Risk of endometrial cancer after RRSO in BRCA 1/2 carriers: a multicentre cohort study.

OBJECTIVE: To know the risk of endometrial cancer (EC) in a population of women with BRCA 1/2 pathogenic or likely pathogenic variants after risk-reducing salpingo-oophorectomy (RRSO). METHODS: The study cohort included data from 857 women with BRCA mutations who underwent RRSO visited four hospitals in Catalonia, Spain, from January 1, 1999 to April 30, 2019. Standardized incidence ratio (SIR) of EC was calculated in these patients using data from a regional population-based cancer registry. RESULTS: After RRSO, eight cases of EC were identified. Four in BRCA 1 carriers and four in BRCA2 carriers. The expected number of cases of EC was 3.67 cases, with a SIR of 2.18 and a 95% CI (0.93-3.95). CONCLUSIONS: In our cohort, the risk of EC in BRCA1/2 carriers after RRSO is not greater than expected. Hysterectomy is not routinely recommended for these patients.

Blue prescription: A pilot study of health benefits for oncological patients of a short program of activities involving the sea.

Performing outdoor activities in blue spaces can help improve human health and mental well-being by reducing stress and promoting social relationships. The number of people surviving cancer has increased globally to experience this disease as a life-changing and chronic condition with physical and psychosocial symptoms that have negative impacts on their quality of life. While there has been a growth of programs in green spaces to meet the needs of cancer patients, such as follow-up post-treatment care, support groups and physical activity programs, very few studies have examined the effects of activities involving the sea for the health and well-being of oncology patients. This is the first study to evaluate whether different outdoor activities in blue spaces can benefit oncological patients' physical and mental health using smartwatches, sphygmomanometers and Profile of Mood States (POMS) questionnaires. We assessed changes in blood pressure, heart rate, sleep quality and mental health of 16 patients after twelve sessions of three different activities (walking, beach and snorkelling) and four sessions of a control activity. While no significant differences between activities were observed in terms of the data gathered by the smartwatches, a gradient of positive results for human mental health was observed towards exposure to a blue space, assessed through POMS questionnaires. Results show that exposure to blue spaces contributes to tension and anger reduction and improves the vigour mood state of oncology patients. No significant increases in patients' heart rate were recorded after the beach and snorkelling activities, with results similar to the control activity, suggesting that the contribution may be to participants' relaxation.

Wheat Oxylipins in Response to Aphids, CO2 and Nitrogen Regimes.

Wheat is critical for food security, and is challenged by biotic stresses, chiefly aphids and the viruses they transmit. The objective of this study was to determine whether aphids feeding on wheat could trigger a defensive plant reaction to oxidative stress that involved plant oxylipins. Plants were grown in chambers with a factorial combination of two nitrogen rates (100% N vs. 20% N in Hoagland solution), and two concentrations of CO2 (400 vs. 700 ppm). The seedlings were challenged with Rhopalosiphum padi or Sitobion avenae for 8 h. Wheat leaves produced phytoprostanes (PhytoPs) of the F1 series, and three types of phytofurans (PhytoFs): ent-16(RS)-13-epi-ST-Δ14-9-PhytoF, ent-16(RS)-9-epi-ST-Δ14-10-PhytoF and ent-9(RS)-12-epi-ST-Δ10-13-PhytoF. The oxylipin levels varied with aphids, but not with other experimental sources of variation. Both Rhopalosiphum padi and Sitobion avenae reduced the concentrations of ent-16(RS)-13-epi-ST-Δ14-9-PhytoF and ent-16(RS)-9-epi-ST-Δ14-10-PhytoF in relation to controls, but had little or no effect on PhytoPs. Our results are consistent with aphids affecting the levels of PUFAs (oxylipin precursors), which decreased the levels of PhytoFs in wheat leaves. Therefore, PhytoFs could be postulated as an early indicator of aphid hosting for this plant species. This is the first report on the quantification of non-enzymatic PhytoFs and PhytoPs in wheat leaves in response to aphids.

Antifungal Activity of Guiera senegalensis: From the Chemical Composition to the Mitochondrial Toxic Effects and Tyrosinase Inhibition.

