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Previous publications have reported a potent effect of COVID-19 on platelet function and that the Spike protein enhances washed human platelet aggregation induced by various agonists. This study aims to evaluate whether mRNA vaccination for COVID-19 affects human platelet-rich plasma (hPRP) aggregation response, whether a recombinant Spike protein modulates PAF-induced aggregation in hPRP and in washed rabbit platelets (WRP), and to investigate the effect of recombinant Spike protein on the PAF production in the U-937 cell line. Our results showed that PRP from vaccinated individuals exhibited ex vivo lower EC

Background: Platelet-activating-factor (PAF) is a lipid inflammatory mediator implicated in liver disease. Its main biosynthetic enzymes are cytidine diphosphate (CDP)-choline: 1-alkyl-2-acetyl-sn-glycerol-cholinephosphotransferase (PAF-CPT) and acetyl-coenzyme A: lyso-PAF-acetyltransferases (Lyso-PAF-AT). At the same time, PAF acetylhydrolase (PAF-AH) and lipoprotein-associated phospholipase A2 (Lp-PLA2) degrade PAF. Objective: To explore the relation of PAF metabolism with liver diseases and non-alcoholic fatty liver disease, as reflected by the fatty liver index (FLI). Methods: In 106 healthy volunteers, PAF concentration, the activity of its metabolic enzymes and gamma-glutamyl transferase (GGT) were measured in whole blood, leukocytes and serum, respectively and the FLI was calculated. Partial correlations and linear regression models were used. Results: In males, serum GGT activity was positively correlated with abdominal fat (as assessed by analysis of a manually defined region of interest in dual-energy X-ray absorptiometry), triacylglycerols, bound-PAF and Lp-PLA2, while the FLI was positively correlated with Lp-PLA2 activity. In females, serum GGT activity was negatively associated with high-density lipoprotein cholesterol (HDL-C) (age adjusted correlations, all p2 was a significant determinant of serum GGT activity in males after controlling for age, low- density lipoprotein cholesterol (LDL-C) and abdominal fat. The addition of bound-PAF in the model significantly increased the explained variance of serum GGT activity (total variance explanation 30%). Conclusions : Bound-PAF and Lp-PLA2 activity predicted serum GGT activity while Lp-PLA2 was also related to FLI. Our findings shed light on the metabolic pathways linking Lp-PLA2 to other atherosclerosis and/or oxidative markers, such as HDL-C, LDL-C, GGT and FLI and underline the important role of PAF.

Summary Background and aims We assessed the association of Mediterranean diet with NAFLD and their interaction in predicting ten-year diabetes onset and first fatal/non-fatal cardiovascular disease (CVD) incidence. Methods The ATTICA prospective observational study in Athens, Greece included 1,514 men and 1,528 women (>18 years old) free-of-CVD at baseline. Liver steatosis and fibrosis indices were calculated. Mediterranean diet adherence was assessed through MedDietScore. At the ten-year follow-up visit, CVD evaluation was performed in an a priori specified subgroup of n = 2,020 participants and diabetes onset in n = 1,485 free-of-diabetes participants. Results MedDietScore was inversely associated with steatosis and fibrosis; e.g. in the case of the TyG index the Odds Ratio (OR) of the 3rd vs. 1st MedDietScore tertile was = 0·53, [95% Confidence Interval (95% CI) (0·29, 0·95)] and the associations persisted in multi-adjusted models. NAFLD predicted incident diabetes prospectively over a ten year period [HR = 1·87, 95% CI (0·75, 4·61)] and the association remained significant only in subjects with low MedDietScore (below median) whereas diabetes onset among subjects with higher MedDietScore was not influenced by NAFLD. Similarly, NAFLD predicted CVD [Hazard Ratio (HR) = 3·01, 95%CI(2·28, 3·95)]; the effect remained significant only in subjects with MedDietScore below median [HR = 1·38, 95% CI (1·00, 1·93)] whereas it was essentially null [HR = 1·00,95% CI (0·38, 2·63)] among subjects with higher score. Mediation analysis revealed that adiponectin and adiponectin-to-leptin ratio were the strongest mediators. Conclusions We report an inverse association between Mediterranean diet and NAFLD. Mediterranean diet protected against diabetes and CVD prospectively among subjects with NAFLD.

Recent articles report elevated markers of coagulation, endothelial injury, and microthromboses in lungs from deceased COVID-19 patients. However, there has been no discussion of what may induce intravascular coagulation. Platelets are critical in the formation of thrombi and their most potent trigger is platelet activating factor (PAF), first characterized by Demopoulos and colleagues in 1979. PAF is produced by cells involved in host defense and its biological actions bear similarities with COVID-19 disease manifestations. PAF can also stimulate perivascular mast cell activation, leading to inflammation implicated in severe acute respiratory syndrome (SARS). Mast cells are plentiful in the lungs and are a rich source of PAF and of inflammatory cytokines, such as IL-1β and IL-6, which may contribute to COVID-19 and especially SARS. The histamine-1 receptor antagonist rupatadine was developed to have anti-PAF activity, and also inhibits activation of human mast cells in response to PAF. Rupatadine could be repurposed for COVID-19 prophylaxis alone or together with other PAF-inhibitors of natural origin such as the flavonoids quercetin and luteolin, which have antiviral, anti-inflammatory, and anti-PAF actions.

