Involvement of mitochondrial-mediated caspase-3 activation and lysosomal labilization in acrylamide-induced liver toxicity

Acrylamide (ACR) is a chemical frequently used in both industrial and synthetic processes and may be produced during food processing. ACR at very high concentrations is postulated to exert its toxicity through the stimulation of an oxidative stress. ACR in excessive doses induces the central nervous system, reproduction, and genetic toxicity. However, ACR effects on the liver, a major organ of drug metabolism, have not been adequately explored. In addition, the role of mitochondria in an ACR-mediated hepatotoxicity is still unclear. The aim of this study was to investigate the cytotoxic mechanisms attributed to ACR using isolated rat hepatocytes. Hepatocytes were isolated by the collagenase perfusion method and incubated with an EC50_2hr concentration of ACR for 3 hr. The EC50_{2 hr} of ACR on isolated rat hepatocytes was determined to be 1 mM. Based on our results, hepatocytes cytotoxicity of ACR (1 mM) was mediated by a reactive oxygen species formation and lipid peroxidation. Incubation of hepatocytes with ACR produced rapid hepatocyte glutathione depletion which is another marker of the cellular oxidative stress. ACR cytotoxicity was also associated with mitochondrial injury as evidenced by the decline of mitochondrial membrane potential and lysosomal membrane leakiness. Our results also showed that ACR induced caspase-3 activation, the final mediator of apoptosis signaling. These findings contribute to a better understanding underlying mechanisms involved in ACR hepatotoxicity originating from the oxidative stress and ending in mitochondrial/lysosomal damage and cell death signaling.     

Influence of hypothyroidism on oxidative stress,c-Fos expression,cell cycle,and apoptosis in rats testes

The molecular basis of male reproduction for cross-regulation between androgen and thyroid hormone axes is still rudimentary. This study aims to define a possible mechanism of hypothyroidism-induced reproductive influence with respect to sex hormone, mineral, sperm motility, oxidative stress, c-Fos expression, cell cycle, and apoptosis in rat testes. The Wistar rats were randomly divided into control group (NS) and hypothyroidism group [1 ml/100g BW/day, 0.1% propylthiouracil (PTU)] by intragastric gavage for 60 days. Blood samples were collected to measure the serum levels. The epididymis was excised to measure sperm motility and testes were excised to measure mineral, oxidative stress, c-Fos expression, cell cycle, and apoptosis. After 60 days, body weight, relative testes weight, triiodothyronine, and total thyroxine were all significantly decreased, whereas thyroid stimulating hormone was increased in the hypothyroidism group. A significant increase in sex hormone level of estradiol (E2) and significant decreases in testosterone (T) and T/E2 ratio were observed following PTU treatment. And sperm quality was also significantly changed. There were significant decreases in the contents of calcium (Ca²⁺) and zinc (Zn²⁺). On the other hand, malondialdehyde and hydrogen peroxide contents significantly increased, whereas the activity of superoxide dismutase, catalase and nitric oxide synthase and nitric oxide content significantly decreased in hypothyroid rats. The mRNA and protein expressions of c-Fos decreased significantly. The cell percentage in G0/G1 phase increased significantly, whereas decreased significantly in S and G2/M phases. Also, a significant increase in testicular cell apoptosis was observed in hypothyroid-treated rats. These results suggested that hypothyroidism could affect reproductive function in the form of changed sex hormone levels, sperm motility and testicular Ca²⁺ and Zn²⁺, and enhanced oxidative stress leading to c-Fos abnormal expression and increased apoptosis.     

