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large-scale clinical trials are lacking, and findings show dose- and context-dependent variability (U-shaped dose-response curve in some cases)

At the receptor level, IGF-1 LR3 binds the IGF-1 receptor (IGF1R) and activates its intrinsic tyrosine kinase domain, which initiates downstream signaling through the PI3K/AKT and MAPK/ERK cascades

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Thus, SARS-CoV-2-mediated cell surface reduction of hACE2 receptors could trigger widespread inflammatory sequelae observed in COVID-19, which may linger through long-COVID for an extended period of time

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