The severity of COVID-19 upon hospital admission is associated with plasma omega-3 fatty acids.

Fatty acids are precursors of inflammatory oxylipins. In the context of COVID-19, an excessive production of pro-inflammatory cytokines is associated with disease severity. The objective was to investigate whether the baseline omega 3/omega 6 fatty acids ratio and the oxylipins were associated with inflammation and oxidative stress in unvaccinated patients with COVID-19, classified according to the severity of the disease during hospitalization. This Prospective population-based cohort study included 180 hospitalized patients with COVID-19. The patients were classified into five groups according to the severity of their disease. Group 1 was the least severe and Group 5 was the most severe. Three specific types of fatty acids-eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA)-as well as their enzymatic and non-enzymatic oxylipins were determined using chromatography coupled mass spectrometry. There was no difference in the ratio of omega-3 to omega-6 fatty acids between the groups (p = 0.276). However, the EPA/AA ratio was lower in Group 4 compared to Group 1 (p = 0.015). This finding was associated with an increase in both C-Reactive Protein (p < 0.001) and Interleukin-6 (p = 0.002). Furthermore, the concentration of F2-Isoprostanes was higher in Group 4 than in Group 1 (p = 0.009), while no significant changes were observed for other oxylipins among groups. Multivariate analysis did not present any standard of biomarkers, suggesting the high complexity of factors involved in the disease severity. Our hypothesis was confirmed in terms of EPA/AA ratio. A higher EPA/AA ratio upon hospital admission was found to be associated with lower concentration of C-Reactive Protein and Interleukin-6, leading to a better prognosis of hospitalized SARS-CoV-2 patients. Importantly, this beneficial outcome was achieved without any form of supplementation. The trial also provides important information that can be further applied to reduce the severity of infections associated with an uncontrolled synthesis of pro-inflammatory cytokines.Trial registration: https://clinicaltrials.gov/study/NCT04449718 -01/06/2020. ClinicalTrials.gov Identifier: NCT04449718.

Effect of nanocapsules containing docosahexaenoic acid in mice with chronic inflammation.

BACKGROUND: Omega 3 fatty acids, such as docosahexaenoic acid (DHA) have been widely consumed as supplements to control chronic inflammation. Nanocapsules containing DHA (MLNC-DHA-a1) were developed and showed excellent stability. Thus, our objective was to evaluate the effect of MLNC-DHA-a1 nanocapsules on biomarkers of chronic inflammation. METHODS: Cells viability was determined by flow cytometry. The uptake of MLNC-DHA-a1 nanocapsules by macrophages and their polarization were determined. In vivo, LDLr(-,-) mice were fed a Western diet to promote chronic inflammation and were treated with MLNC-DHA-a1 nanocapsules, intravenously injected via the caudal vein once a week for 8 weeks. RESULTS: MLNC-DHA-a1 nanocapsules decreased the concentration of TNFα (p = 0.02) in RAW 264.7 cells compared to the non-treated group (NT), with no changes in IL-10 (p = 0.29). The nanocapsules also exhibited an increase in the M2 (F4/80+ CD206) phenotype (p < 0.01) in BMDM cells. In vivo, no difference in body weight was observed among the groups, suggesting that the intervention was well tolerated. However, compared to the CONT group, MLNC-DHA-a1 nanocapsules led to an increase in IL-6 (90.45 ×13.31 pg/mL), IL-1ß (2.76 ×1.34 pg/mL) and IL-10 (149.88 ×2.51 pg/mL) levels in plasma. CONCLUSION: MLNC-DHA-a1 nanocapsules showed the potential to promote in vitro macrophage polarization and were well-tolerated in vivo. However, they also increased systemic pro-inflammatory cytokines. Therefore, considering that this immune response presents a limitation for clinical trials, further studies are needed to identify the specific compound in MLNC-DHA-a1 that triggered the immune response. Addressing this issue is essential, as MLNC-DHA-a1 tissue target nanocapsules could contribute to reducing chronic inflammation.

