(1) and the present Alu-mediated deletion are the first Alu-mediated events to be described for any type of isolated hair loss.
ConclusionsIn conclusion, the present report is the first to describe a homozygous loss of the entire LPAR6 gene. The presence of three Alu sequences around the deletion breakpoints suggests that these Alu elements form intrastrand hairpin loops that are easily rearranged. Formation of a 'triple-barrel' structure may promote primer-template slippage during DNA replication, thereby promoting LPAR6 deletion if polymerase is able to bypass the loop. This expands the spectrum of LPAR6 mutations and suggests a novel mechanism for this gene and for the formation of DNA rearrangements in general.
Bacterial lipopolysaccharide (LPS) induces expression of pro-inflammatory cytokines and enzymes producing nitric oxide (NO) and prostaglandins (PGs) in immune cells. This process is mediated by the activation of nuclear factor kappaB (NF-κB). In this study, we investigated the anti-inflammatory characteristics of Codium fragile ethanolic extract (CFE) mediated by the regulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) using LPS-stimulated murine macrophage RAW 264.7 cells. CFE significantly inhibited LPS-induced NO and PGE 2 production in a dose-dependent manner and suppressed the expression of iNOS and COX-2 proteins in LPS-stimulated RAW 264.7 cells with no cytotoxicity. Pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, were significantly reduced by treatment of CFE in LPS-stimulated RAW 264.7 cells. CFE inhibited the promoter activity of (NF)-κB in LPS-stimulated macrophages. Treatment with CFE suppressed translocation of the NF-κB p65 subunit by preventing proteolytic degradation of inhibitor of κB-α. These results indicate that the CFE-mediated inhibition of NO and PGE 2 production in LPS-stimulated RAW 264.7 cells is mediated through the NF-κB-dependent transcriptional downregulation of iNOS and COX-2, suggesting the potential of CFE as a nutraceutical with antiinflammatory activity.
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