• 【氧化应激期间线粒体衍生的ATP受损会损害小鼠MII卵母细胞纺锤体。】 复制标题 收藏 收藏
    DOI:10.1038/sj.cr.7310095 复制DOI
    作者列表:Zhang X,Wu XQ,Lu S,Guo YL,Ma X
    BACKGROUND & AIMS: :Although the role of oxidative stress in maternal aging and infertility has been suggested, the underlying mechanisms are not fully understood. The present study is designed to determine the relationship between mitochondrial function and spindle stability in metaphase II (MII) oocytes under oxidative stress. MII mouse oocytes were treated with H2O2 in the presence or absence of permeability transition pores (PTPs) blockers cyclosporin A (CsA). In addition, antioxidant N-acetylcysteine (NAC), F0/F1 synthase inhibitor oligomycin A, the mitochondria uncoupler carbonyl cyanide 4-trifluoro-methoxyphenylhydrazone (FCCP) or thapsigargin plus 2.5 mM Ca2+ (Th+2.5 mM Ca2+) were used in mechanistic studies. Morphologic analyses of oocyte spindles and chromosomes were performed and mitochondrial membrane potential (DeltaPsim), cytoplasmic free calcium concentration ([Ca2+]c) and cytoplasmic ATP content within oocytes were also assayed. In a time- and H2O2 dose-dependent manner, disruption of meiotic spindles was found after oocytes were treated with H2O2, which was prevented by pre-treatment with NAC. Administration of H2O2 led to a dissipation of DeltaPsim, an increase in [Ca2+]c and a decrease in cytoplasmic ATP levels. These detrimental responses of oocytes to H2O2 treatment could be blocked by pre-incubation with CsA. Similar to H2O2, both oligomycin A and FCCP dissipated DeltaPsim, decreased cytoplasmic ATP contents and disassembled MII oocyte spindles, while high [Ca2+]c alone had no effects on spindle morphology. In conclusion, the decrease in mitochondria-derived ATP during oxidative stress may cause a disassembly of mouse MII oocyte spindles, presumably due to the opening of the mitochondrial PTPs.
    背景与目标: :尽管有人提出了氧化应激在孕产妇衰老和不育中的作用,但其潜在机制尚未完全被理解。本研究旨在确定氧化应激下中期II(MII)卵母细胞线粒体功能与纺锤体稳定性之间的关系。在存在或不存在通透性转换孔(PTP)阻断剂环孢菌素A(CsA)的情况下,用H2O2处理MII小鼠卵母细胞。此外,在机理研究中还使用了抗氧化剂N-乙酰半胱氨酸(NAC),F0 / F1合酶抑制剂寡霉素A,线粒体解偶联剂羰基氰化物4-三氟-甲氧基苯基zone(thaspsigargin)加2.5 mM Ca2(Th 2.5 mM Ca2)。进行了卵母细胞纺锤体和染色体的形态学分析,还测定了卵母细胞中的线粒体膜电位(DeltaPsim),细胞质游离钙浓度([Ca2] c)和细胞质ATP含量。以时间和H2O2剂量依赖性,在用H2O2处理卵母细胞后发现减数分裂纺锤体的破坏,这可以通过用NAC预处理来预防。施用H2O2导致DeltaPsim的耗散,[Ca2] c的增加和细胞质ATP水平的降低。卵母细胞对H2O2处理的有害反应可以通过与CsA预先孵育来阻止。与H2O2相似,寡霉素A和FCCP都消散了DeltaPsim,降低了细胞质ATP含量并分解了MII卵母细胞纺锤体,而单独的高[Ca2] c对纺锤体形态没有影响。总之,氧化应激期间线粒体ATP的减少可能导致小鼠MII卵母细胞纺锤体分解,可能是由于线粒体PTP的开放所致。
  • 【氧化和亚硝化应激对氨的神经毒性。】 复制标题 收藏 收藏
    DOI:10.1016/j.neuint.2012.10.013 复制DOI
    作者列表:Skowrońska M,Albrecht J
    BACKGROUND & AIMS: :Increased ammonia accumulation in the brain due to liver dysfunction is a major contributor to the pathogenesis of hepatic encephalopathy (HE). Fatal outcome of rapidly progressing (acute) HE is mainly related to cytotoxic brain edema associated with astrocytic swelling. An increase of brain ammonia in experimental animals or treatment of cultured astrocytes with ammonia generates reactive oxygen and nitrogen species in the target tissues, leading to oxidative/nitrosative stress (ONS). In cultured astrocytes, ammonia-induced ONS is invariably associated with the increase of the astrocytic cell volume. Interrelated mechanisms underlying this response include increased nitric oxide (NO) synthesis which is partly coupled to the activation of NMDA receptors and increased generation of reactive oxygen species by NADPH oxidase. ONS and astrocytic swelling are further augmented by excessive synthesis of glutamine (Gln) which impairs mitochondrial function following its accumulation in there and degradation back to ammonia ("the Trojan horse" hypothesis). Ammonia also induces ONS in other cell types of the CNS: neurons, microglia and the brain capillary endothelial cells (BCEC). ONS in microglia contributes to the central inflammatory response, while its metabolic and pathophysiological consequences in the BCEC evolve to the vasogenic brain edema associated with HE. Ammonia-induced ONS results in the oxidation of mRNA and nitration/nitrosylation of proteins which impact intracellular metabolism and potentiate the neurotoxic effects. Simultaneously, ammonia facilitates the antioxidant response of the brain, by activating astrocytic transport and export of glutathione, in this way increasing the availability of precursors of neuronal glutathione synthesis.
