Treponema pallidum inhibits CD4+ T-cell proliferation through METAP2: insights from Mendelian randomization analysis

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Xuất bản năm:AMB Express vol. 15, no. 1 (Dec 2025), p. 126
Tác giả chính: Liu, Zhaoping
Tác giả khác: Zhang, Xiaohong, Lin, Ting, Ding, Xuan, Yu, Han, Yao, Jiangchen, Gao, Ke, Wu, Yimou, Zhao, Feijun
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Springer Nature B.V.
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024 7 |a 10.1186/s13568-025-01940-3  |2 doi 
035 |a 3243584658 
045 2 |b d20251201  |b d20251231 
084 |a 242430  |2 nlm 
100 1 |a Liu, Zhaoping  |u University of South China, Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hunan Province Clinical Research Center for Accurate Diagnosis and Treatment of High-incidence Sexually Transmitted Diseases, The First Affiliated Hospital, Hengyang Medical School, Hengyang, People’s Republic of China (GRID:grid.412017.1) (ISNI:0000 0001 0266 8918) 
245 1 |a <i>Treponema pallidum</i> inhibits CD4+ T-cell proliferation through METAP2: insights from Mendelian randomization analysis 
260 |b Springer Nature B.V.  |c Dec 2025 
513 |a Journal Article 
520 3 |a Neurosyphilis (NS) is a chronic central nervous system infection caused by Treponema pallidum. Owing to its diverse clinical manifestations and the limited sensitivity of current diagnostic methods, NS is difficult to diagnose. Understanding the molecular mechanisms of NS and identifying reliable biomarkers are essential for improving diagnostic and therapeutic strategies. This study employed Mendelian randomization (MR) analysis to explore the causal relationships among protein ratio quantitative trait loci (rQTLs), cerebrospinal fluid (CSF) metabolites, and syphilis risk at various stages. The results revealed that several rQTLs, including CD46/TNFRSF14 and TBC1D23/TBC1D5, were closely associated with syphilis risk, whereas others, such as BANK1/HEXIM1 and GOPC/HEXIM1, exhibited protective effects. Mediation analysis further identified key CSF metabolites, such as N-acetyltaurine and bilirubin, as important mediators linking rQTLs and syphilis progression. Through integrated analysis of cis-proteins from rQTLs and transcriptomic data from CD4 + T-cells of NS patients, METAP2 was identified as a key biomarker in NS, with the potential mechanisms elucidated. Importantly, T. pallidum may inhibit CD4 + T-cell proliferation by modulating METAP2, thereby accelerating disease progression. These findings offer new insights into the pathogenesis of NS and highlight METAP2 as a potential biomarker, laying a foundation for improving diagnostic and therapeutic strategies. 
610 4 |a UK Biobank Ltd 
651 4 |a Wisconsin 
651 4 |a United Kingdom--UK 
651 4 |a United States--US 
653 |a Syphilis 
653 |a Cerebrospinal fluid 
653 |a Alzheimer's disease 
653 |a Datasets 
653 |a Quantitative trait loci 
653 |a Disease 
653 |a Lymphocytes T 
653 |a Cytokines 
653 |a Cell proliferation 
653 |a Quality control 
653 |a Neurosyphilis 
653 |a Chronic infection 
653 |a Molecular modelling 
653 |a Biobanks 
653 |a Metabolites 
653 |a Metabolism 
653 |a Transcriptomics 
653 |a Central nervous system 
653 |a CD4 antigen 
653 |a Proteins 
653 |a Protein synthesis 
653 |a Bilirubin 
653 |a Biomarkers 
653 |a Immune response 
653 |a Randomization 
653 |a Pathogenesis 
653 |a Methods 
653 |a CD46 antigen 
653 |a Cell growth 
653 |a Treponema pallidum 
700 1 |a Zhang, Xiaohong  |u University of South China, MOE Key Lab of Rare Pediatric Diseases&amp;Institute of Pathogenic Biology and Key Laboratory of Special Pathogen Prevention and Control of Hunan Province, Hengyang Medical College, Hengyang City, People’s Republic of China (GRID:grid.412017.1) (ISNI:0000 0001 0266 8918) 
