Assessment of the anthelmintic activity of medicinal plant extracts and purified condensed tannins against free-living and parasitic stages of Oesophagostomum dentatum

Background: Plant-derived condensed tannins (CT) show promise as a complementary option to treat gastrointestinal helminth infections, thus reducing reliance on synthetic anthelmintic drugs. Most studies on the anthelmintic effects of CT have been conducted on parasites of ruminant livestock. Oesophagostomum dentatum is an economically important parasite of pigs, as well as serving as a useful laboratory model of helminth parasites due to the ability to culture it in vitro for long periods through several life-cycle stages. Here, we investigated the anthelmintic effects of CT on multiple life-cycles stages of O. dentatum. Methods: Extracts and purified fractions were prepared from five plants containing CT and analysed by HPLC-MS. Anthelmintic activity was assessed at five different stages of the O. dentatum life cycle; the development of eggs to infective third-stage larvae (L3), the parasitic L3 stage, the moult from L3 to fourth-stage larvae (L4), the L4 stage and the adult stage. Results: Free-living larvae of O. dentatum were highly susceptible to all five plant extracts. In contrast, only two of the five extracts had activity against L3, as evidenced by migration inhibition assays, whilst three of the five extracts inhibited the moulting of L3 to L4. All five extracts reduced the motility of L4, and the motility of adult worms exposed to a CT-rich extract derived from hazelnut skins was strongly inhibited, with electron microscopy demonstrating direct damage to the worm cuticle and hypodermis. Purified CT fractions retained anthelmintic activity, and depletion of CT from extracts by pre-incubation in polyvinylpolypyrrolidone removed anthelmintic effects, strongly suggesting CT as the active molecules. Conclusions: These results suggest that CT may have promise as an alternative parasite control option for O. dentatum in pigs, particularly against adult stages. Moreover, our results demonstrate a varied susceptibility of different life-cycle stages of the same parasite to CT, which may offer an insight into the anthelmintic mechanisms of these commonly found plant compounds

Dietary fatty acid composition is sensed by the NLRP3 inflammasome: omega-3 fatty acid (DHA) prevents NLRP3 activation in human macrophages

The Nod-like receptor protein 3 (NLRP3) inflammasome is considered to be a pivotal host platform responsible for sensing of exogenous and endogenous danger signals, including those generated as a result of metabolic dysregulation, and for the subsequent, IL-1β-mediated orchestration of inflammatory and innate immunity responses. In this way, although the molecular link between diet-induced obesity and inflammasome activation is still unclear, free fatty acids (FFA) have been proposed as a triggering event. We report that dietary fatty acid (FA) composition is sensed by the NLRP3 inflammasome in human macrophages. For this purpose, we have analysed three roles of FA supplementation: as a priming signal for ATP-activated macrophages, in determining where the administration of dietary FAs interferes with LPS-mediated inflammasome activation and by inducing inflammasome activation per se. In this study, we confirm that saturated (SFAs) activated the NLRP3 inflammasome and stimulated the secretion of the IL-1β cytokine, while PUFAs were mainly inhibitors. Moreover, in general, DHA (n-3 PUFA) was more effective in preventing inflammasome activation than arachidonic acid (n-6 PUFA)

Clinical significance of circulating microRNAs as markers in detecting and predicting congenital heart defects in children

© 2018 The Author(s). Background: Circulating microRNAs (miRNAs) are emerging as novel biomarkers for detecting cardiovascular diseases. In this study, we aimed to investigate the usefulness of miRNAs as biomarkers in diagnosing and predicting children with congenital heart defects (CHD), particularly in the context of multiple subtypes of CHD. Methods: We recruited 26 families, each having a child with CHD and parents who do not have any cardiovascular disorder. 27 families unaffected by cardiovascular disease were also included as controls. Firstly, we screened 84 circulating miRNAs relating to cardiovascular development in 6 children with atrial septal defects (ASD) and 5 healthy children. We validated the selected miRNAs with differential expression in a larger sample size (n = 27 for controls, n = 26 for cases), and evaluated their signal in different types of septal defects. Finally, we examined the identified miRNAs signatures in the parent population and assessed their diagnostic values for predicting CHD. Results: The three miRNAs hsa-let-7a, hsa-let-7b and hsa-miR-486 were significantly upregulated in children with ASD. A further validation study showed that overexpression of hsa-let-7a and hsa-let-7b was specifically present in ASD children, but not in children with other subtypes of septal defects. A similar expression profile of hsa-let-7a and hsa-let-7b was discovered in mothers of ASD children. Receiver-operating characteristic curve analyses indicated that hsa-let-7a and hsa-let-7b had significant diagnostic values for detecting ASD and in maternal samples predicting the occurrence of ASD in offspring. Conclusions: Circulating miRNAs are important markers not only for diagnosing CHD, but also for predicting CHD risk in offspring. The distinct miRNA signatures are likely to present in various subtypes of CHD, and the phenotypic heterogeneity of CHD should be considered to develop such miRNA-based assays