Search

Specialized pro-resolving mediators (SPM) are a family of lipids controlling the resolution of inflammation and playing a role in many processes including organ protection and tissue repair. While synthetic SPM are potent bioactive molecules in vivo, their role in epimorphic regeneration of organs in vertebrates has never been proved. Using the zebrafish larvae as a robust regenerative vertebrate system, we show that the SPM neuroprotectin/protectin D1 (PD1) improves the regeneration of the zebrafish caudal fin. Acting in a narrow time window during regeneration, PD1 accelerates the resolution of inflammation without affecting the initial kinetic of neutrophil infiltration but instead, promoting their reverse migration potential. In addition, PD1 induces macrophage polarization switch toward non-inflammatory states in both zebrafish and mammalian system. Finally, macrophages but not neutrophils are essential for PD1-mediated regeneration. Thus, our findings strongly support the development of pro-resolving mediators as promising natural therapeutic candidates for inflammatory and degenerative disorders.

Additional file 1. Names of the I) diseases, II) pathogen agents, and III) vector species.

The enantioselective total synthesis of the highly reactive isoketal 5-D2-IsoK has been accomplished. The synthesis features construction of the isoketals core via an organocatalyzed Michael addition between ideally functionalized aldehyde and nitroolefin partners in good enantioselectivity. The lateral chains are branched through Horner-Wadsworth-Emmons and Wittig olefinations in order to provide flexibility while the final deprotections and oxidation steps are run under mild conditions to avoid known racemization and/or degradation of the very sensitive isoketal.

Conference Theme: Lipidomics Impact on Metabolic, Cancer, Cardiovascular and Inflammatory Diseases ; Isoprostanoids are a group of non-enzymatic oxygenated metabolites of polyunsaturated fatty acids. It belongs to oxylipins group, which are important lipid mediators in biological processes, such as tissue repair, blood clotting, blood vessel permeability, inflammation and immunity regulation. Recently, isoprostanoids from eicosapentaenoic, docosahexaenoic, adrenic and α-linolenic namely F3-isoprostanes, F4-neuroprostanes, F2-dihomo-isoprostanes and F1-phytoprostanes, respectively have attracted attention because of their putative contribution to health. Since isoprostanoids are derived from different substrate of PUFAs and can have similar or opposing biological consequences, a total isoprostanoids profile is essential to understand the overall effect in the testing model. However, the concentration of most isoprostanoids range from picogram to nanogram, therefore a sensitive method to quantify 20 isoprostanoids simultaneously was formulated and measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The lipid portion from various biological samples was extracted prior to LC-MS/MS evaluation. For all the isoprostanoids LOD and LOQ, and the method was validated on plasma samples for matrix effect, yield of extraction and reproducibility were determined. The methodology was further tested for the isoprostanoids profiles in brain and liver of LDLR(-/-) mice with and without docosahexaenoic acid (DHA) supplementation. Our analysis showed similar levels of total F2-isoprostanes and F4-neuroprostanes in the liver and brain of non-supplemented LDLR(-/-) mice. The distribution of different F2-isoprostane isomers varied between tissues but not for F4-neuroprostanes which were predominated by the 4(RS)-4-F4t-neuroprostane isomer. DHA supplementation to LDLR(-/-) mice concomitantly increased total F4-neuroprostanes levels compared to F2-isoprostanes but this effect was more pronounced in the liver than brain.

International audience; A wide variety of metabolic products of polyunsaturated fatty acids is of paramount importance for improving our medical knowledge in the field of oxidized lipids. Two novel metabolites of n-3 polyunsaturated fatty acids, 8-F3t-IsoP and 10-F4t-NeuroP as well as a deuterated derivativethereof were synthesized based on an acetylenic intermediate.An original approach achieved lateral chain insertion of 8-F3t-IsoP by a ring-closing alkyne metathesis/semi-reduction strategy together with a temporary tether.