Although, three decades have pasted from the introduction of “French Paradox”, is still an issue for debate. Epidemiology supports the J-shaped relationship between wine consumption and vascular events as well as cardiovascular mortality with a maximum protection at 21 g of alcohol consumption in the form of wine per day. Nevertheless, the aforementioned studies have used an observational design that raises concerns about potential confounding. Randomized clinical studies may provide data to end the controversy and in parallel with in vitro experiments to elucidate the mechanisms by which wine affects cardiovascular disease. In this concept, this review aims to address the presence of bioactive wine micro constituents, their potential mechanisms of action and also to summarize the cardio-protective effects of wine intake based on clinical trials. The role of wine micro-constituents in inflammation and haemostasis is discussed in detail.

We aimed to evaluate colonisation patterns of Akkermansia muciniphila in a Greek adult population and to investigate model-adjusted associations of A. muciniphila with host adiposity and cardiometabolic markers. Participants (n=125) underwent anthropometric, dietary, physical activity and lifestyle evaluation. Blood sampling for determination of blood lipid indices, glucose metabolism, adiponectin, lipoprotein-associated phospholipase A2 (Lp-PLA2), inflammation and oxidative stress parameters was also performed. Stool A. muciniphila presence and levels were determined by quantitative PCR and subjects were grouped based on bimodal distribution of levels (Low vs High). A. muciniphila was detected in 88.6% of participants. Overweight/obese (OW/OB) subjects were more prone in low bimodal levels of A. muciniphila compared to normal-weight (NW) individuals (58.75 vs 27.59%, P=0.004), with a 4-time greater likelihood after multi-adjusted logistic regression analysis (P=0.016). Levels of A. muciniphila were negatively associated with total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) ratio (log10:-0.009±0.004, P=0.033), whereas detection of this bacterium was negatively associated with both TC/HDL-C ratio (log10: -0.049±0.023, P=0.036) and low-density lipoprotein cholesterol/HDL-C ratio (-0.407±0.176, P=0.023). Furthermore, low bimodal levels of A. muciniphila were positively associated with fasting blood glucose (log10: 0.018±0.009, P=0.037). In terms of inflammation markers, levels of A. muciniphila were positively associated with soluble cluster of differentiation-14 (sCD14) (log10: 0.012±0.004, P=0.003) and faecal detection of this bacterium had a positive association with anti-inflammatory interleukin 10 levels (log10: 0.325±0.131, P=0.015). In addition, A. muciniphila levels were positively associated with total adiponectin (log10: 0.046±0.015, P=0.002), whereas low bimodal levels of A. muciniphila had an inverse relationship with this blood marker (log10: -0.131±0.053, P=0.016). In conclusion, we confirmed the previously reported association of A. muciniphila with metabolic health for the first time in a Greek urban population; furthermore, we shed some light to novel atherosclerotic risk markers with rather unexplored connections with A. muciniphila colonisation patterns in human subjects.

Lipoprotein-associated phospholipase A2 (Lp-PLA2 ) is associated with increased risk of cardiovascular diseases (CVD) and type 2 diabetes mellitus. Lp-PLA2 activity is positively associated with male sex, Caucasian race, the presence of metabolic syndrome (MetS) and low-density lipoprotein (LDL)-cholesterol, but it is negatively associated with high-density lipoprotein (HDL)-cholesterol. Associations with other cardiometabolic risk factors, inflammation markers, and lifestyle factors are few or inconsistent. We investigated potential determinants of Lp-PLA2 activity among both nonmodifiable and modifiable CVD risk factors in a middle-aged Greek cohort without overt CVD. Two hundred eighty four subjects (159 men, 53 ± 9 years and 125 women 52 ± 9 years) participated in a cross-sectional study carried out during 2011-2012 in Athens, Attica. Cardiometabolic risk factors, inflammation markers, lifestyle factors, and Lp-PLA2 activity were evaluated with established methods. The American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) criteria were used to define MetS. Lp-PLA2 activity was not associated with MetS, but was associated with MetS components, markers of liver function, and macronutrient intake. Increased total energy intake was associated with increased Lp-PLA2 activity (odds ratio, 95% confidence interval: 1.07, 1.01-1.14 and 1.10, 1.03-1.16 for the 4th and 3rd quartiles, respectively, compared to the 1st quartile) after adjustments for sex, pack-years of smoking, LDL-cholesterol, and statin treatment. Adiponectin tended to be inversely associated with Lp-PLA2 activity (0.91, 0.82-1.00, and 4th versus 1st quartile). Our results suggested that total energy intake and adiponectin levels are potential determinants of Lp-PLA2 activity.

