Exploring Human Metabolome after Wine Intake-A Review.

Wine has a rich history dating back to 2200 BC, originally recognized for its medicinal properties. Today, with the aid of advanced technologies like metabolomics and sophisticated analytical techniques, we have gained remarkable insights into the molecular-level changes induced by wine consumption in the human organism. This review embarks on a comprehensive exploration of the alterations in human metabolome associated with wine consumption. A great number of 51 studies from the last 25 years were reviewed; these studies systematically investigated shifts in metabolic profiles within blood, urine, and feces samples, encompassing both short-term and long-term studies of the consumption of wine and wine derivatives. Significant metabolic alterations were observed in a wide variety of metabolites belonging to different compound classes, such as phenolic compounds, lipids, organic acids, and amino acids, among others. Within these classes, both endogenous metabolites as well as diet-related metabolites that exhibited up-regulation or down-regulation following wine consumption were included. The up-regulation of short-chain fatty acids and the down-regulation of sphingomyelins after wine intake, as well as the up-regulation of gut microbial fermentation metabolites like vanillic and syringic acid are some of the most important findings reported in the reviewed literature. Our results confirm the intact passage of certain wine compounds, such as tartaric acid and other wine acids, to the human organism. In an era where the health effects of wine consumption are of growing interest, this review offers a holistic perspective on the metabolic underpinnings of this centuries-old tradition.

Synthesis and Biological Evaluation of Resveratrol Methoxy Derivatives.

Resveratrol, a naturally occurring stilbene, exhibits numerous beneficial health effects. Various studies have demonstrated its diverse biological actions, including anti-oxidant, anti-inflammatory, and anti-platelet properties, thereby supporting its potential for cardio protection, neuroprotection, and anti-cancer activity. However, a significant limitation of resveratrol is its weak bioavailability. To overcome this challenge, multiple research groups have investigated the synthesis of new resveratrol derivatives to enhance bioavailability and pharmacological activities. Nevertheless, there are limited data on the effects of resveratrol derivatives on platelet function. Therefore, the objective of this study was to synthesize resveratrol methoxy derivatives and evaluate their anti-platelet and anti-proliferative activity. Platelet-rich plasma (PRP) obtained from healthy volunteers was utilized to assess the derivatives' ability to inhibit platelet aggregation induced by platelet activating factor (PAF), adenosine diphosphate (ADP), and thrombin receptor activating peptide (TRAP). Additionally, the derivatives' anti-tumor activity was evaluated against the proliferation of PC-3 and HCT116 cells. The results revealed that some methoxy derivatives of resveratrol exhibited comparable or even superior anti-platelet activity compared to the original compound. The most potent derivative was the 4'-methoxy derivative, which demonstrated approximately 2.5 orders of magnitude higher anti-platelet activity against TRAP-induced platelet aggregation, indicating its potential as an anti-platelet agent. Concerning in silico studies, the 4'-methyl group of 4'-methoxy derivative is oriented similarly to the fluorophenyl-pyridyl group of Vorapaxar, buried in a hydrophobic cavity. In terms of their anti-tumor activity, 3-MRESV exhibited the highest potency in PC-3 cells, while 3,4'-DMRESV and TMRESV showed the greatest efficacy in HCT116 cells. In conclusion, methoxy derivatives of resveratrol possess similar or improved anti-platelet and anti-cancer effects, thereby holding potential as bioactive compounds in various pathological conditions.

The effect of moderate wine consumption on cytokine secretion by peripheral blood mononuclear cells: A randomized clinical study in coronary heart disease patients.

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 1ß (IL-1ß) 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.

A weight-loss Mediterranean diet/lifestyle intervention ameliorates inflammation and oxidative stress in patients with obstructive sleep apnea: results of the "MIMOSA" randomized clinical trial.

