p300

P300
  • 文章类型: Journal Article
    这项研究检查了与冲突监测相关的神经特征,反馈隐藏信息测试(fCIT)中的识别和反馈处理,并检查了所有ERP是否可用于检测隐藏的自传信息。参与者被随机分配到两组(有罪或无辜)中的一组,然后在进行脑电图(EEG)时进行fCIT测试。结果显示,与有罪参与者中的无关者相比,该探针(参与者的名字)引起的N200更为负面,而P300则更为正面。此外,与不相关的反馈相比,探针之后的反馈引起的反馈P300更大。Further,我们发现三个指标,包括冲突监测N200、识别P300和反馈P300,可以显著区分有罪和无辜的参与者,而FRN不能。结合它们在区分有罪和无辜参与者方面非常有效(AUC=0.91)。这些发现不仅阐明了fCIT的神经处理,而且表明了使用fCIT来检测隐藏的自传信息的潜力。
    This study examined the neural signatures associated with conflict-monitoring, recognition and feedback processing in a feedback Concealed Information Test (fCIT), and also examined whether all the ERPs can be used to detect concealed autobiographical information. Participants were randomly assigned to one of two groups (guilty or innocent) and then tested in the fCIT while undergoing electroencephalograms (EEGs). The results showed that the probe (participants\' name) elicited a more negative N200, and a more positive recognition P300 than irrelevants among guilty participants. Additionally, feedback following the probe elicited a larger feedback P300 than feedback following irrelevants. Further, we found that three indicators, including the conflict-monitoring N200, recognition P300, and feedback P300, could significantly discriminate between guilty and innocent participants, whereas the FRN could not. Combining them is highly effective in discriminating between guilty and innocent participants (AUC = 0.91). These findings not only shed light on the neural processing of the fCIT but also suggest the potential of using the fCIT to detect concealed autobiographical information.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    经济决策在个人和国家利益中都起着至关重要的作用。个人在经济决策中具有公平偏好,但是提案人的道德相关信息可能会影响公平考虑。在先前的ERP研究中,研究人员认为,道德认同会影响最后通牒博弈(UG)中的公平偏好,但是结果有差异。此外,是否榜样(其他人希望帮助决定合适行为的个人),谁能调节人们的道德标准,UG中可能影响公平的担忧仍未得到充分研究。为了解决这些问题,我们通过剔除那些具有非法信息的陈述来选择道德相关陈述,并利用ERP技术来探索提案人的角色模型和道德相关行为的相互作用是否影响了改良UG中的公平处理以及相应的神经机制.我们主要发现,上述对UG中提案考虑因素的交互作用可以反映在拒绝率和P300变化中。结果表明,提出者的角色模型与道德行为之间的相互作用可以调节UG中的公平关注。我们目前的工作为阐明在复杂的社会环境中公平分配的影响机制的时间过程提供了新的途径。
    Economic decision-making plays a paramount role in both individual and national interests. Individuals have fairness preferences in economic decision-making, but a proposer\'s moral-related information may affect fairness considerations. In prior ERP studies, researchers have suggested moral identity influences fairness preferences in the Ultimatum Game (UG), but there are discrepancies in the results. Furthermore, whether role models (individuals whom someone else looks to help decide suitable behaviors), who can modulate people\'s moral standards, can affect fairness concerns in UG is still understudied. To address the questions, we selected the moral-related statements by eliminating those with illegal information and employed the ERP technique to explore whether the interplay of the proposer\'s role model and moral-related behavior influenced fairness processing in the modified UG and the corresponding neural mechanisms. We mainly found that the aforementioned interaction effect on proposal considerations in UG could be mirrored in both rejection rates and P300 variations. The results demonstrate that the interaction between the proposer\'s role model and moral behavior can modulate fairness concerns in UG. Our current work provides new avenues for elucidating the time course of the influencing mechanism of fair distributions in complicated social environments.