Lipid-induced hepatocyte-derived extracellular vesicles regulate hepatic stellate cell via microRNAs targeting PPAR-γ.

Background&aimsHepatic stellate cells (HSCs) play a key role in liver fibrosis in various chronic liver disorders including nonalcoholic fatty liver disease (NAFLD). The development of liver fibrosis requires a phenotypic switch from quiescent to activated HSCs. The triggers for HSCs activation in NAFLD remain poorly understood. We investigated the role and molecular mechanism of extracellular vesicles (EVs) released by hepatocytes during lipotoxicity in modulation of HSC phenotype.MethodsEVs were isolated from fat-laden hepatocytes by differential centrifugation and incubated with HSCs. EV internalization and HSCs activation, migration and proliferation were assessed. Loss- and gain-of-functions studies were performed to explore the potential role of PPAR-γ-targeting miRNAs carried by EVs into HSC.ResultsHepatocyte-derived EVs released during lipotoxicity are efficiently internalized by HSCs resulting in their activation, as shown by marked up-regulation of pro-fibrogenic genes (Collagen-I, α-SMA and TIMP-2), proliferation, chemotaxis and wound healing responses. These changes were associated with miRNAs shuttled by EVs and suppression of PPAR-γ expression in HSC. Hepatocyte-derived EVs miRNA content included various miRNAs that are known inhibitors of PPAR-γ expression with miR-128-3p being the most effectively transferred. Furthermore loss- and gain-of-function studies identified miR-128-3p as a central modulator of the effects of EVs on PPAR-γ inhibition and HSC activation.ConclusionOur findings demonstrate a link between fat-laden hepatocyte-derived EVs and liver fibrosis and have potential implications for the development of novel anti-fibrotic targets for NAFLD and other fibrotic diseases

Reduced dietary omega-6 to omega-3 fatty acid ratio and 12/15-lipoxygenase deficiency are protective against chronic high fat diet-induced steatohepatitis

Obesity is associated with metabolic perturbations including liver and adipose tissue inflammation, insulin resistance, and type 2 diabetes. Omega-6 fatty acids (ω6) promote and omega-3 fatty acids (ω3) reduce inflammation as they can be metabolized to pro- and anti-inflammatory eicosanoids, respectively. 12/15-lipoxygenase (12/15-LO) enzymatically produces some of these metabolites and is induced by high fat (HF) diet. We investigated the effects of altering dietary ω6/ω3 ratio and 12/15-LO deficiency on HF diet-induced tissue inflammation and insulin resistance. We examined how these conditions affect circulating concentrations of oxidized metabolites of ω6 arachidonic and linoleic acids and innate and adaptive immune system activity in the liver. For 15 weeks, wild-type (WT) mice were fed either a soybean oil-enriched HF diet with high dietary ω6/ω3 ratio (11∶1, HFH), similar to Western-style diet, or a fat Kcal-matched, fish oil-enriched HF diet with a low dietary ω6/ω3 ratio of 2.7∶1 (HFL). Importantly, the total saturated, monounsaturated and polyunsaturated fat content was matched in the two HF diets, which is unlike most published fish oil studies in mice. Despite modestly increased food intake, WT mice fed HFL were protected from HFH-diet induced steatohepatitis, evidenced by decreased hepatic mRNA expression of pro-inflammatory genes and genes involved in lymphocyte homing, and reduced deposition of hepatic triglyceride. Furthermore, oxidized metabolites of ω6 arachidonic acid were decreased in the plasma of WT HFL compared to WT HFH-fed mice. 12/15-LO knockout (KO) mice were also protected from HFH-induced fatty liver and elevated mRNA markers of inflammation and lymphocyte homing. 12/15-LOKO mice were protected from HFH-induced insulin resistance but reducing dietary ω6/ω3 ratio in WT mice did not ameliorate insulin resistance or adipose tissue inflammation. In conclusion, lowering dietary ω6/ω3 ratio in HF diet significantly reduces steatohepatitis.Fil: Lazic, Milos. University of California at San Diego; Estados UnidosFil: Inzaugarat, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Povero, Davide. University of California at San Diego; Estados UnidosFil: Zhao, Iris C.. University of California at San Diego; Estados UnidosFil: Chen, Mark. University of California at San Diego; Estados UnidosFil: Nalbandian, Madlena. University of California at San Diego; Estados UnidosFil: Miller, Yury I.. University of California at San Diego; Estados UnidosFil: Cherñavsky, Alejandra Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Feldstein, Ariel E.. University of California at San Diego; Estados UnidosFil: Sears, Dorothy D.. University of California at San Diego; Estados Unido

Structure and Functionality of the Mesozooplankton Community in a Coastal Marine Environment: Portofino Marine Protected Area (Liguria)

This research is part of the LTER (Long-Term Ecological Research) project, a network of terrestrial, freshwater, transitional water and marine sites, on which ecological research is conducted on a multi-decade scale. LTER studies ecosystems, their dynamics and evolution, the relationships between biodiversity and ecological functionality, water quality, productivity, the role of resource availability, the effects of pollution and climate change. The research focuses on the study of the variability of zooplankton groups in the Portofino marine protected area, in Punta Faro. The samplings were carried out in the years 2018\u20132019, and the results were compared with the values of the years 2003\u20132005, interesting from a meteorological climatic and biological point of view. The plankton community of the Punta Faro system was analyzed by means of a modeling approach to obtain information on the functionality and health status of the system and to verify whether this has undergone any alterations in the last decade. The analyses carried out show a clear difference between the three-year period 2003\u20132005 and the two-year period 2018\u20132019, highlighting how environmental changes, such as the increase in temperature, have led to higher costs of system functioning in the last two years. The mesozooplankton community has changed both in terms of abundance of organisms and in terms of organization and functionality