PURPOSE: Inflammation and oxidative stress are implicated in obstructive sleep apnea (OSA) pathophysiology. We aimed at exploring whether the combination of a weight-loss Mediterranean diet/lifestyle intervention with OSA standard care, i.e., continuous positive airway pressure (CPAP) prescription, can lead to greater improvements in inflammation and oxidative stress, compared to standard care alone. METHODS: This was a randomized controlled clinical trial in 187 adult, overweight patients with moderate-to-severe OSA. Participants were randomized to a standard care (SCG, n = 65), a Mediterranean diet (MDG, n = 62) or a Mediterranean lifestyle group (MLG, n = 60). All groups received OSA standard care. Intervention arms participated in a 6-month behavioral weight-loss intervention based on the Mediterranean diet, while the MLG also received counselling on physical activity and sleep habits. RESULTS: Seven patients were excluded and 53/180 were lost to follow-up. In intention to treat analysis (n = 180), the SCG did not exhibit changes in any of the markers assessed. Post-intervention age-, sex-, baseline- and CPAP use-adjusted plasma high sensitivity C-reactive protein levels (mg/L) were lower in the MDG and the MLG compared to the SCG (mean difference - 1.33, P = 0.039 and - 1.68, P = 0.007, respectively). The MLG also exhibited lower urinary 8-iso prostaglandin F2a levels (ng/mg creatinine) compared to the SCG and the MDG (mean difference - 1.10, P < 0.0001 and - 0.80, P = 0.001, respectively). Adiponectin and oxidized guanine levels were not altered in any of the study groups. Results were similar in per protocol analysis (n = 127). CONCLUSION: A weight-loss Mediterranean diet/lifestyle intervention on top of CPAP has anti-inflammatory and antioxidant benefits in OSA. REGISTRATION: The trial was prospectively registered at ClinicalTrials.gov (NCT02515357) on August 4, 2015.

Evaluation of Anti-Inflammatory, Anti-Platelet and Anti-Oxidant Activity of Wine Extracts Prepared from Ten Different Grape Varieties.

Inflammation, thrombosis and oxidative stress are rarely studied together when wine's biological activity is concerned; hence the existing literature lacks a holistic point of view in the biological outcome. The scope of the present study is to parallel evaluate the effect of wine extracts on those mechanisms. Ten wine varieties and two different extraction methods were used leading to five extracts for each wine: total lipids (TL) and fractions with different phenolic compound classes (FI, FII, FIII and FIV). Their effect on oxidative stress, platelet aggregation and the secretion of cytokines from mononuclear cells was measured and a biological score was calculated. FII of white wines is the most potent extract and the extracts FIII and TL are following. Specifically, FII had higher anti-oxidant and anti-inflammatory score while all three fractions had a similar anti-platelet score. Furthermore, FII and FIII extracts were the most potent red wine extracts and revealed the highest anti-oxidant and anti-inflammatory scores. White wine FII extracts were more potent than the red wine ones while FI and FIV extracts of red wine were more potent than the white wine ones. In conclusion, the protective effect of a wine is independent of its color but is strongly associated with its microconstituents profile. FII extract revealed the highest biological score and further examination is needed in order to identify the compounds that are responsible for the aforementioned actions.

Fish consumption and cardiovascular disease related biomarkers: A review of clinical trials.

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.

Consumption of plant extract supplement reduces platelet activating factor-induced platelet aggregation and increases platelet activating factor catabolism: a randomised, double-blind and placebo-controlled trial.

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.

Improvements in clinical characteristics of patients with non-alcoholic fatty liver disease, after an intervention based on the Mediterranean lifestyle: a randomised controlled clinical trial.

