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Application of RNA sequencing to cause-of-death investigation: A pilot study RNA测序在死因调查中的应用:一项初步研究。
IF 1.4 4区 医学 Q3 MEDICINE, LEGAL Pub Date : 2025-12-24 DOI: 10.1016/j.legalmed.2025.102772
Naoki Nakao , Takahiro Harada , Kazuhiro Murata , Takafumi Nagao , Akira Namera , Masataka Nagao

Background

Determining the cause of death in forensic autopsies is often challenging, especially when clinical information is limited. RNA analysis has been explored for this purpose, but conventional qRT-PCR approaches are restricted to preselected targets. RNA sequencing (RNA-seq) enables comprehensive transcriptome profiling and may reduce observer bias, yet its application in forensic cause-of-death investigation remains limited.

Methods

We applied RNA-seq to two forensic cases: one involving fatal insulin overdose and another involving anaphylactic shock. Gene expression profiles were compared with control cases using relative log expression normalization.

Results

In the insulin overdose case, transcripts in the insulin receptor substrate–PI3K–PDK1/2 pathway and related metabolic cascades were upregulated. In the anaphylaxis case, genes downstream of FcεRI signaling (VAV, IL-3, IL-4, GM-CSF, p38, cPLA2) and T cell receptor–associated molecules showed increased expression.

Conclusion

This proof-of-concept pilot study suggests that RNA-seq can capture molecular signatures associated with specific causes of death. These findings indicate the potential of transcriptomic profiling as a complementary tool in forensic diagnostics when conventional methods are inconclusive.
背景:在法医尸检中确定死因往往具有挑战性,特别是在临床信息有限的情况下。RNA分析已经为此目的进行了探索,但传统的qRT-PCR方法仅限于预先选择的目标。RNA测序(RNA-seq)能够实现全面的转录组分析,并可能减少观察者的偏见,但其在法医死因调查中的应用仍然有限。方法:应用RNA-seq技术对两例法医学病例进行分析,一例为致死性胰岛素过量,另一例为过敏性休克。基因表达谱采用相对对数表达归一化进行比较。结果:在胰岛素过量的情况下,胰岛素受体底物- pi3k - pdk1 /2通路及相关代谢级联的转录本上调。在过敏反应病例中,FcεRI信号下游基因(VAV、IL-3、IL-4、GM-CSF、p38、cPLA2)和T细胞受体相关分子表达增加。结论:这项概念验证的初步研究表明,RNA-seq可以捕获与特定死亡原因相关的分子特征。这些发现表明,转录组分析的潜力,作为一个补充工具,在法医诊断时,传统的方法是不确定的。
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引用次数: 0
Postmortem computed tomography reconstructed a lethal orbitocranial-penetrating injury: A case report 死后电脑断层重建致命的眶颅穿透伤:1例报告
IF 1.4 4区 医学 Q3 MEDICINE, LEGAL Pub Date : 2025-12-24 DOI: 10.1016/j.legalmed.2025.102768
Shigeki Tsuneya , Go Inokuchi , Maiko Yoshida , Yohsuke Makino , Masatoshi Kojima , Suguru Torimitsu , Fumiko Chiba , Yumi Hoshioka , Yukiko Uemura , Hirotaro Iwase
In forensic pathology, identifying weapons and injury mechanisms is often necessary. Computed tomography (CT) can be used to detect intracerebral hemorrhage due to penetrating injury; however, reports on CT-based estimation of weapons and injury mechanisms are limited. In this case study, we aimed to reconstruct a case using postmortem CT (PMCT) images and an object file of the suspected knife.
A male in his 30 s died following arrival at the hospital after a fight. PMCT and autopsy revealed that an orbitocranial-penetrating injury severed the right anterior cerebral artery and inflicted lethal subarachnoid hemorrhage. Both PMCT and targeted PMCT angiography (PMCTA) depicted bone fractures and a wound in the brain as hemorrhage or contrast leakage.
