## 3 Results
### TF-miRNA-DEP Interacted Network  
The TF-miRNA interacted network was constructed through network analysis of 29 DEPs in Cytoscape (Figure 6B), which included 27 DEPs, 27 TFs, and 15 miRNAs, involving 99 associations between the TFs and DEPs, and 34 associations between the miRNAs and DEPs. We separately analyzed the degree of 27 DEPs in the TF-DEP network and the miRNA-DEP network (Table 2). Then, we found that MYC and SP1 regulated seven interacting DEPs. Simultaneously, hsa-miR-17 regulated five DEPs and hsa-miR-330-3p regulated three interacted DEPs.  
Figure 5: The most relevant biological processes (BPs), molecular functions (MFs), and cellular components (CCs) through GO enrichment analysis, and KEGG pathway enrichment analysis of differentially expressed proteins between EVs isolated from the Icarini-treated group and the Model group.  
\begin{table}
\begin{tabular}{c c c c} \hline \hline
**MCC** & **MNC** & **Degree** \\ \hline ICAM1 & ICAM1 & ICAM1 & ICAM1 \\ MMP3 & MMP3 & MMP3 \\ BSG & BSG & BSG \\ LGALS3 & CXCL9 & LGALS3 \\ CXCL9 & CXCL16 & CXCL9 \\ CXCL16 & LGALS3 & CXCL16 \\ MMP10 & MMP10 & MMP10 \\ IL36 RN & IL36 RN & IL36 RN \\ TNFR1B & TNFRSF1B & TNFR1B \\ \hline \hline \end{tabular}
\end{table}
Table 1: List of the top nine hub genes selected by MCC, MNC and degree methods in CytoHubba.  
\begin{table}
\begin{tabular}{c c c c c} \hline \hline
**MiRNAs** & **Targeted Genes** & \begin{tabular}{c} **Gene** \\ **Counts** \\ \end{tabular} & \begin{tabular}{c} **Transcription** \\ **Factors (TF)** \\ \end{tabular} & \
\begin{tabular}{c} **Targeted Genes** \\ **Counts** \\ \end{tabular} &
\begin{tabular}{c} **Gene** \\ **Counts** \\ \end{tabular} \\ \hline hsa-miR-17 & ICAM1, MMP3, & 4 & MYC & ICAM1, BSG, ICAM2, FTL, \\  & SIGLEC10, RGMB & & & LGALS1, CSTB, ENO2 \\ hsa-miR-330-3p & DKK3, MME, WIF1 & 3 & SP1 & ICAM1, ICA2, FT, CSTB, \\  & & & & SICLEC10, LGALS9, MME \\ hsa-miR-22 & FTL, LGALS1, BMP7 & 3 & NFKB1 & ICAM1, ICAM2, MMP3, GH1, \\  & & & & FSTL3, TNFRSF1B \\ hsa-let-7d & DKK3, LYVE1 & 2 & MAX & ICAM, BSG, ICAM2, IGFBP6, \\  & & & & CSTB, TNFRSF1B \\ hsa-miR-106a & MMP3, RGMB & 2 & JUN & ICAM1, MMP3, FTL, CSTB, \\  & & & & LGALS3, CXCL16 \\ hsa-miR-124 & LRP6, FSTL3 & 2 & SPI1 & ICAM1, FTL, IGFBP6, \\  & & & & SICLEC10, GHI, MME \\ hsa-miR-129-5p & LRP6, WIF1 & 2 & CTCF & LGALS1, MMP10, BMP7, \\  & & & & TNFRSF1B, WIF1, RGMB, \\ hsa-miR-19a & LRP6, TNFRSF1B & 2 & RELA & ICAM1, ICAM2, MMP3, FST13, \\  & & & & TNFRSF1B \\ hsa-miR-216b & MME, WIF1 & 2 & TFAP2A & BSG, CSTB, TIMP4, SIGLEC10 & 4 \\ hsa-miR-32 & DKK3, MMP10 & 2 & FOS & MMP3, FTL, LGALS3, \\  & & & & TNFRSF1B \\ hsa-miR-329 & DKK3, FSTL3 & 2 & TBP & MMP3, FTL, MMP10, GH1 & 4 \\ hsa-miR-577 & MMP3, LRP6 & 2 & TFAP2C & BGS, LGALS3, TIMP4 & 3 \\ hsa-miR-708 & DKK3, CXCL9 & 2 & STAT1 & ICAM1, CXCL9, TNFRSF1B & 3 \\ hsa-miR-9 & MME, LYVE1 & 2 & EBF1 & LGALS1, LGALS3, GH1 & 3 \\ \hline \hline \end{tabular}
\end{table}
Table 2: TF-miRNA-DEP interacted network.  
Figure 6: (**A**) The interactions between the 29 differentially expressed proteins between EVs isolated EVs from the Model group and the Icarin-treated group; (**B**) The TF–gene–miRNA interaction network.