The primary aim was to investigate the effects of nut and seed consumption on markers of glucose metabolism in adults with prediabetes. Studies with a randomised controlled trial (RCT) design, comparing the effects of a diet containing nuts or seeds against a diet without nuts or seeds in adults with prediabetes, were considered eligible. Primary outcome measures included fasting plasma glucose (FPG), 2-h plasma glucose during oral glucose tolerance test and glycated Hb (HbA1c) concentrations. Studies were identified by searching PubMed and Scopus electronic databases and by checking full texts and reference lists of relevant records. Risk of bias was assessed using the Cochrane Collaboration’s tool. We included five RCT involving 371 adults with prediabetes or at risk of diabetes; three RCT investigated the effects of whole nut consumption and two the effects of ground flaxseed consumption. Consumption of 57 g/d pistachios or mean intake of 60 g/d almonds for 4 months improved FPG and fasting plasma insulin (FPI) concentrations, insulin resistance, cellular glucose uptake in lymphocytes and β-cell function. Consumption of 56 g/d walnuts for 6 months was not found to affect FPG or HbA1c concentrations. Consumption of 13 g/d flaxseed for 3 months improved FPG and FPI concentrations and insulin resistance. In a second study, however, flaxseed consumption was not found to affect markers of glucose metabolism. The risk of bias was generally low, thus the reported results could be reliable. Further investigation of nut and seed consumption effects in the field of prediabetes is warranted.

Platelet-activating factor (PAF), a proinflammatory lipid mediator, plays a crucial role in the formation of the atherosclerotic plaque. Therefore, the inhibition of endothelium inflammation by nutraceuticals, such as PAF inhibitors, is a promising alternative for preventing cardiovascular diseases. The aim of the present study was to evaluate the impact of a new functional yogurt enriched with PAF inhibitors of natural origin from olive oil by-products on PAF metabolism. Ninety-two apparently healthy, but mainly overweight volunteers (35–65 years) were randomly allocated into three groups by block-randomization. The activities of PAF’s biosynthetic and catabolic enzymes were measured, specifically two isoforms of acetyl-CoA:lyso-PAF acetyltransferase (LPCATs), cytidine 5′-diphospho-choline:1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase (PAF-CPT) and two isoforms of platelet activating factor acetylhydrolase in leucocytes (PAF-AH) and plasma (lipoprotein associated phospholipase-A2, LpPLA2). The intake of the enriched yogurt resulted in reduced PAF-CPT and LpPLA2 activities. No difference was observed in the activities of the two isoforms of lyso PAF-AT. In conclusion, intake of yogurt enriched in PAF inhibitors could favorably modulate PAF biosynthetic and catabolic pathways.

Fish consumption beneficially affects coagulation markers. Few dietary intervention studies have investigated differently fed farmed fish against these cardio-metabolic risk factors in humans. This double-blind randomized crossover trial evaluated differently fed farmed gilthead sea bream consumption against platelet aggregation and circulating haemostatic markers among apparently healthy adults. Subjects aged 30–65 years, with a body mass index 24.0–31.0 kg/m2, consuming less than 150 g cooked fish per week, were recruited in Attica, Greece. Participants were randomized (n = 38, 1:1) to one of two sequences, consumption of fish fed with fish oil diet (conventional fish, CF)/fish fed with olive pomace-enriched diet (enriched fish, EF) versus EF/CF. The primary outcomes were ex vivo human platelet aggregation and circulating plasminogen activator inhibitor-1 (PAI-1) and P-selectin (sP-selectin) concentrations. EF consumption had no significant effect on platelet sensitivity or haemostatic markers compared to CF. Platelet sensitivity to platelet-activating factor (PAF) decreased after CF consumption during the second period (p &lt, 0.01). Plasma PAI-1 and sP-selectin concentrations increased after CF consumption during both periods (p &lt, 0.01 for both). Based on current findings, consumption of enriched farmed gilthead sea bream had no greater effect on coagulation markers in adults compared to the conventionally fed fish.

The new coronavirus disease 2019 (COVID-19) pandemic is an emerging situation with high rates of morbidity and mortality, in the pathophysiology of which inflammation and thrombosis are implicated. The disease is directly connected to the nutritional status of patients and a well-balanced diet is recommended by official sources. Recently, the role of platelet activating factor (PAF) was suggested in the pathogenesis of COVID-19. In the present review several micronutrients (vitamin A, vitamin C, vitamin E, vitamin D, selenium, omega-3 fatty acids, minerals), phytonutrients and Mediterranean diet compounds (olive oil, fish, honey, plant foods) with potential anti-COVID activity are presented. We further underline that the well-known anti-inflammatory and anti-thrombotic actions of the investigated nutrients and/ or holistic dietary schemes, such as the Mediterranean diet, are also mediated through PAF. In conclusion, although there is no single food to prevent coronavirus, the aim is to follow a healthy diet containing PAF inhibitors in order to target both inflammation and thrombosis and try to avoid or/and reduce the deleterious effects of the COVID-19 epidemic.

