MYD88, NFKB1, and IL6 transcripts overexpression are associated with poor outcomes and short survival in neonatal sepsis.

MYD88, NFKB1, and IL6 transcripts overexpression are associated with poor outcomes and short survival in neonatal sepsis.
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DOI:
10.1038/s41598-021-92912-7
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发表时间:
2021-06-28
期刊:
影响因子:
4.6
通讯作者:
Helal GM
Helal GM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
AbdAllah NB;Toraih EA;Al Ageeli E;Elhagrasy H;Gouda NS;Fawzy MS;Helal GM

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Toll 样受体 (TLR) 家族特征与脓毒症病因病理有关。我们的目的是评估TLR通路相关关键基因的遗传图谱;对脓毒症新生儿入院时和治疗后可用配对样本的血液中的骨髓分化蛋白 88 (MYD88)、IL1 受体相关激酶 1 (IRAK1)、核因子 kappa-B1 (NFKB1) 和白细胞介素 6 (IL6) 进行分析。这项病例对照研究包括 124 名入住新生儿重症监护病房的败血症婴儿和 17 名对照婴儿。通过 TaqMan 实时 qPCR 对相对基因表达进行定量,并与临床实验室数据相关。脓毒症病例中 MYD88、NFKB1 和 IL6 的相对表达显着高于对照组。在男性新生儿中发现了较高水平的 MYD88 和 IL6,这有助于通过主成分分析对病例进行性别分离。 ROC 分析显示 MYD88 和 NFKB1 转录本是败血症的良好生物标志物。此外,Kaplan-Meier 曲线分析显示,循环 MYD88 水平高的患者与较差的生存率相关。 MYD88、NFKB1 和 IL6 转录本与不同的不良结果表现相关。聚类分析根据患者的转录组特征和 CRP 水平将患者队列分为三个不同的组。总之,该研究的 TLR 通路相关转录本在新生儿败血症中具有性别特异性特征、诊断和预后临床实用性。
Toll-like receptor (TLR) family signature has been implicated in sepsis etiopathology. We aimed to evaluate the genetic profile of TLR pathway-related key genes; the myeloid differentiation protein 88 (MYD88), IL1 receptor-associated kinase 1 (IRAK1), the nuclear factor kappa-B1 (NFKB1), and interleukin 6 (IL6) in the blood of neonates with sepsis at the time of admission and post-treatment for the available paired-samples. This case–control study included 124 infants with sepsis admitted to the neonatal intensive care unit and 17 controls. The relative gene expressions were quantified by TaqMan Real-Time qPCR and correlated to the clinic-laboratory data. MYD88, NFKB1, and IL6 relative expressions were significantly higher in sepsis cases than controls. Higher levels of MYD88 and IL6 were found in male neonates and contributed to the sex-based separation of the cases by the principal component analysis. ROC analysis revealed MYD88 and NFKB1 transcripts to be good biomarkers for sepsis. Furthermore, patients with high circulatory MYD88 levels were associated with poor survival, as revealed by Kaplan–Meier curves analysis. MYD88, NFKB1, and IL6 transcripts showed association with different poor-outcome manifestations. Clustering analysis split the patient cohort into three distinct groups according to their transcriptomic signature and CRP levels. In conclusion, the study TLR pathway-related transcripts have a gender-specific signature, diagnostic, and prognostic clinical utility in neonatal sepsis.
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