Lifestyle interventions remain the cornerstone therapy for non-alcoholic fatty liver disease (NAFLD). This randomised controlled single-blind clinical trial investigated the effect of Mediterranean diet (MD) or Mediterranean lifestyle, along with weight loss, in NAFLD patients. In all, sixty-three overweight/obese patients (50 (sd 11) years, BMI=31·8 (sd 4·5) kg/m2, 68 % men) with ultrasonography-proven NAFLD (and elevated alanine aminotransferase (ALT) and/or γ-glutamyl transpeptidase (GGT) levels) were randomised to the following groups: (A) control group (CG), (B) Mediterranean diet group (MDG) or (C) Mediterranean lifestyle group (MLG). Participants of MDG and MLG attended seven 60-min group sessions for 6 months, aiming at weight loss and increasing adherence to MD. In the MLG, additional guidance for increasing physical activity and improving sleep habits were given. Patients in CG received only written information for a healthy lifestyle. At the end of 6 months, 88·8 % of participants completed the study. On the basis of intention-to-treat analysis, both MDG and MLG showed greater weight reduction and higher adherence to MD compared with the CG (all P<0·05) at the end of intervention. In addition, MLG increased vigorous exercise compared with the other two study groups (P<0·001) and mid-day rest/naps compared with CG (P=0·04). MLG showed significant improvements in ALT levels (i.e. ALT<40 U/l (P=0·03) and 50 % reduction of ALT levels (P=0·009)) and liver stiffness (P=0·004) compared with CG after adjusting for % weight loss and baseline values. MDG improved only liver stiffness compared with CG (P<0·001) after adjusting for the aforementioned variables. Small changes towards the Mediterranean lifestyle, along with weight loss, can be a treatment option for patients with NAFLD.

Suppression of DNA/RNA and protein oxidation by dietary supplement which contains plant extracts and vitamins: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Excessive oxidative stress may impair bio-molecules and cellular function. Multi antioxidant supplementation is thought to be more effective than a single antioxidant probably through the synergistic or complementary action of natural substances that could enhance the prospective effect. METHODS: In order to estimate the effect of a plant extract based supplement in apparently healthy volunteers' oxidative stress markers, a double-blind and placebo controlled intervention was performed. 62 apparently healthy volunteers, overweight with medium adherence to the Mediterranean diet, were recruited and randomly allocated into two intervention groups (supplement or placebo) for 8 weeks. Basic biochemical markers, oxidized LDL (oxLDL), resistance of serum in oxidation, protein carbonyls in serum and 8-isoprostane and DNA/RNA damage in urine were measured. RESULTS: No differentiation was observed in basic biochemical markers, in oxLDL levels as well as in serum resistance against oxidation, during intervention in the examined groups. A significant resistance regarding urine isoprostanes levels in the supplement group compared to the placebo one, was observed. Reduction on DNA/RNA damage and on protein carbonyls levels (almost 30% and 20% respectively, at 8 weeks) was detected in volunteers who consumed the supplement compared to the control group. CONCLUSION: Consumption of plant extract based supplement seems to reduce DNA/RNA and protein oxidation and in less extent lipids peroxidation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier for this study is: NCT02837107.

Antiproliferative Effects of Red and White Wine Extracts in PC-3 Prostate Cancer Cells.

Experimental and epidemiological studies have shown that antioxidant polyphenols can act as chemopreventive agents against prostate cancer. Cabernet Sauvignon and Rombola wine were extracted in order to obtain fractions containing different classes of compounds. All extracts inhibited the androgen-insensitive human prostate cancer cells (PC-3) proliferation in a dose-dependent manner. The most potent compounds were selected to be further tested.Treatment of PC-3 cells with the selected wine extracts marginally increased the cell distribution in S phase, while producing a remarkable induction of autophagy. Finally, the levels of glutathione along with the concentration of hydrogen peroxide and nitrogen oxide were modulated in the treated cells. Herein, we show that red and wine extracts have direct effects on the proliferation, survival, oxidative status, and the induction of autophagy of PC-3 cells. Our data may have important implications for the design of a more effective adjuvant treatment for prostate cancer patients.

Postprandial effects of wine consumption on Platelet Activating Factor metabolic enzymes.