Herein, the suspected knife was converted into an object file (.stl) and fitted to the PMCTA images on a workstation. The results showed that the knife image was fitted with the bone fractures and intracerebral hemorrhage to the fullest extent, although some minor discrepancies persisted.
Notably, this is the first report of CT-based precise reconstruction of transcranial penetration. Altogether, the findings highlight the importance of radiological modalities, including CT, for estimating weapon and injury mechanisms in forensic pathology.
在法医病理学中,识别武器和伤害机制往往是必要的。计算机断层扫描(CT)可用于检测穿透性损伤引起的脑出血;然而,关于基于ct的武器和伤害机制估计的报告有限。在这个案例研究中,我们的目的是利用死后CT (PMCT)图像和疑似刀具的目标文件来重建一个病例。一名30多岁的男性在一场打斗后被送往医院后死亡。PMCT和尸检显示眶颅穿透伤切断了右大脑前动脉并造成了致命的蛛网膜下腔出血。PMCT和靶向PMCT血管造影(PMCTA)都将骨折和脑内伤口描述为出血或造影剂泄漏。在这里,可疑的刀被转换成一个目标文件(.stl),并拟合到工作站的PMCTA图像。结果表明,刀形图像与骨折和脑出血的吻合程度最高,但仍存在轻微差异。值得注意的是,这是首次报道基于ct的经颅穿透精确重建。总之,研究结果强调了包括CT在内的放射学模式在法医病理学中评估武器和损伤机制的重要性。
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引用次数: 0
Hypoxia-induced LONP1 overexpression and mtDNA damage may serve as biomarkers for death from mechanical asphyxia 缺氧诱导的LONP1过表达和mtDNA损伤可能是机械性窒息死亡的生物标志物
IF 1.4 4区 医学 Q3 MEDICINE, LEGAL Pub Date : 2025-12-24 DOI: 10.1016/j.legalmed.2025.102769
Tianpu Wu , Heng Zhang , Dongchuan Zhang , Yikai Hu , Lu Tian , Wencan Li , Fu Zhang , Bi Xiao , Jianlong Ma , Yi Shi , Yue Chen , Hanfeng Jiang , Xinbiao Liao , Kaijun Ma , Long Chen
Due to the absence of reliable signs, the authentication of death from mechanical asphyxia (DMA), commonly seen in forensic pathology, can be rather challenging especially when the criminal case is obscure. Lon protease-1 (LONP1) is an ATP-dependent serine protease located in mitochondria that participates in maintaining the integrity of the mitochondrial genome and regulating mitochondrial DNA (mtDNA) replication. In this research, cerebral tissues of corpses with different causes of death were collected to compare the expression of LONP1 and the changes of mtDNA to see the authenticating value of these markers. It was found that LONP1 was up-regulated in the cerebral tissue of DMA corpses while the integrity of mtDNA was destroyed conditionally. In neuroblastoma cancer cell line SH-SY5Y, LONP1 would suppress the repair and replication of mtDNA under hypoxia and partly lead to mitochondrial damage. In general, LONP1 is responsible for longer duration of hypoxic mtDNA damage and the repression of the replication of mtDNA. LONP1 and mtDNA integrity can both serve as biomarkers for DMA.
