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1.
Sci Rep ; 14(1): 10238, 2024 05 03.
Article in English | MEDLINE | ID: mdl-38702342

ABSTRACT

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.


Subject(s)
COVID-19 , Fatty Acids, Omega-3 , Hospitalization , Severity of Illness Index , Humans , COVID-19/blood , Male , Female , Middle Aged , Fatty Acids, Omega-3/blood , Aged , Prospective Studies , SARS-CoV-2/isolation & purification , Oxylipins/blood , Eicosapentaenoic Acid/blood , Oxidative Stress , Docosahexaenoic Acids/blood , Adult , Inflammation/blood
2.
Clin Nutr ESPEN ; 47: 240-245, 2022 02.
Article in English | MEDLINE | ID: mdl-35063208

ABSTRACT

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.


Subject(s)
Citrus sinensis , Diabetes Mellitus, Type 2 , Hyperglycemia , MicroRNAs , Cross-Over Studies , Diabetes Mellitus, Type 2/prevention & control , Eating , Humans , Hyperglycemia/prevention & control
3.
Fink, Thais T.; Marques, Heloisa H.S.; Gualano, Bruno; Lindoso, Livia; Bain, Vera; Astley, Camilla; Martins, Fernanda; Matheus, Denise; Matsuo, Olivia M.; Suguita, Priscila; Trindade, Vitor; Paula, Camila S.Y.; Farhat, Sylvia C.L.; Palmeira, Patricia; Leal, Gabriela N.; Suzuki, Lisa; Odone Filho, Vicente; Carneiro-Sampaio, Magda; Duarte, Alberto José S.; Antonangelo, Leila; Batisttella, Linamara R.; Polanczyk, Guilherme V.; Pereira, Rosa Maria R.; Carvalho, Carlos Roberto R.; Buchpiguel, Carlos A.; Xavier, Ana Claudia L.; Seelaender, Marilia; Silva, Clovis Artur; Pereira, Maria Fernanda B.; Sallum, Adriana M. E.; Brentani, Alexandra V. M.; Neto, Álvaro José S.; Ihara, Amanda; Santos, Andrea R.; Canton, Ana Pinheiro M.; Watanabe, Andreia; Santos, Angélica C. dos; Pastorino, Antonio C.; Franco, Bernadette D. G. M.; Caruzo, Bruna; Ceneviva, Carina; Martins, Carolina C. M. F.; Prado, Danilo; Abellan, Deipara M.; Benatti, Fabiana B.; Smaria, Fabiana; Gonçalves, Fernanda T.; Penteado, Fernando D.; Castro, Gabriela S. F. de; Gonçalves, Guilherme S.; Roschel, Hamilton; Disi, Ilana R.; Marques, Isabela G.; Castro, Inar A.; Buscatti, Izabel M.; Faiad, Jaline Z.; Fiamoncini, Jarlei; Rodrigues, Joaquim C.; Carneiro, Jorge D. A.; Paz, Jose A.; Ferreira, Juliana C.; Ferreira, Juliana C. O.; Silva, Katia R.; Bastos, Karina L. M.; Kozu, Katia; Cristofani, Lilian M.; Souza, Lucas V. B.; Campos, Lucia M. A.; Silva Filho, Luiz Vicente R. F.; Sapienza, Marcelo T.; Lima, Marcos S.; Garanito, Marlene P.; Santos, Márcia F. A.; Dorna, Mayra B.; Aikawa, Nadia E.; Litvinov, Nadia; Sakita, Neusa K.; Gaiolla, Paula V. V.; Pasqualucci, Paula; Toma, Ricardo K.; Correa-Silva, Simone; Sieczkowska, Sofia M.; Imamura, Marta; Forsait, Silvana; Santos, Vera A.; Zheng, Yingying; HC-FMUSP Pediatric Post-COVID-19 Study Group.
Clinics ; 76: e3511, 2021. tab
Article in English | LILACS | ID: biblio-1350613

ABSTRACT

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.


Subject(s)
Humans , Male , Child , Adolescent , COVID-19/complications , Quality of Life , Prospective Studies , Tertiary Care Centers , COVID-19 Testing , SARS-CoV-2 , Latin America
4.
Free Radic Biol Med ; 156: 190-199, 2020 08 20.
Article in English | MEDLINE | ID: mdl-32653511

ABSTRACT

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.