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    尽管许多研究记录了命题真值在人类心理阅读行为中的作用,关于差分命题真值在处理中国反事实条件中的作用的研究相对缺乏。本研究旨在探讨差分命题值在通过事件相关电位(ERP)处理中国反事实条件中的作用。这项研究是基于理解两种类型的中国反事实条件,这是两种不同的条件连接标记在protasis和apodosis中引入的命题真值,如句子中的真反事实条件标记嘉如(if)&jiu(so)wo香yu嘉如你tuijiujiukeyizaishuixiazhify(我认为如果鱼有腿,它们可以在水下窒息),和错误的反事实条件标记如果(如果)和namo(那么)在句子中wo香沟如果你林namokeyizaishuixiahuxi(我认为如果狗有鳞片,然后他们可以在水下呼吸)。通过操纵protasis和apodosis中的真和假反事实条件标记之间的句子反事实,构造了两个反事实命题值(即真和假命题值)。24名全日制中国大学生参加了ERP研究。结果表明,使用条件标记jiaru(if)和jiu(so)处理真实的反事实命题句子会引起相对于使用条件标记ruguo(if)和namo(then)的错误命题句子的N400效应。此外,具有真实命题条件的反事实句子与原虫中N400效应的启发和自拟中N400效应的缺失不同,表明语义角色可能在命题反事实条件真值的影响下逐渐消失,和/或语义异常在累积句子处理中的作用被消除。而对于虚假的反事实条件句,显示了P300在protasis中的激发和N400在apodosis中的强大作用,表明语义在处理中的作用越来越大。有趣的是,没有P600效应来处理句法违反的句子,这表明在处理具有虚假命题条件的句子时几乎没有额外的句法成本。
    Although many studies document the role of propositional truth-value in human psychological reading behavior, there is a relative paucity of research examining the role of differential propositional truth-value in processing Chinese counterfactual conditionals. This study is to investigate the role of differential propositional value in processing Chinese counterfactual conditionals by means of ERPs (event-related potentials). The study is based on comprehending two types of Chinese counterfactual conditionals, which is propositional truth value introduced by two different markers of conditional conjunctions in the protasis and apodosis, such as true counterfactual conditional markers jiaru (if) & jiu (so) in the sentence wo xiang yu jiaru you tui jiu keyi zai shuixia zhixi (I think if fish had legs so they could stifle under water), and false counterfactual conditional markers ruguo (if) & namo (then) in the sentence wo xiang gou ruguo you lin namo keyi zai shuixia huxi (I think if dogs had scales, then they could breathe under water). Two counterfactual propositional values (i.e. true and false propositional values) are constructed through manipulating sentence counterfactuality between the true and false counterfactual conditional markers in the protasis and the apodosis. Twenty-four full-time Chinese college students participated in the ERP study. The results demonstrated that processing the true counterfactual propositional sentences with conditional markers jiaru (if) & jiu (so) elicited the N400 effect relative to false propositional sentences with conditional markers ruguo (if) & namo (then). Moreover, the counterfactual sentences with true propositional conditions varied from the elicitation of the N400 effect in the protasis and absence of the N400 effect in the apodosis, showing that semantic roles may gradually disappear under the impact of truth value of propositional counterfactual condition, and/or the roles of semantic anomaly was eliminated in the accumulated sentence processing. While for the false counterfactual conditional sentences, elicitations of P300 in the protasis and robust N400 effect in the apodosis were shown, indicating the increasing semantic role in the processing. Interestingly, there was the absence of the P600 effect for processing sentences with syntactic violation, suggesting little extra syntactic cost in processing sentences with false propositional condition.