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Exosomal miR-1246 in Syphilis Serofast State: Diagnostic Value and NLRP3 Inflammasome Suppression
Yue Mou1, Caifeng He2, Fanxiang Wang1
1Department of Dermatology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, China.
Background:
Serofast state (SF), defined as persistent low-titer antibodies after treatment, poses a diagnostic challenge because of the overlap with serologic features of active infection. Exosomal miRNAs are stable in body fluids and have potential as diagnostic markers.
Objectives:
This study aimed to identify plasma exosomal miR-1246 as a diagnostic biomarker for SF and elucidate its role in NLRP3 inflammasome suppression, providing mechanistic insights into SF pathogenesis.
Methods:
Using microarray analysis and reverse transcription quantitative polymerase chain reaction (RT-qPCR), differential miRNA expression was measured in the plasma samples of SF patients. Microarray analysis, target gene prediction, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to identify differentially expressed microRNAs (DEmiRNAs). The plasma levels of NLRP3 and related cytokines were quantified using enzyme-linked immunosorbent assay (ELISA), and the regulatory effect of miR-1246 on NLRP3 was measured in vitro. Diagnostic performance was assessed based on receiver operating characteristic (ROC) curve analysis for miR-1246 alone and in combination with the rapid plasma reagin (RPR) test.
Results:
Plasma exosomal miR-1246 was significantly upregulated in SF patients (p < 0.001), whereas NLRP3 and its associated factors were downregulated (p < 0.05). In vitro experiments confirmed that miR-1246 negatively regulated NLRP3 inflammasome activity. GO and KEGG analyses revealed that the target genes of DEmiRNAs were involved in multiple biological processes and signalling pathways. ROC analysis showed that miR-1246 alone yielded an area under the curve (AUC) of 0.760 (sensitivity 77.4%, specificity 62.9%). When combined with RPR, the AUC increased to 0.824 (sensitivity 83.3%, specificity 65.7%).
Conclusions:
Exosomal miR-1246 is elevated in SF and may contribute to its pathogenesis by inhibiting NLRP3 inflammasome. It demonstrates potential as a diagnostic biomarker, particularly when combined with RPR.
Insights
Plasma exosomal miR-1246 is elevated in serofast patients and may suppress the NLRP3 inflammasome. This microRNA shows promise as a diagnostic biomarker, especially when combined with the RPR test.
Area of Science:
- Biochemistry
- Immunology
- Molecular Biology
Background:
- Serofast state (SF) presents diagnostic challenges due to overlapping serologic features with active infections.
- Exosomal microRNAs (miRNAs) are stable biomarkers in body fluids, offering diagnostic potential.
Purpose of the Study:
- Identify plasma exosomal miR-1246 as a diagnostic biomarker for SF.
- Elucidate miR-1246's role in NLRP3 inflammasome suppression and SF pathogenesis.
Main Methods:
- Microarray and RT-qPCR to measure differential miRNA expression in SF patient plasma.
- ELISA to quantify NLRP3 and cytokine levels; in vitro experiments to assess miR-1246's regulatory effect on NLRP3.
- ROC curve analysis for diagnostic performance of miR-1246 alone and with RPR test.
Main Results:
- Plasma exosomal miR-1246 was significantly upregulated in SF patients, while NLRP3 and associated factors were downregulated.
- In vitro studies confirmed miR-1246 negatively regulates NLRP3 inflammasome activity.
- Combined miR-1246 and RPR test achieved an AUC of 0.824, improving diagnostic accuracy.
Conclusions:
- Exosomal miR-1246 is elevated in SF and may inhibit NLRP3 inflammasome, contributing to pathogenesis.
- miR-1246 shows potential as a diagnostic biomarker for SF.
- Combining miR-1246 with the RPR test enhances diagnostic performance for SF.
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