由于缺乏可靠的迹象,法医病理学中常见的机械性窒息(DMA)死亡的鉴定可能相当具有挑战性,特别是在刑事案件模糊不清的情况下。LONP1是一种atp依赖性丝氨酸蛋白酶,位于线粒体中,参与维持线粒体基因组的完整性和调节线粒体DNA (mtDNA)的复制。本研究收集不同死因尸体的脑组织,比较LONP1的表达和mtDNA的变化,看看这些标记物的鉴定价值。我们发现,在DMA尸体脑组织中,LONP1表达上调,mtDNA的完整性被有条件地破坏。在神经母细胞瘤细胞系SH-SY5Y中,LONP1会在缺氧条件下抑制mtDNA的修复和复制,部分导致线粒体损伤。一般来说,LONP1负责较长时间的缺氧mtDNA损伤和mtDNA复制的抑制。LONP1和mtDNA完整性都可以作为DMA的生物标志物。
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引用次数: 0
Mixed planned and unplanned complex suicide by cut-throat and poisoning in a hemiplegic person − case report 有计划和无计划的混合复杂自杀由割伤和中毒在一个偏瘫的人的案件报告。
IF 1.4 4区 医学 Q3 MEDICINE, LEGAL Pub Date : 2025-12-24 DOI: 10.1016/j.legalmed.2025.102771
Hasan A. Abder-Rahman , Imad M. Al-Abdallat , Lamia K. Alsenaidi , Hasan K. Alhawwari , Safaa Z. Mahfoz , Nadia N. Jendli , Nada M. Al-Masad , Abed-Alraheem Ali
Cutthroat cases are considered rare, especially suicidal cutthroat which is scarce. This case study presents a mix between planned and unplanned complex suicidal cutthroat that complicated the decision of the manner of death. A 60 year old male with a left sided hemiplegia was found dead with deep cutthroat and had incised wounds on both wrists with a bucket filled with blood next to him, the toxicology test revealed the presence of permethrin insecticide in the stomach. This paper shows the difficulty in deciding whether the case is a planned or unplanned complex suicide and some cases might mix between the two. However, both planned and unplanned complex suicide may point to homicidal act, which is why it is recommended to record these cases especially since complex suicide is rare and there are different methods used that are unfamiliar to us. The bizarre factors that raise suspicion in our case are the hemiplegia, the age, the use of pesticides, the cut of both wrists, and the fatal cut-throat. We didn’t find any reported cases of complex suicide by poisoning with pesticides or successful cutthroat.
割喉的病例被认为是罕见的,尤其是自杀式的割喉更是罕见。这个案例研究提出了一个混合计划和非计划的复杂自杀杀手,复杂的死亡方式的决定。一名60岁男性左偏瘫患者被发现死于深喉,双手腕有切口伤口,旁边有一桶血,毒理学测试显示胃中有氯菊酯杀虫剂。这篇论文展示了在判定一个案件是有计划的还是没有计划的复杂自杀时的困难,并且一些案件可能混合了这两种情况。然而,有计划的和计划外的复杂自杀都可能指向杀人行为,这就是为什么建议记录这些案件的原因,特别是因为复杂自杀是罕见的,而且使用的方法不同,我们不熟悉。在我们的案件中引起怀疑的奇怪因素是偏瘫,年龄,农药的使用,两个手腕的割伤,以及致命的割断喉咙。我们没有发现任何报告的复杂的农药中毒自杀案例或成功的杀手。
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引用次数: 0
Application of anatomical and histological features of testis to age estimation 睾丸解剖组织学特征在年龄估计中的应用
IF 1.4 4区 医学 Q3 MEDICINE, LEGAL Pub Date : 2025-12-24 DOI: 10.1016/j.legalmed.2025.102767
Takato Murai , Masaki Inoue , Kenichi Mukaisho , Mami Nakamura , Kazuki Takaoka , Masahito Hitosugi
In forensic practice, when parts of an unidentified human body are found, age estimation with limited materials is required. This study investigated age-related anatomical and histological changes in testes to evaluate their applicability for forensic age estimation. Testicular samples from 228 male autopsy cases (aged 0–96 years) were analyzed. The Johnsen score, testicular weight, basement membrane thickness, number of seminiferous tubules per field, and percentage of hyalinized tubules were examined. Basement membrane thickness showed a strong positive correlation with age across all subjects (r = 0.733). In individuals under 20 years, testicular weight was positively correlated with age (r = 0.89), while the number of seminiferous tubules negatively correlated (r =  − 0.90). In those aged ≥ 20 years, Johnsen score, testicular weight, and hyalinization rate showed significant age-related differences between groups. Receiver operating characteristic curve analysis identified cutoff values for age discrimination: hyalinization rate of ≥ 9.0 % for ≥ 60 years (sensitivity 69.7 %, specificity 89.5 %), and testicular weight of ≤ 10.1 g for ≥ 80 years (sensitivity 85.7 %, specificity 73.3 %). Basement membrane thickness, testicular weight, and seminiferous tubule count are useful indicators for forensic age estimation under 20 years of age; on the other hand, basement membrane thickness, testicular weight, and hyalinization rate are more informative in individuals aged ≥ 20 years. These findings suggest the potential contribution of these indicators to forensic age estimation, while further studies are needed to validate their practical applicability.
