Ochratoxin A

曲霉毒素 A
  • 文章类型: Journal Article
    曲霉毒素A(OTA)是在饲料中发现的一种普遍的霉菌毒素,其在动物中引起显著的肾损伤。需要进一步的研究来设计通过肠-肾轴治疗OTA诱导的肾损伤的策略。证据表明肠道微生物群在肾脏损害发展中的关键作用。菊粉,一种膳食纤维,通过调节肠道微生物群和促进短链脂肪酸(SCFA)的产生来保护肾脏。然而,其在OTA诱导的肾损害中的确切机制尚不清楚。在这项研究中,鸡口服OTA和菊粉2周,以研究菊粉对OTA诱导的肾脏损伤的影响及其潜在机制。肠道微生物群的改变,SCFA内容,进一步分析SCFA受体。结果表明,菊粉补充影响肠道菌群,SCFA产量增加,减轻了OTA诱导的鸡肾损伤。抗生素和粪便微生物移植实验进一步证实了微生物在介导菊粉肾脏保护中的重要性。此外,菊粉表现出抗氧化和抗炎特性,减轻NLRP3炎性体激活和焦亡。总之,菊粉保护鸡免受OTA诱导的肾脏损伤,这可能提供一种潜在的策略,通过益生元减轻霉菌毒素的有害影响并保护肾脏健康。
    Ochratoxin A (OTA) is a prevalent mycotoxin found in feed that causes significant kidney injury in animals. Further investigation was needed to devise strategies for treating OTA-induced kidney damage through the gut-kidney axis. Evidence indicates the crucial role of intestinal microbiota in kidney damage development. Inulin, a dietary fiber, protects kidneys by modulating intestinal microbiota and promoting short-chain fatty acid (SCFA) production. However, its precise mechanism in OTA-induced kidney damage remained unclear. In this study, chickens were orally administered OTA and inulin for 2 weeks to investigate inulin\'s effects on OTA-induced kidney damage and underlying mechanisms. The alteration of intestinal microbiota, SCFAs contents, and SCFA receptors was further analyzed. Results demonstrated that inulin supplementation influenced intestinal microbiota, increased SCFAs production, and mitigated OTA-induced kidney damage in chickens. The importance of microbiota in mediating inulin\'s renal protection was further confirmed by antibiotic and fecal microbiota transplantation experiments. Additionally, inulin exhibited antioxidant and anti-inflammatory properties, alleviating NLRP3 inflammasome activation and pyroptosis. In summary, inulin protected chickens from OTA-induced kidney damage, which might provide a potential strategy to mitigate the harmful effects of mycotoxins through prebiotics and safeguard renal health.
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  • 文章类型: Journal Article
    葡萄干的生产,一种自古以来保存葡萄的方法,随着各种干燥技术的发展,这些技术显着影响最终产品的质量和安全性。这项研究评估了太阳能间接干燥机与传统的阳光干燥方法相比的功效,以干燥克里特岛的百年无核和Sultanina葡萄品种,希腊。评估的关键参数包括环境条件,干燥时间,葡萄的颜色,真菌污染,和曲霉毒素A(OTA)水平。葡萄在受控的太阳能室中和在开放的阳光条件下干燥。与外部条件(24.2°C和58.7%,太阳能室保持较高的平均温度(34°C)和较低的相对湿度(39.7%),分别),显著减少干燥时间从12到7天。在太阳能室内干燥的葡萄干显示出改善的颜色质量,具有较高的亮度(L*),色调角(h),和色度(C*)值,归因于最小化的酶和非酶褐变。真菌学分析显示,室内干燥的葡萄干中的黑曲霉切片Nigri污染大大减少,每克的平均菌落形成单位显着低于晒干的葡萄干。因此,室内干葡萄干中的OTA水平也显着降低,百年无核的平均浓度为1.01µg/kg,而晒干的样品为2.66µg/kg,Sultanina显示0.70µg/kg与2.05µg/kg,分别。这些发现强调了使用太阳能间接干燥机提高干燥效率的优势。改善颜色质量,减少真菌和OTA污染,强调采用受控干燥技术以提高安全性的重要性,更高质量的葡萄干.
