Plasma-Derived Small Extracellular Vesicles miR- 182 - 5p Is a Potential Biomarker for Diagnosing Major Depressive Disorder

Figures

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  Fig. 1. Characterization of plasma-derived sEVs. a sEVs isolation protocol. b TEM images revealed that sEVs were oval or bowl-shaped capsules devoid of the nucleus. c NTA results suggested that plasma-derived sEVs ranged in diameter from approximately 50 to 120 nm. d Western blot analysis of CD9, CD63, TSG101, Calnexin, and ApoA1 expression in plasma-derived sEVs samples. sEVs, small extracellular vesicles

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  Fig. 2. MicroRNA profile of plasma-derived sEVs. a Heatmap illustrating the differentially expressed microRNAs between HCs and MDD cases. The red and blue markers represent the differentially expressed miRNAs that target depression-related genes, with the red markers representing miRNAs that we have validated in Fig. 2b. b Validation of miR- 182 - 5p expression in sEVs through RT-qPCR. MDD group: n = 11; HC group: n = 7. Relative expression was calculated using the 2^−△△.Ct method, ** represents P < 0.01

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  Fig. 3. Validated candidate miRNAs in the plasma of CMS mice. a Flow chart outlining the experimental design. b–d Behavioral assessments were conducted using the open field test (OFT); tail suspension test (TST); and sucrose preference test (SPT); sample sizes were as follows: CMS group: n = 18–20; control group: n = 15. Data are presented as mean ± SEM. Statistical significance is indicated by ** (P < 0.01) and *** (P < 0.001). e The levels of candidate miRNAs in plasma-derived sEVs from CMS and control mice were quantified via RT-qPCR (n = 7). ** represents P < 0.01

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  Fig. 4. MDD plasma-derived sEVs enhanced HPA axis activity in mice. a Representation of CRF protein expression. No injection, C57BL/6 J mice without any treatment. Control-sEVs, C57BL/6 J mice injected with sEVs from HCs. Depression-sEVs, C57BL/6 J mice injected with sEVs from MDD (n = 9). b Statistical analysis is presented. Data are expressed as mean ± SEM. ***P < 0.001

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  Fig. 5. GO enrichment and KEGG pathway analysis of miRNA target genes in plasma-derived sEVs. a Bubble plot illustrating the results of the GO enrichment analysis for miRNA target genes. b Bubble plot depicting the findings of the KEGG pathway analysis for miRNA target genes