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Scope: The purpose of the study is to characterize the chemical diversity in Rice bran (RB) lipidome and determine whether daily RB consumption for 4 weeks may modulate plasma lipid profiles in children. Methods and Results: Untargeted and targeted lipidomics via ultra-performance liquid chromatography coupled with high-resolution tandem mass spectrometry (UPLC-MS/MS) were applied to identify bioactive RB lipids from a collection of 17 rice varieties. To determine the impact of RB (Calrose-USA variety) supplementation on plasma lipid profile, a secondary analysis of plasma lipidome was conducted on data recorded in a clinical study (NCT01911390, n = 18 moderately hypercholesterolemic children) before and after 4 weeks of dietary intervention (15 g/d) with a control or RB supplemented snack. Untargeted lipidomic revealed 118 lipids as the core of lipidome across all 17 varieties among which phospholipids were abundant and oxylipins present. Phytoprostanes and phytofurans were quantified and characterized. Lipidome analysis of the children plasma following RB consumption revealed the presence of novel polar lipids and oxylipins alongside putative modulations in endocannabinoids associated with RB consumption. Conclusion: The investigation of novel polar lipids, oxylipins, phytoprostanes, and phytofurans in RB extracts provides support for new health-promoting properties especially interesting for people at risk for cardiometabolic disease.

Isoprostanes (IsoPs) are lipid peroxidation biomarkers that reveal the oxidative status of the organism without specifying which organs or tissues it occurs in. Similar compounds have recently been identified that can assess central nervous system (CNS) lipid peroxidation status, usually oxidated by reactive oxygen species. These compounds are the neuroprostanes (NeuroPs) derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the F2t-dihomo-isoprotanes derived from adrenic acid (AdA). The aim of the present investigation was to evaluate whether the long-term nutraceutical consumption of high polyphenolic contents (600 mg) from fruits (such as berries) and vegetables shows efficacy against CNS lipid peroxidation in urine biomarkers. A total of 92 subjects (47 females, 45 males, age 34 ± 11 years old, weight 73.10 ± 14.29 kg, height 1.72 ± 9 cm, body mass index (BMI) 24.40 ± 3.43 kg/m2) completed a randomized, cross-over, double-blind study after an intervention of two periods of 16 weeks consuming either extract (EXT) or placebo (PLA) separated by a 4-week washout period. The results showed significant reductions in three AdA-derived metabolites, namely, 17-epi-17-F2t-dihomo-IsoPs (Δ −1.65 ng/mL; p < 0.001), 17-F2t-dihomo-IsoPs (Δ −0.17 ng/mL; p < 0.015), and ent-7(RS)-7-F2t-dihomo-IsoPs (Δ −1.97 ng/mL; p < 0.001), and one DHA-derived metabolite, namely, 4-F4t-NeuroP (Δ −7.94 ng/mL; p < 0.001), after EXT consumption, which was not observed after PLA consumption. These data seem to show the effectiveness of the extract for preventing CNS lipid peroxidation, as determined by measurements of oxylipins in urine through Ultra-High-Performance Liquid Chromatography triple quadrupole tandem mass spectrometry (UHPLC-QqQ-ESI-MS/MS).

Plant phytoprostanes (PhytoPs) are lipid oxidative stress mediators that share structural similarities with mammal prostaglandins (PGs). They have been demonstrated to modulate inflammatory processes mediated by prostaglandins. The present study aims to test the effects of the most abundant oxylipin from Gracilaria longissima, ent-9-D1t-Phytoprostane (9-D1t-PhytoP), on platelet activation and vascular cells as well as clarify possible interactions with platelets and the endothelial EP3 receptor Platelet and monocyte activation was assessed by flow cytometry in the presence of purified 9-D1t-PhytoP. Cell migration was studied using the human Ea.hy926 cell line by performing a scratch wound healing assay. The RNA expression of inflammatory markers was evaluated by RT-PCR under inflammatory conditions. Blind docking consensus was applied to the study of the interactions of selected ligands against the EP3 receptor protein. The 9D1t-PhytoP exerts several pharmacological effects; these include prothrombotic and wound-healing properties. In endothelial cells, 9D1t-PhytP mimics the migration stimulus of PGE2. Computational analysis revealed that 9D1t-PhytP forms a stable complex with the hydrophobic pocket of the EP3 receptor by interaction with the same residues as misoprostol and prostaglandin E2 (PGE2), thus supporting its potential as an EP3 agonist. The potential to form procoagulant platelets and the higher endothelial migration rate of the 9-D1t-PhytoP, together with its capability to interact with PGE2 main target receptor in platelets suggest herein that this oxylipin could be a strong candidate for pharmaceutical research from a multitarget perspective

The present study aimed to discover the effects of exogenously foliar-applied salicylic acid (SA) in concentrations of 0, 1 and 15 mM (applied 7 and 21 days after heading) on oxidative stress. The effects were monitored through the concentrations of phytoprostanes (PhytoPs) and phytofurans (PhytoFs) in immature and mature grains of three genotypes of rice (‘R52’, ‘R45’ and ‘Yerua’), and their influence on grains per panicle and chalkiness. Chromatographic separation of PhytoPs and PhytoFs was performed using a UHPLC coupled to triple quadrupole-MS/MS (Agilent Technologies, Germany). The concentrations of oxylipins showed differences in both harvest times (immature and mature) for each genotype. The advanced lines, ‘R52’ and ‘R45’, showed concentrations that were 24.0 and 79.0% lower than those of the immature grains, respectively. The PhytoFs concentration in “R45” was 46.0% lower in the mature grains. In unripe grains, SA reduced a single oxylipin of all those analyzed, while in mature grains, a significant decrease in six of the ten monitored biomarkers was observed. The SA produced an increase in grains per panicle, and a decrease in chalkiness. Therefore, salicylic acid-mediated antioxidant regulatory capacities due to oxylipin down-regulation could favor grain filling and, hence, rice production

Branched fatty acid esters of hydroxy fatty acids are endogenous lipids reported to have antidiabetic and anti-inflammatory effects. Recently, we showed that 9-palmitic acid esters of hydroxypalmitic acid (9-PAHPA) and 9-oleic acid esters of hydroxypalmitic acid increased insulin sensitivity in mice when incorporated to a chow diet or to a high fat and high sucrose diet. However, preventive supplementation with 9-PAHPA and 9-oleic acid esters of hydroxy-palmitic acid in high fat and high sucrose diet mice did not impair significant weight gain or the development of hyperglycemia. The aim of this work was therefore to study whether in two animal models of obesity, namely the classical diet-induced obesity (DIO) and the db/db mice, 9-PAHPA may have ben-eficial effects against obesity and liver and skeletal muscle metabolic dysfunction. In DIO mice, we observed that 9-PAHPA increased body weight and fat mass. In line with this observation, we found that 9-PAHPA supplementation decreased energy expenditure. In liver and in skeletal muscle, mitochondrial activities and oxidative stress parameters were not modified by 9-PAHPA supplementation. In db/db mice, 9-PAHPA had no effect on the dramatic weight gain and hyperglycemia. In addition, 9-PAHPA supplementation did not correct either the hepatomegaly and hepatic steatosis or the severe muscle atrophy recorded compared with db/ + animals. Likewise, supplementation with 9-PAHPA did not impact the different metabolic parameters analyzed, either in the liver or in the skeletal muscles. However, it decreased insulin resistance in DIO and db/db mice. In conclusion, our study indicated that a long-term intake of 9-PAHPA in DIO and db/db mice improved insulin sensitivity but had only few effects on obesity and associated metabolic di

