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Inflammation plays a crucial role in atherosclerosis and nonalcoholic fatty liver disease (NAFLD). We previously engineered a recombinant Lactococcus lactis strain expressing the Ling-Zhi immunomodulatory protein (L. lactis-LZ8). This study investigated the anti-atherosclerotic effects of L. lactis-LZ8 in rabbits fed a high-fat diet (HFD). Changes in body weight, serum lipid profiles, and liver function were monitored. The aorta and liver tissues were analyzed for gross pathology and histopathology. Eight-week administration of L. lactis-LZ8 with HFD ameliorated atherosclerosis by downregulating protein and gene expression associated with lipid metabolism and inflammation in the aortas. The rabbits receiving L. lactis-LZ8 exhibited a significant dose-dependent reduction in hepatic fat accumulation. RNA sequencing of the livers revealed that inflammatory genes in the L. lactis-LZ8 groups were downregulated compared to the HFD group. Disease ontology enrichment analysis indicated that these genes were involved in atherosclerosis. Gene set enrichment analysis plots revealed significant enrichment in the gene sets related to cholesterol homeostasis. CIBERSORT immune cell fraction analysis indicated significant infiltration by regulatory T cells, CD8+ T cells, activated dendritic cells, and natural killer cells in the L. lactis-LZ8 group. Our studies underscore LZ8's role in precision nutrition, providing a potential solution to the current challenges in modifying atherosclerosis and NAFLD. [ABSTRACT FROM AUTHOR]

RationaleIn atherosclerotic lesions, synthetic smooth muscle cells (sSMCs) induce aberrant microRNA (miR) profiles in endothelial cells (ECs) under flow stagnation. Increase in shear stress induces favorable miR modulation to mitigate sSMC-induced inflammation.ObjectiveTo address the role of miRs in sSMC-induced EC inflammation and its inhibition by shear stress.Methods and resultsCoculturing ECs with sSMCs under static condition causes initial increases of 4 anti-inflammatory miRs (146a/708/451/98) in ECs followed by decreases below basal levels at 7 days; the increases for miR-146a/708 peaked at 24 hours and those for miR-451/98 lasted for only 6 to 12 hours. Shear stress (12 dynes/cm(2)) to cocultured ECs for 24 hours augments these 4 miR expressions. In vivo, these 4 miRs are highly expressed in neointimal ECs in injured arteries under physiological levels of flow, but not expressed under flow stagnation. MiR-146a, miR-708, miR-451, and miR-98 target interleukin-1 receptor-associated kinase, inhibitor of nuclear factor-κB kinase subunit-γ, interleukin-6 receptor, and conserved helix-loop-helix ubiquitous kinase, respectively, to inhibit nuclear factor-κB signaling, which exerts negative feedback control on the biogenesis of these miRs. Nuclear factor-E2-related factor (Nrf)-2 is critical for shear-induction of miR-146a in cocultured ECs. Silencing either Nrf-2 or miR-146a led to increased neointima formation of injured rat carotid artery under physiological levels of flow. Overexpressing miR-146a inhibits neointima formation of rat or mouse carotid artery induced by injury or flow cessation.ConclusionsNrf-2-mediated miR-146a expression is augmented by atheroprotective shear stress in ECs adjacent to sSMCs to inhibit neointima formation of injured arteries.

The primary goal of our study was to investigate the importance of originality in divergent thinking (DT) tests and to determine whether originality is the best reflection of creativity. To accomplish this, we cross-validated the DT test and creative writing task rating by consensual assessment technique (CAT). Thirty-seven elementary school pupils (18 males, 19 females) were asked to complete the imagination test (a type of DT test) and a creative writing task ("If I were a principal") with CAT rating. The composite creativity score, sub-scores and originality-ratio score derived from the DT and CAT-creativity scores were obtained. The data were analysed using Pearson product-moment correlations and the difference analysis of these correlation coefficients. The results revealed a significantly higher correlation between DT-originality and CAT-creativity than between DT-composite creativity and CAT-creativity, and the originality-ratio score was more highly correlated with CAT than with the other scores. We confirmed the importance of originality in DT tests, and we here propose primary (originality) and supportive (fluency and flexibility) abilities as alternative ways to explain creative potential.

Objective: Low monoamine oxidase (MAO) activity and the neurotransmitter dopamine are 2 important factors in the development of alcohol dependence. MAO is an important enzyme associated with the metabolism of [...]

This article, published in the European Heart Journal, discusses a rare complication involving the dislodgement of an Amplatzer Septal Occluder (ASO) in a patient with fulminant perimyocarditis. The patient initially received mechanical circulatory support through left atrial veno-arterial extracorporeal membrane oxygenation (LAVA-ECMO) and later underwent implantation of an Impella CP device. However, the Impella CP device caused right-to-left shunting through an iatrogenic atrial septal defect (ASD), leading to upper limb and brain hypoxemia. The ASD was sealed off with a 19 mm ASO, but six days later, the ASO became dislodged and migrated into the left ventricle. The dislodged ASO was successfully removed and replaced, and the patient's condition improved with the support of VA-ECMO and Impella CP. [Extracted from the article]