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Ethical considerations in the design and conduct of a cluster-randomised mycotoxin mitigation trial in Tanzania 坦桑尼亚群随机真菌毒素缓解试验设计和实施中的伦理考虑
IF 2 4区 医学 Q3 FOOD SCIENCE & TECHNOLOGY Pub Date : 2022-01-24 DOI: 10.3920/wmj2021.2705
E. Phillips, P. Turner, F. Ngure, N. Kassim, E. Makule, L. E. Smith, R. Nelson, R. Stoltzfus
Aflatoxins are fungal metabolites that commonly contaminate staple food crops in tropical regions. Acute aflatoxin consumption in very high concentration causes aflatoxicosis and acute liver failure, while chronic, moderate levels of intake cause hepatocellular carcinoma. The effects of frequent moderate- to high-level exposure during infancy, however, is less clearly understood. Half a billion people in low- and middle-income countries continue to be exposed to aflatoxins through dietary consumption, in part because of lack of enforcement of regulatory limits and few feasible long-term mitigation options in these settings. Several epidemiologic studies have shown an association between aflatoxin exposure in infants and young children and growth failure, but strong experimental evidence is lacking. The Mycotoxin Mitigation Trial conducted in Tanzania was a cluster-randomised trial to assess the effect of a reduced aflatoxin diet on linear growth. Prior to the design and implementation of this trial, a group of multi-disciplinary and multi-national scientists reviewed literature in biomedical, public health, environmental health ethics. In this paper we outline the most salient ethical questions and dilemmas in the potential conduct of such a study and describe the ethical precedents and principles that informed our decision-making processes and ultimate study protocol.
黄曲霉毒素是真菌代谢产物,通常会污染热带地区的主要粮食作物。高浓度的急性黄曲霉毒素摄入会导致黄曲霉毒素中毒和急性肝衰竭,而慢性、中等水平的摄入会导致肝细胞癌。然而,婴儿期频繁的中度至高度暴露的影响尚不清楚。中低收入国家的5亿人继续通过饮食消费接触黄曲霉毒素,部分原因是缺乏监管限制,在这些环境中几乎没有可行的长期缓解方案。几项流行病学研究表明,婴幼儿接触黄曲霉毒素与生长衰竭之间存在关联,但缺乏强有力的实验证据。在坦桑尼亚进行的真菌毒素缓解试验是一项集群随机试验,旨在评估减少黄曲霉毒素饮食对线性生长的影响。在设计和实施这项试验之前,一组多学科和多国科学家审查了生物医学、公共卫生和环境卫生伦理方面的文献。在本文中,我们概述了在进行此类研究的潜在过程中最突出的伦理问题和困境,并描述了为我们的决策过程和最终研究方案提供信息的伦理先例和原则。
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引用次数: 1
HepG2 liver cells treated with fumonisin B1 in galactose supplemented media have altered expression of genes and proteins known to regulate cholesterol flux 在半乳糖补充的培养基中用伏马菌素B1处理的HepG2肝细胞改变了已知调节胆固醇流量的基因和蛋白质的表达
IF 2 4区 医学 Q3 FOOD SCIENCE & TECHNOLOGY Pub Date : 2021-12-17 DOI: 10.3920/wmj2021.2723
T. Adimulam, N. S. Abdul, A. Chuturgoon
Fumonisin B1 (FB1) contributes to mycotoxicosis in animals and has been associated with the incidence of some cancers in humans. The effect of FB1 on lipidomic profiles, sphingolipids and cholesterol levels have been demonstrated in experimental models, however, the events leading to altered cholesterol levels are unclear. This study investigates the molecular mechanisms that regulate the effect of FB1 on cholesterol homeostasis in galactose supplemented HepG2 liver cells. Galactose supplementation is a proven method utilised to circumvent the Crabtree effect exhibited by cancer cells, which forces cancer cells to activate the mitochondria. HepG2 cells were cultured in galactose supplemented media and treated with FB1 (IC50 = 25 μM) for 6 h. Cell viability was determined using the MTT assay. Metabolic status was evaluated using ATP luciferase assay, and cholesterol regulatory transcription factors (SIRT1, SREBP-1C, LXR, LDLR, PCSK9, and ABCA1) were investigated using western blotting and qPCR. FB1 in galactose supplemented HepG2 cells increased gene expression of SIRT1 (P<0.05), SREBP-1C, LXR, and LDLR; however, PCSK9 (P<0.05) was decreased. Furthermore, protein expression of SIRT1, LXR, and LDLR was elevated upon FB1 treatment, while SREBP-1C and PCSK9 were reduced. The data provides evidence that SIRT1 reduced the expression of PCSK9 and deacetylated LXR to prevent degradation of LDLR. This could result in a dysregulated cholesterol flux, which may contribute to FB1 mediated toxicity.