Omega-3 fatty acids in parenteral nutrition: a systematic review with network meta-analysis on clinical outcomes

Background & aims: Accumulating scientific evidence supports the benefits of parenteral nutrition (PN) with fish oil (FO) containing intravenous lipid emulsions (ILEs) on clinical outcomes. Yet, the question of the most effective ILE remains controversial. We conducted a network meta-analysis (NMA) to compare and rank different types of ILEs in terms of their effects on infections, sepsis, ICU and hospital length of stay, and in-hospital mortality in adult patients.Methods: MEDLINE, EMBASE, and Web of Science databases were searched for randomized controlled trials (RCTs) published up to May 2022, investigating ILEs as a part of part of PN covering at least 70% of total energy provision. Lipid emulsions were classified in four categories: FO-ILEs, olive oil (OO)-ILEs, medium-chain triglyceride (MCT)/soybean oil (SO)-ILEs, and pure SO-ILEs. Data were statistically com-bined through Bayesian NMA and the Surface Under the Cumulative RAnking (SUCRA) was calculated for all outcomes. Results: 1651 publications were retrieved in the original search, 47 RCTs were included in the NMA. For FO-ILEs, very highly credible reductions in infection risk versus SO-ILEs [odds ratio (OR) = 0.43 90% credibility interval (CrI) (0.29-0.63)], MCT/soybean oil-ILEs [0.59 (0.43-0.82)], and OO-ILEs [0.56 (0.33-0.91)], and in sepsis risk versus SO-ILEs [0.22 (0.08-0.59)], as well as substantial reductions in hospital length of stay versus SO-ILEs [mean difference (MD) =-2.31 (-3.14 to-1.59) days] and MCT/SO-ILEs (-2.01 (-2.82 to-1.22 days) were shown. According to SUCRA score, FO-ILEs were ranked first for all five outcomes.Conclusions: In hospitalized patients, FO-ILEs provide significant clinical benefits over all other types of ILEs, ranking first for all outcomes investigated. Registration no: PROSPERO 2022 CRD42022328660.(c) 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Enhanced Botrytis cinerea resistance of Arabidopsis plants grown in compost may be explained by increased expression of defense-related genes, as revealed by microarray analysis

Composts are the products obtained after the aerobic degradation of different types of organic matter waste and can be used as substrates or substrate/soil amendments for plant cultivation. There is a small but increasing number of reports that suggest that foliar diseases may be reduced when using compost, rather than standard substrates, as growing medium. The purpose of this study was to examine the gene expression alteration produced by the compost to gain knowledge of the mechanisms involved in compost-induced systemic resistance. A compost from olive marc and olive tree leaves was able to induce resistance against Botrytis cinerea in Arabidopsis, unlike the standard substrate, perlite. Microarray analyses revealed that 178 genes were differently expressed, with a fold change cut-off of 1, of which 155 were up-regulated and 23 were down-regulated in compost-grown, as against perlite-grown plants. A functional enrichment study of up-regulated genes revealed that 38 Gene Ontology terms were significantly enriched. Response to stress, biotic stimulus, other organism, bacterium, fungus, chemical and abiotic stimulus, SA and ABA stimulus, oxidative stress, water, temperature and cold were significantly enriched, as were immune and defense responses, systemic acquired resistance, secondary metabolic process and oxireductase activity. Interestingly, PR1 expression, which was equally enhanced by growing the plants in compost and by B. cinerea inoculation, was further boosted in compost-grown pathogen-inoculated plants. Compost triggered a plant response that shares similarities with both systemic acquired resistance and ABA-dependent/independent abiotic stress responses

Formation of ionospheric irregularities over Southeast Asia during the 2015 St. Patrickˈs Day storm

We investigate the geospace response to the 2015 St. Patrickˈs Day storm leveraging on instruments spread over Southeast Asia (SEA), covering a wide longitudinal sector of the low-latitude ionosphere. A regional characterization of the storm is provided, identifying the peculiarities of ionospheric irregularity formation. The novelties of this work are the characterization in a broad longitudinal range and the methodology relying on the integration of data acquired by Global Navigation Satellite System (GNSS) receivers, magnetometers, ionosondes, and Swarm satellites. This work is a legacy of the project EquatoRial Ionosphere Characterization in Asia (ERICA). ERICA aimed to capture the features of both crests of the equatorial ionospheric anomaly (EIA) and trough (EIT) by means of a dedicated measurement campaign. The campaign lasted from March to October 2015 and was able to observe the ionospheric variability causing effects on radio systems, GNSS in particular. The multiinstrumental and multiparametric observations of the region enabled an in-depth investigation of the response to the largest geomagnetic storm of the current solar cycle in a region scarcely reported in literature. Our work discusses the comparison between northern and southern crests of the EIA in the SEA region. The observations recorded positive and negative ionospheric storms, spread F conditions, scintillation enhancement and inhibition, and total electron content variability. The ancillary information on the local magnetic field highlights the variety of ionospheric perturbations during the different storm phases. The combined use of ionospheric bottomside, topside, and integrated information points out how the storm affects the F layer altitude and the consequent enhancement/suppression of scintillations.Published12211–122331A. Geomagnetismo e Paleomagnetismo2A. Fisica dell'alta atmosfera1IT. Reti di monitoraggio e Osservazioni5IT. Osservazioni satellitariJCR Journalope