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The pathogenesis of DN involves complex interactions among metabolic dysregulation, oxidative stress, inflammatory responses, and fibrotic signaling pathways (Figure 1)

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Functional HIF-1 corresponding elements were found in the promoter sequence of the human BNP gene, proving that HIF-1 can induce the activation of the BNP promoter, the transcription of BNP mRNA, and the synthesis and secretion of BNP under hypoxic conditions [90]

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Samples from different conditions are combined early in processing, with relative protein abundance determined by heavy-to-light peptide signal ratios (Peters-Hall et al., 2015)