Effects of microplastics (MPs) and tributyltin (TBT) alone and in combination on bile acids and gut microbiota crosstalk in mice.

Microplastics (MPs) and tributyltin (TBT) are both potential environmental pollutants that enter organisms through the food chain and affect bodily functions. However, the effects and mechanisms of MPs and TBT exposure (especially the co-exposure of both pollutants) on mammals remain unclear. In this study, Ф5µm MPs (5MP) was administered alone or in combination with TBT to investigate the health risk of oral exposure in mice. All three treatments induced inflammation in the liver, altered gut microbiota composition and disturbed fecal bile acids profiles. In addition to decreasing triglyceride (TG) and increasing aspartate aminotransferase (AST) and macrophage-expressed gene 1 (Mpeg1), 5MP induced hepatic cholestasis by stimulating the expression of the cholesterol hydroxylase enzymes CYP8B1 and CYP27A1, and inhibiting multidrug resistance-associated protein 2 and 3 (MRP2, MRP3), and bile-salt export pump (BSEP) to prevent bile acids for entering the blood and bile. Correspondingly, 5MP treatment decreased 7-ketolithocholic acid (7-ketoLCA) and taurocholic acid (TCA), which were positively correlated with decreased Bacteroides and Marvinbryantia and negatively correlated with increased Bifidobacterium. In addition, TBT increased interferon γ (IFNγ) and Mpeg1 levels to induce inflammation, accompanied by decreased 7-ketoLCA, tauro-alpha-muricholic acid (T-alpha-MCA) and alpha-muricholic acid (alpha-MCA) levels, which were negatively related to Coriobacteriaceae_UCG-002 and Bifidobacterium. Co-exposure to 5MP and TBT also decreased TG and induced bile acids accumulation in the liver due to inhibited BSEP, which might be attributed to the co-regulation of decreased T-alpha-MCA and Harryflintia. In conclusion, the administration of 5MP and TBT alone and in combination could cause gut microbiome dysbiosis and subsequently alter bile acids profiles, while the combined exposure of 5MP and TBT weakened the toxic effects of 5MP and TBT alone.

Three-dimensional modeling and numerical analysis of fractional flow reserve in human coronary arteries.

INTRODUCTION: Noninvasive fractional flow reserve (FFR) computed from CT (FFRCT) is a novel method for determining the physiologic significance of coronary artery disease (CAD). Several clinical trials have been conducted, but its diagnostic performance varied among different trials. AIM: To determine the cut-off value of FFRCT and its correlation with the gold standard used to diagnose CAD in clinical practice. MATERIAL AND METHODS: Forty patients with single vessel disease were included in our study. Computed tomography scan and coronary angiography with FFR were conducted for these patients. Three-dimensional geometric reconstruction and numerical analysis based on the computed tomographic angiogram (CTA) of coronary arteries were applied to obtain the values of FFRCT. The correlation between FFRCT and the gold standard used in clinical practice was tested. RESULTS: For FFRCT, the best cut-off value was 0.76, with the sensitivity, specificity, positive predictive value and negative predictive values of 84.6%, 92.9%, 88% and 73.3%, respectively. The area under the receiver-operator characteristics curve was 0.945 (p < 0.0001). There was a good correlation of FFRCT values with FFR values (r = 0.94, p < 0.0001), with a slight overestimation of FFRCT as compared with measured FFR (mean difference 0.01 ±0.11, p < 0.05). For inter-observer agreement, the mean κ value was 0.69 (0.61 to 0.78) and for intra-observer agreement the mean κ value was 0.61 (0.50 to 0.72). CONCLUSIONS: FFRCT derived from CT of the coronary artery is a reliable non-invasive way providing reliable functional information of coronary artery stenosis.