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This dual action (proliferate but dont yet differentiate) is mechanistically distinct from mature IGF-1, which primarily drives differentiation, and explains why MGF and IGF-1Ea have sequential, complementary roles in the muscle regeneration programme: Acute phase (024 hours post-injury): MGF/IGF-1Ec mRNA peaks locally in damaged muscle confirmed at T24 in human muscle following eccentric exercise activating satellite cells to exit quiescence and enter the cell cycle Proliferative phase (2472 hours): Satellite cells proliferate, fuelled by MGF signalling, while differentiation is suppressed Differentiation phase (72120+ hours): IGF-1Ea mRNA rises as MGF declines shifting the programme toward myoblast differentiation, myotube fusion, and myofibre maturation PEG-MGF allows researchers to deliver the MGF signal at controlled intervals across this entire time course without the pharmacokinetic limitations of native MGF

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4), is derived from the balance between the GEF and GAP activity-mediated processes

Complementing these transcriptional insights, spatial transcriptomics offers the resolution necessary to define the oxidative barriers inherent to the tumor architecture