PCSK-9 modulation by oral administration of Berberine using nanotechnology approach can improve its pharmacokinetic profile. Further studies are needed to maximize its delivery efficiency.
Depression is an independent risk factor of cardiovascular disease morbidity. Serotonin is a key neurotransmitter in depressive pathology, contained within platelets, and is a weak activator of platelets. Our study assessed the link between platelet reactivity traits, depression, and antidepressant (AD) use in a large population sample. Our study was conducted in the Framingham Heart Study (n = 3,140), and AD use (n = 563) and aspirin use (n = 681) were noted. Depression was measured using the Center for Epidemiological Studies-Depression (CES-D) survey. Platelet reactivity traits were measured across multiple agonists using five distinct assays. We utilized a linear mixed effects model to test associations between platelet traits and depression, adjusting for age, sex, aspirin use, and AD use. Similarly, we analyzed trait associations with any AD use, serotonin-affecting ADs, and norepinephrine-affecting ADs, respectively. There were strong associations with reduced platelet function and AD use, particularly with serotonin-affecting medications. This included lower Optimul epinephrine maximal aggregation (P = 4.87E-13), higher U46619 half maximal effective concentration (P = 9.09E-11), lower light transmission aggregometry (LTA) adenosine diphosphate (ADP) final aggregation (P = 1.03E-05), and higher LTA ADP disaggregation (P = 2.28E-05). We found similar associations with serotonin-affecting ADs in an aspirin-taking subset of our sample. There were no significant associations between platelet traits and depression. In the largest study yet of AD use and platelet function we show that antidepressants, particularly serotonin-affecting ADs, inhibit platelets. We did not find evidence that depressive symptomatology in the absence of medication is associated with altered platelet function. Our results are consistent with AD use leading to platelet serotonin depletions, decreased stability of platelet aggregates, and overall decreased aggregation to multiple agonists, which may be a mechanism by which ADs increase risk of bleeding and decrease risk of thrombosis.
Introduction Triglyceride (TG) is an independent risk factor for coronary heart disease. Previous work has shown that short-term supplementations of mouse chow with oxidized linoleic acid (OxLA) significantly reduce the level of plasma triglycerides. Study Objective This study aims to determine the effects of longer-term supplementation of mouse chow with various concentrations of oxidized linoleic acid (OxLA) on plasma triglycerides. Study Design The study consisted of forty C57BL/6 wildtype mice divided into four groups (n = 10). Two groups were kept as controls. One control group (P) was fed plain chow and the second control group (C) was fed chow supplemented with linoleic acid. The other two experimental groups (A) and (B) were fed oxidized linoleic acid supplemented chow in the following doses: 9 mg/day of oxidized linoleic acid and 18 mg/day of oxidized linoleic acid/mouse. Results and Conclusion Mice that were on a diet supplemented with the higher dose of oxidized linoleic acid showed a 39% decrease in hepatic PPAR-α and a significant decrease in the plasma HDL levels compared to the mice that were fed diets of plain and linoleic acid supplemented chow. Interestingly, the longer-term consumption of oxidized linoleic acid may predispose to atheropathogenesis.
Introduction: FGF-23 is a phosphatouric hormone which also serves as a plasma biomarker that mediates pathologic cardiac remodeling, such as left ventricular hypertrophy or myocardial fibrosis, and is associated with increased cardiovascular mortality. However, limited evidence is available on lifestyle-related factors associated with circulating concentration of this emerging cardiovascular risk factor. Objective: Our aim was to measure the association between the American Heart Association’s Life’s Simple 7 (LS7) and circulating FGF-23 concentration among Puerto Rican adults. Methods: Data are from Boston Puerto Rican Health Study (BPRHS) participants (mean age 56.2 years, 77% female) at baseline and at approximately 8-y follow-up (n=410). LS7 was calculated at baseline and includes 4 physiological (BMI, total cholesterol, blood pressure, and fasting glucose) and 3 behavioral factors (smoking, physical activity, and diet). Each component was categorized using a constituent scoring system (ideal=2; intermediate=1; Poor=0) and these were summed to calculate the total LS7 score. Participants were categorized into 5 LS7 groups as follows: 1) score 1-4 (n=105), 2) 5 (n=76), 3) 6 (n=89), 4) 7 (n=69), and 5) 8-12 (n=71). Fasting plasma FGF-23 concentration at 8-y follow-up was measured by ELISA. Associations between baseline LS7 score and 8-y FGF-23 were assessed using ANCOVA, adjusted for age and sex (model 1), and additionally for history of cardiovascular disease and poverty-income-ratio (model 2). Results: Relative to participants in LS7 group 1 (2.98 ± 1.09 mg/dL), those in groups 5 (1.63 ± 1.12 mg/dL, p=0.0001) had significantly lower FGF-23 concentration (model 1, P-trend=0.0001). After considering additional confounders, FGF-23 concentration among LS7 group 5 (1.69 ± 1.12 mg/dL, p=0.0007) remained significantly lower than in group 1 (2.95 ± 1.09 mg/dL). The p-trend across categories was also significant at p=0.0007. In additional analyses, LS7 components for smoking (ideal vs. poor, 2.07 ± 1.10 mg/dL vs. 2.87 ± 1.10 mg/dL, p=0.01) and fasting glucose (ideal vs. poor, 2.03 ± 1.07 mg/dL vs. 2.90 ± 1.09 mg/dL, p=0.004), but no other components, were associated with FGF-23 concentration. Conclusions: Optimal LS7 status was associated with lower 8-y mean plasma FGF-23 concentration. Efforts to target LS7 components, particularly smoking and glucose control, may improve FGF-23 concentration among Puerto Rican adults.
