Identification of the miRNA-3185/CYP4A11 axis in cardiac tissue as a biomarker for mechanical asphyxia

Han, Liangxiu; Zhang, Heng; Zeng, Yan; Lv, Yubao; Li, Tao; Ma, Jun; Xu, H. C.; Ma, Kaijun; Shi, Qun; Bi, Xiao; Chen, Long

doi:10.1016/j.forsciint.2020.110293

Cited by 15 publications

(16 citation statements)

References 30 publications

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“…A brief review of the recent literature revealed just a small number of articles addressing asphyxia through experimental protocols. Several approaches have been proposed 1 – 7 , mainly focused on the effects of asphyxial mechanisms, while little is known about the real-time biological modifications that occur during hypoxic-ischaemic insult. It was recently demonstrated 8 that only exceptionally long asphyxial periods can produce lungs histological modifications, whilst alterations can be observed at cellular and, especially, molecular level.…”

Section: Introductionmentioning

confidence: 99%

Metabolomics improves the histopathological diagnosis of asphyxial deaths: an animal proof-of-concept model

Locci

Chighine

Noto

et al. 2021

Sci Rep

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The diagnosis of mechanical asphyxia remains one of the most difficult issues in forensic pathology. Asphyxia ultimately results in cardiac arrest (CA) and, as there are no specific markers, the differential diagnosis of primitive CA and CA secondary to asphyxiation relies on circumstantial details and on the pathologist experience, lacking objective evidence. Histological examination is currently considered the gold standard for CA post-mortem diagnosis. Here we present the comparative results of histopathology versus those previously obtained by 1H nuclear magnetic resonance (NMR) metabolomics in a swine model, originally designed for clinical purposes, exposed to two different CA causes, namely ventricular fibrillation and asphyxia. While heart and brain microscopical analysis could identify the damage induced by CA without providing any additional information on the CA cause, metabolomics allowed the identification of clearly different profiles between the two groups and showed major differences between asphyxiated animals with good and poor outcomes. Minute-by-minute plasma sampling allowed to associate these modifications to the pre-arrest asphyxial phase showing a clear correlation to the cellular effect of mechanical asphyxia reproduced in the experiment. The results suggest that metabolomics provides additional evidence beyond that obtained by histology and immunohistochemistry in the differential diagnosis of CA.

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Section: Introductionmentioning

confidence: 99%

Metabolomics improves the histopathological diagnosis of asphyxial deaths: an animal proof-of-concept model

Locci

Chighine

Noto

et al. 2021

Sci Rep

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“…In any case, our findings suggest that multivariate approaches should be investigated further, albeit with a significantly larger number of cases, precisely defined groups, and taking into account other (immunohistochemical and molecular) parameters with diagnostic relevance. Interesting parameters could be further immunohistochemical markers as the hypoxia-inducible factor 1-alpha (HIF1-α [50]) or altered expression patterns of microRNAs from specific proteins in other organs like the myocardium or brain [70,71]. Furthermore, markers secreted by alveolar macrophages in a hypoxic environment might be of interest, such as MCP-1 [72][73][74].…”

Section: Discussionmentioning

confidence: 99%

Acute or chronic pulmonary emphysema? Or both?—A contribution to the diagnosis of death due to violent asphyxiation in cases with pre-existing chronic emphysema

et al. 2021

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The diagnosis of death due to violent asphyxiation may be challenging if external injuries are missing, and a typical acute emphysema (AE) “disappears” in pre-existing chronic emphysema (CE). Eighty-four autopsy cases were systematically investigated to identify a (histo-) morphological or immunohistochemical marker combination that enables the diagnosis of violent asphyxiation in cases with a pre-existing CE (“AE in CE”). The cases comprised four diagnostic groups, namely “AE”, “CE”, “acute and chronic emphysema (AE + CE)”, and “no emphysema (NE)”. Samples from all pulmonary lobes were investigated by conventional histological methods as well as with the immunohistochemical markers Aquaporin 5 (AQP-5) and Surfactant protein A1 (SP-A). Particular attention was paid to alveolar septum ends (“dead-ends”) suspected as rupture spots, which were additionally analyzed by transmission electron microscopy. The findings in the four diagnostic groups were compared using multivariate analysis and 1-way ANOVA analysis. All morphological findings were found in all four groups. Based on histological and macroscopic findings, a multivariate analysis was able to predict the correct diagnosis “AE + CE” with a probability of 50%, and the diagnoses “AE” and “CE” with a probability of 86% each. Three types of “dead-ends” could be differentiated. One type (“fringed ends”) was observed significantly more frequently in AE. The immunohistochemical markers AQP-5 and SP-A did not show significant differences among the examined groups. Though a reliable identification of AE in CE could not be achieved using the examined parameters, our findings suggest that considering many different findings from the macroscopical, histomorphological, and molecular level by multivariate analysis is an approach that should be followed.

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“…Current studies have mainly focused on nding differentially expressed mRNAs, miRNAs, proteins, or metabolites during asphyxia [5][6][7][8] or SCD. 9,10 Although these biomarkers have shown promising sensitivity, their specicity remains insufficiently studied for their practical applications.…”

Section: Introductionmentioning

confidence: 99%

Use of Raman spectroscopy to study rat lung tissues for distinguishing asphyxia from sudden cardiac death

Zhang,

Liu,

Wei

et al. 2024

RSC Adv.

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Identification of the miRNA-3185/CYP4A11 axis in cardiac tissue as a biomarker for mechanical asphyxia

Cited by 15 publications

References 30 publications

Metabolomics improves the histopathological diagnosis of asphyxial deaths: an animal proof-of-concept model

Metabolomics improves the histopathological diagnosis of asphyxial deaths: an animal proof-of-concept model

Acute or chronic pulmonary emphysema? Or both?—A contribution to the diagnosis of death due to violent asphyxiation in cases with pre-existing chronic emphysema

Use of Raman spectroscopy to study rat lung tissues for distinguishing asphyxia from sudden cardiac death

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