Occlusal disharmony leads to causes chronic stress and lead to sympathetic nerve activity. Various types of chronic stress are associated with increased incidence of cardiovascular disease, but the relationship between occlusal disharmony and cardiovascular disease remain poorly understood. Therefore, we examined the effects of occlusal disharmony on cardiac function in bite-opening (BO) mice, in which a 0.7 mm space was introduced by cementing a suitable applicance onto the mandibular incisor. Our data shown in this reviewpt indicated that occlusal disharmony might cause sympathetic nerve activity in the heart, leading to cardiac remodeling and dysfunction.

　Background: This study investigated the acute effects of heat-not-burn cigarettes and combustion cigarettes on vascular endothelial function.

　Methods: Eight healthy young males with a smoking habit were included in this study. Each participant used either new-generation heat-not-burn or traditional tobacco combustion cigarettes, and vascular endothelial function was measured before and 120 min after using either type of cigarette.

　Results: In both conditions, the reactive hyperemia index was significantly lower at 90 and 120 min after smoking than before smoking (p ＜ 0.05); however, no significant difference was observed between the two conditions at any point.

　Conclusion: These results indicate that heat-not-burn and combustion cigarettes have similar acute effects on vascular endothelial function.

　Background: Basophils circulating in the blood play a proinflammatory role at sites of allergic inflammation in two stages: tissue accumulation and activation. This study analyzed the activation-enhancing effects of chemokines on chemokine-pretreated basophils using a two-step stimulation model.

　Methods: Basophils were obtained from volunteers with no history of allergic disease. Cells were pretreated with chemokines for 30 minutes and then activated for 45 minutes with IgE-mediated stimulus plus chemokines. The percent histamine release of basophils was measured.

　Results: The activation-enhancing effect of MCP-1 in the presence of basophils (24.3％±6.3％) was significantly decreased (6.8％±4.1％) when the cells were pretreated with MCP-1 (p ＜ 0.01). On the other hand, the enhancing effect of eotaxin (9.5％±8.0％) was maintained (8.8％±3.8％) when the cells were pretreated with eotaxin (p ＞ 0.05).

　Conclusion: The results indicate that basophils retain their histamine release-enhancing effect when eotaxin is used at both the pretreatment and activation steps. However, the activation enhancing effect of MCP-1 was reduced when basophils were pretreated with MCP-1. Our two-step model of human basophil pretreatment and activation showed different patterns of chemokine action.

　Background: E-selectin, a cell adhesion molecule, is involved in the early stage of atherosclerosis, and lipopolysaccharide (LPS) is involved in upregulating E-selectin expression. The effect of nobiletin, a polymethoxylated flavone derived from citrus fruits, on LPS-induced E-selectin expression remains unclear.

　Objectives: This study explored the inhibitory effects of nobiletin on LPS-induced E-selectin expression in human umbilical vascular endothelial cells (HUVECs) and the involvement of reactive oxygen species (ROS) in the inhibitory mechanism.

　Methods: HUVECs were exposed to LPS (0−50 ng/ml) after pretreatment with nobiletin (0−200 μM), and E-selectin mRNA expression was quantified by real-time polymerase chain reaction in a concentration- and time-dependent manner. Differences in LPS-induced E-selectin mRNA expression between pretreatment and nontreatment with nobiletin were statistically analyzed. The production of superoxide, which is a precursor of most ROS, was quantified using the tetrazolium salt (WST-1) assay, and intracellular ROS production was detected using the highly sensitive DCFH-DA dye under a fluorescence microscope.

　Results: The LPS and nobiletin exposure exerted no significant effect on cell viability in the concentration range used. E-selectin mRNA expression increased in a concentration-dependent manner when HUVECs were exposed to LPS (0−50 ng/ml) for 3 h (10 ng/ml, p ＜ 0.05; 25 and 50 ng/ml, p ＜ 0.01). After LPS stimulation (10 ng/ml), E-selectin mRNA expression significantly increased in a time-dependent manner and reached the maximum at 12 h (3, 6, 12, and 24 h, p ＜ 0.01). Pretreatment of HUVECs with nobiletin downregulated the LPS-induced E-selectin mRNA expression in a concentration-dependent manner (50, 100, and 200 μM, p＜0.01). Apocynin, an NADPH oxidase inhibitor, downregulated the LPS-induced E-selectin mRNA expression in a concentration-dependent manner (100μM, p ＜ 0.01). Moreover, nobiletin (200μM) exerted significant inhibitory effects on LPS-induced ROS production in both the WST-1 assay (p ＜ 0.01) and cell images.

　Conclusion: Nobiletin downregulated LPS-induced E-selectin mRNA expression through inhibition of LPS-induced superoxide production.