Injury of cortical neurons is caused by the advanced glycation end products-mediated pathway

Advanced glycation end products lead to cell apoptosis, and cause cell death by increasing endoplasmic reticulum stress. Advanced glycation end products alone may also directly cause damage to tissues and cells, but the precise mechanism remains unknown. This study used primary cultures of rat cerebral cortex neurons, and treated cells with different concentrations of glycation end products （50, 100, 200, 400 mg/L）, and with an antibody for the receptor of advanced glycation end products before and after treatment with advanced glycation end products. The results showed that with increasing concentrations of glycation end products, free radical content increased in neurons, and the number of apoptotic cells increased in a dose-dependent manner. Before and after treatment of advanced glycation end products, the addition of the antibody against advanced glycation end-products markedly reduced hydroxyl free radicals, malondialdehyde levels, and inhibited cell apoptosis. This result indicated that the antibody for receptor of advanced glycation end-products in neurons from the rat cerebral cortex can reduce glycation end product-induced oxidative stress damage by suppressing glycation end product receptors. Overall, our study confirms that the advanced glycation end products-advanced glycation end products receptor pathway may be the main signaling pathway leading to neuronal damage.

MyD88 in macrophages protects against colitis via inhibiting the activation of NLRP3 inflammasome in epithelial cells

The signal adaptor myeloid differentiation primary response 88(MyD88)of Toll-like receptor(TLR)signaling is universally expressed in immune cells and non-immune cells,and myeloid cells play a significant role in modulating colitis.Macrophages are myeloid lineage cells which is important for maintaining intestinal homeostasis in inflammation.1 And macrophages can recognize invading pathogens through pattern recognition receptors(PRRs),such as TLRs and the nucleotide oligomerization domain(NOD)-like receptor family,pyrin domain-containing 3(NLRP3),and quickly infiltrate the injured site leading to inflammation.2 MyD88 expression in myeloid cells can rescue the intestinal injury induced by dextran sulfate sodium(DSS)in murine models.However,the mechanism whereby MyD88 works in myeloid cells and influence the progress of the disease remain elusive.In this study,we used DSS induced colitis mouse model and found Lysm-cre-MyD88fl/fl(MyD88ΔМΦ)mice were more susceptible to colitis.The deficiency of MyD88 leads to up-regulation of S100A8,which activate NLRP3 inflammasome and their associated pyroptosis in intestinal epithelial cells in a RAGE dependent manner.Thus,MyD88 signaling in macrophages,which is necessary to maintain intestinal homeostasis,crucially prevents the development of colitis.Our results may shed new lights on potential targets that can be applied in colitis therapy.

The economic value of grassland ecosystem services: A global meta-analysis

Background:Grasslands provide a wide variety of ecosystem services that contribute to human wellbeing.While an increasing number of studies are evaluating the monetary value of grassland ecosystem services,most of them focus on specific grassland ecosystem services at regional or local scales,and they use different assessment methods.Methods:This paper provides a comprehensive assessment of the economic value of global grassland ecosystem services based on a meta-analysis of 702 observations from 134 primary studies.Results:The economic values of different ecosystem services cover a wide range of grassland types,regions,and estimation methods.The annual economic value per hectare ranges from$3955 for semidesert grasslands to$5466 for tropical grasslands.On average,regulating services have the highest value,which is approximately four times that of provisioning services or approximately eight times that of food supply services.Several factors impact the estimated ecosystem service values,including the evaluation method,source and year of publication,and study site.The results indicate that the annual economic value of global grasslands exceeds$20.8 trillion.Conclusions:The findings of this study not only provide useful information for understanding the economic value of various ecosystem services associated with different types of grasslands but also have important policy implications for the ecological conservation of grassland globally.