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    巨自噬,自噬的主要调节形式,维持细胞稳态并降解运输的货物。它由蛋白激酶复合物启动,通过两个信号通路调节哺乳动物雷帕霉素复合物1(mTORC1)-腺苷5'一磷酸活化蛋白激酶(AMPK)-Unc51样激酶1(ULK1)和ULK1-PI3K-磷脂酰肌醇3-磷酸(PI3P)。目前,自体溶酶体在体外CD8+T细胞的衰老过程中积累,并可能参与诱导衰老细胞的死亡敏化。再生障碍性贫血的主要机制,一种高免疫疾病,T细胞亚群失衡如CD8+T细胞异常活化和功能亢进。因此,自噬在CD8+T细胞中的作用以及某些免疫抑制药物是否诱导细胞自噬死亡以治疗高免疫性疾病成为研究热点。发现再生障碍性贫血患者的乙酰转移酶p300明显升高,并与疾病的严重程度有关。先前的研究已经报道,典型的自噬受mTORC1-p300轴的调节。p300是p300-VPS34轴介导的非经典自噬的关键桥。在CD8+T细胞中存在自噬和乙酰化的缺陷。在免疫抑制药物治疗后,p300的表达也显著降低。我们的发现为理解免疫抑制药物如何影响AA自噬缺乏机制提供了框架,并证明了免疫抑制药物通过p300介导的经典自噬途径和非经典自噬途径负调节CD8+T细胞的功能。
    Macroautophagy, the mainly regulated form of autophagy, maintains the cellular homeostasis and degrades the transported cargoes. It is initiated by the protein kinase complex regulating by two signals pathway Mammalian target of rapamycin complex 1 (mTORC1)-Adenosine 5\' monophosphate activated protein kinase (AMPK)-Unc 51 like kinase 1(ULK1) and ULK1-PI3K- phosphatidylinositol 3-phosphate (PI3P). Currently, autolysosomes are accumulated during the aging process of CD8+T cells in vitro and may participate in inducing death sensitization of senescent cells. The main mechanism of aplastic anemia, a hyperimmune disease, is the T cells subsets imbalance such as CD8+T cells abnormal activation and hyperfunction. Therefore, the role of autophagy in the CD8+T cells and supposed whether some immunosuppress drugs induced the cells autophagic death to treat the hyperimmune diseases were focused. It was decided found that the acetyltransferase p300 obviously increased in the aplastic anemia patients and was related with the severity of disease. Previous studies have reported that canonical autophagy is regulated by the mTORC1-p300 axis. p300 is a critical bridge in the p300-VPS34 axis mediated non-canonical autophagy. There is the deficiency of autophagy and acetylation in the CD8+T cells. The expression of p300 also decreased notably after the immunosuppressive drugs therapy. Our findings provide a framework for understanding how immunosuppressive drugs effect on the AA autophagy deficiency mechanism and proved that immunosuppressive drugs negatively regulated the function of CD8+T cells by p300-mediated canonical autophagy pathway and non-canonical autophagy pathway.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    背景:本研究的目的是探讨错配阴性(MMN)和P300事件相关电位在昏迷和其他意识障碍(DOC)患者6个月时辨别意识状态和预测意识改善的价值。
    方法:我们对42例DOC患者进行了MMN和P300,平均起效时间为40.21±19.43天。这些患有DOC的患者被归类为昏迷,反应迟钝的觉醒综合征(UWS),最小意识减去(MCS-),根据神经行为评估和昏迷恢复量表修订评分,以及最低意识加(MCS)组。主要结果是DOC患者在6个月时意识的改善。我们评估了MMN和P300在6个月时定量预测预后的功效以及MMN和P300参数区分DOC的能力。
    结果:在DOC组中显示出至少一个MMN或P300参数的显着差异,但在MCS-组和MCS+组之间没有(显著性水平:0.05)。MMN和P300振幅在6个月时均显示出理想的预测准确性,曲线下面积(AUC)分别为0.859和0.856。MMN和P300振幅的最佳阈值为2.044和1.095μV。然而,组合的MMN-P300振幅显示出更好的6个月预测准确性(AUC0.934,95%置信区间0.860-1.000),灵敏度为85%,特异性为90.9%。
    结论:MMN和P300可能有助于区分昏迷,UWS,MCS,但不是在MCS患者和MCS+患者之间。MMN振幅,P300振幅,尤其是6个月时的MMN-P300振幅组合可能是DOC患者6个月时意识改善的有趣预测因子。
    背景:中国临床试验注册标识符ChiCTR2400083798。
    BACKGROUND: The objective of this study was to investigate the value of mismatch negativity (MMN) and P300 event-related potentials for discriminating the consciousness state and predicting improvement of consciousness at 6 months in patients with coma and other disorders of consciousness (DOC).