Polyunsaturated fatty acids (PUFAs) are structural components of membrane phospholipids, and influence cellular function via effects on membrane properties, and also by acting as a precursor pool for lipid mediators. These lipid mediators are formed via activation of pathways involving at least one step of dioxygen-dependent oxidation, and are consequently called oxylipins. Their biosynthesis can be either enzymatically-dependent, utilising the promiscuous cyclooxygenase, lipoxygenase, or cytochrome P450 mixed function oxidase pathways, or nonenzymatic via free radical-catalyzed pathways. The oxylipins include the classical eicosanoids, comprising prostaglandins, thromboxanes, and leukotrienes, and also more recently identified lipid mediators. With the advent of new technologies there is growing interest in identifying these different lipid mediators and characterising their roles in health and disease. This review brings together contributions from some of those at the forefront of research into lipid mediators, who provide brief introductions and summaries of current understanding of the structure and functions of the main classes of nonclassical oxylipins. The topics covered include omega-3 and omega-6 PUFA biosynthesis pathways, focusing on the roles of the different fatty acid desaturase enzymes, oxidized linoleic acid metabolites, omega-3 PUFA-derived specialized pro-resolving mediators, elovanoids, nonenzymatically oxidized PUFAs, and fatty acid esters of hydroxy fatty acids.

Polyunsaturated fatty acids (PUFAs) are structural components of membrane phospholipids, and influence cellular function via effects on membrane properties, and also by acting as a precursor pool for lipid mediators. These lipid mediators are formed via activation of pathways involving at least one step of dioxygen-dependent oxidation, and are consequently called oxylipins. Their biosynthesis can be either enzymatically-dependent, utilising the promiscuous cyclooxygenase, lipoxygenase, or cytochrome P450 mixed function oxidase pathways, or nonenzymatic via free radical-catalyzed pathways. The oxylipins include the classical eicosanoids, comprising prostaglandins, thromboxanes, and leukotrienes, and also more recently identified lipid mediators. With the advent of new technologies there is growing interest in identifying these different lipid mediators and characterising their roles in health and disease. This review brings together contributions from some of those at the forefront of research into lipid mediators, who provide brief introductions and summaries of current understanding of the structure and functions of the main classes of nonclassical oxylipins. The topics covered include omega-3 and omega-6 PUFA biosynthesis pathways, focusing on the roles of the different fatty acid desaturase enzymes, oxidized linoleic acid metabolites, omega-3 PUFA-derived specialized pro-resolving mediators, elovanoids, nonenzymatically oxidized PUFAs, and fatty acid esters of hydroxy fatty acids.

Recently, lipophenols (or phenolipids), which are composed of a fatty acid (FA) and a phenolic core such as hydroxytyrosol (HT), have been detected in extra virgin olive oils (EVOO), promoted by the esterification reaction between FA and HT in a unique lipophenolic molecule (HT-FAs). However, the levels of HT-FAs, as well as potential alterations in their concentrations during the storage of EVOO, are still unexplored. Thus, the present study uncovers, by UHPLC-MS/MS triple quadrupole analyzer, the changes of HT-FA levels in extra virgin olive oil (EVOO) during 12 months of storage, mimicking both commercial temperatures (room temperature (RT)), as well as inappropriate conditions of storage at high temperatures (40 °C). In addition, levels of HT-FAs in olive oils (blends with refined olive oil) compared to EVOO were assessed to investigate the effect of the refining process on lipophenol generation. Free HT concentration in EVOO was increased, after 12 months, by 121.31% and 236.80% at RT and 40 °C, respectively. Additionally, HT-FAs in EVOO samples, mainly, esterified with linoleic acid and oleic acid, enhanced up to 2.6-fold and 5.5-fold, respectively after 12 months at 40 °C. Nonetheless, in blends with refined oils, the levels of free HT decreased by 80.2%, whereas esterified HT augmented significantly. The type of FA linked to HT core, as well as the degree of unsaturation of FA seem to influence the lipophenolic derivative generation. Significant concentration differences found during storage time supported their potential use as candidate markers, but these findings so require further assessment to establish the HT-FAs concentration range for authentication purposes. Likewise, the ratio between esterified/free HT could be employed as freshness or aging indices of the EVOO during its shelf life, when used in conjunction with validated olive quality parameters.

Lipophenols (also called phenolipids) are polyphenolic compounds acylated by a fatty acid (saturated, mono or polyunsaturated) [1]. Lipophenols have recently been identified in food matrices naturally rich in both polyphenols and fatty acids, making them natural derivatives present in human diet [2]. Recently, we demonstrated that synthetic flavonoids-PUFA derivatives leads to the protection of retinal cells against carbonyl and oxidative stresses, both toxic mechanisms involved in retina dystrophy such as macular degeneration and Stargardt disease. We also showed that a proper alkyl substituent allowed to dramatically increase their anti-carbonyl stress capacity leading to strong interest on quercetine derivative bearing both an isopropyl and a docosahexaenoic acid part (Q-iP-DHA) [3]. We now report the chemical synthesis of lipophenol of resveratrol using polyunsaturated fatty acids, and highlight the new antitumor properties of resveratrol-EPA (linked to eicosapentaenoic acid) on SF188 glioblastoma cells and others cancerous cell lines. Comparaison of the anti-proliferative action of resveratrol-EPA compared to resveratrol and EPA will be presented

Background: The control and prevention of vector-borne and zoonotic diseases is often based on the reduction of host or vector populations, involving but not limited to preventative culling and use of insecticides. Yet, destructive interventions such as these have shown several limitations including ineffectiveness on arthropods and negative impacts on ecosystems. An alternative strategy would be to rely on the natural ecosystem functions and their careful management to regulate such diseases. The goal of our work was to evaluate existing scientific evidence on potential links between ecosystem components/functions and 14 vector-borne and zoonotic diseases impacting human health and answer the question: “What evidence exists on the impact of specific ecosystem components and functions on infectious diseases?”. Methods: We searched for scientific articles published in English and French and screened them in a 3-round process (title, abstract and full-text). Articles were retained, without any geographical limitation, if they matched the following eligibility criteria: an exposure/intervention linked to changes in biological communities, habitats, or landscapes; an outcome consisting of any measure of infection in vector, animal or human hosts; and the presence of a comparator, in time and/or in space. The results are presented as a systematic map, followed by a narrative review where the amount of papers allowed for synthesis. Results: Searches in 5 scientific publication databases allowed to retrieve 9723 unique articles, among which 207 were retained after the screening process. The amount of relevant literature was highly variable depending on diseases, and the types of exposures also varied greatly among studies focusing on the same disease. A hundred articles presented in the map were unique in their “disease x exposure” combination and thus not eligible for further narrative description. The remaining 107 articles were organized in 34 “disease x exposure” group