在法医实践中,当发现身份不明的人体部分时,需要用有限的材料估计年龄。本研究调查了与年龄相关的睾丸解剖和组织学变化,以评估其在法医年龄估计中的适用性。本文分析了228例男性尸检病例(年龄0 ~ 96岁)的睾丸样本。检查约翰森评分、睾丸重量、基底膜厚度、每野精小管数量和玻璃化小管百分比。基底膜厚度与年龄呈显著正相关(r = 0.733)。在20岁以下的个体中,睾丸重量与年龄呈正相关(r = 0.89),精管数量与年龄呈负相关(r = - 0.90)。在年龄≥20岁的患者中,Johnsen评分、睾丸重量和透明化率在组间存在显著的年龄相关差异。受试者工作特征曲线分析确定了年龄歧视的临界值:≥60岁时透明化率≥9.0%(敏感性69.7%,特异性89.5%),≥80岁时睾丸重量≤10.1 g(敏感性85.7%,特异性73.3%)。基底膜厚度、睾丸重量和精管计数是20岁以下法医年龄估计的有用指标;另一方面,基底膜厚度、睾丸重量和透明化率在年龄≥20岁的个体中更有价值。这些发现表明这些指标对法医年龄估计的潜在贡献,但需要进一步研究来验证其实际适用性。
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引用次数: 0
The stability of novel synthetic cannabinoids in blood samples in different storage conditions 新型合成大麻素在血液样品中不同贮存条件下的稳定性
IF 1.4 4区 医学 Q3 MEDICINE, LEGAL Pub Date : 2025-12-18 DOI: 10.1016/j.legalmed.2025.102762
Murat Akbaba , Oğuz Özdemir , Aysun Baransel Isır
The synthetic cannabinoids dominated the market with a detrimental effect on society. Determining the stability of synthetic cannabinoids (SCs) in samples is crucial for accurate detection and quantification in drug testing. Since designer narcotics emerge rather quickly, a new generation of cannabinoid-associated compounds also appears rapidly. Thus, it is crucial to identify, detect, and determine the confidence of drug testing to provide fairer judgments. In this study, we aimed to determine optimal storage conditions to prevent degradation and preserve the samples of four new-generation SCs (MDMB-4en-PINACA, 4-Fluoro MDMB-BICA, 5F-MDMB-PICA, and 5F-MDMB-PINACA) in blood samples due to the lack of available information on the stability. Blood samples were collected from 20 healthy volunteers, treated with cannabinoids at concentrations of 10 and 50 ng/mL, and stored at temperatures of room temperature, +4°C, and −20 °C over 35 days. Our findings revealed a gradual decline in cannabinoid concentrations over time, with 5F-MDMB-PINACA exhibiting the highest degradation rate. Storage temperature significantly influenced degradation rates, with the most rapid reduction observed at room temperature and the slowest degradation at −20 °C. Our findings are a reference study providing valuable insights into the preservation of the samples for the testing of the most prevalent SCs of the present day.
