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AHR mediates the aflatoxin B1 toxicity associated with hepatocellular carcinoma

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Signal Transduction and Targeted Therapy 2021年第9期6卷 2809-2821页

作者： Qing Zhu Yarui Ma Junbo Liang Zhewen Wei Mo Li Ying Zhang Mei Liu Huan He Chunfeng Qu Jianqiang Cai Xiaobing Wang Yixin Zeng Yuchen Jiao State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina State Key Laboratory of Medical Molecular Biology Institute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijingChina Department of Hepatobiliary Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Key Laboratory of Gene Editing Screening and R&D of Digestive System Tumor Drugs Chinese Academy of Medical SciencesPeking Union Medical CollegeBeijingChina State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhouChina Department of Clinical Laboratory National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

aflatoxin exposure is a crucial factor in promoting the development of primary hepatocellular carcinoma(HCC)in individuals infected with the hepatitis ***,the molecular pathways leading to its bioactivation and subsequent toxicity in hepatocytes have not been ***,we carried out a genome-wide CRISPR-Cas9 genetic screen to identify aflatoxin B1(AFB1)*** the most significant hits was the aryl hydrocarbon receptor(AHR),a ligand-binding transcription factor regulating cell metabolism,differentiation,and immunity.

关键词： aflatoxin metabolism hepatocellular

Evaluation of maize inbred lines for resistance to pre-harvest aflatoxin and fumonisin contamination in the field

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The Crop Journal 2017年第3期5卷 259-264页

作者： Baozhu Guo Xiangyun Ji Xinzhi Ni Jake C.Fountain Hong Li Hamed K.Abbas Robert D.Lee Brian T.Scully United States Department of Agriculture-Agricultural Research Service(USDA-ARS) Crop Protection and Management Research UnitTiftonGAUnited States The University of Georgia Department of Plant PathologyTiftonGAUnited States Ecological Environment Protection Research Institute Shanghai Academy of Agricultural SciencesShanghaiChina USDA-ARS Crop Genetics and Breeding Research UnitTiftonGAUnited States Shanxi Academy of Agricultural Sciences Millet Research InstituteChangzhiChina USDA-ARS Biological Control of Pests Research UnitStonevilleMSUnited States The University of Georgia Department of Crop and Soil SciencesTiftonGAUnited States USDA-ARS U.S.Horticultural Research LaboratoryFort PierceFLUnited States

Two important mycotoxins, aflatoxin and fumonisin, are among the most potent naturally occurring carcinogens, contaminating maize(Zea mays) and affecting crop yield and *** of maize to pre-harvest mycotoxin contamination, specifically aflatoxin produced by Aspergillus flavus and fumonisin produced by Fusarium verticillioides, is a goal in breeding programs that screen for these important traits with the aim of developing resistant commercial hybrids. We conducted two years of field evaluations on 87 inbred lines originating primarily in China and Mexico and not previously screened for *** objectives of our study were to identify resistant germplasm for breeding purposes and to examine possible relationships between resistances to the two mycotoxins. aflatoxin and fumonisin were present in samples harvested from all lines in both *** of total aflatoxin ranged from 52.00 ± 20.00 to 1524.00 ± 396.00 μg kg^(-1),while those of fumonisin ranged from 0.60 ± 0.06 to 124.00 ± 19.50 mg kg^(-1). The inbred lines TUN15, TUN61, TUN37, CY2, and TUN49 showed the lowest aflatoxin accumulation and CN1, GT601, TUN09, TUN61, and MP717 the lowest fumonisin accumulation. TUN61 showed the lowest accumulation of both mycotoxins. This study confirmed previous observations that high levels of aflatoxin can coexist with fumonisin, with 55 maize lines showing a positive correlation coefficient between the concentrations of aflatoxin and fumonisin and 32 lines showing a negative correlation coefficient. These selected lines,particularly TUN61, may provide sources of resistance to mycotoxin contamination in breeding programs. However, the mechanism of resistance in this germplasm remains to be identified. Future research should also address factors that influence the fungus–plant interaction, such as herbivory and environmental stress.

