In M1-polarizing conditions (Fig. 7A–C, Supplemental Table S2, Data File S5A), 65–79*SE was predicted to stimulate activation of pro-inflammatory, pro-RA upstream regulators, such as Stat3, Rel, Rela, Jun, Ctnnb1 and Hif1a, among others, and to inhibit anti-arthritis or anti-inflammatory regulators (e.g. Klf2, Xbp1, Foxp3) (Fig. 7A). This evidence concerns the gene REL and rheumatoid arthritis.