Subject(s)
Coronavirus Infections/diet therapy , Cytokine Release Syndrome/diet therapy , Dietary Supplements , Docosahexaenoic Acids/administration & dosage , Eicosapentaenoic Acid/administration & dosage , Leukopenia/diet therapy , Pandemics , Pneumonia, Viral/diet therapy , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/metabolism , Coronavirus Infections/virology , Cytokine Release Syndrome/epidemiology , Cytokine Release Syndrome/metabolism , Cytokine Release Syndrome/virology , Disseminated Intravascular Coagulation/diet therapy , Disseminated Intravascular Coagulation/epidemiology , Disseminated Intravascular Coagulation/metabolism , Disseminated Intravascular Coagulation/virology , Humans , Hypoxia/diet therapy , Hypoxia/epidemiology , Hypoxia/metabolism , Hypoxia/virology , Leukopenia/epidemiology , Leukopenia/metabolism , Leukopenia/virology , Oxidative Stress , Pneumonia, Viral/epidemiology , Pneumonia, Viral/metabolism , Pneumonia, Viral/virology , Randomized Controlled Trials as Topic , Reactive Oxygen Species/antagonists & inhibitors , Reactive Oxygen Species/metabolism , SARS-CoV-2
5.
Food Chem ; 302: 125340, 2020 Jan 01.
Article in English | MEDLINE | ID: mdl-31419775

ABSTRACT

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.


Subject(s)
Food Analysis/statistics & numerical data , Phenols/analysis , Volatile Organic Compounds/analysis , Wine/analysis , Butanols/analysis , Caprylates/analysis , Catechin/analysis , Food Analysis/methods , Gas Chromatography-Mass Spectrometry/methods , Gas Chromatography-Mass Spectrometry/statistics & numerical data , Multivariate Analysis , Quercetin/analysis , South America , Sulfur Dioxide/analysis , Wine/classification
6.
Environ Toxicol ; 35(4): 518-527, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31804025

ABSTRACT

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.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antioxidants/therapeutic use , Arctium/chemistry , Liver Neoplasms/prevention & control , Non-alcoholic Fatty Liver Disease/drug therapy , Plant Extracts/therapeutic use , Precancerous Conditions/prevention & control , Animals , Anti-Inflammatory Agents/isolation & purification , Antioxidants/isolation & purification , Antioxidants/metabolism , Caffeic Acids , Diet, High-Fat/adverse effects , Humans , Liver Neoplasms/pathology , Male , Medicine, Chinese Traditional , Non-alcoholic Fatty Liver Disease/pathology , Plant Extracts/isolation & purification , Plant Roots/chemistry , Precancerous Conditions/pathology , Rats , Rats, Wistar , Thioacetamide/toxicity
7.
Int J Mol Sci ; 21(1)2019 Dec 24.
Article in English | MEDLINE | ID: mdl-31878116

ABSTRACT

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.


Subject(s)
Cardiovascular Diseases/metabolism , Cardiovascular Diseases/prevention & control , Phytosterols/metabolism , Dietary Supplements , Humans , Intestinal Absorption , Lipid Metabolism/physiology
8.
J Nutr Biochem ; 61: 48-55, 2018 11.
Article in English | MEDLINE | ID: mdl-30184518

ABSTRACT

Moderate consumption of red wine has been widely associated with reduced cardiovascular risk, mainly due to its composition in phenolic compounds with antioxidant activity, such as resveratrol. The objective of this study was to compare the effect of red wine vs. trans-resveratrol consumption on the prevention and regression of atherosclerosis in LDLr (-/-) mice. This study consisted of two protocols: "Prevention" (PREV) and "Regression" (REGR). Both protocols included four groups: red wine (WINE), dealcoholized red wine (EXT), trans-resveratrol (RESV), and control (CONT). In PREV protocol, animals received a regular diet for 8 weeks and then switched to an atherogenic diet for the following 8 weeks, while the opposite was performed in REGR. Animals that received atherogenic diet after an initial period of standard diet (PREV) gained more body weight (39.25±2.30%) than the opposite (29.27±1.91%, P=.0013), suggesting an interaction between age and weight gain. Trans-resveratrol showed the highest hypocholesterolemic effect during PREV, reducing total cholesterol, LDL-C, VLDL-C and HDL-C. Supplementation with trans-resveratrol and dealcoholized red wine changed the fatty acids profile in the liver in both protocols, leading to an increase of MDA concentrations and SOD activity in the PREV protocol. In conclusion, supplementation with trans-resveratrol, red wine and the same wine without alcohol altered biomarkers of oxidative stress and lipidemia but had no effect on the prevention or regression of fatty streaks. These data suggest that cardiovascular protection associated with the "French Paradox" may be a result of synergistic effects between wine and the Mediterranean diet.