伏马菌素B1(FB1)导致动物的真菌中毒,并与人类某些癌症的发生率有关。FB1对脂质组学特征、鞘脂和胆固醇水平的影响已在实验模型中得到证实,但导致胆固醇水平改变的事件尚不清楚。本研究探讨了调节FB1对半乳糖补充的HepG2肝细胞胆固醇稳态影响的分子机制。补充半乳糖是一种已被证实的方法,用于规避癌症细胞表现出的Crabtree效应,该效应迫使癌症细胞激活线粒体。HepG2细胞在补充半乳糖的培养基中培养,并用FB1(IC50=25μM)处理6小时。使用MTT法测定细胞活力。使用ATP萤光素酶测定法评估代谢状态,并使用蛋白质印迹和qPCR研究胆固醇调节转录因子(SIRT1、SREBP-1C、LXR、LDLR、PCSK9和ABCA1)。FB1在添加半乳糖的HepG2细胞中增加SIRT1、SREBP-1C、LXR和LDLR的基因表达(P<0.05);PCSK9下降(P<0.05)。此外,FB1处理后SIRT1、LXR和LDLR的蛋白表达升高,而SREBP-1C和PCSK9的蛋白表达降低。该数据提供了SIRT1降低PCSK9和去乙酰基化LXR的表达以防止LDLR降解的证据。这可能导致胆固醇流量失调,这可能导致FB1介导的毒性。
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引用次数: 2
Evaluation of the impact of pre- and post-harvest maize handling practices on mycotoxin contamination on smallholder farms in Guatemala 评估危地马拉小农农场收获前后玉米处理方法对霉菌毒素污染的影响
IF 2 4区 医学 Q3 FOOD SCIENCE & TECHNOLOGY Pub Date : 2021-12-13 DOI: 10.3920/wmj2021.2701
A. Garsow, D. Mendez, O. Torres, B. Kowalcyk
Mycotoxins are secondary metabolites produced by fungi including Aspergillus and Fusarium that commonly contaminate crops, such as maize, resulting in economic losses and food insecurity. Mycotoxins can contaminate crops during pre- and post-harvest stages. Consumption of mycotoxin-contaminated foods has been linked to a variety of negative health outcomes including liver cancer, stunting, and neural tube defects. In countries such as Guatemala where maize constitutes a major portion of the diet, mycotoxins can be a significant contributor to disease burden. This review describes maize pre- and post-harvest practices in Guatemala that can lead to the development of mycotoxins and subsequent exposure to humans and animals, current information gaps, and opportunities for future research. There are specific challenges to minimising fungal growth and subsequent mycotoxin production during storage of maize in Guatemala, including reducing moisture content, minimising pest damage, and controlling temperature. Research on maize-handling practices that are associated with the greatest mycotoxin exposure in Guatemala is needed to prioritise allocation of resources and reduce exposure.