合成大麻素主导了市场,对社会产生了有害影响。确定样品中合成大麻素(SCs)的稳定性对于药物检测中的准确检测和定量至关重要。由于设计麻醉剂出现得相当快,新一代大麻素相关化合物也迅速出现。因此,识别、检测和确定药物检测的可信度,以提供更公平的判断是至关重要的。在本研究中,由于缺乏关于稳定性的可用信息,我们旨在确定最佳储存条件,以防止血液样品中四种新一代SCs (MDMB-4en-PINACA, 4-Fluoro MDMB-BICA, 5F-MDMB-PICA和5F-MDMB-PINACA)的降解和保存。收集20名健康志愿者的血液样本,用浓度为10和50 ng/mL的大麻素处理,并在室温、+4°C和- 20°C的温度下保存35天。我们的研究结果显示,随着时间的推移,大麻素浓度逐渐下降,5F-MDMB-PINACA的降解率最高。储存温度对降解率有显著影响,在室温下降解最快,在- 20℃时降解最慢。我们的研究结果是一项参考研究,为当今最普遍的sc测试的样品保存提供了有价值的见解。
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引用次数: 0
Artificial intelligence in healthcare: Proposal for a new medico-legal methodology in medical liability 医疗保健中的人工智能:医疗责任中新的医学-法律方法论的建议。
IF 1.4 4区 医学 Q3 MEDICINE, LEGAL Pub Date : 2025-12-11 DOI: 10.1016/j.legalmed.2025.102764
Rossana Cecchi , Francesco Calabrò , Jessika Camatti , Anna Laura Santunione , Michela Sperti , Eric Adriano Zizzi , Marco Agostino Deriu
The rapid integration of Artificial Intelligence (AI) into healthcare promises significant benefits but also raises unprecedented ethical, clinical, and legal challenges. Current medico-legal frameworks, primarily designed for human decision-making, are often inadequate to address liability issues arising from algorithmic errors or opaque “black box” models. This paper introduces a novel medico-legal methodology that combines proactive and reactive approaches to risk assessment, originally developed within European forensic medicine, and adapts it to the context of AI in healthcare. By systematically analyzing data collection, dataset validation, error identification, and causal reconstruction, the proposed framework provides a structured path for evaluating medical liability when AI systems are involved. This dual approach not only supports clinicians, developers, and policymakers in preventing harm, but also establishes a robust forensic tool for liability assessment. The methodology offers a step toward internationally applicable standards for addressing the medico-legal implications of AI in medicine.
人工智能(AI)与医疗保健的快速融合带来了巨大的好处,但也带来了前所未有的伦理、临床和法律挑战。目前的医疗法律框架主要是为人类决策而设计的,往往不足以解决由算法错误或不透明的“黑箱”模型引起的责任问题。本文介绍了一种新的医学法律方法,该方法结合了欧洲法医学中最初开发的主动和被动风险评估方法,并使其适应医疗保健中的人工智能背景。通过系统地分析数据收集、数据集验证、错误识别和因果重构,该框架为涉及人工智能系统时的医疗责任评估提供了结构化路径。这种双重方法不仅支持临床医生、开发人员和政策制定者预防伤害,而且还为责任评估建立了强大的法医工具。该方法为解决人工智能在医学中的医学法律影响的国际适用标准迈出了一步。
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引用次数: 0
Three deaths, one diagnosis: Forensic perspectives on giant ovarian tumors 三个死亡,一个诊断:巨大卵巢肿瘤的法医视角
IF 1.4 4区 医学 Q3 MEDICINE, LEGAL Pub Date : 2025-12-11 DOI: 10.1016/j.legalmed.2025.102765
Veljko Milošević, Bojana Radnić, Tijana Petrović, Milenko Bogdanović, Tatjana Atanasijević, Irina Banjanin
When ovarian tumors (OTs) reach a size of more than 10 cm in diameter, they are classified as a giant ovarian tumor (GOTs). Thanks to modern diagnostics and treatment, GOTs have become rare autopsy findings and are typically associated with cases of severe neglect. Here, we present a series of three autopsy cases involving GOTs. The first case involved a 59-year-old woman with a cystic GOT containing 48 L of fluid. The second case was a 67-year-old woman with multiple cystic and solid GOTs. The third case concerned a 57-year-old woman with a giant, primarily solid OT, accompanied by bilateral pleural effusion, suggestive of Meigs syndrome. All three women were found in a state of advanced putrefaction, which limited the ability to determine the exact cause of death. Although GOTs are rarely fatal, they can lead to death through various complex pathophysiological mechanisms. These include spontaneous haemorrhage, torsion, infection, and tumor rupture resulting in acute peritonitis – conditions that represent surgical emergencies. Additionally, increased intra-abdominal pressure can elevate the diaphragm, impairing the function of the respiratory, cardiovascular, digestive, and urinary systems. Despite the limitations posed by postmortem decomposition, this case series provides an opportunity to summarize and discuss potential mechanisms of death associated with large intra-abdominal masses such as GOTs.
