Assessment of the estrogenicity of the diet of a healthy female Spanish population based on its isoflavone content

Phytoestrogens are natural components of plants consumed by humans. The hormonal activity of these substances has long been known. Various in vitro tests have demonstrated the agonistic or antagonistic estrogenic activity of some phytoestrogens. The objective of this study was to estimate the supply of isoflavones in the diet of a healthy adult female population and to assess its estrogenic effect. The diet was assessed by questionnaire and the estrogenicity of the estimated isoflavone content was tested by E-screen, finding a mean total estrogenic capacity of 0.129 × 10^?10 eq.E₂ (12.9 pmol day^–1), corresponding to a daily isoflavone intake of 265.8 μg day^–1. This study offers a preliminary insight into the phytoestrogen content of the diet of a healthy active population of Spanish women. The effects of this additional hormonal burden are highly controversial, and this approach to estimating dietary phytoestrogen intake of specific populations may help to elucidate its implications for human health.     

Natural Dibenzo-α-Pyrones: Friends or Foes?

Natural dibenzo-α-pyrones (DAPs) can be viewed from two opposite angles. From one angle, the gastrointestinal metabolites urolithins are regarded as beneficial, while from the other, the emerging mycotoxin alternariol and related fungal metabolites are evaluated critically with regards to potential hazardous effects. Thus, the important question is: can the structural characteristics of DAP subgroups be held responsible for distinct bioactivity patterns? If not, certain toxicological and/or pharmacological aspects of natural DAPs might yet await elucidation. Thus, this review focuses on comparing published data on the two groups of natural DAPs regarding both adverse and beneficial effects on human health. Literature on genotoxic, estrogenic, endocrine-disruptive effects, as well as on the induction of the cellular anti-oxidative defense system, anti-inflammatory properties, the inhibition of kinases, the activation of mitophagy and the induction of autophagy, is gathered and critically reviewed. Indeed, comparing published data suggests similar bioactivity profiles of alternariol and urolithin A. Thus, the current stratification into hazardous Alternaria toxins and healthy urolithins seems debatable. An extrapolation of bioactivities to the other DAP sub-class could serve as a promising base for further research. Conclusively, urolithins should be further evaluated toward high-dose toxicity, while alternariol derivatives could be promising chemicals for the development of therapeutics.     

污水处理工艺中雌激素活性分布与去除途径分析

针对内分泌干扰物在水中质量浓度低、危害大、去除困难的现状,采用固相萃取/重组酵母法调查了城市污水厂各工艺过程中雌激素活性的分布并对其去除途径进行分析.结果表明:雌激素活性主要存在于液相中,悬浮态中只占7.7%±5.5%;雌激素活性的去除主要发生在二级生物处理过程,通过对二级生物处理过程进行质量衡算发现,吸附到剩余污泥中的雌激素活性占进水中的1.2%,对雌激素活性的去除主要依靠微生物降解(占73.9%).通过理论计算证实雌激素活性的去除途径主要是依靠微生物降解作用,通过污泥吸附和挥发去除非常有限(小于15%).总之,城市污水厂出水中雌激素活性仍然较高(3.37～6.76 ng.L-1),强化二级生物处理或者对污水深度处理迫在眉睫.     

松花江水内分泌干扰物及雌激素活性调查

为明确松花江水体中内分泌干扰物的污染状况,利用固相萃取富集-气质联机/重组基因酵母对松花江全江11个典型断面进行全面采样分析.结果表明：江水中∑5ES质量浓度在6.59～30.97 ng/L,平均值为17.23 ng/L,出现最大质量浓度的位置是达连河排污口,雌酮（E1）和雌二醇（E2）是其中贡献最大雌激素,其质量浓度...     