Subject(s)
Atherosclerosis/prevention & control , Resveratrol/pharmacology , Wine , Animals , Atherosclerosis/diet therapy , Body Weight/drug effects , Dietary Supplements , Disease Models, Animal , Fatty Acids/metabolism , Liver/drug effects , Liver/metabolism , Male , Mice, Knockout , Oxidative Stress/drug effects , Receptors, LDL/genetics , Resveratrol/isolation & purification
9.
Molecular metabolism ; 11: 137-144, May. 2018. tab, graf
Article in English | Sec. Est. Saúde SP, CONASS, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1222556

ABSTRACT

OBJECTIVE: Statin intolerance, whether real or perceived, is a growing issue in clinical practice. Our aim was to evaluate the effects of reduced-dose statin therapy complemented with nutraceuticals. METHODS: First phase: Initially, 53 type 2 diabetic statin-treated patients received a supplementation with fish oil (1.7 g EPA + DHA/day), chocolate containing plant sterols (2.2 g/day), and green tea (two sachets/day) for 6 weeks. Second phase: "Good responders" to supple-mentation were identified after multivariate analysis (n»10), and recruited for a pilot protocol of statin dose reduction. "Good responders" were then provided with supplementation for 12 weeks: standard statin therapy was kept during the first 6 weeks and reduced by 50% from weeks 6e12.RESULTS: First phase: After 6 weeks of supplementation, plasma LDL-C (-13.7% 3.7,P».002) and C-reactive protein ( 35.5% 5.9,P».03) were reduced. Analysis of lathosterol and campesterol in plasma suggested that intensity of LDL-C reduction was influenced bycholesterol absorption rate rather than its synthesis. Second phase: no difference was observed for plasma lipids, inflammation, cholesterol effluxcapacity, or HDL particles after statin dose reduction when compared to standard therapy. CONCLUSIONS: Although limited by the small sample size, our study demonstrates the potential for a new therapeutic approach combining lower statin dose and specific dietary compounds. Further studies should elucidate "good responders" profile as a tool for personalized medicine. This may be particularly helpful in the many patients with or at risk for CVD who cannot tolerate high dose statin therapy. Trial registration: ClinicalTrials.gov, NCT02732223.


Subject(s)
Phytosterols , Fatty Acids, Omega-3 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Atherosclerosis , Polyphenols
10.
Am J Med Genet A ; 176(4): 915-924, 2018 04.
Article in English | MEDLINE | ID: mdl-29575623

ABSTRACT

Fetal gastroschisis is a paraumbilical abdominal wall defect with herniation of abdominal organs. The underlying cause of the disease remains unknown; however, studies suggest that nutritional factors may play a role in its development. This prospective case-control study explored the association of serum fatty acid levels of pregnant women and occurrence of gastroschisis. Gastroschisis group comprised 57 pregnant women with fetuses with gastroschisis, and the control group comprised 114 pregnant women with normal fetuses. Serum fatty acids levels were compared between the groups for the overall pregnancy at <34 weeks; ≤25 weeks, and >25 and <34 weeks; and at delivery. Total fatty acids (p = .008), unsaturated fatty acids (p = .002), and the C18:1n9/C18:00 ratio (p = .021) were lower in the gastroschisis group than in the control group during the overall pregnancy; however, the C16:00/C18:2n6 ratio (p = .018) was higher in the gastroschisis group than in the control group during the same period. Total fatty acids (p = .044) and unsaturated fatty acids (p = .024) were lower in the gastroschisis group at ≤25 weeks, and unsaturated fatty acid (p = .025) and the C18:1n9/C18:00 ratio (p = .013) were lower in the gastroschisis group than in the control group at >25 and <34 weeks. Pregnant women with fetuses with gastroschisis have low serum fatty acids levels during pregnancy. These findings suggest that fatty acids levels may be involved in the pathogenesis of fetal gastroschisis.