当卵巢肿瘤(OTs)的直径超过10cm时,它们被归类为巨大卵巢肿瘤(GOTs)。由于现代诊断和治疗,got已成为罕见的尸检结果,通常与严重忽视的病例有关。在这里,我们提出了一系列涉及got的三个尸检病例。第一个病例涉及一名59岁的妇女,她患有囊肿性GOT,其中含有48升液体。第二个病例是一名67岁的女性,患有多发性囊性和实性got。第三例患者为一名57岁女性,伴有巨大实性OT,伴双侧胸腔积液,提示Meigs综合征。这三名妇女被发现时都处于严重腐烂状态,这限制了确定确切死因的能力。虽然got很少致死性,但其可通过多种复杂的病理生理机制导致死亡。这些包括自发性出血、扭转、感染和导致急性腹膜炎的肿瘤破裂——这些都是外科紧急情况。此外,腹内压升高可使横膈膜升高,损害呼吸、心血管、消化和泌尿系统的功能。尽管死后分解存在局限性,但本病例系列提供了一个总结和讨论与腹腔内大型肿块(如got)相关的潜在死亡机制的机会。
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引用次数: 0
Mechanism of postmortem drastic increase of blood myoglobin concentration: its permeability through vascular wall 死后血肌红蛋白浓度急剧升高的机制:其通过血管壁的渗透性
IF 1.4 4区 医学 Q3 MEDICINE, LEGAL Pub Date : 2025-12-11 DOI: 10.1016/j.legalmed.2025.102763
Sella Takei , Masanobu Miura , Takehiko Murase , Hiroshi Kinoshita , Satoru Miyaishi
We provide the first direct experimental evidence that myoglobin (Mb) diffuses through vascular walls and enters the blood after death. Postmortem Mb concentration in the blood increases rapidly; however, up to this date, no one has reported the responsible mechanism. We hypothesized the direct diffusion of Mb from skeletal muscle into the blood through the vessel wall is causing this concentration change, and proved this morphologically and biochemically, through experiments using animal samples. Firstly, IHC Mb staining of the artery which was directly contacted with skeletal muscle on the adventitia, revealed that the Mb diffuses from adventitia to the intima with time. Then, Mb quantification using ELISA showed Mb exudes through vascular walls into the vessel lumen. For this experiment, a diffusion model was established by sandwiching the artery between gelatin discs with or without Mb. The Mb concentration increased in a time-dependent manner, with approximately 16 % of Mb in its source exuding into the lumen within 5 days. This rate increased significantly when vein was used instead of aorta. These findings clarify a fundamental mechanism of postmortem biochemical redistribution and may enhance the reliability of interpreting postmortem blood protein levels in forensic practice.
