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基于炎症细胞因子谱的埃及 COVID-19 预测,以及某些海洋衍生化合物的 2 种潜在治疗效果。

Predictions based on inflammatory cytokine profiling of Egyptian COVID-19 with 2 potential therapeutic effects of certain marine-derived compounds.

机构信息

Al-Azhar University, Faculty of Science, Botany and Microbiology Department, 11884 Nasr City, Cairo, Egypt.

Marine Biotechnology and Natural Products Laboratory, National Institute of Oceanography & Fisheries, Egypt.

出版信息

Int Immunopharmacol. 2024 Jan 5;126:111072. doi: 10.1016/j.intimp.2023.111072. Epub 2023 Nov 24.

Abstract

BACKGROUNDS

A worldwide coronavirus pandemic has affected many healthcare systems in 2019 (COVID-19). Following viral activation, cytokines and chemokines are released, causing inflammation and tissue death, particularly in the lungs, resulting in severe COVID-19 symptoms such as pneumonia and ARDS. COVID-19 induces the release of several chemokines and cytokines in different organs, such as the cardiovascular system and lungs.

RESEARCH IDEA

COVID-19 and its more severe effects, such as an elevated risk of death, are more common in patients with metabolic syndrome and the elderly. Cytokine storm and COVID-19 severity may be mitigated by immunomodulation targeting NF-κB activation in conjunction with TNF- α -inhibition. In severe cases of COVID-19, inhibiting the NF-κB/TNF- α, the pathway may be employed as a therapeutic option.

MATERIAL AND METHODS

The study will elaborate on the Egyptian pattern for COVID-19 patients in the first part of our study. An Egyptian patient with COVID-19 inflammatory profiling will be discussed in the second part of this article using approved marine drugs selected to inhabit the significant inflammatory signals. A biomarker profiling study is currently being performed on Egyptian patients with SARS-COV-2. According to the severity of the infection, participants were divided into four groups. The First Group was non-infected with SARS-CoV-2 (Control, n = 16), the Second Group was non-intensive care patients (non-ICU, n = 16), the Third Group was intensive care patients (ICU, n = 16), and the Fourth Group was ICU with endotracheal intubation (ICU + EI, n = 16). To investigate COVID-19 inflammatory biomarkers for Egyptian patients, several inflammatory, oxidative, antioxidant, and anti-inflammatory biomarkers were measured. The following are examples of blood tests: CRP, Ferritin, D-dimer, TNF-α, IL-8, IL-6., IL-Ib, CD8, NF-κB, MDA, and total antioxidants.

RESULTS AND DISCUSSION

The results of the current study revealed many logical findings, such as the elevation of CRP, Ferritin, D-dimer, TNF- α, CD8, IL-6, IL-, NF-κB, and MDA. Where a significant increase showed in ICU group results (23.05 ± 0.30, 2.35 ± 0.86, 433.4 ± 159.3, 26.67 ± 3.51, 7.52 ± 1.48, 7.49 ± 1.04, 5.76 ± 1.31, 7.41 ± 0.73) respectively, and also ICU group results (54.75 ± 3.44, 0.65 ± 0.13, 460.2 ± 121.42, 27.43 ± 2.52, 8.63 ± 2.68, 10.65 ± 2.75, 5.93 ± 1.4, 10.64 ± 0.86) respectively, as well as ICU + EI group results (117.63 ± 11.89, 1.22 ± 0.65, 918.8 ± 159.27, 26.68 ± 2.00, 6.68 ± 1.08, 11.68 ± 6.16, 6.23 ± 0.07, 22.41 ± 1.39),respectively.The elevation in laboratory biomarkers of cytokines storm in three infected groups with remarkable increases in the ICU + EI group was due to the elevation of oxidative stress and inflammatory storm molecules, which lead to highly inflammatory responses, specifically in severe patients of COVID-19. Another approach to be used in the current study is investigating new computational drug compounds for SARS-COV-2 protective agents from the marine environment. The results revealed that (Imatinib and Indinavir) had the highest affinity toward Inflammatory molecules and COVID-19 proteins (PDB ID: -7CZ4 and 7KJR), which may be used in the future as possible COVID-19 drug candidates.