真菌毒素是真菌产生的次生代谢产物,包括曲霉菌和镰刀菌,它们通常污染玉米等作物,导致经济损失和粮食不安全。真菌毒素会在收获前和收获后污染作物。食用霉菌毒素污染的食物与多种负面健康结果有关,包括肝癌、发育迟缓和神经管缺陷。在危地马拉等国,玉米是饮食的主要组成部分,真菌毒素可能是造成疾病负担的重要因素。这篇综述描述了危地马拉玉米收获前和收获后的做法,这些做法可能导致真菌毒素的发展和随后暴露于人类和动物、当前的信息差距以及未来研究的机会。在危地马拉,在玉米储存过程中,最大限度地减少真菌生长和随后的真菌毒素生产面临着具体挑战,包括降低水分含量、最大限度地降低害虫危害和控制温度。需要对危地马拉霉菌毒素暴露量最大的玉米处理方法进行研究,以优先分配资源并减少暴露。
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引用次数: 0
A novel chemical marker of tremorgenic mycotoxicosis detected by gas-chromatography/mass-spectrometry 气相色谱/质谱法检测震颤性真菌毒素新的化学标志物
IF 2 4区 医学 Q3 FOOD SCIENCE & TECHNOLOGY Pub Date : 2021-12-13 DOI: 10.3920/wmj2020.2633
C. Pickard, J. Fortin, D. Holmes, J. Buchweitz, A. Lehner
Tremorgenic mycotoxicosis can arise from dietary exposure to secondary metabolite products of various fungal species, particularly those from the Penicillium genus. Although general toxin screens often rely on gas chromatography-mass spectrometry (GC/MS) and well-developed mass spectral library databases, two principal representative Penicillium mycotoxins, roquefortine and penitrem A, are unamenable to GC/MS owing to high molecular weights, low volatilities and/or high thermal instabilities. Reliance on GC/MS screens alone could therefore inadvertently result in failure to collect evidence of exposure to such tremorgenic mycotoxins. In this report we describe a newly discovered tremorgenic marker compound (TMC), the presence of which correlates highly with conclusive exposure to Penicillium toxins in explanation of clinical manifestations of tremorgenic mycotoxicosis. According to detailed mass spectral deconvolution, the compound is 210.0892 molecular weight, and amenable to GC/MS whether chemically underivatized or derivatized by methylation or trimethylsilylation. 1D and 2D NMR (nuclear magnetic resonance) studies on the isolated compound determined the TMC to be the Penicillium product terrestric acid, C11H14O4, which matches the molecular formula determined by high resolution mass spectrometry and thus provides an excellent target for assessment of mycotoxicosis by GC/MS.
致震颤性真菌中毒可由饮食中接触各种真菌的次级代谢产物引起,尤其是青霉属的次级代谢产品。尽管一般的毒素筛选通常依赖于气相色谱-质谱法(GC/MS)和完善的质谱库数据库,但两种主要的代表性青霉真菌毒素,罗奎福汀和青霉烯甲,由于高分子量、低挥发性和/或高热不稳定性,对GC/MS不适用。因此,仅依赖GC/MS筛查可能会无意中导致无法收集暴露于此类震颤真菌毒素的证据。在本报告中,我们描述了一种新发现的震颤标志物化合物(TMC),其存在与青霉毒素的决定性暴露高度相关,以解释震颤真菌中毒的临床表现。根据详细的质谱反褶积,该化合物的分子量为210.0892,无论是化学衍生化还是通过甲基化或三甲基甲硅烷基化衍生,都能进行GC/MS。对分离的化合物进行1D和2D NMR(核磁共振)研究,确定TMC为青霉菌产物terrestric acid C11H14O4,其与高分辨率质谱法确定的分子式相匹配,因此为GC/MS评估真菌中毒提供了一个极好的靶点。
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引用次数: 1
Inhibition of Aspergillus flavus growth and aflatoxin B1 production by natamycin 纳他霉素对黄曲霉生长和黄曲霉毒素B1产生的抑制作用
IF 2 4区 医学 Q3 FOOD SCIENCE & TECHNOLOGY Pub Date : 2021-12-02 DOI: 10.3920/wmj2020.2620
P. Chang, B. Tai, M. Zheng, Qing Yang, F. Xing
Aspergillus flavus causes huge crop losses, reduces crop quality and has adverse effects on human and animal health. A large amount of food contaminated with aflatoxin can greatly increase the risk of liver cancer. Therefore, prevention and control of aflatoxin production have aroused attention of research in various countries. Natamycin extracted from Streptomyces spp. has been widely used in production practice due to its good specificity and safety. Here, we found that natamycin could significantly inhibit fungal growth, conidia germination, ergosterol and AFB1 production by A. flavus in a dose-dependent manner. Scanning electron microscope analysis indicated that the number of conidia was decreased, the outer wall of conidia was destroyed, and the mycelia were shrivelled and tangled by natamycin. RNA-Seq data indicated that natamycin inhibited fungal growth and conidia development of A. flavus by significantly down-regulating some genes involved in ergosterol biosynthesis, such as Erg13, HMG1 and HMG2. It inhibited conidia germination by significantly down-regulating some genes related to conidia development, such as FluG and VosA. After natamycin exposure, the decreased ratio of aflS/aflR caused by the down-regulation of all the structural genes, which subsequently resulted in the suppression of AFB1 production. In conclusion, this study served to reveal the inhibitory mechanisms of natamycin on fungal growth and AFB1 biosynthesis in A. flavus and to provide solid evidence for its application in controlling AFB1 contamination.
