{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:23:48Z","timestamp":1787311428906,"version":"build-2736575974"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>DENV virus (DENV) infection can cause various symptoms and organ damage, even severe dengue fever. However, the underlying host response products and interfering metabolic pathways and mechanisms of DENV infection remain unclear. In this study, we characterized the metabolites and metabolic pathway changes during DENV infection using liquid chromatography- (LC-MS) and gas chromatography-mass spectrometry (GC-MS). And identify the hub differentially expressed targets associated with major metabolism pathways combining transcriptomics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Plasma from adult patients infected with DENV infection was characterized by untargeted metabolomics using LC-MS and GC-MS. Potential diagnostic biomarkers for dengue fever were indicated using ROC curve analysis. KEGG and GSEA functional enrichment analysis was the strategy to determine the mechanisms of key metabolic pathways in dengue fever. Potential targets were identified by combining transcriptomic in Gene Expression Omnibus (GEO) datasets, and gene databases from GeneCards and the Comparative Toxicogenomics Database (CTD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 41 dengue patients and 23 healthy volunteers were recruited for the study. 61 up-regulated and 136 down-regulated metabolites were identified via untargeted metabolomics. The top10 up-regulated metabolites with high AUC values included trans-cinnamic acid, L-Acetylcarnitine, SM(d17:1\/17:0), 1,2,4,5-cyclohexanetetrol, 5-(hydroxymethyl) pyrrolidin-2-one, 1,2,3,4-tetrahydro-6-propanoylpyridine, 2-C-methyl-D-erythritol-4-phosphate, Physalolactone, S-Japonin, and 9-tridecynoic acid, and they were supposed to be the potential diagnostic biomarkers for dengue fever. The disturbance of ATP-binding cassette (ABC) transporters, protein digestion and absorption, aminoacyl-tRNA biosynthesis, mineral absorption, and D-amino acid metabolism were enriched in the metabolic pathways. ABCC5, ABCB1, and ABCG5 were identified as hub differentially expressed targets through transcriptome profiling and protein-protein interaction networks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The current study revealed a shift in metabolite profiles and disturbance in ABC transporters in dengue fever, which can be used for further functional verification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2025.1749051","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T06:51:39Z","timestamp":1770792699000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["The disturbance of ABC transporters in patients with dengue fever: integration of metabolomics and transcriptomics"],"prefix":"10.3389","volume":"15","author":[{"given":"Chengxin","family":"Liu","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital, Guangzhou University of Chinese Medicine","place":["Guangzhou, China"]},{"name":"The First Clinical Medical School, Guangzhou University of Chinese Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Ye","sequence":"additional","affiliation":[{"name":"The First Clinical Medical School, Guangzhou University of Chinese Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Guangzhou University of Chinese Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiafang","family":"Chen","sequence":"additional","affiliation":[{"name":"Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiting","family":"Huang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Guangzhou University of Chinese Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geng","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory Animal Center, Guangzhou University of Chinese Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaofeng","family":"Zhan","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Guangzhou University of Chinese Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1146\/annurev-biophys-111622-091232","article-title":"Structure and Mechanism of Human ABC Transporters","volume":"52","author":"Alam","year":"2023","journal-title":"Annu. Rev. Biophys."