    背景与目标: :由于肝功能不全导致大脑中氨的积累增加是肝性脑病(HE)发病机理的主要贡献者。快速进展(急性)HE的致命结局主要与星形胶质细胞肿胀相关的细胞毒性脑水肿有关。实验动物脑氨的增加或用氨处理培养的星形胶质细胞会在目标组织中产生活性氧和氮,从而导致氧化/亚硝化应激(ONS)。在培养的星形胶质细胞中,氨诱导的ONS总是与星形胶质细胞体积的增加相关。引起这种反应的相互关联的机制包括增加一氧化氮(NO)的合成,该合成与NMDA受体的激活部分耦合,以及通过NADPH氧化酶增加的活性氧种类的产生。谷氨酰胺(Gln)的过度合成会进一步加剧ONS和星形胶质细胞的肿胀,这会破坏线粒体的功能,使其积累在那里并降解回氨(“特洛伊木马”假设)。氨还会在中枢神经系统的其他细胞类型中诱导ONS:神经元,小胶质细胞和脑毛细血管内皮细胞(BCEC)。小胶质细胞中的ONS有助于中枢炎症反应,而其在BCEC中的代谢和病理生理后果则演变为与HE相关的血管源性脑水肿。氨诱导的ONS导致mRNA的氧化和蛋白质的硝化/亚硝基化,这影响细胞内代谢并增强神经毒性作用。同时,氨通过激活谷胱甘肽的星形细胞运输和输出,促进了大脑的抗氧化反应,从而增加了神经元谷胱甘肽合成前体的可用性。
  • 【Cynara scolymus叶片提取物对四氧嘧啶糖尿病大鼠代谢紊乱和氧化应激的保护作用。】 复制标题 收藏 收藏
    DOI:10.1186/s12906-017-1835-8 复制DOI
    作者列表:Ben Salem M,Ben Abdallah Kolsi R,Dhouibi R,Ksouda K,Charfi S,Yaich M,Hammami S,Sahnoun Z,Zeghal KM,Jamoussi K,Affes H
    BACKGROUND & AIMS: BACKGROUND:Diabetes mellitus (DM) is associated with hyperglycemia, inflammatory disorders and abnormal lipid profiles, currently the extracts from leaves of cynara scolymus has been discovered to treat metabolic disorders and has been stated by multitudinous scientists according to a good source of polyphenols compounds. The present study aimed to evaluate the protective effect of the ethanol leaves extract of C. scolymus in alloxan induced stress oxidant, hepatic-kidney dysfunction and histological changes in liver, kidney and pancreas of different experimental groups of rats. METHODS:We determinate the antioxidant activity by ABTS .+ and antioxidant total capacity (TAC) of all extracts of C. scolymus leaves, the inhibition of α-amylase activity in vitro was also investigated. Forty male Wistar rats were induced to diabetes with a single dose intraperitoneal injection (i.p.) of alloxan (150 mg/kg body weight (b.w.)). Diabetic rats were orally and daily administrated of ethanol extract from C. scolymus at two doses (200-400 mg/kg, b.w) or (12 mg/kg, b.w) with anti-diabetic reference drug, Acarbose for one month. Ethanol extract of C. scolymus effect was confirmed by biochemical analysis, antioxidant activity and histological study. RESULTS:The results indicated that the ethanol extract from leaves of C. scolymus showed the highest antioxidant activity by ABTS .+ (499.43g± 39.72 Trolox/g dry extract) and (128.75 ± 8.45 mg VC /g dry extract) for TAC and endowed the powerful inhibition in vitro of α-amylase activity with IC50=72,22 ug/uL. In vivo, the results showed that ethanol extract from the leaves of C. scolymus (200-400 mg/kg) decreased significantly (p < 0.001) the α-amylase levels in serum of diabetic rats, respectively associated with significant reduction (p < 0.001) in blood glucose rate of 42,84% and 37,91% compared to diabetic groups after 28 days of treatment, a significant lowered of plasma total cholesterol (T-Ch) by 18,11% and triglyceride (TG) by 60,47%, significantly and low-density lipoproteins (LDL-C) by 37,77%, compared to diabetic rats, moreover, the administration of ethanol extract appears to exert anti-oxidative activity demonstrated by the increase of CAT, SOD and GSH activities in liver, kidney and pancreas of diabetic rats. This positive effect of the ethanol extract from C. scolymus was confirmed by histological study. CONCLUSION:These observed strongly suggest that ethanol extract from the leaves of C. scolymus has anti-hyperglycemic properties, at least partly mediated by antioxidant and hypolipidemic effects.