黄曲霉会造成巨大的作物损失,降低作物质量,并对人类和动物健康产生不利影响。大量被黄曲霉毒素污染的食物会大大增加患癌症的风险。因此,预防和控制黄曲霉毒素的产生引起了各国研究的重视。从链霉菌中提取的纳他霉素具有良好的特异性和安全性,在生产实践中得到了广泛应用。在这里,我们发现纳他霉素可以以剂量依赖的方式显著抑制黄曲霉的真菌生长、分生孢子萌发、麦角甾醇和AFB1的产生。扫描电镜分析表明,纳他霉素使分生孢子数量减少,分生孢子外壁被破坏,菌丝皱缩缠结。RNA-Seq数据表明,纳他霉素通过显著下调一些参与麦角甾醇生物合成的基因,如Erg13、HMG1和HMG2,抑制黄曲霉的真菌生长和分生孢子发育。它通过显著下调与分生孢子发育相关的一些基因,如FluG和VosA,抑制分生孢子萌发。纳他霉素暴露后,所有结构基因的下调导致aflS/aflR比率降低,随后导致AFB1产生的抑制。总之,本研究揭示了纳他霉素对黄曲霉真菌生长和AFB1生物合成的抑制机制,并为其在控制AFB1污染方面的应用提供了坚实的证据。
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引用次数: 1
Effects of aflatoxin B1 and monensin interaction on liver and intestine of poultry – influence of a biological additive (Pichia kudriavzevii RC001) 黄曲霉毒素B1和莫能菌素相互作用对家禽肝脏和肠道的影响——生物添加剂(毕赤酵母RC001)的影响
IF 2 4区 医学 Q3 FOOD SCIENCE & TECHNOLOGY Pub Date : 2021-12-02 DOI: 10.3920/wmj2021.2692
A. Magnoli, V. Poloni, L.A. Cristofolini, C. Merkis, F. Escobar, C. Torres, S. Chiacchiera, L. Cavaglieri
The aim of this study was to evaluate the effects of aflatoxin B1 (AFB1) and monensin (MONS) interaction on the liver and intestinal histological changes in poultry, and the influence of Pichia kudriavzevii RC001. One-day-old commercial line (Ross 308) broilers (n=120) were individually weighed and randomly assigned to 8 treatments (15 broilers/treatment, 5 broilers per cage and 3 replicates/treatment). The experimental diets were: Group 1: basal diet (BD); Group 2: BD + MONS (50 mg/kg); Group 3: BD + P. kudriavzevii RC001 (1 g/kg); Group 4: BD + AFB1 (100 μg/kg); Group 5: BD + MONS + P. kudriavzevii RC001; Group 6: BD + AFB1 + P. kudriavzevii RC001; Group 7: BD + AFB1 + MONS + P. kudriavzevii RC001; Group 8: BD + AFB1 + MONS. When MONS was added, the typical AFB1 macroscopic and microscopic alterations were intensified. The P. kudriavzevii RC001 cytotoxicity and genotoxicity assays with Vero cells and with broiler chicken’s erythrocytes, demonstrated that P. kudriavzevii RC001 neither were non-cytotoxic nor genotoxic. When MONS was added in the presence of P. kudriavzevii RC001, the toxic effect of AFB1 on liver was not prevented. When P. kudriavzevii was present alone, the same prevention of the pathological damage was observed in the intestine of poultry fed with AFB1. The smallest apparent absorption area was obtained when AFB1 and MONS were added in the feed (P<0.05). AFB1 and MONS interaction demonstrated important toxic effects. Although P. kudriavzevii was effective in ameliorating the adverse effects of AFB1 alone on liver pathology and gut morphology, it was not able to diminish the toxic effects of AFB1 in presence of MONS. It suggests that P. kudriavzevii could be used as feed additive or counteracting the toxic effects of AFB1 in poultry production in the absence of MONS.