关键词： aflatoxin Fumonisin Inbredline Maize Mycotoxin

Biological control of aflatoxin contamination of crops

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2008年第10期9卷 787-792页

作者： Yan-ni YIN Lei-yan YAN Jin-hua JIANG Zhong-hua MA Institute of Biotechnology Zhejiang University Hangzhou 310029 China

aflatoxins produced primarily by two closely related fungi, Aspergillus flavus and Aspergillus parasiticus, are mutagenic and carcinogenic in animals and humans. Of many approaches investigated to manage aflatoxin contamination, bio-logical control method has shown great promise. Numerous organisms, including bacteria, yeasts and nontoxigenic fungal strains of A. flavus and A. parasiticus, have been tested for their ability in controlling aflatoxin contamination. Great successes in reducing aflatoxin contamination have been achieved by application of nontoxigenic strains of A. flavus and A. parasiticus in fields of cotton, peanut, maize and pistachio. The nontoxigenic strains applied to soil occupy the same niches as the natural occurring toxigenic strains. They, therefore, are capable of competing and displacing toxigenic strains. In this paper, we review recent development in biological control of aflatoxin contamination.

关键词： aflatoxin Aspergillus Biocontrol Food safety

A simple aptamer molecular beacon assay for rapid detection of aflatoxin B1

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Chinese Chemical Letters 2019年第5期30卷 1017-1020页

作者： Chao Wang Linlin Sun Qiang Zhao State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China University of Chinese Academy of Sciences Beijing 100049China

aflatoxin B1(AFB1)is a highly toxic mycotoxin,and rapid and sensitive detection of AFB1 is in demand for food safety and environmental *** we described a simple aptamer molecular beacon assay for rapid detection of aflatoxin B1(AFB1)by using an aptamer with a fluorescein(FAM)label at the 50 end and a fluorescence quencher(black hole quencher 1,BHQ1)at the 30 *** the presence of AFB1,the aptamer probe bound with AFB1 and induced a hairpin structure,drawing FAM and BHQ1 into close proximity and leading to fluorescence *** assay allowed for a detection limit of 3.9 nmol/L and a dynamic range from 3.9 nmol/L to 4 mmol/*** test showed other mycotoxins including ochratoxin A,ochratoxin B,fumonisin B1,fumonisin B2,and zearalenone had negligible influence on detection of ***1 spiked in diluted liquor wine,methanol,or corn flour samples was successfully detected by using this aptamer probe,and the assay showed potential for real sample analysis.

关键词： Aptamer aflatoxin B1 Fluorescence Molecular beacons Mycotoxin Sensor

Evaluation of maize inbred lines and topcross progeny for resistance to pre-harvest aflatoxin contamination

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The Crop Journal 2019年第1期7卷 118-125页

作者： Jake C.Fountain Hamed K.Abbas Brian T.Scully Hong Li Robert D.Lee Robert C.Kemerait Baozhu Guo USDA-ARS Crop Protection and Management Research Unit Department of Plant Pathology University of Georgia USDA-ARS Biological Control of Pests Research Unit USDA-ARS National Horticultural Research Laboratory Shanxi Academy of Agricultural Sciences Millet Research Institute Department of Crop and Soil Sciences University of Georgia

Pre-harvest aflatoxin contamination occurs in maize following kernel colonization by Aspergillus flavus. aflatoxin contamination resistance is a highly desired trait in maize breeding *** identification of novel sources of resistance to pre-harvest aflatoxin contamination is a major focus in germplasm screening efforts. Here, we performed a field evaluation of 64 inbred lines over two years for pre-harvest aflatoxin contamination. Topcrosses were also performed with two testers, B73 and Mo17, to generate 128 F1 hybrids which were also evaluated over two years. Hybrid performance was used to calculate both general combining ability(GCA) of the inbreds, and observed heterosis for aflatoxin resistance. Over both years of the study, aflatoxin concentrations ranged from 80 ± 47 to 17,617 ± 8816 μg kg^(-1) for inbreds, and from 58 ± 39 to 2771 ± 780 μg kg^(-1) for hybrids with significant variation between years and lines. The inbred lines CML52, CML69, CML247, GT-603, GEMS-0005, Hi63, Hp301, and M37 W showed aflatoxin accumulation in both years of the study and less than the resistant check, Mp313 E, in at least one season. Among these, CML52, GT-603, and Hi63 also showed significant GCA with the testers in hybrid progeny. CML52, GT-603, and M37 W also showed heterotic effects of-13.64%,-12.47%, and-24.50%, respectively, with B73 resulting in reduced aflatoxin contamination. GT-603 also showed a similar heterotic effect for aflatoxin contamination,-13.11%, with Mo17 indicating that this line may serve as a versatile source of aflatoxin contamination resistance in breeding programs.