    The production of raisins, a method of grape preservation since antiquity, has evolved with various drying techniques that significantly impact the quality and safety of the final product. This study evaluates the efficacy of a solar indirect dryer compared to traditional sun-drying methods for drying Centennial Seedless and Sultanina grape cultivars in Crete, Greece. Key parameters assessed include environmental conditions, drying time, grape color, fungal contamination, and Ochratoxin A (OTA) levels. Grapes were dried in a controlled solar chamber and under open sun conditions. The solar chamber maintained higher average temperatures (34°C) and lower relative humidity (39.7%) than outside conditions (24.2°C and 58.7%, respectively), significantly reducing the drying time from 12 to 7 days. Raisins dried in the solar chamber exhibited improved color quality, with higher Lightness (L*), Hue Angle (h), and Chroma (C*) values, attributed to minimized enzymatic and non-enzymatic browning. Mycological analysis revealed a substantial reduction in Aspergillus section Nigri contamination in chamber-dried raisins, with mean colony-forming units per gram significantly lower than those of sun-dried raisins. Consequently, OTA levels were also significantly reduced in chamber-dried raisins, with Centennial Seedless showing a mean concentration of 1.01 µg/kg compared to 2.66 µg/kg in sun-dried samples, and Sultanina showing 0.70 µg/kg versus 2.05 µg/kg, respectively. These findings underscore the advantages of using solar indirect dryers to enhance drying efficiency, improve color quality, and reduce fungal and OTA contamination, highlighting the importance of adopting controlled drying technologies for safer, higher-quality raisins.
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  • 文章类型: Journal Article
    曲霉毒素A(OTA),作为最重要和最有害的真菌毒素之一,被归类为可能的人类致癌物(2B组)。我们都知道,DNA损伤可能导致基因组不稳定,细胞周期紊乱,激活DNA损伤途径,和刺激DNA修复系统。探讨DNA损伤修复蛋白(hMLH1)在OTA诱导G2阻滞中的作用,DNA损伤,染色体畸变,在永生化人胃上皮细胞(GES-1)中不同时间(6、12、24、48h)暴露OTA后,评估细胞周期分布和p53-p21信号通路。我们的结果表明,OTA暴露可能引发基因组不稳定,GES-1细胞的DNA损伤和G2期阻滞。同时,OTA处理可以增加hMLH1的表达,并诱导p53蛋白的磷酸化,以及p21,对DNA损伤的反应。最后,siRNA对hMLH1的抑制作用有效地阻止了p53-p21信号通路的激活,并挽救了OTA引起的G2阻滞。本研究表明hMLH1-p53-p21信号通路在OTA介导的GES-1细胞DNA损伤和G2细胞周期阻滞中起重要作用。
    Ochratoxin A (OTA), as one of the most important and harmful mycotoxins, is classed as possible human carcinogen (group 2B). As we all know, DNA damage may cause genomic instability, cell cycle disorder, activation of DNA damage pathway, and stimulation of DNA repair system. To explore the roles of DNA damage repair protein (hMLH1) on OTA-induced G2 arrest, the DNA damage, chromosome aberration, cell cycle distribution and p53-p21 signaling pathway were evaluatd after different time OTA exposure (6, 12, 24, 48h) in immortalized human gastric epithelial cells (GES-1). Our results demonstrated that OTA exposure could trigger genomic instability, DNA damage and G2 phase arrest of GES-1 cells. At the same time, OTA treatment could increase the expression of hMLH1, and induce phosphorylation of the p53 protein, as well as p21, in response to DNA damage. Finally, inhibition of hMLH1 by siRNA effectively prevented the activation of p53-p21 signaling pathway and rescued the G2 arrest elicited by OTA. This study demonstrated that hMLH1-p53-p21 signaling pathway played an important role in DNA damage and G2 cell cycle arrest the mediated by OTA in GES-1 cells.
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  • 文章类型: Journal Article
    曲霉毒素A(OTA)是一种在储存中污染谷物的肾毒素。水分和温度传感器由于其在筒仓内的缓慢动力学运动而给出延迟响应。这项研究检查了CO2产生是否可以预测OTA污染并确定超过最大限制(5μg/kg)的储存条件。水活度水平的影响(0.70-0.90aw),温度(15和20°C),和(a)疣状青霉菌种群的储存持续时间,(b)CO2呼吸速率(RR),(c)研究了储存小麦中的曲霉毒素浓度。用LCMS-MS分析了96个样品的曲霉毒素。在较湿润条件下的RR比在较干燥的aw水平下高>7倍。CO2、OTA、OTB,在最潮湿的条件下观察到OTα。OTA在>0.80aw(16%水分含量)时超过极限,RR>0.01mgCO2kg-1h-1。对储存谷物RR的了解将提醒谷物农民/管理者改善谷物储存管理。
    Ochratoxin A (OTA) is a nephrotoxin that contaminates grains in storage. Moisture and temperature sensors give delayed responses due to their slow kinetic movement within the silo. This study examines if CO2 production could predict OTA contamination and identify storage conditions exceeding the maximum limit (5 μg/kg). The impact of water activity levels (0.70-0.90 aw), temperatures (15 and 20 °C), and storage duration on (a)Penicillium verrucosum population, (b)CO2 respiration rates (RR), and (c)ochratoxins concentrations in stored wheat was investigated. 96 samples were analysed for ochratoxins with LCMS-MS. RR was >7 times higher at wetter conditions than at drier aw levels. A positive correlation between CO2, OTA, OTB, and OTα was observed at the wettest conditions. OTA exceeded the limit at >0.80 aw (16% moisture content) with RR > 0.01 mg CO2 kg-1 h-1. The knowledge of the RR of stored grain would alert grain farmers/managers to improve grain storage management.
