Identification of TRAF2, CAMK2G, and TIMM17A as biomarkers distinguishing mechanical asphyxia from sudden cardiac death base on 4D-DIA Proteomics: A pilot study

IF 3.1 3区 医学 Q2 CHEMISTRY, ANALYTICAL Journal of pharmaceutical and biomedical analysis Pub Date : 2025-02-03 DOI:10.1016/j.jpba.2025.116730
Yuebing Huang, Hai Qiu, Wen Chen, Zilin Meng, Yu Cai, Dongfang Qiao, Xia Yue
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Abstract

In the context of forensic medicine, the differential diagnosis between mechanical asphyxia and sudden cardiac death is very important regarding the establishment of the cause of death. Traditional autopsy findings have generally been very nonspecific; accordingly, highlighting the need for more specific molecular biomarkers. This study employed four-dimensional data-independent acquisition (4D-DIA) proteomics technology, in combination with both animal models and human samples, to conduct a comprehensive protein expression analysis of cardiac tissues, identifying 7557 proteins, among which 142 shared differentially expressed proteins (DEPS) were screened out. Based on the protein interaction network and through rigorous screening, this study identified three proteins, namely TNF receptor-associated factor 2 (TRAF2), Calcium/calmodulin-dependent protein kinase II gamma (CAMK2G), and translocase of inner mitochondrial membrane 17 homolog A (TIMM17A), as biomarkers for differentiating mechanical asphyxia from sudden cardiac death. Further verification using Western Blot (WB) and immunohistochemistry (IHC) proved the differential expression of these biomarkers in both animal and human samples. These findings, besides deepening the molecular understanding of the pathophysiological differences between sudden cardiac death and mechanical asphyxia, also provided new biomarkers for forensic applications that could enable the improvement of accuracy and reliability in the determination of the cause of death.
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来源期刊
CiteScore
6.70
自引率
5.90%
发文量
588
审稿时长
37 days
期刊介绍: This journal is an international medium directed towards the needs of academic, clinical, government and industrial analysis by publishing original research reports and critical reviews on pharmaceutical and biomedical analysis. It covers the interdisciplinary aspects of analysis in the pharmaceutical, biomedical and clinical sciences, including developments in analytical methodology, instrumentation, computation and interpretation. Submissions on novel applications focusing on drug purity and stability studies, pharmacokinetics, therapeutic monitoring, metabolic profiling; drug-related aspects of analytical biochemistry and forensic toxicology; quality assurance in the pharmaceutical industry are also welcome. Studies from areas of well established and poorly selective methods, such as UV-VIS spectrophotometry (including derivative and multi-wavelength measurements), basic electroanalytical (potentiometric, polarographic and voltammetric) methods, fluorimetry, flow-injection analysis, etc. are accepted for publication in exceptional cases only, if a unique and substantial advantage over presently known systems is demonstrated. The same applies to the assay of simple drug formulations by any kind of methods and the determination of drugs in biological samples based merely on spiked samples. Drug purity/stability studies should contain information on the structure elucidation of the impurities/degradants.
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