Introduction Platelet-activating-factor is an inflammatory lipid mediator. Key enzymes of its biosynthesis are CDP-choline:1-alkyl-2-acetyl-sn-glycerol-cholinephosphotransferase (PAF-CPT) and acetyl-CoA:lyso-PAF-acetyltransferases (Lyso-PAF-AT) while PAF-AH/Lp-PLA2 degrade PAF. The interplay between PAF and fatty acids metabolism was explored. Material and methods In a healthy population, PAF levels, its metabolic enzymes activity and RBC fatty acids were measured while desaturases indices (D) were estimated. A principal component analysis was also applied to assess patterns of RBC fatty acids. Results SFA were related to increased PAF biosynthesis and decreased Lp-PLA2 only in women. MUFA were inversely associated with PAF biosynthesis and positively with Lp-PLA2. Omega-6 fatty acids were positively correlated only with PAF-CPT while no significant correlations were observed with n3 fatty acids. D6 index was positively related with PAF biosynthetic enzymes and inversely with Lp-PLA2 while D9 correlated positively with Lp-PLA2. The pattern of high MUFA and low n6 was associated with reduced PAF biosynthesis and/or increased catabolism in both sexes. Conclusion The role of fatty acids in amplifying or reducing inflammation seems to be also reflected in PAF metabolism.

Platelet Activating Factor (PAF) is a pro-inflammatory mediator of atherogenesis. Food enriched with PAF inhibitors may have potential cardioprotective properties. For this purpose, we created a yogurt enriched with PAF inhibitors derived from byproducts of olive oil industry, which was consumed by volunteers in order to investigate whether its consumption can affect favorable cardiovascular risk factors. Ninety two (n=92) apparently healthy volunteers (35-65 years) were randomized into three groups based on age, sex and BMI. Volunteers in the Group A consumed a maximum of one plain yogurt every 2 weeks, volunteers in the Group B consumed a non-enriched yogurt daily and volunteers in the Group C ate an enriched yogurt daily. The intervention lasted eight weeks. Biological samples (blood, urine and faeces) were collected at the beginning, in the meantime and at the end of intervention. The article aims to present the rationale, the detailed methodology and the baseline characteristics of the three intervention groups.

Platelets aggregation plays a crucial role in atherothrombosis. Therefore, the aim of the present study was to examine the anti-platelet activity of winery by-products extracts, to find the most potent one and to be further analyzed in order to be used for food fortification. For this purpose, grape pomace from four red varieties was extracted with four solvents of different polarity. The extracts' phenolic content, antioxidant capacity and their ability to inhibit human platelet aggregation against PAF, ADP, TRAP were determined by Light Transmission Aggregometry. The ethanolic extract was further analyzed concerning its anti-platelet effect and its chemical composition by LC-MS/MS and GC-MS. The ethanolic and Bligh-Dyer water phase extracts showed the highest phenolic compounds/anthocyanin content and the best antioxidant activity. However, the most potent inhibition of platelet aggregation was revealed by ethanol extracts, followed by the Bligh-Dyer lipoid phase extracts. Ethanolic extract, found to contain micro-constituents such as phospho-compounds, phenolic compounds and fatty acids. The most abundant phenolic compounds were catechin, epicatechin and quercetin and the most abundant fatty acids were linoleic acid (C18:2n6), linolenic acid (C18:3n3) and palmitic acid (C16:0). Ethanolic extract was capable of inhibiting platelets aggregation in a wide range of agonist concentrations and it also seems that its action is sustained when platelets from coronary heart disease patient were used. Ethanol extract of winery by-products exerts a potent anti-platelet effect and its valorization could lead to the production of functional foods with cardioprotective properties.

Background: The influence of biomarkers in human lifespan has been investigated but with no clear results yet. Materials and methods: Lipids, Uric Acid (UA), Adiponectin (ADIPOQ), Insulin-like Growth Factor (IGF-1), cholesteryl ester transfer protein (CETP) and angiotensin-converting enzyme (ACE) proteins, as well as CETP, ADIPOQ, insulin-like growth factor binding protein-3 (IGFBP3) and ACE-gene polymorphisms were evaluated in 149 Greek individuals. The Long-Lived Families (LON) (n=84) comprised of 3 generations: long-lived aged ≥90 years (P), offspring (FL1) and their grandchildren (FL2), while the Short-Lived Families (EAD) (n=65) where both parents died Results: Serum CETP and IGF-1 levels were lower, whereas AdipoQ concentrations were higher in P compared with FL1 and FL2 members (CETP: p = 0.03 for both comparisons; IGF-1 p < 0.001 for both comparisons and ADIPOQ: p = 0.001 and p = 0.004, respectively). Furthermore, serum triglycerides, UA and glucose concentrations were higher in FD1 compared with FD2 subjects (p=0.001, 0.02 and ≤0.001, respectively). In FD2 and FL2, CETP levels were lower in individuals with B2B2 compared with B1B1 genotype (p=0.007). Additionally, ACE concentrations were higher in individuals with DD compared with II genotype in both Families (p=0.001). After adjustment for age and gender, CETP levels were lower in P and FL2 individuals with B2B2 compared with the B1B1 genotype (p=0.004 and 0.007, respectively). Conclusion: Increase serum TGs, UA and GL concentrations were higher in the middle-aged individuals compared with their children in families independently of their lifespan. The serum adiponectin concentration was the highest in the oldest old individuals implying beneficial influence on lifespan. Independently of family’s lifespan history, the youngest individuals with CETPB2B2 genotype, compared with individuals with CETPB1B1 genotypes, had lower serum CETP concentrations. The knowledge of the unfavourable gene(s)influencing human lifespan may be helpful in encouraging individuals to follow healthier lifestyle habits and better control their high-risk biomarkers.

