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The therapeutic mechanisms of methotrexate in RA include: inhibition of dihydrofolate reductase to reduce nucleic acid production and promote cell death (78), downregulation of Th1 cells and upregulation of Th2 cells and Tregs (79), amelioration of bone destruction by increasing osteoprotegerin (OPG) and decreasing RANKL (80), suppression of osteoclast differentiation (92), and inhibition of MMP expression and cartilage matrix absorption (93)

At the mechanistic level, research predominantly remains at descriptive correlations

Q J Med 75(3):617633 Matsuzaki M, Nakamura K, Akutsu S, Onodera K, Sekino M (1976) Fundamental studies on fusaric acid and calcium fusarate

To date, microorganisms and plant tissue cultures can serve as factories for synthesizing semiochemicals through metabolic pathway reconstruction and/or plant elicitation (Nabi et al., 2025)