日粮中铜胁迫对吉富罗非鱼幼鱼抗氧化、脂质过氧化及肝脏组织结构的影响

吉富罗非鱼是我国南方沿海地区水产养殖中的主要经济鱼类之一,但近年来,随着我国城镇化和工业化进程的推进,罗非鱼养殖面临着前所未有的铜富集的挑战。为探明日粮中铜胁迫对吉富罗非鱼幼鱼抗氧化系统和肝脏组织结构的影响,将1 080条罗非鱼幼鱼暴露于6个浓度梯度(0、3、30、300、1 000、3 000 mg·kg-1)的高铜日粮中,通过60 d的暴露试验,实时测定罗非鱼血清与肝脏抗氧化能力,监测肝脏病理变化。结果表明,在本试验条件下,罗非鱼幼鱼血清和肝脏中MDA的含量随日粮中铜含量的增加和胁迫时间的延长显著升高,而SOD、GSH-PX和Cu Zn-SOD的活性表现出先升高后降低的趋势;各组间肝脏表现出不同程度的病变,主要是浊肿变性和脂肪变性,且第Ⅲ、Ⅳ、Ⅴ组肝脏病变严重。综上,日粮中铜胁迫对吉富罗非鱼幼鱼的抗氧化机能有较明显的抑制作用,长时间的暴露能严重损伤其肝脏的组织结构,因此,建议吉富罗非鱼幼鱼日粮中铜的实际含量应控制在42.36 mg·kg-1以下。     

2000年1月15日姚安6.5级地震余震序列震源机制解与震源区应力场分析

本文利用垂直向的Pg和Sg波的最大振幅比方法,计算2000年1月15日云南姚安6.5级地震后余震序列震源机制解,通过统计和系统聚类分析,再结合震中分布图,综合分析了云南姚安6.5级地震的震源机制解和震源区应力场破裂特征,研究结果表明震源断层的走向为SEE-NWW占主导,其平均解为120°,震区主压应力轴平均解为145°,即SSE向,与震源区现今构造应力场主压应力方向一致,表明余震的应力场主要受区域应力场的控制.     

CdSe/ZnS量子点对稀有鮈鲫胚胎发育的影响及其氧化应激作用

本研究以稀有鮈鲫(Gobiocypris rarus)为对象,研究了不同浓度CdSe/ZnS量子点(QDs)暴露下,稀有鮈鲫胚胎发育过程中自主运动频率、内心率和体长的变化,以及利用体内超氧化物歧化酶(SOD)和丙二醛(MDA)作为毒性指标,反映CdSe/ZnS QDs暴露对稀有鮈鲫胚胎发育的氧化应激作用.结果显示:CdSe/ZnS QDs对稀有鮈鲫胚胎72 hpf(hours post fertilization)的半致死浓度(LC50)为319.629 nmol·L-1,96 hpf的半致畸浓度(EC50)为203.312 nmol·L-1.CdSe/ZnS QDs暴露不仅影响稀有鮈鲫胚胎死亡率、畸形率、自主运动频率、孵化时间和孵化率,而且使其内心率减缓、体长缩短,导致胚胎卵凝结,心包囊肿,出现脊椎弯曲等多种毒性现象.同时发现,CdSe/ZnS QDs暴露导致稀有鮈鲫体内MDA含量增加以及SOD活力的降低.这表明CdSe/ZnS QDs对稀有鮈鲫胚胎发育具有致畸、致死作用,而氧化应激可能是引起其胚胎致畸、致死的重要机制之一.     

Primary neuronal-astrocytic co-culture platform for neurotoxicity assessment of di-(2-ethylhexyl) phthalate

Plastics such as polyvinyl chlorides （PVC） are widely used in many indoor constructed environments; however, their unbound chemicals, such as di-（2-ethylhexyl） phthalates （DEHP）, can leach into the surrounding environment. This study focused on DEHP＇s effect on the central nervous system by determining the precise DEHP content in mice brain tissue after exposure to the chemical, to evaluate the specific exposure range. Primary neuronal-astrocyte co-culture systems were used as in vitro models for chemical hazard identification of DEHP. Oxidative stress was hypothesized as a probable mechanism involved, and therefore the total reactive oxygen species （ROS） concentration was determined as a biomarker of oxidative stress. In addition, NeuriteTracer, a neurite tracing plugin with ImageJ, was used to develop an assay for neurotoxicity to provide quantitative measurements of neurological parameters, such as neuronal number, neuron count and neurite length, all of which could indicate neurotoxic effects. The results showed that with 1 nmol/L DEHP exposure, there was a significant increase in ROS concentrations, indicating that the neuronal-astrocyte cultures were injured due to exposure to DEHP. In response, astrocyte proliferation （gliosis） was initiated, serving as a mechanism to maintain a homeostatic environment for neurons and protect neurons from toxic chemicals. There is a need to assess the cumulative effects of DEHP in animals to evaluate the possible uotake and effects on the human neuronal system from exoosure to DEHP in the indoor environment.     