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  • 文章类型: Journal Article
    制备了一种新型的电化学传感器,用于同时测定黄曲霉毒素B1(AFB1)和曲霉毒素A(OTA)。采用具有良好导电性和高比表面积的Au纳米颗粒和聚乙烯亚胺还原的氧化石墨烯(AuNP/PEI-RGO)的复合材料作为支撑基底,证明了为适体提供更多结合位点并加速电子转移的能力。将适体固定在AuNP/PEI-RGO表面上以特异性识别AFB1和OTA。UiO-66-NH2的金属有机骨架充当信号载体,负载Cu2和Pb2的金属离子,这促进了独立电流峰的产生,有效地改善了电化学信号。制备的aptasensor对AFB1和OTA表现出灵敏的电流响应,线性范围为0.01至1000ng/mL,AFB1的检测限为6.2ng/L,OTA的检测限为3.7ng/L,分别。应用aptasensor检测谷物样品中的AFB1和OTA,达到与HPLC-MS相当的结果,回收率为92.5%~104.1%。具有灵敏度高、选择性和稳定性好等优点,准备好的aptasensor被证明是评估受污染谷物的有力工具。
    A novel electrochemical aptasensor was prepared for the simultaneous determination of aflatoxin B1 (AFB1) and ochratoxin A (OTA). Composites of Au nanoparticles and polyethyleneimine-reduced graphene oxide (AuNPs/PEI-RGO) with good electrical conductivity and high specific surface area were employed as the supporting substrate, demonstrating the ability to provide more binding sites for aptamers and accelerate the electron transfer. Aptamers were immobilized on a AuNPs/PEI-RGO surface to specifically recognize AFB1 and OTA. A metal-organic framework of UiO-66-NH2 served as the signal carrier to load metal ions of Cu2+ and Pb2+, which facilitated the generation of independent current peaks and effectively improved the electrochemical signals. The prepared aptasensor exhibited sensitive current responses for AFB1 and OTA with a linear range of 0.01 to 1000 ng/mL, with detection limits of 6.2 ng/L for AFB1 and 3.7 ng/L for OTA, respectively. The aptasensor was applied to detect AFB1 and OTA in cereal samples, achieving results comparable with HPLC-MS, with recovery results from 92.5% to 104.1%. With these merits of high sensitivity and good selectivity and stability, the prepared aptasensor proved to be a powerful tool for evaluating contaminated cereals.
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  • 文章类型: Journal Article
    抗菌肽(AMP)具有广泛抑制各种问题因素的功能,被认为是改善牲畜健康和增强免疫调节的新替代方法。在这项研究中,我们使用猪肠上皮细胞系(IPEC-J2细胞)研究了AMP调节是否对OchratoxinA(OTA)暴露有积极影响。我们构建了β-防御素1(DEFB1)表达载体,并将其用于转染IPEC-J2细胞以构建AMP过表达细胞系。结果表明,OTA诱导的细胞毒性,细胞迁移减少,IPEC-J2细胞中炎症标志物mRNA增加。在DEFB1过表达细胞系中,OTA诱导的细胞迁移减少和炎症标志物mRNA增加得到缓解。此外,一种能够诱导DEFB1表达的天然产物,通过高通量筛选筛选,显示细胞毒性的显著缓解,细胞迁移,和炎症标志物与OTA处理的IPEC-J2细胞相比。我们的发现为猪业提供了新的见解和线索,受到OTA曝光的影响。
    Antimicrobial peptides (AMPs) function to extensively suppress various problematic factors and are considered a new alternative for improving livestock health and enhancing immunomodulation. In this study, we explored whether AMP regulation has positive influences on Ochratoxin A (OTA) exposure using a porcine intestinal epithelial cell line (IPEC-J2 cells). We constructed a beta-defensin 1 (DEFB1) expression vector and used it to transfection IPEC-J2 cells to construct AMP overexpression cell lines. The results showed that OTA induced cytotoxicity, decreased cell migration, and increased inflammatory markers mRNA in IPEC-J2 cells. In DEFB1 overexpressing cell lines, OTA-induced reduced cell migration and increased inflammatory markers mRNA were alleviated. Additionally, a natural product capable of inducing DEFB1 expression, which was selected through high-throughput screening, showed significant alleviation of cytotoxicity, cell migration, and inflammatory markers compared to OTA-treated IPEC-J2 cells. Our finding provides novel insights and clues for the porcine industry, which is affected by OTA exposure.
