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10.1038/s41587-021-01195-w

In the detection of methylation of bladder cancer protective genes that are also Wnt antagonist genes such as secreted frizzled-related protein 1 (SFRP1), WNT inhibitory factor-1 (WIF1), APC and CDH1, it was found that in all the samples, at least one gene was found to be methylated and then down-regulated, leading to excessive activation of Wnt pathway and uncontrolled proliferation of bladder cells, which promote the occurrence and development of bladder cancer (243,244)

Mice lacking functional leptin receptors present dysregulated circadian behavioral rhythms, changes in body temperature, severe overeating and altered photic responses of the SCN 129

The integrated approach involves: First, employing network pharmacology to predict potential multi-target interactions, followed by molecular docking against three-dimensional structures of relevant targets (e.g., Mpro and RdRp) to prioritize potential synergistic pairs