700 1 |a Lin, Ting  |u University of South China, School of Public Health, Hengyang Medical School, Hengyang, People’s Republic of China (GRID:grid.412017.1) (ISNI:0000 0001 0266 8918) 
700 1 |a Ding, Xuan  |u University of South China, MOE Key Lab of Rare Pediatric Diseases&amp;Institute of Pathogenic Biology and Key Laboratory of Special Pathogen Prevention and Control of Hunan Province, Hengyang Medical College, Hengyang City, People’s Republic of China (GRID:grid.412017.1) (ISNI:0000 0001 0266 8918) 
700 1 |a Yu, Han  |u University of South China, MOE Key Lab of Rare Pediatric Diseases&amp;Institute of Pathogenic Biology and Key Laboratory of Special Pathogen Prevention and Control of Hunan Province, Hengyang Medical College, Hengyang City, People’s Republic of China (GRID:grid.412017.1) (ISNI:0000 0001 0266 8918) 
700 1 |a Yao, Jiangchen  |u University of South China, MOE Key Lab of Rare Pediatric Diseases&amp;Institute of Pathogenic Biology and Key Laboratory of Special Pathogen Prevention and Control of Hunan Province, Hengyang Medical College, Hengyang City, People’s Republic of China (GRID:grid.412017.1) (ISNI:0000 0001 0266 8918) 
700 1 |a Gao, Ke  |u University of South China, MOE Key Lab of Rare Pediatric Diseases&amp;Institute of Pathogenic Biology and Key Laboratory of Special Pathogen Prevention and Control of Hunan Province, Hengyang Medical College, Hengyang City, People’s Republic of China (GRID:grid.412017.1) (ISNI:0000 0001 0266 8918) 
700 1 |a Wu, Yimou  |u University of South China, MOE Key Lab of Rare Pediatric Diseases&amp;Institute of Pathogenic Biology and Key Laboratory of Special Pathogen Prevention and Control of Hunan Province, Hengyang Medical College, Hengyang City, People’s Republic of China (GRID:grid.412017.1) (ISNI:0000 0001 0266 8918); University of South China, Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hunan Province Clinical Research Center for Accurate Diagnosis and Treatment of High-incidence Sexually Transmitted Diseases, The First Affiliated Hospital, Hengyang Medical School, Hengyang, People’s Republic of China (GRID:grid.412017.1) (ISNI:0000 0001 0266 8918); University of South China, Institute of Pathogenic Biology and Key Laboratory of Special Pathogen Prevention and Control of Hunan Province, Department of Clinical Laboratory Medicine, The First Affiliated Hospital, Hengyang Medical College, Hengyang, People’s Republic of China (GRID:grid.412017.1) (ISNI:0000 0001 0266 8918) 
700 1 |a Zhao, Feijun  |u University of South China, MOE Key Lab of Rare Pediatric Diseases&amp;Institute of Pathogenic Biology and Key Laboratory of Special Pathogen Prevention and Control of Hunan Province, Hengyang Medical College, Hengyang City, People’s Republic of China (GRID:grid.412017.1) (ISNI:0000 0001 0266 8918); University of South China, Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hunan Province Clinical Research Center for Accurate Diagnosis and Treatment of High-incidence Sexually Transmitted Diseases, The First Affiliated Hospital, Hengyang Medical School, Hengyang, People’s Republic of China (GRID:grid.412017.1) (ISNI:0000 0001 0266 8918); Changsha Central Hospital, Department of Clinical Laboratory Medicine, Changsha, People’s Republic of China (GRID:grid.452210.0); University of South China, School of Public Health, Hengyang Medical School, Hengyang, People’s Republic of China (GRID:grid.412017.1) (ISNI:0000 0001 0266 8918); University of South China, Institute of Pathogenic Biology and Key Laboratory of Special Pathogen Prevention and Control of Hunan Province, Department of Clinical Laboratory Medicine, The First Affiliated Hospital, Hengyang Medical College, Hengyang, People’s Republic of China (GRID:grid.412017.1) (ISNI:0000 0001 0266 8918) 
773 0 |t AMB Express  |g vol. 15, no. 1 (Dec 2025), p. 126 
786 0 |d ProQuest  |t Engineering Database 
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