spain) and determined the geographic distribution of areas with the highest potential risk of flea presence. Pulex irritans, Ctenocephalides felis, Spilopsyllus cuniculi and Nosopsyllus fasciatus were identified. The overall prevalence was 76.13%. This is the first time that N. fasciatus has been reported in foxes from Murcia Region. The predictive model established a certain pattern to determine the areas with the highest risk of acquiring fleas. Positive correlation of daily potential evapotranspiration (ET0) in winter and the opposite effect occurring for ET0 in summer were obtained, as well as positive correlations for mean daily temperature (Tmean) in summer and mean precipitation (Pmean) in winter and summer. The model was also found positively correlated in the forest habitat ecotone areas and the anthropized area

African and Latin American family reunifications in Mediterranean Spain: dynamics and socio-demographic structures

Los extranjeros autorizados en 2006-2009 a residir en España por motivos de reagrupación familiar, muestran la importancia que ha alcanzado esta forma de inmigración en el total de nuevos extranjeros empadronados. La investigación se basa en una encuesta específica a reagrupantes africanos y latinoamericanos, que también informan sobre sus familiares reagrupados, hayan utilizado, o no, las leyes de reagrupación. Africanos y latinoamericanos ofrecen dinámicas y estructuras sociodemográficas muy diferentes, a resultas, entre otras causas, de la antigüedad de sus flujos, su fecundidad, su dominio del idioma español, su nivel de instrucción, sus posibilidades de ingresos, su estructura por sexo y edad, tamaño de las familias reagrupadas, etc. Se ofrece información para los dos colectivos continentales y para los subgrupos familiares —reagrupantes, cónyuges, hijos, progenitores y otros familiares—, y se utilizan escalas del conjunto estudiado y de ámbitos territoriales —Cataluña litoral, Comunidad Valenciana, Murcia-Almería—. Los africanos concentran los aspectos estructurales más negativos —idioma español, instrucción, ingresos,…—, pero también son los que declaran intenciones más firmes y generalizadas de permanencia en España. Las conclusiones orientan sobre el futuro de estos flujos.The amount of foreigners authorised to live in Spain as residents between 2006 and 2009 due to family reunification reflects the significance of this type of immigration in the number of new registered foreigners. This research is based on a specific survey carried out on Africans and Latin Americans, who also provide information on the family members who have joined them here, in accordance with reunification laws or not. Africans and Latin Americans have very different dynamics and socio-demographic structures due, amongst other reasons, to the antiquity of their flows, their fertility rates, their command of Spanish, their level of education, their possibility of income, their structure by sex and age, the size of the reunited families, etc. Information is provided on both continental groups and family subgroups —those who reunite the family, spouses, children, parents and other family members— using scales for the group studied and for the geographical area —coastal Catalonia, the Region of Valencia, Murcia and Almeria—. Africans report the most negative structural aspects —Spanish language, education, income, etc.—; nevertheless it is this group that claim to have more firm and generalised intentions of staying in Spain. The conclusions in this paper give an indication of future flows for these two groups.Investigación realizada dentro del Proyecto «La reagrupación familiar de los inmigrantes africanos y latinoamericanos en la España mediterránea», Ref. CSO2008-01796, financiado por el Ministerio de Ciencia e Innovación

Explorative analysis on Mullus barbatus ageing data variability in Mediterranean basin

The uncertainty in age estimation by otolith reading may be at the root of the large variability in red mullet (Mullus barbatus) growth models in the Mediterranean. In the MEDITS survey, red mullet age data are produced following the same sampling protocol and otolith reading methodology. However, ageing is assigned using different interpretation schemes, including variations in theoretical birthdate and number of false rings considered, in addition to differences in the experience level of readers. The present work analysed the influence of these variations and the geographical location of sampling on red mullet ageing using a multivariate approach (principal component analysis). Reader experience was the most important parameter correlated with the variability. The number of rings considered false showed a significant effect on the variability in the first age groups but had less influence on the older ones. The effect of the theoretical birthdate was low in all age groups. Geographical location had a significant influence, with longitude showing greater effects than latitude. In light of these results, workshops, exchanges and the adoption of a common ageing protocol based on age validation studies are considered fundamental tools for improving precision in red mullet ageing