Ultrasound-assisted deep eutectic solvents extraction of glabridin and isoliquiritigenin from Glycyrrhiza glabra: Optimization, extraction mechanism and in vitro bioactivities.

Licorice (Glycyrrhiza glabra) is extensively used owing to the superior pharmacological effects. However, its maximum application potential has not been fully exploited due to the limitation of currently available extraction solvent and methods. In this study, an eco-friendly deep eutectic solvent (NADESs) based ultrasound-assisted extraction (DES-UAE) method was applied to prepare licorice extracts. The DES-UAE using choline chloride and lactic acid as solvent was optimized and modeled by using response surface methodology to maximize the extraction yields of glabridin (GLA) and isoliquiritigenin (ISL). The optimized extracts possessed higher contents of GLA and ISL than available extraction methods, and the enriched products showed superior pharmacological activities in vitro. Furthermore, scanning electron microscopy (SEM) and molecular dynamic simulation analyses were performed to deeply investigate the interaction between solvent and targeted compounds. This study not only provides an eco-friendly method for high-efficient extraction of GLA and ISL from licorice but also illustrates the mechanism of the increased extraction efficacy, which may contribute to the application of licorice and deep insight into extraction mechanism using DES.

Increased soluble OX40L is associated with carotid intima-media thickness.

BACKGROUND: Recent studies indicated that soluble OX40 ligand (OX40L) levels were increased in acute coronary syndrome. But the association between sOX40L and carotid intima-media thickness (IMT) has not been evaluated. METHODS: We measured plasma soluble OX40L (sOX40L) and Interleukin-10 (IL-10) levels in 35 patients with stable angina pectoris, 30 patients with risk factors of coronary artery disease, and 20 age and sex-matched controls. Carotid (IMT) was measured by B-mode ultrasound. RESULTS: Plasma sOX40L levels were positively correlated with Carotid IMT (r = 0.376, P = 0.001) and inversely correlated with IL-10 (P = -0.394, P = 0.000). Multivariate linear regression analysis revealed that sOX40L (p = 0.019) was an independent predictor for Carotid IMT progression after adjusting for the classical cardiovascular risk factors. CONCLUSIONS: sOX40L is independently related to Carotid IMT, suggesting the possible relationship of OX40L to atherosclerosis. The positive relation of sOX40L to C-reactive protein (CRP) and the negative relation to IL-10 indicated the possible proinflammatory effects of OX40L on the pathogenesis of atherosclerois.

Exploration of pathological prediction of chronic kidney diseases by a novel theory of bi-directional probability.

In the clinic, the pathological types of chronic kidney diseases (CKD) are considered references for choosing treatment protocols. From a statistical viewpoint, a non-invasive method to predict pathological types of CKD is a focus of our work. In the current study, following a frequency analysis of the clinical indices of 588 CKD patients in the department of nephrology, a third-grade class-A hospital, a novel theory is proposed: "bi-directional cumulative probability dichotomy". Further, two models for the prediction and differential diagnosis of CKD pathological type are established. The former indicates an occurrence probability of the pathological types, and the latter indicates an occurrence of CKD pathological type according to logistic binary regression. To verify the models, data were collected from 135 patients, and the results showed that the highest accuracy rate on membranous nephropathy (MN-100%), followed by IgA nephropathy (IgAN-83.33%) and mild lesion type (MLN-73.53%), whereas lower prediction accuracy was observed for mesangial proliferative glomerulonephritis (0%) and focal segmental sclerosis type (21.74%). The models of bi-directional probability prediction and differential diagnosis indicate a good prediction value in MN, IgAN and MLN and may be considered alternative methods for the pathological discrimination of CKD patients who are unable to undergo renal biopsy.

HDL and ApoA-I inhibit antigen presentation-mediated T cell activation by disrupting lipid rafts in antigen presenting cells.

OBJECTIVE: Depletion of cholesterol by methyl-ß-cyclodextrin (MCD) on peptide-loaded antigen presenting cells (APCs) inhibits antigen presentation and T cell activation. However, whether membrane cholesterol efflux induced by high-density lipoprotein (HDL) and apolipoprotein A-I (apoA-I) also results in inhibition of antigen presentation and T cell activation is still unknown. METHODS AND RESULTS: Various types of APCs, including B cells, macrophages and dendritic cells (DCs), were first loaded with antigen, then incubated with HDL and apoA-I to decrease cellular membrane cholesterol content. After being treated with HDL and apoA-I, APCs demonstrated decreased potential to activate T cells, and this decrease correlated with an increase in cholesterol efflux from APCs. Cholesterol repletion reversed the inhibitory effects of HDL and apoA-I, demonstrating that the observed reduction in T cell proliferation is mediated through cholesterol. Furthermore, lipid raft analysis showed that HDL and apoA-I reduced cholesterol and major histocompatibility (MHC) class II protein content in lipid rafts, suggesting that cholesterol efflux from APCs to HDL and apoA-I inhibits antigen presentation and T cell activation by reducing lipid rafts assembly in APCs. CONCLUSION: HDL and apoA-I inhibit the capacity of APCs to stimulate T cell activation, and this inhibition can be attributed to cholesterol efflux and the ensuing disruption of plasma membrane lipid rafts in APCs. Overall, these findings suggest that cholesterol efflux mediated by HDL and apoA-I may serve to link immunity and cardioprotection.

Serum adipocyte fatty acid binding proteins and adiponectin in patients with coronary artery disease: the significance of A-FABP/adiponectin ratio.

BACKGROUND: Adipocyte fatty acid binding protein (A-FABP) and adiponectin have been shown to play important roles in atherosclerosis. We investigated serum A-FABP, adiponectin and A-FABP/adiponectin ratio in patients with coronary artery disease (CAD). METHODS: A total of 340 subjects who underwent coronary angiography (CAG) were classified into CAD group (n=211) and non-CAD group (n=129) according to the CAG. Serum A-FABP and adiponectin concentrations were determined by enzyme-linked immunosorbent assays. RESULTS: CAD patients tend to have higher A-FABP concentrations than non-CAD subjects, the difference is significant only between female CAD patients and controls [22.8 (18.6-25.7) ng/ml vs 18.1 (15.6-21.8) ng/ml, P=0.008]. Serum A-FABP concentration was independently associated with Gensini scores in female subjects (P=0.018). CAD patients have significant higher serum A-FABP/adiponectin ratio [1.51 ± 0.05 vs 0.89 ± 0.03 ng/µg, P<0.01] than controls in both genders. CONCLUSIONS: Serum A-FABP is associated with CAD more closely in female than in male. The A-FABP/adiponectin ratio may be a more useful indicator for CAD than A-FABP or adiponectin alone.