The effect of coffee and cocoa on oxidative damage to macromolecules has been investigated in several studies, often with controversial results. This study aimed to investigate the effect of one-month consumption of different doses of coffee or cocoa-based products containing coffee on markers of DNA damage and lipid peroxidation in young healthy volunteers. Twenty-one volunteers were randomly assigned into a three-arm, crossover, randomized trial. Subjects were assigned to consume one of the three following treatments: one cup of espresso coffee/day (1C), three cups of espresso coffee/day (3C), and one cup of espresso coffee plus two cocoa-based products containing coffee (PC) twice per day for 1 month. At the end of each treatment, blood samples were collected for the analysis of endogenous and H2O2-induced DNA damage and DNA oxidation catabolites, while urines were used for the analysis of oxylipins. On the whole, four DNA catabolites (cyclic guanosine monophosphate (cGMP), 8-OH-2′-deoxy-guanosine, 8-OH-guanine, and 8-NO2-cGMP) were detected in plasma samples following the one-month intervention. No significant modulation of DNA and lipid damage markers was documented among groups, apart from an effect of time for DNA strand breaks and some markers of lipid peroxidation. In conclusion, the consumption of coffee and cocoa-based confectionery containing coffee was apparently not able to affect oxidative stress markers. More studies are encouraged to better explain the findings obtained and to understand the impact of different dosages of these products on specific target groups.

The effect of coffee and cocoa on oxidative damage to macromolecules has been investigated in several studies, often with controversial results. This study aimed to investigate the effect of one-month consumption of different doses of coffee or cocoa-based products containing coffee on markers of DNA damage and lipid peroxidation in young healthy volunteers. Twenty-one volunteers were randomly assigned into a three-arm, crossover, randomized trial. Subjects were assigned to consume one of the three following treatments: one cup of espresso coffee/day (1C), three cups of espresso coffee/day (3C), and one cup of espresso coffee plus two cocoa-based products containing coffee (PC) twice per day for 1 month. At the end of each treatment, blood samples were collected for the analysis of endogenous and H2O2-induced DNA damage and DNA oxidation catabolites, while urines were used for the analysis of oxylipins. On the whole, four DNA catabolites (cyclic guanosine monophosphate (cGMP), 8-OH-2′-deoxy-guanosine, 8-OH-guanine, and 8-NO2-cGMP) were detected in plasma samples following the one-month intervention. No significant modulation of DNA and lipid damage markers was documented among groups, apart from an effect of time for DNA strand breaks and some markers of lipid peroxidation. In conclusion, the consumption of coffee and cocoa-based confectionery containing coffee was apparently not able to affect oxidative stress markers. More studies are encouraged to better explain the findings obtained and to understand the impact of different dosages of these products on specific target groups.

Background: The control and prevention of vector-borne and zoonotic diseases is often based on the reduction of host or vector populations, involving but not limited to preventative culling and use of insecticides. Yet, destructive interventions such as these have shown several limitations including ineffectiveness on arthropods and negative impacts on ecosystems. An alternative strategy would be to rely on the natural ecosystem functions and their careful management to regulate such diseases. The goal of our work was to evaluate existing scientific evidence on potential links between ecosystem components/functions and 14 vector-borne and zoonotic diseases impacting human health and answer the question: “What evidence exists on the impact of specific ecosystem components and functions on infectious diseases?”. Methods: We searched for scientific articles published in English and French and screened them in a 3-round process (title, abstract and full-text). Articles were retained, without any geographical limitation, if they matched the following eligibility criteria: an exposure/intervention linked to changes in biological communities, habitats, or landscapes; an outcome consisting of any measure of infection in vector, animal or human hosts; and the presence of a comparator, in time and/or in space. The results are presented as a systematic map, followed by a narrative review where the amount of papers allowed for synthesis. Results: Searches in 5 scientific publication databases allowed to retrieve 9723 unique articles, among which 207 were retained after the screening process. The amount of relevant literature was highly variable depending on diseases, and the types of exposures also varied greatly among studies focusing on the same disease. A hundred articles presented in the map were unique in their “disease x exposure” combination and thus not eligible for further narrative description. The remaining 107 articles were organized in 34 “disease x exposure” group

Recently, new bioactive compounds were identified in olive oil, lipophenols, which are composed of a fatty acid (FA) and a phenolic core, such as HT (HT-FA). However, their bioaccessibility remains unknown. Thus, the present study uncovers the impact of the separate phases of gastrointestinal digestion on the release and stability of HT-FAs from oily matrices under in vitro simulated conditions. Accordingly, it was found that the bioaccessibility of HT derivatives is largely dependent on the type of FA that esterifies HT, as well as the food matrix. Also, the generation of HT-FAs during intestinal digestion was observed, with pancreatin being the enzyme responsible, to a higher extent, for the de novo formation of lipophenolic derivatives. These findings prompt us to identify new applications to oily matrices and their byproducts as potential functional ingredients for the promotion of health, where the possible formation of new lipophenols during digestion should be taken into consideration.

Presently, the attention given to natural substances to counteract damage produced by oxidative stress (OS) has risen sharply. In this scenario, hydroxytyrosol (HT) derivatives, formed as a result of HT conjugation with fatty acids (FAs) (lipophenols), have been recently described in foodstuffs such as extra virgin olive oil, as being powerful bioactive compounds with a higher activity than the unesterified phenolic compound. The present work describes the capacity of HT lipophenols to act on the course of OS and secondary inflammatory processes, based on their capacity to modulate the isoprostanoid profile induced by HO in THP-1 monocytic cells. A UHPLC-QqQ-ESI-MS/MS-based lipidomics workflow was applied over a range of 37 human oxylipins. The main outcomes retrieved suggest both HT and HT-lipophenols as regulators of the cellular redox balance, acting as pro-oxidants in vitro, which is highly dependent on the experimental conditions. Our outcomes suggest the anti-inflammatory potential of both HT and HT-lipophenols, where the type of the FAs on the HT core appears to be critical for defining the bioactivity of lipophenols, highlighting that a lipidomic approach, with the simultaneous analysis of multiple oxylipins, is critical for the understanding of the bioactivity of lipophenols on isoprostanoid generation and hence, on pathophysiological processes.

The effect of coffee and cocoa on oxidative damage to macromolecules has been investigated in several studies, often with controversial results. This study aimed to investigate the effect of one-month consumption of different doses of coffee or cocoa-based products containing coffee on markers of DNA damage and lipid peroxidation in young healthy volunteers. Twenty-one volunteers were randomly assigned into a three-arm, crossover, randomized trial. Subjects were assigned to consume one of the three following treatments: one cup of espresso coffee/day (1C), three cups of espresso coffee/day (3C), and one cup of espresso coffee plus two cocoa-based products containing coffee (PC) twice per day for 1 month. At the end of each treatment, blood samples were collected for the analysis of endogenous and H2O2-induced DNA damage and DNA oxidation catabolites, while urines were used for the analysis of oxylipins. On the whole, four DNA catabolites (cyclic guanosine monophosphate (cGMP), 8-OH-2′-deoxy-guanosine, 8-OH-guanine, and 8-NO2-cGMP) were detected in plasma samples following the one-month intervention. No significant modulation of DNA and lipid damage markers was documented among groups, apart from an effect of time for DNA strand breaks and some markers of lipid peroxidation. In conclusion, the consumption of coffee and cocoa-based confectionery containing coffee was apparently not able to affect oxidative stress markers. More studies are encouraged to better explain the findings obtained and to understand the impact of different dosages of these products on specific target groups.

