Amphoterin is 1 ligand of the receptor for advanced glycation end products (RAGE). We studied expression of amphoterin and RAGE mRNA and proteins in colorectal carcinoma cells and investigated their associations with the invasive activities of cells exposed to advanced glycation end products (AGE). Expression of RAGE and amphoterin was examined in 4 colorectal carcinoma cell lines. All cell lines expressed both RAGE and amphoterin. The effects of RAGE and amphoterin on cell growth (MTT assay), migration (wound healing assay) and invasion (in vitro invasion assay) were tested by treatment of cells with RAGE and amphoterin antisense S-oligodeoxynucleotides (ODNs). Cell growth, migration and invasion were inhibited significantly in Colo320 and WiDr carcinoma cells treated with RAGE and amphoterin antisense S-ODNs compared with sense-treated cells. Differences in ligand activity between amphoterin and AGE were examined with AGE-bovine serum albumin (BSA). AGE-BSA decreased cell growth, migration and invasion of amphoterin antisense S-ODN-treated Colo320 and WiDr cells compared with those of cells treated with Colo320 conditioned medium. Phosphorylation of extracellular signalregulated kinase-1/2, Rac1 and AKT and production of matrix metalloproteinase 9 were increased to a greater degree by amphoterin than by AGE-BSA. In contrast, production of inducible nitric oxide synthase and nuclear factor-Bp65 were increased to a greater degree by AGE-BSA than by amphoterin.

The study confirmed reduced CSF histamine levels in hypocretin-deficient narcolepsy with cataplexy. Similar degrees of reduction were also observed in hypocretin non-deficient narcolepsy and in idiopathic hypersomnia, while those in OSAS (non central nervous system hypersomnia) were not altered. The decrease in histamine in these subjects were more specifically observed in non-medicated subjects, suggesting CSF histamine is a biomarker reflecting the degree of hypersomnia of central origin.

Aim: The cardio-ankle vascular index (CAVI) reflects functional arterial stiffness, which is related to endothelial dysfunction. CD34-positive cells carry out an important function in endothelial repair. However, there have been no reports assessing the association between CAVI and the number of circulating CD34-positive cells.Methods: We carried out a cross-sectional study of 249 Japanese men, aged 60-69 years, who underwent annual health checkups between 2013 and 2015. As individuals with high levels of circulating CD34-positive cells might indicate the influence of consumptive reduction of circulating CD34-positive cells as a result of aggressive endothelial repair, participants were stratified by circulating CD34-positive cell levels, using the median value in this population (0.95 cells/μL) as the cut-off.Results: For participants with low circulating CD34-positive cell levels, logarithmic values of circulating CD34-positive cells were inversely associated with CAVI (multivariable standardized parameter estimate [β] = −0.22, P = 0.014), but not for participants with high levels (β = −0.04, P = 0.638). In addition, even when no significant associations between CAVI and carotid intima-media thickness were detected for participants with low circulating CD34-positive cell levels (β = −0.02, P = 0.865), significant positive associations were identified for participants with high levels (β = 0.22, P = 0.028). Conclusions:As circulating CD34-positive cell count might indicate endothelial repair activity, the present results show that CAVI is affected by insufficient endothelial repair in individuals with low circulating CD34-positive cell counts. Our results also show that a positive association between CAVI and carotid intima-media thickness exists only in individuals with aggressive endothelial repair, which indicates the presence of organic arterial disease, such as atherosclerosis.

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We examined the biological effects of nitric oxide (NO) and its mediator, heme oxygenase-1 (HO-1), in cancer. Urogenital cancer cell lines, SKRC, T24 and DU145, were treated with various concentrations of sodium nitroprusside (SNP), a NO donor. The medium nitrite concentration was exponentially increased according to the concentration of SNP. Cell growth inhibition by NO was observed only at high nitrite concentrations (>20 microM) in DU145 and T24 cells. Nitrite did not inhibit the growth of SKRC cells at any of the concentrations used. Doxorubicin (DXR) inhibited cell growth in the three cell lines, whereas growth inhibition recovered in the presence of <10 microM nitrite. The recovery of DXR-induced growth inhibition was closely associated with an increase in Bcl-2 in the presence of <10 microM nitrite. Vascular endothelial growth factor (VEGF) secretion was also increased in the presence of <10 and <20 microM nitrite, respectively, in DU145 and SKRC or T24 cells. The expression of HO-1 was associated with sensitivity to NO-induced growth inhibition at constitutive levels, and was induced by SNP treatment. HO-1 inhibition by HO-1 antisense S-oligodeoxynucleotide treatment increased NO-induced growth inhibition, and decreased Bcl-2 expression or VEGF secretion in the three cell lines. These findings suggest that the NO/HO-1 system has protumoral effects.

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