Grape seed proanthocyanidins suppressed macrophage foam cell formation by miRNA-9 via targeting ACAT1 in THP-1 cells.

Abnormal lipid metabolism in macrophages leads to atherosclerosis (AS). Excessive LDL cholesterol uptake by macrophages in the aortic endothelium leads to formation of foam cells. Previous studies suggested that proanthocyanidins effectively suppress this process, while the in-depth mechanism has not been elucidated. In mononuclear THP-1 cells, we found that the oligomeric fraction of proanthocyanidins was more effective in suppressing foam cell formation and 25 µg ml-1 for 48 h were the optimum conditions. Under these model conditions, we investigated gene expression and for the first time reported expression of regulatory microRNA (miRNA). It was found that the proanthocyanidins restrained macrophage foaming mainly by lowering the expression levels of cholesterol influx-related receptors CD36 and SR-A, and promoting the expression of cholesterol efflux-related receptor ABCA1. Further, it was latest revealed that proanthocyanidins could notably inhibit the expression of ACAT1, a key gene for intracellular cholesterol esterification. Further investigation was performed on the expression of regulatory miRNAs (miR-134 for CD36, miR-134, miR-155 for SR-A, miR-155, let-7g for LOX-1, miR-9 for ACAT1, miR-27a, miR-19b, miR-10b and miR-33a for ABCA1). The relative expression of miR-9, a miRNA targeting ACAT1, was decreased after the treatment of proanthocyanidins. It was most likely that proanthocyanidins suppressed the expression of ACAT1 via up-regulating the expression of miR-9, thus lessening the intracellular lipid accumulation and eventually inhibiting macrophage foam cell formation. This assumption was further verified by use of miR-9 mimic and its inhibitor.

Production of bioproducts by endophytic fungi: chemical ecology, biotechnological applications, bottlenecks, and solutions.

Endophytes are microorganisms that colonize the interior of host plants without causing apparent disease. They have been widely studied for their ability to modulate relationships between plants and biotic/abiotic stresses, often producing valuable secondary metabolites that can affect host physiology. Owing to the advantages of microbial fermentation over plant/cell cultivation and chemical synthesis, endophytic fungi have received significant attention as a mean for secondary metabolite production. This article summarizes currently reported results on plant-endophyte interaction hypotheses and highlights the biotechnological applications of endophytic fungi and their metabolites in agriculture, environment, biomedicine, energy, and biocatalysts. Current bottlenecks in industrial development and commercial applications as well as possible solutions are also discussed.

Dietary compounds have potential in controlling atherosclerosis by modulating macrophage cholesterol metabolism and inflammation via miRNA.

Atherosclerosis (AS) is a typical example of a widespread fatal cardiovascular disease. Accumulation of cholesterol-laden macrophages in the artery wall forms the starting point of AS. Increased influx of oxidized low-density lipoprotein to macrophages and decreased efflux of free cholesterol out of macrophages constitute major factors promoting the development of AS. Inflammation further aggravates the development of AS along or via interaction with the cholesterol metabolism. Many microRNAs (miRNAs) are related to the regulation of macrophage in AS in aspects of cholesterol metabolism and inflammation signaling. Dietary compounds perform AS inhibitory effects via miRNAs in the cholesterol metabolism (miR-19b, miR-378, miR-10b, miR-33a, and miR-33b) and two miRNAs in the inflammation signaling (miR-155 and miR-146a). The targeted miRNAs in the cholesterol metabolism vary greatly among different food compounds; however, in inflammation signaling, most food compounds target miR-155. Many receptors are involved in macrophages via miRNAs, including ABCA1 and ABCG1 as major receptors in the cholesterol metabolism, while nuclear factor-κB (NF-κB) and Nrf2 signaling and PI3K/AKT signaling pathways are targeted during inflammation. This article reviews current literature to investigate possible AS therapy with dietary compounds via targeting miRNAs. Currently existing problems were also discussed to guide further studies.