The Protective Effect of Nutraceuticals on Hepatic Ischemia-Reperfusion Injury in Wistar Rats.

Nutraceuticals are bioactive compounds present in foods, utilized to ameliorate health, prevent diseases, and support the proper functioning of the human body. They have gained attention due to their ability to hit multiple targets and act as antioxidants, anti-inflammatory agents, and modulators of immune response and cell death. Therefore, nutraceuticals are being studied to prevent and treat liver ischemia-reperfusion injury (IRI). This study evaluated the effect of a nutraceutical solution formed by resveratrol, quercetin, omega-3 fatty acid, selenium, ginger, avocado, leucine, and niacin on liver IRI. IRI was performed with 60 min of ischemia and 4 h of reperfusion in male Wistar rats. Afterward, the animals were euthanized to study hepatocellular injury, cytokines, oxidative stress, gene expression of apoptosis-related genes, TNF-α and caspase-3 proteins, and histology. Our results show that the nutraceutical solution was able to decrease apoptosis and histologic injury. The suggested mechanisms of action are a reduction in gene expression and the caspase-3 protein and a reduction in the TNF-α protein in liver tissue. The nutraceutical solution was unable to decrease transaminases and cytokines. These findings suggest that the nutraceuticals used favored the protection of hepatocytes, and their combination represents a promising therapeutic proposal against liver IRI.

Could a lipid oxidative biomarker be applied to improve risk stratification in the prevention of cardiovascular disease?

There is significant evidence demonstrating the influence of oxidative stress on atherosclerosis and cardiovascular diseases (CVD). However, oxidative biomarkers have not been applied to follow patients under primary or secondary prevention. Many factors can explain this paradox: the higher complexity of the methods applied to quantify oxidative markers, the high variability observed among the studies, the lack of reference values, and the weak correlation with clinical endpoints. This review presents the role of the major reactive oxygen species (ROS) involved in cardiovascular pathophysiology and how they can be neutralized by endogenous and exogenous antioxidants based on classical and recent studies, highlighting the importance of the secondary products of fatty acid oxidation as potential biomarkers. Furthermore, we discuss the great variability of oxidative stress biomarkers, using as an example data obtained from 55 studies. Among the molecules directly formed from lipid oxidation, such as malondialdehyde (MDA), oxidized LDL (oxLDL), and isoprostanes (F2-IsoP), and those associated with general oxidative conditions (ferric-reducing antioxidant power (FRAP), superoxide dismutase (SOD), glutathione (GSH)), MDA was the most lipid biomarker evaluated in the treatments and proved to be an independent factor compared with traditional markers used in the algorithms to stratify the patient's risk. Finally, this review suggests four steps to follow, aiming to include MDA in the algorithms applied to estimate CVD risk.

Could a lipid oxidative biomarker be applied to improve risk stratification in the prevention of cardiovascular disease?

There is significant evidence demonstrating the influence of oxidative stress on atherosclerosis and cardiovascular diseases (CVD). However, oxidative biomarkers have not been applied to follow patients under primary or secondary prevention. Many factors can explain this paradox: the higher complexity of the methods applied to quantify oxidative markers, the high variability observed among the studies, the lack of reference values, and the weak correlation with clinical endpoints. This review presents the role of the major reactive oxygen species (ROS) involved in cardiovascular pathophysiology and how they can be neutralized by endogenous and exogenous antioxidants based on classical and recent studies, highlighting the importance of the secondary products of fatty acid oxidation as potential biomarkers. Furthermore, we discuss the great variability of oxidative stress biomarkers, using as an example data obtained from 55 studies. Among the molecules directly formed from lipid oxidation, such as malondialdehyde (MDA), oxidized LDL (oxLDL), and isoprostanes (F2-IsoP), and those associated with general oxidative conditions (ferric-reducing antioxidant power (FRAP), superoxide dismutase (SOD), glutathione (GSH)), MDA was the most lipid biomarker evaluated in the treatments and proved to be an independent factor compared with traditional markers used in the algorithms to stratify the patient's risk. Finally, this review suggests four steps to follow, aiming to include MDA in the algorithms applied to estimate CVD risk.