关键词： Aspergillus flavus Pre-harvest aflatoxin Maize Topcross

Vitamin E ameliorates aflatoxin-induced biochemical changes in the testis of mice

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Asian Journal of Andrology 2001年第4期3卷 305-309页

作者： R.J.Verma Anita Nair Department of Zoology University School of Sciences Gujarat University Ahmedabad-380 009 IndiaDepartment of Zoology University School of Sciences Gujarat University Ahmedabad-380 009 India

Aim: To assess the effect of aflatoxin on biochemical changes in the testis of mice and the possibility of ameliorationby vitamin E treatment. Methods: Adult male albino mice were orally administered with 25 or 50μg of aflatoxin/animal/day (750 or 1500 μg/kg body weight) for 45 days. The testis was isolated and processed for biochemical anal-ysis. Results; There was a significant, dose-dependent reduction in DNA, RNA, protein, sialic acid contents andthe activities of succinic dehydrogenase, adenosine triphosphatase and alkaline phosphatase in the testis of aflatoxin-treated mice as compared to the vehicle control. However, the acid phosphatase activity was significantly increased inthe aflatoxin-treated mice. Vitamin E (2 mg/animal/day) treatment significantly ameliorated the aflatoxin-inducedchanges, except the acid and alkaline phosphatase activities in the high dose group. Conclusion; Vitamin E treat-ment ameliorates the aflatoxin-induced changes in the testis of mice. (Asian J Androl 2001 Dec; 3: 305 - 309)

关键词： aflatoxin vitamin E testis biochemical changes

A Saccharomyces cerevisiae RC016-based feed additive reduces liver toxicity,residual aflatoxin B1 levels and positively influences intestinal morphology in broiler chickens fed chronic aflatoxin B1-contaminated diets

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Animal Nutrition 2020年第1期6卷 31-38页

作者： Valeria Poloni Alejandra Magnoli Analía Fochesato Andrea Cristofolini Matias Caverzan Cecilia Merkis Maríana Montenegro Lilia Cavaglieri Departamento de Microbiología e Inmunología Universidad Nacional de Río CuartoRío CuartoArgentina Consejo Nacional de Investigaciones Científicas y Tecnólogicas(CONICET) Buenos AiresArgentina Departamento de Microscopía Electrónica Universidad Nacional de Río CuartoRío CuartoArgentina Centro de Investigaciones y Transferencia Villa María Universidad Nacional de Villa MaríaVilla MaríaArgentina

The present study was conducted to investigate the ability of Saccharomyces cerevisiae RC016(Sc)-based feed additive to reduce liver toxicity,residual aflatoxin B1(AFB1)levels and influence intestinal structure in broiler chickens fed chronic aflatoxin B1-contaminated diets.A total of 100 one-day-old male commercial line(Ross)broiler chickens were divided into 4 treatments,with 5 pens per treatment and 5 broiler chickens per *** were randomly assigned to 4 treatments,which were namely treatment 1(T1),control diet(CD);T2,CD+Sc at 1 g/kg;T3,CD+AFB1 at 100μg/kg;T4,CD+Sc at 1 g/kg+AFB1 at100μg/*** liver histopathology of broiler chickens fed diets with AFB1 showed diffused microvacuolar fatty *** addition of Sc showed normal hepatocytes similar to the *** small intestine villi from AFB1 group showed atrophy,hyperplasia of goblet cells,prominent inflammatory infiltrate and *** contrast,the small intestine villi from birds that received the yeast plus AFB1 showed an absence of inflammatory infiltrate,and atrophy;moreover,a lower number of goblet cells compared to the groups with AFB1 was *** morphometric intestine studies showed that a significant decrease(P0.05),there was a tendency to improve these *** residual levels of AFB1 in livers were significantly reduced(P<0.05)in the presence of the *** present work demonstrated that the addition of Sc alone or in combination with AFB1 in the broiler chicken diets had a beneficial effect in counteracting the toxic effects of AFB1 in livers besides improving the histomorphometric parameters and modulating the toxic effect of AFB1 in the intestine.