A comprehensive and standardized system to report lipid structures analyzed by MS is essential for the communication and storage of lipidomics data. Herein, an update on both the LIPID MAPS classification system and shorthand notation of lipid structures is presented for lipid categories Fatty Acyls (FA), Glycerolipids (GL), Glycerophospholipids (GP), Sphingolipids (SP), and Sterols (ST). With its major changes, i.e., annotation of ring double bond equivalents and number of oxygens, the updated shorthand notation facilitates reporting of newly delineated oxygenated lipid species as well. For standardized reporting in lipidomics, the hierarchical architecture of shorthand notation reflects the diverse structural resolution powers provided by mass spectrometric assays. Moreover, shorthand notation is expanded beyond mammalian phyla to lipids from plant and yeast phyla. Finally, annotation of atoms is included for the use of stable isotope-labeled compounds in metabolic labeling experiments or as internal standards. This update on lipid classification, nomenclature, and shorthand annotation for lipid mass spectra is considered a standard for lipid data presentation.

A comprehensive and standardized system to report lipid structures analyzed by MS is essential for the communication and storage of lipidomics data. Herein, an update on both the LIPID MAPS classification system and shorthand notation of lipid structures is presented for lipid categories Fatty Acyls (FA), Glycerolipids (GL), Glycerophospholipids (GP), Sphingolipids (SP), and Sterols (ST). With its major changes, i.e., annotation of ring double bond equivalents and number of oxygens, the updated shorthand notation facilitates reporting of newly delineated oxygenated lipid species as well. For standardized reporting in lipidomics, the hierarchical architecture of shorthand notation reflects the diverse structural resolution powers provided by mass spectrometric assays. Moreover, shorthand notation is expanded beyond mammalian phyla to lipids from plant and yeast phyla. Finally, annotation of atoms is included for the use of stable isotope-labeled compounds in metabolic labeling experiments or as internal standards. This update on lipid classification, nomenclature, and shorthand annotation for lipid mass spectra is considered a standard for lipid data presentation.

A comprehensive and standardized system to report lipid structures analyzed by MS is essential for the communication and storage of lipidomics data. Herein, an update on both the LIPID MAPS classification system and shorthand notation of lipid structures is presented for lipid categories Fatty Acyls (FA), Glycerolipids (GL), Glycerophospholipids (GP), Sphingolipids (SP), and Sterols (ST). With its major changes, i.e., annotation of ring double bond equivalents and number of oxygens, the updated shorthand notation facilitates reporting of newly delineated oxygenated lipid species as well. For standardized reporting in lipidomics, the hierarchical architecture of shorthand notation reflects the diverse structural resolution powers provided by mass spectrometric assays. Moreover, shorthand notation is expanded beyond mammalian phyla to lipids from plant and yeast phyla. Finally, annotation of atoms is included for the use of stable isotope-labeled compounds in metabolic labeling experiments or as internal standards. This update on lipid classification, nomenclature, and shorthand annotation for lipid mass spectra is considered a standard for lipid data presentation.

A comprehensive and standardized system to report lipid structures analyzed by MS is essential for the communication and storage of lipidomics data. Herein, an update on both the LIPID MAPS classification system and shorthand notation of lipid structures is presented for lipid categories Fatty Acyls (FA), Glycerolipids (GL), Glycerophospholipids (GP), Sphingolipids (SP), and Sterols (ST). With its major changes, i.e., annotation of ring double bond equivalents and number of oxygens, the updated shorthand notation facilitates reporting of newly delineated oxygenated lipid species as well. For standardized reporting in lipidomics, the hierarchical architecture of shorthand notation reflects the diverse structural resolution powers provided by mass spectrometric assays. Moreover, shorthand notation is expanded beyond mammalian phyla to lipids from plant and yeast phyla. Finally, annotation of atoms is included for the use of stable isotope-labeled compounds in metabolic labeling experiments or as internal standards. This update on lipid classification, nomenclature, and shorthand annotation for lipid mass spectra is considered a standard for lipid data presentation.

Pyruvate kinase catalyses the last step in glycolysis and has been suggested to contribute to the regulation of aerobic glycolysis in cancer cells. It can be inhibited by oxidation of cysteine residues in vitro and in vivo, which is relevant to the more pro-oxidant state in cancer and proliferating tissues. These conditions also favour lipid peroxidation and the formation of electrophilic fragmentation products, including short-chain aldehydes that can covalently modify proteins. However, as yet few studies have investigated their interactions with pyruvate kinase, so we investigated the effects of three different aldehydes, acrolein, malondialdehyde and 4-hydroxy-2(E)-hexenal (HHE), on the structure and activity of the enzyme. Analysis by LC-MS/MS showed unique modification profiles for each aldehyde, but Cys152, Cys423 and Cys474 were the residues most susceptible to electrophilic modification. Analysis of enzymatic activity under these conditions showed that acrolein was the strongest inhibitor, and at incubation times longer than 2 h, pathophysiological concentrations induced significant effects. Treatment of MCF-7 cells with the aldehydes caused similar losses of pyruvate kinase activity to those observed in vitro, and at lower concentrations than those required to cause cell death, with time and dose-dependent effects; acrolein adducts on Cys152 and Cys358 were detected. Cys358 and Cys474 are located at or near the allosteric or active sites, and formation of adducts on these residues probably contributes to loss of activity at low treatment concentrations. This study provides the first detailed analysis of the structure-activity relationship of C3 and C6 aldehydes with pyruvate kinase, and suggests that reactive short-chain aldehydes generated in diseases with an oxidative aetiology or from environmental exposure such as smoking could be involved in the metabolic alterations observed in cancer cells, through alteration of pyruvate kinase activity.