Subject(s)
Fatty Acids/blood , Gastroschisis/blood , Gastroschisis/mortality , Adolescent , Adult , Biomarkers , Case-Control Studies , Female , Gastroschisis/epidemiology , Gestational Age , Humans , Lipids/blood , Metabolome , Metabolomics/methods , Pregnancy , Young Adult
11.
Mol Metab ; 11: 137-144, 2018 05.
Article in English | MEDLINE | ID: mdl-29503145

ABSTRACT

OBJECTIVE: Statin intolerance, whether real or perceived, is a growing issue in clinical practice. Our aim was to evaluate the effects of reduced-dose statin therapy complemented with nutraceuticals. METHODS: First phase: Initially, 53 type 2 diabetic statin-treated patients received a supplementation with fish oil (1.7 g EPA + DHA/day), chocolate containing plant sterols (2.2 g/day), and green tea (two sachets/day) for 6 weeks. Second phase: "Good responders" to supplementation were identified after multivariate analysis (n = 10), and recruited for a pilot protocol of statin dose reduction. "Good responders" were then provided with supplementation for 12 weeks: standard statin therapy was kept during the first 6 weeks and reduced by 50% from weeks 6-12. RESULTS: First phase: After 6 weeks of supplementation, plasma LDL-C (-13.7% ± 3.7, P = .002) and C-reactive protein (-35.5% ± 5.9, P = .03) were reduced. Analysis of lathosterol and campesterol in plasma suggested that intensity of LDL-C reduction was influenced by cholesterol absorption rate rather than its synthesis. Second phase: no difference was observed for plasma lipids, inflammation, cholesterol efflux capacity, or HDL particles after statin dose reduction when compared to standard therapy. CONCLUSIONS: Although limited by the small sample size, our study demonstrates the potential for a new therapeutic approach combining lower statin dose and specific dietary compounds. Further studies should elucidate "good responders" profile as a tool for personalized medicine. This may be particularly helpful in the many patients with or at risk for CVD who cannot tolerate high dose statin therapy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02732223.


Subject(s)
Diet Therapy/methods , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Precision Medicine/methods , Aged , Cholesterol, LDL/blood , Dietary Supplements , Drug Administration Schedule , Female , Fish Oils/administration & dosage , Fish Oils/therapeutic use , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/blood , Male
12.
Br J Nutr ; 117(12): 1663-1673, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28633686

ABSTRACT

The aim of the present study was to investigate the relationship of four TNF-α SNP with inflammatory biomarkers and plasma fatty acids (FA), and the interaction among them in a population-based, cross-sectional study in São Paulo, Brazil. A total of 281 subjects, aged >19 and <60 years, participated in a cross-sectional, population-based study performed in Brazil. The following SNP spanning the TNF-α gene were genotyped: -238G/A (rs361525), -308G/A (rs1800629), -857C/T (rs1799724) and -1031T/C (rs1799964). In all, eleven plasma inflammatory biomarkers and plasma FA profile were determined. To analyse the interaction between TNF-α SNP and plasma FA, a cluster analysis was performed to stratify individuals based on eleven inflammatory biomarkers into two groups used as outcome: inflammatory (INF) and non-inflammatory clusters. The -238A allele carriers had higher TNF-α (P=0·033), IL-6 (P=0·013), IL-1ß (P=0·037), IL-12 (0·048) and IL-10 (P=0·010) than the GG genotype. The -308A allele carriers also had lower levels of plasma palmitoleic acid (P=0·009), oleic acid (P=0·039), total MUFA (P=0·014), stearoyl-CoA desaturase (SCD) activity index-16 (P=0·007), SCD-18 (P=0·020) and higher levels of PUFA (P=0·046) and DHA (P=0·044). Significant interactions modifying the risk of belonging to the INF cluster were observed with inflammatory cluster as outcome between -857C/T and plasma α-linolenic acid (P=0·026), and also between -308G/A and plasma stearic acid (P=0·044) and total SFA (P=0·040). Our study contributes to knowledge on TNF-α SNP and their association with inflammatory biomarker levels, plasma FA and the interaction among them, of particular interest for the Brazilian population.


