TNF and rheumatoid arthritis: Immune dysregulation in RA activates inflammatory pathways and pro-inflammatory cytokines like TNF-α, IL-1, and IL-6, causing synovial hyperplasia and cartilage destruction. RA also impacts cardiovascular health, increasing the risk of CVDs due to systemic inflammation. The NLRP3 inflammasome is a key mediator in RA inflammation, and inhibiting it reduces disease severity. NRF2, a transcription factor, downregulates NLRP3 and protects joint cells from oxidative stress. Promising NRF2 activators like RTA 408, bardoxolone methyl, sulforaphane, curcumin, and EGCG are in development.