Pest resistance against fungicides is a widespread and increasing problem, with impact on crop production and public health, making the development of new fungicides an urgent need. Chemical analyses of a crude methanol extract (CME) of Guiera senegalensis leaves revealed the presence of sugars, phospholipids, phytosterols, guieranone A, porphyrin-containing compounds, and phenolics. To connect chemical composition with biological effects, solid-phase extraction was used to discard water-soluble compounds with low affinity for the C18 matrix and obtain an ethyl acetate fraction (EAF) that concentrates guieranone A and chlorophylls, and a methanol fraction (MF) dominated by phenolics. While the CME and MF exhibited poor antifungal activity against Aspergillus fumigatus, Fusarium oxysporum and Colletotrichum gloeosporioides, the EAF demonstrated antifungal activity against these filamentous fungi, particularly against C. gloeosporioides. Studies with yeasts revealed that the EAF has strong effectiveness against Saccharomyces cerevisiae, Cryptococcus neoformans and Candida krusei with MICs of 8, 8 and 16 µg/mL, respectively. A combination of in vivo and in vitro studies shows that the EAF can function as a mitochondrial toxin, compromising complexes I and II activities, and as a strong inhibitor of fungal tyrosinase (Ki = 14.40 ± 4.49 µg/mL). Thus, EAF appears to be a promising candidate for the development of new multi-target fungicides.

Anti-inflammatory effects of naringenin 8-sulphonate from Parinari excelsa Sabine stem bark and its semi-synthetic derivatives.

The inflammatory response is a vital mechanism for repairing damage induced by aberrant health states or external insults; however, persistent activation can be linked to numerous chronic diseases. The nuclear factor kappa ß (NF-κB) inflammatory pathway and its associated mediators have emerged as critical targets for therapeutic interventions aimed at modulating inflammation, necessitating ongoing drug development. Previous studies have reported the inhibitory effect of a hydroethanol extract derived from Parinari excelsa Sabine (Chrysobalanaceae) on tumour necrosis factor-alpha (TNF-α), but the phytoconstituents and mechanisms of action remained elusive. The primary objective of this study was to elucidate the phytochemical composition of P. excelsa stem bark and its role in the mechanisms underpinning its biological activity. Two compounds were detected via HPLC-DAD-ESI(Ion Trap)-MS2 analysis. The predominant compound was isolated and identified as naringenin-8-sulphonate (1), while the identity of the second compound (compound 2) could not be determined. Both compound 1 and the extract were assessed for anti-inflammatory properties using a cell-based inflammation model, in which THP-1-derived macrophages were stimulated with LPS to examine the treatments' effects on various stages of the NF-κB pathway. Compound 1, whose biological activity is reported here for the first time, demonstrated inhibition of NF-κB activity, reduction in interleukin 6 (IL-6), TNF-α, and interleukin 1 beta (IL-1ß) production, as well as a decrease in p65 nuclear translocation in THP-1 cells, thus highlighting the potential role of sulphur substituents in the activity of naringenin (3). To explore the influence of sulphation on the anti-inflammatory properties of naringenin derivatives, we synthesized naringenin-4'-O-sulphate (4) and naringenin-7-O-sulphate (5) and evaluated their anti-inflammatory effects. Naringenin derivatives 4 and 5 did not display potent anti-inflammatory activities; however, compound 4 reduced IL-1ß production, and compound 5 diminished p65 translocation, with both exhibiting the capacity to inhibit TNF-α and IL-6 production. Collectively, the findings demonstrated that the P. excelsa extract was more efficacious than all tested compounds, while providing insights into the role of sulphation in the anti-inflammatory activity of naringenin derivatives.

Kitul, a food plant with antidiabetic-like effects: Reduction of intracellular reactive species in glucose-stimulated RIN-5F pancreatic ß-cells and mitigation of pro-inflammatory mediators in activated RAW 264.7 macrophages.

Kitul (Caryota urens L.) inflorescences are broadly used for sweet sap production in Asian countries and Kitul food products are known as being suitable for diabetic patients. Considering the strong ability to inhibit α-glucosidase, we hypothesize that kitul antidiabetic properties might also involve the modulation of inflammatory pathways and hyperglycaemia-induced oxidative damage. Hence, the effects of an inflorescence's methanol extract were investigated in glucose-stimulated pancreatic cells (RIN-5F) and LPS-stimulated RAW 264.7 macrophages. The extract reduced the overproduction of intracellular reactive species in pancreatic cells and also NO, L-citrulline and IL-6 levels in LPS-stimulated RAW 264.7 macrophages. Inhibition of 5-lipoxygenase (IC50 = 166.1 µg/mL) through an uncompetitive manner was also recorded upon treatment with C. urens inflorescences extract. The phenolic profile of the inflorescences was characterized by HPLC-DAD, six hydroxycinnamic acids being identified and quantified. Overall, our data provide additional evidence on the pleiotropic mechanisms of Kitul inflorescences as an antidiabetic agent.

Ability of a Polyphenol-Rich Nutraceutical to Reduce Central Nervous System Lipid Peroxidation by Analysis of Oxylipins in Urine: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

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).

Pressurized Liquid Extraction for the Production of Extracts with Antioxidant Activity from Borututu (Cochlospermum angolense Welw.).

Borututu (Cochlospermum angolense Welw.) roots have been described as a rich source of phenolic compounds. Despite the potential of this plant for the production of bioactive extracts, studies reported until now have been scarce, and they have been based on the use of inefficient conventional extraction techniques. In this study, pressurized liquid extraction (PLE) was investigated for the production of borututu root extracts. Different temperatures (50-200 °C) and solvents (water, ethanol, and 50% ethanol:water) were applied. The total phenolic compound (TPC) content, the main phenolic compounds and the in vitro antioxidant activity of the extracts were evaluated. The results were compared with those obtained by conventional decoction with water. The highest concentrations of TPC and antioxidant activity were obtained with 50% ethanol:water, followed by water. The extract obtained with 50% ethanol:water at 150 °C had a TPC concentration of 343.80 mg/g and presented the largest antioxidant activity (1488 and 4979 µmol Trolox/g extract, determined by DDPH and ABTS assay, respectively). These values were considerably higher than those obtained by conventional decoction. Ellagic acid, and ellagic and methyl ellagic acid glycosides were the main phenolic compounds found in the extracts. Therefore, was PLE demonstrated to be a selective and efficient technique to obtain extracts with high concentrations of phenolic compounds and high antioxidant activity form borututu roots.

Allophylus africanus Stem Bark Extract Modulates the Mitochondrial Apoptotic Pathway in Human Stomach Cancer Cells.

The present work aimed to detail the mechanisms elicited by Allophylus africanus P. Beauv. stem bark extract in human stomach cancer cells and to identify the bioactives underlying the cytotoxicity. MTT reduction and LDH leakage assays allowed characterizing the cytotoxic effects in AGS cells, which were further detailed by morphological analysis using phalloidin and Hoechst 33258. Proapoptotic mechanisms were elucidated through a mitochondrial membrane potential assay and by assessing the impact upon the activity of caspase-9 and -3. The extract displayed selective cytotoxicity against AGS cells. The absence of plasma membrane permeabilization, along with apoptotic body formation, suggested that pro-apoptotic effects triggered cell death. Intrinsic apoptosis pathway activation was verified, as mitochondrial membrane potential decrease and activation of caspase-9 and -3 were observed. HPLC-DAD profiling enabled the identification of two apigenin-di-C-glycosides, vicenin-2 (1) and apigenin-6-C-hexoside-8-C-pentoside (3), as well as three mono-C-glycosides-O-glycosylated derivatives, apigenin-7-O-hexoside-8-C-hexoside (2), apigenin-8-C-(2-rhamnosyl)hexoside (4) and apigenin-6-C-(2-rhamnosyl)hexoside (5). Isovitexin-2″-O-rhamnoside (5) is the main constituent, accounting for nearly 40% of the total quantifiable flavonoid content. Our results allowed us to establish the relationship between the presence of vicenin-2 and other apigenin derivatives with the contribution to the cytotoxic effects on the presented AGS cells. Our findings attest the anticancer potential of A. africanus stem bark against gastric adenocarcinoma, calling for studies to develop herbal-based products and/or the use of apigenin derivatives in chemotherapeutic drug development.

A Phytoprostane from Gracilaria longissima Increases Platelet Activation, Platelet Adhesion to Leukocytes and Endothelial Cell Migration by Potential Binding to EP3 Prostaglandin Receptor.

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.

Carvacrol and HP-ß-Cyclodextrin Complexes: Extensive Characterization and Potential Cytotoxic Effect in Human Colorectal Carcinoma Cells.

The aim of this study was to obtain solid carvacrol-cyclodextrin (CD) complexes for use in the pharmaceutical industry. To this end, the complexation of carvacrol at different pH values was studied in detail, to determine the type of CD and the reaction environment that supported the highest amount of encapsulated carvacrol. Evidence of the capability of hydroxypropyl-ß-cyclodextrins (HP-ß-CD) to form inclusion complexes with carvacrol (KC = 5042 ± 176 L mol-1) and more high complexation efficiency (2.824) was demonstrated for HP-ß-CDs using two different energy sources, ultrasound (US) (KC = 8129 ± 194 L mol-1 24 h) and microwave irradiation (MWI) (KC = 6909 ± 161 L mol-1), followed by spraying the resulting solution in a spray dryer. To confirm complex formation, the complexes were characterized using various instrumental methods to corroborate the carvacrol incorporation into the hydrophobic cavity of HP-ß-CD. The obtained carvacrol solid complexes were analyzed by 1H nuclear magnetic resonance (1H-NMR) and 2D nuclear magnetic resonance (ROSEY), differential scanning calorimetry (DSC), thermogravimetric analysis (TG) and Fourier transform infrared spectroscopy (FTIR) characterization. The structures of the resulting complexes were also characterized by molecular modeling. Furthermore, 1 mM HP-ß-CD-carvacrol complex has been shown to reduce cell proliferation in HCT-116 colorectal cancer cells by 43%, much more than in a healthy lung fibroblast MRC-5 cell line (11%).

Acute and Rapid Response of Melissa officinalis and Mentha spicata to Saline Reclaimed Water in Terms of Water Relations, Hormones, Amino Acids and Plant Oxylipins.

The use of reclaimed water is considered an efficient tool for agricultural irrigation; however, the high salinity associated to this water could compromise plant quality and yields. Balm and spearmint plants were submitted for 15 days to three irrigation treatments in a controlled chamber: control with EC: 1.2 dS m-1 (control), reclaimed water from secondary effluent (EC: 1.6 dS m-1) (S) and water from secondary effluent with brine (EC: 4.4 dS m-1) (SB). The plant water status, stomatal and hormonal regulation, nutritional response, concentration of amino acids and plant oxidative stress-based markers, as well as growth were evaluated. Both species irrigated with saline reclaimed water reduced leaf water potential and gas exchange in comparison with control plants, following 2 days of exposure to irrigation treatments. Nevertheless, spearmint plants recovered photosynthetic activity from the seventh day onwards, maintaining growth. This was attributed to hormonal changes and a greater accumulation of some amino acids and some plant oxylipins (phytoprostanes) in comparison to balm plants, which contributed to the improvement in the organoleptic and health-promoting properties of spearmint. A longer irrigation period with saline reclaimed water would be necessary to assess whether the quality of both species, especially spearmint, could further improve without compromising their growth.

Sports supplements use in mountain runners: differences by sex and competitive level.

Introduction: Introduction: sports supplements (SS) are widely used by all types of athletes to improve their performance. These SS are classified according to the ABCD system of the Australian Institute of Sports (AIS) from higher to lower scientific evidence. In mountain runners, their use could be necessary due to the physiological demands required by this sport. However, the literature on the use of SS by mountain runners is scarce. Objective: to analyze the pattern of SS consumption in mountain runners by studying differences according to sex and competitive level (regional vs national). Methodology: this was a descriptive and cross-sectional study on the consumption and use of SS by mountain runners participating in the Alcoy Solidarity Trail. Data were collected through a validated questionnaire based on content, applicability, structure, and presentation. This questionnaire was completed online by the athletes, who could fill it out voluntarily and at their convenience, as well as anonymously. Results: the results showed that 87.5 % of participants reported consuming SS, with no significant differences observed with respect to competitive level, although differences were found with respect to sex (92.7 % in men vs 70.6 % in women; p = 0.029), with a higher consumption found in men compared to women. The most consumed SS were sports bars (81.9 %), sports drinks (75.0 %), caffeine (48.6 %), magnesium (38.9 %), and electrolytes (27.8 %). Conclusions: among mountain runners consumption of SS is high, and 4 of the 5 most habitually consumed SS belong in the category of greater scientific evidence.