The purpose of this review is to collect and compare fish intervention studies. Prospective studies have outlined the beneficial effect of frequent fish consumption on cardiovascular incidents that is attributed to n-3 fatty acids incorporated in fish, mainly eicosapentaenoic (EPA), and docosahexaenoic (DHA) acids. This outcome triggered clinical trials to examine the effect of either fish intake or consumption of n-3 fatty acids via capsules on biomarkers related to cardiovascular disease (CVD). The absence of a recent review focusing on clinical trials regarding fish intake and not n-3 fatty acids supplements rendered necessary the composition of this article. In total, 28 studies on healthy volunteers were found to meet the inclusion criteria. With EPA and DHA intake varying between 0.03 to 5 g per day, biomarkers, such as triglycerides, high-density lipoprotein and platelet aggregation, tended to ameliorate when daily intake exceeded 1 g per day, while the most common inflammatory marker, C-reactive protein, was not affected. In all, fish consumption gives promising results; yet fish micronutrients, total diet fat, as well as other dietary habits may also affect biomarkers. Therefore, all these factors should be considered in future clinical trials in order for one to draw more reliable conclusions.

Many studies conclude that wine consumption is related to lower risk for cardiovascular diseases partially through the amelioration of inflammatory biomarkers. The aim of the present study was to examine the effects of wine consumption on the inflammatory response and to compare these effects with the consumption of similar amount of alcohol without the wine micro-constituents in cardiovascular disease patients. Therefore, a randomized, single-blind, controlled, three-arm parallel intervention study was designed. Cardiovascular disease patients were randomly assigned to one of the three groups. In Group A participants consumed no alcohol, in Group B (ethanol group) and Group C (wine group) participants consumed 27 g of alcohol per day. Biological samples were collected at the beginning, on the 4th and 8th week and several biomarkers were measured. Peripheral blood mononuclear cells that were isolated from patients were incubated under basal and inflammatory conditions for 4 and 24 h and the secretion of interleukin 1β (IL-1β) and tumor necrosis factor α (TNFα) was measured. No significant difference was observed among the three groups before the initiation or during the intervention in the most soluble biomarkers. Higher TNFα secretion by peripheral blood mononuclear cells was observed at basal conditions in the ethanol group both at 4 and 24 h of incubation versus baseline secretion. Furthermore, lower secretion of the ΤNFα was observed after 8 weeks of intake in the wine group versus the ethanol group, both at 4 and 24 h of incubation. In conclusion, the light to moderate wine consumption for 8 weeks revealed an attenuation of the ethanol consumption effect on cytokine secretion at basal conditions from the patients’ peripheral blood mononuclear cells.

This study aimed to explore the potential associations of adherence to the Mediterranean diet with gut microbiota characteristics and gastrointestinal symptomatology in an adult population. Other long-term dietary habits (e.g. consumption of snacks and junk food or stimulant intake) were also evaluated in terms of the gut microbiota profile. Participants (n 120) underwent anthropometric, dietary, physical activity and lifestyle evaluation. Adherence to the Mediterranean diet was assessed using a Mediterranean diet score, the MedDietScore, and subjects were classified into three tertiles according to individual adherence scoring. Gut microbiota composition was determined using quantitative PCR and plate-count techniques, and faecal SCFA were analysed using GC. Gastrointestinal symptoms were also evaluated. Participants with a high adherence to the Mediterranean diet had lower Escherichia coli counts (P=0·022), a higher bifidobacteria:E. coli ratio (P=0·025), increased levels and prevalence of Candida albicans (P=0·039 and P=0·050, respectively), greater molar ratio of acetate (P=0·009), higher defaecation frequency (P=0·028) and a more pronounced gastrointestinal symptomatology compared with those reporting low adherence. A lower molar ratio of valerate was also observed in the case of high adherence to the Mediterranean diet compared with the other two tertiles (Pfor trend=0·005). Positive correlations of MedDietScore with gastrointestinal symptoms, faecal moisture, total bacteria, bifidobacteria:E. coli ratio, relative share of Bacteroides, C. albicans and total SCFA, as well as negative associations with cultivable E. coli levels and valerate were indicated. Fast food consumption was characterised by suppressed representation of lactobacilli and butyrate-producing bacteria. In conclusion, our findings support a link between adherence to the Mediterranean diet and gut microbiota characteristics.

