Explore the vast range of titles available.

The metabolism of anthocyanins in humans is still not fully understood, which is partly due to the lack of reference compounds. It is known that sulfation is one way of the complex phase II biotransformation mechanism. Therefore, cyanidin-3-O-glucoside and the cyanidin aglycone were chemically converted to their sulfates by reaction with sulfur trioxide-N-triethylamine complex in dimethylformamide. The reaction products were characterized by UHPLC coupled to linear ion trap and IMS-QTOF mass spectrometry. Based on MS data, retention times, and UV-Vis spectra, the compounds could tentatively be assigned to A-, C-, or B-ring sulfates. Analysis of urine samples from two volunteers after ingestion of commercial blackberry nectar demonstrated the presence of two sulfated derivatives of the cyanidin aglycone and one sulfated derivative of the cyanidin-3-O-glucoside. It was found that both the A ring and the B ring are sulfated by human enzymes. This study marks an important step toward a better understanding of anthocyanin metabolism.

The approach presented in this study is the first for the hemisynthesis of methylated anthocyanins. It was possible to obtain cyanidin-3-O-glucoside derivatives with different degrees of methylation. Cautious identification of 4′-, 5-, and 7-OH monomethylated derivatives was also accomplished. The methylation agent used was the “green chemical” dimethyl carbonate (DMC), which is characterized by low human and ecological toxicity. The influence of the temperature, reaction time, and amount of the required diazabicyclo[5.4.0]undec-7-en (DBU) catalyst on the formation of the products was examined. Compared to conventional synthesis methods for methylated flavonoids using DMC and DBU, the conditions identified in this study result in a reduction of reaction time, and an important side reaction, so-called carboxymethylation, was minimized by using higher amounts of catalyst.

The present study evaluates the effect of olive (Olea europaea L.) vegetation water on human cells regarding its antioxidant properties and radical scavenger bioactivities. To this aim, two food supplements containing concentrated olive water in combination with 6% lemon juice or 70% grape juice, respectively, were assessed in different oxidation assays. From the investigated polyphenols, hydroxytyrosol, present in olives and in a lesser extent in grapes, was found to be the most abundant in both formulations, followed by tyrosol and oleuropein for the olive-derived concentrate with lemon juice, and by proanthocyanidins and tyrosol for the olive concentrate with grape juice. Cellular studies suggest that both formulations are effective antioxidants. In particular, the combination of olive and grape extracts showed a remarkable superoxides-, hydroxyl radicals-, and hydrogen peroxides-scavenging activity, while the formulation containing 94% olive concentrate wasmore potent in protecting the cells against lipoxidation. Both products showed a significant and similar effect in preventing advanced glycation end products’ (AGEs) formation. In addition, preliminary data indicate that hydroxytyrosol is absorbed into the human body when administered via these hydrophilic matrices, as confirmed by the urinary excretion of free hydroxytyrosol. Since the availability of phytochemicals largely depends on the vehicle in which they are solved, these findings are of relevance and contribute to supporting the healthful effects here assessed in a cellular environment.

Polyphenols are considered healthy because they are supposed to protect people from civilization diseases such as cardiovascular diseases, cancer, or diabetes. This may be due to the inhibition of inflammation or their antioxidant effects. However, there is still a lot of research to be done in this direction because their absorption, distribution, metabolism, and excretion depend on many factors. Moreover, it is possible that the metabolites have a different bioactivity than the original substances. Therefore, it is necessary to accurately identify and quantify the anthocyanin metabolites, and for that reference substances are urgently needed. Because they are not commercially available and cannot be isolated from plants or physiological samples their synthesis is indispensable. Their synthesis can be achieved in different ways: the most obvious realized in this work are enzymatic or chemical approaches. To analyze the results in an advanced way, ion mobility mass spectrometry coupled to a qToF was used. From the obtained data it is possible to establish a database, which may be used to identify metabolites in real biological samples. This is a benefit for the untargeted metabolomics and allows further elucidation of the metabolism of anthocyanins and thus the health-promoting effect of anthocyanins.

