Deoxynivalenol(DON)is a mycotoxin that is produced by various species of Fusarium and is ubiquitous in food and feed.At low concentrations,it can cause metabolic disorders in animals and humans and,at high concentrati...Deoxynivalenol(DON)is a mycotoxin that is produced by various species of Fusarium and is ubiquitous in food and feed.At low concentrations,it can cause metabolic disorders in animals and humans and,at high concentrations,it can lead to pathological changes in the body.The impact of DON on human/animal health and animal productivity has thus attracted a great deal of attention around the world.DON causes severe damage to the intestine,including compromised intestinal barrier,mucosal damage,weakened immune function,and alterations in gut microbiota composition.These effects exacerbate intestinal infections and inflammation in livestock and poultry,posing adverse effects on overall health.Furthermore,research into biological methods for DON detoxification is a crucial avenue for future studies.This includes the utilization of adsorption,enzymatic degradation,and other biological approaches to mitigate DON's impact,offering new strategies for prevention and treatment of DON-induced diseases.Future research will focus on identifying highly efficient detoxifying microorganisms or enzymes to reduce DON levels in food and feed,thereby mitigating its risks to both animals and human health.展开更多
Background Deoxynivalenol(DON)is a mycotoxin that has received recognition worldwide because of its ability to cause growth delay,nutrient malabsorption,weight loss,emesis,and a reduction of feed intake in livestock.S...Background Deoxynivalenol(DON)is a mycotoxin that has received recognition worldwide because of its ability to cause growth delay,nutrient malabsorption,weight loss,emesis,and a reduction of feed intake in livestock.Since DON-contaminated feedstuff is absorbed in the gastrointestinal tract,we used chicken organoids to assess the DON-induced dysfunction of the small intestine.Results We established a culture system using chicken organoids and characterized the organoids at passages 1 and 10.We confirmed the mRNA expression levels of various cell markers in the organoids,such as KI67,leucine-rich repeat containing G protein-coupled receptor 5(Lgr5),mucin 2(MUC2),chromogranin A(CHGA),cytokeratin 19(CK19),lysozyme(LYZ),and microtubule-associated doublecortin-like kinase 1(DCLK1),and compared the results to those of the small intestine.Our results showed that the organoids displayed functional similarities in permeability compared to the small intestine.DON damaged the tight junctions of the organoids,which resulted in increased permeability.Conclusions Our organoid culture displayed topological,genetic,and functional similarities with the small intes-tine cells.Based on these similarities,we confirmed that DON causes small intestine dysfunction.Chicken organoids offer a practical model for the research of harmful substances.展开更多
Deoxynivalenol（DON） is a type B trichothecenes mycotoxin produced by several Fusarium species, often found in foodstuffs for humans and animals. DON is in great demand for the toxicological researches both in vivo a...Deoxynivalenol（DON） is a type B trichothecenes mycotoxin produced by several Fusarium species, often found in foodstuffs for humans and animals. DON is in great demand for the toxicological researches both in vivo and in vitro. In this work, wheat culture was inoculated with a Fusarium graminearum PH-1 strain for DON production. The solvent system for crude extraction was acetonitrile-water（84：16, v/v）. A simple two-step silica gel column chromatography was employed to separate the DON mycotoxin from wheat culture, combined with preparative high performance liquid chromatography（preparative HPLC） to purify the compound. The solvent system for the second silica gel column chromatography was methylene chloride-methanol（17：1, v/v）, which provided a good elution effect selected on thin layer chromatography（TLC）. The target compound was identified by HPLC, and the chemical structure was confirmed by mass spectrometry（MS） and ~1H and ^（13）C nuclear magnetic resonance（NMR） spectroscopy. A total of 433 mg of purified DON was obtained from 1 kg of wheat culture, with a purity of 99.01%. The study had provided an easy-operating and cost-effective method to isolate an expensive compound in a simple way.展开更多