From 1994 to 1996, an actual and retrospective inquest on pastoral practices and Alpine Chamois (Rupicapra r. rupicapra ) home ranges was performed in Vanoise National Park, Écrins National Park and in the Bauges Game Reserve (France), to investigate the patterns of inter specific cohabitation between livestock and wild ungulates. Statistical treatments performed on a sanitary data base, recording the results of parasitological examinations performed on 307 Chamois, permitted an estimation of parasite diversity in ten groups of chamois populations. Looking for the influence of environmental factors on diversity indices, we revealed significant species-area relationships. Whereas no correlation was found between diversity indices and the total surface of Chamois home range, H (Shannon & Weaver) and N, (Hill) were significantly correlated with the surface of spring home ranges of Chamois and with the surface grazed by livestock within spring preferential ranges. Moreover, a significant correlation between species richness (S) and the surface grazed by livestock in chamois summer preferential home ranges is noted. These results suggest an influence of cattle breeding on diversity fluctuations in helminth communities of Rupicaprinae., De 1994 à 1996, des enquêtes instantanées et rétrospectives portant, d’une part sur les pratiques pastorales et d’ autre part sur l’étendue du domaine vital du Chamois (Rupicapra r. rupicapra, Linné, 1758), ont été conduites, dans le Parc National de la Vanoise, le Parc National des Écrins et la Réserve Nationale de Chasse et de Faune sauvage des Bauges. Cette étude visait à analyser certains aspects de la cohabitation entre ongulés sauvages et cheptels domestiques. Des traitements statistiques réalisés à partir d’une banque de données sanitaires contenant les résultats de bilans parasitaires pratiqués sur 307 Chamois, ont permis, parallèlement, d’estimer la diversité parasitaire en helminthes digestifs dans les différents groupes de populations de Chamois. L’étude de la relation entre environnement pastoral et indices de diversité a montré des relations surface-diversité significatives. Alors qu’aucune corrélation n’a été trouvée entre les indices de diversité et la surface totale du domaine vital du Chamois, H' (Shannon-Weaver) et N1 (Hill) sont corrélés significativement avec la surface totale des quartiers saisonniers de printemps et avec la surface pâturée par les troupeaux à l’intérieur des quartiers saisonniers préférentiels de printemps. Qui plus est, une corrélation significative est trouvée entre la richesse spécifique (S) et la surface pâturée par les troupeaux dans les quartiers préférentiels d’été du Chamois. Ces résultats suggèrent une influence du pastoralisme sur les fluctuations de la diversité parasitaire dans les communautés d’helminthes des Rupicaprinae., Durand Thierry. Ecological significance of a species-area relationship in helminth communities of the Alpine Chamois (Rucicapra r. rupicapra Linné, 1758). In: Revue d'Écologie (La Terre et La Vie), tome 55, n°4, 2000. pp. 321-335.

Short-term exposure to ultraviolet A (UVA) radiation can directly injure our skin through inflammatory response and indirectly through oxidative stress, triggering polyunsaturated fatty acid (PUFA) peroxidation in skin cell membrane and formation of DNA adduct, 8-hydroxy-2′-deoxyguanosine (8-OHdG). It is known that UVA exposure leads to photoaging, immunosuppression and skin cancer. However, the changes in PUFA and its oxidized metabolites, and cell cycle after short UVA exposure, are debatable. In this study, human keratinocytes (HaCaT) were exposed to low dose (5 J/cm2) and high dose (20 J/cm2) of UVA and assessed immediately, 8 h, 12 h, and 24 h post-treatment. Both doses showed a transient suppression in S-phase after 8 h of UVA exposure, and G2/M phase arrest after 12-h UVA exposure in the cell cycle but subsequently returned to normal cycle. Also, no observable DNA damage took place, where 8-OHdG levels were below par after 24-h UVA exposure. A dose of 20 J/cm2 UVA stimulated significant amount of arachidonic acid, n-3 docosapentaenoic acid, and docosahexaenoic acid (DHA) but lowered adrenic acid and eicospentaenoic acid after 24-h exposure. Among the 43 oxidized PUFA products determined, enzyme-dependent oxidized PUFAs, namely, 14-hydroxy-DHA (HDoHE) level reduced, and 8- and 13-HDoHE levels elevated significantly in a linear trend with post-treatment time. Out of the nonenzymatic oxidized PUFAs, a significant linear trend with post-treatment time was shown on the reduction of 5-F2t-Isoprostane (IsoP), 15-F2t-IsoP, Isofurans, 5-F3t-IsoP, Neurofurans, and 20-HDoHE. Our observations indicate oxidative stress through short UVA exposure on human keratinocytes did not have detrimental consequences.

Short-term exposure to ultraviolet A (UVA) radiation can directly injure our skin through inflammatory response and indirectly through oxidative stress, triggering polyunsaturated fatty acid (PUFA) peroxidation in skin cell membrane and formation of DNA adduct, 8-hydroxy-2′-deoxyguanosine (8-OHdG). It is known that UVA exposure leads to photoaging, immunosuppression and skin cancer. However, the changes in PUFA and its oxidized metabolites, and cell cycle after short UVA exposure, are debatable. In this study, human keratinocytes (HaCaT) were exposed to low dose (5 J/cm2) and high dose (20 J/cm2) of UVA and assessed immediately, 8 h, 12 h, and 24 h post-treatment. Both doses showed a transient suppression in S-phase after 8 h of UVA exposure, and G2/M phase arrest after 12-h UVA exposure in the cell cycle but subsequently returned to normal cycle. Also, no observable DNA damage took place, where 8-OHdG levels were below par after 24-h UVA exposure. A dose of 20 J/cm2 UVA stimulated significant amount of arachidonic acid, n-3 docosapentaenoic acid, and docosahexaenoic acid (DHA) but lowered adrenic acid and eicospentaenoic acid after 24-h exposure. Among the 43 oxidized PUFA products determined, enzyme-dependent oxidized PUFAs, namely, 14-hydroxy-DHA (HDoHE) level reduced, and 8- and 13-HDoHE levels elevated significantly in a linear trend with post-treatment time. Out of the nonenzymatic oxidized PUFAs, a significant linear trend with post-treatment time was shown on the reduction of 5-F2t-Isoprostane (IsoP), 15-F2t-IsoP, Isofurans, 5-F3t-IsoP, Neurofurans, and 20-HDoHE. Our observations indicate oxidative stress through short UVA exposure on human keratinocytes did not have detrimental consequences.

The rise in prevalence of obesity in women of reproductive age in developed and developing countries might propagate intergenerational cycles of detrimental effects on metabolic health. Placental lipid metabolism is disrupted by maternal obesity, which possibly affects the life-long health of the offspring. Here, we investigated placental lipid metabolism in women with pre-gestational obesity as a sole pregnancy complication and compared it to placental responses of lean women. Open profile and targeted lipidomics were used to assess placental lipids and oxidised products of docosahexaenoic (DHA) and arachidonic acid (AA), respectively, neuroprostanes and isoprostanes. Despite no overall signs of lipid accumulation, DHA and AA levels in placentas from obese women were, respectively, 2.2 and 2.5 times higher than those from lean women. Additionally, a 2-fold increase in DHA-derived neuroprostanes and a 1.7-fold increase in AA-derived isoprostanes were seen in the obese group. These changes correlated with a 70% decrease in placental FABP1 protein. Multivariate analyses suggested that neuroprostanes and isoprostanes are associated with maternal and placental inflammation and with birth weight. These results might shed light on the molecular mechanisms associated with altered placental fatty acid metabolism in maternal pre-gestational obesity, placing these oxidised fatty acids as novel mediators of placental function.

The rise in prevalence of obesity in women of reproductive age in developed and developing countries might propagate intergenerational cycles of detrimental effects on metabolic health. Placental lipid metabolism is disrupted by maternal obesity, which possibly affects the life-long health of the offspring. Here, we investigated placental lipid metabolism in women with pre-gestational obesity as a sole pregnancy complication and compared it to placental responses of lean women. Open profile and targeted lipidomics were used to assess placental lipids and oxidised products of docosahexaenoic (DHA) and arachidonic acid (AA), respectively, neuroprostanes and isoprostanes. Despite no overall signs of lipid accumulation, DHA and AA levels in placentas from obese women were, respectively, 2.2 and 2.5 times higher than those from lean women. Additionally, a 2-fold increase in DHA-derived neuroprostanes and a 1.7-fold increase in AA-derived isoprostanes were seen in the obese group. These changes correlated with a 70% decrease in placental FABP1 protein. Multivariate analyses suggested that neuroprostanes and isoprostanes are associated with maternal and placental inflammation and with birth weight. These results might shed light on the molecular mechanisms associated with altered placental fatty acid metabolism in maternal pre-gestational obesity, placing these oxidised fatty acids as novel mediators of placental function.