Table olives and olive oils are the main dietary sources of hydroxytyrosol (HT), a natural antioxidant compound that has emerged as a potential aid in protection against cardiovascular risk. Bioavailability studies with olive oils showed that HT is bioavailable from its free form and from conjugated forms such as oleuropein and its aglycone. Still, its low dietary intake, poor bioavailability, and high inter-individual variability after absorption through the gastrointestinal tract hamper its full benefits. In a randomized, controlled, blinded, cross-over study, we investigated the impact of HT metabolism and bioavailability by comparing two olive-derived watery supplements containing different doses of HT (30.58 and 61.48 mg of HT/dosage). Additionally, HT-fortified olive oil was used in the control group. To this aim, plasma and urine samples were evaluated in 12 healthy volunteers following the intake of a single dose of the supplements or fortified olive oil. Blood and urine samples were collected at baseline and at 0.5, 1, 1.5, 2, 4, and 12 h after intake. HT and its metabolites were analyzed using UHPLC-DAD-MS/MS. Pharmacokinetic results showed that dietary HT administered through the food supplements is bioavailable and bioavailability increases with the administered dose. After intake, homovanillic acid, HT-3-O-sulphate, and 3,4-dihydroxyphenylacetic acid are the main metabolites found both in plasma and urine. The maximum concentrations in plasma peaked 30 min after intake. As bioavailability of a compound is a fundamental prerequisite for its effect, these results promise a good potential of both food supplements for protection against oxidative stress and the consequent cardiovascular risk.

Table olives and olive oils are the main dietary sources of hydroxytyrosol (HT), a natural antioxidant compound that has emerged as a potential aid in protection against cardiovascular risk. Bioavailability studies with olive oils showed that HT is bioavailable from its free form and from conjugated forms like oleuropein and its aglycone. Still, its low dietary intake, poor bioavailability, and high inter-individual variability after absorption through the gastrointestinal tract hamper its full benefits. In a randomized, controlled, blind, cross-over study, we investigated the impact of HT metabolism and bioavailability by comparing two olive-derived watery supplements containing different doses of HT (30.58 and 61.48 mg of HT/dosage, respectively); additionally, HT-fortified olive oil was used in the control group. To this aim, plasma and urine samples were evaluated in 12 healthy volunteers following the intake of a single dose of the supplements or fortified olive oil. Blood and urine samples were collected at baseline and at 0.5, 1, 1.5, 2, 4, and 12 hours after intake. HT and its metabolites were analyzed by UHPLC-DAD-MS/MS. Pharmacokinetic results showed that dietary HT administered through the food supplements is bioavailable and biovailability increases with the administered dose. After intake, homovanillic acid, HT-3-O-sulfate, and 3,4-dihydroxyphenylacetic acid are the main metabolites found both in plasma and urine. The maximum concentrations in plasma peaked 30 minutes after intake. Being the bioavailability of a compound a fundamental prerequisite for its effect, these results promise a good potential of both food supplements for the protection against oxidative stress and the consequent cardiovascular risk.Competing Interest StatementThe authors have declared no competing interest.Footnotes* https://www.clinicaltrials.gov/ct2/show/NCT04876261

Sexual reproduction brings genes from two parents (matrigenes and patrigenes) together into one individual. These genes, despite being unrelated, should show nearly perfect cooperation because each gains equally through the production of offspring. However, an individual’s matrigenes and patrigenes can have different probabilities of being present in other relatives, so kin selection could act on them differently. Such intragenomic conflict could be implemented by partial or complete silencing (imprinting) of an allele by one of the parents. Evidence supporting this theory is seen in offspring–mother interactions, with patrigenes favoring acquisition of more of the mother’s resources if some of the costs fall on half-siblings who do not share the patrigene. The kinship theory of intragenomic conflict is little tested in other contexts, but it predicts that matrigene–patrigene conflict may be rife in social insects. We tested the hypothesis that honey bee worker reproduction is promoted more by patrigenes than matrigenes by comparing across nine reciprocal crosses of two distinct genetic stocks. As predicted, hybrid workers show reproductive trait characteristics of their paternal stock, (indicating enhanced activity of the patrigenes on these traits), greater patrigenic than matrigenic expression, and significantly increased patrigenic-biased expression in reproductive workers. These results support both the general prediction that matrigene–patrigene conflict occurs in social insects and the specific prediction that honey bee worker reproduction is driven more by patrigenes. The success of these predictions suggests that intragenomic conflict may occur in many contexts where matrigenes and patrigenes have different relatednesses to affected kin.