Pyruvate kinase catalyses the last step in glycolysis and has been suggested to contribute to the regulation of aerobic glycolysis in cancer cells. It can be inhibited by oxidation of cysteine residues in vitro and in vivo, which is relevant to the more pro-oxidant state in cancer and proliferating tissues. These conditions also favour lipid peroxidation and the formation of electrophilic fragmentation products, including short-chain aldehydes that can covalently modify proteins. However, as yet few studies have investigated their interactions with pyruvate kinase, so we investigated the effects of three different aldehydes, acrolein, malondialdehyde and 4-hydroxy-2(E)-hexenal (HHE), on the structure and activity of the enzyme. Analysis by LC-MS/MS showed unique modification profiles for each aldehyde, but Cys152, Cys423 and Cys474 were the residues most susceptible to electrophilic modification. Analysis of enzymatic activity under these conditions showed that acrolein was the strongest inhibitor, and at incubation times longer than 2 h, pathophysiological concentrations induced significant effects. Treatment of MCF-7 cells with the aldehydes caused similar losses of pyruvate kinase activity to those observed in vitro, and at lower concentrations than those required to cause cell death, with time and dose-dependent effects; acrolein adducts on Cys152 and Cys358 were detected. Cys358 and Cys474 are located at or near the allosteric or active sites, and formation of adducts on these residues probably contributes to loss of activity at low treatment concentrations. This study provides the first detailed analysis of the structure-activity relationship of C3 and C6 aldehydes with pyruvate kinase, and suggests that reactive short-chain aldehydes generated in diseases with an oxidative aetiology or from environmental exposure such as smoking could be involved in the metabolic alterations observed in cancer cells, through alteration of pyruvate kinase activity.

Background: Many infectious pathogens can be transmitted from animals to humans and vice versa, or by animals (especially arthropods) to humans. Such diseases are called zoonotic and/or vector-borne diseases. To control or prevent them, it is often recommended to target population reduction of host or vector species, through preventive culling or insecticide use for example. But these types of destructive interventions have shown several limits altering their efficiency, including acquired resistance of arthropods to insecticides, unpredicted change in the ecology of host populations, unexpected negative functional consequences on ecosystems, as well as economic embrittlement when livestock is concerned. An alternative pathway of action would be to rely on the functioning of ecosystems, and on their careful management, to regulate diseases and thus reduce their impact on human health. In this perspective, a thorough evaluation of the conditions that can potentially promote such a positive regulation of infectious pathogens by ecosystems, and their efficiency, is needed. Here, we present the protocol of a systematic review that will evaluate the scientific evidence existing on potential links between ecosystem components or functions and 14 vector-borne and zoonotic diseases impacting human health. Methods: We will search for studies that tested the effect of changes in (i) biological communities, and (ii) habitats and landscapes, on diseases. Scientific literature from 5 publication databases will be screened in a 3-rounds process: title, abstract and full-text screening. At each stage, articles will be either rejected or kept for the next round, depending on whether they fall in the exclusion or inclusion criteria. We will present results in two parts: a systematic map and a systematic review. The systematic map will present, for the 14 diseases, the number of publications, their geographical distribution, the type of ecosystem component/function they studied, as w

Pyruvate kinase catalyses the last step in glycolysis and has been suggested to contribute to the regulation of aerobic glycolysis in cancer cells. It can be inhibited by oxidation of cysteine residues in vitro and in vivo, which is relevant to the more pro-oxidant state in cancer and proliferating tissues. These conditions also favour lipid peroxidation and the formation of electrophilic fragmentation products, including short-chain aldehydes that can covalently modify proteins. However, as yet few studies have investigated their interactions with pyruvate kinase, so we investigated the effects of three different aldehydes, acrolein, malondialdehyde and 4-hydroxy-2(E)-hexenal (HHE), on the structure and activity of the enzyme. Analysis by LC-MS/MS showed unique modification profiles for each aldehyde, but Cys152, Cys423 and Cys474 were the residues most susceptible to electrophilic modification. Analysis of enzymatic activity under these conditions showed that acrolein was the strongest inhibitor, and at incubation times longer than 2 h, pathophysiological concentrations induced significant effects. Treatment of MCF-7 cells with the aldehydes caused similar losses of pyruvate kinase activity to those observed in vitro, and at lower concentrations than those required to cause cell death, with time and dose-dependent effects; acrolein adducts on Cys152 and Cys358 were detected. Cys358 and Cys474 are located at or near the allosteric or active sites, and formation of adducts on these residues probably contributes to loss of activity at low treatment concentrations. This study provides the first detailed analysis of the structure-activity relationship of C3 and C6 aldehydes with pyruvate kinase, and suggests that reactive short-chain aldehydes generated in diseases with an oxidative aetiology or from environmental exposure such as smoking could be involved in the metabolic alterations observed in cancer cells, through alteration of pyruvate kinase activity.

Pyruvate kinase catalyses the last step in glycolysis and has been suggested to contribute to the regulation of aerobic glycolysis in cancer cells. It can be inhibited by oxidation of cysteine residues in vitro and in vivo, which is relevant to the more pro-oxidant state in cancer and proliferating tissues. These conditions also favour lipid peroxidation and the formation of electrophilic fragmentation products, including short-chain aldehydes that can covalently modify proteins. However, as yet few studies have investigated their interactions with pyruvate kinase, so we investigated the effects of three different aldehydes, acrolein, malondialdehyde and 4-hydroxy-2(E)-hexenal (HHE), on the structure and activity of the enzyme. Analysis by LC-MS/MS showed unique modification profiles for each aldehyde, but Cys152, Cys423 and Cys474 were the residues most susceptible to electrophilic modification. Analysis of enzymatic activity under these conditions showed that acrolein was the strongest inhibitor, and at incubation times longer than 2 h, pathophysiological concentrations induced significant effects. Treatment of MCF-7 cells with the aldehydes caused similar losses of pyruvate kinase activity to those observed in vitro, and at lower concentrations than those required to cause cell death, with time and dose-dependent effects; acrolein adducts on Cys152 and Cys358 were detected. Cys358 and Cys474 are located at or near the allosteric or active sites, and formation of adducts on these residues probably contributes to loss of activity at low treatment concentrations. This study provides the first detailed analysis of the structure-activity relationship of C3 and C6 aldehydes with pyruvate kinase, and suggests that reactive short-chain aldehydes generated in diseases with an oxidative aetiology or from environmental exposure such as smoking could be involved in the metabolic alterations observed in cancer cells, through alteration of pyruvate kinase activity.

Background: Many infectious pathogens can be transmitted from animals to humans and vice versa, or by animals (especially arthropods) to humans. Such diseases are called zoonotic and/or vector-borne diseases. To control or prevent them, it is often recommended to target population reduction of host or vector species, through preventive culling or insecticide use for example. But these types of destructive interventions have shown several limits altering their efficiency, including acquired resistance of arthropods to insecticides, unpredicted change in the ecology of host populations, unexpected negative functional consequences on ecosystems, as well as economic embrittlement when livestock is concerned. An alternative pathway of action would be to rely on the functioning of ecosystems, and on their careful management, to regulate diseases and thus reduce their impact on human health. In this perspective, a thorough evaluation of the conditions that can potentially promote such a positive regulation of infectious pathogens by ecosystems, and their efficiency, is needed. Here, we present the protocol of a systematic review that will evaluate the scientific evidence existing on potential links between ecosystem components or functions and 14 vector-borne and zoonotic diseases impacting human health. Methods: We will search for studies that tested the effect of changes in (i) biological communities, and (ii) habitats and landscapes, on diseases. Scientific literature from 5 publication databases will be screened in a 3-rounds process: title, abstract and full-text screening. At each stage, articles will be either rejected or kept for the next round, depending on whether they fall in the exclusion or inclusion criteria. We will present results in two parts: a systematic map and a systematic review. The systematic map will present, for the 14 diseases, the number of publications, their geographical distribution, the type of ecosystem component/function they studied, as w

