AIM:To determine global DNA methylation in paired hepatocellular carcinoma(HCC) samples using several different assays and explore the correlations between hypomethylation and clinical parameters and biomarkers,includ...AIM:To determine global DNA methylation in paired hepatocellular carcinoma(HCC) samples using several different assays and explore the correlations between hypomethylation and clinical parameters and biomarkers,including that of aflatoxin B 1 exposure.METHODS:Using the radio labeled methyl acceptance assay as a measure of global hypomethylation,as well as two repetitive elements,including satellite 2(Sat2) by MethyLight and long interspersed nucleotide elements(LINE1),by pyrosequencing.RESULTS:By all three assays,mean methylation levels in tumor tissues were significantly lower than that in adjacent tissues.Methyl acceptance assay log(mean ± SD) disintegrations/min/ng DNA are 70.0 ± 54.8 and 32.4 ± 15.6,respectively,P = 0.040;percent methylation of Sat2 42.2 ± 55.1 and 117.9 ± 88.8,respectively,P < 0.0001 and percent methylation LINE1 48.6 ± 14.8 and 71.7 ± 1.4,respectively,P < 0.0001.Aflatoxin B 1 albumin(AFB 1-Alb) adducts,a measure of exposure to this dietary carcinogen,were inversely correlated with LINE1 methylation(r =-0.36,P = 0.034).CONCLUSION:Consistent hypomethylation in tumor compared to adjacent tissue was found by the three different methods.AFB 1 exposure is associated with DNA global hypomethylation,suggesting that chemical carcinogens may influence epigenetic changes in humans.展开更多
Aflatoxin B_(1)(AFB_(1))is a naturally-occurring mycotoxin and recognized as the most toxic foodborne toxin,particularly causing damages to kidney.Glomerular podocytes are terminally differentiated epithelial cells.AF...Aflatoxin B_(1)(AFB_(1))is a naturally-occurring mycotoxin and recognized as the most toxic foodborne toxin,particularly causing damages to kidney.Glomerular podocytes are terminally differentiated epithelial cells.AFB_(1)induces podocyte inflammation,proteinuria and renal dysfunction.Studying the mechanism of AFB_(1)-induced podocyte inflammation and murine kidney dysfunction,we detected that AFB_(1)increased ubiquitindependent degradation of the transcription factor RelA through enhanced interaction of RelA with E3 ubiquitin ligase tripartite motif containing 7(TRIM7)in mouse podocyte clone-5(MPC-5)and mouse glomeruli.Reduction of RelA resulted in decreasing microRNA-9(miR-9)and activating the chemokine receptor 4(CXCR4),thioredoxin interacting protein(TXNIP),and NOD-like receptor pyrin domain-containing 3(NLRP3)signaling axis(CXCR4/TXNIP/NLRP3 pathway),leading to podocyte inflammation.We also determined that downregulation of miR-9 led to CXCR4 expression and the downstream TXNIP/NLRP3 pathway activation.Overexpression of miR-9 or deletion of CXCR4 suppressed AFB_(1)-induced CXCR4/TXNIP/NLRP3 pathway,resulting in alleviating podocyte inflammation and kidney dysfunction.Our findings indicated that ubiquitin-dependent proteolysis of RelA,downregulation of miR-9,and activation of CXCR4/TXNIP/NLRP3 pathway played an essential role in AFB_(1)-induced glomerular podocyte inflammation.Our study revealed a novel mechanism,via RelA,for the control of AFB_(1)’s nephrotoxicity,leading to an effective protection of food safety and public health.展开更多
Background:The current study was conducted to investigate the individual and combined occurrence of aflatoxin B_(1)(AFB_(1)),deoxynivalenol(DON)and zearalenone(ZEN)in feeds from various Provinces of China during 2018 ...Background:The current study was conducted to investigate the individual and combined occurrence of aflatoxin B_(1)(AFB_(1)),deoxynivalenol(DON)and zearalenone(ZEN)in feeds from various Provinces of China during 2018 to 2020.A total of 3,507 feed samples,including 2,090 feed ingredients and 1,417 complete feed samples,were collected from different areas of China for mycotoxins analysis.Results:The individual contamination of AFB_(1),DON and ZEN were present in more than 81.9%,96.4% and 96.9% of feed