Development of Annexin A1-surface-functionalized metal-complex multi-wall lipid core nanocapsules and effectiveness on experimental colitis.

Annexin A1 (AnxA1), a 37KDa protein, is secreted by inflammatory and epithelial cells and displays anti-inflammatory and wound healing activities in intestinal bowel diseases. Herein, we aimed to functionalize recombinant AnxA1 (AnxA1) on multi-wall lipid core nanocapsules (MLNC) and investigate its effectiveness on experimental colitis. MLNC were prepared by covering lipid core nanocapsules (LNC) with chitosan, which coordinates metals to specific protein chemisorption sites. Therefore, MLNC were linked to Zn2+ and AnxA1 was added to form MLNC-AnxA1. LNC, MLNC and MLNC-AnxA1 presented average size of 129, 152 and 163 nm, respectively, and similar polydispersity indexes (0.xx); incorporation of chitosan inverted the negative potential zeta; the coordination efficiency of AnxA1 was 92.22 %, and transmission electron microscope photomicrograph showed MLNC-AnxA1 had a spherical shape. The effectiveness of MLNC-AnxA1 was measured in Dextran Sulfate Sodium (DSS)-induced colitis in male C57BL/6 mice. DSS (2 % solution) was administered from days 1-6; saline, LNC, MLNC, MLNC-AnxA1 or AnxA1 were administered, once a day, by oral or intraperitoneal (i.p.) routes, from days 6-9. Clinical parameters of the disease were measured from day 0-10 and gut tissues were collected for histopathology, immunohistochemistry and flow cytometry analyses. Only i.p. treatment with MLNC-AnxA1 reduced weight loss, diarrhea and disease activity index, and prevented loss of colonic structure integrity; induced the switch of macrophages into M2 phenotype in the lamina propria; recovered the colonic histoarchitecture by decreasing dysplasia of crypts, inflammation and ulcerations; restored the expression of claudin-1 Zonna-occludens-1 tight junctions in the inflamed gut; and induced stem cell proliferation in intestinal crypts. Associated, data highlight the functionalization of MLNC with AnxA1 as a tool to improve the local actions of such protein in the inflamed gut by inducing resolution of inflammation and tissue repair.

Selenium Supplementation during Puberty and Young Adulthood Mitigates Obesity-Induced Metabolic, Cellular and Epigenetic Alterations in Male Rat Physiology.

Selenium (Se) role in obesity is not clear. In addition, information on Se's role in male physiology, specifically in obesity, is scarce. We conducted this study to evaluate the efficacy of Se supplementation, specifically during puberty until young adulthood, against obesity-induced deregulation of metabolic, cellular, and epigenetic parameters in epididymal fat and/or sperm cells in a rat model. High-fat-diet consumption by male rats during puberty and young adulthood significantly increased body weight, adipocyte size, oxidative stress, deregulated expression of genes associated with inflammation (Adiponectin, IL-6, TNF-α), adipogenesis (CEBPα), estrogen biosynthesis (CYP19) and epigenetic processes in epididymal adipose tissue (Dnmt3a), as well as altered microRNA expression vital for spermatogenesis in sperm cells (miR-15b and miR-497). On the other hand, Se supplementation significantly decreased oxidative stress and mitigated these molecular/epigenetic alterations in epididymal adipose tissue or sperm cells. Our results indicate that selenium supplementation during puberty/young adulthood could improve male physiology in the context of obesity. In addition, it suggests that Se could potentially positively affect offspring health.

Ingestion of orange juice prevents hyperglycemia and increases plasma miR-375 expression.