Gelatinolytic matrix metalloproteinases (MMP-2, -9) play a critical role not only in mammals physiology but also during inflammation and healing processes. The natural stilbenoid, resveratrol (RES), exhibits potent antioxidant effects, in a hormetic mode of action, and is known to inhibit MMP-9. However, RES administration exhibits major issues, including poor bioavailability and water solubility, hampering its potential therapeutic effect in vivo. In the present study, we synthesized and evaluated five novel RES–lipid conjugates to increase their cell membrane penetration and improve their bioavailability. The best in vitro MMP-9 inhibitory activity of RES–lipids conjugates was observed with RES-linoleic acid (LA) (5 µM), when dissolved in a natural deep eutectic solvent (NADES), composed of an equimolar content of 1,2-propanediol:choline chloride (ChCl):water. The inhibition of MMP-9 expression by RES-LA in activated THP-1 monocytes, was, at least due to the deactivation of ERK1/2 and JNK1/2 MAP kinase signaling pathways. Moreover, RES-LA exhibited a strong effect protecting the TNF-α-induced exacerbated permeability in an HUVEC in vitro monolayer (by 81%) via the integrity protection of intercellular junction proteins from the MMP-9 activity. This effect was confirmed by using several complementary approaches including, the real-time monitoring of trans-endothelial electric resistance (TEER), the Transwell HUVEC permeability level, the microscopic examination of the platelet endothelial cell adhesion molecule-1 (CD31/PECAM-1) integrity as well as the fluorescence in intercellular spaces. Consequently, following this strong in vitro proof-of-concept, there is a need to test this promising RES–lipid derivative compound to control the pathological endothelial permeability in vivo.

Coffee pulp (CP), cocoa husk {CH) and cocoa pod husk (CPH), are the main by-products (CP, CH) and co-product (CPH) derived from green coffee and cocoa transformation. These wastes represent a non-expensive source of interesting biomolecules. Phytoprostanes {PhytoPs) derived from peroxidation of a-linolenic acid (C18:3 n-3, ALA) are biomarkers of oxidative stress in plants and humans and possess biological properties. Under high oxygen tension, phytofurans (PhytoFs) derived from ALA, were recently discovered in seeds, nuts, oils, and melon's leaves. There is a growing interest in the profile of these compounds in plant foods and their response to cultural, postharvest, and/or environmental conditions. The goal of this work was to identify and to quantify the PhytoPs and PhytoFs in the vegetal matrices, by micro-Le coupled to a QTRAP detector method. The content of PhytoPs and PhytoFs, found, were, respectively, of 663 and 543.1 {from CP), 438.8 and 278 {from CH), and, 149.8 and 393.7 {from CPH) ng/g dry basis {d.b.). 9-epi-9-Flt-PhytoP was the main PhytoP found in CP {171.4 ng/g d.b.) and CPH {37.1 ng/g d.b.), while ent-9-Llt-PhytoP was the main PhytoP in CH {109.8 ng/g d.b.). Additionally, ent-16(RS)-13-epi-ST-ti14-9-PhytoF was the main PhytoF found in our samples {196.5, 126.2, and 207.6 ng/g d.b., from CP, CH, and CPH, respectively). This is the first time that a complete profile of these oxygenated lipids is realized in coffee and cocoa, showing the potential of plant biomass by- and co-products to be used as a source of these biomolecules.

Coffee pulp (CP), cocoa husk {CH) and cocoa pod husk (CPH), are the main by-products (CP, CH) and co-product (CPH) derived from green coffee and cocoa transformation. These wastes represent a non-expensive source of interesting biomolecules. Phytoprostanes {PhytoPs) derived from peroxidation of a-linolenic acid (C18:3 n-3, ALA) are biomarkers of oxidative stress in plants and humans and possess biological properties. Under high oxygen tension, phytofurans (PhytoFs) derived from ALA, were recently discovered in seeds, nuts, oils, and melon's leaves. There is a growing interest in the profile of these compounds in plant foods and their response to cultural, postharvest, and/or environmental conditions. The goal of this work was to identify and to quantify the PhytoPs and PhytoFs in the vegetal matrices, by micro-Le coupled to a QTRAP detector method. The content of PhytoPs and PhytoFs, found, were, respectively, of 663 and 543.1 {from CP), 438.8 and 278 {from CH), and, 149.8 and 393.7 {from CPH) ng/g dry basis {d.b.). 9-epi-9-Flt-PhytoP was the main PhytoP found in CP {171.4 ng/g d.b.) and CPH {37.1 ng/g d.b.), while ent-9-Llt-PhytoP was the main PhytoP in CH {109.8 ng/g d.b.). Additionally, ent-16(RS)-13-epi-ST-ti14-9-PhytoF was the main PhytoF found in our samples {196.5, 126.2, and 207.6 ng/g d.b., from CP, CH, and CPH, respectively). This is the first time that a complete profile of these oxygenated lipids is realized in coffee and cocoa, showing the potential of plant biomass by- and co-products to be used as a source of these biomolecules.

Structure-activity relationship (SAR) constitutes a crucial topic to discover new bioactive molecules. This approach initiates with the comparison of a target candidate with a molecule or a collection of molecules and their attributed biological functions to shed some light in the details of one or more SARs and subsequently using that information to outline valuable application of the newly identified compounds. Thus, while the empiric knowledge of medicinal chemistry is critical to these tasks, the results retrieved upon dedicated experimental demonstration retrieved resorting to modern high throughput analytical approaches and techniques allow to overwhelm the constraints adduced so far to the successful accomplishment of such tasks. Therefore, the present work reviews critically the evidences reported to date on the occurrence of phytoprostanes and phytofurans in plant foods, and the information available on their bioavailability and biological activity, shedding some light on the expectation waken up due to their structural similarities with prostanoids and isoprostanes.

The genus Passiflora, comprising about 500 species, is the largest in the Passion flower family. Passiflora edulis Sims f. edulis (gulupa) is one of the most important fruits cultivated in Colombia. In recent years and due to its organoleptic and bioactive properties, its exports have significantly increased. In this work, six new bioactive oxylipins –phytoprostanes – were detected in gulupa shell by a UHPLC-QqQ-MS/MS method: F1t-phytoprostanes and D1t-phytoprostanes were the predominant and minor classes, respectively. Moreover, the polyphenol profile of the shell was investigated and we were able to detect and quantify phenolic compounds that have not been described previously, like luteolin-8-C-(2-O-rhamnosyl)hexoside and quercetin-3-O-(6″-acetyl)glucosyl-2″-sinapic acid. Consequently, this study provides new insights into the importance of gulupa shell as a valuable option in the design of new beverages rich in antioxidant phytochemicals, as part of a well-balanced diet, and in the process and quality control of such products

The aim of the this study was to determine the effect of a polyphenols-rich juice (aronia-citrus juice, ACJ) on F4-neuroprostanes and F2-dihomo-isoprostanes—markers of oxidative stress associated with the central nervous system (CNS)—in 16 elite triathletes under a controlled diet for triathlon training (145 days). In the triathletes, a decrease of the lipid peroxidation markers after ACJ intake, associated with neuronal membrane degradation (10-epi-10-F4t-neuroprostane and 10-F4t-neuroprostane), was observed when compared with placebo stage values. Regarding the F2-dihomo-isoprostanes, a significant decrease of the neuromotor system damage biomarkers (17-F2t-dihomo-isoprostane) with an increase of training load during the study was observed, although the decrease of the load training at the last stage showed a significant increase of the values of ent-7-(RS)-7-F2t-dihomo-IsoP, suggesting a possible role in adaptation post-training. On the other hand, the changes in the excretion of 17-epi-17-F2t-dihomo-IsoP provided a positive connection between physical exercise and ACJ intake. Thus, the results showed in this clinical study in young triathletes will help to elucidate novel interactions and mechanisms between the excretion of lipid peroxidation metabolites from CNS, supplementation of polyphenols-rich juice in the diet and physical exercise during a training season.

