Mycotoxin contamination in food and feed poses a significant global challenge,adversely affecting poultry productivity and compromising both human and animal health.Among mycotoxins,T-2 toxin is of particular concern ...Mycotoxin contamination in food and feed poses a significant global challenge,adversely affecting poultry productivity and compromising both human and animal health.Among mycotoxins,T-2 toxin is of particular concern due to its potent acute toxicity,multi-organ targeting capacity,immunosuppressive effects,and environmental persistence.Biodegradation,particularly enzyme-catalyzed degradation,offers a sustainable and eco-friendly strategy with high specificity for T-2 toxin detoxification.This review comprehensively summarizes key enzymes capable of degrading T-2 toxin,including esterases,glucosyltransferases,glutathione S-transferases,and laccases,with a focus on their respective mechanisms and degradation product profiles.Moreover,the growing demand for enzymes as mycotoxin biodegraders highlights the need for extensive and diverse enzyme resources that can endure harsh reaction conditions.To address this,we propose several methods,including inverse virtual screening,machine learning,and metagenomics,to discover novel enzymes for degradation of mycotoxins including T-2 toxin.Additionally,we highlight the potential of enzyme engineering and genetic optimization strategies to enhance catalytic properties,stability,and production yields of candidate biocatalysts.Overall,this review aims to provide insights and future perspectives to advance the development and practical implementation of enzymatic degradation method for mitigating T-2 toxin contamination.展开更多
T-2 toxin,an omnipresent environmental contaminant,poses a serious risk to the health of humans and animals due to its pronounced cardiotoxicity.This study aimed to elucidate the molecular mechanism of cardiac tissue ...T-2 toxin,an omnipresent environmental contaminant,poses a serious risk to the health of humans and animals due to its pronounced cardiotoxicity.This study aimed to elucidate the molecular mechanism of cardiac tissue damage by T-2 toxin.Twenty-four male Sprague-Dawley rats were orally administered T-2 toxin through gavage for 12 weeks at the dose of 0,10,and 100 nanograms per gram body weight per day(ng/(g·day)),respectively.Morphological,pathological,and ultrastructural alterations in cardiac tissue were meticulously examined.Non-targeted metabolomics analysis was employed to analyze alterations in cardiac metabolites.The expression of the Sirt3/FoxO3α/MnSOD signaling pathway and the level of oxidative stress markers were detected.The results showed that exposure to T-2 toxin elicited myocardial tissue disorders,interstitial hemorrhage,capillary dilation,and fibrotic damage.Mitochondria were markedly impaired,including swelling,fusion,matrix degradation,and membrane damage.Metabonomics analysis unveiled that T-2 toxin could cause alterations in cardiacmetabolic profiles as well as in the Sirt3/FoxO3α/MnSOD signaling pathway.T-2 toxin could inhibit the expressions of the signaling pathway and elevate the level of oxidative stress.In conclusion,the T-2 toxin probably induces cardiac fibrotic impairment by affecting amino acid and choline metabolism as well as up-regulating oxidative stress mediated by the Sirt3/FoxO3α/MnSOD signaling pathway.This study is expected to provide targets for preventing and treating T-2 toxin-induced cardiac fibrotic injury.展开更多
研究采用网络药理学的方法,旨在探讨芸香柚皮苷缓解T-2毒素所致炎性损伤的靶点和通路。首先,通过Swiss Target Prediction、Pharmmapper、BATMAN-TCM、TCMSP和PubMed数据库归纳芸香柚皮苷与T-2毒素的靶点,构建韦恩图。其次,运用Cytoscap...研究采用网络药理学的方法,旨在探讨芸香柚皮苷缓解T-2毒素所致炎性损伤的靶点和通路。首先,通过Swiss Target Prediction、Pharmmapper、BATMAN-TCM、TCMSP和PubMed数据库归纳芸香柚皮苷与T-2毒素的靶点,构建韦恩图。其次,运用Cytoscape 3.9.1软件进行PPI交互网络构建。再次,应用DAVID数据库对关键靶点进行GO功能注释和KEGG富集分析。最后,通过分子对接技术分析芸香柚皮苷与核心靶点的结合能力。结果表明:与芸香柚皮苷相关的潜在靶点得到140个,与T-2毒素相关的潜在靶点得到319个,其中芸香柚皮苷和T-2毒素的交集靶点有31个,核心靶点分别是雌激素受体1(estrogen receptor 1,ESR1)、雌激素受体2(estrogen receptor 2,ESR2)、生长因子受体结合蛋白(growth factor receptor bound protein 2,GRB2)、热休克蛋白90α家族A类1型(heat shock protein 90 alpha family class A member 1,HSP90AA1)。GO富集分析显示,芸香柚皮苷可能通过调节细胞信号转导、细胞外间隙、钙调蛋白的生物过程缓解T-2毒素的毒性,KEGG通路主要富集在PI3K-Akt和HIF-1α等30条信号通路。综上所述,芸香柚皮苷可能通过靶向ESR1、ESR2、GRB2等核心靶点,参与PI3K-Akt、HIF-1α等多个信号通路,发挥缓解T-2毒素所致炎性损伤的作用。展开更多
基金supported by the Hubei Province Regional Science and Technology Innovation Plan Project(2025EHA016).
