Project description:Deoxynivalenol (DON) frequently detected in a wide range of foods and feeds, inducing cytotoxicity to animals and humans. N6-methyladenosine (m6A) is an important epitranscriptomic marker with high abundance in eukaryotic mammals mRNAs. However, the role of the m6A methylomes in DON damage is still poorly understood. Here, we investigated the m6A transcriptome-wide profile in intestinal porcine epithelial cells (IPEC-J2) with and without 1000 ng/mL DON treatment via m6A sequencing and RNA sequencing. In total, 5406 new m6A peaks appeared with the disappearance of 2615 peaks in DON-induced IPEC-J2. The unique m6A-modified genes in DON-induced IPEC-J2 were associated with TNF signaling pathway. We identified 733 differentially expressed mRNA transcripts with hyper-methylated or hypo-methylated m6A peaks between DON-induced IPEC-J2 and normal IPEC-J2. Protein interaction network analysis and qPCR validation suggested that CSF2 probably acts as a promising new target for combating DON damage in IPEC-J2. Our first report of m6A transcriptome-wide map of IPEC-J2 cells presented here provides a starting roadmap for uncovering m6A functions that may affect DON infection.
Project description:We employed whole genome gene expression analysis to characterize the intestinal exposure to 5 closely related food contaminants belonging to the type B trichocene mycotoxins groups The few data available on fusarenon-X (FX) do no support derivation of health-based guidance values for this mycotoxin, although preliminary results suggest higher toxicity compared to other regulated trichothecenes. Using histo-morphological analysis and whole-transcriptome profiling, the present study was designed to get a global view of intestinal alterations induced by FX. The well-described trichothecene deoxynivalenol (DON) served as a benchmark. FX exposure induced more severe intestinal histological alterations compared to DON. Intestinal inflammation was the hallmark of the molecular toxicity of DON, but also of FX. The dose-response analysis for FX revealed that benchmark doses for up-regulation of key-inflammatory genes expression were 4 to 45-fold higher than the previously reported ones for DON. Transcriptome analysis revealed that both mycotoxins down-regulated PPAR and LXR-RXR signaling pathways controlling lipid metabolism. Interestingly, several pathways including VDR/RXR activation, ephrin receptor signaling, and GNRH signaling were specific to FX and thus, discriminate the intestinal transcriptomic fingerprint of the two mycotoxins. Altogether, these results demonstrate that FX induces a more potent intestinal inflammation than DON. This study also reveals specific FX-targeted pathways, indicating that the toxicity of DON cannot serve as a benchmark for FX, and that toxicity evaluation of each trichothecene should be conducted separately.
Project description:We constructed E. coli transcriptome under deoxynivalenol (DON) and nivalenol (NIV) condition from Fusarium spp. To identify differentially expressed genes in mycotoxin condition, we compared mycotoxin (DON and NIV) transcriptome to acetonitrile (ACN) transcriptome as the solvent of myxotoxin. As a result, 435-929 transcripts were identified from all conditions, respectively.
Project description:Deoxynivalenol (DON) and zearalenone (ZEA) are the most common mycotoxins, which are damage to the reproductive system of human and animal. Endometrium cells perform vital roles of female reproduction. In the present study, transcriptomic was conducted on different dosage (0 μM, 10 μM and 30 μM) of DON and ZEA treatment donkey endometrium cells. Transcriptomic analysis showed 7386 differentially expressed genes (DEGs) were identified between DON 10 μM treatment group and control group, with 3655 up regulated and 3731 down; 8694 DEGs were identified between DON 30 μM treatment group and control group, with 4532 up regulated and 4162 down; 1768 DEGs were identified between ZEA 10 μM treatment group and control group, with 763 up regulated and 1005 down; and 3311 DEGs were identified between ZEA 30 μM treatment group and control group, with 1501 up regulated and 1810 down. In DEGs, Caspase-1, GSDMD-NT, ESR 1, PRDX 4, NOX 1, MSH 6 and CD 44, were expressed changed in DON and ZEA treatment group, which related to pyroptosis, hormone secretion, oxidative stress and cancerous. It is unprecedented that DON induced cell death by pyroptosis. This study provides valuable genetic resources for understanding the mechanisms and pathways of the toxin effect of DON and ZEA for Equus asinus’ endometrium cells.