    METHODS: We performed MMN and P300 on 42 patients with DOC with a mean onset time of 40.21 ± 19.43 days. These patients with DOC were categorized into coma, unresponsive wakefulness syndrome (UWS), minimal consciousness minus (MCS-), and minimal consciousness plus (MCS +) groups according to neurobehavioral assessment and the Coma Recovery Scale-Revised score. The primary outcome was the improvement of consciousness at 6 months in patients with DOC. We assessed the efficacy of MMN and P300 in quantitatively predicting the prognosis at 6 months and the capability of MMN and P300 parameters to differentiate between DOC.
    RESULTS: At least one significant difference in either MMN or P300 parameters was displayed among the DOC groups, but not between the MCS- and MCS+ groups (significance level: 0.05). Both MMN and P300 amplitudes showed desirable predictive accuracy at 6 months, with areas under the curve (AUCs) of 0.859 and 0.856, respectively. The optimal thresholds for MMN and P300 amplitudes were 2.044 and 1.095 μV. However, the combined MMN-P300 amplitude showed better 6-month predictive accuracy (AUC 0.934, 95% confidence interval 0.860-1.000), with a sensitivity of 85% and a specificity of 90.9%.
    CONCLUSIONS: MMN and P300 may help discriminate among coma, UWS, and MCS, but not between patients with MCS- and patients with MCS+ . The MMN amplitude, P300 amplitude, and especially combined MMN-P300 amplitude at 6 months may be interesting predictors of consciousness improvement at 6 months in patients with DOC.
    BACKGROUND: Chinese Clinical Trial Registry identifier ChiCTR2400083798.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    目的:虽然基于快速串行视觉呈现(RSVP)的脑机接口(BCI)被广泛用于目标检测,事件相关电位(ERP)模式,以及检测不显眼目标的性能仍然未知。此外,仍然缺乏排除“BCI盲”用户的参与者筛查方法。
    方法:设计了一种RSVP范例,其目标是各种隐藏,尺寸,和位置。在这些条件之间比较了ERPs(例如P300和N2pc)和目标检测准确性。还分析了参与者注意力得分与目标检测准确性之间的关系,以测试注意力水平作为参与者筛选的标准。
    结果:统计分析显示目标隐藏条件和大小对ERP有显著影响。特别是,不显眼的目标的ERP,例如隐蔽的小目标,具有较低的振幅和较长的潜伏期。在一致的情况下,在不明显的条件下检测的准确性明显低于明显的条件。此外,伪装目标的注意力得分与目标检测准确性之间存在显著关联.
    结论:这项研究首次解决了隐藏的多个维度中的ERP特征,尺寸,和位置。结论为ERP解码与目标属性之间的关系提供了见解。此外,注意力得分与检测准确性之间的关联暗示了一种有前景的方法,可以筛选表现良好的参与者以进行伪装目标检测.
