GEO database analysis of synovial tissue revealed that malate-related enzymes, including malic enzyme (ME) and malate dehydrogenase (MDH), as well as enzymes involved in the aspartate-malate shuttle, were significantly upregulated in RA synovium compared to healthy controls (Figure S8E), suggesting abnormal malate metabolism in RA. This evidence concerns the gene MMP12 and rheumatoid arthritis.