Melatonin Receptor Agonist Ramelteon Suppresses LPS-Induced Neuroinflammation in Astrocytes.

Astrocytes-mediated neuroinflammation has been involved in the process of several neurodegenerative diseases. Ramelteon is a novel agonist of melatonin receptors and licensed for the management of insomnia. In this study, our results demonstrate that Ramelteon ameliorated lipopolysaccharide (LPS)-induced inflammatory responses in astrocytes. First, we found that the optimized incubation concentrations of Ramelteon applied in the present study were 50 and 100 nM. Second, treatment with Ramelteon reduced expressions of IL-6, TNF-α, and IL-1ß. Additionally, Ramelteon prevented an LPS-induced increase in the expressions of iNOS, COX-2, NO, and PGE2. Importantly, we found that Ramelteon reduced the expression of GFAP. Mechanistically, we found that Ramelteon inhibited the TLR4/IκBα/NF-κB p65 axis. Notably, the protective effects of Ramelteon were verified in an in vivo rodent model. Based on these findings, we concluded that Ramelteon might prevent LPS-induced damage in astrocytes.

Association of serum vaspin, apelin, and visfatin levels and stroke risk in a Chinese case-control study.

ABSTRACT: Adipose tissue acts as an active endocrine organ secreting a number of adipokines and may be involved in biological mechanism of stroke. Vaspin, apelin, and visfatin play important roles in the regulation of vascular disorders.Our aim was to evaluate whether the concentrations of vaspin, apelin, and visfatin were associated with stroke risk.A total of 235 patients with stroke (156 patients with ischemic stroke and 79 patients with hemorrhagic stroke) and 235 age- and gender-matched healthy controls were included in this study. A sandwich ELISA was developed to measure the serum vaspin, apelin, and visfatin levels.There was a statistically significant difference in the median levels of serum vaspin, apelin, and visfatin levels between stroke cases and controls (vaspin: 1.50 vs 1.07 ng/ml; apelin: 1.56 vs 1.32 pg/ml; visfatin: 23.40 vs 19.65 ng/ml; all P values <.001). Multiple logistic regression analysis showed that, serum vaspin and visfatin levels were significantly inversely associated with increased risk of stroke, and the odds ratios (ORs) in the highest tertile were 2.25 [95% confidence interval (CI) 1.38-3.67; P for trend <.001] for vaspin and 2.56 (95% CI 1.46-4.47; P for trend <.001) for visfatin, respectively, compared with the lowest tertile. Higher apelin levels were marginally associated with lower stroke risk (P for trend =.060).Our study indicated that higher vaspin, apelin, and visfatin levels might be associated with increased stroke risk. Necessary prospective cohort studies should be conducted to confirm this association in the future.

Effect of fluoride exposure on bone metabolism indicators ALP, BALP, and BGP.

OBJECTIVE: To analyze the changes in serum alkaline phosphatase (ALP) and bone alkaline phosphatase (BALP) activity and changes in osteocalcin (BGP) content following fluoride exposure and, thereby, determine the reference indications of fluoride-induced changes in bone metabolism. METHODS: In the animal study, rats were allowed free access to drinking water containing different concentrations (10, 150, or 400 mg/L) of sodium fluoride. Serum ALP and BALP activity and serum BGP content were assessed at three exposure time-points. In the spot study, serum ALP and BALP activity and serum BGP content were assessed in workers exposed to fluoride in their working environment for different periods of time. RESULTS: Compared with the control group, on days 15 and 30, the activity of serum ALP in the low- and medium-dose group was significantly higher (p < 0.05), while in the high-dose group it was significantly lower (p < 0.05). Only on day 30 was the activity of serum BALP in the medium-dose group significantly higher than that of the control group (p < 0.05). BGP content was lower in the high-dose group than in the control group (p < 0.05) on days 30 and 90, but it was higher in the medium-dose group on day 90. Compared with the control group, BGP content in the fluoride-exposed group was higher (p < 0.05). In the spot study, serum ALP activity and serum BGP content in the medium working-age group were higher than that in the short working-age group (p < 0.05). However, serum ALP activity and serum BGP content were lower in the long working-age group than in the medium working-age group (p < 0.05). CONCLUSIONS: Our results suggest that serum fluoride and urinary fluoride can be used as reference indications to provide an overall reflection of the body's fluoride-load and fluoride exposure level. Serum ALP activity and serum BGP content can be used as important reference indications for diagnosing bone metabolism changes resulting from fluoride exposure.