    背景与目标: 背景:糖尿病(DM)与高血糖,炎性疾病和异常脂质状况相关,目前已发现粘虫c叶片的提取物可治疗代谢紊乱,许多科学家已经根据多酚化合物的良好来源进行了陈述。本研究旨在评价鳞球菌乙醇叶提取物对四氧嘧啶诱导的应激氧化剂,肝肾功能障碍以及不同实验组大鼠肝,肾和胰腺组织学变化的保护作用。
    方法:我们通过ABTS测定抗氧化活性。鼠尾草叶片的所有提取物的抗氧化剂和总抗氧化剂(TAC),还研究了其对α-淀粉酶活性的体外抑制作用。通过单剂量腹膜内注射(i.p.)四氧嘧啶(150 mg / kg体重(b.w.))将40只雄性Wistar大鼠诱发为糖尿病。糖尿病大鼠口服和每天服用两种剂量(200-400 mg / kg,b.w)或(12 mg / kg,b.w)的鼠尾草乙醇提取物和抗糖尿病参考药物阿卡波糖(acarbose)。通过生化分析,抗氧化活性和组织学研究证实了粘液梭状芽胞杆菌的乙醇提取物作用。
    结果:结果表明,ABTS从粘枝sco叶片中提取的乙醇具有最高的抗氧化活性。 (499.43g±39.72 Trolox / g干提取物)和(128.75±8.45 mg VC / g干提取物)用于TAC,并在体外有效抑制α-淀粉酶活性,IC50 = 72.22 ug / uL。在体内,结果显示,从粘液梭菌的叶子中提取乙醇(200-400 mg / kg)显着降低(p <0.001)糖尿病大鼠血清中的α-淀粉酶水平,分别与显着降低有关(p <0.001)。在治疗28天后,与糖尿病组相比,血糖比率分别为0.001、42.84%和37.91%,血浆总胆固醇(T-Ch)显着降低了18.11%,甘油三酸酯(TG)显着降低了60与糖尿病大鼠相比,低密度脂蛋白(LDL-C)降低了47.7%,低密度脂蛋白(LDL-C)降低了37.77%,此外,乙醇提取物的给药似乎表现出抗氧化活性,这是由于CAT,SOD和GSH的增加所证明的在糖尿病大鼠肝,肾和胰腺中的活性。组织学研究证实了粘液梭菌乙醇提取物的这种积极作用。
    结论:这些观察结果强烈表明,从粘液梭菌的叶子中提取乙醇具有抗降血糖作用,至少部分是由抗氧化剂和降血脂作用介导的。
  • 【轮虫(Aspalathus linearis)中的天冬酰胺对秀丽隐杆线虫的急性氧化应激的改善作用。】 复制标题 收藏 收藏
    DOI:10.1016/j.phymed.2012.10.006 复制DOI
    作者列表:Chen W,Sudji IR,Wang E,Joubert E,van Wyk BE,Wink M
    BACKGROUND & AIMS: :Rooibos leaves and fine stems (Aspalathus linearis; Fabaceae) are increasingly enjoyed as herbal tea, largely in fermented (oxidised) red-brown form, but also in unfermented (unoxidised) green form. Rooibos is rich in antioxidant polyphenols, with the dihydrochalcone, aspalathin, as a major active ingredient. We used Caenorhabditis elegans as model organism to investigate the effect of rooibos extracts against oxidative stress in vivo. In a high glucose environment, C. elegans treated with rooibos extract exhibited an extended lifespan. Furthermore, green rooibos was a more potent antioxidant than red rooibos, probably due to its substantially higher aspalathin content. In addition, rooibos decreased acute oxidative damage caused by the superoxide anion radical generator, juglone, with aspalathin playing a major role in improving the survival rate of C. elegans. Quantitative real-time PCR results demonstrated that aspalathin targets stress and ageing related genes, reducing the endogenous intracellular level of ROS. These findings suggest that rooibos increases stress resistance and promotes longevity under stress, probably mediated via a regulation of the DAF-16/FOXO insulin-like signalling pathway, supporting some of the health claims put forward for rooibos tea.
    背景与目标: :茶树茶和细茎(Aspalathus linearis;豆科)越来越被用作凉茶,主要是发酵(氧化)的红棕色形式,但也有未发酵(未氧化)的绿色形式。如意宝(Rooibos)富含抗氧化剂多酚,其中二氢查耳酮,阿斯帕拉丁为主要活性成分。我们以秀丽隐杆线虫为模型生物,研究了路易宝提取物在体内对氧化应激的影响。在高葡萄糖环境中,用如意宝提取物处理的秀丽隐杆线虫显示出延长的寿命。此外,绿色如意宝比红色如意宝具有更强的抗氧化剂作用,这可能是由于其芦笋素含量高得多。此外,如意宝减少了由超氧阴离子自由基产生剂juglone引起的急性氧化损伤,其中天冬酰胺在提高秀丽隐杆线虫的存活率中起主要作用。实时定量PCR结果表明,阿斯帕拉丁可靶向应激和衰老相关基因,从而降低ROS的内源性细胞内水平。这些发现表明,如意宝可增加对压力的抵抗力,并在压力下延长寿命,这可能是通过调节DAF-16 / FOXO胰岛素样信号通路介导的,支持了如意宝茶提出的一些健康主张。
  • 【NLRX1通过控制线粒体活性来抑制组织损伤中的氧化应激和细胞凋亡。】 复制标题 收藏 收藏
    DOI:10.1084/jem.20161031 复制DOI
    作者列表:Stokman G,Kors L,Bakker PJ,Rampanelli E,Claessen N,Teske GJD,Butter L,van Andel H,van den Bergh Weerman MA,Larsen PWB,Dessing MC,Zuurbier CJ,Girardin SE,Florquin S,Leemans JC
    BACKGROUND & AIMS: :Mitochondrial dysfunction is the most prominent source of oxidative stress in acute and chronic kidney disease. NLRX1 is a receptor of the innate immune system that is ubiquitously expressed and localized in mitochondria. We investigated whether NLRX1 may act at the interface of metabolism and innate immunity in a model of oxidative stress. Using a chimeric mouse model for renal ischemia-reperfusion injury, we found that NLRX1 protects against mortality, mitochondrial damage, and epithelial cell apoptosis in an oxidative stress-dependent fashion. We found that NLRX1 regulates oxidative phosphorylation and cell integrity, whereas loss of NLRX1 results in increased oxygen consumption, oxidative stress, and subsequently apoptosis in epithelial cells during ischemia-reperfusion injury. In line, we found that NLRX1 expression in human kidneys decreased during acute renal ischemic injury and acute cellular rejection. Although first implicated in immune regulation, we propose that NLRX1 function extends to the control of mitochondrial activity and prevention of oxidative stress and apoptosis in tissue injury.