Subject(s)
Fatty Acids/blood , Polymorphism, Single Nucleotide , Tumor Necrosis Factor-alpha/blood , Tumor Necrosis Factor-alpha/genetics , Adolescent , Adult , Alleles , Biomarkers/blood , Brazil , Child , Cholesterol/blood , Cross-Sectional Studies , Exercise , Fatty Acids, Monounsaturated/blood , Female , Genotyping Techniques , Humans , Interleukins/blood , Logistic Models , Male , Middle Aged , Oleic Acid/blood , Stearic Acids/blood , Stearoyl-CoA Desaturase/blood , Stearoyl-CoA Desaturase/genetics , Surveys and Questionnaires , Triglycerides/blood , Waist Circumference , Young Adult , alpha-Linolenic Acid/blood
13.
Nutrition ; 35: 106-111, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28241976

ABSTRACT

OBJECTIVE: The aim of this study was to investigate the interaction of toll-like receptor 4 (TLR4) gene single nucleotide polymorphism (SNP) and plasma fatty acid (FA) profile in modulating risk for systemic inflammation. METHODS: In all, 262 adult (19-59 y) participants of the Health Survey of São Paulo met the inclusion criteria. Anthropometric parameters, blood pressure, plasma inflammatory biomarker concentration, and fatty acid profile were measured and four SNPs of the TLR4 gene (rs4986790, rs4986791, rs11536889, and rs5030728) were genotyped. Multivariate cluster analysis was performed to stratify individuals based on levels of 11 plasma inflammatory biomarkers into two groups: inflammatory (INF) and noninflammatory (NINF). RESULTS: No association was found between any of the SNPs studied and systemic inflammation. The INF cluster had higher palmitic acid levels (P = 0.039) and estimated stearoyl coenzyme A desaturase activity (P = 0.045) and lower polyunsaturated fatty acid (P = 0.011), ω-6 fatty acid (P = 0.018), arachidonic acid (P = 0.002) levels, and estimated δ-5 desaturase activity (P = 0.025) compared with the NINF cluster. Statistically significant interaction between rs11536889 and arachidonic acid/eicosapentaenoic acid (AA/EPA) ratio (P = 0.034) was found to increase the odds of belonging to the INF cluster when individuals had the variant allele C and were at the higher percentile of AA/EPA plasma ratio. CONCLUSION: Plasma fatty acid profile modulated the odds of belonging to the INF cluster depending on genotypes of TRL4 gene polymorphisms.


Subject(s)
Fatty Acids/blood , Inflammation/blood , Inflammation/genetics , Polymorphism, Single Nucleotide , Toll-Like Receptor 4/genetics , Adult , Blood Pressure , Body Mass Index , Cross-Sectional Studies , Delta-5 Fatty Acid Desaturase , Fatty Acid Desaturases/blood , Fatty Acids, Omega-3/blood , Fatty Acids, Omega-6/blood , Female , Humans , Logistic Models , Male , Mental Recall , Sequence Analysis, DNA , Stearoyl-CoA Desaturase/blood , Toll-Like Receptor 4/metabolism , Triglycerides/blood , Waist Circumference , Young Adult
14.
Int J Cancer ; 139(8): 1873-82, 2016 10 15.
Article in English | MEDLINE | ID: mdl-27270969

ABSTRACT

Breast cancer is a global public health problem and accumulating evidence indicates early-life exposures as relevant factors in the disease risk determination. Recent studies have shown that paternal nutrition can influence offspring health including breast cancer risk. Selenium is a micronutrient with essential role in central aspects of embryogenesis, male fertility and cancer and that has been extensively studied as a chemopreventive agent in several breast cancer experimental models. Thus, we designed an animal study to evaluate whether paternal selenium deficiency or supplementation during preconception could affect the female offspring mammary gland development and breast cancer susceptibility. Male Sprague-Dawley rats were fed AIN93-G diet containing 0.15 ppm (control diet), 0.05 ppm (deficient diet) or 1 ppm (supplemented diet) of selenium for 9 weeks and mated with control female rats. Mammary carcinogenesis was induced with 7,12-dimethylbenz[a]anthracene (DMBA) in their female offspring. Paternal selenium deficiency increased the number of terminal end buds, epithelial elongation and cell proliferation in the mammary gland of the female rat offspring and these effects were associated with higher susceptibility to DMBA-induced mammary tumors (increased incidence and higher grade tumors). On the other hand, paternal selenium supplementation did not influence any of these parameters. These results highlight the importance of father's nutrition including selenium status as a relevant factor affecting daughter's breast cancer risk and paternal preconception as a potential developmental stage to start disease preventive strategies.