Background Deoxynivalenol(DON)is a widespread issue for feed and food safety,leading to animal and human health risks.The objective of this study was to determine whether ferroptosis is involved in DON-induced intesti...Background Deoxynivalenol(DON)is a widespread issue for feed and food safety,leading to animal and human health risks.The objective of this study was to determine whether ferroptosis is involved in DON-induced intestinal injury in piglets.Three groups of 21-day-old male weanling piglets(n 4,serum and small intestines were=7/group)were fed a control diet,or diet adding 1.0 or 3.0 mg DON/kg.At week collected to assay for biochemistry,histology,redox status and ferroptosis-related genes expression.In addition,the involvement of ferroptosis and the role of FTL gene in DON-induced cell death were further verified in the IPEC-J2 cells.Results Compared to the control,dietary supplementation of DON at 1.0 and 3.0 mg/kg induced different degrees of damage in the duodenum,jejunum and ileum,and increased(P<0.05)serum lipopolysaccharide concentration by 46.2%-51.4%.Dietary DON supplementation at 1.0 and(or)3.0 mg/kg increased(P<0.05)concentrations of malondialdehyde(17.4%-86.5%)and protein carbonyl by 33.1%-92.3%in the duodenum,jejunum and ileum.In addition,dietary supplemented with DON upregulated(P<0.05)ferroptotic gene(DMT1)and anti-ferroptotic genes(FTL and FTH1),while downregulated(P<0.05)anti-ferroptotic genes(FPN,FSP1 and CISD1)in the duodenum of the porcine.Furthermore,the in vitro study has demonstrated that deferiprone,a potent ferroptotic inhibitor,mitigated(P<0.05)DON-induced cytotoxicity in porcine small intestinal IPEC-J2 cells.Additionally,deferiprone prevented or alleviated(P<0.05)the dysregulation of ferroptosis-related genes(ACSL4 and FTL)by DON in IPEC-J2 cells.Moreover,specific siRNA knockdown FTL gene expression compromised the DON-induced cell death in IPEC-J2 cells.Conclusions In conclusion,this study revealed that ferroptosis is involved in DON-induced intestinal damage in porcine,and sheds a new light on the toxicity of DON to piglets.展开更多
Background:Cholesterol is an essential component of lipid rafts in cell plasma membrane,which exerts a hepatoprotective role against mycotoxin exposure in pigs,and cholesterol metabolism is vulnerable to epigenetic hi...Background:Cholesterol is an essential component of lipid rafts in cell plasma membrane,which exerts a hepatoprotective role against mycotoxin exposure in pigs,and cholesterol metabolism is vulnerable to epigenetic histone acetylation.Therefore,our present study aimed to investigate whether a histone deacetylase inhibitor(sodium butyrate [NaBu]) could protect the porcine liver from deoxynivalenol(DON) exposure by modulating cholesterol metabolism.Herein,we randomly divided 28 pigs into four groups,which were fed an uncontaminated basal diet,contaminated diet(4 mg DON/kg),uncontaminated diet supplemented with 0.2% NaBu or 4 mg/kg DON contaminated diet(4 mg DON/kg) supplemented with 0.2% NaBu for 28 d.Results:We found that the serum alanine transaminase(ALT),aspartate transaminase(AST),and alkaline phosphatase(ALP) were all increased in pigs exposed to DON,indicative of significant liver injury.Furthermore,the cholesterol content in the serum of DON-exposed pigs was significantly reduced,compared to the healthy Vehicle group.Transcriptome analysis of porcine liver tissues revealed that the cholesterol homeostasis pathway was highly enriched due to DON exposure.In which we validated by qRT-PCR and western blotting that the cholesterol program was markedly activated.Importantly,NaBu effectively restored parameters associated with liver injury,along with the cholesterol content and the expression of key genes involved in the cholesterol biosynthesis pathway.Mechanistically,we performed a ChIP-seq analysis of H3K27ac and showed that NaBu strongly diminished DON-increased H3K27ac genome-wide enrichment.We further validated that the elevated H3K27ac and H3K9ac occupancies on cholesterol biosynthesis genes were both decreased by NaBu,as determined by ChIP-qPCR analysis.Notably,nuclear