Marilita M Moschos,1,2 Giannis A Moustafa,1 Vasiliki D Papakonstantinou,3 Michael Tsatsos,4 Konstantinos Laios,1 Smaragdi Antonopoulou3 11st Department of Ophthalmology, Medical School, University of Athens, Athens, Greece; 2Biomedical Research Foundation, Academy of Athens, Athens, Greece; 3Laboratory of Biology, Biochemistry, Physiology and Microbiology, Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece; 4Royal Eye Infirmary, Dorset County Hospital NHS Foundation Trust, Dorchester, UK Purpose: Altered platelet aggregability has been implicated in the pathogenesis of glaucoma. This study aims to investigate the anti-platelet potential of intraocular pressure lowering drops, with the possibility of establishing it as an additional mechanism of anti-glaucomatous action.Materials and methods: The anti-aggregating effects of a series of anti-glaucomatous eye drops were determined on human platelets in the platelet aggregation model, using four known aggregating factors (platelet activating factor [PAF], adenosine diphosphate [ADP], thrombin receptor-activating peptide [TRAP], and arachidonic acid [AA]).Results: Almost all of the tested samples inhibited platelet aggregation induced by PAF, ADP, TRAP, and AA, except for Alphagan, which did not demonstrate inhibition of ADP- and TRAP-induced aggregation at a wide range of concentrations. Trusopt, Betoptic, and Azarga eye drops were the most potent inhibitors of all four aggregating factors, while Alphagan was the least potent (P

Purpose The aim of the study was to investigate the effect of a 6-week, low-dose bovine colostrum (BC) supplementation on exercise-induced muscle damage (EIMD) and performance decline in soccer players following the Loughborough Intermittent Shuttle Test (LIST) during a competitive season period. Methods In a double-blind, randomized, placebo-controlled design, two groups of soccer players were allocated to a 3.2 g/day of whey protein (WP, N = 8) or BC (N = 10) and performed a pre- and a post-supplementation LIST. Maximum isometric voluntary contraction, squat jump (SQJ), countermovement jump, muscle soreness, blood cell counts, creatine kinase (CK), C-reactive protein (CRP) and interleukin-6 (IL-6) were monitored for 2, 24, 48, 72 h post-LIST. Results LIST induced transient increases in leukocytes, granulocytes, CK, muscle soreness, CRP, IL-6 and declines in lymphocytes and performance indices. Supplementation resulted in a faster recovery of SQJ, CK and CRP compared to pre-supplementation kinetics (trial × time: p = 0.001, 0.056, 0.014, respectively) and lower incremental area under the curve (iAUC) for IL-6, only in the BC group [pre-: 31.1 (6.78–46.9), post-: 14.0 (−0.16 to 23.5) pg h/ml, p = 0.034]. Direct comparison of the two groups after supplementation demonstrated higher iAUC of SQJ [WP: −195.2 (−229.0 to (−52.5)), BC: −15.8 (−93.2 to 16.8) cm h, p = 0.034], a trend for lower iAUC of CK in the BC group [WP: 18,785 (4651–41,357), BC: 8842 (4807–14,802) U h/L, p = 0.081] and a significant intervention × time interaction for CRP (p = 0.038) in favor of BC. Conclusions Post-exercise EIMD may be reduced and performance better maintained by a low dose of BC administration following LIST in soccer players. Electronic supplementary material The online version of this article (doi:10.1007/s00394-017-1401-7) contains supplementary material, which is available to authorized users.

Previous reports support that wine contains a mixture of micro-constituents in a proper quality and quantity that possess cardio-protective effect partly through Platelet-Activating Factor (PAF) inhibition. Grape pomace (GP) is a source of wine-like micro-constituents that may be a suitable alternative in food fortification. Limited data exist concerning their effects on thrombosis and inflammation. Therefore, the purpose of this study was to examine a grape pomace extract regarding its anti-platelet and anti-inflammatory properties. GP from four red grape varieties were extracted with 80% ethanol (GP:solvent 1:5w/v). The extract's total phenolic compounds were evaluated and the phenolic profile was performed by Ultrahigh-Performance-Liquid-Chromatography coupled to Mass-Spectrometry and the determination of fatty acids profile was performed by Gas-Chromatography. The extract's anti-platelet properties were tested in healthy volunteers’ platelet rich plasma by the light transmittance method, against three agonists: PAF, ADP and TRAP. The results expressed as IC50 values (μg of extract that cause 50% inhibition of aggregation) and EC50 values (agonist concentration that causes 50% of the maximum aggregation) in the extract's presence and absence. Concerning the extract's anti-inflammatory properties, peripheral blood mononuclear cells from healthy volunteers were pre-incubated with different extract concentrations, which were tested for their effect on cell viability, for 1 h and then stimulated with LPS for 4 h. Secretion of IL-1β and TNF-a was measured and normalized with the total cell protein. Phenolic compounds were calculated at 8.79 ± 1.17 mg gallic acid per g of GP. The most abundant ones were catechin, epicatechin and quercetin at 202.9 ± 6.9, 84.8 ± 1.5 and 83.7 ± 3.5μg per g of GP respectively. Out of the 18 fatty acids detected, the most abundant ones were palmitic, oleic, linoleic, and linolenic acid at 28.7 ± 0.1, 11.4 ± 0.01, 32.5 ± 0.07, 12.7 ± 0.005 g per 100 g of fat. The extract's IC50 was calculated at 162.1 ± 66.9, 181.2 ± 82.3 and 156.3 ± 97.5μg against PAF, ADP and TRAP, respectively. The EC50 values in the presence of 150μg extract were increased (lower platelet aggregation sensitivity) approximately at 100%, 45% and 13% against PAF, ADP and TRAP respectively, compared to EC50 values in the absence of extract. The presence of 500 and 1000μg/mL of extract reduced LPS-induced TNF-a secretion at approximately 38.2% (p = 0.04) and 6.0% (p < 0.000), respectively. Potent anti-platelet and anti-inflammatory properties are combined in a grape pomace extract. The use of its bioactive micro-constituents is likely to lead to the production of functional foods with cardioprotective properties.