BACKGROUND & AIMS: The intake of high-fat, high-carbohydrate (HFHC) meals is associated with an increased risk of type 2 diabetes. There is evidence that the association of orange juice to a HFHC meal can modulate the expression of microRNAs (miRNAs) linked to pancreatic ß-cell function such as miR-375. We evaluated the effect of a commercial orange juice intake with HFHC meal on plasma miRNAs expression in twelve healthy subjects in a crossover design study. METHODS: Subjects ingested water, orange juice, or an isocaloric beverage along with a 1037 kcal HFHC meal. Blood glucose and miRNAs were evaluated at baseline and 1, 3, and 5 h after the intake. RESULTS: The area under the curve (AUC) for glycemia after ingestion of HFHC + orange juice did not differ from ingestion of HPHC + glucose or HFHC + water. However, the AUC was higher in HFHC meal + glucose compared to HFHC meal + water (p = 0.034). Glucose and insulin concentrations were significantly higher in HFHC meal + glucose group after 1 h, when compared with other groups and times (p < 0.001). There was an increase in plasma miR-375 expression after 3 h of ingestion of HFHC + orange juice versus water (p = 0.026), and a decrease in plasma miR-205-5p expression after HFHC meal + glucose versus water (p = 0.023). CONCLUSIONS: A single HFHC meal + orange juice modulated plasma miR-375 expression, which is a biomarker of pancreatic ß-cell function, and contributed to preventing hyperglycemia.

Effect of resveratrol supplementation on biomarkers associated with atherosclerosis in humans.

Previous studies have suggested the beneficial effects of resveratrol against cardiovascular disease (CVD). However, there are inconsistent results on cardiovascular-related biomarkers mainly because of variable dosage, intervention time and baseline characteristics of the population. Thus, the exact effect of resveratrol remains unclear. We conducted a review to classify the studies that applied resveratrol to supplement humans according to the major biomarkers and identify which protocol characteristics would be associated with each result profile. Randomized clinical trials that assessed resveratrol effect on biomarkers related to atherosclerosis were searched in databases. Biochemical data were collected from 27 studies on the baseline and post-intervention time. We selected 12 biomarkers to compose the matrix, based on their clinical relevance and higher variation level. A total of 32 assays were obtained from these 27 studies. The net change (%) was calculated for each biomarker. Applying multivariate analysis, the assays were grouped into 3 clusters. Studies that composed Cluster II were characterized by a mean dose of 454.14 mg/day for 74.21 days and showed higher reduction of triglyceride concentration and blood pressure, while those composing Cluster III applied doses around 273.75 mg/day for about 175.33 days and showed the highest HDL increase. Thus, interventions with resveratrol could be customized according to the patient condition, in terms of "dose/time of intervention". This information can be applied to combine resveratrol with drugs to reduce blood pressure or improve lipid profile in further clinical studies.

Chemical characterization of Echium plantagineum seed oil obtained by three methods of extraction.

Echium seed oil has been considered an important alternative source of omega 3 fatty acids (n-3 FA) for human consumption. Considering the oxidative instability of n-3 FA richer oils, the objective of this study was to determine the chemical and sensory parameters of the oil obtained from Echium plantagineum seeds obtained by three extraction methods (hydraulic press: HYD; continuous screw press: PRESS; and solvent technique: SOLV). Stearidonic acid (C18:4, n3), the most important n-3 FA present in the oil, changed from 12.5% to 12.7%. Regarding the minor compounds, PRESS sample showed the highest concentration of gamma-tocopherol (782.24 mg/kg oil), while SOLV samples presented the highest amount of ß-sitosterol (73.46 mg/100 g) with no difference of campesterol concentration (159.56 mg/100 g) among the samples. Higher values of total phenolics (19.65 mg GAE/kg oil) and ß-carotene (34.83 mg/kg oil) were also found in the SOLV samples, suggesting the influence of hexane in the extraction of these bioactive compounds. High resolution mass spectrometry identified caffeic acid and its derivatives as the main phenolic compounds present in the echium oil. PRESS sample showed the best oxidative stability as measured by PV (0.61 mmol/kg oil) and malondialdehyde (173.13 µmol), probably due to faster time of processing compared to HYD and SOLV samples. Our data showed that the extraction method changed the chemical composition of the minor compounds in the echium oil, but these alterations did not reduce its nutritional quality or sensory acceptability. PRACTICAL APPLICATION: Echium oil represents a great potential source of omega 3 fatty acids, but there is not enough information about its oxidative stability and chemical composition, especially toward minor compounds. Our study characterizes echium oil composition obtained from three extraction methods, contributing to amplify the technical information about this important alternative oil for human consumption.

