Fig. 3

Bioinformatics analysis of expression profiling by high throughput sequencing on GSE80178 and regulation of miR-21 by PEP@GO A PCA of hierarchical cluster analysis of all the 12 samples. B Volcano plot for DEGs between the DFU and normal samples. Red and blue dots represent up- and down-regulated genes, respectively, while grey are no significantly differentially expressed genes. C Heatmap of top 25 up- (red) and down-regulated (blue) genes in the DFU and Normal samples, and the color depth of the blocks represents the degree of mediation. D, E KEGG pathway enrichment analysis of infection-associated (D) up- and (E) down-regulated pathways. The color of the dots increases from blue to red to indicate the significance of enrichment gradually, and the number of differential genes found in each pathway is indicated by the size of the dots. Characterization of sEVs stimulated by PEP and PEP@GO (F–I). F, G The mean particle size distribution of PEP-sEVs and PEP@GO-sEVs. G TEM pictures of the ultrastructure of the two kinds of sEVs. Scale bar: 200 nm. H The marker protein levels of CD9, CD63, and TSG 101. I The sEVs of two groups marked with the red fluorescence dye PKH26 were co-cultured with HUVECs Scale bar: 50 μm. qPCR results of relative level of three miRNAs in ADSCs after co-cultured with PEP@GO and PEP (J) and in sEVs of two groups (K)