samples,respectively,with average concentration ranges of AFB_(1) between 1.2-27.4μg/kg,DON between 458.0-1,925.4μg/kg and ZEN between 48.1-326.8μg/kg.Notably,0.9%,0.5% and 0.1% of feed ingredients,and 1.2-12.8%,0.9-2.9% and 0-8.9% of complete feeds for pigs,poultry and ruminants with AFB_(1),ZEN and DON that exceeded China’s safety standards,respectively.Moreover,more than 81.5%of feed ingredients and 95.7% of complete feeds were co-contaminated with various combinations of these mycotoxins.Conclusion:This study indicates that the feeds in China were universally contaminated with AFB_(1),DON and ZEN during the past 3 years.These findings highlight the significance of monitoring mycotoxin contaminant levels in the domestic animal feed,and the importance of carrying out feed administration and remediation strategies for mycotoxin control.展开更多
Hazelnuts are an economically important nut which is consumed world-wide.It is prone to infection by Aspergillus flavus and contamination with aflatoxins.Taking Tukey’s hazelnuts as a research object,the objective of...Hazelnuts are an economically important nut which is consumed world-wide.It is prone to infection by Aspergillus flavus and contamination with aflatoxins.Taking Tukey’s hazelnuts as a research object,the objective of this study were to(a)quantify respiration rates and(b)dry matter losses(DMLs)and(c)aflatoxin B_(1)(AFB_(1))contamination of naturally stored shelled hazelnuts at different temperatures and water availabilities.Subsequently,shelled hazelnuts were inoculated with additional A.flavus inoculum prior to storage to examine effects on dry matter losses and on AFB_(1) contamination.Maximum respiration of hazelnuts and associated mycoflora was under wetter conditions of 0.90~0.95 water activity(aw=12.5%~18%moisture content).This resulted in between approx.10%DML at 25 and 30℃after 5 days storage.Inoculation and storage of shelled hazelnuts+A.flavus inoculum resulted in similar patterns of respiration with optimal levels at 25~30℃and>0.90 aw.Indeed,AFB_(1) contamination was highest at the maximum water levels tested of 0.90 aw.Indeed the contamination level exceeded the legislative limits set by the EU for AFB_(1) contamination of these nuts.Correlation between DMLs and all the AFB_(1) data in both sets of studies showed that very small changes in DML due to poor drying or storage of≥0.6%resulted in AFB_(1) contamination levels exceeding the EU legislative limits.Thus,efficient drying and safe monitored storage is necessary to minimise the risk of AFB_(1) contamination in this economically important commodity and to avoid exposure of consumers to such toxins.展开更多
基金Supported by A grant from the National Institute of Health,No. ES005116 and No.P30ES009089
文摘AIM:To determine global DNA methylation in paired hepatocellular carcinoma(HCC) samples using several different assays and explore the correlations between hypomethylation and clinical parameters and biomarkers,including that of aflatoxin B 1 exposure.METHODS:Using the radio labeled methyl acceptance assay as a measure of global hypomethylation,as well as two repetitive elements,including satellite 2(Sat2) by MethyLight and long interspersed nucleotide elements(LINE1),by pyrosequencing.RESULTS:By all three assays,mean methylation levels in tumor tissues were significantly lower than that in adjacent tissues.Methyl acceptance assay log(mean ± SD) disintegrations/min/ng DNA are 70.0 ± 54.8 and 32.4 ± 15.6,respectively,P = 0.040;percent methylation of Sat2 42.2 ± 55.1 and 117.9 ± 88.8,respectively,P < 0.0001 and percent methylation LINE1 48.6 ± 14.8 and 71.7 ± 1.4,respectively,P < 0.0001.Aflatoxin B 1 albumin(AFB 1-Alb) adducts,a measure of exposure to this dietary carcinogen,were inversely correlated with LINE1 methylation(r =-0.36,P = 0.034).CONCLUSION:Consistent hypomethylation in tumor compared to adjacent tissue was found by the three different methods.AFB 1 exposure is associated with DNA global hypomethylation,suggesting that chemical carcinogens may influence epigenetic changes in humans.
