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Experimental studies demonstrate that BRNPs significantly upregulate Wnt pathway activity in myocardial ischemia-reperfusion models (Kim et al., 2024), whereas research in colon cancer shows that biliverdin reductase A-mediated BL production modulates Wnt/-catenin signaling through bidirectional regulation of its target genes (Mao et al., 2020)

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Collagen-stimulating peptides like GHK-Cu and Matrixyl address wrinkles through structural improvement rather than muscle effects - increasing dermal collagen synthesis by 70-80% in vitro studies, promoting organized matrix formation rather than disorganized scar-like deposition, enhancing skin thickness obscuring fine lines, and improving overall skin quality creating fresher appearance even without direct wrinkle targeting

Table 2 Summary of the risk of bias assessment of the included studies

1 vaccine (single or combination vaccine/toxoid)