本研究的目的是评估黄曲霉毒素B1(AFB1)和莫能菌素(MONS)相互作用对家禽肝脏和肠道组织学变化的影响,以及库氏毕赤酵母RC001的影响。一日龄商品系(Ross 308)肉鸡(n=120)被单独称重并随机分配到8个处理(15只肉鸡/处理,5只肉鸡/笼和3个重复/处理)。实验日粮为:第1组:基础日粮(BD);第2组:BD+MONS(50mg/kg);第3组:BD+P.kudriavzevii RC001(1g/kg);第4组:BD+AFB1(100μg/kg);第5组:BD+MONS+P.kudriavzevii RC001;第6组:BD+AFB1+P.kudriavzevii RC001;第7组:BD+AFB1+MONS+P.kudriavzevii RC001;第8组:BD+AFB1+MONS。当加入MONS时,典型的AFB1宏观和微观变化增强。用Vero细胞和肉鸡红细胞进行的P.kudriavzevii RC001细胞毒性和基因毒性试验表明,P.kudriavzevii RC0.001既没有细胞毒性,也没有基因毒性。当在P.kudriavzevii RC001存在下添加MONS时,AFB1对肝脏的毒性作用没有被阻止。当P.kudriavzevii单独存在时,在喂食AFB1的家禽的肠道中观察到同样的病理损伤预防作用。在饲料中添加AFB1和MONS时,表观吸收面积最小(P<0.05)。AFB1与MONS的相互作用表现出重要的毒性作用。尽管P.kudriavzevii能够有效地改善单独的AFB1对肝脏病理和肠道形态的不良影响,但在MONS存在的情况下,它不能减少AFB1的毒性作用。这表明P.kudriavzevii可以作为饲料添加剂或在没有MONS的情况下在家禽生产中对抗AFB1的毒性作用。
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引用次数: 0
Abiotic factors affect growth and aflatoxin B1 production by Aspergillus flavus strains on chilli powder and red chillies 非生物因素影响黄曲霉菌株在辣椒粉和红辣椒上的生长和黄曲霉毒素B1的产生
IF 2 4区 医学 Q3 FOOD SCIENCE & TECHNOLOGY Pub Date : 2021-11-26 DOI: 10.3920/wmj2021.2715
D. Al-Jaza, Á. Medina, N. Magan
Chillies and chilli-based products are important spices on a global basis. The production, processing, transport and storage phases of chillies are prone to infection by Aspergillus Section Flavi and contamination with aflatoxins (AFs), especially aflatoxin B1 (AFB1) for which legislative limits exist in many countries. We have examined the effect of the interacting abiotic factors of water availability (water activity, aw; 0.995-0.850 aw) and temperature (15-37 °C) on (a) lag phases prior to growth, (b) growth, (c) AFB1 production and (d) contour maps of optimum and boundary conditions for colonisation and toxin production by three Aspergillus flavus strains on a 10% chilli-based medium. Additional studies with whole red chillies + A. flavus conidial inoculum on AFB1 contamination during storage for 10-20 days at 30 °C were also carried out. In vitro, the lag phases before growth were delayed by lower temperatures (15, 20 °C) and aw levels (0.928-0.901 aw). There was no statistical difference in growth between the three strains. Optimal growth was at 37 °C and 0.982 aw with no growth at 0.85 aw. Optimal temperature × aw conditions for AFB1 production were at 30 °C and 0.982 aw with no statistical difference in production between strains. No AFB1 was produced at 15-20 °C at 0.901 and 0.928 aw levels, respectively. In situ studies with A. flavus inoculated whole red chillies at 0.90 and 0.95 aw found that this species became the major component of the total fungal populations at 30 °C after 10-20 days storage. AFB1 contamination was above the European legislative limits (5 μg/kg) for spices at 0.90 aw after 20 days storage and at 0.95 aw after 10 and 20 days. This suggests that storage conditions of ≥0.90 aw, especially at ≥25-30 °C represents a significant risk of contamination with AFB1 at levels where rejection might occur, even after only 10-20 days storage.