The postprandial state is characterized by a net input of energy substrates and micronutrients and regulated in a complex neurohormonal milieu. Postprandial dysmetabolism (PD) can trigger, in a transient but daily fashion, proinflammatory, procoagulant mechanisms, and endothelial dysfunction. Since postprandial dysmetabolism is an independent risk factor for cardiovascular diseases (CVDs) and adherence to the Mediterranean diet (MD) has been associated with low CVD incidence, it sounds plausible that the cardioprotective properties of MD could also be attributed to its beneficial actions on PD. This review investigates the impact of the most effective/well-studied components of the MD, namely, olive oil, fish, wine, and nuts, on postprandial inflammation, hemostasis, and endothelial function. Despite the heterogeneity of the studies, there are promising results concerning the ability of those foods to restrain the activation of proinflammatory and procoagulant mechanisms leading to endothelial dysfunction. Whether this is another cardioprotective mechanism of MD requires further studies.

IntroductionCumulative findings have recently highlighted the role of gut microbiota as a novel environmental factor in the fight against obesity and related comorbidities. We aimed to investigate (1) the gut microbiome characteristics of a Greek adult population in terms of adiposity prevalence and (2) to further elucidate the potential effect of physical activity level and adherence to a-priori (Mediterranean Diet) and a-posteriori dietary patterns in gut microbiota profiling after accounting for sex, age and obesity status.Materials and MethodsAdult participants (n = 125) underwent clinical, anthropometric, dietary, physical activity and lifestyle evaluation. Obesity status [normal-weight (NW), overweight (OW), obesity (OB)] was defined based on body weight and height measurements, Body Mass Index calculation and the World Health Organization criteria. Levels of physical activity (low/medium/high) were estimated according to International Physical Activity Questionnaire (IPAQ) scoring. Dietary intake was evaluated through a food frequency questionnaire. Adherence to the Mediterranean diet was based on the MedDietScore and Principal Component Analysis (PCA) was applied for dietary patterns analysis. Gut microbial community characteristics (diversity, richness and proportions at phylum level) were calculated based on 16S rRNA gene sequencing.ResultsA total of 122 subjects (58 females; mean age 42.4 ± 13.1 years) completed the study. OB was characterized by lower proportions of Verrucomicrobia compared to NW state (p = 0.034 for univariate), unidentified bacteria (p = 0.014) and the Archaea Euryarchaeota (p = 0.003) compared to OW status, and the phylum Candidatus Saccharibacteria compared to NW (p = 0.027) and OW (p = 0.039) after sex and age adjustments. Regarding lifestyle parameters, our data proposed no significant effect of total physical activity levels on gut microbiome; notably, a ‘fruit and vegetables’ dietary pattern and adherence to Mediterranean diet were both characterized by lower microbial diversity and proportions of Actinobacteria but higher proportions of Cyanobacteria/Chloroplast and Lentisphaerae, respectively. Furthermore, a Western-type dietary pattern (high in full fat dairy products, potatoes, refined cereals, red meat, snacks and junkfood) was characterized by lower gut microbial richness (Chao1 index), whereas a healthy dietary pattern (high in low fat dairy and wholegrain cereals and low in snack and junk food) was characterized by higher proportion of Firmicutes.DiscussionOur data proposed variable connections of metabolic health and dietary patterns with features of gut microbiota; design of gut microbiome studies is advisable to account for host- and lifestyle-related potential confounders.

Anti-inflammatory properties of olive oil are partly attributed to the inhibition of the Platelet-Activating Factor (PAF), a potent inflammatory mediator that is implicated in the initiation and prolongation of atherosclerosis. PAF inhibitors also exist in an extract from olive pomace that inhibits development and regression of atherosclerotic plaques in hypercholesterolemic rabbits. On the other hand, fish consumption is recommended for prevention of cardiovascular diseases, leading to a constantly increasing demand for fish supply, which is further enhanced by the rising consumers’ awareness. As a result a significant growth of aquaculture worldwide has been occurred, which among others strives for improving the nutritional value of the produced fish. Important breakthroughs have occurred in the replacement of fish oil, traditionally used, by plant oils in compounded fish feeds contributing to more nutritious fish products. Under this perspective, present work aimed to evaluate the cardioprotective properties of a novel seabream fed with olive pomace extract.In this crossover study, thirty apparently healthy, men and women were randomly assigned in two diet sequences for 8-week duration (6-week washout period between them), consuming either normal or enriched with olive pomace fish, twice a week. The study was approved by the Bioethics Committee of Harokopio University. Dietary intake was assessed with a validated for the Greek population semi-quantitative food-frequency questionnaire. Lifestyle parameters, biochemical factors, P-selectin and Plasminogen-activator inhibitor-1 (PAI-1) levels were determined. In addition, ex-vivo platelet aggregation in platelet-rich plasma against PAF, ADP and thrombin were measured and the results expressed as EC50 values (the concentration of the agonist that cause 50% of maximum aggregation). Also, PAF key metabolic enzymes activities, responsible for PAF levels, were determined.Concerning dietary habits and biochemical markers only total cholesterol revealed a small increase, within the normal range, after enriched fish consumption, compared to baseline levels. Both fishes resulted in higher EC50 (lower platelet sensitivity) values only against PAF without being differentiated (ptime = 0.02, ptrial = 0.9), while PAI-1 levels were only increased after normal fish consumption (p0–8 weeks = 0.01). The ratio of Lipoprotein-Associated-Phospholipase A2 (catabolic enzyme of PAF) to LDL and PAF-CDP-choline:cholinephosphotransferase (biosynthetic enzyme of PAF) were decreased after the enriched (p0–8 weeks = 0.003) and the normal (p0–8 weeks = 0.01) fish consumption, respectively.Seabream fed with olive pomace seems to exhibit cardioprotective properties by decreasing platelet sensitivity against PAF and modulate PAF metabolism.This research has been co-financed by the European Regional Development Fund of the EU and Greek national funds (project code:T1EDK-00687).