基金funded by Suzhou Science and Technology Council(SNG201907)Universities Natural Science Foundation of Jiangsu Province(20KJB330002)+6 种基金General Program of China Postdoctoral Science Foundation(2022M711369)the Startup Funding of Soochow University,Jiangsu Province-Suzhou Science and Technology Planning Project(SL T201917)National Natural Science Foundation of China(32172922,31972741)Natural Science Foundation of Jiangsu Province of China(BK20211216,BK20221091)the Startup Funding of Hefei University of Technology(1302003712022058)China-CEEC Joint University Education Project(202010)the Excellence Project PrF UHK(2217/2022-2023)。
文摘Aflatoxin B_(1)(AFB_(1))is a naturally-occurring mycotoxin and recognized as the most toxic foodborne toxin,particularly causing damages to kidney.Glomerular podocytes are terminally differentiated epithelial cells.AFB_(1)induces podocyte inflammation,proteinuria and renal dysfunction.Studying the mechanism of AFB_(1)-induced podocyte inflammation and murine kidney dysfunction,we detected that AFB_(1)increased ubiquitindependent degradation of the transcription factor RelA through enhanced interaction of RelA with E3 ubiquitin ligase tripartite motif containing 7(TRIM7)in mouse podocyte clone-5(MPC-5)and mouse glomeruli.Reduction of RelA resulted in decreasing microRNA-9(miR-9)and activating the chemokine receptor 4(CXCR4),thioredoxin interacting protein(TXNIP),and NOD-like receptor pyrin domain-containing 3(NLRP3)signaling axis(CXCR4/TXNIP/NLRP3 pathway),leading to podocyte inflammation.We also determined that downregulation of miR-9 led to CXCR4 expression and the downstream TXNIP/NLRP3 pathway activation.Overexpression of miR-9 or deletion of CXCR4 suppressed AFB_(1)-induced CXCR4/TXNIP/NLRP3 pathway,resulting in alleviating podocyte inflammation and kidney dysfunction.Our findings indicated that ubiquitin-dependent proteolysis of RelA,downregulation of miR-9,and activation of CXCR4/TXNIP/NLRP3 pathway played an essential role in AFB_(1)-induced glomerular podocyte inflammation.Our study revealed a novel mechanism,via RelA,for the control of AFB_(1)’s nephrotoxicity,leading to an effective protection of food safety and public health.
基金supported by the Chinese Natural Science Foundation projects(32072775 and 31772636)National Key Research and Development Program of China(2016YFD0501207)JiangSu Aomai Bio-Technology Co.,Ltd.(Nanjing,China).
文摘Background:The current study was conducted to investigate the individual and combined occurrence of aflatoxin B_(1)(AFB_(1)),deoxynivalenol(DON)and zearalenone(ZEN)in feeds from various Provinces of China during 2018 to 2020.A total of 3,507 feed samples,including 2,090 feed ingredients and 1,417 complete feed samples,were collected from different areas of China for mycotoxins analysis.Results:The individual contamination of AFB_(1),DON and ZEN were present in more than 81.9%,96.4% and 96.9% of feed samples,respectively,with average concentration ranges of AFB_(1) between 1.2-27.4μg/kg,DON between 458.0-1,925.4μg/kg and ZEN between 48.1-326.8μg/kg.Notably,0.9%,0.5% and 0.1% of feed ingredients,and 1.2-12.8%,0.9-2.9% and 0-8.9% of complete feeds for pigs,poultry and ruminants with AFB_(1),ZEN and DON that exceeded China’s safety standards,respectively.Moreover,more than 81.5%of feed ingredients and 95.7% of complete feeds were co-contaminated with various combinations of these mycotoxins.Conclusion:This study indicates that the feeds in China were universally contaminated with AFB_(1),DON and ZEN during the past 3 years.These findings highlight the significance of monitoring mycotoxin contaminant levels in the domestic animal feed,and the importance of carrying out feed administration and remediation strategies for mycotoxin control.
文摘Hazelnuts are an economically important nut which is consumed world-wide.It is prone to infection by Aspergillus flavus and contamination with aflatoxins.Taking Tukey’s hazelnuts as a research object,the objective of this study were to(a)quantify respiration rates and(b)dry matter losses(DMLs)and(c)aflatoxin B_(1)(AFB_(1))contamination of naturally stored shelled hazelnuts at different temperatures and water availabilities.Subsequently,shelled hazelnuts were inoculated with additional A.flavus inoculum prior to storage to examine effects on dry matter losses and on AFB_(1) contamination.Maximum respiration of hazelnuts and associated mycoflora was under wetter conditions of 0.90~0.95 water activity(aw=12.5%~18%moisture content).This resulted in between approx.10%DML at 25 and 30℃after 5 days storage.Inoculation and storage of shelled hazelnuts+A.flavus inoculum resulted in similar patterns of respiration with optimal levels at 25~30℃and>0.90 aw.Indeed,AFB_(1) contamination was highest at the maximum water levels tested of 0.90 aw.Indeed the contamination level exceeded the legislative limits set by the EU for AFB_(1) contamination of these nuts.Correlation between DMLs and all the AFB_(1) data in both sets of studies showed that very small changes in DML due to poor drying or storage of≥0.6%resulted in AFB_(1) contamination levels exceeding the EU legislative limits.Thus,efficient drying and safe monitored storage is necessary to minimise the risk of AFB_(1) contamination in this economically important commodity and to avoid exposure of consumers to such toxins.
