广西扶绥县肝癌高发区和相对低发区儿童黄曲霉毒素B1摄入量对比研究

对广西扶绥县肝癌高发区和相对低发区385例5～13岁儿童的黄曲霉毒素B_1(AFB_1)摄入量进行了对比研究,结果表明,肝癌高发区儿童AFB_1摄入量明显大于相对低发区儿童(P<0.01),分别为123.51ng/kg体重/日和30.58ng/kg体重/日,前者是后者4倍多;同时,高发区儿童24小时尿中黄曲霉毒素M_1(AFM_1)排出量亦高于相对低发区儿童,分别为2.71ng/kg体重/日和1.00ng/kg体重/日(P<0.01),前者是后者两倍多。研究结果提示,该县境内出现肝癌高发区和相对低发区之差别,原因之一是不同地区居民从儿童时期起暴露于AFB_1水平不同,肝癌高发区是AFB_1高摄入量区。因此,从儿童时期起就开始注意减少AFB_1摄入量,对预防原发性肝癌有十分重要意义。     

Occurrence of aflatoxin M1 in raw cow,goat and sheep milk during spring and autumn in Croatia during 2016

Raw cow, goat and sheep milk samples were collected in different regions of Croatia during spring and autumn 2016. Aflatoxin M1 (AFM1) concentrations were measured in the following ranges (ng/kg): cow milk 0.93–85.4; goat milk 2.0–18.6; sheep milk 2.27–11.2. AFM1 levels exceeding the European Union maximum residue levels of 50?ng/kg were found in two cow milk samples in spring and 10 cow milk samples in autumn. The probable daily intakes (PDIs) for all three dairy species were from 0.0108 to 0.0165?ng/kg b.w./day and contributing 1.08–1.65% to the proposed provisional maximum tolerable daily intake (PMTDI; 1?ng/kg b.w./day), indicating low risk exposure for consumers. The mean positive cow milk PDI was 0.15?ng/kg b.w./day, contributing 15.2% to the PMTDI.     

Infants exposure to aflatoxin M1 as a novel foodborne zoonosis

Occurrence of aflatoxin M₁ (AFM₁) in infant formula milk powder (IFMP) and maternal breast milk (MBM) was investigated as a risk factor affects the health of newborns in Egypt. A total of 125 IFMP and 125 MBM samples were collected and examined for the presence of AFM₁ using competitive ELISA test. The results indicated that the relative risk (RR) of exposure to AFM₁ via consumption of MBM was higher than IFMP (RR; 1.6, 95% CI; 1.28–2.03, p = 0.0001). The mean concentrations of AFM₁ were significantly differed (p < 0.0001) between MBM (74.413 ± 7.070 ng/l) and IFMP (9.796 ± 1.036 ng/l). High frequency distributions were detected within the range of 5–25 ng/l and >50–100 ng/l in IFMP and MBM, respectively. The average daily exposure of newborns to AFM₁ via consumption of MBM and IFMP was 52.684 and 8.170 ng, respectively, with a significant difference at p < 0.0001. Consumption of raw milk by lactating mothers exhibited a significant correlation (p < 0.0001) with the presence of AFM₁ in their milk. In conclusion, this work established a pioneering concept that AFM₁ may be considered as an etiological factor for a novel foodborne zoonosis identified as Aflatoxicosis M₁.     

基于RNA-seq分析黄曲霉毒素B1诱导大鼠肝癌的可变剪接事件

目的 探讨黄曲霉毒素B1（aflatoxin B1，AFB1）诱发大鼠致肝癌的可能机制及其阻断肝癌分子机制的可变剪接事件。方法 构建AFB1诱发大鼠致肝癌模型，提取大鼠肝组织总RNA，采用Illumina HiSeq 2000测序平台对大鼠肝组织进行RNA-seq测序，以大鼠基因组数据为参考，纳入目前已知的具有多种可变剪接存在的332个参考基因，鉴定和分析大鼠基因组的可变剪接基因，并对具有差异表达的可变剪接基因进行GO分类的生物过程（biological process，BP）富集分析。结果 RNA-seq测序结果显示，未成癌组与对照组有18个基因的可变剪接模式存在较大差异，差异基因主要富集在刺激反应功能上；成癌组与对照组有37个基因的可变剪接模式存在差异，差异基因主要富集在刺激反应和细胞增殖调节功能上；成癌组与未成癌组有32个基因的可变剪接模式存在明显差异，差异基因主要富集在细胞增殖调节功能上。成癌组发现7个与细胞增殖调节相关基因的可变剪接模式发生异常，其中成癌组、未成癌组和对照组IgfI、Carm1、Tcfe2a基因的可变剪接模式存在显著差异。结论 IgfI、Carm1、Tcfe2a基因的可变剪接改变可能在AFB1诱导大鼠肝癌形成过程中发挥重要作用。     