Platelet Activating factor (PAF) is a potent inflammatory mediator that is involved in the initiation and the prolongation of atherosclerosis. The purpose of the study was to investigate the effect of wine consumption on the activity of PAF metabolic enzymes and on IL-6 levels as a cytokine inflammatory marker. Healthy men participated in 4 daily trials and consumed a standardized meal along with Robola wine (trial R), or Cabernet Sauvignon (trial CS), or ethanol solution (trial E), or water (trial W). A significant trial effect was found in the activity of lyso-PAF acetyltransferase (Lyso-PAF AT) (ptrial=0.01). In specific, R trial decreased enzyme activity compared to E trial (p=0.03) while a trend for differentiation was observed between CS trial and E one (p=0.06) as well as between R trial and W one (p=0.07). Concerning PAF-cholinephosphotransferase (PAF-CPT) activity, a significant trial effect was found (ptrial<0.00). Specifically, both R (p=0.002) and CS (p=0.001) trials decreased enzyme activity compared to E trial. Concerning lipoprotein-associated phospholipase A2 (LpPLA2) no time either trial effect was observed. Concerning IL-6 levels a significant time effect was found (ptime<0.00) while no trial effect was revealed. In conclusion, the protective effect of wine consumption could partly be explained through the modulation of PAF metabolism by wine micro-constituents that lead to lower PAF levels.

Wine consumption reduced postprandial platelet sensitivity against platelet activating factor in healthy men.

PURPOSE: Platelet activating factor (PAF) is a potent inflammatory and thrombotic mediator that participates in the initiation and prolongation of atherosclerosis. The aim of the present study was to evaluate the potential effect of wine consumption on platelet aggregation against PAF. METHODS: The study had cross-over design. Ten healthy men participated in four daily trials on separate days: They consumed a standardized meal along with white wine, Robola variety (trial R), or red wine, Cabernet Sauvignon variety (trial CS), or an ethanol solution (trial E), or water (trial W). Blood samples were collected before and after meal consumption and at several time points during the next 6 h. Platelet aggregation against PAF (EC50 values) and several blood biomarkers were measured, and incremental areas under the curve (iAUC) were calculated. RESULTS: A significant trial effect was found in platelet sensitivity against PAF (p trial = 0.01). Moreover, the iAUC-PAF EC50 of CS trial was higher compared to both iAUC-PAF EC50 of E and W trials (P = 0.04, P = 0.02). Plasminogen activator inhibitor-1 iAUC was higher in all alcoholic beverages compare with the one of W trial (P E  = 0.05, P R  = 0.01, P CS = 0.01). Triacylglycerol iAUC increased significantly only in E compared to W trial (P = 0.04) and were significantly lower at 60-120 min in wine trials compared to the one of E (P < 0.05). CONCLUSIONS: Wine consumption improved platelet sensitivity independently of alcohol, kept triacylglycerols at lower levels during their postprandial elevation, and did not affect plasminogen activator inhibitor-1 levels more adversely than ethanol per se.

Platelet Activating Factor (PAF) biosynthesis is inhibited by phenolic compounds in U-937 cells under inflammatory conditions.

Interleukin 1 beta (IL-1ß) induced platelet activating factor (PAF) synthesis in U-937 cells through stimulation of acetyl-CoA:lysoPAF-acetyltransferase (lyso PAF-AT) at 3 h and DTT-independentCDP-choline-1-alkyl-2-acetyl-sn-glycerol cholinophosphotransferase (PAF-CPT) at 0.5 h. The aim of this study was to investigate the effect of tyrosol (T), resveratrol (R) and their acetylated derivatives(AcDs) which exhibit enhanced bioavailability, on PAF synthesis in U-937 after IL-1ß stimulation. The specific activity of PAF enzymes and intracellular levels were measured in cell homogenates. T and R concentration capable of inducing 50% inhibition in IL-1ß effect on lyso PAF-AT was 48 µΜ ± 11 and 157 µΜ ± 77, for PAF-CPT 246 µΜ ± 61 and 294 µΜ ± 102, respectively. The same order of concentration was also observed on inhibiting PAF levels produced by IL-1ß. T was more potent inhibitor than R (p<0.05). AcDs of T retain parent compound inhibitory activity, while in the case of R only two AcDs retain the activity. The observed inhibitory effect by T,R and their AcDs, may partly explain their already reported beneficial role.