文摘Mycotoxin contamination in food and feed poses a significant global challenge,adversely affecting poultry productivity and compromising both human and animal health.Among mycotoxins,T-2 toxin is of particular concern due to its potent acute toxicity,multi-organ targeting capacity,immunosuppressive effects,and environmental persistence.Biodegradation,particularly enzyme-catalyzed degradation,offers a sustainable and eco-friendly strategy with high specificity for T-2 toxin detoxification.This review comprehensively summarizes key enzymes capable of degrading T-2 toxin,including esterases,glucosyltransferases,glutathione S-transferases,and laccases,with a focus on their respective mechanisms and degradation product profiles.Moreover,the growing demand for enzymes as mycotoxin biodegraders highlights the need for extensive and diverse enzyme resources that can endure harsh reaction conditions.To address this,we propose several methods,including inverse virtual screening,machine learning,and metagenomics,to discover novel enzymes for degradation of mycotoxins including T-2 toxin.Additionally,we highlight the potential of enzyme engineering and genetic optimization strategies to enhance catalytic properties,stability,and production yields of candidate biocatalysts.Overall,this review aims to provide insights and future perspectives to advance the development and practical implementation of enzymatic degradation method for mitigating T-2 toxin contamination.
基金supported by the National Natural Science Foundation of China(No.81872567).
文摘T-2 toxin,an omnipresent environmental contaminant,poses a serious risk to the health of humans and animals due to its pronounced cardiotoxicity.This study aimed to elucidate the molecular mechanism of cardiac tissue damage by T-2 toxin.Twenty-four male Sprague-Dawley rats were orally administered T-2 toxin through gavage for 12 weeks at the dose of 0,10,and 100 nanograms per gram body weight per day(ng/(g·day)),respectively.Morphological,pathological,and ultrastructural alterations in cardiac tissue were meticulously examined.Non-targeted metabolomics analysis was employed to analyze alterations in cardiac metabolites.The expression of the Sirt3/FoxO3α/MnSOD signaling pathway and the level of oxidative stress markers were detected.The results showed that exposure to T-2 toxin elicited myocardial tissue disorders,interstitial hemorrhage,capillary dilation,and fibrotic damage.Mitochondria were markedly impaired,including swelling,fusion,matrix degradation,and membrane damage.Metabonomics analysis unveiled that T-2 toxin could cause alterations in cardiacmetabolic profiles as well as in the Sirt3/FoxO3α/MnSOD signaling pathway.T-2 toxin could inhibit the expressions of the signaling pathway and elevate the level of oxidative stress.In conclusion,the T-2 toxin probably induces cardiac fibrotic impairment by affecting amino acid and choline metabolism as well as up-regulating oxidative stress mediated by the Sirt3/FoxO3α/MnSOD signaling pathway.This study is expected to provide targets for preventing and treating T-2 toxin-induced cardiac fibrotic injury.
文摘研究采用网络药理学的方法,旨在探讨芸香柚皮苷缓解T-2毒素所致炎性损伤的靶点和通路。首先,通过Swiss Target Prediction、Pharmmapper、BATMAN-TCM、TCMSP和PubMed数据库归纳芸香柚皮苷与T-2毒素的靶点,构建韦恩图。其次,运用Cytoscape 3.9.1软件进行PPI交互网络构建。再次,应用DAVID数据库对关键靶点进行GO功能注释和KEGG富集分析。最后,通过分子对接技术分析芸香柚皮苷与核心靶点的结合能力。结果表明:与芸香柚皮苷相关的潜在靶点得到140个,与T-2毒素相关的潜在靶点得到319个,其中芸香柚皮苷和T-2毒素的交集靶点有31个,核心靶点分别是雌激素受体1(estrogen receptor 1,ESR1)、雌激素受体2(estrogen receptor 2,ESR2)、生长因子受体结合蛋白(growth factor receptor bound protein 2,GRB2)、热休克蛋白90α家族A类1型(heat shock protein 90 alpha family class A member 1,HSP90AA1)。GO富集分析显示,芸香柚皮苷可能通过调节细胞信号转导、细胞外间隙、钙调蛋白的生物过程缓解T-2毒素的毒性,KEGG通路主要富集在PI3K-Akt和HIF-1α等30条信号通路。综上所述,芸香柚皮苷可能通过靶向ESR1、ESR2、GRB2等核心靶点,参与PI3K-Akt、HIF-1α等多个信号通路,发挥缓解T-2毒素所致炎性损伤的作用。