Subject(s)
Mammary Neoplasms, Experimental/etiology , Selenium/administration & dosage , Selenium/deficiency , 9,10-Dimethyl-1,2-benzanthracene , Animals , Carcinogenesis , Dietary Supplements , Female , Male , Mammary Glands, Animal/growth & development , Mammary Glands, Animal/pathology , Mammary Neoplasms, Experimental/chemically induced , Mammary Neoplasms, Experimental/pathology , Rats , Rats, Sprague-Dawley
15.
Toxicol Mech Methods ; 26(5): 362-370, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27268753

ABSTRACT

OBJECTIVE: Liver fibrosis results from the perpetuation of the normal wound healing response to several types of injury. Despite the wealth of knowledge regarding the involvement of intracellular and extracellular signaling pathways in liver fibrogenesis, information about the role of intercellular communication mediated by gap junctions is scarce. METHODS: In this study, liver fibrosis was chemically induced by carbon tetrachloride in mice lacking connexin32, the major liver gap junction constituent. The manifestation of liver fibrosis was evaluated based on a series of read-outs, including collagen morphometric and mRNA analysis, oxidative stress, apoptotic, proliferative and inflammatory markers. RESULTS: More pronounced liver damage and enhanced collagen deposition were observed in connexin32 knockout mice compared to wild-type animals in experimentally triggered induced liver fibrosis. No differences between both groups were noticed in apoptotic signaling nor in inflammation markers. However, connexin32 deficient mice displayed decreased catalase activity and increased malondialdehyde levels. CONCLUSION: These findings could suggest that connexin32-based signaling mediates tissue resistance against liver damage by the modulation of the antioxidant capacity. In turn, this could point to a role for connexin32 signaling as a therapeutic target in the treatment of liver fibrosis.


Subject(s)
Carbon Tetrachloride/toxicity , Chemical and Drug Induced Liver Injury/metabolism , Connexins/deficiency , Liver Cirrhosis, Experimental/metabolism , Liver/drug effects , Animals , Antioxidants/metabolism , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/pathology , Collagen/metabolism , Connexins/genetics , Cytokines/immunology , Enzyme-Linked Immunosorbent Assay , Female , Liver/immunology , Liver/metabolism , Liver/pathology , Liver Cirrhosis, Experimental/etiology , Liver Cirrhosis, Experimental/pathology , Liver Function Tests , Mice, Knockout , Real-Time Polymerase Chain Reaction , Gap Junction beta-1 Protein
16.
Nutrition ; 32(1): 88-94, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26456189

ABSTRACT

OBJECTIVE: To assess the interaction of three single nucleotide polymorphisms in the C-reactive protein (CRP) gene and plasma fatty acid (FA) levels in modulating inflammatory profile. METHODS: A total of 262 subjects, aged >19 y and <60 y, participated in a cross-sectional, population-based study performed in Brazil. Three single nucleotide polymorphisms (rs1205, rs1417938, and rs2808630) spanning the CRP gene were genotyped. Eleven plasma inflammatory biomarkers and plasma FA profile were determined. Cluster analysis was performed to stratify individuals based on eleven inflammatory biomarkers into two groups: an inflammatory (INF) and a noninflammatory group. RESULTS: The INF cluster had higher age, waist circumference, systolic blood pressure, and diastolic blood pressure; higher levels of triacylglycerol, high-sensitivity CRP, tumor necrosis factor-α, interleukin (IL)-8, IL-6, IL-1ß, IL-12, IL-10, soluble monocyte chemoattractant protein-1, soluble intercellular adhesion molecule-1, C16:0, polyunsaturated fatty acid, and omega (n)-6 polyunsaturated fatty acid; and greater C20:4n-6, C18:1/18:0, and C20:4/20:3 ratios than the noninflammatory group. Statistically significant gene-plasma C16:1n-7 interaction was detected for rs1417938 (P = 0.047). Those with a dominant homozygous rs2808630 had a lower risk of belonging to the INF group with the upper 50th percentile of C20:4n-6, n-3 highly unsaturated FA, and C20:4/20:3 ratio. Regarding rs1205, A allele carriers had lower risk of being in the INF group when C20:5n-3 and n-3 highly unsaturated FA levels were greater than the median. CONCLUSIONS: The INF group exhibited changes in metabolic parameters that predispose this group to chronic disease, where polymorphisms in the CRP gene modulated the risk of being in the INF group depending on individual plasma fatty acid and lipid profile.