Background Veno-venous extracorporeal CO 2 removal (vv-ECCO 2 R) and non-invasive neurally adjusted ventilator assist (NIV-NAVA) are two promising techniques which may prevent complications related to prolonged invasive mechanical ventilation in patients with acute exacerbation of COPD. Methods A physiological study of the electrical activity of the diaphragm (Edi) response was conducted with varying degrees of extracorporeal CO 2 removal to control the respiratory drive in patients with severe acute exacerbation of COPD breathing on NIV-NAVA. Results Twenty COPD patients (SAPS II 37 ± 5.6, age 57 ± 9 years) treated with vv-ECCO 2 R and supported by NIV-NAVA were studied during stepwise weaning of vv-ECCO 2 R. Based on dyspnea, tolerance, and blood gases, weaning from vv-ECCO 2 R was successful in 12 and failed in eight patients. Respiratory drive (measured via the Edi) increased to 19 ± 10 μV vs. 56 ± 20 μV in the successful and unsuccessful weaning groups, respectively, resulting in all patients keeping their CO 2 and pH values stable. Edi was the best predictor for vv-ECCO 2 R weaning failure (ROC analysis AUC 0.95), whereas respiratory rate, rapid shallow breathing index, and tidal volume had lower predictive values. Eventually, 19 patients were discharged home, while one patient died. Mortality at 90 days and 180 days was 15 and 25%, respectively. Conclusions This study demonstrates for the first time the usefulness of the Edi signal to monitor and guide patients with severe acute exacerbation of COPD on vv-ECCO 2 R and NIV-NAVA. The Edi during vv-ECCO 2 R weaning was found to be the best predictor of tolerance to removing vv-ECCO 2 R.

Veno-venous extracorporeal CO removal (vv-ECCO R) and non-invasive neurally adjusted ventilator assist (NIV-NAVA) are two promising techniques which may prevent complications related to prolonged invasive mechanical ventilation in patients with acute exacerbation of COPD. A physiological study of the electrical activity of the diaphragm (Edi) response was conducted with varying degrees of extracorporeal CO removal to control the respiratory drive in patients with severe acute exacerbation of COPD breathing on NIV-NAVA. Twenty COPD patients (SAPS II 37 ± 5.6, age 57 ± 9 years) treated with vv-ECCO R and supported by NIV-NAVA were studied during stepwise weaning of vv-ECCO R. Based on dyspnea, tolerance, and blood gases, weaning from vv-ECCO R was successful in 12 and failed in eight patients. Respiratory drive (measured via the Edi) increased to 19 ± 10 μV vs. 56 ± 20 μV in the successful and unsuccessful weaning groups, respectively, resulting in all patients keeping their CO and pH values stable. Edi was the best predictor for vv-ECCO R weaning failure (ROC analysis AUC 0.95), whereas respiratory rate, rapid shallow breathing index, and tidal volume had lower predictive values. Eventually, 19 patients were discharged home, while one patient died. Mortality at 90 days and 180 days was 15 and 25%, respectively. This study demonstrates for the first time the usefulness of the Edi signal to monitor and guide patients with severe acute exacerbation of COPD on vv-ECCO R and NIV-NAVA. The Edi during vv-ECCO R weaning was found to be the best predictor of tolerance to removing vv-ECCO R.

Background: The impact of nitrogen dioxide (NO2 ) and particulate matter with an aerodynamic diameter of less than or equal to 2.5. microns (PM2.5 ) exposures on lung function has been investigated mainly in children and less in adults. Furthermore, it is unclear whether short-term deviations of air pollutant concentration need to be considered in long-term exposure models. Objectives: The aims of this study were to investigate the association between short-term air pollution exposure and lung function and to assess whether short-term deviations of air pollutant concentration should be integrated into long-term exposure models. Methods: Short-term (daily averages 0–7 d prior) and long-term (1- and 4-y means) NO2 and PM2.5 concentrations were modeled using satellite, land use, and meteorological data calibrated on ground measurements. Forced expiratory volume within the first second (FEV1) of forced exhalation and forced vital capacity (FVC) were measured during a LuftiBus assessment (2003–2012) and linked to exposure information from the Swiss National Cohort for 36,085 adults (ages 18–95 y). We used multiple linear regression to estimate adjusted associations, and additionally adjusted models of long-term exposures for short-term deviations in air pollutant concentrations. Results: A 10μg/m3 increase in NO2 and PM2.5 on the day of the pulmonary function test was associated with lower FEV1 and FVC (NO2 : FEV1 −8.0 ml [95% confidence interval: −13.4 , −2.7 ], FVC −16.7 ml [−23.4 , −10.0 ]; PM2.5 : FEV1 −15.3 ml [−21.9 , −8.7 ], FVC −18.5 ml [−26.5 , −10.5 ]). A 10μg/m3 increase in 1-y mean NO2 was also associated with lower FEV1 (−7.7 ml ; −15.9 , 0.5) and FVC (−21.6 ml ; −31.9 , −11.4 ), as was a 10μg/m3 increase in 1-y mean PM2.5 (FEV1: −42.2 ml ; −56.9 , −27.5 ; FVC: −82.0 ml ; −100.1 , −63.9 ). These associations were robust to adjustment for short-term deviations in the concentration of each air pollutant. Conclusions: Short- and long-term air pollution exposures were negatively associated with lung function, in particular long-term PM2.5 exposure with FVC. Our findings contribute substantially to the evidence of adverse associations between air pollution and lung function in adults.