Combination of natural strategies to improve the oxidative stability of echium seed oil.

Echium seed oil is an alternative source of omega 3 fatty acids but it is highly susceptible to oxidation. A combination of three natural strategies was proposed in this study aiming to improve the oxidative stability of echium oil obtained by pressing (PO) or solvent extraction (PSO), kept in the storage condition for 180 days or during the consumption for 30 days. Our results showed that the reduction of temperature was sufficient to keep the oil stable during storage for both samples. During the consumption time, the best stability was achieved by adding a mixture of antioxidants, composed of sinapic (500 ppm), ascorbic (250 ppm), and citric (150 ppm) acids, and/or 20% of high oleic sunflower oil. The combined strategies promoted a 34 to 80% reduction of peroxide value and 0 to 85% reduction of malondialdehyde concentrations in the samples, showing to be a feasible and natural alternative to improve the oxidative stability of echium oil. PRACTICAL APPLICATION: Our study successfully applied an optimized combination of simple and low-cost strategies to enhance the chemical stability of echium seed oil. As the use of echium oil expands around the world, the oil industry and final consumers may benefit from our results to increase the oil shelf-life.

Docosahexaenoic acid nanoencapsulated with anti-PECAM-1 as co-therapy for atherosclerosis regression.

Atherosclerosis is a non-resolving inflammatory condition that underlies major cardiovascular diseases.Recent clinical trial using an anti-inflammatory drug has showna reduction of cardiovascular mortality, but increased the susceptibility to infections. For this reason, tissue target anti-inflammatory therapies can represent a better option to regress atherosclerotic plaques. Docosahexaenoic acid (DHA) is a natural omega 3 fatty acidcomponentof algae oil and acts asaprecursor of several anti-inflammatory compounds, such the specialized proresolving lipid mediators(SPMs). During the atherosclerosis process, the inflammatory condition of the endothelium leads to the higher expression of adhesion molecules, such as Endothelial Cell Adhesion Molecule Plate 1 (PECAM-1 or CD31), as part of the innate immune response. Thus, the objective of this study was to develop lipid-core nanocapsules with DHA constituting the nucleus and anti-PECAM-1 on their surface and drive this structure to the inflamed endothelium. Nanocapsules were prepared by interfacial deposition of pre-formed polymer method. Zinc-II was added to bind anti-PECAM-1 to the nanocapsule surface by forming an organometallic complex. Swelling experiment showed that the algae oil act as non-solvent for the polymer (weight constant weight for 60 days, p > 0.428) indicating an adequate material to produce kinetically stable lipid-core nanocapsules (LNC). Five formulations were synthesized: Lipid-core nanocapsules containing DHA (LNC-DHA) or containing Medium-chain triglycerides (LNC-MCT), multi-wall nanocapsules containing DHA (MLNC-DHA) or containing MCT (MLNC-MCT) and the surface-functionalized (anti-PECAM-1) metal-complex multi-wall nanocapsules containing DHA (MCMN-DHA-a1). All formulations showed homogeneous macroscopic aspects without aggregation. The mean size of the nanocapsules measured by laser diffraction did not show difference among the samples (p = 0.241). Multi-wall nanocapsules (MLNC) showed a slight increase in the mean diameter and polydispersity index (PDI) measured by DLS, lower pH and an inversion in the zeta-potential (ξP) compared to LNCs. Conjugation test for anti-PECAM-1 showed 94.80% of efficiency. The mean diameter of the formulation had slightly increased from 160 nm (LCN-DHA) and 162 nm (MLNC-DHA) to 164 nm (MCMN-DHA-a1) indicating that the surface functionalization did not induce aggregation of the nanocapsules. Biological assays showed that the MCMN-DHA-a1 were uptaken by the HUVEC cells and did not decrease their viability. The surface-functionalized (anti- PECAM-1) metal-complex multi-wall nanocapsules containing DHA (MCMN-DHA-a1) can be considered adequate for pharmaceutical approaches.