    Objective.While brain-computer interface (BCI) based on rapid serial visual presentation (RSVP) is widely used in target detection, patterns of event-related potential (ERP), as well as the performance on detecting inconspicuous targets remain unknown. Moreover, participant-screening methods to excluded \'BCI-blind\' users are still lacking.Approach.A RSVP paradigm was designed with targets of varied concealment, size, and location. ERPs (e.g. P300 and N2pc) and target detection accuracy were compared among these conditions. The relationship between participants\' attention scores and target detection accuracy was also analyzed to test attention level as a criterion for participant screening.Main results.Statistical analysis showed that the conditions of target concealment and size significantly influenced ERP. In particular, ERP for inconspicuous targets, such as concealed and small targets, exhibited lower amplitudes and longer latencies. In consistent, the accuracy of detection in inconspicuous condition was significantly lower than that of conspicuous condition. In addition, a significant association was found between attention scores and target detection accuracy for camouflaged targets.Significance.The study was the first to address ERP features among multiple dimensions of concealment, size, and location. The conclusion provided insights into the relationship between ERP decoding and properties of targets. In addition, the association between attention scores and detection accuracy implied a promising method in screening well-behaved participants for camouflaged target detection.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    足球裁判员的决策是受环境压力和个体情绪等因素影响的典型形式之一。虽然以前的研究已经探讨了个人焦虑和场上压力等常见因素如何影响足球裁判的决定,焦虑影响压力下决策的机制尚不清楚.这项研究根据真实的足球比赛场景制定了点球任务,并招募了76名经验丰富的足球裁判。这些裁判被分成两组,高焦虑和低焦虑,根据他们的焦虑程度,在模拟真实匹配的不同压力环境下执行决策任务。此外,这项研究采用事件相关电位(ERP)技术来比较足球裁判在各种压力环境下面对犯规时焦虑程度不同的大脑信号。发现焦虑程度较高的裁判员在低压环境中表现出较大的P300和N400振幅(p=0.0059,t=2.9437)。然而,在高压条件下,焦虑程度高和焦虑程度低的裁判员之间,P300和N400振幅没有显著差异(p=0.1890,t=1.3411).本研究不仅揭示了裁判员决策过程中焦虑的复杂机制,而且强调了认识和管理裁判员在竞技体育中的心理状态对提高裁判员决策质量的重要性。我们的发现为未来在类似高压环境中减轻焦虑影响和优化决策过程提供了经验基础。
    The decision-making of soccer referees is one of the typical forms influenced by factors such as environmental pressure and individual emotions. While previous studies have explored how common factors like personal anxiety and on-field pressure affect the decisions of soccer referees, the mechanisms by which anxiety influences decision-making under pressure remain unclear. This study developed a penalty task based on real soccer match scenarios and recruited 76 experienced soccer referees. These referees were divided into two groups, high anxiety and low anxiety, based on their anxiety levels, to perform decision-making tasks under different pressure environments simulated to mimic real matches. Additionally, this research employed Event-Related Potential (ERP) technology to compare the brain signals of soccer referees with different levels of anxiety when facing foul play under various pressure environments. It was found that referees with high levels of anxiety displayed larger P300 and N400 amplitudes in a low-pressure environment (p = 0.0059, t = 2.9437). However, no significant differences in P300 and N400 amplitudes were observed between referees with high and low levels of anxiety under high-pressure conditions (p = 0.1890, t = 1.3411). This study not only reveals the complex mechanisms of anxiety in the decision-making process of referees but also emphasizes the importance of understanding and managing the psychological state of referees in competitive sports to improve the quality of their decisions. Our findings provide an empirical basis for future efforts to mitigate the impact of anxiety and optimize the decision-making process in similar high-pressure environments.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    目的:研究三环癸基苯并恶唑(TDB)是否通过p300介导的FOXO乙酰化调节肝癌细胞的增殖和凋亡。
    方法:测序,腺病毒,在人肝癌细胞株SMMC-7721中进行慢病毒转染,并通过Tunel检测细胞凋亡,Hoechst,和流式细胞术。线粒体形态学的TEM,MTT对细胞增殖能力、蛋白质印迹,和PCR检测蛋白水平和mRNA变化。
    结果:测序分析和细胞实验证实,TDB可以促进FOXO3表达的上调。TDB以剂量依赖性方式诱导FOXO3上调,促进了p300和Bim的表达,并增强FOXO3的乙酰化和去磷酸化,从而促进细胞凋亡。p300通过Bim和其他蛋白质促进癌细胞凋亡,而HAT增强FOXO3的磷酸化并抑制细胞凋亡。FOXO3的过表达可以增加外凋亡途径的表达(FasL,TRAIL),内源性凋亡途径(Bim),和蛋白水平的乙酰化,抑制细胞增殖和凋亡能力,而FOXO3沉默或p300突变可部分逆转细胞凋亡。在过表达FOXO3的肿瘤组织中,TDB干预可以进一步增加肿瘤细胞中p53和caspase-9蛋白的表达,导致细胞凋亡过程中线粒体膜完整性的丧失,信号转导过程中细胞质的释放,caspase-9的激活和生长的协同抑制。
    结论:TDB通过激活p300介导的FOXO3乙酰化诱导SMMC-7721细胞增殖抑制和凋亡。
    OBJECTIVE: To investigate whether tricyclic decylbenzoxazole (TDB) regulates liver cancer cell proliferation and apoptosis through p300-mediated FOXO acetylation.
