Hypoxia, a common feature of the tumor microenvironment in various types of cancers, weakens cytotoxic T cell function and causes recruitment of regulatory T cells, thereby reducing tumoral immunogenicity. Studies have demonstrated that hypoxia and hypoxia-inducible factors (HIFs) 1 and 2 alpha (HIF1A and HIF2A) are involved in tumor immune escape. Under hypoxia, activation of HIF1A induces a series of signaling events, including through programmed death receptor-1/programmed death ligand-1. Moreover, hypoxia triggers shedding of complex class I chain-associated molecules through nitric oxide signaling impairment to disrupt immune surveillance by natural killer cells. The HIF-1-galactose-3-O-sulfotransferase 1-sulfatide axis enhances tumor immune escape via increased tumor cell-platelet binding. HIF2A upregulates stem cell factor expression to recruit tumor-infiltrating mast cells and increase levels of cytokines interleukin-10 and transforming growth factor-β, resulting in an immunosuppressive tumor microenvironment. Additionally, HIF1A upregulates expression of tumor-associated long noncoding RNAs and suppresses immune cell function, enabling tumor immune escape. Overall, elucidating the underlying mechanisms by which HIFs promote evasion of tumor immune surveillance will allow for targeting HIF in tumor treatment. This review discusses the current knowledge of how hypoxia and HIFs facilitate tumor immune escape, with evidence to date implicating HIF1A as a molecular target in such immune escape. This review provides further insight into the mechanism of tumor immune escape, and strategies for tumor immunotherapy are suggested.

• MeSH
• faktor 1 indukovatelný hypoxií - podjednotka alfa MeSH
• hypoxie metabolismus   MeSH
• imunitní dozor MeSH
• lidé MeSH
• nádorové mikroprostředí MeSH
• nádory * MeSH
• únik nádoru z imunitní kontroly * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

A host's immune system can be invaded by mycotoxin deoxynivalenol (DON) poisoning and porcine circovirus type 2 (PCV2) infections, which affect the host's natural immune function. Pro-inflammatory cytokines, IL-1β and IL-6, are important regulators in the process of natural immune response, which participate in inflammatory response and enhance immune-mediated tissue damage. Preliminary studies have shown that DON promotes PCV2 infection by activating the MAPK signaling pathway. Here, we explored whether the mRNA expression of IL-1β and IL-6, induced by the combination of DON and PCV2, would depend on the MAPK signaling pathway. Specific pharmacological antagonists U0126, SP600125 and SB203580, were used to inhibit the activities of ERK, JNK and p38 in the MAPK signaling pathway, respectively. Then, the mRNA expression of IL-1β and IL-6 in PK-15 cells was detected to explore the effect of the MAPK signaling pathway on IL-1β and IL-6 mRNA induced by DON and PCV2. The results showed that PK-15 cells treated with DON or PCV2 induced the mRNA expression of IL-1β and IL-6 in a time- and dose-dependent manner. The combination of DON and PCV2 has an additive effect on inducing the mRNA expression of IL-1β and IL-6. Additionally, both DON and PCV2 could induce the mRNA expression of IL-1β and IL-6 via the ERK and the p38 MAPK signal pathways, while PCV2 could induce it via the JNK signal pathway. Taken together, our results suggest that MAPKs play a contributory role in IL-1β and IL-6 mRNA expression when induced by both DON and PCV2.

• MeSH
• buněčné linie MeSH
• Circovirus * MeSH
• infekce viry čeledi Circoviridae genetika   metabolismus   MeSH
• interleukin-1beta genetika   MeSH
• interleukin-6 genetika   MeSH
• MAP kinasový signální systém účinky léků   MeSH
• messenger RNA MeSH
• prasata MeSH
• trichotheceny toxicita   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Mushroom poisoning has always been a threat to human health. There are a large number of reports about ingestion of poisonous mushrooms every year around the world. It attracts the attention of researchers, especially in the aspects of toxin composition, toxic mechanism and toxin application in poisonous mushroom. Inocybe is a large genus of mushrooms and contains toxic substances including muscarine, psilocybin, psilocin, aeruginascin, lectins and baeocystin. In order to prevent and remedy mushroom poisoning, it is significant to clarify the toxic effects and mechanisms of these bioactive substances. In this review article, we summarize the chemistry, most known toxic effects and mechanisms of major toxic substances in Inocybe mushrooms, especially muscarine, psilocybin and psilocin. Their available toxicity data (different species, different administration routes) published formerly are also summarized. In addition, the treatment and medical application of these toxic substances in Inocybe mushrooms are also discussed. We hope that this review will help understanding of the chemistry and toxicology of Inocybe mushrooms as well as the potential clinical application of its bioactive substances to benefit human beings.

