Alcoholic liver disease is the most prevalent chronic liver disease. Melatonin is known to control many vital processes. Here, we explored a novel molecular mechanism by which melatonin‐induced SIRT1 signaling protects against alcohol‐mediated oxidative stress and liver injury. Gene expression profiles and metabolic changes were measured in liver specimens of mice and human subjects. Expression levels of Cb1r, Crbn, Btg2, Yy1, pro‐inflammatory cytokines, and Cyp2e1 were significantly enhanced in chronic alcohol‐challenged mice and human subjects. Levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic CYP2E1 protein, and reactive oxygen species (ROS) were elevated in alcohol‐fed WT mice but not in Cb1r antagonist‐treated, Crbn null, or Yy1‐silenced mice. Importantly, alcohol‐induced Yy1 and Cyp2e1 expression, ROS amount, and liver injury were markedly diminished by melatonin treatment and the transduction of Sirt1 in mice, whereas this phenomenon was prominently ablated by silencing of Sirt1. Notably, SIRT1 physically interacted with YY1 and attenuated YY1 occupancy on the Cyp2e1 gene promoter. Melatonin‐SIRT1 signaling ameliorates alcohol‐induced oxidative liver injury by disrupting the CRBN‐YY1‐CYP2E1 signaling pathway. The manipulation of CRBN‐YY1‐CYP2E1 signaling network by the melatonin‐SIRT1 pathway highlights a novel entry point for treating alcoholic liver disease.
Mycotoxins are secondary metabolites produced by various fungi and are known to have a significant negative impact on human and animal health. When feedstuffs are contaminated with mycotoxins, their toxicities may be caused a variety of diseases. In this study, the residual mycotoxins in feedstuffs were analyzed using LC–MS/MS incorporated with QuEChERS extraction. Analytical method validation was performed for LOD, LOQ, linearity, and recoveries with consideration of matrix effects prior to the residual analysis. They were all reached to the accepted range of validation level. Using 39 feedstuff samples (5 g) for mycotoxin analysis, nine samples were contaminated by four major mycotoxins such as fumonisin B1 (FB1), deoxynivalenol, fumonisin B2, and zearalenone. Among them, FB1 was detected at the highest concentration as 18.0943 mg/kg. The total sum of fumonisins in 39 samples did not exceed the maximum residual level (MRL) criterion set by Korean Food and Drug Administration. Altogether, intensive management of mycotoxins in Korean feedstuffs should be implemented with proper and routine monitoring, even their residual concentrations are not exceeded over the MRL levels because of high frequent detection found in this study.
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants that are released by incomplete combustion of carbon-containing materials. The top soils of rice paddies were collected from Gyeonggi-do (18 sites), Ulsan (20 sites), and Pohang (19 sites) in Korea to assess the spatial distribution and potential sources of PAHs. The total concentrations of 15 PAHs in the soils were 19.53-672.93, 125.01-3106.27, and 51.94-8106.21 mg/kg in Gyeonggi province, Ulsan, and Pohang, respectively. The concentration of 7 key carcinogenic PAHs were followed the order: Pohang (38.54-4826.63 ng/g) > Ulsan (28.54-1561.39 ng/g) > Gyeonggi province (19.53-206.51 ng/g). Three-ring PAHs were predominant in the soils from Gyeonggi-do while 3-5 ring compounds were abundant in the agricultural soils from the two industrial regions (Ulsan and Pohang). The PAH isomeric diagnostic ratios indicated that PAH contamination in the two cities mainly originated from pyrogenic sources. The principal component analysis indicated that pyrogenic coal burning and residential biomass combustion were major contributors to the soil contamination in the two cities. The transportation of PAHs through the air from industrial complexes and high volume of traffic may influence the PAHs distribution in the soils of the two cities in Korea.
Regulation of melanin production via the MC1R signaling pathway is a protective mechanism of the skin of living organisms against exposure to ultraviolet rays. The discovery of human skin-whitening agents has been one of the most intense pursuits of the cosmetic industry. The MC1R signaling pathway is activated by its agonist, alpha-melanocyte stimulating hormone (α-MSH), and mainly regulates melanogenesis. Here, we evaluated the antimelanogenic activities of curcumin (CUR) and its two derivatives, dimethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC), in B16F10 mouse melanoma cells and zebrafish embryos. CUR and BDMC reduced the α-MSH-induced melanin production in B16F10 cells and also downregulated the expression of the melanin-production-related genes Tyr, Mitf, Trp-1, and Trp-2. Moreover, the biological activity of these two compounds against melanogenesis was confirmed in in vivo experiments using zebrafish embryos. However, the highest concentration of CUR (5 µM) resulted in slight malformations in zebrafish embryos, as indicated by acute toxicity tests. In contrast, DMC did not show any biological activity in vitro or in vivo. Conclusively, BDMC is a strong candidate as a skin-whitening agent.
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