receptor RORγ,a novel regulator of cholesterol biosynthesis,was found in the hyperacetylated regions.Again,a remarkable increase of RORγ at both mRNA and protein levels in DON-exposed porcine livers was drastically reduced by NaBu.Consistent with RORγ expression,NaBu also hindered RORγ transcriptional binding enrichments on these activated cholesterol biosynthesis genes like HMGCR,SQLE,and DHCR24.Furthermore,we conducted an in vitro luciferase reporter assay to verify that porcine RORγ directly bonds to the promoters of the above target genes.Conclusions:Collectively,our results demonstrate the utility of the natural product Na Bu as a potential anti-mycotoxin nutritional strategy for regulating cholesterol metabolism via RORγ-mediated histone acetylation modification.展开更多
为明确品种抗性和杀菌剂对赤霉病发生及呕吐毒素积累的影响,2022年对8个不同抗性小麦品种和4种杀菌剂防治赤霉病和呕吐毒素进行防效评价。结果表明:在4月10日(扬花株率5%左右)和4月17日2次施药后,200 g/L氟唑菌酰羟胺SC 50 m L/667 m^(2...为明确品种抗性和杀菌剂对赤霉病发生及呕吐毒素积累的影响,2022年对8个不同抗性小麦品种和4种杀菌剂防治赤霉病和呕吐毒素进行防效评价。结果表明:在4月10日(扬花株率5%左右)和4月17日2次施药后,200 g/L氟唑菌酰羟胺SC 50 m L/667 m^(2)+25%丙环唑SC 30 m L/667 m^(2)、40%丙硫菌唑·戊唑醇SC 40 m L/667 m^(2)对赤霉病的防效均在95%左右,25%吡唑醚菌酯SC40 m L/667 m^(2)+27%戊唑·噻霉酮EW 35 m L/667 m^(2)对赤霉病的防效在91%左右,480 g/L氰烯·戊唑醇SC 50 m L/667 m^(2)对赤霉病的防效在84%左右;清水对照区的赤霉病自然发生程度、DON含量及药剂处理区的赤霉病发生程度呈现中感品种>中抗品种>抗性品种趋势。品种抗性和杀菌剂在防治赤霉病过程中存在交互作用,效应量依次为药剂>品种×药剂>品种。结论:利用品种抗性和杀菌剂能够有效控制赤霉病,其协同防效随品种抗性增强而提高;在小麦扬花初期施用氟唑菌酰羟胺、丙硫菌唑、氰烯菌酯等,即使扬花期遇连阴雨天气,可在第1次施药后间隔6~7 d再次施药,也能够保证防效。展开更多
基金funded by the National Natural Science Foundation of China(32273074,31972746,31872538 and 31772809)the Basic Scientific Research Project of Liaoning Provincial Department of Education,China(LJKZ0632)。
文摘Deoxynivalenol(DON)is a mycotoxin that is produced by various species of Fusarium and is ubiquitous in food and feed.At low concentrations,it can cause metabolic disorders in animals and humans and,at high concentrations,it can lead to pathological changes in the body.The impact of DON on human/animal health and animal productivity has thus attracted a great deal of attention around the world.DON causes severe damage to the intestine,including compromised intestinal barrier,mucosal damage,weakened immune function,and alterations in gut microbiota composition.These effects exacerbate intestinal infections and inflammation in livestock and poultry,posing adverse effects on overall health.Furthermore,research into biological methods for DON detoxification is a crucial avenue for future studies.This includes the utilization of adsorption,enzymatic degradation,and other biological approaches to mitigate DON's impact,offering new strategies for prevention and treatment of DON-induced diseases.Future research will focus on identifying highly efficient detoxifying microorganisms or enzymes to reduce DON levels in food and feed,thereby mitigating its risks to both animals and human health.
基金This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(2022R1I1A3070740).
文摘Background Deoxynivalenol(DON)is a mycotoxin that has received recognition worldwide because of its ability to cause growth delay,nutrient malabsorption,weight loss,emesis,and a reduction of feed intake in livestock.Since DON-contaminated feedstuff is absorbed in the gastrointestinal tract,we used chicken organoids to assess the DON-induced dysfunction of the small intestine.Results We established a culture system using chicken organoids and characterized the organoids at passages 1 and 10.We confirmed the mRNA expression levels of various cell markers in the organoids,such as KI67,leucine-rich repeat containing G protein-coupled receptor 5(Lgr5),mucin 2(MUC2),chromogranin A(CHGA),cytokeratin 19(CK19),lysozyme(LYZ),and microtubule-associated doublecortin-like kinase 1(DCLK1),and compared the results to those of the small intestine.Our results showed that the organoids displayed functional similarities in permeability compared to the small intestine.DON damaged the tight junctions of the organoids,which resulted in increased permeability.Conclusions Our organoid culture displayed topological,genetic,and functional similarities with the small intes-tine cells.Based on these similarities,we confirmed that DON causes small intestine dysfunction.Chicken organoids offer a practical model for the research of harmful substances.
