An Antagonism Joint Action of Lead and Di-2-Ethylhexyl Phthalate Explains an Improved Ability of Learning and Memory after Combined Exposure in Weaning Rats

Lead and di-2-ethylhexyl phthalate (DEHP) are widely distributed in the environment, and their neurotoxicity has caused a widespread concern. The complexity of environmental exposure provides the possibility of their combined exposure. The present study aims to describe a joint neurotoxicity and clarify the potential mechanism after combined exposure to lead and DEHP. A 2 × 3 factorial design was used to analyze either single effects or their interaction by a subchronic lead and DEHP exposure model of the male weaning rats. Similar to the previous study, lead or DEHP single exposure showed an increased neurotoxicity. Interestingly, our neurobehavioral test showed the rats in the combined exposure groups had a better ability of learning and memory compared with the single-exposure ones. It seemed to reflect an antagonism joint action in neurotoxicity after combined exposure. The content of dehydroepiandrosterone (DHEA) in serum and the mRNA level of brain-derived neurotrophic factor (Bdnf) in the hippocampus showed a similar trend to the ability of learning and memory. However, there was insufficient evidence to support the joint action on some indexes of oxidative stress such as malondialdehyde (MDA), the ratio of reduced glutathione(GSH) to oxidized glutathione(GSSG), γglutamylcysteine synthetase (γ-GCS), glutathione-s transferase (GST), and nuclear factor E2-related factor 2 (Nrf2) mRNA expression in the hippocampus. In a word, our current study reminded a unique antagonism joint action of neurotoxicity after combined exposure to lead and DEHP, which may contribute to understanding some shallow mechanism of the joint toxicity due to the complexity of environmental pollutant exposure.

     

Bisphenol A at a human exposed level can promote epithelial-mesenchymal transition in papillary thyroid carcinoma harbouring BRAFV600E mutation

Bisphenol A (BPA), a ubiquitous endocrine-disrupting chemical, alters the function of endocrine system and enhances the susceptibility to tumorigenesis in several hormone-dependent tumours as thyroid carcinoma. About 50% of papillary thyroid cancers (PTC), the most common type of thyroid malignancy, harbours the BRAF^V600E mutation. This study aimed to investigate a potential combined effect of BPA exposure and BRAF^V600E mutation on epithelial-mesenchymal transition (EMT) in PTC. Firstly, the level of BPA in plasma, the evaluation of BRAF^V600E mutation and the level of EMT-related proteins in PTC samples were individually determined. Additionally, the migration, invasion, colony formation capacity and the expression of EMT-related proteins after exposure to BPA were precisely analysed in vitro thyroid cells genetically modified by the introduction of BRAF^V600E mutation. Moreover, ERK-Cox2 signalling pathway was also introduced to explore the possible mechanism in PTC development. As expected, whether the clinical investigation or cultured thyroid cells demonstrated that BPA at a concentration compatible with human exposed levels (10^-7 M) synergized with the BRAF^V600E mutation promoted EMT via the activation of ERK-Cox2 signalling pathway. Our findings offer some evidence that BPA as an environmental risk factor can facilitate the progression of PTC harbouring BRAF^V600E mutation.     

创伤弧菌溶细胞素中类蓖麻毒素功能模序的细胞毒活性研究

创伤弧菌溶细胞素(Vibrio vulnificus cytolysin,VVC)氨基酸序列的313-445位(Gi No.M34670)与蓖麻毒素B链(Ricinchain B,RTB)的一段高度同源,为类蓖麻毒素。基因克隆表达创伤弧菌溶细胞素类蓖麻毒素(rRicin B),Ni2+亲和层析法及透析复性法进行纯化、复性。用纯化的rRi-cin B免疫日本大耳兔获得多克隆抗体,兔抗rRicin B多克隆抗体经盐析法、分子筛纯化后,得到较纯的IgG分子。免疫印迹结果显示,抗rRicin B多克隆抗体与纯化抗原呈现特异性反应条带。流式细胞术结果显示,rRicin B诱导细胞凋亡呈剂量依赖关系,多抗能够阻断其细胞毒性。至此,该工作成功制备了兔抗rRicin B的多克隆抗体,并证明了创伤弧菌溶细胞素结构基因的类蓖麻毒素功能域具有细胞毒活性,能诱导Hela细胞凋亡,且其细胞毒活性能被其多抗成功阻断。     