Objectives To quantify the associations between adherence to U.S. dietary guidelines and inflammation among Bhutanese refugee adults who are eligible to receive SNAP (Supplemental Nutrition Assistance Program) benefits. Methods A convenience sample of Bhutanese refugee adults (n = 53, mean age = 47 ± 2 years, 83% female) residing in New Hampshire was recruited. A bilingual community health worker conducted study visits. We estimated diet using the average of three 24-hour recalls. Adherence to U.S. dietary guidelines was defined using the 2015 Healthy Eating Index (HEI), where a higher score indicates greater adherence to guidelines. A fasting blood sample was analyzed for inflammatory biomarkers, IL-6 and TNF-α. The HEI score and score components were expressed in tertiles, and related to biomarkers using ANCOVA. Food rankings were conducted to identify contributors to HEI components. Results On average, participants lived in the U.S. for 7.8 ± 0.5 years, with a household size of 3.8 ± 0.2 members. The prevalence of overweight/obesity and type 2 diabetes was 82% and 41%, respectively. In multivariate adjusted models, individuals with higher HEI scores had significantly lower IL-6 concentrations (3.1 ± 0.5 pg/mL, 2.5 ± 0.4 pg/mL, and 2.0 ± 0.5 pg/mL by increasing HEI tertile, P-trend = 0.019). In examining the individual HEI components, greater consumption of total fruit (P-trend = 0.02) and whole fruit (P-trend = 0.017) was related to lower IL-6 concentrations, whereas refined grains was associated with higher values (P-trend = 0.036). We observed null associations with TNF-α. The top 5 contributors to fruit consumption were bananas (21.5%), apples (15.5%), mangos (15%), avocados (9.6%), and kiwis (8.8%); those for refined grains included parboiled rice (78.8%), white rice (6.1%), pasta (4.6%), crackers (1.3%), and white bread (1.3%). Conclusions In this cross-sectional study of low-income Bhutanese refugee adults, greater adherence to U.S. Dietary Guidelines, particularly for fruit and refined grain consumption, was associated with lower IL-6 concentrations. Over 70% of fruit and 90% of refined grains were represented by only a few foods, which can inform cultural tailoring of SNAP Education interventions in this understudied population. Funding Sources The New Hampshire Agricultural Experiment Station.
Introduction: Gum arabic (GA) (Acacia Senegal) is widely used agent in both the pharmaceutical and food industries as an emulsifier and stabilizer. It is a branched complex polysaccharide molecule rich in calcium, potassium, and magnesium in addition to other minerals. Its aqueous solution is either neutral or slightly acidic. Human intake of GA with atorvastatin was reported to significantly reduce plasma low density lipoprotein, and triglyceride. This study is designed to test mechanism (s) of its action on HepG2 cell. Hypothesis: The plasma lipids reduction associated with GA intake is likely associated with PCSK9/LDLr mechanism. Methods: Gum Arabic was dissolved in water and irradiated under UV light for 5 hours. Three final concentrations: 5ng/ml, 100ng/ml and 500 ng/ml were used for treatment of HepG2 cells at 6 hours, 12 hours and 24 hours using 12 well plates. Following treatment cells were collected into Trizol® solution; RNA was extracted for gene expression following Trizol® supplier protocol. cDNA was synthesized and the expression of PSCK9, LDLR and other related genes were tested using real time PCR. Results: The use of viscous (soluble) fiber (e.g., oats, guar, pectin, and psyllium) as therapeutic dietary options to enhance lowering of LDL cholesterol in primary and secondary prevention of CHD was well known, however there is no study to date that have shown the GA cholesterol lowering mechanism(s). In this study cell treated with GA for six hours has resulted in approximately 50 fold reductions of PCSK9 gene expression across the various concentrations, and approximately 25 fold up regulation of LDLr gene. Prolonged treatments beyond the six hours have shown differential responses. Conclusions: This study demonstrates that Gum Arabic has acute anti PCSK9 properties, as well as beneficial LDLr modulation effects. Our data explain the modulatory mechanism of Gum Arabic plasma LDL lowering effects associated with its intake in humans.
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