Evidence map›Paper›PMID 39692504›Full record

ArticleAntimicrobial agents and chemotherapy2025

Metabolomic analysis reveals an important role of sphingosine 1-phosphate in the development of HFMD due to EV-A71 infection.

Wangquan Ji, Dejian Dang, Guangyuan Zhou, Ling Tao, Tiantian Sun, Dong Li, Cheng Cheng, Huifen Feng, Jinzhao Long, Shuaiyin Chen and 3 more

Abstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

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5 · Who and what money

Authors and funding

13 authors.

Wangquan JiDepartment of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.ORCID 0000-0002-4489-1592
Dejian DangDepartment of Infection Control, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Guangyuan ZhouSchool of Public Health, Xinxiang Medical University, Xinxiang, Henan, China.
Ling TaoSchool of Public Health, Xinxiang Medical University, Xinxiang, Henan, China.
Tiantian SunDepartment of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.
Dong LiDepartment of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.
Cheng ChengDepartment of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.
Huifen FengDepartment of Infection Control, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Jinzhao LongDepartment of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.
Shuaiyin ChenDepartment of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.ORCID 0000-0001-6129-0310
Haiyan YangDepartment of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.ORCID 0000-0002-1797-304X
Guangcai DuanDepartment of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.
Yuefei JinDepartment of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.ORCID 0000-0002-1523-0808

Funding

China Postdoctoral Science Foundation (China Postdoctoral Foundation Project) 2024T170246,2024M750815Henan Province Science and Technology Research Project 242102311147MOST | National Natural Science Foundation of China (NSFC) 82002147,82372229MOST | National Natural Science Foundation of China (NSFC) 82073618MOST | National Natural Science Foundation of China (NSFC) 82273695Open Grant from the Pingyuan Laboratory 2023PY-OP-0202Open Project of Henan Province Engineering Research Center of Diagnosis and Treatment of Pediatric Infection and Critical Care ERC202302Open Research Fund of National Health Commission Key Laboratory of Birth Defects Prevention & Henan Key Laboratory of Population Defects Prevention ZD202301
6 · The paper itself

Abstract

Hand, foot, and mouth disease (HFMD) is a serious pediatric infectious disease that causes immeasurable physical and mental health burdens. Currently, there is a lack of information on the mechanisms of HFMD severity and early diagnosis. We performed metabolomic profiling of sera from 84 Enterovirus A71 (EV-A71) infections and 45 control individuals. Targeted metabolomics assays were employed to further validate some of the differential metabolic molecules. We identified significant molecular changes in the sera of HFMD patients compared to healthy controls (HCs). A total of 54, 60, 35, and 62 differential metabolites were screened between mild cases and HCs, severe cases and HCs, severe cases and mild cases, and among the three groups, respectively. These differential metabolites implicated dysregulation of the tricarboxylic acid cycle, alanine, aspartate, and glutamate metabolism, and valine, leucine, and isoleucine biosynthesis. The diagnostic panel based on some overlapped differential metabolites could effectively discriminate severe cases from mild cases with an AUC of 0.912 (95% CI: 0.85-0.97) using the logistic regression model. Next, we found the elevation of serum sphingosine 1-phosphate (S1P) level in EV-A71 infection mice, which was similar to clinical observation. Importantly, after blocking the release of S1P by MK571, the clinical symptoms and survival of mice were significantly improved, involving the reduction of leukocyte infiltration in infected brain tissues. Collectively, our data provided a landscape view of metabolic alterations in EV-A71 infected children and revealed regulating S1P metabolism was an exploitable therapeutic target against EV-A71 infection.

Indexed as

Enterovirus A, HumanHand, Foot and Mouth DiseaseLysophospholipidsSphingosineAnimalsChildChild, PreschoolFemaleHumansInfantMaleMetabolomicsMiceLysophospholipidsSphingosinesphingosine 1-phosphateEV-A71hand, foot, and mouth diseasemetabolomic analysissphingosine 1-phosphate

Identifiers

PMID39692504
PMCPMC11823611

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.