## 3 Results
### GO and KEGG Enrichment Analyses of DEG  
Functional enrichment analysis was performed using the 176 DEGs by looking for overrepresentation of functional categories. Using the DAVID functional enrichment tool, annotations were found for 173 genes, and the most significant categories, along with the genes and the direction of change, are shown in Table 3. Three genes without annotation in the DAVID database are listed in Table S3. The most highly enriched GO functional categories among the DEG were \"nucleosome\" and \"nuclear nucleosome\", which are comprised of DNA wound around a multi-subunit core and associated proteins and form the primary packing unit of DNA into higher-order structures. As expected, genes related to inflammatory processes and immune system-related signaling, including systemic lupus erythematosus (SLE), were clearly downregulated in the HMLS compared to the DSS group. The most significantly enriched GO biological processes were \"nucleosome assembly\", \"regulation of gene silencing\", and \"DNA methylation on cytosine\" caused by histone-coding proteins (Hist1h2 ah, Hist1h3b, and Hist1h2 ag). All functionally enriched categories are listed in Table S4. KEGG pathway analysis revealed a reduction in the inflammatory response in HMLS-treated samples; cytokine-related genes, _TNF_, _LTA_, and genes in the _CCL_ family were downregulated. KEGG biological pathway analysis revealed an enrichment for genes downregulated in SLE in the HMLS group.  
\begin{table}
\begin{tabular}{c c c c} \hline \hline
**Gene ID** & **Gene Name** & **Fold Change** & **FDR** \\ \hline Downregulated & & & \\ _NOS2_ & Nitric oxide synthase 2 & 0.129 & \(1.13\times 10^{-3}\) \\ _C2 cd4b_ & C2 calcium dependent domain containing 4B & 0.163 & \(1.13\times 10^{-3}\) \\ _Ccl8_ & C-C motif chemokine ligand 8 & 0.222 & \(9.43\times 10^{-2}\) \\ _Reg3g_ & Regenerating family member 3 gamma & 0.372 & \(1.13\times 10^{-3}\) \\ _Sepina3n_ & Serine (or cysteine) peptidase inhibitor, clade A, member 3N & 0.380 & \(1.13\times 10^{-3}\) \\ _Crfl2_ & Cytokine receptor like factor 2 & 0.413 & \(9.42\times 10^{-3}\) \\ _Tac4_ & Tachykinin 4 & 0.431 & \(8.63\times 10^{-2}\) \\ _Ido1_ & Indoleamine 2,3-dioxygenase 1 & 0.434 & \(1.13\times 10^{-3}\) \\ _Gbp5_ & Guanylate binding protein 5 & 0.442 & \(3.10\times 10^{-2}\) \\ _Hck_ & HCK proto-oncogene, Src family tyrosine kinase & 0.443 & \(1.33\times 10^{-2}\) \\ _Tuf_ & Tumor necrosis factor & 0.479 & \(1.11\times 10^{-2}\) \\ _Reg3a_ & Regenerating family member 3 alpha & 0.482 & \(4.53\times 10^{-2}\) \\ \begin{tabular}{c} Hypeulated \\ _Hmox1_ \\ _Cd20_ \\ \end{tabular} & \begin{tabular}{c} Heme oxygenase 1 \\ C-C motif chemokine ligand 20 \\ \end{tabular} & \
\begin{tabular}{c} 2.027 \\ 2.940 \\ \end{tabular} &
\begin{tabular}{c} \(5.79\times 10^{-3}\) \\ \(2.05\times 10^{-3}\) \\ \end{tabular} \\ \hline \hline \end{tabular}
\end{table}
Table 2: Inflammatory Differential Gene Expression in the DSS vs. HMLS Group.  
Figure 7: PPI network of identified DEGs in DSS vs. HMLS groups constructed using the STRING database. Circles represent proteins, lines represent the interaction of proteins, and the results within the circle represent the structure of proteins. Line thickness represents the degree of interaction between proteins (Confidence cut-off score \(>\) 0.4). Circle color indicates log2 fold change, with blue indicating downregulated and red indicating upregulated expression. The larger is the circle, the lower is the \(p\)-value. (**a**) PPI network of identified DEGs in DSS vs. HMLS groups (**b**) PPI network of inflammatory reaction DEGs in DSS vs. HMLS groups.