Simultaneous modulation of COX-2, p300, Akt, and Apaf-1 signaling by melatonin to inhibit proliferation and induce apoptosis in breast cancer cells

Melatonin exhibits anti-inflammatory and anticancer effects and could be a chemopreventive and chemotherapeutic agent against cancers, but the precise mechanisms involved remain largely unresolved. In this study, we evaluated the mechanism of action of melatonin in human MDA-MB-361 breast cancer cells. Melatonin at pharmacological concentrations (10(-3) m) significantly suppressed cell proliferation and induced apoptosis in a dose-dependent manner. The observed suppression of proliferation was accompanied by the melatonin-mediated inhibition of COX-2, p300, and NF-κB signaling. Melatonin significantly inhibited COX-2 expression and prostaglandin E(2) (PGE2) production, abrogated p300 histone acetyltransferase activity and p300-mediated NF-κB acetylation, thereby blocking NF-κB binding and p300 recruitment to COX-2 promoter. Pretreatment with a COX-2- or p300-selective inhibitor abrogated the melatonin-induced inhibition of cell proliferation, whereas PGE2 treatment or COX-2 transfection reversed the inhibition by melatonin. Moreover, melatonin markedly inhibited phosphorylation of PI3K, Akt, PRAS40, and GSK-3 proteins, thereby inactivating the PI3K/Akt signaling pathway. Pretreatment with a PI3K- or an Akt-selective inhibitor or an Akt-specific siRNA blocked the melatonin-mediated inhibition of cell proliferation. Conversely, gene delivery of a constitutively active Akt effectively reversed the inhibition by melatonin. Furthermore, melatonin induced Apaf-1 expression, triggered cytochrome C release, and stimulated caspase-3 and caspase-9 activities and cleavage, leading to an activation of the Apaf-1-dependent apoptotic pathway. Pretreatment with an Apaf-1-specific siRNA effectively attenuated the melatonin-induced apoptosis. These results therefore indicate that melatonin inhibits cell proliferation and induces apoptosis in MDA-MB-361 breast cancer cells in vitro by simultaneously suppressing the COX-2/PGE2, p300/NF-κB, and PI3K/Akt/signaling and activating the Apaf-1/caspase-dependent apoptotic pathway.     

Interactions between perceived emotions and executive attention in an interpersonal game

The emotions displayed by others can be cues to predict their behavior. Happy expressions are usually linked to positive consequences, whereas angry faces are associated with probable negative outcomes. However, there are situations in which the expectations we generate do not hold. Here, control mechanisms must be put in place. We designed an interpersonal game in which participants received good or bad economic offers from several partners. A cue indicated whether the emotion of their partner could be trusted or not. Trustworthy partners with happy facial expressions were cooperative, and angry partners did not cooperate. Untrustworthy partners cooperated when their expression was angry and did not cooperate when they displayed a happy emotion. Event-Related Potential (ERP) results showed that executive attention already influenced the frontal N1. The brain initially processed emotional expressions regardless of their contextual meaning but by the N300, associated to affective evaluation, emotion was modulated by control mechanisms. Our results suggest a cascade of processing that starts with the instantiation of executive attention, continues by a default processing of emotional features and is then followed by an interaction between executive attention and emotional factors before decision-making and motor stages.     

Breastfeeding: An overview of oral and general health benefits

Background

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Breastfeeding is the reference against which alternative infant feeding models must be measured with regard to growth, development and other health outcomes. Although not a systematic review, this report provides an update for dental professionals, including an overview of general and oral health–related benefits associated with breastfeeding.Types of Studies ReviewedThe authors examined the literature regarding general health protections that breastfeeding confers to infants and mothers and explored associations between breastfeeding, occlusion in the primary dentition and early childhood caries. To accomplish these goals, they reviewed systematic reviews when available and supplemented them with comparative studies and with statements and reports from major nongovernmental and governmental organizations.ResultsWhen compared with health outcomes among formula-fed children, the health advantages associated with breastfeeding include a lower risk of acute otitis media, gastroenteritis and diarrhea, severe lower respiratory infections, asthma, sudden infant death syndrome, obesity and other childhood diseases and conditions. Evidence also suggests that breastfed children may develop a more favorable occlusion in the primary dentition. The results of a systematic review in which researchers examined the relationship between breastfeeding and early childhood caries were inconclusive.Conclusions and Clinical ImplicationsThe American Academy of Pediatric Dentistry, Chicago, suggests that parents gently clean infants' gums and teeth after breastfeeding. The American Academy of Pediatrics, Elk Grove Village, Ill., recommends that breastfeeding should be exclusive for about the first six months of life and should continue, with the introduction of appropriate complementary foods, to at least age 12 months or beyond, as desired by mother and child. Dentists and staff members can take steps to ensure they are familiar with the evidence and guidelines pertaining to breastfeeding and to oral health. They are encouraged to follow the surgeon general's recommendations to promote and support optimal breastfeeding and oral health practices among their patients.     

老年原发性失眠的神经心理学测验与P300检测的关系及其意义

目的 了解老年原发性失眠患者认知功能有无损害及其程度. 方法 用神经心理学检测(MMSE、MoCA量表)、P300检测52例老年原发性失眠患者及60例正常体检者. 结果老年原发性失眠患者MoCA量表中视空间与执行功能、注意、延迟回忆得分及总分较对照组显著下降,差异有统计学意义(P＜0.01).MMSE量表评分亦有下降趋势,但差异无统计学意义.P300结果显示无论是靶刺激还是非靶刺激,其诱发出的波明显低平及后移,差异有统计学意义(P＜0.01). 结论 老年原发性失眠患者存在认知功能损害,联合MoCA量表评估及P300检测有助于老年原发性失眠患者早期认知功能损害的诊断.     

