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Description
JAK inhibitors treatment for rheumatoid arthritis increases the risk of cardiovascular events and malignancies, leading to the FDA to class black-box warning for baricitinib, ritlecitinib, and upadacitinib [45, 46]

Surface modification of drug delivery systems with such molecules allows them to penetrate the BBB and get into the brain via the AME

Patent 6,288,040(i.e., carbodiimide, n-ethoxycarbonyl-2-ethoxy-1,2-dihycroquinoline, glutardioldehyde, bromozyane, meta-periodate (Na-salt or K-salt), tosyl chloride and chloroformic acid ester)

Thus, the transition from crystal deposition to acute inflammation can be conceptualized as a two-hit process: First hit: MSU crystal deposition on cartilage surfaces activates synovial fibroblasts to release CCL2/MCP-1, recruiting monocytes and establishing subclinical inflammation