    背景与目标: 线粒体功能障碍是急性和慢性肾脏疾病中最主要的氧化应激源。 NLRX1是先天免疫系统的受体,在线粒体中普遍表达和定位。我们调查了NLRX1是否可能在氧化应激模型中的新陈代谢和先天免疫的界面上起作用。使用针对肾缺血-再灌注损伤的嵌合小鼠模型,我们发现NLRX1以氧化应激依赖性的方式防止死亡,线粒体损伤和上皮细胞凋亡。我们发现NLRX1调节氧化磷酸化和细胞完整性,而NLRX1的缺失导致缺血再灌注损伤期间上皮细胞的耗氧量增加,氧化应激和随后的细胞凋亡。一致地,我们发现在急性肾缺血性损伤和急性细胞排斥期间,人肾脏中的NLRX1表达降低。尽管首先涉及免疫调节,但我们认为NLRX1功能扩展到线粒体活性的控制以及组织损伤中氧化应激和细胞凋亡的预防。
  • 【青少年内在化和外在化症状的测试,可以作为创伤暴露和创伤后应激障碍类型的前瞻性预测指标。】 复制标题 收藏 收藏
    DOI:10.1002/jts.21751 复制DOI
    作者列表:Haller M,Chassin L
    BACKGROUND & AIMS: :The present study utilized longitudinal data from a high-risk community sample (N = 377; 166 trauma-exposed; 202 males; 175 females; 73% non-Hispanic Caucasian) to test pretrauma measures of adolescent internalizing and externalizing symptoms as unique prospective predictors of type of trauma exposure and PTSD over and above the influence of correlated family adversity (a composite of family conflict, stress, and parental psychopathology). Data were analyzed with logistic and multinomial logistic regressions. Results indicated that females, but not males, with higher levels of internalizing (OR = 2.91) and externalizing (OR = 2.37) symptoms during adolescence were significantly more likely to be exposed to assaultive violence (over and above family adversity). In fact, males with higher levels of internalizing symptoms were significantly less likely to be exposed to assaultive violence (OR = 0.54). Neither internalizing nor externalizing symptoms uniquely predicted exposure to traumatic events that did not involve assaultive violence. Among trauma-exposed participants, the unique association between internalizing symptoms and later PTSD yielded an odds ratio of 1.79 (p = .07) over and above the influences of family adversity, type of trauma exposure, and gender. Assaultive violence exposure fully mediated the association between females' externalizing symptoms and future PTSD. Findings may help inform the prevention of both assaultive violence exposure and PTSD.
    背景与目标: :本研究利用来自高风险社区样本(N = 377;暴露于166的外伤​​; 202男性; 175女性; 73%的非西班牙裔白种人)的纵向数据来测试青少年内在和外在症状的创伤前测量方法,作为独特的前瞻性研究除了相关的家庭逆境影响(家庭冲突,压力和父母的心理病理因素的综合影响)以外,还可以预测创伤暴露和PTSD的类型。使用logistic和多项式logistic回归分析数据。结果表明,青春期出现内在化(OR = 2.91)和外在化(OR = 2.37)症状的女性(而非男性)明显更有可能遭受攻击性暴力(家庭逆境以上)。实际上,具有较高内在症状水平的男性遭受攻击性暴力的可能性大大降低(OR = 0.54)。内在或外在症状都不能唯一预测暴露于不涉及攻击性暴力的创伤事件。在遭受创伤的参与者中,内在症状与后来的创伤后应激障碍之间的独特关联产生了1.79(p = .07)的优势比,高于家庭逆境,创伤暴露类型和性别的影响。攻击性暴力暴露完全介导了女性的外在症状与未来PTSD之间的关联。研究结果可能有助于预防攻击性暴力暴露和PTSD。
  • 【实验诱发的压力后,二元应对,不安全的依恋和皮质醇压力恢复。】 复制标题 收藏 收藏
    DOI:10.1037/a0030356 复制DOI
    作者列表:Meuwly N,Bodenmann G,Germann J,Bradbury TN,Ditzen B,Heinrichs M
    BACKGROUND & AIMS: :Evidence for the stress-buffering effects of social support in intimate relationships raises important questions about whether partner support promotes recovery in physiological systems implicated in physical health. The present study examined (a) whether observed dyadic coping enhances cortisol stress recovery and (b) whether a stressed partner's self-reported attachment anxiety and avoidance moderate these effects. Stress was experimentally induced by asking either the man or woman in 123 heterosexual couples to participate in a standardized public speaking task. Stressed individuals recovered faster from stress the more positive dyadic coping they received from the partner, with women high in attachment anxiety benefiting less from these behaviors. Attachment avoidance did not moderate these associations. This study highlights the value of examining the interplay between partners' behaviors and attachment orientations in order to understand the impact of stress on close relationships and partners' health.
    背景与目标: :在亲密关系中社会支持对压力的缓冲作用的证据提出了一个重要问题,即伴侣支持是否会促进与身体健康有关的生理系统的恢复。本研究调查了(a)观察到的二元应对是否增强了皮质醇应激恢复,以及(b)应激伴侣的自我报告的焦虑和避免焦虑是否减轻了这些影响。通过让123对异性恋夫妇中的男人或女人参加标准化的公开演讲任务,实验性地诱发了压力。压力大的人从伴侣那里得到的积极积极的应对使他们从压力中恢复得更快,而依恋焦虑高的女性则从这些行为中受益较少。避免依恋并没有减轻这些联系。这项研究强调了检查伴侣行为与依恋取向之间相互作用的价值,以了解压力对亲密关系和伴侣健康的影响。
  • 【更正:肝p63通过IKKβ/ ER应激调节脂肪变性。】 复制标题 收藏 收藏
    DOI:10.1038/ncomms16059 复制DOI
    作者列表:
    BACKGROUND & AIMS: :This corrects the article DOI: 10.1038/ncomms15111.
