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多组学揭示一种机制:糖原合成、半乳糖代谢和乙醇降解途径,中和抗体在预防新冠病毒病中的持久作用。

Multiomics Reveals a Mechanism: Glycogen Synthesis, Galactose Metabolism, and Ethanol Degradation Pathways, the Durable Role of Neutralizing Antibodies in Preventing COVID-19.

作者信息

Luo Huayu, Fan Linrui, Cao Feng, Ren Tong, He Yujie, Shen Tao, Liu Dan, Ren Hongzheng

机构信息

Department of Pathology, Gongli Hospital of Shanghai Pudong New Area, 219 Miao Pu Road, Shanghai 200135, China.

Department of Pathology, Changzhi Medical College Affiliated Heping Hospital, Changzhi, Shanxi Province 046000, China.

出版信息

ACS Omega. 2024 Oct 10;9(42):42757-42765. doi: 10.1021/acsomega.4c04047. eCollection 2024 Oct 22.

Abstract

Since the emergence and rapid dissemination of Coronavirus disease 2019 (COVID-19), over 774 million individuals globally have achieved recovery to today. There is some case flashing into here and there all over the world. Neutralizing Antibody (NAb) against Severe Acute Respiratory Syndrome Coronavirus-Type 2 (SARS-CoV-2) play a paramount role in conferring effective and lasting protection for several months. This protective effect decreases with time thus increasing the chance of reinfection. Therefore, we can provide the body with a lasting protective effect by maintaining NAb level. However, how to maintain Nab level remains elusive. To address this question, we recruited 80 patients with confirmed COVID-19 and collected 480 consecutive blood samples and performed NAb testing six months after their recovery. The NAb level were categorized into two groups: a low-titer NAb group (≤20) and a high-titer NAb group (>20). To achieve a comprehensive understanding of the changes in NAb level, 16 serum samples were randomly selected for an untargeted metabolomic analysis, whereas 9 samples were designated for a label-free proteomic analysis. We successfully identified differentially expressed 751 metabolites and 845 proteins. In both the low and high NAb titer groups, we identified three key differential proteins, phosphoglucose translocase 2(PGM2), UDP-Glc 4-epimerase (GALE), and alcohol dehydrogenase 1B (ADH1B), that play important roles in fluctuating NAb level through the glycogen synthesis, galactose metabolism and ethanol degradation pathways. These three key differential proteins may serve as potential biomarkers for maintaining NAb level and enhancing immune protection in patients recovering from COVID-19.

摘要

自2019年冠状病毒病(COVID-19)出现并迅速传播以来,全球已有超过7.74亿人康复至今。世界各地仍不时有病例出现。针对严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)的中和抗体(NAb)在提供数月的有效持久保护方面起着至关重要的作用。这种保护作用会随着时间减弱,从而增加再次感染的几率。因此,我们可以通过维持NAb水平为机体提供持久的保护作用。然而,如何维持NAb水平仍不清楚。为解决这个问题,我们招募了80例确诊的COVID-19患者,收集了480份连续血样,并在他们康复6个月后进行了NAb检测。NAb水平分为两组:低滴度NAb组(≤20)和高滴度NAb组(>20)。为全面了解NAb水平的变化,随机选择16份血清样本进行非靶向代谢组学分析,9份样本进行无标记蛋白质组学分析。我们成功鉴定出751种差异表达的代谢物和845种蛋白质。在低NAb滴度组和高NAb滴度组中,我们都鉴定出三种关键差异蛋白,磷酸葡萄糖转运酶2(PGM2)、UDP-葡萄糖4-表异构酶(GALE)和乙醇脱氢酶1B(ADH1B),它们通过糖原合成、半乳糖代谢和乙醇降解途径在NAb水平波动中起重要作用。这三种关键差异蛋白可能作为维持COVID-19康复患者NAb水平和增强免疫保护的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d221/11500150/0a0394d832c2/ao4c04047_0001.jpg

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