Project description:From the result of the gene expression analyses of human hepatoma cell line, HepG2, a number of genes associated with cell proliferation and DNA repair were distinctively up-regulated by Ag-nanoparticle exposure, suggesting that Ag-nanoparticles might stimulate cell proliferation and DNA damage, which are considered to be mechanisms playing an important role for carcinogenesis and tumor progression. The inductions of these genes involved in cell proliferation were also observed in PS-nanoparticles and Ag2CO3-exposed cells. In addition, the inductions of DNA repair-associated genes were also observed in Ag2CO3-exposure. These results suggest that both “nanoshape” and “silver” can cause the inductions of these gene expression patterns. Furthermore, cysteine, a strong ionic silver ligand partially abolished these gene expressions induced by silver nanoparticles. Ionic silver sourced from Ag-nanoparticles could not fully explain these gene expressions.
Project description:Dietary lipids and gut microbiota may both influence adipose tissue physiology. By feeding conventional and germ-free mice high fat diets with different lipid compositon we aimed to investigate how dietary lipids and the gut microbiota interact to influence inflammation and metabolism in the liver
Project description:Dietary lipids and gut microbiota may both influence adipose tissue physiology. By feeding conventional and germ-free mice high fat diets with different lipid compositon we aimed to investigate how dietary lipids and the gut microbiota interact to influence inflammation and metabolism in epididymal adipiose tissue (EWAT)
Project description:Silver nanoparticles cause toxicity in exposed organisms and are an environmental health concern. The mechanisms of silver nanoparticle toxicity, however, remain unclear. We examined the effects of exposure to silver in nano-, bulk- and ionic forms on zebrafish embryos (Danio rerio) using a Next Generation Sequencing approach in an Illumina platform (High-Throughput SuperSAGE). Significant alterations in gene expression were found for all treatments and many of the gene pathways affected, most notably those associated with oxidative phosphorylation and protein synthesis, overlapped strongly between the three treatments indicating similar mechanisms of toxicity for the three forms of silver studied. Changes in oxidative phosphorylation indicated a down-regulation of this pathway at 24h of exposure, but with a recovery at 48h. This finding was consistent with a dose-dependent decrease in oxygen consumption at 24h, but not at 48h, following exposure to silver ions. Overall, our data provide support for the hypothesis that the toxicity caused by silver nanoparticles is principally associated with bioavailable silver ions in exposed zebrafish embryos. These findings are important in the evaluation of the risk that silver particles may pose to exposed vertebrate organisms. mRNA profiles of whole zebrafish embryos at 24 and 48 hours post-fertilisation (hpf) exposed to silver in nano, bulk and ionic forms were generated by deep sequencing using HT-SuperSAGE (Illumina GA2).
Project description:Because of their small size, nanoparticles that enter the human body can easily penetrate biological barriers and can be circulated throughout the entire body, ultimately reaching the vascular endothelium. In this study aimed to identify cell reponses by distinguishing endothelial cell and exposing them to silver nanoparticles. The study also assesseed several gene expression levels that increased significantly in the microarray assay. We verified through microarray that 5 nm silver nanoparticles affect the variation of gene expression in cells, and a noticeable increase in the expression of interleukin (IL)-8 and IL-11 genes in early time was also verified. This study found that the variation on oxidative stress related genes in early time, amd among them the variation of metallothionein(MT), heme oxygenase 1(HO1), and heat shock 70kDa protein(HSP70) expression, was noticeable. This study finds that intracellular genes specifically respond to exposure to silver nanoparticles and that the expression of IL-11 among cytokines is noticeable.