Project description:Deoxynivalenol (DON) is a frequent mycotoxin in grains, produced by Fusarium fungi, which demonstre multiple side effects such as modulation of immune responses, reduced feed intake and weight gain or impairment of the intestinal barrier function. Among animal species, pigs are the best model for humans and are very sensitive to DON. In wheat, DON can be conjugated to glucose to form DON-3-β-D-glucoside (D3G). Some bacteria isolated from digestive tracts or soil, are also able to de-epoxydize or epimerize DON to metabolites such as deepoxy-deoxynivalenol (DOM-1) or 3-epi-deoxynivalenol (epi-DON). The toxicity of these DON metabolites is poorly documented. By the way of ingestion, the intestine is the first organ exposed to these molecules and so constitute a relevant model. The aim of this study was to compare the intestinal toxicity of three DON metabolites (D3G, DOM-1 and epi-DON) with the one of DON. Intestinal explants from 6 pigs were treated with 10mM DON, D3G, DOM-1 or epi-DON for 4 hours and transcriptomic analysis was performed using an “Agilent Porcinet 60K”.
Project description:DON impaired the male spermatogenesis and induced oxidative stress, testicular apoptosis and disruption of blood-testis barrier (BTB). The milk protein lactoferrin (LF) is an iron-binding glycogenprotein with multifunctions including anti-inflammation and antioxidant. The current study was aimed to investigate the beneficial effects of LF on spermatogenesis and integray of BTB of mice treated with diet DON.
Project description:Deoxynivalenol (DON) and zearalenone (ZEA) are the most common mycotoxins, which are damaging to the reproductive system of humans and animals. Sertoli cells perform vital roles of male reproduction include composition of the blood testis barrier, support and release sperm. In the present study, transcriptomic analysis was conducted on different dosages (0 μM, 10 μM and 30 μM) of DON and ZEA treated donkey Sertoli cells. Transcriptomic analysis showed 6551 differentially expressed genes (DEGs) were identified between DON 10 μM treatment group and control group, with 3300 up regulated and 3251 down; 8605 DEGs were identified between DON 30 μM treatment group and control group, with 4841 up regulated and 3764 down; 803 DEGs were identified between ZEA 10 μM treatment group and control group, with 391 up regulated and 412 down; and 5947 DEGs were identified between ZEA 30 μM treatment group and control group, with 2816 up regulated and 3131 down. In DEGs, Caspase-1, GSDMD-NT, ESR 1, AR, PRDX 4, NOX 1, MSH 6 and CDK 1, were expressed highly in DON and ZEA treatment group, which related to pyroptosis, hormone secretion, oxidative stress and cancerous. It is unprecedented that DON induced cell death by pyroptosis. This study provides valuable genetic resources for understanding the mechanisms and pathways of the toxin effect of DON and ZEA for Equus asinus' Sertoli cells.
Project description:To screen cellular effects on Caco-2 cells by deoxynivalenol (DON) and 15-acetyldeoxynivalenol (15ADON), toxin-treated Caco-2 cells were analyzed by DNA microarray. Exposure to either toxin induced up- or downregulation of genes in Caco-2 cells. Upregulation of 1290 and 3238 genes was observed for the DON- and 15ADON-treated groups, respectively, after a 60-min incubation period. This represented a greater than 1.5-fold change relative to the 0-min exposure (control) group. Five hundred and sixty-one genes showed a 1.5-fold upregulation in the both the DON- and 15ADON-treated groups. Similarly, 13 genes and 105 genes were upregulated with a log2 ratio > 2 (4-fold change) in the DON- and 15ADON-treated groups, respectively. The most remarkable gene upregulation corresponded to the inflammatory chemokine, IL-8, which showed a greater than 4-fold upregulation in response to both treatments.
Project description:Genome-wide DNA methylation profiling of white blood cells was conducted using the Illumina Infinium Human Methylation 850K Genechip. According to the internal exposure level of deoxynivalenol, 32 participants were divided into two groups (high exposure DON group and low exposure DON group). Samples included 16 peripheral blood samples from children with high DON exposure and 16 peripheral blood samples from children with low DON exposure.
Project description:Trichothecenes, like deoxynivalenol (DON) are secondary metabolites of Fusarium species, and are major pollutants in cereal food and feed products. They inhibit eukaryotic protein synthesis, however with only partly resolved consequences for the cellular homeostasis. Here we report a systematic functional investigation of the effects of DON on exponential phase growing yeast cells using either short doses of DON or continuos treatment with DON.