    背景与目标: :这样可以更正文章DOI:10.1038 / ncomms15111。
  • 【海地地震后的精神病理学:基于人群的创伤后应激障碍和重度抑郁症研究。】 复制标题 收藏 收藏
    DOI:10.1002/da.22007 复制DOI
    作者列表:Cerdá M,Paczkowski M,Galea S,Nemethy K,Péan C,Desvarieux M
    BACKGROUND & AIMS: BACKGROUND:In the first population-based study of psychopathology conducted in Haiti, we documented earthquake-related experiences associated with risk for posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) 2-4 months following the 2010 Haiti earthquake. METHODS:A population-based survey was conducted of 1,323 survivors randomly selected from the general nondisplaced community, internally displaced persons camps, and a community clinic. Respondents were from the Nazon area of Port-au-Prince, ∼20 miles from the epicenter. RESULTS:Respondents (90.5%) reported at least one relative/close friend injured/killed, 93% saw dead bodies, and 20.9% lost their job post-earthquake. The prevalence of PTSD (24.6%) and MDD (28.3%) was high. History of violent trauma was associated with risk of PTSD and MDD (adjusted odds ratio [AOR] 1.4, 95% confidence interval [CI], 1.0-1.9; AOR, 1.7, 95% CI 1.3, 2.2, respectively). Low social support (AOR, 1.7, 95% CI 1.2, 2.3; AOR 1.4, 95% CI 1.0, 1.9, respectively) increased risk of PTSD and MDD among women. Suffering damage to the home increased risk of MDD in males (AOR 2.8, 95% CI 1.5, 5.5). Associations between being trapped in rubble, major damage to house, job loss, and PTSD; and participation in rescue/recovery, friends/family injured/killed, and MDD varied based on prior history of violent trauma. CONCLUSIONS:Addressing mental health in a post-earthquake setting such as Haiti will require focusing resources on screening and treatment of identified vulnerable groups while targeting improvement of post-earthquake living conditions. Investment in sources of social support for women may make help mitigate the vulnerability of women to PTSD and MDD.
    背景与目标: 背景:在海地进行的第一项基于人群的心理病理学研究中,我们记录了与地震相关的经历,这些经历与2010年海地地震发生后2-4个月的创伤后应激障碍(PTSD)和重度抑郁症(MDD)风险有关。
    方法:基于人口的调查是对从普通非流离失所社区,国内流离失所者营地和社区诊所中随机选择的1,323名幸存者进行的。受访者来自太子港的纳松地区,距震中约20英里。
    结果:受访者(90.5%)报告说,至少有一个亲戚/密友受伤/被杀,93%的人有尸体,20.9%的人在地震后丧生。 PTSD(24.6%)和MDD(28.3%)的患病率很高。暴力创伤史与PTSD和MDD的风险有关(校正比值比[AOR] 1.4,95%置信区间[CI],1.0-1.9; AOR,1.7,95%CI 1.3,2.2)。较低的社会支持(分别为AOR,1.7、95%CI 1.2、2.3,AOR 1.4、95%CI 1.0、1.9)增加了妇女罹患PTSD和MDD的风险。房屋遭受损坏会增加男性罹患MDD的风险(AOR 2.8,95%CI 1.5,5.5)。被困在瓦砾中,对房屋的重大破坏,失业和PTSD之间的关联;根据先前的暴力创伤史,参与救援/恢复,朋友/家人受伤/被杀以及MDD的情况也有所不同。
    结论:在海地这样的地震后环境中解决心理健康问题,将需要把资源集中在筛查和治疗已确定的弱势群体上,同时着眼于改善地震后的生活条件。对妇女的社会支持来源的投资可能有助于减轻妇女对PTSD和MDD的脆弱性。
  • 【在小鼠下丘脑器官型培养物中,Sequestosome 1(SQSTM1 / p62)在内质网应激下维持蛋白质折叠能力。】 复制标题 收藏 收藏
    DOI:10.1016/j.neulet.2017.06.014 复制DOI
    作者列表:Tominaga T,Goto M,Onoue T,Mizoguchi A,Sugiyama M,Tsunekawa T,Hagiwara D,Morishita Y,Ito Y,Iwama S,Suga H,Banno R,Arima H
    BACKGROUND & AIMS: :Sequestosome 1 (SQSTM1) also known as ubiquitin-binding protein p62 (p62) is a cargo protein involved in the degradation of misfolded proteins via selective autophagy. Disruption of autophagy and resulting accumulation of misfolded proteins in the endoplasmic reticulum (ER) leads to ER stress. ER stress is implicated in several neurodegenerative diseases and obesity. As knockout of p62 (p62KO) reportedly induces obesity in mice, we examined how p62 contributes to ER stress and the ensuing unfolded protein response (UPR) in hypothalamus using mouse organotypic cultures in the present study. Cultures from p62KO mice showed significantly reduced formation of LC3-GFP puncta, an index of autophagosome formation, in response to the chemical ER stressor thapsigargin compared to wild-type (WT) cultures. Hypothalamic cultures from p62KO mice exhibited higher basal expression of the UPR/ER stress markers CHOP mRNA and ATF4 mRNA than WT cultures. Thapsigargin enhanced CHOP, ATF4, and BiP mRNA as well as p-eIF2α protein expression in both WT and p62KO cultures, but all peak values were greater in p62KO cultures. A proteasome inhibitor increased p62 expression in WT cultures and upregulated the UPR/ER stress markers CHOP mRNA and ATF4 mRNA in both genotypes, but to a greater extent in p62KO cultures. Therefore, p62 deficiency disturbed autophagosome formation and enhanced both basal and chemically induced ER stress, suggesting that p62 serves to prevent ER stress in mouse hypothalamus by maintaining protein folding capacity.
