Serum peptidome: diagnostic window into pathogenic processes following occupational exposure to carbon nanomaterials.

Serum peptidome: diagnostic window into pathogenic processes following occupational exposure to carbon nanomaterials.
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DOI:
10.1186/s12989-021-00431-0
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发表时间:
2021-10-28
影响因子:
10
通讯作者:
Ottens AK
Ottens AK
中科院分区:
医学1区
文献类型:
--
作者:
Mostovenko E;Dahm MM;Schubauer-Berigan MK;Eye T;Erdely A;Young TL;Campen MJ;Ottens AK

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碳纳米管和纳米纤维(CNT/F)日益增长的工业用途值得考虑对人类健康的影响。CNT/F在动物中产生肺、心血管和其他毒性作用,同时显著释放生物活性肽进入循环,增加血清肽量。虽然CNT/F工作人员的流行病学报告很少出现急性症状,但仍然存在对亚临床CNT/F效应的担忧,这些效应可能会引发慢性疾病,因此需要对纵向随访进行敏感的健康结果诊断标记。在这里,使用无标签数据独立的质谱法评估血清肽球在检测CNT/F工人亚症状病理生物学方面的生物标志物潜力。研究采用了工业环境中高(0.5 μ g/m3)和低(< 0.1 μ g/m3)可吸入碳纳米管/氟暴露的分层设计。肽生物标志物模型的建立和改进采用线性回归和偏最小二乘判别分析。然后对排名靠前的肽进行序列鉴定并评估其病理相关性。在建立模型后,总共发现41个多肽具有高度歧视性,与个人CNT/F暴露有很强的线性相关性。前5个多肽模型预测理想,准确度高(Q2 = 0.99916)。无监督验证证实43.5%的血清肽组变异可归因于CNT/F暴露。肽序列鉴定揭示了与血管病理的主要关联。ARHGAP21、ADAM15和PLPP3多肽提示心血管通透性升高,F13A1、FBN1和VWDE多肽提示高CNT/F工人的促血栓形成状态。血清肽丘为CNT/F暴露工人的亚症状病理提供了一个诊断窗口,用于系统性健康风险的纵向监测。在线版本包含补充材料,可在10.1186/s12989-021-00431-0获得。
Growing industrial use of carbon nanotubes and nanofibers (CNT/F) warrants consideration of human health outcomes. CNT/F produces pulmonary, cardiovascular, and other toxic effects in animals along with a significant release of bioactive peptides into the circulation, the augmented serum peptidome. While epidemiology among CNT/F workers reports on few acute symptoms, there remains concern over sub-clinical CNT/F effects that may prime for chronic disease, necessitating sensitive health outcome diagnostic markers for longitudinal follow-up. Here, the serum peptidome was assessed for its biomarker potential in detecting sub-symptomatic pathobiology among CNT/F workers using label-free data-independent mass spectrometry. Studies employed a stratified design between High (> 0.5 µg/m3) and Low (< 0.1 µg/m3) inhalable CNT/F exposures in the industrial setting. Peptide biomarker model building and refinement employed linear regression and partial least squared discriminant analyses. Top-ranked peptides were then sequence identified and evaluated for pathological-relevance. In total, 41 peptides were found to be highly discriminatory after model building with a strong linear correlation to personal CNT/F exposure. The top-five peptide model offered ideal prediction with high accuracy (Q2 = 0.99916). Unsupervised validation affirmed 43.5% of the serum peptidomic variance was attributable to CNT/F exposure. Peptide sequence identification reveals a predominant association with vascular pathology. ARHGAP21, ADAM15 and PLPP3 peptides suggest heightened cardiovasculature permeability and F13A1, FBN1 and VWDE peptides infer a pro-thrombotic state among High CNT/F workers. The serum peptidome affords a diagnostic window into sub-symptomatic pathology among CNT/F exposed workers for longitudinal monitoring of systemic health risks. The online version contains supplementary material available at 10.1186/s12989-021-00431-0.
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