Cell adhesion molecules, plasminogen activator inhibitor type 1, and metabolic syndrome in patients with psoriasis
银屑病患者的细胞黏附分子、纤溶酶原激活物抑制剂 1 与代谢综合征
- 作者列表："Teixeira, Guilherme Gomes","Mari, Naiara Lourenço","de Paula, Jaqueline Costa Castardo","Cataldi de Alcantara, Camila","Flauzino, Tamires","Lozovoy, Marcell Alysson Batisti","Martin, Ligia Márcia Mário","Reiche, Edna Maria Vissoci","Maes, Michael","Dichi, Isaias","Simão, Andréa Name Colado
The objective of this study is to delineate the cellular adhesion molecule (CAM) profile and plasminogen activator inhibitor type 1 (PAI-1), and their association with metabolic syndrome (MetS) and carbohydrate metabolism biomarkers in psoriasis patients with mild and moderate severity. Sixty-seven patients with psoriasis as well as 102 healthy subjects were recruited. Insulin and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), but not glucose, were significantly higher in psoriasis than in controls. Psoriasis was characterized by increased plasma levels of platelet endothelial cell adhesion molecule 1 (PECAM-1), vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), E-selectin, and PAI-1 as compared with controls. Psoriasis diagnosis could explain 59.0% of CAM and PAI-1 variance, with a particularly strong impact on E-selectin (45.6%), VCAM-1 (32.7%), and PAI-1 (24.8%). Subjects with MetS showed significantly higher E-selectin and PAI-1 than those without MetS. Using VCAM-1, E-selectin, PAI-1 (all positively), and P-selectin (inversely) in a binary regression equation, it was found that 87.6% of all patients were correctly classified with a sensitivity of 92.5% and a specificity of 84.3%. CAM and PAI-1 were correlated with carbohydrate metabolism biomarkers (glucose, insulin, and HOMA-IR). In conclusion, CAM levels are associated with psoriasis diagnosis and MetS may influence E-selectin and PAI-1 concentrations. More studies are needed to verify the causality among these factors, as well as their relation to the different degrees of disease severity.
本研究的目的是描述细胞粘附分子 (CAM) 和纤溶酶原激活物抑制剂 1 型 (PAI-1) 及其与代谢综合征 (MetS) 的关系。和轻度和中度严重程度银屑病患者的碳水化合物代谢生物标志物。67 名银屑病患者和 102 名健康受试者被招募。胰岛素和胰岛素抵抗稳态模型评估 (HOMA-IR)，而非葡萄糖，在银屑病患者中显著高于对照组。银屑病以血浆血小板内皮细胞黏附分子 1 (PECAM-1) 、血管细胞黏附分子 1 (VCAM-1) 、细胞间黏附分子 1 (ICAM-1) 、 E-选择素、与对照组相比，PAI-1。银屑病诊断可以解释 59.0% 的 CAM 和 PAI-1 变异，对 E-选择素 (45.6%) 、 VCAM-1 (32.7%) 和 PAI-1 (24.8%) 的影响特别大。患有 MetS 的受试者显示出显著高于无 MetS 的受试者的 E-选择素和 PAI-1。使用二元回归方程中的 VCAM-1 、 E-选择素、 PAI-1 (均为阳性) 和 P-选择素 (反向), 发现所有患者中有 87.6% 被正确分类，敏感性为 92.5%，特异性为 84.3%。CAM 和 PAI-1 与碳水化合物代谢生物标志物 (葡萄糖、胰岛素和 HOMA-IR) 相关。总之，CAM 水平与银屑病的诊断相关，MetS 可能影响 E-选择素和 PAI-1 浓度。需要更多的研究来验证这些因素之间的因果关系，以及它们与疾病严重程度不同的关系。
METHODS:BACKGROUND:Given the importance of habitual dietary protein intake, distribution patterns and dietary sources in the aetiology of age-related declines of muscle mass and function, the present study examined these factors as a function of sex and age in Irish adults aged 18-90 years comprising The National Adult Nutrition Survey (NANS). METHODS:In total, 1051 (males, n = 523; females, n = 528) undertook a 4-day semi-weighed food diary. Total, body mass relative intake and percentage contribution to total energy intake of dietary protein were determined in addition to protein distribution scores (PDS), as well as the contribution of food groups, animal- and plant-based foods to total protein intake. RESULTS:Total and relative protein intake [mean (SD)] were highest in those aged 18-35 years [96 (3) g day , 1.32 (0.40) g kg day ], with lower protein intakes with increasing age (i.e. in adults aged ≥65 years [82 (22) g, 1.15 (0.34) g kg day , P < 0.001 for both]. Differences in protein intake between age groups were more pronounced in males compared to females. Protein distribution followed a skewed pattern for all age groups [breakfast, 15 (10) g; lunch, 30 (15) g; dinner, 44 (17) g]. Animal-based foods were the dominant protein source within the diet [63% (11%) versus 37% (11%) plant protein, P < 0.001]. CONCLUSIONS:Protein intake and the number of meals reaching the purported threshold for maximising post-prandial anabolism were highest in young adults, and lower with increasing age. For main meals, breakfast provided the lowest quantity of protein across all age categories and may represent an opportunity for improving protein distribution, whereas, in older adults, increasing the number of meals reaching the anabolic threshold regardless of distribution pattern may be more appropriate.