CONCLUSION

The investigated inflammatory biomarkers in Egyptian COVID-19 patients showed a strong correlation between IL6, TNF-α, NF-κB, CRB, DHL, and ferritin as COVID-19 biomarkers and determined the severity of the infection. Also, the oxidative /antioxidant showed good biomarkers for infection recovery and progression of the patients.

摘要

背景

2019 年(COVID-19),一种全球范围内的冠状病毒大流行影响了许多医疗体系。病毒激活后,细胞因子和趋化因子被释放,导致炎症和组织死亡,特别是在肺部,导致严重的 COVID-19 症状,如肺炎和 ARDS。COVID-19 在不同的器官中诱导释放多种趋化因子和细胞因子,如心血管系统和肺部。

研究思路

代谢综合征和老年人患者的 COVID-19 及其更严重的影响(如死亡风险增加)更为常见。通过针对 NF-κB 激活的免疫调节与 TNF-α 抑制联合使用,可能减轻细胞因子风暴和 COVID-19 的严重程度。在 COVID-19 的严重病例中,抑制 NF-κB/TNF-α 可能是一种治疗选择。

材料和方法

我们的研究的第一部分将详细阐述埃及 COVID-19 患者的模式。本文的第二部分将讨论使用选定的海洋药物来抑制炎症信号,对患有 COVID-19 的埃及患者进行炎症特征分析。目前正在对埃及 SARS-COV-2 患者进行生物标志物分析研究。根据感染的严重程度,参与者被分为四组。第一组未感染 SARS-CoV-2(对照组,n=16),第二组是非重症监护患者(非 ICU,n=16),第三组是重症监护患者(ICU,n=16),第四组是 ICU 并气管插管(ICU+EI,n=16)。为了研究埃及 COVID-19 患者的炎症生物标志物,测量了几种炎症、氧化、抗氧化和抗炎生物标志物。以下是血液测试的例子:CRP、铁蛋白、D-二聚体、TNF-α、IL-8、IL-6、IL-1b、CD8、NF-κB、MDA 和总抗氧化剂。

结果与讨论

目前的研究结果显示出许多合理的发现,例如 CRP、铁蛋白、D-二聚体、TNF-α、CD8、IL-6、IL-1b、NF-κB 和 MDA 的升高。ICU 组的结果显示出显著的增加(23.05±0.30、2.35±0.86、433.4±159.3、26.67±3.51、7.52±1.48、7.49±1.04、5.76±1.31、7.41±0.73),ICU 组(54.75±3.44、0.65±0.13、460.2±121.42、27.43±2.52、8.63±2.68、10.65±2.75、5.93±1.4、10.64±0.86),以及 ICU+EI 组(117.63±11.89、1.22±0.65、918.8±159.27、26.68±2.00、6.68±1.08、11.68±6.16、6.23±0.07、22.41±1.39)。三个感染组的细胞因子风暴的实验室生物标志物升高,特别是在 COVID-19 重症患者中,ICU+EI 组的升高更为明显,这是由于氧化应激和炎症风暴分子的升高,导致高度炎症反应。目前研究的另一种方法是从海洋环境中寻找 SARS-COV-2 保护剂的新型计算药物化合物。结果表明,(伊马替尼和茚地那韦)对炎症分子和 COVID-19 蛋白(PDB ID:-7CZ4 和 7KJR)具有最高的亲和力,可能在未来作为 COVID-19 药物候选物使用。

结论

对埃及 COVID-19 患者的炎症生物标志物的研究表明,IL6、TNF-α、NF-κB、CRB、DHL 和铁蛋白作为 COVID-19 生物标志物与感染的严重程度之间存在很强的相关性。此外,氧化/抗氧化生物标志物对感染的恢复和患者病情的进展有很好的指示作用。

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