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FOXO3a 的表达作为创伤性脑损伤法医诊断工具的研究:免疫组织化学研究。

The Expression of FOXO3a as a Forensic Diagnostic Tool in Cases of Traumatic Brain Injury: An Immunohistochemical Study.

机构信息

Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, Section of Legal Medicine, University of Pisa, 56126 Pisa, Italy.

Department of Anatomical, Histological, Forensic and Orthopedical Sciences, Sapienza University of Rome, Viale Regina Elena 336, 00161 Rome, Italy.

出版信息

Int J Mol Sci. 2023 Jan 30;24(3):2584. doi: 10.3390/ijms24032584.

Abstract

Traumatic brain injury (TBI) is one of the most well-known causes of neurological impairment and disability in the world. The Forkhead Box class O (FOXO) 3a is a transcription factor that is involved in different molecular processes, such as cell apoptosis regulation, neuroinflammation and the response to oxidative stress. This study is the first to evaluate the post-mortem immunohistochemical (IHC) positivity of FOXO3a expression in human cases of TBI deaths. The autopsy databases of the Legal Medicine and Forensic Institutes of the "Sapienza" University of Roma and the University of Pisa were retrospectively reviewed. After analyzing autopsy reports, 15 cases of TBI deaths were selected as the study group, while the other 15 cases were chosen among non-traumatic brain deaths as the control group. Decomposed bodies and those with initial signs of putrefaction were excluded. Routine histopathological studies were performed using hematoxylin-eosin (H&E) staining. Furthermore, an IHC investigation on cerebral samples was performed. To evaluate FOXO3a expression, anti-FOXO3a antibodies (GTX100277) were utilized. Concerning the IHC analysis, all 15 samples of TBI cases showed positivity for FOXO3a in the cerebral parenchyma. All control cerebral specimens showed FOXO3a negativity. In addition, the longer the survival time, the greater the positivity to the reaction with FOXO3a was. This study shows the important role of FOXO3a in neuronal autophagy and apoptosis regulation and suggests FOXO3a as a possible potential pharmacological target.

摘要

创伤性脑损伤(TBI)是世界上最著名的神经功能障碍和残疾原因之一。叉头框转录因子 O 亚家族 3a(FOXO3a)是一种参与不同分子过程的转录因子,如细胞凋亡调节、神经炎症和对氧化应激的反应。这项研究首次评估了 FOXO3a 在 TBI 死亡的人体病例中的免疫组织化学(IHC)阳性表达。回顾性地审查了罗马“萨皮恩扎”大学和比萨大学的法医学和法医研究所的法医数据库。在分析尸检报告后,选择 15 例 TBI 死亡作为研究组,而另 15 例非创伤性脑死亡作为对照组。排除了分解尸体和有最初腐败迹象的尸体。使用苏木精-伊红(H&E)染色进行常规组织病理学研究。此外,对脑样本进行了 IHC 研究。为了评估 FOXO3a 的表达,使用了抗 FOXO3a 抗体(GTX100277)。关于 IHC 分析,TBI 病例的所有 15 个样本在脑实质中均显示 FOXO3a 阳性。所有对照脑标本均显示 FOXO3a 阴性。此外,存活时间越长,与 FOXO3a 反应的阳性率越高。这项研究表明 FOXO3a 在神经元自噬和凋亡调节中的重要作用,并提示 FOXO3a 可能是一个潜在的药物靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9c4/9916452/bc628c09f3f1/ijms-24-02584-g001.jpg

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