Total mercury (Hg) concentration was determined in the tissues of 10 pelagic fishes in the northern Gulf of Mexico, and dietary tracers (stable isotopes and fatty acids) were used to evaluate the relationship between Hg and feeding history. Highest Hg levels were observed in blue marlin (Makaira nigricans), carcharhinid sharks (Carcha rhinus spp.), and little tunny (Euthynnus alletteratus), ranging from 1.08 to 10.52 ppm. Moderate to low concentrations (<1.0 ppm) were observed in blackfin tuna (Thunnus atlanticus), cobia (Rachycentron canadum), dolphinfish (Cory phaena hippurus), greater amberjack (Seriola dumerili), king mackerel (Scomberomorus cavalla), wahoo (Acantho cybium solandri), and yellowfin tuna (Thunnus albacares). For the majority of species examined, Hg concentrations did not vary significantly between location (Texas vs. Louisiana) or collection period (2002 and 2003). Significant positive relationships between Hg concentration and body size and (or) weight were detected for 6 of the 10 taxa examined. Hg concentration was also positively associated with trophic position. Three natural associations were identified using stable isotope and fatty acid signatures. Still, no connection between these natural trophic associations and Hg concentration was observed, suggesting that Hg concentration in pelagic fishes was more closely linked to trophic position and size than feeding history.
Dietary fibre, such as indigestible oligosaccharides and polysaccharides, occurs in many foods and has gained considerable importance related to its beneficial effects on host health and specific diseases. Dietary fibre is neither digested nor absorbed in the small intestine and modulates the composition of the gut microbiota. New evidence indicates that dietary fibre also interacts directly with the epithelium and immune cells throughout the gastrointestinal tract by microbiota‐independent effects. This review focuses on how dietary fibre improves human health and the reported health benefits that are connected to molecular pathways, in (a) a microbiota‐independent manner, via interaction with specific surface receptors on epithelial and immune cells regulating intestinal barrier and immune function, and (b) a microbiota‐dependent manner via maintaining intestinal homeostasis by promoting beneficial microbes, including Bifidobacteria and Lactobacilli, limiting the growth, adhesion, and cytotoxicity of pathogenic microbes, as well as stimulating fibre‐derived microbial short‐chain fatty acid production.
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This article is part of a themed section on The Pharmacology of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.6/issuetoc
Glioblastoma multiforme (GBM) is highly invasive, with a high recurrence rate and limited treatment options, and is the deadliest glioma. Exosomes (Exos) have attracted much attention in the diagnosis and treatment of GBM and are expected to address the severe limitations of biopsy conditions. Exos in the cerebrospinal fluid (CSF) have great potential in GBM dynamic monitoring and intervention strategies. Here, we evaluated the difference in the proteome information of Exos from the CSF (CSF-Exos) between GBM patients and low-grade glioma patients, and the correlations between GBM-CSF-Exos and immunosuppressive properties. Our results indicates that GBM-CSF-Exos contained a unique protein, LGALS9 ligand, which bound to the TIM3 receptor of dendritic cells (DCs) in the CSF to inhibit antigen recognition, processing and presentation by DCs, leading to failure of the cytotoxic T-cell-mediated antitumor immune response. Blocking the secretion of exosomal LGALS9 from GBM tumors could cause mice to exhibit sustained DC tumor antigen-presenting activity and long-lasting antitumor immunity. We concluded that GBM cell-derived exosomal LGALS9 acts as a major regulator of tumor progression by inhibiting DC antigen presentation and cytotoxic T-cell activation in the CSF and that loss of this inhibitory effect can lead to durable systemic antitumor immunity.
BackgroundThe development of antinociceptive tolerance following repetitive administration of opioid analgesics significantly hinders their clinical use. Evidence has accumulated indicating that microglia within the spinal cord plays a critical role in morphine tolerance. The inhibitor of microglia is effective to attenuate the tolerance; however, the mechanism is not fully understood. Our present study investigated the effects and possible mechanism of a natural product procyanidins in improving morphine tolerance via its specific inhibition on NOD-like receptor protein3 (NLRP3) inflammasome in microglia.MethodsCD-1 mice were used for tail-flick test to evaluate the degree of pain. The microglial cell line BV-2 was used to investigate the effects and the mechanism of procyanidins. Reactive oxygen species (ROS) produced from BV-2 cells was evaluated by flow cytometry. Cell signaling was measured by western blot assay and immunofluorescence assay.ResultsCo-administration of procyanidins with morphine potentiated its antinociception effect and attenuated the development of acute and chronic morphine tolerance. Procyanidins also inhibited morphine-induced increase of interleukin-1β and activation of NOD-like receptor protein3 (NLRP3) inflammasome. Furthermore, procyanidins decreased the phosphorylation of p38 mitogen-activated protein kinase, inhibited the translocation of nuclear factor-κB (NF-κB), and suppressed the level of reactive oxygen species in microglia.ConclusionsProcyanidins suppresses morphine-induced activation of NLRP3 inflammasome and inflammatory responses in microglia, and thus resulting in significant attenuation of morphine antinociceptive tolerance.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0520-z) contains supplementary material, which is available to authorized users.
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