In vivo effect of two first-line ART regimens on inflammatory mediators in male HIV patients.

BACKGROUND: Persistent immune activation and inflammation are lying behind HIV-infection even in the setting of ART mediated viral suppression. The purpose of this study is to define the in vivo effect of two first-line ART regimens on certain inflammatory mediators in male HIV patients. METHODS: Male, naive, HIV-infected volunteers were assigned either to tenofovir-DF/emtricitabine/efavirenz (Group_T) or abacavir/lamivudine/efavirenz (Group_A). Platelet Activating Factor (PAF) levels and metabolic enzymes together with HIV-implicated cytokines (IL-1beta, IL-6, IL-8, IL-10, IL-12p70, TNFa) and VEGF were determined for a 12-month period. Differences within each group were determined by non-parametric Friedman and Wilcoxon test, while the differences between the groups were checked by ANOVA repeated measures. RESULTS: Both ART regimens present pronounced effect on inflammatory mediators, resulting in decreased PAF levels and Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity for tenofovir-containing regimen and same as baseline PAF levels with a peak though at the 3rd month as well as elevated Lp-PLA2 activity for abacavir-containing regimen. CONCLUSIONS: Studies regarding the effect of first-line ART regimens on inflammation may be beneficial in preventing chronic morbidities during HIV-treatment. From this point of view, the present study suggests an anti-inflammatory effect of tenofovir-containing ART, while the temporary increase of PAF levels in abacavir-containing ART may be the link between the reported cardiovascular risk and abacavir administration.

Does Yogurt Enriched with Platelet-Activating Factor Inhibitors from Olive Oil By-Products Affect Gut Microbiota and Faecal Metabolites in Healthy Overweight Subjects? (A randomized, parallel, three arm trial.).

OBJECTIVE: The effect of the daily consumption of a low-fat yogurt (150 g) enriched with Platelet-Activating Factor receptor (PAF-R) antagonists, or the plain one, on gut microbiota and faecal metabolites was investigated in healthy overweight subjects. METHODS: A randomized, three-arm, double-blind, placebo-controlled, parallel-group study was performed that lasted 8 weeks. Blood and stools were collected and analyzed before and after the intervention. RESULTS: Our findings revealed that the intake of the enriched yogurt resulted in a significant increase in the levels of Bifidobacterium spp., Clostridium perfringens group and Firmicutes-to-Bacteroidetes (F/B) ratio. On the other hand, a significant increase in the levels of Lactobacillus and C. perfringens group was detected after the intake of the plain yogurt. The increase in the levels of C. perfringens group was inversely associated with the plasma catabolic enzyme of PAF, namely LpPLA2 (lipoprotein-associated phospholipase A2), a cardiovascular risk marker that has been linked with inflammation and atherosclerosis. Moreover, in the enriched with PAF-R antagonists yogurt group, the increased levels of C. perfringens group were also associated with lower PAF action assessed as ex vivo human platelet-rich plasma (PRP) aggregation. Additionally, a higher % increase in molar ratio of Branched Short Chain Fatty Acids (BSCFAs) was detected for both yogurt groups after the 8 week-intervention compared to control. The consumption of the enriched yogurt also resulted in a significant drop in faecal caproic levels and a trend for lower ratio of butyrate to total volatile fatty acids (VFAs) compared to baseline levels. CONCLUSION: Yogurt consumption seems to favorably affect gut microbiota while its enrichment with PAF-R antagonists from olive oil by-products, may provide further benefits in healthy overweight subjects. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT02259205).

Interleukin-1beta stimulates platelet-activating factor production in U-937 cells modulating both its biosynthetic and catabolic enzymes.