基金supported by the National Natural Science Foundation of China (31402268)the Natural Science Foundation of Jiangsu Province of China (BK20140691)+1 种基金Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), ChinaThe Introduction of International Advanced Agricultural Science and Technology Project from the Ministry of Agriculture of China (2012-Z22)
文摘Deoxynivalenol（DON） is a type B trichothecenes mycotoxin produced by several Fusarium species, often found in foodstuffs for humans and animals. DON is in great demand for the toxicological researches both in vivo and in vitro. In this work, wheat culture was inoculated with a Fusarium graminearum PH-1 strain for DON production. The solvent system for crude extraction was acetonitrile-water（84：16, v/v）. A simple two-step silica gel column chromatography was employed to separate the DON mycotoxin from wheat culture, combined with preparative high performance liquid chromatography（preparative HPLC） to purify the compound. The solvent system for the second silica gel column chromatography was methylene chloride-methanol（17：1, v/v）, which provided a good elution effect selected on thin layer chromatography（TLC）. The target compound was identified by HPLC, and the chemical structure was confirmed by mass spectrometry（MS） and ~1H and ^（13）C nuclear magnetic resonance（NMR） spectroscopy. A total of 433 mg of purified DON was obtained from 1 kg of wheat culture, with a purity of 99.01%. The study had provided an easy-operating and cost-effective method to isolate an expensive compound in a simple way.
基金partially supported by the National Key Research and Development Program of ChinaProjects(2016YFD0501207 and 2018YFD0500601)a donation from Jiangsu Aomai Bio-technology Co.,Ltd。
文摘Background Deoxynivalenol(DON)is a widespread issue for feed and food safety,leading to animal and human health risks.The objective of this study was to determine whether ferroptosis is involved in DON-induced intestinal injury in piglets.Three groups of 21-day-old male weanling piglets(n 4,serum and small intestines were=7/group)were fed a control diet,or diet adding 1.0 or 3.0 mg DON/kg.At week collected to assay for biochemistry,histology,redox status and ferroptosis-related genes expression.In addition,the involvement of ferroptosis and the role of FTL gene in DON-induced cell death were further verified in the IPEC-J2 cells.Results Compared to the control,dietary supplementation of DON at 1.0 and 3.0 mg/kg induced different degrees of damage in the duodenum,jejunum and ileum,and increased(P<0.05)serum lipopolysaccharide concentration by 46.2%-51.4%.Dietary DON supplementation at 1.0 and(or)3.0 mg/kg increased(P<0.05)concentrations of malondialdehyde(17.4%-86.5%)and protein carbonyl by 33.1%-92.3%in the duodenum,jejunum and ileum.In addition,dietary supplemented with DON upregulated(P<0.05)ferroptotic gene(DMT1)and anti-ferroptotic genes(FTL and FTH1),while downregulated(P<0.05)anti-ferroptotic genes(FPN,FSP1 and CISD1)in the duodenum of the porcine.Furthermore,the in vitro study has demonstrated that deferiprone,a potent ferroptotic inhibitor,mitigated(P<0.05)DON-induced cytotoxicity in porcine small intestinal IPEC-J2 cells.Additionally,deferiprone prevented or alleviated(P<0.05)the dysregulation of ferroptosis-related genes(ACSL4 and FTL)by DON in IPEC-J2 cells.Moreover,specific siRNA knockdown FTL gene expression compromised the DON-induced cell death in IPEC-J2 cells.Conclusions In conclusion,this study revealed that ferroptosis is involved in DON-induced intestinal damage in porcine,and sheds a new light on the toxicity of DON to piglets.