辣椒和辣椒制品是全球重要的香料。辣椒的生产、加工、运输和储存阶段容易受到黄曲霉的感染,并受到黄曲霉毒素(AF)的污染,尤其是黄曲霉毒素B1(AFB1),许多国家对其存在立法限制。我们研究了水有效性(水活度,aw;0.995-0.850 aw)和温度(15-37°C)等相互作用的非生物因素对(a)生长前的滞后期、(b)生长、(C)AFB1产生和(d)三个黄曲霉菌株在10%辣椒基培养基上定殖和毒素产生的最佳和边界条件的等高线图的影响。此外,还对全红辣椒+黄曲霉分生孢子接种物在30°C下储存10-20天期间对AFB1污染的影响进行了额外研究。在体外,生长前的滞后期因较低的温度(15-20°C)和aw水平(0.928-0.901 aw)而延迟。三个菌株之间的生长没有统计学差异。最适生长温度为37°C和0.982 aw,0.85 aw时无生长。AFB1生产的最适温度×aw条件为30°C和0.9 82 aw。菌株之间的生产没有统计学差异。在15-20°C、0.901和0.928 aw水平下,分别未产生AFB1。黄曲霉在0.90和0.95 aw下接种全红辣椒的原位研究发现,在储存10-20天后,该物种在30°C下成为总真菌种群的主要组成部分。储存20天后0.90 aw和储存10和20天后0.95 aw时,香料的AFB1污染高于欧洲立法限值(5μg/kg)。这表明,≥0.90 aw的储存条件,尤其是在≥25-30°C的储存条件下,即使在储存10-20天后,也存在AFB1污染的显著风险。
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引用次数: 2
Review of good agricultural practices for smallholder maize farmers to minimise aflatoxin contamination 审查玉米小农的良好农业规范,以尽量减少黄曲霉毒素污染
IF 2 4区 医学 Q3 FOOD SCIENCE & TECHNOLOGY Pub Date : 2021-11-03 DOI: 10.3920/wmj2021.2685
F. Xu, R. Baker, T. Whitaker, H. Luo, Y. Zhao, A. Stevenson, C. Boesch, G. Zhang
Maize is consumed world-wide as staple food, livestock feed, and industrial raw material. However, it is susceptible to fungal attack and at risk of aflatoxin contamination under certain conditions. Such contamination is a serious threat to human and animal health. Ensuring that the maize used by food industry meets standards for aflatoxin levels requires significant investment across the supply chain. Good Agricultural Practices (GAP) form a critical part of a broader, integrated strategy for reduction of aflatoxin contamination. We reviewed and summarised the GAP of maize that would be effective and practicable for aflatoxin control within high-risk regions for smallholder farmers. The suggested practicable GAP for smallholder farmers were: use of drought-tolerant varieties; timely harvesting before physiological maturity; sorting to remove damaged ears and those having poor husk covering; drying properly to 13% moisture content; storage in suitable conditions to keep the crop clean and under condition with minimally proper aeration, or ideally under hermetic conditions. This information is intended to provide guidance for maize growers that will help reduce aflatoxin in high-risk regions, with a specific focus on smallholder farmers. Following the proposed guidelines would contribute to the reduction of aflatoxin contamination during pre-harvest, harvest, and post-harvest stages of the maize value chain.
玉米作为主食、牲畜饲料和工业原料在世界范围内被消费。然而,它容易受到真菌的攻击,在某些条件下有黄曲霉毒素污染的危险。这种污染对人类和动物健康构成严重威胁。确保食品工业使用的玉米符合黄曲霉毒素水平标准,需要在整个供应链上进行大量投资。良好农业规范(GAP)是减少黄曲霉毒素污染的更广泛的综合战略的重要组成部分。本文综述了在黄曲霉毒素高风险地区对小农有效可行的玉米GAP。建议对小农可行的GAP是:使用耐旱品种;生理成熟前及时采收;分拣拣去受损的耳和外壳覆盖度差的耳;适当干燥至13%水分含量;储存在适当的条件下,以保持作物清洁,并在最低限度的适当通风条件下,或理想的密封条件下。这些信息旨在为玉米种植者提供指导,以帮助在高风险地区减少黄曲霉毒素,并特别关注小农。遵循拟议的指导方针将有助于减少玉米价值链的收获前、收获和收获后阶段的黄曲霉毒素污染。
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引用次数: 12
An update on genotoxic and epigenetic studies of fumonisin B1 伏马菌素B1基因毒性和表观遗传学研究进展
IF 2 4区 医学 Q3 FOOD SCIENCE & TECHNOLOGY Pub Date : 2021-11-03 DOI: 10.3920/wmj2021.2720
I. B. Molina-Pintor, A. Rojas-García, I. Medina-Díaz, B. Barrón-Vivanco, Y. Y. Bernal-Hernández, L. Ortega-Cervantes, A. Ramos, J. F. Herrera-Moreno, C. A. González-Arias
Fumonisins (FBs), a widespread group of mycotoxins produced by Fusarium spp., are natural contaminants in cereals and foodstuffs. Fumonisin B1 (FB1) is the most toxic and prevalent mycotoxin of this group, and it has been reported that FB1 accounts for 70-80% of FBs produced by the mycotoxigenic strains. The mode of action of FB1 depends on the structural similarity with sphinganine/sphingosine N-acyltransferase. This fact causes an accumulation of sphingoid bases and blocks the sphingolipid biosynthesis or the function of sphingolipids. Diverse toxic effects and diseases such as hepatocarcinogenicity, hepatotoxicity, nephrotoxicity, and cytotoxicity have been reported, and diseases like leukoencephalomalacia in horses and pulmonary oedema in horses and swine have been described. In humans, FBs have been associated with oesophageal cancer, liver cancer, neural tube defects, and infantile growth delay. However, despite the International Agency for Research on Cancer designated FB1 as a possibly carcinogenic to humans, its genotoxicity and epigenetic properties have not been clearly elucidated. This review aims to summarise the progress in research about the genotoxic and epigenetics effects of FB1.