    METHODS: Sequencing, adenovirus, and lentivirus transfection were performed in human liver cancer cell line SMMC-7721 and apoptosis was detected by Tunel, Hoechst, and flow cytometry. TEM for mitochondrial morphology, MTT for cell proliferation ability, Western blot, and PCR were used to detect protein levels and mRNA changes.
    RESULTS: Sequencing analysis and cell experiments confirmed that TDB can promote the up-regulation of FOXO3 expression. TDB induced FOXO3 up-regulation in a dose-dependent manner, promoted the expression of p300 and Bim, and enhanced the acetylation and dephosphorylation of FOXO3, thus promoting apoptosis. p300 promotes apoptosis of cancer cells through Bim and other proteins, while HAT enhances the phosphorylation of FOXO3 and inhibits apoptosis. Overexpression of FOXO3 can increase the expression of exo-apoptotic pathways (FasL, TRAIL), endo-apoptotic pathways (Bim), and acetylation at the protein level and inhibit cell proliferation and apoptotic ability, while FOXO3 silencing or p300 mutation can partially reverse apoptosis. In tumor tissues with overexpression of FOXO3, TDB intervention can further increase the expression of p53 and caspase-9 proteins in tumor cells, resulting in loss of mitochondrial membrane integrity during apoptosis, the release of cytoplasm during signal transduction, activation of caspase-9 and synergistic inhibition of growth.
    CONCLUSIONS: TDB induces proliferation inhibition and promotes apoptosis of SMMC-7721 cells by activating p300-mediated FOXO3 acetylation.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    甲基苯丙胺(MA)是一种神经药物,滥用时对整体大脑认知功能有害。基于MA的这一属性,人可分为滥用MA的人和健康人。然而,迄今为止,很少有研究基于神经活动来自动检测MA滥用者。出于这个原因,这项研究的目的是调查MA滥用者与健康人之间神经活动的差异,并据此区分MA滥用者。首先,我们进行了事件相关电位(ERP)分析,以确定P300的时间范围.然后,提取P300分量的小波系数作为主要特征,以及所选P300范围内的时域和频域特征进行分类。要优化功能集,F_score用于去除低于平均分数的特征。最后,进行双向长短期记忆(BiLSTM)网络分类。实验结果表明,BiLSTM的检测准确率可达83.85%。总之,MA滥用者的EEG信号的P300分量与正常人不同。基于这种差异,本研究提出了预防和诊断MA滥用的新方法。
    Methamphetamine (MA) is a neurological drug, which is harmful to the overall brain cognitive function when abused. Based on this property of MA, people can be divided into those with MA abuse and healthy people. However, few studies to date have investigated automatic detection of MA abusers based on the neural activity. For this reason, the purpose of this research was to investigate the difference in the neural activity between MA abusers and healthy persons and accordingly discriminate MA abusers. First, we performed event-related potential (ERP) analysis to determine the time range of P300. Then, the wavelet coefficients of the P300 component were extracted as the main features, along with the time and frequency domain features within the selected P300 range to classify. To optimize the feature set, F_score was used to remove features below the average score. Finally, a Bidirectional Long Short-term Memory (BiLSTM) network was performed for classification. The experimental result showed that the detection accuracy of BiLSTM could reach 83.85%. In conclusion, the P300 component of EEG signals of MA abusers is different from that in normal persons. Based on this difference, this study proposes a novel way for the prevention and diagnosis of MA abuse.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