3R疗法对阿尔茨海默病患者认知功能和血浆β淀粉样蛋白_(1-42)的影响

目的评价3R疗法对轻、中度阿尔茨海默病患者认知功能和血浆β淀粉样蛋白_(1-42)(Aβ_(1-42))的影响。方法选择轻、中度阿尔茨海默病患者34例,随机分为2组,每组17例。对照组给予药物常规治疗,治疗组在药物常规治疗基础上,采用3R疗法进行认知功能训练。测定血浆Aβ_(1-42),并进行神经心理学指标检查:简易智能状态检查量表、日常生活活动能力量表(ADL)、社会功能活动调查(FAQ)、神经精神量表(NPI)以及事件相关电位P300的基线评定,在开始实施训练后的第3、6个月时,分别对患者进行各项指标的评定与分析。结果治疗组经过3、6个月的3R治疗后,ADL、FAQ、NPI评分较治疗前明显减低,且明显低于对照组(P<0.05,P<0.01);P300潜伏期明显缩短,波幅明显增加(P<0.01);治疗组经过6个月的3R治疗后,血浆Aβ_(1-42)含量较治疗前明显下降,且较对照组明显下降(p<0.05)。结论 3R疗法能有效提高阿尔茨海默病患者生活自理能力、社会活动能力,从而延缓认知功能减退;3R治疗后,认知功能改善可能与血浆Aβ_(1-42)含量变化有关。     

Auditory P3 Event Related Potentials (ERP) and Brainstem Auditory Evoked Responses (BAER) after Spinal Cord Injury in Humans

Abstract

Previous studies have observed altered somatotopic sensory fields after experimental deafferentation in animals as well as enhanced somatosensory evoked potentials and altered cortical motor pathways following spinal cord injury (SCI) in humans. These observations indicate that cortical reorganization may occur subsequent to SCI. In earlier work, we have observed attenuated amplitudes for both tactile P3 and auditory N1/P2 orienting event-related potentials (ERP) in spinal cord injured groups. These results suggest that the reorganization process may have functional perceptual and cognitive consequences. In an effort to determine if deafferentation affects the P3 ERP using stimuli other than somatosensory, we measured brain activity from central recording sites during an auditory “oddball” task. Additionally, we obtained brainstem auditory evoked responses (BAER) in order to assess subcortical primary auditory pathways as well. Results show that the SCI groups produced significantly attenuated N1/P2 complexes and P3 when compared to controls. Also, the quadriplegic group exhibited increased latencies of the P3 at frontal and central sites. There were no differences between groups in BAER results. These findings suggest that primary subcortical auditory information processing stages remain intact after SCI although later stages may be significantly altered. (J Spinal Cord Meet, 18:208–215)     

P300 in obsessive–compulsive disorder: Source localization and the effects of treatment

Converging evidence suggests that frontostriatal abnormalities underlie OCD symptoms. The event-related potential P300 is generated along a widely distributed network involving several of the areas implicated in OCD. P300 abnormalities reported in patients with OCD suggest increased activity in these areas. The aim of the present study was to investigate this assumption in unmedicated patients with OCD, and to assess the effects of OCD treatment on P300 brain activity patterns. Seventy-one unmedicated patients with a DSM-IV diagnosis of OCD and 71 age- and gender-matched healthy control subjects participated in the study. The P300 was obtained through 32-channel EEG during an auditory oddball paradigm. Forty-three patients underwent a second EEG assessment after treatment with sertraline and behavioural therapy. Low-resolution electromagnetic tomography (LORETA) was used to localize the sources of brain electrical activity. Results: Increased P300-related activity was observed predominantly in the left orbitofrontal cortex, but also in left prefrontal, parietal and temporal areas, in patients compared to controls at baseline. After treatment, reduction of left middle frontal cortex hyperactivity was observed in patients. Conclusions: Findings of increased activity in frontoparietal areas in patients are consistent with several previous studies. Importantly, OCD treatment led to reduction of hyperactivity in the left middle frontal cortex, an area associated with context processing and uncertainty that might be important for the emergence of OCD symptoms. Thus, the present study is the first to show an association between P300 abnormalities and activity in brain regions postulated to be involved in the pathophysiology of OCD.     

酒精所致精神障碍患者事件诱发电位P300的研究

目的：探讨酒精所致精神障碍患者事件诱发电位P300的特点。方法：对30例酒精所致精神障碍患者（研究组）和31名正常人（正常对照组）进行事件诱发电位P300的检测,并与正常对照组进行配对t检验和相关分析。结果：与正常对照组比较,酒精所致精神障碍患者P300潜伏期N2、P3显著延长（t=2．318,沁2．335;P〈0．05）;P300波幅N1、N2、P3显著降低（t=-2．414;t=-2．613,t=-4．453;P〈0．05或P〈0．001）。相关分析显示,酒精所致精神障碍患者饮酒年限以及饮酒量与P300潜伏期、波幅之间无明显相关（r=-0．128～-0．274,r=-0．075～0．328;P均〉0．05）。结论：酒精所致精神障碍患者存在认知功能损害,P300可作为酒精所致精神障碍患者检测项目之一。