    背景与目标: :Sequestosome 1(SQSTM1)也称为泛素结合蛋白p62(p62)是一种货物蛋白,通过选择性自噬作用参与错折叠蛋白的降解。自噬的中断和错误折叠的蛋白质在内质网(ER)中的积累会导致ER应激。内质网应激与几种神经退行性疾病和肥胖有关。由于据报道,敲除p62(p62KO)会诱发小鼠肥胖,因此在本研究中,我们使用小鼠器官培养物检查了p62如何导致ER应激以及下丘脑中未折叠的蛋白反应(UPR)。与野生型(WT)培养相比,来自p62KO小鼠的培养物响应化学ER应激毒胡萝卜素,显示出LC3-GFP点的形成显着减少,这是自噬体形成的指标。来自p62KO小鼠的下丘脑培养物比WT培养物具有更高的UPR / ER应激标志物CHOP mRNA和ATF4 mRNA的基础表达。 Thapsigargin在WT和p62KO培养物中均增强了CHOP,ATF4和BiP mRNA以及p-eIF2α蛋白的表达,但在p62KO培养物中所有峰值均更大。蛋白酶体抑制剂增加了WT培养物中p62的表达,并上调了两种基因型的UPR / ER应激标记CHOP mRNA和ATF4 mRNA,但在p62KO培养物中的表达更大。因此,p62缺乏会干扰自噬体的形成,并增强基础和化学诱导的ER应激,提示p62通过维持蛋白质折叠能力来预防小鼠下丘脑的ER应激。
  • 【新加坡和印度对压力的心血管反应。】 复制标题 收藏 收藏
    DOI:10.1016/j.ijpsycho.2012.11.011 复制DOI
    作者列表:Kaur D,Bishop GD
    BACKGROUND & AIMS: BACKGROUND:Epidemiological studies have shown significant ethnic differences in coronary heart disease death rates with South Asians showing significantly greater coronary heart disease mortality than other groups. PURPOSE:This research examined ethnic differences in cardiovascular reactivity (CVR) among Chinese, Malays and Indians in Singapore as well as a sample of Indians living in India. METHODS:Experiment 1 examined differences across 303 Chinese, Malay and Indian undergraduates in Singapore, while Experiment 2 looked at differences in CVR between Indian participants from Singapore, and 145 Indians living in India. Systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), cardiac index (CI) and total peripheral resistance index (TPRI) were measured during baselines and five laboratory tasks. RESULTS:Ethnicity main effects for SBP and CI reactivity were obtained in Experiment 1, with Indians showing significantly lower BP and CI reactivity than the Chinese and Malays. Significant main effects for sex were found with females showing lower reactivity than males for TPRI, and greater reactivity than males for HR and CI. Experiment 2 found that participants from India showed higher reactivity for SBP, HR and CI, while Indian participants from Singapore showed higher TPRI reactivity. These differences, however, often varied by task. CONCLUSIONS:These results point to differences in CVR among ethnic groups in Singapore as well as between Indians living in India and those living in Singapore. These differences may reflect cultural differences and need to be explored further with respect to their relationship to different rates of coronary heart disease among these groups.
    背景与目标: 背景:流行病学研究表明,冠心病死亡率的种族差异显着,南亚人显示冠心病死亡率明显高于其他人群。
    目的:本研究调查了新加坡华人,马来人和印第安人以及居住在印度的印第安人样本中心血管反应性(CVR)的种族差异。
    方法:实验1考察了新加坡303名华裔,马来裔和印度裔本科生之间的差异,而实验2则考察了来自新加坡的印度裔参与者和居住在印度的145名印度裔之间的CVR差异。在基线和五个实验室任务期间测量了收缩压和舒张压(SBP,DBP),心率(HR),心脏指数(CI)和总外周阻力指数(TPRI)。
    结果:种族对SBP和CI反应性的主要影响是在实验1中获得的,印度人的BP和CI反应性明显低于华人和马来人。发现性别具有重大的主要影响,女性对TPRI的反应性低于男性,而对HR和CI的反应性则高于男性。实验2发现印度参与者对SBP,HR和CI的反应性更高,而新加坡印度参与者对TPRI的反应性更高。但是,这些差异通常因任务而异。
    结论:这些结果表明,新加坡各族裔之间以及居住在印度的印度人与居住在新加坡的印度人之间的CVR差异。这些差异可能反映了文化差异,因此需要进一步探讨这些差异与这些人群中冠心病发病率的关系。
  • 【MDMA(±3,4-亚甲二氧基甲基苯丙胺)辅助的心理疗法用于治疗顽固性慢性创伤后应激障碍(PTSD)的随机对照试验研究。】 复制标题 收藏 收藏
    DOI:10.1177/0269881112464827 复制DOI
    作者列表:Oehen P,Traber R,Widmer V,Schnyder U
    BACKGROUND & AIMS: :Psychiatrists and psychotherapists in the US (1970s to 1985) and Switzerland (1988-1993) used MDMA legally as a prescription drug, to enhance the effectiveness of psychotherapy. Early reports suggest that it is useful in treating trauma-related disorders. Recently, the first completed pilot study of MDMA-assisted psychotherapy for PTSD yielded encouraging results. Designed to test the safety and efficacy of MDMA-assisted psychotherapy in patients with treatment-resistant PTSD; our randomized, double-blind, active-placebo controlled trial enrolled 12 patients for treatment with either low-dose (25 mg, plus 12.5 mg supplemental dose) or full-dose MDMA (125 mg, plus 62.5 mg supplemental dose). MDMA was administered during three experimental sessions, interspersed with weekly non-drug-based psychotherapy sessions. Outcome measures used were the Clinician-Administered PTSD Scale (CAPS) and the Posttraumatic Diagnostic Scale (PDS). Patients were assessed at baseline, three weeks after the second and third MDMA session (end of treatment), and at the 2-month and 1-year follow-ups. We found that MDMA-assisted psychotherapy can be safely administered in a clinical setting. No drug-related serious adverse events occurred. We did not see statistically significant reductions in CAPS scores (p = 0.066), although there was clinically and statistically significant self-reported (PDS) improvement (p = 0.014). CAPS scores improved further at the 1-year follow-up. In addition, three MDMA sessions were more effective than two (p = 0.016).