The aim of the this study was to determine the effect of a polyphenols-rich juice (aronia-citrus juice, ACJ) on F4-neuroprostanes and F2-dihomo-isoprostanes—markers of oxidative stress associated with the central nervous system (CNS)—in 16 elite triathletes under a controlled diet for triathlon training (145 days). In the triathletes, a decrease of the lipid peroxidation markers after ACJ intake, associated with neuronal membrane degradation (10-epi-10-F4t-neuroprostane and 10-F4t-neuroprostane), was observed when compared with placebo stage values. Regarding the F2-dihomo-isoprostanes, a significant decrease of the neuromotor system damage biomarkers (17-F2t-dihomo-isoprostane) with an increase of training load during the study was observed, although the decrease of the load training at the last stage showed a significant increase of the values of ent-7-(RS)-7-F2t-dihomo-IsoP, suggesting a possible role in adaptation post-training. On the other hand, the changes in the excretion of 17-epi-17-F2t-dihomo-IsoP provided a positive connection between physical exercise and ACJ intake. Thus, the results showed in this clinical study in young triathletes will help to elucidate novel interactions and mechanisms between the excretion of lipid peroxidation metabolites from CNS, supplementation of polyphenols-rich juice in the diet and physical exercise during a training season.

The aim of the this study was to determine the effect of a polyphenols-rich juice (aronia-citrus juice, ACJ) on F4-neuroprostanes and F2-dihomo-isoprostanes—markers of oxidative stress associated with the central nervous system (CNS)—in 16 elite triathletes under a controlled diet for triathlon training (145 days). In the triathletes, a decrease of the lipid peroxidation markers after ACJ intake, associated with neuronal membrane degradation (10-epi-10-F4t-neuroprostane and 10-F4t-neuroprostane), was observed when compared with placebo stage values. Regarding the F2-dihomo-isoprostanes, a significant decrease of the neuromotor system damage biomarkers (17-F2t-dihomo-isoprostane) with an increase of training load during the study was observed, although the decrease of the load training at the last stage showed a significant increase of the values of ent-7-(RS)-7-F2t-dihomo-IsoP, suggesting a possible role in adaptation post-training. On the other hand, the changes in the excretion of 17-epi-17-F2t-dihomo-IsoP provided a positive connection between physical exercise and ACJ intake. Thus, the results showed in this clinical study in young triathletes will help to elucidate novel interactions and mechanisms between the excretion of lipid peroxidation metabolites from CNS, supplementation of polyphenols-rich juice in the diet and physical exercise during a training season

This randomized and controlled trial investigated whether the increase in elite training at different altitudes altered the oxidative stress biomarkers of the nervous system. This is the first study to investigate four F4-neuroprostanes and four F2-dihomo-isoprostanes quantified in 24-hour urine. The quantification was carried out by Ultra High Pressure Liquid Chromatography-triple Quadrupole-Tandem Mass Spectrometry (UHPLC-QqQ-MS/MS). Sixteen elite triathletes agreed to participate in the project. They were randomized in two groups, a group submitted to Altitude Training (n=8) and a group submitted to Sea Level Training (n=8), with a Control group of non-athletes (n=8). After experimental period, the Altitude Training group triathletes gave significant data: 17-epi-17-F2t-dihomo-IsoP (from 5.2 ± 1.4 µg/mL 24 h-1 to 6.6 ± 0.6 µg/mL 24 h-1), ent-7(RS)-7-F2t-dihomo-IsoP (from 6.6 ± 1.7 µg/mL 24 h-1 to 8.6 ± 0.9 µg /mL 24 h-1), and ent-7-epi-7-F2t-dihomo-IsoP (from 8.4 ± 2.2 µg/mL 24 h-1 to 11.3 ± 1.8 µg/mL 24 h-1) increased, while, of the neuronal degeneration-related compounds, only 10-epi-10-F4t-NeuroP (8.4 ± 1.7 µg/mL 24 h-1) and 10-F4t-NeuroP (5.2 ± 2.9 µg/mL 24 h-1) were detected in this group. For the control group and sea level training groups, no significant changes had occurred at the end of the 2-weeks experimental period. Therefore, and as the main conclusion, the training at moderate altitude increased the F4-NeuroPs- and F2-dihomo-isoPs-related oxidative damage of the central nervous system (CNS) compared to similar training at sea level.

BACKGROUND: The effect of regulated deficit irrigation (RDI) on the phytoprostane (PhytoP) content in extra virgin olive (Olea europaea L., cv. Cornicabra) oil (EVOO) was studied. During the 2012 and 2013 seasons, T0 plants were irrigated at 100% ETc, while T1 and T2 plants were irrigated avoiding water deficit during phases I and III of fruit growth and saving water during the non-critical phenological period of pit hardening (phase II), developing amore severewater deficit in T2 plants. In 2013, a fourth treatment (T3) was also performed, which was similar to T2 except that water saving was from the beginning of phase II to 15 days after the end of phase II. RESULTS: 9-F1t-PhytoP, 9-epi-9-F1t-PhytoP, 9-epi-9-D1t-PhytoP, 9-D1t-PhytoP, 16-B1-PhytoP and 9-L1-PhytoP were present in Cornicabra EVOO, and their contents increased in the EVOO fromRDI plants. CONCLUSION: Deficit irrigation during pit hardening or for a further period of 2 weeks thereafter to increase irrigation water saving is clearly critical for EVOO composition because of the enhancement of free PhytoPs, which have potential beneficial effects on human health. The response of individual free PhytoPs to changes in plant water status was not as perceptible as expected, preventing their use as biomarkers of water stress.