Subject(s)
C-Reactive Protein/genetics , Fatty Acids/blood , Genotype , Inflammation Mediators/blood , Inflammation/genetics , Polymorphism, Single Nucleotide , Adult , Alleles , Biomarkers/blood , Blood Pressure , Brazil , Cross-Sectional Studies , Cytokines/blood , Humans , Inflammation/blood , Middle Aged , Triglycerides/blood , Waist Circumference , Young Adult
17.
J Sci Food Agric ; 94(1): 119-25, 2014 Jan 15.
Article in English | MEDLINE | ID: mdl-23649523

ABSTRACT

BACKGROUND: This study evaluated the effect of inulin and okara flour on textural and sensory properties of probiotic soy yoghurt (SY) throughout 28 days of storage at 4 °C. Employing a 2(2) design, four formulations of SY produced from soymilk and fermented with an ABT-4 culture (Lactobacillus acidophilus La-5, Bifidobacterium animalis Bb-12 and Streptococcus thermophilus) were studied: SY-C (control); SY-I (with inulin); SY-O (with okara); SY-IO (with inulin + okara). RESULTS: The addition of okara and the refrigerated storage led to significant differences in the instrumental texture parameters of SY (P < 0.05). Inulin and okara did not affect SY sensory acceptability (P > 0.05), but there was a tendency for higher scores in the presence of inulin. On the other hand, the storage period, particularly at 21 days, was unfavourable regarding the acceptance of the different SY. CONCLUSION: The results showed that the addition of okara flour and the storage were significant factors to increase firmness of the soy yoghurts. SY acceptability was not affected by the incorporation of inulin or okara. These results suggest that okara, discarded as industrial waste, may be used in probiotic soy yoghurt, helping to increase the nutritional and functional properties without altering its acceptability.


Subject(s)
Glycine max , Inulin/administration & dosage , Plant Proteins/administration & dosage , Polysaccharides/administration & dosage , Probiotics/administration & dosage , Sensation , Soy Foods/analysis , Bifidobacterium/metabolism , Consumer Behavior , Fermentation , Humans , Industrial Waste , Lactobacillus acidophilus/metabolism , Nutritive Value , Soy Foods/microbiology , Glycine max/chemistry
18.
J Agric Food Chem ; 59(22): 12183-92, 2011 Nov 23.
Article in English | MEDLINE | ID: mdl-21961646

ABSTRACT

The objective of this study was to demonstrate how different factors can simultaneously influence the oxidative stability of an oil-in-water emulsion, and how these factors can be used to enlarge the variation range of oxidation markers, expressed as peroxide value (PV) and TBARS. Initially, a Plackett-Burman design was used to screen seven factors (temperature, pH, and iron, copper, ascorbyl palmitate, ascorbic acid, and sodium chloride concentrations). A temperature elevation of 30 to 60 °C reduced PV and TBARS, a pH change from 3.0 to 7.0 increased PV and reduced TBARS, and the presence of ascorbic acid (1 mmol/L) had no significant effect on PV but increased TBARS (p < 0.05). Thus, the temperature was fixed at 30 °C, and an emulsion was formulated with different combinations of ascorbic acid, iron, and pH according to a central composite rotatable design. Regression models were fitted to PV and TBARs responses and optimized to get the higher values of both markers of oxidation. The optimized emulsion contained 1.70 mmol/L AH (ascorbic acid) and 0.885 mmol/L FeSO(4) · 7H(2)O (1.0 mmol/L Fe(2+)) at pH 5.51 and 30 °C. The range of variation observed for oxidation markers in the optimized emulsion model (PV, 0-4.27 mequiv/L; TBARS, 0-13.55 mmol/L) was larger than the variation observed in the nonoptimized model (PV, 0-1.05 mequiv/L; TBARS, 0-1.00 mmol/L). The antioxidant activity of six compounds (Trolox, α-tocopherol, caffeic acid, gallic acid, catechin, and TBHQ) was evaluated using the optimized emulsion conditions. After application of the Tukey HSD post hoc statistical test, the samples that were not different (p < 0.05) in the nonoptimized emulsions showed a significant difference in the optimized emulsions. Considering the importance of the interactions on oxidation studies, our model represents a significant improvement in a direct methodology that can be applied to evaluate natural compounds under different combination of factors.