伏马菌素是镰刀菌产生的一组广泛的真菌毒素,是谷物和食品中的天然污染物。伏马菌素B1(FB1)是这一组中毒性最强、最普遍的真菌毒素,据报道,FB1占真菌毒素产生菌株产生的FBs的70-80%。FB1的作用模式取决于与鞘氨醇/鞘氨醇N-酰基转移酶的结构相似性。这一事实导致类鞘脂碱基的积累,并阻断鞘脂生物合成或鞘脂的功能。已经报道了多种毒性作用和疾病,如肝癌、肝毒性、肾毒性和细胞毒性,并描述了马脑白质软化和马和猪肺水肿等疾病。在人类中,FBs与食管癌症、癌症、神经管缺陷和婴儿生长迟缓有关。然而,尽管国际癌症研究机构将FB1指定为可能对人类致癌,但其遗传毒性和表观遗传特性尚未明确阐明。本文综述了FB1基因毒性和表观遗传学效应的研究进展。
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引用次数: 6
Association of exposure to deoxynivalenol with DNA methylation in white blood cells in children in China 中国儿童接触脱氧雪腐镰刀菌烯醇与白细胞DNA甲基化的关系
IF 2 4区 医学 Q3 FOOD SCIENCE & TECHNOLOGY Pub Date : 2021-10-22 DOI: 10.3920/wmj2021.2699
P. Cao, X.D. Wang, J. Sun, J. Liang, P. Zhou, H. Xu, H. Yang, L. Zhang
Deoxynivalenol (DON) is a mycotoxin that commonly contaminates cereals worldwide. Dietary exposure to DON is a subject of great public health concern, but studies on the health effects of chronic exposure to DON are not available. In this study, we investigated the connection between DNA methylation levels and DON exposure in children. The DNA methylation status of white blood cells from 32 children aged 2~15 years old in Henan, China, was profiled. A total of 378 differentially methylated CpGs were identified between the high and low DON exposure groups, and 8 KEGG pathways were found to be significantly enriched among the differentially methylated genes. In addition, the quantitative methylation of EIF2AK4, EMID2 and GNASAS was analysed using the Sequenom MassARRAY platform. The results showed that the methylation level of EIF2AK4 was significantly different between the two groups, and the methylation levels were associated with exposure to DON. Conclusively, our study found that chronic exposure to DON during childhood could affect DNA methylation levels.
脱氧雪腐镰刀菌烯醇(DON)是一种常见于世界各地谷物的真菌毒素。DON的饮食暴露是一个备受公众健康关注的主题,但目前还没有关于长期接触DON对健康影响的研究。在这项研究中,我们调查了儿童DNA甲基化水平与DON暴露之间的联系。对河南地区32名2~15岁儿童白细胞DNA甲基化状况进行了分析。在高和低DON暴露组之间共鉴定出378个差异甲基化CpG,并且发现8个KEGG途径在差异甲基化基因中显著富集。此外,使用Sequenom MassARRAY平台分析了EIF2AK4、EMID2和GNASAS的定量甲基化。结果表明,EIF2AK4的甲基化水平在两组之间存在显著差异,并且甲基化水平与DON暴露有关。总之,我们的研究发现,儿童时期长期接触DON会影响DNA甲基化水平。
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World Mycotoxin Journal
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