Introducción: Introducción: los suplementos deportivos (SS) son muy utilizados por todo tipo de deportistas para mejorar su rendimiento. Estos SS se clasifican según el sistema ABCD del Australian Institute of Sports (AIS) de mayor a menor evidencia científica. En corredores de montaña, su uso podría ser necesario debido a las exigencias fisiológicas de este deporte. Sin embargo, la literatura sobre el uso de SS por corredores de montaña es escasa. Objetivo: analizar el patrón de consumo de SS en corredores de montaña, estudiando las diferencias según el sexo y el nivel competitivo (autonómico vs. nacional). Metodología: se trata de un estudio descriptivo y transversal sobre el consumo y uso de SS por parte de los corredores de montaña participantes en el Trail Solidario de Alcoy. Los datos fueron recolectados a través de un cuestionario validado en base al contenido, la aplicabilidad, la estructura y la presentación. El cuestionario fue completado de manera online por los atletas que pudieron rellenarlo voluntariamente y a conveniencia, y de manera anónima. Resultados: los resultados mostraron que el 87,5 % de los participantes reportaron consumir SS, no observándose diferencias significativas con respecto al nivel competitivo, aunque sí se encontraron diferencias con respecto al sexo (92,7 % en hombres y 70,6 % en mujeres; p = 0,029), donde los hombres tenían un mayor consumo en comparación con las mujeres. Los SS más consumidos fueron las barritas deportivas (81,9 %), las bebidas deportivas (75,0 %), la cafeína (48,6 %), el magnesio (38,9 %) y los electrólitos (27,8 %). Conclusiones: entre los corredores de montaña, el consumo de SS es alto y 4 de los 5 SS más consumidos pertenecen a la categoría de mayor evidencia científica.

Removal of an Azo Dye from Wastewater through the Use of Two Technologies: Magnetic Cyclodextrin Polymers and Pulsed Light.

Water pollution by dyes is a huge environmental problem; there is a necessity to produce new decolorization methods that are effective, cost-attractive, and acceptable in industrial use. Magnetic cyclodextrin polymers offer the advantage of easy separation from the dye solution. In this work, the ß-CD-EPI-magnetic (ß-cyclodextrin-epichlorohydrin) polymer was synthesized, characterized, and tested for removal of the azo dye Direct Red 83:1 from water, and the fraction of non-adsorbed dye was degraded by an advanced oxidation process. The polymer was characterized in terms of the particle size distribution and surface morphology (FE-SEM), elemental analysis (EA), differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), infrared spectrophotometry (IR), and X-ray powder diffraction (XRD). The reported results hint that 0.5 g and pH 5.0 were the best conditions to carry out both kinetic and isotherm models. A 30 min contact time was needed to reach equilibrium with a qmax of 32.0 mg/g. The results indicated that the pseudo-second-order and intraparticle diffusion models were involved in the assembly of Direct Red 83:1 onto the magnetic adsorbent. Regarding the isotherms discussed, the Freundlich model correctly reproduced the experimental data so that adsorption was confirmed to take place onto heterogeneous surfaces. The calculation of the thermodynamic parameters further demonstrates the spontaneous character of the adsorption phenomena (ΔG° = −27,556.9 J/mol) and endothermic phenomena (ΔH° = 8757.1 J/mol) at 25 °C. Furthermore, a good reusability of the polymer was evidenced after six cycles of regeneration, with a negligible decline in the adsorption extent (10%) regarding its initial capacity. Finally, the residual dye in solution after treatment with magnetic adsorbents was degraded by using an advanced oxidation process (AOP) with pulsed light and hydrogen peroxide (343 mg/L); >90% of the dye was degraded after receiving a fluence of 118 J/cm2; the discoloration followed a pseudo first-order kinetics where the degradation rate was 0.0196 cm2/J. The newly synthesized ß-CD-EPI-magnetic polymer exhibited good adsorption properties and separability from water which, when complemented with a pulsed light-AOP, may offer a good alternative to remove dyes such as Direct Red 83:1 from water. It allows for the reuse of both the polymer and the dye in the dyeing process.