Platelet Activating Factor (PAF) is a pro-inflammatory mediator of atherogenesis. Food enriched with PAF inhibitors may have potential cardioprotective properties. In this attempt our group along with a well-known Greek dairy company incorporated bioactive ingredients (BAL) from olive-oil by-products, rich in PAF receptor specific inhibitors, into another typical food of the Mediterranean diet, namely yogurt. The aim of the present study was to evaluate the cardioprotective properties of the enriched yogurt in apparently healthy volunteers.Ninety two apparently healthy volunteers (35–65 years) were randomly allocated into three groups by block-randomization based on age, sex and BMI. The volunteers in Group A did not consume any yogurt. The volunteers of Group B consumed a non-enriched yogurt daily. The Group C volunteers ate daily an enriched yogurt. The intervention lasted 8 weeks. Volunteers’ adherence to the study protocol was assessed by two 24 h recalls every two weeks conducted by trained personnel. Blood and urine samples were collected at baseline, at 4th week and at 8th week of the intervention and biochemical and inflammatory markers were determined. In addition, platelet aggregation in volunteers’ platelet rich plasma against PAF, ADP and TRAP were measured and the results expressed as the concentration of the agonist that cause 50% of the maximum aggregation (EC50, efficient concentration fifty values).Among classical anthropometric and biochemical markers, only a decrease of blood pressure (systolic and diastolic) levels was observed (p0–8weeks < 0.05) in group B but with no clinical significance. Reduced levels of IL-10 was observed in group C compared to B both in the meantime (p4weeks = 0.01) and at the end of the intervention (p8weeks = 0.04). Furthermore, platelet sensitivity against PAF was only decreased (higher EC50 PAF,) in group C (p0–4weeks = 0.005 and p0–8weeks = 0.05). A trial effect was observed in the meantime among the three groups (p = 0.03).The consumption of the enriched yogurt led to attenuation of subclinical inflammation and platelet sensitivity to thrombotic stimuli in apparently healthy volunteers, indicating a potential cardioprotective role of PAF inhibitors.The work is funded by SYNERGASIA 2011 PROGRAMME. This Programme is co-funded by the European Regional Development Fund and National Resources, Project Code 11SYN-2-652.

Platelet-activating factor (PAF) is a potent mediator of inflammation that plays a crucial role in atherosclerosis. The purpose of this study was to evaluate the effect of a dietary supplement containing mainly plant extracts on PAF actions and metabolism in healthy volunteers. A double-blind, placebo-controlled, 8 weeks’ duration study was performed. Healthy volunteers were randomly allocated into the supplement or the placebo group and fifty-eight of them completed the study. The supplement contained plant extracts (Aloe gel, grape juice, Polygonum cuspidatum) and vitamins. The activities of PAF metabolic enzymes: the two isoforms of acetyl-CoA:lyso-PAF acetyltransferase, cytidine 5’-diphospho-choline:1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase (PAF-cholinephosphotransferase) and platelet-activating factor–acetylhydrolase (PAF-AH) in leucocytes and lipoprotein associated phospholipase-A2 in plasma were measured along with several markers of endothelial function. Platelet aggregation against PAF, ADP and thrombin receptor activating peptide was measured in human platelet-rich plasma by light transmission aggregometry. No difference was observed on soluble vascular cell adhesion molecule-1, sP-selectin and IL-6 levels at the beginning or during the study period between the two groups. Concerning PAF metabolism enzymes’ activity, no difference was observed at baseline between the groups. PAF-AH activity was only increased in the supplement group at 4 and 8 weeks compared with baseline levels. In addition, supplement consumption led to lower platelet sensitivity against PAF and ADP compared with baseline levels. However, a trial effect was only observed when platelets were stimulated by PAF. In conclusion, supplementation with plant extracts and vitamins ameliorates platelet aggregation primarily against PAF and secondarily against ADP and affects PAF catabolism by enhancing PAF-acetylhydrolase activity in healthy subjects.