解毒酶基因谷胱甘肽硫转移酶M1多态性与黄曲霉毒素B1相关性肝细胞癌易患性研究

目的探讨解毒酶基因谷胱甘肽硫转移酶M1(GSTM 1)多态性与黄曲霉毒素B1(AFB1) 相关性肝细胞癌(HCC)风险的相关性。方法应用聚合酶链反应技术对广西地区AFB1高污染区140 例HCC患者和536例对照人群的GSTM1基因多态性进行检测,进行以医院为基础的病例对照研究。结果(1)GSTM1-present基因型为HCC保护基因型,而GSTM1-null基因型为HCC风险基因型,其校正风险值OR(95%可信区间CI)为2.07(1.20-3.5 7);(2)在AFB1暴露中低度与高度两个层次, GSTM1基因多态性均增加HCC危险性,其校正OR(95%CI)分别为1.92(0.92-4.00)和1.80(0.77- 4.17)。结论解毒酶基因GSTM1多态性与HCC易患性相关,其缺失型增加患HCC风险;GSTM1在中低度和高度AFB1暴露时均与HCC易患性相关,但在中低度暴露时更明显。     

Integrative molecular characterisation of gallbladder cancer reveals micro-environment-associated subtypes

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广西黄曲霉毒素B1高污染区肝细胞癌与细胞色素P3A5基因多态性的相关性

广西西南部为黄曲霉毒素B1（AFB1）高污染区，加上HBV感染率高，造成地区性HCC发生率异常高。研究表明，AFB1经细胞色素P450（CYP450）酶氧化为AFB1-外-8，9环氧化物（AFBO）才有诱变作用，AFBO与DNA共价结合成AFB1-DNA加合物，引起DNA改变，从而导致个体HCC发生。在肝脏受多种CYP450酶的代谢激活，其中最主要的是CYP3A4和CYP3A5。[第一段]     

慢性乙型肝炎病毒感染者中黄曲霉毒素暴露与肝癌发生关系的纵向研究

目的 研究慢性乙型肝炎病毒(HBV)感染者中黄曲霉毒素(AF)暴露与肝癌发生的关系.方法 在肝癌高发现场,对515例感染HBV的肝癌高危人群进行了21年定群纵向研究.结果 (1)观察人群肝癌人年发生率为1437.25/10万,极显著地高于相应自然人群的184.53/10万(P=0.000,RR=7.79),其他肿瘤两组问差异无统计学意义(P=0.576).(2)定期观察人群中发现的肝癌患者平均年龄较相应自然人群提前了1.4年,治后平均生存期延长了6.42个月.(3)AF暴露对象的肝癌人年发生率为2784.96/10万,极显著地高于非暴露人群的1251.02/10万(P=0.008,RR=2.23),其他肿瘤的发生率与AF暴露与否无关.(4)AF暴露人群肝癌发生率随着尿中AFM1排出量增加而上升,当24 h尿中AFM1排出量＞100 ng时,肝癌的人年发生率高达4717.82/10万.尿中AFM1排出量与肝功能异常明显相关(P=0.035),与HBeAg无明显相关性(P=0.812).(5)HBV感染同时伴有AF暴露人群的人年肝癌发病率(2784.96/10万)极显著地高于观察人群(P=0.001)和相应自然人群(P=0.000,RR=15.09).(6)诊断乙肝到肝癌发生的平均时间为14.65年,中位时间13.68年;诊断肝硬化到肝癌发生的平均时间为7.38年,中位时间6.40年.结论 HBV是肝癌发生的主要病因因素,AF暴露在肝癌的发生中具有明显的协同作用;定期观察肝癌高危人群能有效地实现早诊早治,提高疗效;防治肝炎和AF污染是预防肝癌的有效途径.     

Reduction of aflatoxin in fermented milks during production and storage

Aflatoxins are a group of secondary fungal metabolites produced by toxigenic strains of Aspergillus flavus, A. parasiticus and A. nomius. They are one of the most common food contamination problems. Aflatoxins M₁ and M₂ are the hydroxylated metabolites of aflatoxins B₁ and B₂ and emerge in raw milk when lactating animals ingest feed contaminated with these mycotoxins. They may contaminate other dairy products including fermented milks. Aflatoxins are fairly stable in many foods and are rather resistant to degradation. Its stability can be affected by different factors. This article mainly reviews the impact of process, formulation and storage factors on the amount of aflatoxins in fermented milks while consider related mechanisms.