VenomPred: A Machine Learning Based Platform for Molecular Toxicity Predictions

The use of in silico toxicity prediction methods plays an important role in the selection of lead compounds and in ADMET studies since in vitro and in vivo methods are often limited by ethics, time, budget and other resources. In this context, we present our new web tool VenomPred, a user-friendly platform for evaluating the potential mutagenic, hepatotoxic, carcinogenic and estrogenic effects of small molecules. VenomPred platform employs several in-house Machine Learning (ML) models developed with datasets derived from VEGA QSAR, a software that includes a comprehensive collection of different toxicity models and has been used as a reference for building and evaluating our ML models. The results showed that our models achieved equal or better performance than those obtained with the reference models included in VEGA QSAR. In order to improve the predictive performance of our platform, we adopted a consensus approach combining the results of different ML models, which was able to predict chemical toxicity better than the single models. This improved method was thus implemented in the VenomPred platform, a freely accessible webserver that takes the SMILES (Simplified Molecular-Input Line-Entry System) strings of the compounds as input and sends the prediction results providing a probability score about their potential toxicity.     

E2弱化双酚A雌激素活性机制

前期研究发现天然雌激素E2可以弱化一种常见雌激素类污染物双酚A的活性,为探讨这一现象的机制,利用人体乳腺癌细胞MCF7,从细胞周期、雌激素受体途径、MAPKs信号途径进行实验．结果表明:E2可诱导DNA合成期细胞显著增高,抑制受体蛋白表达,提高ERK蛋白的表达,进而激活多种转录因子;双酚A显著抑制受体蛋白表达,对MAPKs信号通路基本没有影响,可同时提高DNA分裂期与间歇期细胞比例;两者联合后活化了受体途径和ERK途径,促进Cfos的转录表达,激活cyclin D1蛋白,增加S期及G2期细胞比例．E2弱化双酚A的可能机制为Cmyc蛋白表达下降．     

In Vitro Evaluation of the Individual and Combined Cytotoxic and Estrogenic Effects of Zearalenone,Its Reduced Metabolites,Alternariol, and Genistein

Mycotoxins are toxic metabolites of filamentous fungi. Previous studies demonstrated the co-occurrence of Fusarium and Alternaria toxins, including zearalenone (ZEN), ZEN metabolites, and alternariol (AOH). These xenoestrogenic mycotoxins appear in soy-based meals and dietary supplements, resulting in the co-exposure to ZEN and AOH with the phytoestrogen genistein (GEN). In this study, the cytotoxic and estrogenic effects of ZEN, reduced ZEN metabolites, AOH, and GEN are examined to evaluate their individual and combined impacts. Our results demonstrate that reduced ZEN metabolites, AOH, and GEN can aggravate ZEN-induced toxicity; in addition, the compounds tested exerted mostly synergism or additive combined effects regarding cytotoxicity and/or estrogenicity. Therefore, these observations underline the importance and the considerable risk of mycotoxin co-exposure and the combined effects of mycoestrogens with phytoestrogens.     

内分泌干扰物层级筛选中的定量构效关系

大量的科学研究、监管和大众媒体一直关注于内分泌干扰物,它们主要是能够模仿天然激素功能的合成化学物质。法律要求开发一种程序,用以筛选和测试水和食品添加剂中是否含有潜在内分泌干扰物。根据法规,大量的化学品将会接受各种体外和体内的实验用以测试其潜在荷尔蒙的活性,例如雌激素活性。因此,需要对这些化学物质进行分层筛选,以降低测试成本及加快筛选和测试的速度。在已经开发的内分泌干扰物知识数据库(EDKB)项目中,将实验和建模进行了整合,以便于更加高效地进行优先级的设置。     

呋喃丹和氯氰菊酯的类雌激素活性研究

[目的]探究呋喃丹和氯氰菊酯的类雌激素活性。[方法]采用重组人雌激素受体α基因的双杂交酵母测定了17β-雌二醇和2种农药诱导产生β-半乳糖苷酶活性的EC50值。[结果]17β-雌二醇、呋喃丹、氯氰菊酯对应的EC50值分别为4.04×10-10、2.34×10-7、1.04×10-6mol/L,诱导的最大酶活分别为4.97、1.82、1.59 U。[结论]2种农药均具有不同程度的类雌激素活性,且呋喃丹的类雌激素活性高于氯氰菊酯。