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GGT activity was reported to be particularly high in tissues with secretory and absorptive function such as kidney, biliary system, intestine and epididymis and the enzyme activity is greatest in the ductal luminal surface of these tissues (3)

Regulation of TIMP-1 expression involves the activation of transcription factors including AP-1, Sp1, STAT, and Pea3/Ets families, as well as signaling pathways such as the ERK1/2 pathway [51]-[53]

Morever, immune cells such as T cells and innate lymphocytes, which have only recently been discovered, still require a great deal of research to demonstrate the role and mechanisms of UA in their regulation

A randomized double-blind placebo-controlled phase IIB trial treated patients with oral leukoplakia using curcumin (3.6 g daily for 6 months) and noted a significant and durable clinical response, including reduction in lesion size and histopathological improvement in terms of reduced dysplasia in some cases (Kuriakose et al., 2016)

In conclusion, although the limited number of our validation cohort, these results suggested the same characteristics in the public cohort and Beijing cohort based on the FRGs classification

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