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  • 文章类型: Journal Article
    葡萄酒中的曲霉毒素A(OTA)的存在是众所周知的,但是关于它在葡萄泥和德国葡萄酒中的发生的信息有限。气候变化导致德国南部地区气温升高,这可能会增加与OTA生产相关的真菌的生长,并增加葡萄中这种真菌毒素的含量。开发并验证了一种安全,快速的UHPLC-FLD方法,以评估OTA对葡萄浆和葡萄酒的污染。共有来自巴登-符腾堡州各个葡萄酒生产商的71种葡萄泥和30种葡萄酒样品,德国,对OTA含量进行了分析。结果表明,没有样品含有浓度高于检测限的OTA。需要进一步监测来自不同年份的样品。
    The occurrence of Ochratoxin A (OTA) in wine is commonly known, but there is only limited information about its occurrence in grape mash and wines of German origin. Climate change has led to higher temperatures in the southern regions of Germany, which may increase the growth of fungi associated with the production of OTA and increase the content of this mycotoxin in grapes. A safe and rapid UHPLC-FLD method was developed and validated to assess the contamination of grape mash and wine with OTA. A total of 71 samples of grape mash and 30 wines from various wine producers in Baden-Württemberg, Germany, were analysed for OTA content. The results showed that no samples contained OTA in concentrations above the limit of detection. Further monitoring of samples from different vintages is needed.
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  • 文章类型: Journal Article
    植酸(PA)是一种具有多种生物活性的天然抗氧化剂。在多种动物中提供保护作用。曲霉毒素A(OTA)是一种常见的霉菌毒素,在饲料中,导致多器官损伤,肾脏是其毒性的靶器官。本研究探讨了PA对OTA诱导的雏鸡肾损伤的保护作用及其潜在机制。结果表明,PA治疗可以恢复OTA引起的肾脏病理损伤,逆转抗氧化酶活性的减少,减少丙二醛的积累,并使促炎细胞因子的表达正常化,这证实了PA可以减轻OTA诱导的肾损伤。进一步的研究表明,OTA诱导的肾损伤伴随着组织铁含量的增加和铁凋亡相关基因的转录水平(TFR,ACSL4和HO-1),SLC7A11和GPX4的水平下降。PA治疗逆转了所有这些影响,表明PA减轻了OTA诱导的肾铁性凋亡。此外,PA补充改善肠道形态和粘膜功能,纠正OTA诱导的肠道微生物群变化。此外,PA微生物移植减轻OTA引起的肾脏炎症和氧化应激。总之,PA通过调节铁细胞凋亡和肠道菌群对肾损伤具有保护作用,可能为OTA相关肾毒性的控制和预防提供新的见解。
    Phytic acid (PA) is a natural antioxidant with various biological activities, providing protective effects in multiple animals. Ochratoxin A (OTA) is a mold toxin commonly found in feed, which induces multi-organ damage, with kidney being the target organ of its toxicity. This study investigates the protective effects of PA on OTA-induced renal damage and its potential mechanisms in chicks. The results demonstrates that PA treatment restores OTA-induced renal pathological injuries, reverses the diminished activities of antioxidant enzymes, reduces the accumulation of malondialdehyde, and normalizes the expression of pro-inflammatory cytokines, which confirms that PA can alleviate OTA-induced renal damage. Further investigations reveal that OTA-induced renal injury accompanied by an increase in tissue iron content and the transcription levels of ferroptosis-related genes (TFR, ACSL4, and HO-1), and a decrease in the levels of SLC7A11 and GPX4. PA treatment reverses all these effects, indicating that PA mitigates OTA-induced renal ferroptosis. Moreover, PA supplementation improves intestinal morphology and mucosal function, corrects OTA-induced changes in the intestinal microbiota. Besides, PA microbiota transplantation alleviates renal inflammation and oxidative stress caused by OTA. In conclusion, PA plays a protective role against renal damage through the regulation of ferroptosis and the intestinal microbiota, possibly providing novel insights into the control and prevention of OTA-related nephrotoxicity.
