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In the TME, macrophages can manifest as the M1 type (characterized by inflammatory and antitumour responses) or M2 type (involved in the repair of damaged tissues and anti-inflammation), but the TME tends to induce the differentiation of macrophages towards the M2 type (120122)

More interestingly, research has found that using siRNA to knock down the Growth factor independence 1 (Gfi1) gene in chondrocytes, or overexpressing this gene via intra-articular AAV-Gfi1 injection, inactivated the MAPK signaling pathway, subsequently observing downregulation of ferroptosis promoters such as Cox2 and Acsl4 and upregulation of ferroptosis inhibitors such as GPX4 and SLC7A11, ultimately alleviating cartilage degeneration, osteophyte formation, and synovitis, and improving OA progression (Jin et al., 2025)

GRK2 interacts with and phosphorylates Nedd4 and Nedd4-2

So I really spent a huge amount of my career having to look deeply into the interrelationships so I could figure out what system causes problems in that system

10.1016/j.canlet.2016.07.035 139 RohJ.-L.KimE

Clinical trials in certain cancer types have shown that vitamin C IV therapy can make tumour cells more sensitive to chemotherapy and radiotherapy