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

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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.     

Unlocking the Secrets Behind Secondary Metabolism: A Review of Aspergillus flavus from Pathogenicity to Functional Genomics

Aspergillus flavus has received a considerable amount of attention due to its ability to produce aflatoxin, a secondary metabolite that is both immunosuppressive and carcinogenic to animals and humans. Research on aflatoxin over the last 40 years has made it one of the best studied fungal secondary metabolites. In spite of the large volume of research in this area, many unanswered questions remain concerning the genetic regulation of aflatoxin production and the molecular signals that intimately associate the synthesis of aflatoxin with specific environmental and nutritional conditions. It is anticipated that the tools now available in the field of genomics will build upon our existing knowledge and provide answers to some of these questions. Complete genome sequences are now available for a number of fungal species that are closely related to A. flavus. This information can be used along with current genomic analyses in A. flavus to more closely examine the biosynthesis and regulation of secondary metabolism. The intent of this review is to summarize the large body of knowledge that exists from many years of research on A. flavus, with the hope that this information in the light of new genomic studies may bring scientists closer to unraveling the web of regulatory circuits that govern aflatoxin biosynthesis. Specifically, scientific findings in the following areas will be presented: classification and phylogenetic analyses of A. flavus, population biology, ecology and pathogenicity in agricultural environments, classical genetics including linkage group and mutant analyses, gene clusters, regulation of aflatoxin biosynthesis, and genomics.     

Cyclopiazonic acid biosynthesis by Aspergillus flavus

Cyclopiazonic acid (CPA) is an indole-tetramic acid mycotoxin produced by some strains of Aspergillus flavus. Characterization of the CPA biosynthesis gene cluster confirmed that formation of CPA is via a three-enzyme pathway. This review examines the structure and organization of the CPA genes, elucidates the specific roles of functional domains of each enzyme in carrying out catalytic conversions leading to CPA production, and delineates the molecular basis for the lack of CPA production by A. flavus strains currently being used in biocontrol of aflatoxin contamination of crops.     

Modulation of aflatoxin toxicity and biomarkers by lycopene in F344 rats

Modulation by lycopene of aflatoxin B(1) (AFB(1))-induced toxic effects, metabolism, and metabolic activations was studied in young F344 rats. Animals were pretreated orally with either corn oil (control group) or lycopene [100 mg/kg body weight (b.w.), intervention group] 5 days/week for 2 weeks. Control animals were then treated daily with AFB(1) (250 microg/kg b.w) alone. Intervention animals were administered lycopene (100 mg/kg b.w.) at 1 h following a daily treatment with AFB(1) (250 mug/kg b.w.). Pretreatment and intervention with lycopene significantly reduced the toxic effect caused by AFB(1) and greatly modulated AFB(1) metabolism and metabolic activation. Urinary excretion of AFB(1) phase 1 metabolites, AFM(1), AFQ(1), and AFP(1), was significantly decreased in lycopene-treated animals. Formation of serum AFB(1)-albumin adducts was also significantly reduced. The rate of reduction was from approximately 30% on day 1 (p<0.05) to 67.7% on day 15 (p<0.001). Lycopene intervention also significantly reduced formation of AFB(1)-DNA adducts in liver compared to control animals, with the highest reduction (52.7%) occurring on day 3 (p<0.05). Levels of AFB(1)-N(7)-guanine excreted in urine were also significantly decreased. Urinary excretion of the phase 2 detoxification metabolite, AFB(1)-mecapturic acid, was significantly increased in lycopene-intervened animals. AFB(1)-induced urinary excretion of 8-hydroxydeoxyguanosine was also reduced to 50% on day 7 after lycopene intervention. Collectively, these results suggest that inhibition of phase 1 metabolism and metabolic activation, as well as induction of phase 2 detoxification enzyme activity are the potential mechanisms for the chemopreventive effects of lycopene.     

Aflatoxin M<Subscript>1</Subscript> Levels in Surk Samples,a Traditional Turkish Cheese from Southern Turkey

In this study, aflatoxin M₁ (AFM₁) contamination was investigated in Surk cheese, a traditional Turkish cheese consumed particularly in southern Turkey. For this purpose, 120 Surk cheese samples were collected from different retail markets and analysed by enzyme-linked immunoassay. The level of AFM₁ varied from 16 to 1,043 ng/kg in 72 of the Surk samples (60%), 16 of which (13.3% of 120 samples) contained AFM₁ amounts exceeding the maximum tolerance limit (250 ng/kg) established in Turkey. The results indicated that the occurrence of AFM₁ in Surk cheese samples may be considered as a possible risk for consumer health.     

Chemical composition,antifungal and antiaflatoxigenic activities of Ocimum sanctum L. essential oil and its safety assessment as plant based antimicrobial

The study deals with the efficacy of Ocimum sanctum essential oil (EO) and its major component, eugenol against the fungi causing biodeterioration of food stuffs during storage. O. sanctum EO and eugenol were found efficacious in checking growth of Aspergillus flavus NKDHV8; and, their minimum inhibitory concentrations (MICs) were recorded as 0.3 and 0.2 μl ml⁻¹, respectively. The O. sanctum EO and eugenol also inhibited the aflatoxin B₁ production completely at 0.2 and 0.1 μl ml⁻¹, respectively. Both of these were found superior over some prevalent synthetic antifungals and exhibited broad fungitoxic spectrum against 12 commonly occurring fungi. The LD₅₀ value of O. sanctum EO on mice was found to be 4571.43 μl kg⁻¹ suggesting its non-mammalian toxic nature. The findings of present study reveals the possible exploitation of O. sanctum EO and eugenol as plant based safe preservatives against fungal spoilage of food stuffs during storage.