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  • 文章类型: Journal Article
    这项研究回顾了婴儿配方食品和谷物食品中的OchratoxinA(OTA)的全球水平,使用蒙特卡罗模拟来评估风险。该评论发现了24项关于婴儿食品和谷物产品中全球OTA水平的研究,使用包括PubMed在内的数据库,Scopus,WebofScience和Embase至2024年3月。我们根据浓度估计了婴儿食品中的OTA暴露,摄入量和体重。使用BMDL10和TDI值计算暴露量和危险商裕度。蒙特卡罗模拟评估了OTA在婴儿配方食品和谷物食品中的人类健康风险。来自14个国家的一项全球研究显示了不同的水平,超越欧盟在突尼斯的限制,厄瓜多尔,美国,一般来说,在非洲,特别是在婴儿谷物中,比配方更高的水平。全球范围内,在分析的3348个样品中,有29.3%存在OTA,黎巴嫩占95.2%,巴西占0%。分析表明婴儿只有非致癌风险。虽然婴儿的健康风险大多很低,持续的研究和监测对于减少婴儿食品中的OTA暴露至关重要。
    This study reviews global levels of ochratoxin A (OTA) in infant formula and cereal-based foods, using Monte Carlo simulation to assess risks. The review found 24 studies on global OTA levels in infant food and cereal-based products, using databases including PubMed, Scopus, Web of Science and Embase until March 2024. We estimated OTA exposure in infant food based on concentration, intake and body weight. The exposure and hazard quotient margin were calculated using BMDL10 and TDI values. Monte Carlo simulation evaluated human health risks from OTA in infant formula and cereal-based foods. A global study from 14 countries shows varying levels, surpassing EU limits in Tunisia, Ecuador, the USA, and generally in Africa, notably in infant cereals, which had higher levels than formula. Globally, OTA was present in 29.3% of the 3348 samples analyzed, with Lebanon at 95.2% and Brazil at 0%. Analysis indicates only non-carcinogenic risk for infants. While health risks for infants are mostly low, ongoing research and monitoring are vital to minimize OTA exposure in infant food.
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  • 文章类型: Journal Article
    作为一种剧毒的霉菌毒素,曲霉毒素A(OTA)广泛污染农产品,具有多种毒理学作用。用于OTA降解的生物酶已显示出有希望的解毒潜力。除了以前有效的酰胺水解酶ADH3,本研究获得了两种新的酰胺水解酶ADH1和AMD3。在大肠杆菌表达过程中,表达的蛋白质溶解度非常低,将限制未来的工业应用。这里,筛选高拷贝数整合,酰胺水解酶被巴斯德毕赤酵母GS115有效地分泌表达。1.0L发酵上清液的蛋白质产量对于ADH1为53.5mg,对于ADH3为89.15mg,对于AMD3为79.5mg。分泌蛋白的催化效率(Kcat/Km)对于ADH3为124.95s-1mM-1,对于ADH1为123.21s-1mM-1,对于AMD3为371.99s-1mM-1。与大肠杆菌表达相比,活性蛋白产量大幅增加15.78-51.53倍。同时,两种新的酰胺水解酶(ADH1和AMD3)显示出比分泌表达产生的ADH3高得多的活性。
    As a highly toxic mycotoxin, ochratoxin A (OTA) is widely contaminating agricultural products and has various toxicological effects. Bioenzymes for OTA degradation have shown promising potential for detoxification. Other than the efficient amidohydrolase ADH3 previously, two novel amidohydrolases ADH1 and AMD3 were obtained in this study. During Escherichia coli expression, the expressed protein solubility was very low and will limit future industrial application. Here, high copy number integrations were screened, and the amidohydrolases were efficiently secretory expressed by Pichia pastoris GS115. The protein yields from 1.0 L of fermentation supernatant were 53.5 mg for ADH1, 89.15 mg for ADH3, and 79.5 mg for AMD3. The catalytic efficiency (Kcat/Km) of secretory proteins was 124.95 s-1 mM-1 for ADH3, 123.21 s-1 mM-1 for ADH1, and 371.99 s-1 mM-1 for AMD3. In comparison to E. coli expression, the active protein yields substantially increased 15.78-51.53 times. Meanwhile, two novel amidohydrolases (ADH1 and AMD3) showed much higher activity than ADH3 that produced by secretory expression.
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