Natural environments and suicide mortality in the Netherlands: a cross-sectional, ecological study

Background: Natural outdoor environments, such as green spaces (ie, grass, forests, or parks), blue spaces (ie, visible bodies of fresh or salt water), and coastal proximity, have been increasingly shown to promote mental health. However, little is known about how and the extent to which these natural environments are associated with suicide mortality. Our aim was to investigate whether the availability of green space and blue space within people's living environments and living next to the coast are protective against suicide mortality. Methods: In this cross-sectional, ecological study, we analysed officially confirmed deaths by suicide between 2005 and 2014 per municipality in the Netherlands. We calculated indexes to measure the proportion of green space and blue space per municipality and the coastal proximity of each municipality using a geographical information system. We fitted Bayesian hierarchical Poisson regressions to assess associations between suicide risk, green space, blue space, and coastal proximity, adjusted for risk and protective factors. Findings: Municipalities with a large proportion of green space (relative risk 0·879, 95% credibility interval 0·779–0·991) or a moderate proportion of green space (0·919, 0·846–0·998) showed a reduced suicide risk compared with municipalities with less green space. Green space did not differ according to urbanicity in relation to suicide. Neither blue space nor coastal proximity was associated with suicide risk. The geographical variation in the residual relative suicide risk was substantial and the south of the Netherlands was at high risk. Interpretation: Our findings support the notion that exposure to natural environments, particularly to greenery, might have a role in reducing suicide mortality. If confirmed by future studies on an individual level, the consideration of environmental exposures might enrich suicide prevention programmes

PAR2 modulators derived from GB88

PAR2 antagonists have potential for treating inflammatory, respiratory, gastrointestinal, neurological, and metabolic disorders, but few antagonists are known. Derivatives of GB88 (3) suggest that all four of its components bind at distinct PAR2 sites with the isoxazole, cyclohexylalanine, and isoleucine determining affinity and selectivity, while the C-terminal substituent determines agonist/antagonist function. Here we report structurally similar PAR2 ligands with opposing functions (agonist vs antagonist) upon binding to PAR2. A biased ligand AY117 (65) was found to antagonize calcium release induced by PAR2 agonists trypsin and hexapeptide 2f-LIGRLO-NH2 (IC50 2.2 and 0.7 mu M, HT29 cells), but it was a selective PAR2 agonist in inhibiting cAMP stimulation and activating ERK1/2 phosphorylation. It showed antiinflammatory properties both in vitro and in vivo

Anti-epileptic effect of Ganoderma lucidum polysaccharides by inhibition of intracellular calcium accumulation and stimulation of expression of CaMKII a in epileptic hippocampal neurons

Purpose: To investigate the mechanism of the anti-epileptic effect of Ganoderma lucidum polysaccharides (GLP), the changes of intracellular calcium and CaMK II a expression in a model of epileptic neurons were investigated. Method: Primary hippocampal neurons were divided into: 1) Control group, neurons were cultured with Neurobasal medium, for 3 hours; 2) Model group I: neurons were incubated with Mg2+ free medium for 3 hours; 3) Model group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with the normal medium for a further 3 hours; 4) GLP group I: neurons were incubated with Mg2+ free medium containing GLP (0.375 mg/ml) for 3 hours; 5) GLP group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with a normal culture medium containing GLP for a further 3 hours. The CaMK II a protein expression was assessed by Western-blot. Ca2+ turnover in neurons was assessed using Fluo-3/AM which was added into the replacement medium and Ca2+ turnover was observed under a laser scanning confocal microscope. Results: The CaMK II a expression in the model groups was less than in the control groups, however, in the GLP groups, it was higher than that observed in the model group. Ca2+ fluorescence intensity in GLP group I was significantly lower than that in model group I after 30 seconds, while in GLP group II, it was reduced significantly compared to model group II after 5 minutes. Conclusion: GLP may inhibit calcium overload and promote CaMK II a expression to protect epileptic neuron

Efficient chemical synthesis of human complement protein C3a

We report the total chemical synthesis of human C3a by one-pot native chemical ligation of three unprotected peptide segments, followed by efficient in vitro folding that yielded the anaphylatoxin C3a in high yield and excellent purity. Synthetic C3a was fully active and its crystal structure at 2.1 Å resolution showed 3 helices and a C-terminal turn motif