再悬浮过程中河流底泥PAHs的迁移与释放

利用再悬浮模拟(particle entrainment simulator,PES)装置模拟了河流底泥在受到上层扰动力后的再悬浮过程.结果表明,沉积物性质如粒径组成及PAHs含量对沉积物再悬浮过程中PAHs的释放影响显著.再悬浮过程中上覆水体总悬浮颗粒物(total suspended solids,TSS)含量与颗粒态PAHs之间存在极显著相关关系.切应力对再悬浮过程中PAHs释放的影响体现在两方面.一方面,单位体积的颗粒态PAHs随切应力增大而增大;另一方面,悬浮颗粒上PAHs的富集效应随切应力增大而减弱,是由于切应力强烈导致吸附作用弱的大颗粒进入水体.上覆水体中的PAHs总量在一段时间上升后于120 min或240min趋于稳定,而颗粒态与溶解态之间具有良好响应.高低环PAHs释放行为差异显著,由于中高环PAHs的疏水性,上覆水体中检测到的多为3~4环个体.     

河段水质压力目标管理模式的概念与方法

目前我国主流的流域水质目标管理模式中,在河段污染责任认定方面普遍存在难以界定上下游之间各自责任的问题,为此提出了一种基于河段水质压力概念的河流水质管理新模式.以水质压力为基础,配套建立了包括水质压力目标、水质压力纯水当量、水质压力偿罚金等在内的一系列相关概念及其设定与计量方法,完成对各河段的责任认定,并实现以河段处罚金与补偿金为调控手段的流域水质管理运行机制.结果表明,该管理模式有助于增强水质污染处罚与水质生态补偿的区域公平性和针对性,其中的概念和方法可作为现行河流水污染控制方法体系的一种改进性补充,同时能为流域生态补偿标准的确定提供一定借鉴.     

电路板的高加速应力筛选仿真设计技术研究

针对某型电路板高加速应力筛选剖面设计中耗费大量人力物力的实际情况,结合目前计算机辅助及仿真技术所具有的成本低、周期短、精度高等特点,将高加速应力筛选及计算机仿真技术融合,提出了运用计算机仿真手段来研究产品的高加速应力筛选剖面的方法及基本思路。对剩余有效寿命的预计、缺陷影响以及应力影响等方面进行了研究分析。从而在高加速应力筛选剖面设计信息量的扩充、成本的节省、周期的缩短等方面起到了一定的促进作用。     

The continuing conundrum of the LEA proteins

Research into late embryogenesis abundant (LEA) proteins has been ongoing for more than 20 years but, although there is a strong association of LEA proteins with abiotic stress tolerance particularly dehydration and cold stress, for most of that time, their function has been entirely obscure. After their initial discovery in plant seeds, three major groups (numbered 1, 2 and 3) of LEA proteins have been described in a range of different plants and plant tissues. Homologues of groups 1 and 3 proteins have also been found in bacteria and in certain invertebrates. In this review, we present some new data, survey the biochemistry, biophysics and bioinformatics of the LEA proteins and highlight several possible functions. These include roles as antioxidants and as membrane and protein stabilisers during water stress, either by direct interaction or by acting as molecular shields. Along with other hydrophilic proteins and compatible solutes, LEA proteins might also serve as “space fillers” to prevent cellular collapse at low water activities. This multifunctional capacity of the LEA proteins is probably attributable in part to their structural plasticity, as they are largely lacking in secondary structure in the fully hydrated state, but can become more folded during water stress and/or through association with membrane surfaces. The challenge now facing researchers investigating these enigmatic proteins is to make sense of the various in vitro defined functions in the living cell: Are the LEA proteins truly multi-talented, or are they still just misunderstood?