},{"key":"B2","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1093\/cid\/ciz850","article-title":"Predictors and Clinical Outcomes of Poor Platelet Recovery in Adult Dengue With Thrombocytopenia: A Multicenter, Prospective Study","volume":"71","author":"Archuleta","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"B3","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1038\/nature12060","article-title":"The global distribution and burden of dengue","volume":"496","author":"Bhatt","year":"2013","journal-title":"Nature"},{"key":"B4","doi-asserted-by":"publisher","first-page":"225","DOI":"10.3390\/v11030225","article-title":"Metabolomic Insights into Human Arboviral Infections: Dengue, Chikungunya, and Zika Viruses","volume":"11","author":"Byers","year":"2019","journal-title":"Viruses"},{"key":"B5","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1186\/s13071-021-05106-5","article-title":"Drug targeting of aminoacyl-tRNA synthetases in Anopheles species and Aedes aegypti that cause malaria and dengue","volume":"14","author":"Chakraborti","year":"2021","journal-title":"Parasit Vectors"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002373","article-title":"Serum metabolome and lipidome changes in adult patients with primary dengue infection","volume":"7","author":"Cui","year":"2013","journal-title":"PloS Negl. Trop. Dis."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0004607","article-title":"Serum Metabolomics Reveals Serotonin as a Predictor of Severe Dengue in the Early Phase of Dengue Fever","volume":"10","author":"Cui","year":"2016","journal-title":"PloS Negl. Trop. Dis."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00386-17","article-title":"Serum Metabolomics Investigation of Humanized Mouse Model of Dengue Virus Infection","volume":"91","author":"Cui","year":"2017","journal-title":"J. Virol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"2572","DOI":"10.1111\/jth.15431","article-title":"Platelet activation and aggregation response to dengue virus nonstructural protein 1 and domains","volume":"19","author":"Garcia-Larragoiti","year":"2021","journal-title":"J. Thromb. Haemost."},{"key":"B10","doi-asserted-by":"publisher","first-page":"3064","DOI":"10.1021\/acs.jproteome.3c00761","article-title":"Plasma Instead of Serum Avoids Critical Confounding of Clinical Metabolomics Studies by Platelets","volume":"23","author":"Hagn","year":"2024","journal-title":"J. Proteome Res"},{"key":"B11","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.antiviral.2019.03.002","article-title":"Stearoyl-CoA desaturase-1 is required for flavivirus RNA replication","volume":"165","author":"Hishiki","year":"2019","journal-title":"Antiviral Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"30429","DOI":"10.1074\/jbc.M115.692103","article-title":"ATP-binding Cassette Subfamily C Member 5 (ABCC5) Functions as an Efflux Transporter of Glutamate Conjugates and Analogs","volume":"290","author":"Jansen","year":"2015","journal-title":"J. Biol. Chem."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2732","DOI":"10.1182\/blood-2013-06-510461","article-title":"Platelet hyperreactivity explains the bleeding abnormality and macrothrombocytopenia in a murine model of sitosterolemia","volume":"122","author":"Kanaji","year":"2013","journal-title":"Blood"},{"key":"B14","doi-asserted-by":"publisher","first-page":"20499361231167274","DOI":"10.1177\/20499361231167274","article-title":"A dengue vaccine whirlwind update","volume":"10","author":"Kariyawasam","year":"2023","journal-title":"Ther. Adv. Infect. Dis."},{"key":"B15","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1002\/jssc.201400749","article-title":"Profiling of esterified fatty acids as biomarkers in the blood of dengue fever patients using a microliter-scale extraction followed by gas chromatography and mass spectrometry","volume":"38","author":"Khedr","year":"2015","journal-title":"J. Sep Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"101452","DOI":"10.1016\/j.bbrep.2023.101452","article-title":"Blood levels of d-amino acids reflect the clinical course of COVID-19","volume":"34","author":"Kimura-Ohba","year":"2023","journal-title":"Biochem. Biophys. Rep."},{"key":"B17","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1038\/s41564-019-0376-y","article-title":"Past and future spread of the arbovirus vectors Aedes aegypti and Aedes albopictus","volume":"4","author":"Kraemer","year":"2019","journal-title":"Nat. Microbiol."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens10091127","article-title":"Delineating the Role of Aedes aegypti ABC Transporter Gene Family during Mosquito Development and Arboviral Infection via Transcriptome Analyses","volume":"10","author":"Kumar","year":"2021","journal-title":"Pathogens"},{"key":"B19","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.chom.2014.06.001","article-title":"Dengue virus infection induces expansion of a CD14(+)CD16(+) monocyte population that stimulates plasmablast differentiation","volume":"16","author":"Kwissa","year":"2014","journal-title":"Cell Host Microbe"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005457","article-title":"Transcriptomics technologies","volume":"13","author":"Lowe","year":"2017","journal-title":"PloS Comput. Biol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.molmed.2022.11.001","article-title":"ABC transporters: human disease and pharmacotherapeutic potential","volume":"29","author":"Moore","year":"2023","journal-title":"Trends Mol. Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.cmet.2016.09.018","article-title":"Metabolomics and Metabolic Diseases: Where Do We Stand","volume":"25","author":"Newgard","year":"2017","journal-title":"Cell Metab."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1194\/jlr.R084244","article-title":"ABCG5 and ABCG8: more than a defense against xenosterols","volume":"59","author":"Patel","year":"2018","journal-title":"J. Lipid Res."},{"key":"B24","doi-asserted-by":"publisher","first-page":"114267","DOI":"10.1016\/j.ejpb.2024.114267","article-title":"Exploring the potential of P-glycoprotein inhibitors in the targeted delivery of anti-cancer drugs: A comprehensive review","volume":"198","author":"Patel","year":"2024","journal-title":"Eur. J. Pharm. Biopharm"},{"key":"B25","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1038\/nrm3314","article-title":"Innovation: Metabolomics: the apogee of the omics trilogy","volume":"13","author":"Patti","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1911","DOI":"10.1093\/infdis\/jiy434","article-title":"Early Transcriptional Responses After Dengue Vaccination Mirror the Response to Natural Infection and Predict Neutralizing Antibody Titers","volume":"218","author":"Popper","year":"2018","journal-title":"J. Infect. Dis."},{"key":"B27","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1007\/s12033-017-0029-4","article-title":"Oleic acid Enhances Dengue Virus But Not Dengue Virus-Like Particle Production from Mammalian Cells","volume":"59","author":"Ramphan","year":"2017","journal-title":"Mol. Biotechnol."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2022.100842","article-title":"A robust host-response-based signature distinguishes bacterial and viral infections across diverse global populations","volume":"3","author":"Rao","year":"","journal-title":"Cell Rep Med"},{"key":"B29","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1038\/nrm2646","article-title":"ABC transporters: the power to change","volume":"10","author":"Rees","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/s0140-6736(97)12483-7","article-title":"Dengue and dengue hemorrhagic fever","volume":"352","author":"Rigau-Perez","year":"1998","journal-title":"Lancet"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1126\/science.aaj9384","article-title":"Dengue diversity across spatial and temporal scales: Local structure and the effect of host population size","volume":"355","author":"Salje","year":"2017","journal-title":"Science"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3390\/antiox13020215","article-title":"Regulation of P-Glycoprotein during Oxidative Stress","volume":"13","author":"Shchulkin","year":"2024","journal-title":"Antioxidants (Basel)"},{"key":"B33","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1017\/S0007114518002039","article-title":"Serum fatty acids and progression from dengue fever to dengue hemorrhagic fever\/dengue shock syndrome","volume":"120","author":"Villamor","year":"2018","journal-title":"Br. J. Nutr."},{"key":"B34","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1016\/S0140-6736(18)32560-1","article-title":"Dengue","volume":"393","author":"Wilder-Smith","year":"2019","journal-title":"Lancet"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.892469","article-title":"Liver transcriptomics reveals features of the host response in a mouse model of dengue virus infection","volume":"13","author":"Zheng","year":"2022","journal-title":"Front. Immunol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"4663735","DOI":"10.1155\/2022\/4663735","article-title":"Metabolomic Analysis of Key Regulatory Metabolites in the Urine of Flavivirus-Infected Mice","volume":"2022","author":"Zheng","year":"2022","journal-title":"J. Trop. Med."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1749051\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T06:51:40Z","timestamp":1770792700000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1749051\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,11]]},"references-count":36,"alternative-id":["10.3389\/fcimb.2025.1749051"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2025.1749051","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,11]]},"article-number":"1749051"}}