• MeSH
• Agaricales chemie   metabolismus   fyziologie   MeSH
• lektiny chemie   farmakologie   MeSH
• lidé MeSH
• muskarin chemie   otrava   toxicita   MeSH
• organofosforové sloučeniny chemie   toxicita   MeSH
• otrava houbami etiologie   terapie   MeSH
• psilocybin analogy a deriváty   chemie   otrava   toxicita   MeSH
• tryptaminy chemie   toxicita   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The trichothecene mycotoxins contaminate cereal grains and have been related to alimentary toxicosis resulted in emetic response. This family of mycotoxins comprises type A to D groups of toxic sesquiterpene chemicals. Diacetoxyscirpenol (DAS), one of the most toxic type A trichothecenes, is considered to be a potential risk for human and animal health by the European Food Safety Authority. Other type A trichothecenes, T-2 toxin and HT-2 toxin, as well as type B trichothecene deoxynivalenol (DON), have been previously demonstrated to induce emetic response in the mink, and this response has been associated with the plasma elevation of neurotransmitters peptide YY (PYY) and serotonin (5-hydroxytryptamine, 5-HT). However, it is found that not all the type A and type B trichothecenes have the capacity to induce PYY and 5-HT. It is necessary to identify the roles of these two emetogenic mediators on DAS-induced emesis. The goal of this study was to determine the emetic effect of DAS and relate this effect to PYY and 5-HT, using a mink bioassay. Briefly, minks were fasted one day before experiment and given DAS by intraperitoneally and orally dosing on the experiment day. Then, emetic episodes were calculated and blood collection was employed for PYY and 5-HT test. DAS elicited robust emetic responses that corresponded to upraised PYY and 5-HT. Blocking the neuropeptide Y2 receptor (NPY2R) diminished emesis induction by PYY and DAS. The serotonin 3 receptor (5-HT3R) inhibitor granisetron totally restrained the induction of emesis by serotonin and DAS. In conclusion, our findings demonstrate that PYY and 5-HT have critical roles in DAS-induced emetic response.

• MeSH
• antiemetika farmakologie   MeSH
• granisetron farmakologie   MeSH
• modely nemocí na zvířatech MeSH
• norek MeSH
• peptid YY krev   MeSH
• receptory gastrointestinálních hormonů metabolismus   MeSH
• receptory serotoninové 5-HT3 metabolismus   MeSH
• sekreční dráha MeSH
• serotonin krev   MeSH
• serotoninové receptory 5-HT3 - antagonisté farmakologie   MeSH
• trichotheceny * MeSH
• upregulace MeSH
• zvířata MeSH
• zvracení krev   chemicky indukované   prevence a kontrola   MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The red-crowned crane (Grus japonensis) is a vulnerable bird species. Mycotoxins are toxic substances produced by filamentous fungi and are considered as naturally unavoidable contaminants in animal feed. Our recent survey indicated that feeds designed for captive red-crowned cranes were contaminated with mycotoxins. This study was conducted to investigate the protective effects of the mycotoxin binder montmorillonite on the reproductive behavior, sex hormone levels, and egg quality of red-crowned cranes. Twelve pairs of G. japonensis were divided into four groups, and each group was fed one of the following: a selected diet (with extra low levels of mycotoxins), a regular diet, a selected diet with 0.5% montmorillonite added, or a regular diet with 0.5% montmorillonite added. Consumption of the regular diet decreased courtship and mating behaviors, testosterone concentration, egg weight, and shell thickness. However, feed supplementation with montmorillonite increased the courtship, mating behaviors and testosterone concentration during the pre-breeding period, as well as egg weight and shell thickness. These findings suggest that the addition of dietary montmorillonite is effective for controlling mycotoxins in the feed, resulting in improvements in reproductive behaviors, testosterone concentrations, and some egg quality parameters of the red-crowned crane.

• MeSH
• bentonit chemie   MeSH
• dieta MeSH
• krmivo pro zvířata analýza   normy   MeSH
• mykotoxiny analýza   toxicita   MeSH
• ovum chemie   MeSH
• pohlavní steroidní hormony krev   MeSH
• ptáci fyziologie   MeSH
• rozmnožování účinky léků   MeSH
• sexuální chování zvířat účinky léků   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Fusarium-derived mycotoxin deoxynivalenol (DON) usually induces diarrhea, vomiting and gastrointestinal inflammation. We studied the cytotoxic effect of DON on porcine small intestinal epithelium using the intestinal porcine epithelial cell line IPEC-J2. We screened out differentially expressed genes (DEGs) using RNA-seq and identified 320 upregulated genes and 160 downregulated genes. The enrichment pathways of these DEGs focused on immune-related pathways. DON induced proinflammatory gene expression, including cytokines, chemokines and other inflammation-related genes. DON increased IL1A, IL6 and TNF-α release and DON activated the phosphorylation of extracellular signal-regulated kinase-1 and-2 (ERK1/2), JUN N-terminal kinase (JNK) and p38 MAPK. A p38 inhibitor attenuated DON-induced IL6, TNF-α, CXCL2, CXCL8, IL12A, IL1A, CCL20, CCL4 and IL15 production, while an ERK1/2 inhibitor had only a small inhibitory effect on IL15 and IL6. An inhibitor of p38 MAPK decreased the release of IL1A, IL6 and TNF-α and an inhibitor of ERK1/2 partly attenuated protein levels of IL6. These data demonstrate that DON induces proinflammatory factor production in IPEC-J2 cells by activating p38 and ERK1/2.

• MeSH
• buněčné linie MeSH
• epitelové buňky účinky léků   imunologie   metabolismus   MeSH
• interleukin-1 genetika   MeSH
• interleukin-6 genetika   MeSH
• MAP kinasový signální systém účinky léků   genetika   imunologie   MeSH
• mitogenem aktivované proteinkinasy p38 metabolismus   MeSH
• prasata MeSH
• střevní sliznice účinky léků   imunologie   metabolismus   MeSH
• TNF-alfa genetika   MeSH
• transkriptom účinky léků   MeSH
• trichotheceny toxicita   MeSH
• viabilita buněk účinky léků   MeSH
• zánět MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH