Integrated of multi-omics and molecular docking reveal PHGDH, PSAT1 and PSPH in the serine synthetic pathway as potential targets of T-2 toxin exposure in pig intestinal tract

Cao, Yue; Shan, Yiyi; Wang, Guangzheng; Wu, Zhengchang; Wang, Haifei; Wu, Shenglong; Yin, Zongjun; Wei, Julong; Bao, Wenbin

doi:10.1016/j.ijbiomac.2023.126647

Cited by 3 publications

(4 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…29 Yue et al found that cell viability decreased over time and in a dose-dependent manner; in this experiment, IPEC-J2 cells were exposed to T-2 toxin at concentrations of 0, 1, 3, 5, 7, 10, 15, or 20 nM for 12, 24, or 48 h. The viability of the exposed cells decreased markedly after treatment with 5 nM T-2 toxin (12, 24, and 48 h). The results revealed that the IC50s of T-2 toxin in IPEC-J2 cells were 26.38 nM after 12 h, 11.15 nM after 24 h, and 6.07 nM after 48 h. 33 Moreover, Goossens et al discovered that T-2 toxin promoted cell death and decreased IPEC-J2 cell activity; the IC 50 after 72 h was 9.55 ng/mL. 34 T-2 toxin was added to IPEC-J2 cells at various concentrations (0−100 ng/mL), and the cells were incubated for 72 h, then the cells were subjected to intercellular membrane transmembrane resistance (TEER) testing, which showed that the TEER of the IPEC-J2 single-molecule membrane dramatically decreased when the cells were exposed to T-2 toxin, demonstrating that T-2 toxin disrupted intestinal barrier function.…”

Section: Effects Of T-2 Toxin On the Intestinal Barriermentioning

confidence: 90%

“…Yue et al found that cell viability decreased over time and in a dose-dependent manner; in this experiment, IPEC-J2 cells were exposed to T-2 toxin at concentrations of 0, 1, 3, 5, 7, 10, 15, or 20 nM for 12, 24, or 48 h. The viability of the exposed cells decreased markedly after treatment with 5 nM T-2 toxin (12, 24, and 48 h). The results revealed that the IC50s of T-2 toxin in IPEC-J2 cells were 26.38 nM after 12 h, 11.15 nM after 24 h, and 6.07 nM after 48 h . Moreover, Goossens et al discovered that T-2 toxin promoted cell death and decreased IPEC-J2 cell activity; the IC 50 after 72 h was 9.55 ng/mL .…”

Section: Research Progress On the Enterotoxicity Of T-2 Toxinmentioning

confidence: 99%

“…Molecular simulation docking and gene knockout tests revealed that T-2 toxin-induced cellular oxidative stress and cytotoxicity may be successfully reduced by PSAT1 knockout, suggesting that disordered serine metabolism is a key target in T-2 toxin-induced intestinal cellular oxidative damage. 33 The PSAT1 molecule can be used to develop drugs to reduce T-2 toxin enterotoxicity in the future.…”

Section: The Mechanism Of T-2 Toxin Enterotoxicitymentioning

confidence: 99%

“…IPEC-J2 cells were exposed to T-2 toxin at 1, 2, 3, 5, 7, 10, 15, or 20 nM for 12, 24, or 48 h. The transcription and proteomics analysis results revealed that three key enzymes, PHGDH, PSAT1, and PSPH, were enriched in the serine metabolism pathway. Molecular simulation docking and gene knockout tests revealed that T-2 toxin-induced cellular oxidative stress and cytotoxicity may be successfully reduced by PSAT1 knockout, suggesting that disordered serine metabolism is a key target in T-2 toxin-induced intestinal cellular oxidative damage . The PSAT1 molecule can be used to develop drugs to reduce T-2 toxin enterotoxicity in the future.…”

Section: Research Progress On the Enterotoxicity Of T-2 Toxinmentioning

confidence: 99%

See 3 more Smart Citations

Overview of T-2 Toxin Enterotoxicity: From Toxic Mechanisms and Detoxification to Future Perspectives

Zhang,

Song,

Hua

et al. 2024

J. Agric. Food Chem.

View full text Add to dashboard Cite

Fusarium species produce a secondary metabolite known as T-2 toxin, which is the primary and most harmful toxin found in type A trichothecenes. T-2 toxin is widely found in food and grain-based animal feed and endangers the health of both humans and animals. T-2 toxin exposure in humans and animals occurs primarily through food administration; therefore, the first organ that T-2 toxin targets is the gut. In this overview, the research progress, toxicity mechanism, and detoxification of the toxin T-2 were reviewed, and future research directions were proposed. T-2 toxin damages the intestinal mucosa and destroys intestinal structure and intestinal barrier function; furthermore, T-2 toxin disrupts the intestinal microbiota, causes intestinal flora disorders, affects normal intestinal metabolic function, and kills intestinal epidermal cells by inducing oxidative stress, inflammatory responses, and apoptosis. The primary harmful mechanism of T-2 toxin in the intestine is oxidative stress. Currently, selenium and plant extracts are mainly used to exert antioxidant effects to alleviate the enterotoxicity of T-2 toxin. In future studies, the use of genomic techniques to find upstream signaling molecules associated with T-2 enterotoxin toxicity will provide new ideas for the prevention of this toxicity. The purpose of this paper is to review the progress of research on the intestinal toxicity of T-2 toxin and propose new research directions for the prevention and treatment of T-2 toxin toxicity.

show abstract

Section: Effects Of T-2 Toxin On the Intestinal Barriermentioning

confidence: 90%

Section: Research Progress On the Enterotoxicity Of T-2 Toxinmentioning

confidence: 99%

Section: The Mechanism Of T-2 Toxin Enterotoxicitymentioning

confidence: 99%

Section: Research Progress On the Enterotoxicity Of T-2 Toxinmentioning

confidence: 99%

See 2 more Smart Citations

Overview of T-2 Toxin Enterotoxicity: From Toxic Mechanisms and Detoxification to Future Perspectives

Zhang,

Song,

Hua

et al. 2024

J. Agric. Food Chem.

View full text Add to dashboard Cite

show abstract

Development of a roadmap for action on the application of Omics and associated Bioinformatics Approaches in Risk Assessment

Radio,

Di Marsico,

Bersani

et al. 2024

EFS3

View full text Add to dashboard Cite

The implementation of omics technologies and associated bioinformatics approaches hold significant promise for generating additional evidence for food and feed risk assessments thereby enhancing the European Food Safety Authority (EFSA) capacity to deliver scientific opinions and guidance documents in the future. To explore this possibility, EFSA launched a Call for the development of a roadmap to identify the main actions needed for a wider use of Omics in future risk assessments. To address this objective, this action roadmap outlines six project proposals. These proposals are based on a comprehensive mapping of the state‐of‐the‐art omics and associated bioinformatics technologies in research, EFSA's activities as well as current and planned activities from other relevant regulatory bodies and organisations. The outlined recommendations also address some of the identified main knowledge gaps and highlight the added value that further investments in the different food & feed safety scientific domains could bring. In addition, the work in this roadmap addresses some key challenges and blockers that might hinder a wider integration of omics in risk assessment and leverages on the opportunities for cooperation with external stakeholders. Finally, this roadmap provides suggestions on how EFSA may more broadly and effectively engage with relevant stakeholders in the use of omics technologies and associated bioinformatics approaches in regulatory science.

show abstract

Metabolic Transcriptional Activation in Ulcerative Colitis Identified Through scRNA-seq Analysis

Desterke,

Fu,

Francés

et al. 2024

Genes

View full text Add to dashboard Cite

Background: Ulcerative colitis is a chronic inflammatory disease affecting the colon. During chronic inflammation of epithelial cells, lipid metabolism via pro-inflammatory eicosanoids is known to modify the immune response. Methods: Starting from the Mammalian Metabolic Database, the expression of metabolic enzymes was investigated in two independent cohorts from transcriptome datasets GSE38713 and GSE11223, which analyzed ulcerative colitis tissue samples from the digestive tract. Results: In the first cohort, 145 differentially expressed enzymes were identified as significantly regulated between ulcerative colitis tissues and normal controls. Overexpressed enzymes were selected to tune an Elastic Net model in the second cohort. Using the best parameters, the model achieved a prediction accuracy for ulcerative colitis with an area under the curve (AUC) of 0.79. Twenty-two metabolic enzymes were found to be commonly overexpressed in both independent cohorts, with decreasing Elastic Net predictive coefficients as follows: LIPG (3.98), PSAT1 (3.69), PGM3 (2.74), CD38 (2.28), BLVRA (1.99), CBR3 (1.94), NT5DC2 (1.76), PHGDH (1.71), GPX7 (1.58), CASP1 (1.56), ASRGL1 (1.4), SOD3 (1.25), CHST2 (0.965), CHST11 (0.95), KYNU (0.94), PLAG2G7 (0.92), SRM (0.87), PTGS2 (0.80), LPIN1 (0.47), ME1 (0.31), PTGDS (0.14), and ADA (0.13). Functional enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database highlighted the main implications of these enzymes in cysteine and methionine metabolism (adjusted p-value = 0.01), arachidonic acid and prostaglandin metabolism (adjusted p-value = 0.01), and carbon metabolism (adjusted p-value = 0.04). A metabolic score based on the transcriptional activation of the validated twenty-two enzymes was found to be significantly greater in Ulcerative colitis samples compared to healthy donor samples (p-value = 1.52 × 10−8). Conclusions: A metabolic expression score was established and reflects the implications of heterogeneous metabolic pathway deregulations in the digestive tract of patients with ulcerative colitis.

show abstract

Integrated of multi-omics and molecular docking reveal PHGDH, PSAT1 and PSPH in the serine synthetic pathway as potential targets of T-2 toxin exposure in pig intestinal tract

Cited by 3 publications

References 41 publications

Overview of T-2 Toxin Enterotoxicity: From Toxic Mechanisms and Detoxification to Future Perspectives

Overview of T-2 Toxin Enterotoxicity: From Toxic Mechanisms and Detoxification to Future Perspectives

Development of a roadmap for action on the application of Omics and associated Bioinformatics Approaches in Risk Assessment

Metabolic Transcriptional Activation in Ulcerative Colitis Identified Through scRNA-seq Analysis

Contact Info

Product

Resources

About