    求助全文

  • 文章类型: Journal Article
    背景:E1A相关蛋白p300(p300)由于其在各种癌症中促进致癌信号通路中的关键作用,已成为癌症治疗的有希望的靶标。包括前列腺癌.这种需要在前列腺癌中尤其显著。虽然雄激素剥夺疗法(ADT)在前列腺癌中显示出有希望的疗效,它的长期使用最终会导致去势抵抗前列腺癌(CRPC)和神经内分泌前列腺癌(NEPC)的发展。值得注意的是,p300已被确定为雄激素受体(AR)的重要共激活剂,强调其在前列腺癌进展中的意义。此外,最近的研究表明p300参与与NEPC相关的AR非依赖性癌基因。因此,阻断p300可能成为应对CRPC和NEPC带来的挑战的有效治疗策略.
    方法:我们采用AI辅助设计开发了一种靶向p300的基于肽的PROTAC(蛋白水解靶向嵌合体)药物,利用纳米硒作为肽药物递送系统,在体外和体内有效降解p300。
    结果:我们的p300靶向肽PROTAC药物在两种CRPC中均表现出有效的p300降解和癌细胞杀伤能力,AR-阴性,NEPC细胞。这项研究证明了p300靶向药物在NEPC细胞中的功效。在AR阳性和AR阴性小鼠模型中,p300PROTAC药物显示出有效的p300降解和肿瘤抑制。
    结论:针对p300的肽PROTAC药物的设计是可行的,代表了CRPC的有效治疗策略,AR阴性前列腺癌,NEPC。
    背景:资金详情见“致谢”部分。
    BACKGROUND: The E1A-associated protein p300 (p300) has emerged as a promising target for cancer therapy due to its crucial role in promoting oncogenic signaling pathways in various cancers, including prostate cancer. This need is particularly significant in prostate cancer. While androgen deprivation therapy (ADT) has demonstrated promising efficacy in prostate cancer, its long-term use can eventually lead to the development of castration-resistant prostate cancer (CRPC) and neuroendocrine prostate cancer (NEPC). Notably, p300 has been identified as an important co-activator of the androgen receptor (AR), highlighting its significance in prostate cancer progression. Moreover, recent studies have revealed the involvement of p300 in AR-independent oncogenes associated with NEPC. Therefore, the blockade of p300 may emerge as an effective therapeutic strategy to address the challenges posed by both CRPC and NEPC.
    METHODS: We employed AI-assisted design to develop a peptide-based PROTAC (proteolysis-targeting chimera) drug that targets p300, effectively degrading p300 in vitro and in vivo utilizing nano-selenium as a peptide drug delivery system.
    RESULTS: Our p300-targeting peptide PROTAC drug demonstrated effective p300 degradation and cancer cell-killing capabilities in both CRPC, AR-negative, and NEPC cells. This study demonstrated the efficacy of a p300-targeting drug in NEPC cells. In both AR-positive and AR-negative mouse models, the p300 PROTAC drug showed potent p300 degradation and tumor suppression.
    CONCLUSIONS: The design of peptide PROTAC drug targeting p300 is feasible and represents an efficient therapeutic strategy for CRPC, AR-negative prostate cancer, and NEPC.
    BACKGROUND: The funding details can be found in the Acknowledgements section.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

公众号