不同温度下CO2浓度增高对坛紫菜生长和叶绿素荧光特性的影响

大气CO2浓度升高对海藻的影响已有许多的研究报道,但鲜见有关温度与CO2相互作用的研究.在4种条件下对坛紫菜进行连续通气培养:(1)15℃+ 390tmol/mol CO2,(2) 15℃+700 μmol/mol CO2,(3) 25℃+390 μmol/mol CO2,(4) 25℃+ 700 μmol/mol CO2.从而探讨这种南方海域重要栽培海藻种类的生长和叶绿素荧光特性对温度和CO2相互作用的响应.结果表明:CO2对坛紫菜的生长的影响具有温度依赖性,在低温生长条件下提高CO2浓度更有利于坛紫菜的生长.CO2对坛紫菜叶绿素a(Chlorophyll a,Chl a)和类胡萝卜素(Carotenoid,Car)的促进作用远大于温度对其产生的影响.相对于25℃的生长温度而言,15℃生长温度下的坛紫菜表现出较高的最大相对电子传递速率(rETRmax),表明坛紫菜在低温环境下有较高的光合潜力;而CO2对坛紫菜的rETRmax没有明显影响.对于在不同测定温度下的光合荧光特性而言,在10-30℃测定温度范围内,在各生长条件下的海藻的rETRmax、光能利用效率(α)和最大光化学量子产量(Fv/Fm)随温度的升高变化不明显;但在较高测定温度下(≥30℃),上述荧光参数显著下降,说明高温易引发海藻光能利用效率和光合能力的下降,这可能与光系统(PS)Ⅱ反应中心活性下调有关.同时,当测定温度大于30℃时,15℃生长条件下的坛紫菜的rETRmax、α和F/Fm值下降趋势远大于25℃生长条件下的坛紫菜的值,表明在低温生长条件下的坛紫菜对短期高温胁迫的适应能力较弱;而在高CO2浓度生长条件下的坛紫菜的rETRmax总是低于正常CO2浓度生长下的值,说明CO2浓度升高会抑制坛紫菜在短期高温条件下的光合电子传递能力.     

气候变化对海藻龙须菜生长与光合作用耐热特性的影响

为探讨大气CO2升高和温室效应对龙须菜生长及生理生化特性的影响,在4种条件下培养龙须菜:1)对照组(390μL/L CO2+20℃),2)CO2升高组(700μL/L CO2+20℃),3)温度升高组(390μL/L CO2+24℃),4)温室效应组(700μL/L CO2+24℃),测定藻体生长和生化组分以及高温胁迫下的最大光化学量子产量(Fv/Fm)和光能利用效率(α)、光合速率(Pn)和呼吸速率(Rd)。结果表明,CO2升高、温度升高以及温室效应均促进龙须菜的生长,温室效应下的促进作用更明显。温室效应使龙须菜具较高的Pn和Rd以及较低的可溶性蛋白(SP)和可溶性碳水化合物(SC)含量。高浓度CO2对叶绿素(Chl a)和类胡萝卜素(Car)含量没有显著影响,而高温使其上升;藻红蛋白(PE)和藻蓝蛋白(PC)含量不受CO2浓度和温度的影响。龙须菜Fv/Fm、α、Pn和Rd值,在32℃处理3 h后略有上升,在36℃处理3 h后下降,而在40℃处理20 min后降到极低水平。正常温度(20℃)生长的龙须菜最高耐受温度在32—36℃之间,而较高温(24℃)生长的龙须菜在36—40℃之间;生长温度对光合作用和呼吸作用耐热性能的影响比CO2浓度的影响更大;而温室效应生长条件下的龙须菜光合作用表现出更突出的耐热性能。