关键词： aflatoxin B1 Broiler chickens Histomorphometry Histopathology toxic effects

Transcriptomic Analysis of aflatoxin B1-Regulated Genes in Rat Hepatic Epithelial Cells

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Transactions of Tianjin University 2014年第6期20卷 451-457页

作者： Yang Liu Ji Jing Li Guanghui Li Junwen Chen Zhaoli Wang Haiyong School of Chemical Engineering and Technology Tianjin UniversityTianjin 300072China School of Environmental Science and Technology Tianjin UniversityTianjin 300072China Department of Chemistry Tangshan Normal UniversityTangshan 063000China Institute of Hygiene and Environmental Medicine Academy of Military Medical ScienceTianjin 300050China

aflatoxins are the most popular hepatotoxicants. Chronic exposure to aflatoxins leads to a wide variety ofliver diseases, such as hepatocellular carcinoma. In this study, we analyzed the genome wide expression profiles ofaflatoxin B1-induced rat hepatic epithelial cells. The expression of 325, 184 and 199 special genes was altered whenexposed to 0.03, 0.1 and 0.2 μmol/L aflatoxin B1 respectively, and 239 genes were commonly expressed. After thefunctional analysis on these dose-special genes, we determined several key pathways related to hepatotoxicity, such asTGF-beta signaling pathway, tight junction, adherens junction, the regulation of actin cytoskeleton, ErbB signalingpathway, p53 signaling pathway, pathways in cancer and axon guidance. Common genes were mainly associated withfocal adhesion, ECM-receptor interaction, and cell adhesion molecules. Gene ontology annotations showed a goodconcordance with these pathways. The quantitative real-time polymerase chain reaction（PCR） analysis of selectedgenes showed similar patterns in microarrays. The toxicogenomic study provides a better understanding of molecularmechanisms of aflatoxins.

关键词： aflatoxin microarray gene ontology Kyoto encyclopedia of genes and genomes(KEGG) pathway hepatotoxicity

Aptamer structure switch fluorescence anisotropy assay for aflatoxin B1 using tetramethylrhodamine-guanine interaction to enhance signal change

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Chinese Chemical Letters 2020年第7期31卷 1982-1985页

作者： Yapiao Li Qiang Zhao State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China University of Chinese Academy of Sciences Beijing 100049China

Fluorescence anisotropy(FA)assay in homogenous solution is simple,sensitive and ***,we reported an aptamer structure switch FA assay for detection of aflatoxin B1(AFB1),one of the most toxic mycotoxins,by using tetra methylrhodamine(TMR)-labeled aptamer probe and its complementary DNA(cDNA)with tandem G bases extension,to meet the demand in sensitive and selective detection of AFB1,The hybridization of aptamer and cDNA drew TMR close to the repeated guanine(G)bases,and a high FA value was induced due to TMR-G inte raction and re stricted local rotation of *** the presence of AFB1,aptamer bound to AFB1 instead of the cDNA due to ***,the TMR-G interaction was eliminated,and FA value of TMR *** assay enabled the detection of AFB1 with detection limit of 125 pmol/L and dynamic range from 125 pmol/L to 31.2 nmol/L.

关键词： Aptamer aflatoxin Small molecule Fluorescence anisotropy Structure switch Fluorescence polarization