Dietary antioxidant intake is inversely associated with 2,3-dinor oxylipin metabolites, the major excreted oxylipins in overweight and obese subjects.

Cardiometabolic disease risk factors, including obesity, insulin resistance, high blood pressure, and dyslipidemia, are associated with elevated oxidative stress biomarkers like oxylipins. Increased adiposity by itself induces various isomers of this oxidized lipid family, while dietary polyphenols show benefits in its regulation. Previously, we showed that specific co-abundant microorganisms characterized the gut microbiota of Colombians and associated differentially with diet, lifestyle, obesity, and cardiometabolic health status, which led us to hypothesize that urinary oxylipins would reflect the intensity of oxidative metabolism linked to gut microbiota dysbiosis. Thus, we selected a convenience sample of 105 participants (age: 40.2 ± 11.9 years, 47.6% women), grouped according to microbiota, cardiometabolic health status, and body mass index (BMI); and evaluated 33 urinary oxylipins by HPLC-QqQ-MS/MS (e.g., isoprostanes, prostaglandins, and metabolites), paired with anthropometry and blood chemistry information and dietary antioxidants estimated from a 24-h food recall. In general, oxylipins did not show differences among individuals who differed in gut microbiota. While the unmetabolized oxylipin levels were not associated with BMI, the total content of oxylipin metabolites was highest in obese and cardiometabolically abnormal subjects (e.g., insulin resistant), mainly by prostaglandin-D (2,3-dinor-11ß-PGF2α) and 15-F2t-IsoPs (2,3-dinor-15-F2t-IsoP and 2,3-dinor-15-epi-15-F2t-IsoP) metabolites. The total polyphenol intake in this cohort was 1070 ± 627 mg/day. After adjusting for body weight, the polyphenol intake was significantly higher in lean than overweight and showed an inverse association with dinor-oxylipin levels in principal component analysis. These results suggest that the 2,3-dinor-oxylipins could be more specific biomarkers associated with BMI than their parent oxylipins and that are sensitive to be regulated by dietary antioxidants.

Anti-Inflammatory and Antioxidant Capacity of a Fruit and Vegetable-Based Nutraceutical Measured by Urinary Oxylipin Concentration in a Healthy Population: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Oxylipins, lipid biomarkers of inflammation are considered the gold standard method to evaluate the inflammatory and antioxidant status. The aim of the present study was to investigate whether the administration of a polyphenolic extract shot in the form of a nutraceutical was able to reduce inflammation, measured in urine markers. Ninety-two participants (45 males, 47 females, age 34 ± 11 years, weight 73.10 ± 14.29 kg, height 1.72 ± 9 cm, BMI 24.40 ± 3.43 kg/m2) completed the study after an intervention of two 16-week periods consuming extract or placebo separated by a 4-week washout period. The results showed significant differences in terms of reduction of different pro-inflammatory oxylipins (15-keto-PGF2α (from 0.90 ± 0.25 ng/mL to 0.74 ± 0.19 ng/mL p < 0.05), ent-PGF2α (from 1.59 ± 0.37 ng/mL to 1.44 ± 0.32 ng/mL p < 0.05), 2,3-dinor-15-F2t-Isop) (from 1.17 ± 0.35 ng/mL to 1.02 ± 0.27 ng/mL p < 0.05), in total oxylipins count (from 8.03 ± 1.86 ng/mL to 7.25 ± 1.23 ng/mL p < 0.05), and increase in PGE2 (from 1.02 ± 0.38 ng/mL to 1.26 ± 0.38 ng/mL p < 0.05) which has an anti-inflammatory character, after extract consumption compared to placebo. The available data seem to indicate that long-term consumption of a nutraceutical with high polyphenol content improves inflammation and oxidation parameters measured in urine, through UHPLC-QqQ-ESI-MS/MS.

Using population-based data to evaluate the impact of adherence to endocrine therapy on survival in breast cancer through the web-application BreCanSurvPred.