    背景与目标: 美国(1970年代至1985年)和瑞士(1988-1993年)的精神科医生和心理治疗师合法地将MDMA用作处方药,以提高心理疗法的有效性。早期报道表明,它可用于治疗与创伤有关的疾病。最近,第一个完成的针对PTSD的MDMA辅助心理治疗的初步研究取得了令人鼓舞的结果。旨在测试MDMA辅助心理疗法在治疗难治性PTSD患者中的安全性和有效性;我们的随机,双盲,活性安慰剂对照试验招募了12名患者,分别接受低剂量(25 mg,加上12.5 mg补充剂量)或全剂量MDMA(125 mg,加上62.5 mg补充剂量)治疗。在三个实验阶段中使用MDMA,并在每周的非药物心理治疗阶段中进行穿插。所使用的结果指标是临床医生管理的PTSD量表(CAPS)和创伤后诊断量表(PDS)。在基线时,第二和第三次MDMA疗程后三周(治疗结束)以及2个月和1年的随访中对患者进行评估。我们发现,在临床环境中可以安全地进行MDMA辅助的心理治疗。没有发生与药物有关的严重不良事件。尽管在临床和统计学上自我报告(PDS)的改善(p = 0.014),但CAPS评分没有统计学上的显着降低(p = 0.066)。在1年的随访中,CAPS评分进一步提高。此外,三个MDMA会话比两个更有效(p = 0.016)。
  • 【H3K36甲基化通过增强转录保真度来调节酿酒酵母中的营养应激反应。】 复制标题 收藏 收藏
    DOI:10.1016/j.celrep.2017.05.057 复制DOI
    作者列表:McDaniel SL,Hepperla AJ,Huang J,Dronamraju R,Adams AT,Kulkarni VG,Davis IJ,Strahl BD
    BACKGROUND & AIMS: :Set2-mediated histone methylation at H3K36 regulates diverse activities, including DNA repair, mRNA splicing, and suppression of inappropriate (cryptic) transcription. Although failure of Set2 to suppress cryptic transcription has been linked to decreased lifespan, the extent to which cryptic transcription influences other cellular functions is poorly understood. Here, we uncover a role for H3K36 methylation in the regulation of the nutrient stress response pathway. We found that the transcriptional response to nutrient stress was dysregulated in SET2-deleted (set2Δ) cells and was correlated with genome-wide bi-directional cryptic transcription that originated from within gene bodies. Antisense transcripts arising from these cryptic events extended into the promoters of the genes from which they arose and were associated with decreased sense transcription under nutrient stress conditions. These results suggest that Set2-enforced transcriptional fidelity is critical to the proper regulation of inducible and highly regulated transcription programs.
    背景与目标: :Set2介导的H3K36的组蛋白甲基化调节各种活动,包括DNA修复,mRNA剪接和抑制不适当的(隐式)转录。尽管Set2未能抑制隐式转录与降低寿命有关,但对隐式转录影响其他细胞功能的程度了解甚少。在这里,我们揭示了H3K36甲基化在营养胁迫响应途径调控中的作用。我们发现,对营养胁迫的转录反应在SET2缺失(set2Δ)细胞中失调,并且与源自基因体内的全基因组双向隐秘转录相关。由这些隐性事件引起的反义转录本延伸到它们起源的基因的启动子中,并与在营养胁迫条件下的有义转录减少有关。这些结果表明,Set2增强的转录保真度对于诱导性和高度调控的转录程序的正确调控至关重要。
  • 【神经血管单位和剂量对VEGF毒性的影响:对氧化应激和凝血酶的作用。】 复制标题 收藏 收藏
    DOI:10.3233/JAD-121636 复制DOI
    作者列表:Sanchez A,Tripathy D,Luo J,Yin X,Martinez J,Grammas P
    BACKGROUND & AIMS: :Bidirectional communication between neurons and vascular cells is important to the maintenance of the central nervous system (CNS) milieu. Vascular endothelial growth factor (VEGF), through its ability to affect both vascular and neuronal cells, is likely a key protein in this process. Despite considerable literature documenting a neuroprotective function for VEGF, overexpression of this protein has also been shown in a wide variety of CNS diseases, including Alzheimer's disease (AD). Increased oxidative stress and elevated thrombin levels have also been documented in AD, specifically in the microvasculature. The aim of the current study is to examine endothelial cells and neurons in vitro to determine the effects of oxidative stress and thrombin on VEGF release as well as the effects of low and high dose VEGF on neuronal viability. The data show that microvessels isolated from AD patients secrete significantly higher levels of VEGF compared to control-derived vessels. Exposure of brain endothelial cells to oxidative stress (sodium nitroprusside, menadione, or hydrogen peroxide) or thrombin significantly increases VEGF expression. Exposure of cultured neurons to oxidative stress increases expression of thrombin. Treating rat cortical neurons with high dose VEGF (≥500 ng/ml) decreases neuronal survival and expression of the anti-apoptotic protein Bcl-2 while increasing proapoptic proteins caspase 3 and phosphorylated p38 MAPK. High dose VEGF also negates the decrease in amyloid-β evoked by low dose VEGF. These results suggest that despite literature supporting neuroprotective effects of this protein, caution is warranted prior to implementation of VEGF as a therapeutic in the brain.