我们提供了第一个直接的实验证据,证明肌红蛋白(Mb)在死亡后通过血管壁扩散并进入血液。死后血中Mb浓度迅速升高;然而,到目前为止,还没有人报告负责机制。我们假设Mb从骨骼肌通过血管壁直接扩散到血液中是导致这种浓度变化的原因,并通过动物样本的实验从形态学和生物化学上证明了这一点。首先,对外膜上与骨骼肌直接接触的动脉进行免疫组化Mb染色,发现Mb随时间从外膜向内膜扩散。酶联免疫吸附测定结果显示,Mb可通过血管壁进入血管腔。在本实验中,通过将动脉夹在含有或不含Mb的明胶盘之间建立扩散模型。Mb浓度随时间增加,其来源中约有16%的Mb在5天内渗出到管腔。当使用静脉而不是主动脉时,这一比率显著增加。这些发现阐明了死后生物化学再分配的基本机制,并可能提高法医实践中解释死后血液蛋白水平的可靠性。
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引用次数: 0
MARK4 as a novel biomarker of acute myocardial ischemia-induced sudden cardiac death MARK4作为急性心肌缺血心源性猝死的新生物标志物
IF 1.4 4区 医学 Q3 MEDICINE, LEGAL Pub Date : 2025-12-10 DOI: 10.1016/j.legalmed.2025.102766
Xing Ye , Guanghui Hong , Runting Dou , Zhimin Wang , Zijie Lin , Yu Shao , Jiajia Yang , Junyi Lin , Yiwen Shen
Postmortem diagnosis of acute myocardial ischemia (AMI), especially early myocardial ischemia (EMI; ischemic insults occurring within minutes to a few hours, <6h), remains challenging due to nonspecific morphological changes. Microtubules affinity regulated kinase 4 (MARK4) is a serine/threonine kinase involved in the regulation of microtubule dynamics through the phosphorylation of microtubule-associated proteins. Emerging research has highlighted the significant involvement of MARK4 in cardiovascular diseases. The aim of this study is to evaluate whether MARK4 can serve as a postmortem diagnostic marker for sudden cardiac death (SCD) resulting from AMI. Using a mouse AMI model, hypoxia-treated AC16 cardiomyocytes, and human autopsy material (36 SCD hearts: 18 EMI, 18 myocardial infarction (MI) and 20 noncardiac controls), MARK4 expression was assessed by immunohistochemistry and western blotting, and diagnostic performance was examined by receiver operating characteristic (ROC) analysis. MARK4 expression increased with ischemia/hypoxia in vivo and in vitro, peaking at 3 h. Human myocardial MARK4 was significantly elevated in EMI and MI versus controls, independently of age and postmortem interval. ROC analysis discriminated EMI from controls with an AUC of 0.8028 for MARK4, outperforming cardiac troponin I (cTnI; AUC = 0.7556), and combining both markers improved diagnostic accuracy. In hypoxic AC16 cells, MARK4 overexpression increased cytochrome c and phosphorylated Drp1, suggesting a role in ischemia-related mitochondrial dysfunction. These results indicate MARK4 is a promising postmortem biomarker for AMI-induced SCD.
急性心肌缺血(AMI)的死后诊断,特别是早期心肌缺血(EMI;在几分钟到几小时内发生的缺血损伤,<6h),由于非特异性形态学改变,仍然具有挑战性。微管亲和调节激酶4 (MARK4)是一种丝氨酸/苏氨酸激酶,通过微管相关蛋白的磷酸化参与微管动力学的调节。新兴研究强调了MARK4在心血管疾病中的重要作用。本研究的目的是评估MARK4是否可以作为AMI引起的心源性猝死(SCD)的死后诊断标志物。使用小鼠AMI模型、缺氧处理的AC16心肌细胞和人体尸检材料(36个SCD心脏:18个EMI, 18个心肌梗死(MI)和20个非心脏对照),通过免疫组织化学和western blotting评估MARK4表达,并通过受试者工作特征(ROC)分析检查诊断性能。MARK4的表达随体内和体外缺血/缺氧而增加,在3小时达到峰值。与对照组相比,EMI和MI患者心肌MARK4显著升高,与年龄和死后间隔无关。ROC分析将EMI与对照组区分开来,MARK4的AUC为0.8028,优于心肌肌钙蛋白I (cTnI; AUC = 0.7556),结合这两种标志物可提高诊断准确性。在缺氧的AC16细胞中,MARK4过表达增加细胞色素c和磷酸化Drp1,提示在缺血相关的线粒体功能障碍中起作用。这些结果表明,MARK4是ami诱导的SCD的一个有希望的死后生物标志物。
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引用次数: 0
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