BACKGROUND: The effect of regulated deficit irrigation (RDI) on the phytoprostane (PhytoP) content in extra virgin olive (Olea europaea L., cv. Cornicabra) oil (EVOO) was studied. During the 2012 and 2013 seasons, T0 plants were irrigated at 100% ETc, while T1 and T2 plants were irrigated avoiding water deficit during phases I and III of fruit growth and saving water during the non-critical phenological period of pit hardening (phase II), developing amore severewater deficit in T2 plants. In 2013, a fourth treatment (T3) was also performed, which was similar to T2 except that water saving was from the beginning of phase II to 15 days after the end of phase II. RESULTS: 9-F1t-PhytoP, 9-epi-9-F1t-PhytoP, 9-epi-9-D1t-PhytoP, 9-D1t-PhytoP, 16-B1-PhytoP and 9-L1-PhytoP were present in Cornicabra EVOO, and their contents increased in the EVOO fromRDI plants. CONCLUSION: Deficit irrigation during pit hardening or for a further period of 2 weeks thereafter to increase irrigation water saving is clearly critical for EVOO composition because of the enhancement of free PhytoPs, which have potential beneficial effects on human health. The response of individual free PhytoPs to changes in plant water status was not as perceptible as expected, preventing their use as biomarkers of water stress.

This randomized and controlled trial investigated whether the increase in elite training at different altitudes altered the oxidative stress biomarkers of the nervous system. This is the first study to investigate four F4-neuroprostanes and four F2-dihomo-isoprostanes quantified in 24-hour urine. The quantification was carried out by Ultra High Pressure Liquid Chromatography-triple Quadrupole-Tandem Mass Spectrometry (UHPLC-QqQ-MS/MS). Sixteen elite triathletes agreed to participate in the project. They were randomized in two groups, a group submitted to Altitude Training (n=8) and a group submitted to Sea Level Training (n=8), with a Control group of non-athletes (n=8). After experimental period, the Altitude Training group triathletes gave significant data: 17-epi-17-F2t-dihomo-IsoP (from 5.2 ± 1.4 µg/mL 24 h-1 to 6.6 ± 0.6 µg/mL 24 h-1), ent-7(RS)-7-F2t-dihomo-IsoP (from 6.6 ± 1.7 µg/mL 24 h-1 to 8.6 ± 0.9 µg /mL 24 h-1), and ent-7-epi-7-F2t-dihomo-IsoP (from 8.4 ± 2.2 µg/mL 24 h-1 to 11.3 ± 1.8 µg/mL 24 h-1) increased, while, of the neuronal degeneration-related compounds, only 10-epi-10-F4t-NeuroP (8.4 ± 1.7 µg/mL 24 h-1) and 10-F4t-NeuroP (5.2 ± 2.9 µg/mL 24 h-1) were detected in this group. For the control group and sea level training groups, no significant changes had occurred at the end of the 2-weeks experimental period. Therefore, and as the main conclusion, the training at moderate altitude increased the F4-NeuroPs- and F2-dihomo-isoPs-related oxidative damage of the central nervous system (CNS) compared to similar training at sea level.

The anti-atherogenic effects of omega 3 fatty acids, namely eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) are well recognized but the impact of dietary intake on bioactive lipid mediator profiles remains unclear. Such a profiling effort may offer novel targets for future studies into the mechanism of action of omega 3 fatty acids. The present study aimed to determine the impact of DHA supplementation on the profiles of polyunsaturated fatty acids (PUFA) oxygenated metabolites and to investigate their contribution to atherosclerosis prevention. A special emphasis was given to the non-enzymatic metabolites knowing the high susceptibility of DHA to free radical-mediated peroxidation and the increased oxidative stress associated with plaque formation. Atherosclerosis prone mice (LDLR(-/-)) received increasing doses of DHA (0, 0.1, 1 or 2% of energy) during 20 weeks leading to a dose-dependent reduction of atherosclerosis (R(2) = 0.97, p = 0.02), triglyceridemia (R(2) = 0.97, p = 0.01) and cholesterolemia (R(2) = 0.96, p<0.01). Targeted lipidomic analyses revealed that both the profiles of EPA and DHA and their corresponding oxygenated metabolites were substantially modulated in plasma and liver. Notably, the hepatic level of F4-neuroprostanes, a specific class of DHA peroxidized metabolites, was strongly correlated with the hepatic DHA level. Moreover, unbiased statistical analysis including correlation analyses, hierarchical cluster and projection to latent structure discriminate analysis revealed that the hepatic level of F4-neuroprostanes was the variable most negatively correlated with the plaque extent (p<0.001) and along with plasma EPA-derived diols was an important mathematical positive predictor of atherosclerosis prevention. Thus, oxygenated n-3 PUFAs, and F4-neuroprostanes in particular, are potential biomarkers of DHA-associated atherosclerosis prevention. While these may contribute to the anti-atherogenic effects of DHA, further in vitro inve

The anti-atherogenic effects of omega 3 fatty acids, namely eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) are well recognized but the impact of dietary intake on bioactive lipid mediator profiles remains unclear. Such a profiling effort may offer novel targets for future studies into the mechanism of action of omega 3 fatty acids. The present study aimed to determine the impact of DHA supplementation on the profiles of polyunsaturated fatty acids (PUFA) oxygenated metabolites and to investigate their contribution to atherosclerosis prevention. A special emphasis was given to the non-enzymatic metabolites knowing the high susceptibility of DHA to free radical-mediated peroxidation and the increased oxidative stress associated with plaque formation. Atherosclerosis prone mice (LDLR(-/-)) received increasing doses of DHA (0, 0.1, 1 or 2% of energy) during 20 weeks leading to a dose-dependent reduction of atherosclerosis (R(2) = 0.97, p = 0.02), triglyceridemia (R(2) = 0.97, p = 0.01) and cholesterolemia (R(2) = 0.96, p<0.01). Targeted lipidomic analyses revealed that both the profiles of EPA and DHA and their corresponding oxygenated metabolites were substantially modulated in plasma and liver. Notably, the hepatic level of F4-neuroprostanes, a specific class of DHA peroxidized metabolites, was strongly correlated with the hepatic DHA level. Moreover, unbiased statistical analysis including correlation analyses, hierarchical cluster and projection to latent structure discriminate analysis revealed that the hepatic level of F4-neuroprostanes was the variable most negatively correlated with the plaque extent (p<0.001) and along with plasma EPA-derived diols was an important mathematical positive predictor of atherosclerosis prevention. Thus, oxygenated n-3 PUFAs, and F4-neuroprostanes in particular, are potential biomarkers of DHA-associated atherosclerosis prevention. While these may contribute to the anti-atherogenic effects of DHA, further in vitro inve

The growing importance of lipidomics, and the interest of non-enzymatic metabolites of polyunsaturated fatty acids (PUFAs) prompted us to initiate the synthesis of novel dihomo-IsoF compounds. Such metabolites of adrenic acid, the main PUFA in white matter, were synthesized using a divergent approach based on an orthoester cyclization. LC-MS/MS investigation on pig brains showed the potential of this novel biomarker for the first time, as a powerful new tool for brain lipid peroxidation assessment.

The growing importance of lipidomics, and the interest of non-enzymatic metabolites of polyunsaturated fatty acids (PUFAs) prompted us to initiate the synthesis of novel dihomo-IsoF compounds. Such metabolites of adrenic acid, the main PUFA in white matter, were synthesized using a divergent approach based on an orthoester cyclization. LC-MS/MS investigation on pig brains showed the potential of this novel biomarker for the first time, as a powerful new tool for brain lipid peroxidation assessment.

Doctorat en sciences chimiques -- UCL, 1993