Microglial TLR4/NLRP3 Inflammasome Signaling in Alzheimer's Disease.

Alzheimer's disease is a pervasive neurodegenerative disease that is estimated to represent approximately 70% of dementia cases worldwide, and the molecular complexity that has been highlighted remains poorly understood. The accumulation of extracellular amyloid-ß (Aß), intracellular neurofibrillary tangles formed by tau hyperphosphorylation, and neuroinflammation are the major pathological features of Alzheimer's disease (AD). Over the years, there has been no apparent breakthrough in drug discovery based on the Aß and tau hypotheses. Neuroinflammation has gradually become a hot spot in AD treatment research. As the primary cells of innate immunity in the central nervous system, microglia play a key role in neuroinflammation. Toll-like receptor 4 (TLR4) and nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasomes are vital molecules in neuroinflammation. In the pathological context of AD, the complex interplay between TLR4 and the NLRP3 inflammasomes in microglia influences AD pathology via neuroinflammation. In this review, the effect of the activation and inhibition of TLR4 and NLRP3 in microglia on AD pathology, as well as the cross-talk between TLR4 and the NLRP3 inflammasome, and the influence of essential molecules in the relevant signaling pathway on AD pathology, were expounded. In addition, the feasibility of these factors in representing a potential treatment option for AD has been clarified.

The Institute of Medicine recommendation for gestational weight gain is probably not optimal among non-American pregnant women: a retrospective study from China.

PURPOSE: To investigate whether the Institute of Medicine (IOM) recommended gestational weight gain (GWG) range is optimal among Chinese singleton pregnant women. METHODS: For the purpose of a retrospective observational study, data on 8209 mature singleton deliveries in Shanghai from January 2014 to December 2016 were extracted from medical records in terms of clinical performance. All cases were categorized as undergainers, appropriate-gainers, and above-gainers according to IOM recommended gestational weight gain range after stratification of maternal BMI and proportions of three categories were calculated. Comparisons of maternal and neonatal outcome were conducted among three categories and the associations of those outcome including risks of low birth weight (LBW) and macrosomia (MAC) with GWG were estimated by logistic regression analysis. To examine the applicability of IOM recommendation for Chinese pregnant women, the accumulated risk of LBW and MAC was displayed by stacked column chart and comparison was made among GWG category. The joint predicted risk (JPR) curve of both LBW and MAC in relation to GWG (continuous measurement) was plotted to demonstrate the relation of lowest JPR corresponding GWG with IOM range. RESULTS: The IOM recommended weight gain was achieved only by 3502 (42.7%) pregnant women and 41.6% gained excessive weight during pregnancy, especially for the overweight and obese women, the proportions of above-gainers mounting to 65.7 and 75.9%, respectively. By multivariate analysis GWG significantly influenced the risk of MAC and caesarean section. Although the association between the risk of LBW and GWG was not significant, p value reached .051. The risk of delivering macrosomia and caesarean section doubled when GWG exceeded the IOM rang. Appropriate gainers did not always gain the lowest joint risk of low birth weight and macrosomia from stacked column chart and it is obvious that the GWG point according to the lowest JPR was always located left to the IOM recommended range for each BMI category from the JPR curve chart in relation to GWG. CONCLUSIONS: The IOM recommended GWG range is possibly too much for Chinese singleton pregnant population for each BMI category. It is necessary to build different gestational weight gain standards for specific ethnic population.