Persistent symptoms and decreased health-related quality of life after symptomatic pediatric COVID-19: A prospective study in a Latin American tertiary hospital

OBJECTIVES: To prospectively evaluate demographic, anthropometric and health-related quality of life (HRQoL) in pediatric patients with laboratory-confirmed coronavirus disease 2019 (COVID-19) METHODS: This was a longitudinal observational study of surviving pediatric post-COVID-19 patients (n=53) and pediatric subjects without laboratory-confirmed COVID-19 included as controls (n=52) was performed. RESULTS: The median duration between COVID-19 diagnosis (n=53) and follow-up was 4.4 months (0.8-10.7). Twenty-three of 53 (43%) patients reported at least one persistent symptom at the longitudinal follow-up visit and 12/53 (23%) had long COVID-19, with at least one symptom lasting for >12 weeks. The most frequently reported symptoms at the longitudinal follow-up visit were headache (19%), severe recurrent headache (9%), tiredness (9%), dyspnea (8%), and concentration difficulty (4%). At the longitudinal follow-up visit, the frequencies of anemia (11% versus 0%, p=0.030), lymphopenia (42% versus 18%, p=0.020), C-reactive protein level of >30 mg/L (35% versus 0%, p=0.0001), and D-dimer level of >1000 ng/mL (43% versus 6%, p=0.0004) significantly reduced compared with baseline values. Chest X-ray abnormalities (11% versus 2%, p=0.178) and cardiac alterations on echocardiogram (33% versus 22%, p=0.462) were similar at both visits. Comparison of characteristic data between patients with COVID-19 at the longitudinal follow-up visit and controls showed similar age (p=0.962), proportion of male sex (p=0.907), ethnicity (p=0.566), family minimum monthly wage (p=0.664), body mass index (p=0.601), and pediatric pre-existing chronic conditions (p=1.000). The Pediatric Quality of Live Inventory 4.0 scores, median physical score (69 [0-100] versus 81 [34-100], p=0.012), and school score (60 [15-100] versus 70 [15-95], p=0.028) were significantly lower in pediatric patients with COVID-19 at the longitudinal follow-up visit than in controls. CONCLUSIONS: Pediatric patients with COVID-19 showed a longitudinal impact on HRQoL parameters, particularly in physical/school domains, reinforcing the need for a prospective multidisciplinary approach for these patients. These data highlight the importance of closer monitoring of children and adolescents by the clinical team after COVID-19.

Potential benefits and risks of omega-3 fatty acids supplementation to patients with COVID-19.

Studies have shown that infection, excessive coagulation, cytokine storm, leukopenia, lymphopenia, hypoxemia and oxidative stress have also been observed in critically ill Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) patients in addition to the onset symptoms. There are still no approved drugs or vaccines. Dietary supplements could possibly improve the patient's recovery. Omega-3 fatty acids, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), present an anti-inflammatory effect that could ameliorate some patients need for intensive care unit (ICU) admission. EPA and DHA replace arachidonic acid (ARA) in the phospholipid membranes. When oxidized by enzymes, EPA and DHA contribute to the synthesis of less inflammatory eicosanoids and specialized pro-resolving lipid mediators (SPMs), such as resolvins, maresins and protectins. This reduces inflammation. In contrast, some studies have reported that EPA and DHA can make cell membranes more susceptible to non-enzymatic oxidation mediated by reactive oxygen species, leading to the formation of potentially toxic oxidation products and increasing the oxidative stress. Although the inflammatory resolution improved by EPA and DHA could contribute to the recovery of patients infected with SARS-CoV-2, Omega-3 fatty acids supplementation cannot be recommended before randomized and controlled trials are carried out.