Interleukin-1beta (IL-1ß) is a potent agonist of platelet-activating factor (PAF) synthesis. The monocyte-derived PAF may amplify the inflammatory and thrombotic processes. The IL-1ß-induced enzymatic alterations leading to increased PAF synthesis are ill-defined. In the present study the last enzymatic activities of the remodeling (acetyl-CoA:lyso-PAF acetyltransferase) and de novo (DTT-insensitive CDP-choline:1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase) biosynthetic routes of PAF and its main catabolic enzyme, PAF acetylhydrolase, along with the intracellular and extracellular PAF levels were determined in homogenates and medium of U-937 after their stimulation with recombinant IL-1ß. IL-1ß at 2.5ng/mL induced an early (0.5-3h) and a late (12h) elevation of intracellular PAF levels (2-fold). Only a small portion of intracellular PAF (∼10%) was released to the extracellular medium. IL-1ß increased lyso-PAF acetyltrasnferase activity which was peaked at 3h and kept elevated till 12h. A rapid 1.5-fold increase of cholinephosphotransferase activity was observed in IL-1ß stimulated cells. Finally, a transient stimulation of intracellular PAF-AH was induced by IL-1ß at 3h while incubation of U-937 with the PAF acetylhydrolase inhibitor pefabloc in the presence or absence of IL-1ß led to a strong sustained increase of intracellular PAF levels. In conclusion, both biosynthetic routes of PAF, along with its degradation can be modulated by IL-1ß in a time-specific manner. The inhibition of PAF acetylhydrolase strongly augments PAF's intracellular levels implying its crucial role for the regulation of cellular PAF. The regulation of PAF's enzymatic machinery under inflammatory conditions is more complicated than we thought to be.

Platelet activating factor in heart failure: potential role in disease progression and novel target for therapy.

Heart failure (HF) is a complex syndrome with cardiac, renal, neurohormonal and sympathetic nervous system's manifestations, the pathogenesis of which among others is connected to inflammation. PAF has local and systemic effects pertaining to HF progression since it causes a negative inotropic effect, it induces arrhythmias, it induces apoptosis and it is involved in inflammation and atherosclerosis. In the present review the role of PAF in HF will be thoroughly presented along with the relevant data on PAF enzymes and the potential role of PAF metabolic circuit as a novel pharmacological target.

Associations of phase angle with platelet-activating factor metabolism and related dietary factors in healthy volunteers.

Introduction: Phase angle (PA) is derived from bioelectrical impedance analysis (BIA). It reflects cell membrane function and decreases in disease. It is affected by inflammation, oxidative stress, and diet. Platelet-activating factor (PAF) is a potent inflammatory lipid mediator. Its levels, along with the activity of its metabolic enzymes, including CDP-choline:1-alkyl-2-acetyl-sn-glycerol-cholinephosphotransferase, acetyl-CoA:lyso-PAF-acetyltransferases, and PAF-AH/Lp-PLA2 are also related to dietary factors, such as the dietary antioxidant capacity (DAC). The aim of the study was to estimate whether the PAF metabolic circuit and related dietary factors are associated with PA in healthy volunteers. Methods: In healthy subjects, PAF, its metabolic enzyme activity, and erythrocyte fatty acids were measured, while desaturases were estimated. Food-frequency questionnaires and recalls were used, and food groups, macronutrient intake, MedDietScore, and DAC were assessed. Lifestyle and biochemical variables were collected. DXA and BIA measurements were performed. Results: Lp-PLA2 activity was positively associated with PA (rho = 0.651, p < 0.001, total population; rho = 0.780, p < 0.001, women), while PAF levels were negatively associated with PA only in men (partial rho = -0.627, p = 0.012) and inversely related to DAC. Estimated desaturase 6 was inversely associated with PA (rho = -0.404, p = 0.01, total sample). Moreover, the DAC correlated positively with PA (rho = 0.513, p = 0.03, women). All correlations were adjusted for age, body mass index, and sex (if applicable). Conclusion: PA is associated with PAF levels and Lp-PLA2 activity in a gender-dependent fashion, indicating the involvement of PAF in cell membrane impairment. The relationship of PA with DAC suggests a protective effect of antioxidants on cellular health, considering that antioxidants may inhibit PAF generation.