METHODS:BACKGROUND:Low cardiorespiratory fitness (CRF) increases risk of all-cause mortality and cardiovascular events. Periodic CRF assessment can have an important preventive function. OBJECTIVE:To develop a protocol-free method to estimate CRF in daily life based on heart rate (HR) and body acceleration measurements. METHODS:Acceleration and HR data were collected from 37 subjects (M=49%) while performing a standardized laboratory activity protocol (sitting, walking, running, cycling) and during a 5-days free-living monitoring period. CRF was determined by oxygen uptake (VO2max) during maximal exercise testing. A doubly-labeled water validated equation was used to predict total energy expenditure (TEE) from acceleration data. A fitness index was defined as the ratio between TEE and HR (TEE-pulse). Activity recognition techniques were used to process acceleration features and classify sedentary, ambulatory and other activity types. Regression equations based on TEE-pulse data from each activity type were developed to predict VO2max. RESULTS:TEE-pulse measured within each activity type of the laboratory protocol was highly correlated to VO2max (r from 0.74 to 0.91). Averaging the outcome of each activity-type specific equation based on TEE-pulse from the laboratory data led to accurate estimates of VO2max (RMSE: 300.0 mlO2/min or 10%). The difference between laboratory and free-living determined TEE-pulse was 3.7 ± 11% (r =0.85). The prediction method preserved the prediction accuracy when applied to free-living data (RMSE: 367 mlO2/min or 12%). CONCLUSIONS:Measurements of body acceleration and HR can be used to predict VO2max in daily life. Activity-specific prediction equations are needed to achieve highly accurate estimates of CRF.
METHODS:OBJECTIVE:Postprandial dyslipidemia is a common feature of insulin resistant states and contributes to increased cardiovascular disease risk. Recently, bile acids have been recognized beyond their emulsification properties as important signaling molecules that promote energy expenditure, improve insulin sensitivity, and lower fasting lipemia. While bile acid receptors have become novel pharmaceutical targets, their effects on postprandial lipid metabolism remain unclear. Here we investigated the potential role of bile acids in regulation of postprandial chylomicron production and triglyceride excursion. Approach and Results: Healthy C57BL/6 mice were given an intraduodenal infusion of taurocholic acid (TA) under fat-loaded conditions and circulating lipids were measured. Targeting of bile acid receptors was achieved with GW4064, a synthetic agonist to the farnesoid X receptor (FXR), and with deoxycholic acid (DCA), an activator of the Takeda G-protein-coupled receptor 5. TA, GW4064, and DCA treatments all lowered postprandial lipemia. FXR agonism also reduced intestinal triglyceride content and activity of microsomal triglyceride transfer protein, involved in chylomicron assembly. Importantly, TA effects (but not DCA) were largely lost in FXR knockout mice. These bile acid effects are reminiscent of the anti-diabetic hormone glucagon-like peptide-1 (GLP-1). While the GLP-1 receptor agonist exendin-4 retained its ability to acutely lower postprandial lipemia during bile acid sequestration and FXR deficiency, it did raise hepatic expression of the rate limiting enzyme for bile acid synthesis. CONCLUSIONS:Bile acid signaling may be an important mechanism of controlling dietary lipid absorption and bile acid receptors may constitute novel targets for the treatment of postprandial dyslipidemia.