    背景与目标: :神经元与血管细胞之间的双向通讯对于维持中枢神经系统(CNS)环境至关重要。血管内皮生长因子(VEGF)通过影响血管和神经元细胞的能力,很可能是该过程中的关键蛋白。尽管有大量文献记载了VEGF的神经保护功能,但该蛋白的过表达也已在多种中枢神经系统疾病(包括阿尔茨海默氏病(AD))中显示。在AD中,特别是在微脉管系统中,也已经证明了氧化应激的增加和凝血酶水平的升高。本研究的目的是在体外检查内皮细胞和神经元,以确定氧化应激和凝血酶对VEGF释放的影响以及低剂量和高剂量VEGF对神经元生存力的影响。数据显示,与对照来源的血管相比,从AD患者中分离出的微血管分泌的VEGF水平明显更高。将脑内皮细胞暴露于氧化应激(硝普钠,甲萘醌或过氧化氢钠)或凝血酶会显着增加VEGF的表达。培养的神经元暴露于氧化应激会增加凝血酶的表达。用高剂量VEGF(≥500ng / ml)治疗大鼠皮质神经元可降低神经元存活率和抗凋亡蛋白Bcl-2的表达,同时增加促凋亡蛋白caspase 3和磷酸化的p38 MAPK。高剂量VEGF还可以抵消低剂量VEGF引起的淀粉样β的减少。这些结果表明,尽管有文献支持该蛋白的神经保护作用,但在将VEGF用作脑部治疗剂之前,仍应谨慎行事。
  • 【在生命早期处于应激状态的大鼠的神经发育里程碑异常。】 复制标题 收藏 收藏
    DOI:10.1016/j.neuroscience.2007.04.007 复制DOI
    作者列表:Mesquita AR,Pêgo JM,Summavielle T,Maciel P,Almeida OF,Sousa N
    BACKGROUND & AIMS: :Manipulation of the corticosteroid milieu by interfering with the mother-newborn relationship has received much attention because of its potential bearing on psychopathology later in life. In the present study, infant rats that were deprived of maternal contact between the 2nd and the 15th postnatal days (MS2-15) for 6 h/day were subjected to a systematic assessment of neurodevelopmental milestones between postnatal days 2 and 21. The analyses included measurements of physical growth and maturation and evaluation of neurological reflexes. Although some somatic milestones (e.g. eye opening) were anticipated, MS2-15 animals showed retardation in the acquisition of postural reflex, air righting and surface righting reflexes, and in the wire suspension test; the latter two abnormalities were only found in males. A gender effect was also observed in negative geotaxis, with retardation being observed in females but not males. To better understand the delay of neurological maturation in MS2-15 rats, we determined the levels of various monoamines in different regions of the brain stem, including the vestibular area, the substantia nigra, ventral tegmental area and dorsal raphe nuclei. In the vestibular region of MS2-15 rats the levels of 5-HT were reduced, while 5-HT turnover was increased. There was also a significant increase of the 5-HT turnover in MS2-15 animals in the raphe nuclei, mainly due to increased 5-hydroxyindoleacetic acid (5-HIAA) levels, and an increase of 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the ventral tegmental area (VTA) of stressed females. No significant differences were found in the immunohistochemical sections for tyrosine and tryptophan hydroxylase in these regions of the brain stem. In conclusion, the present results show that postnatal stress induces signs of neurological pathology that may contribute to the genesis of behavioral abnormalities later in life.
    背景与目标: :通过干扰母亲与新生儿的关系来操纵皮质类固醇环境受到了广泛的关注,因为它有可能影响以后的心理病理学。在本研究中,对在出生后第2天和第15天(MS2-15)之间失去母体接触6小时/天的幼鼠进行了系统评估,评估了出生后第2天和第21天之间的神经发育里程碑。身体生长和成熟的测量以及神经反射的评估。尽管可以预见会有一些身体上的里程碑(例如睁眼),但MS2-15动物在姿势反射,空气正直和表面正直反射的获得以及钢丝悬吊测试中表现出迟缓性;后两个异常仅在男性中发现。在负地轴方向上也观察到性别效应,在雌性中观察到发育迟缓,而雄性中观察不到。为了更好地了解MS2-15大鼠神经系统成熟的延迟,我们确定了脑干不同区域(包括前庭区,黑质,腹侧被盖区和背ra核)中各种单胺的水平。在MS2-15大鼠的前庭区域,5-HT水平降低,而5-HT周转增加。缝核中MS2-15动物中5-HT的转换也显着增加,这主要是由于5-羟基吲哚乙酸(5-HIAA)水平的增加和3,4-二羟基苯基乙酸(DOPAC)的增加压力女性腹侧被盖区(VTA)的水平。在脑干的这些区域中,酪氨酸和色氨酸羟化酶的免疫组织化学切片未发现明显差异。总之,本研究结果表明,产后应激会诱发神经病理学征象,这可能有助于以后生活中行为异常的发生。

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