Influence of heated, unheated whey protein isolate and its combination with modified starch on improvement of encapsulated pomegranate seed oil oxidative stability.

This study aimed at encapsulating pomegranate seed oil (PSO) by emulsification followed by spray drying using whey protein isolate (WPI) in its natural form, heated (Pickering), and combined with modified starch (WPI:Capsul®) as emulsifiers/wall materials. Emulsions were stable under different stress conditions. Pickering emulsions presented bigger droplet size (6.49-9.98 µm) when compared to WPI (1.88-4.62 µm) and WPI:Capsul® emulsions (1.68-5.62 µm). Sixteen fatty acids were identified in PSO. WPI treatment was considered the best formulation since it presented the highest fatty acid retention (68.51, 65.47, 47.27, 53.68, 52.95, and 52.28% for linoleic, oleic, punicic, α-eleostearic, catalpic, and ß-eleostearic acids after 30 days-storage, respectively) and protected the oil against volatile compound formation (heptanal, (E,E)-2,4-heptadienal, (Z)-2-heptenal, octanal, pentanal, (E)-2-hexenal, (E)-2-octenal, nonanal, (E)-2-decenal, and (E,E)-2,4-octadienal), which did not occur with free PSO. Overall, encapsulation protected PSO against oxidation over time, which may allow the development of new functional foods.

Chemical typicality of South American red wines classified according to their volatile and phenolic compounds using multivariate analysis.

In this study, 83 wines representating four commercial categories: "Argentinean Malbec", "Brazilian Merlot", "Uruguayan Tannat" and "Chilean Carménère" were analyzed according to their phenolic and volatile compounds. The objective was to identify the chemical compounds that would typify each category. From approximately about 600 peaks obtained by chromatographic techniques, 169 were identified and 53 of them were selected for multivariate statistical analysis. Chilean Carménère was the best discriminated group by the methods applied in our study, followed by Argentinean Malbec. Brazilian Merlot mixed mainly with some Carménère, whileTannat mixed with all wines categories, especially Malbec. In general, Chilean Carménère wines can be characterized by a bluish color, higher amounts of sulphur dioxide, higher content of octanoic acid, isobutanol, ethyl isoamyl succinate and catechin and a smaller amount of quercetin. These data can contribute for further process of authenticity or typification of South American red wines.

Burdock (Arctium lappa L.) root attenuates preneoplastic lesion development in a diet and thioacetamide-induced model of steatohepatitis-associated hepatocarcinogenesis.

Nonalcoholic steatohepatitis (NASH) is considered growing risk factor for hepatocellular carcinoma development in high-income countries. Diet- and chemically induced rodent models have been applied for the translational study of NASH-associated hepatocarcinogenesis due to their morphological and molecular similarities to the corresponding human disease. Arctium lappa L. (burdock) root tea has been extensively consumed in Traditional Chinese Medicine due to its potential therapeutic properties. Indeed, the bioactive compounds of A. lappa root, as the polyphenols, have already showed antioxidant and anti-inflammatory properties in different in vivo and in vitro bioassays. In this study, we investigated whether burdock root ethanolic extract (BRE) administration attenuates NASH-associated hepatocarcinogenesis. Eight-week-old male Wistar rats received choline-deficient high-fat diet for 8 weeks and multiple thioacetamide doses for 4 weeks in order to induce NASH and preneoplastic glutathione-S-transferase pi (GST-P)+ preneoplastic foci. Subsequently, rats were treated with BRE (100 or 200 mg/kg body weight) or vehicle by oral gavage for 2 weeks. BRE displayed high levels of chlorogenic and caffeic acids and BRE administration reduced total fatty acid and lipid hydroperoxide levels, while increasing the activities of antioxidant superoxide dismutase and catalase enzymes in the liver. Furthermore, burdock intervention diminished the size of GST-P+ remodeling preneoplastic lesions (PNLs) and displayed a trend on reducing hepatocyte proliferation (Ki-67) inside them. These findings suggest that short-term exposure to BRE alleviated remodeling PNL development in NASH-associated hepatocarcinogenesis.