Subject(s)
Ascorbic Acid/chemistry , Iron/chemistry , Emulsions/chemistry , Hydrogen-Ion Concentration , Oxidation-Reduction
19.
Mycobiology ; 39(3): 187-93, 2011 Sep.
Article in English | MEDLINE | ID: mdl-22783102

ABSTRACT

Botryosphaeran, a water-soluble exopolysaccharide of the ß-(1 → 3;1 → 6)-D-glucan type that has been isolated from the culture medium of Botryosphaeria rhodina MAMB-05 grown in submerged fermentation using glucose as the sole carbon source, was previously demonstrated to be non-genotoxic in peripheral blood and bone marrow, and exhibited strong anticlastogenic activity. In the present study, the effects of botryosphaeran were investigated in streptozotocin-induced diabetic rats as well as in high-fat diet-fed hyperlipidemic Wistar rats. The plasma glucose level was reduced by 52% in the diabetic group of rats after administration of 12 mg botryosphaeran/kg body weight of the rats (b.w.)/day by gavage over 15 days. A reduction in the median ration intake was accompanied by an increase in the median body weight gain, as well as the efficiency of food conversion. These results demonstrate that botryosphaeran has protective effects by reducing the symptoms of cachexia in Diabetes mellitus. Botryosphaeran administered by gavage at a concentration of 12 mg botryosphaeran/kg b.w./day over 15 days also reduced the plasma levels of total cholesterol and low density lipoprotein-cholesterol by 18% and 27%, respectively, in hyperlipidemic rats. Based on these findings, we conclude that botryosphaeran possesses hypoglycemic and hypocholesterolemic properties in conditions of diabetes mellitus and hyperlipidemia, respectively, and may be used as an oral anti-diabetic agent.

20.
J Clin Invest ; 121(1): 355-68, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21183787

ABSTRACT

Studies in humans and rodents indicate that a minimum amount of stored energy is required for normal pubertal development. The adipocyte-derived hormone leptin is a key metabolic signal to the neuroendocrine reproductive axis. Humans and mice lacking leptin or the leptin receptor (LepR) (ob/ob and db/db mice, respectively) are infertile and fail to enter puberty. Leptin administration to leptin-deficient subjects and ob/ob mice induces puberty and restores fertility, but the exact site or sites of leptin action are unclear. Here, we found that genetic deletion of LepR selectively from hypothalamic Kiss1 neurons in mice had no effect on puberty or fertility, indicating that direct leptin signaling in Kiss1 neurons is not required for these processes. However, bilateral lesions of the ventral premammillary nucleus (PMV) of ob/ob mice blunted the ability of exogenous leptin to induce sexual maturation. Moreover, unilateral reexpression of endogenous LepR in PMV neurons was sufficient to induce puberty and improve fertility in female LepR-null mice. This LepR reexpression also normalized the increased hypothalamic GnRH content characteristic of leptin-signaling deficiency. These data suggest that the PMV is a key site for leptin's permissive action at the onset of puberty and support the hypothesis that the multiple actions of leptin to control metabolism and reproduction are anatomically dissociated.


Subject(s)
Hypothalamus/metabolism , Leptin/metabolism , Proteins/metabolism , Sexual Maturation/physiology , Animals , Base Sequence , Female , Fertility/genetics , Fertility/physiology , Gene Expression , Humans , Kisspeptins , Leptin/deficiency , Leptin/genetics , Male , Mice , Mice, Inbred C57BL , Mice, Obese , Mice, Transgenic , Neurons/metabolism , Pregnancy , Proteins/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, Leptin/deficiency , Receptors, Leptin/genetics , Receptors, Leptin/metabolism , Sexual Maturation/genetics , Signal Transduction
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