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Methotrexate blocks the DHFR enzymethe very enzyme folic acid needs to become active. Its like directing cars onto a road thats completely closed

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Observer bias in randomized clinical trials with measurement scale outcomes: a systematic review of trials with both blinded and nonblinded assessors

The resulting ROS can impair DNA, increase lipid peroxidation, lead to arteriosclerosis, destroy the extracellular matrix, stimulate bone erosion, activate osteoclasts, increase inflammation, and finally destroy joints [39]