Effect of sinapic acid ester derivatives on the oxidative stability of omega-3 fatty acids rich oil-in-water emulsions.

Oil-in-water (O/W) emulsions are important delivery systems of omega-3 fatty acids (n-3 FA). We investigated the effect of sinapic acid esters concentration and chain length, the electrical charge of the emulsifier and emulsion pH on the oxidative stability of n-3 FA rich O/W emulsions. Echium oil was applied as n-3 FA source. A 24 factorial design was used to simultaneously evaluate these factors. Peroxide value, malondialdehyde, 2,4-heptadienal and 2,4-decadienal were measured in the emulsions. pH and the electrical charge of the emulsifier modulated the antioxidant effectiveness of sinapic acid esters, while concentration was not relevant. The combination of positively charged emulsifier with neutral pH provided the best oxidative stability for echium oil emulsions. Our results also suggested that the increase of length chain of sinapic acid, from C4 to C12, reduced the secondary products of oxidation, when echium oil emulsions were prepared using negatively charged emulsifier under acidic conditions.

Cardiovascular Disease Prevention: The Earlier the Better? A Review of Plant Sterol Metabolism and Implications of Childhood Supplementation.

Atherosclerosis is the underlying cause of major cardiovascular events. The development of atherosclerotic plaques begins early in life, indicating that dietary interventions in childhood might be more effective at preventing cardiovascular disease (CVD) than treating established CVD in adulthood. Although plant sterols are considered safe and consistently effective in lowering plasma cholesterol, the health effects of early-life supplementation are unclear. Studies suggest there is an age-dependent effect on plant sterol metabolism: at a younger age, plant sterol absorption might be increased, while esterification and elimination might be decreased. Worryingly, the introduction of low-cholesterol diets in childhood may unintentionally favor a higher intake of plant sterols. Although CVD prevention should start as early as possible, more studies are needed to better elucidate the long-term effects of plant sterol accumulation and its implication on child development.

Dietary zinc deficiency or supplementation during gestation increases breast cancer susceptibility in adult female mice offspring following a J-shaped pattern and through distinct mechanisms.

Zinc is required for fetal development and is involved in key processes associated with breast carcinogenesis. We evaluated whether maternal zinc deficiency or supplementation during gestation influences female offspring susceptibility to breast cancer in adulthood. C57BL/6 mice consumed during gestation control (30 p.p.m. zinc), zinc-deficient (8 p.p.m) or zinc-supplemented (45 p.p.m.) diets. Maternal zinc supplementation increased in female mice offspring the incidence of chemically-induced mammary adenocarcinomas that were heavier, compared to control group. This was accompanied by a decreased number of terminal end buds, increased cell proliferation and apoptosis, and increased tumor suppressors p21, p53 and Rassf1, Zfp382 and Stat3 expression in mammary glands, as well as increased zinc status. Although maternal zinc deficiency did not alter the incidence of these lesions, it also induced heavier mammary adenocarcinomas, compared to control group. These effects were accompanied by a decreased number of terminal end buds, increased proto-oncogenes c-Myc and Lmo4 expression and H3K9Me3 and H4K20Me3 epigenetic marks in mammary glands of offspring, and decreased zinc status and increased levels of oxidative marker malondialdehyde. The data suggest that both maternal zinc deficiency and supplementation during gestation programmed increased breast cancer susceptibility in adult mice offspring following a J-shaped pattern through distinct mechanisms.