基金supported by Key Research and Development Project(Modern Agriculture)of Jiangsu Province(BE2019341)Jiangsu Agricultural Science and Technology Innovation Fund(CX[20]2003)the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Background:Cholesterol is an essential component of lipid rafts in cell plasma membrane,which exerts a hepatoprotective role against mycotoxin exposure in pigs,and cholesterol metabolism is vulnerable to epigenetic histone acetylation.Therefore,our present study aimed to investigate whether a histone deacetylase inhibitor(sodium butyrate [NaBu]) could protect the porcine liver from deoxynivalenol(DON) exposure by modulating cholesterol metabolism.Herein,we randomly divided 28 pigs into four groups,which were fed an uncontaminated basal diet,contaminated diet(4 mg DON/kg),uncontaminated diet supplemented with 0.2% NaBu or 4 mg/kg DON contaminated diet(4 mg DON/kg) supplemented with 0.2% NaBu for 28 d.Results:We found that the serum alanine transaminase(ALT),aspartate transaminase(AST),and alkaline phosphatase(ALP) were all increased in pigs exposed to DON,indicative of significant liver injury.Furthermore,the cholesterol content in the serum of DON-exposed pigs was significantly reduced,compared to the healthy Vehicle group.Transcriptome analysis of porcine liver tissues revealed that the cholesterol homeostasis pathway was highly enriched due to DON exposure.In which we validated by qRT-PCR and western blotting that the cholesterol program was markedly activated.Importantly,NaBu effectively restored parameters associated with liver injury,along with the cholesterol content and the expression of key genes involved in the cholesterol biosynthesis pathway.Mechanistically,we performed a ChIP-seq analysis of H3K27ac and showed that NaBu strongly diminished DON-increased H3K27ac genome-wide enrichment.We further validated that the elevated H3K27ac and H3K9ac occupancies on cholesterol biosynthesis genes were both decreased by NaBu,as determined by ChIP-qPCR analysis.Notably,nuclear receptor RORγ,a novel regulator of cholesterol biosynthesis,was found in the hyperacetylated regions.Again,a remarkable increase of RORγ at both mRNA and protein levels in DON-exposed porcine livers was drastically reduced by NaBu.Consistent with RORγ expression,NaBu also hindered RORγ transcriptional binding enrichments on these activated cholesterol biosynthesis genes like HMGCR,SQLE,and DHCR24.Furthermore,we conducted an in vitro luciferase reporter assay to verify that porcine RORγ directly bonds to the promoters of the above target genes.Conclusions:Collectively,our results demonstrate the utility of the natural product Na Bu as a potential anti-mycotoxin nutritional strategy for regulating cholesterol metabolism via RORγ-mediated histone acetylation modification.
文摘为明确品种抗性和杀菌剂对赤霉病发生及呕吐毒素积累的影响,2022年对8个不同抗性小麦品种和4种杀菌剂防治赤霉病和呕吐毒素进行防效评价。结果表明:在4月10日(扬花株率5%左右)和4月17日2次施药后,200 g/L氟唑菌酰羟胺SC 50 m L/667 m^(2)+25%丙环唑SC 30 m L/667 m^(2)、40%丙硫菌唑·戊唑醇SC 40 m L/667 m^(2)对赤霉病的防效均在95%左右,25%吡唑醚菌酯SC40 m L/667 m^(2)+27%戊唑·噻霉酮EW 35 m L/667 m^(2)对赤霉病的防效在91%左右,480 g/L氰烯·戊唑醇SC 50 m L/667 m^(2)对赤霉病的防效在84%左右;清水对照区的赤霉病自然发生程度、DON含量及药剂处理区的赤霉病发生程度呈现中感品种>中抗品种>抗性品种趋势。品种抗性和杀菌剂在防治赤霉病过程中存在交互作用,效应量依次为药剂>品种×药剂>品种。结论:利用品种抗性和杀菌剂能够有效控制赤霉病,其协同防效随品种抗性增强而提高;在小麦扬花初期施用氟唑菌酰羟胺、丙硫菌唑、氰烯菌酯等,即使扬花期遇连阴雨天气,可在第1次施药后间隔6~7 d再次施药,也能够保证防效。