We show how the use and interpretation of population-based cancer survival indicators can help oncologists talk with breast cancer (BC) patients about the relationship between their prognosis and their adherence to endocrine therapy (ET). The study population comprised a population-based cohort of estrogen receptor positive BC patients (N = 1268) diagnosed in Girona and Tarragona (Northeastern Spain) and classified according to HER2 status (+ / -), stage at diagnosis (I/II/III) and five-year cumulative adherence rate (adherent > 80%; non-adherent ≤ 80%). Cox regression analysis was performed to identify significant prognostic factors for overall survival, whereas relative survival (RS) was used to estimate the crude probability of death due to BC (PBC). Stage and adherence to ET were the significant factors for predicting all-cause mortality. Compared to stage I, risk of death increased in stage II (hazard ratio [HR] 2.24, 95% confidence interval [CI]: 1.51-3.30) and stage III (HR 5.11, 95% CI 3.46-7.51), and it decreased with adherence to ET (HR 0.57, 95% CI 0.41-0.59). PBC differences were higher in non-adherent patients compared to adherent ones and increased across stages: stage I: 6.61% (95% CI 0.05-13.20); stage II: 9.77% (95% CI 0.59-19.01), and stage III: 22.31% (95% CI 6.34-38.45). The age-adjusted survival curves derived from this modeling were implemented in the web application BreCanSurvPred ( https://pdocomputation.snpstats.net/BreCanSurvPred ). Web applications like BreCanSurvPred can help oncologists discuss the consequences of non-adherence to prescribed ET with patients.

HPLC-DAD-ESI/MSn and UHPLC-ESI/QTOF/MSn characterization of polyphenols in the leaves of Neocarya macrophylla (Sabine) Prance ex F. White and cytotoxicity to gastric carcinoma cells.

Among several extracts from species from Guinea-Bissauan flora, the hydroethanol extract obtained from the leaves of gingerbread plum (Neocarya macrophylla (Sabine) Prance ex F. White.) revealed to be one of the most cytotoxic towards human gastric AGS carcinoma cells. Considering the increasing use of N. macrophylla in the food industry and the abundant biomass of agricultural wastes being generated, the identification of phenolic bioactives has been attained by HPLC-DAD-ESI/MSn and UHPLC-ESI/QTOF/MSn. Twenty-seven phenolic constituents were identified for the first time in the monotypic genus Neosartorya, 5-O-caffeoylquinic acid being detected as the major constituent (4.90 ± 0.20 mg g-1 dry extract). While 15 flavan-3-ols derivatives were determined, the extract is predominantly characterized by the occurrence of quercetin, kaempferol, apigenin and chrysoeriol glycosides. Typical apoptotic changes in gastric adenocarcinoma AGS cells upon exposure to N. macrophylla leaf extract were observed. The apoptotic cell death is mediated by the activation of the mitochondrial pathway, as loss of mitochondrial membrane potential was detected, as well as increased caspase-9 and -3 activities. The industrial relevance of this plant material, along with the data presented here on the potential anticancer effects of N. macrophylla and the efficient extraction of phenolic bioactives using water and ethanol (GRAS substance), calls for further research on the leaves as a potential functional food and/or ingredient.

No Excess Mortality up to 10 Years in Early Stages of Breast Cancer in Women Adherent to Oral Endocrine Therapy: A Probabilistic Graphical Modeling Approach.

Breast cancer (BC) is globally the most frequent cancer in women. Adherence to endocrine therapy (ET) in hormone-receptor-positive BC patients is active and voluntary for the first five years after diagnosis. This study examines the impact of adherence to ET on 10-year excess mortality (EM) in patients diagnosed with Stages I to III BC (N = 2297). Since sample size is an issue for estimating age- and stage-specific survival indicators, we developed a method, ComSynSurData, for generating a large synthetic dataset (SynD) through probabilistic graphical modeling of the original cohort. We derived population-based survival indicators using a Bayesian relative survival model fitted to the SynD. Our modeling showed that hormone-receptor-positive BC patients diagnosed beyond 49 years of age at Stage I or beyond 59 years at Stage II do not have 10-year EM if they follow the prescribed ET regimen. This result calls for developing interventions to promote adherence to ET in patients with hormone receptor-positive BC and in turn improving cancer survival. The presented methodology here demonstrates the potential use of probabilistic graphical modeling for generating reliable synthetic datasets for validating population-based survival indicators when sample size is an issue.