Food Compass Score and its association with inflammatory markers and homocysteine in cardiovascular disease-free adults: a cross-sectional analysis of the ATTICA epidemiological study.

BACKGROUND/OBJECTIVES: Several nutrient profiling systems have been developed to assist in food choices and policy. Food Compass Score (FCS) is a novel holistic food score assessing 54 parameters. The aim was to assess the relation of FCS with inflammatory and lipid markers in cardiovascular disease-free volunteers. SUBJECTS/METHODS: Information from the ATTICA epidemiological study participants, with complete data on lipid, inflammatory markers and dietary intake were studied (n = 1018). C-reactive protein (CRP) and amyloid A were determined by immunonephelometry, fibrinogen by nephelometry, homocysteine by fluorometry, while tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), adiponectin and leptin were determined by ELISA in fasting blood samples. Dietary intake was assessed through a semi-quantitative validated food frequency questionnaire. Each food was assigned a FCS value from the published values and then individual's FCS values were calculated. RESULTS: Mean FCS was 56 (standard deviation: 5.7) and it was similar in men and women. FCS was inversely correlated with age (r = -0.06, p = 0.03). In multiple linear regression models, FCS was inversely associated with CRP (-0.03, 0.01), TNF-a (-0.04, 0.01), amyloid A (-0.10, 0.04) and homocysteine (-0.09, 0.04) (b coefficients, standard errors, all p < 0.05) and was not associated with IL-6, fibrinogen, adiponectin, leptin, or lipids levels (all p > 0.05). CONCLUSIONS: The inverse correlations of the FCS with inflammatory markers suggest that a diet containing foods with high FCS might be protective against inflammation process. Our results support the usefulness of the FCS, but future studies should evaluate its relation to cardiovascular and other inflammation-related chronic diseases.

Associations between serum vitamin D status and the cardiometabolic profile of patients with obstructive sleep apnea.

PURPOSE: Obstructive sleep apnea (OSA) and the metabolic syndrome (MetS) frequently coexist. Low serum vitamin D has been positively associated with OSA presence and severity; however, data on its link to cardiometabolic features in patients with OSA remain scarce. We aimed to assess serum 25-hydroxyvitamin D [25(OH)D] and explore its association with cardiometabolic parameters in OSA. METHODS: This was a cross-sectional study among 262 patients (49 ± 9 years old, 73% men) with polysomnography-diagnosed OSA. Participants were evaluated in terms of anthropometric indices, lifestyle habits, blood pressure, biochemical, plasma inflammatory and urinary oxidative stress markers, and the presence of MetS. Serum 25(OH)D was assessed by chemiluminescence, and vitamin D deficiency (VDD) was defined as 25(OH)D < 20 ng/mL. RESULTS: Median (1st, 3rd quartile) serum 25(OH)D levels were 17.7 (13.4, 22.9) ng/mL and 63% of participants had VDD. Serum 25(OH)D correlated negatively with body mass index (BMI), homeostasis model of assessment of insulin resistance (HOMA-IR), total cholesterol, low-density lipoprotein cholesterol, triglycerides, high-sensitivity C-reactive protein (hsCRP), and urinary oxidized guanine species (oxG), and positively with high-density lipoprotein cholesterol (all P < 0.050). In logistic regression analysis, serum 25(OH)D was associated with lower odds of MetS [odds ratio (95% confidence interval): 0.94 (0.90-0.98)], after adjustment for age, sex, season of blood sampling, Mediterranean diet score, physical activity, smoking, apnea-hypopnea index, HOMA-IR, hsCRP, and oxG. In the same multivariate model, VDD was associated with ~ twofold greater odds of MetS [2.39 (1.15, 4.97)]. CONCLUSION: VDD is highly prevalent and is associated with a detrimental cardiometabolic profile among patients with OSA.