Project description:Nanoparticles are compounds of emerging concern with largely unknown risks for human and ecological health. It is crucial to evaluate their potential biological impact to prevent unintended adverse effects on human health and the environment. We analyzed the transcriptional effects of polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) and silver nitrate (AgNO3) on the fathead minnow (Pimephales promelas) to understand their potential toxicity and adverse outcomes. We also tested the feasibility of the fathead minnow as an alternative species to elucidate potential adverse effects on humans. Fathead minnow females were exposed to either 4 µg/L of AgNO3 or 70 µg/L of PVP-AgNPs for 96h. Microarray analyses were performed on liver and brain. Functional analysis identified potential toxicity pathways and molecular initiating events (MIEs) that were confirmed with functional assays. Data suggested that AgNO3 and PVP-AgNPs had both common and distinct transcriptional effects. The nanoparticles were linked to neurotoxicity and oxidative stress, and identified as a dopamine receptor antagonist. Silver nitrate was also identified as a potential neurotoxicant and was confirmed as adrenergic and cannabinoid receptors antagonist. While silver nitrate and PVP-AgNPs were both potential neurotoxicants, they appeared to act through different MIEs. Fathead minnow is a promising alternative species to elucidate potential adverse effects of relevance to human health. We analyzed the transcriptional effects of polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) and silver nitrate (AgNO3) on the fathead minnow (Pimephales promelas) to understand their potential toxicity and adverse outcomes. FHM were obtained from Aquatic Biosystems (Fort Collins, CO), held in aerated dechlorinated tap water and fed three times daily with Zeigler® AquaTox Feed Gardners, PA, USA). Fathead minnow females were exposed to either 4 µg/L of AgNO3 or 70 µg/L of PVP-AgNPs (Luna Innovations, Blackburn, VA) for 96h at 24°C ± 1 with a 90% water change at 48 hours. Microarray analyses were performed on liver and brain.
Project description:Dietary lipids and gut microbiota may both influence adipose tissue physiology. By feeding conventional and germ-free mice high fat diets with different lipid compositon we aimed to investigate how dietary lipids and the gut microbiota interact to influence inflammation and metabolism in the liver Wild-type C57Bl/6 male mice 11 weeks of age were fed isocaloric diets (45% kcal fat) with either menhaden fish oil (Research Diets, D05122102) or lard (Research Diets, D10011202) for 11 weeks. Liver samples were harvested at the end of the experiment and analyzed by microarray.
Project description:Dietary lipids and gut microbiota may both influence adipose tissue physiology. By feeding conventional and germ-free mice high fat diets with different lipid compositon we aimed to investigate how dietary lipids and the gut microbiota interact to influence inflammation and metabolism in epididymal adipiose tissue (EWAT) Wild-type C57Bl/6 male mice 11 weeks of age were fed isocaloric diets (45% kcal fat) with either menhaden fish oil (Research Diets, D05122102) or lard (Research Diets, D10011202) for 11 weeks. Epididymal WAT samples were harvested at the end of the experiment and analyzed by microarray.
Project description:Silver nanoparticles are used in consumer products like food contact materials, drinking water technologies and supplements, due to their antimicrobial properties. This leads to an oral uptake and exposure of intestinal cells. In contrast to other studies we found no apoptosis induction by surfactant coated silver nanoparticles in the intestinal cell model Caco-2 in a previous study, although the particles induced oxidative stress, morphological changes and cell death. Therefore, this study aimed to analyze the molecular mechanism of silver nanoparticles in Caco-2 cells. We used global gene expression profiling in differentiated Caco-2 cells, supported by verification of the microarray data by quantitative real time RT-PCR and microscopic analysis, impedance measurements and assays for apoptosis and oxidative stress. Our results revealed that the majority of surfactant coated silver nanoparticles are not taken up into differentiated Caco-2 cells. and probably affect the cells by outside-in signaling. They induce oxidative stress and have an influence on canonical pathways related to FAK, ILK, ERK, MAPK, integrins and adherence and tight junctions, thereby inducing transcription factors like AP1, NFĸB and NRF2, which mediate cellular reactions in response to oxidative stress and metal ions and induce changes in the cytoskeleton and cell-cell and cell-matrix contacts. The present data confirm the absence of apoptotic cell death. Non-apoptotic, necrotic cell death, especially in the intestine, can cause inflammation and influence the mucosal immune response.