Dietary Supplementation with a Cocoa-Carob Blend Modulates Gut Microbiota and Prevents Intestinal Oxidative Stress and Barrier Dysfunction in Zucker Diabetic Rats.

We have recently developed a cocoa-carob blend (CCB) rich in polyphenols with antidiabetic properties. In this study, we investigated whether its benefits could be related to gut health and gut microbiota (GM) composition and the likely phenolic metabolites involved. Zucker diabetic fatty rats were fed on a standard or a CCB-rich diet for 12 weeks. Intestinal barrier structure and oxidative and inflammatory biomarkers were analyzed in colonic samples. GM composition and phenolic metabolites were evaluated from feces. The results show that CCB improved mucin and tight-junction proteins and counteracted gut oxidative stress and inflammation by regulating sirtuin-1 and nuclear factor erythroid 2-related factor 2 (Nrf2) levels. CCB also modulated the composition of the GM, showing increases in Akkermansia and Bacteroides and decreases in Ruminococcus genera. Correlation analysis strengthened the associations between these genera and improved pathological variables in diabetic animals. Moreover, 12 phenolic metabolites were identified in CCB feces, being2,3-dihydroxybenzoic and 3,4,5-trihydroxybenzoic acids significantly associated with increased levels of Akkermansia and Oscillospira genera. Our findings support the potential use of CCB to prevent intestinal damage and dysbiosis in T2D, which would help to delay the progression of this pathology.

Epidemiological and Clinical Characteristics of Patients Admitted to a Secondary Hospital with Suspected MPOX Virus Infection: Is HIV Playing a Role?

MPOX (monkeypox) is a zoonotic viral disease, endemic in some Central and West African countries. However, in May 2022, cases began to be reported in non-endemic countries, demonstrating community transmission. Since the beginning of the outbreak, different epidemiological and clinical behaviors have been observed. We conducted an observational study at a secondary hospital in Madrid to characterize suspected and confirmed cases of MPOX epidemiologically and clinically. Besides the general descriptive analysis, we compared data between HIV-positive and HIV-negative subjects; 133 patients were evaluated with suspected MPOX, of which 100 were confirmed. Regarding positive cases, 71.0% were HIV positive, and 99.0% were men with a mean age of 33. In the previous year, 97.6% reported having sex with men, 53.6% used apps for sexual encounters, 22.9% practiced chemsex, and 16.7% went to saunas. Inguinal adenopathies were significantly higher in MPOX cases (54.0% vs. 12.1%, p < 0.001), as the involvement of genital and perianal area (57.0% vs. 27.3% and 17.0% vs. 1.0%, p = 0.006 and p = 0.082 respectively). Pustules were the most common skin lesion (45.0%). In HIV-positive cases, only 6.9% had a detectable viral load, and the mean CD4 count was 607.0/mm3. No significant differences were observed in the disease course, except for a greater tendency towards the appearance of perianal lesions. In conclusion, the MPOX 2022 outbreak in our area has been related to sexual intercourse among MSM, with no severe clinical cases nor apparent differences in HIV and non-HIV patients.

Urinary Metabolomics Study on the Protective Role of Cocoa in Zucker Diabetic Rats via 1H-NMR-Based Approach.

Cocoa constitutes one of the richest sources of dietary flavonoids with demonstrated anti-diabetic potential. However, the metabolic impact of cocoa intake in a diabetic context remains unexplored. In this study, metabolomics tools have been used to investigate the potential metabolic changes induced by cocoa in type 2 diabetes (T2D). To this end, male Zucker diabetic fatty rats were fed on standard (ZDF) or 10% cocoa-rich diet (ZDF-C) from week 10 to 20 of life. Cocoa supplementation clearly decreased serum glucose levels, improved glucose metabolism and produced significant changes in the urine metabolome of ZDF animals. Fourteen differential urinary metabolites were identified, with eight of them significantly modified by cocoa. An analysis of pathways revealed that butanoate metabolism and the synthesis and degradation of branched-chain amino acids and ketone bodies are involved in the beneficial impact of cocoa on diabetes. Moreover, correlation analysis indicated major associations between some of these urine metabolites (mainly valine, leucine, and isoleucine) and body weight, glycemia, insulin sensitivity, and glycated hemoglobin levels. Overall, this untargeted metabolomics approach provides a clear metabolic fingerprint associated to chronic cocoa intake that can be used as a marker for the improvement of glucose homeostasis in a diabetic context.

Metabolic regulation of (-)-epicatechin and the colonic metabolite 2,3-dihydroxybenzoic acid on the glucose uptake, lipid accumulation and insulin signalling in cardiac H9c2 cells.

Epicatechin (EC) and main colonic phenolic acids derived from flavonoid intake have been suggested to exert healthful effects, although their mechanism of action remains unknown. Heart damage is highly prevalent in metabolic diseases, and the failure of this organ is a major cause of death worldwide. In this study, the modulation of the energy metabolism and insulin signalling by the mentioned compounds in cardiac H9c2 cells was evaluated. Incubation of cells with EC (1-20 µM) and 2,3-dihydroxybenzoic acid (DHBA, 10 µM) reduced glucose uptake, and both compounds decreased lipid accumulation at concentrations higher than 0.5 µM. EC and DHBA also increased the tyrosine phosphorylated and total insulin receptor (IR) levels, and activated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway in cardiac H9c2 cells. Interestingly, EC and DHBA did not modify glucose transporters (SGLT-1 and GLUT-1) levels, and increased GLUT-4 values. In addition, EC and DHBA decreased cluster of differentiation 36 (CD36) and fatty acid synthase (FAS) values, and enhanced carnitine palmitoyl transferase 1 (CPT1) and proliferator activated receptor α (PPARα) levels. By using specific inhibitors of AKT and 5'-AMP-activated protein kinase (AMPK), the participation of both proteins in EC- and DHBA-mediated regulation on glucose uptake and lipid accumulation was shown. Taken together, EC and DHBA modulate glucose uptake and lipid accumulation via AKT and AMPK, and reinforce the insulin signalling by activating key proteins of this pathway in H9c2 cells.

Safety and tolerability of inhaled antibiotics in patients with bronchiectasis.

INTRODUCTION: Bronchiectasis is typically treated with inhaled antibiotics in clinical practice. However, there is a striking lack of standardised procedures for the preparation of noncommercial solutions. We used biochemical parameters to analyse the safety and tolerability of inhaled antibiotics in patients with bronchiectasis, and determined potential associations between the inhaled antibiotics used and adherence to the medications and quality of life. METHODS: We conducted a literature review, biochemical testing, and a pilot study of patients admitted to our hospital with noncystic fibrosis bronchiectasis. The MEDLINE database was searched for studies involving inhaled antibiotics to treat bronchiectasis. We analysed the pH, osmolality, and sodium and chloride ion concentrations of the antibiotics used. The pilot study included patients receiving inhaled antibiotic treatment. Demographic data, adherence, and quality of life were recorded and assessed. We determined potential associations between the study variables. RESULTS: The literature review identified 429 articles: 106 included precise instructions for diluting antibiotics, and 18 reported data on the biochemical parameters analysed. Laboratory results showed that some antibiotic dilutions were outside the range of tolerability, especially those involving dry powders for intravenous infusion, which must be diluted for their inhalation. Adherence was good in more than 80% of the patients, and higher in men and older patients. Men reported better quality of life. No associations were found between the antibiotics used and the other variables. CONCLUSION: Regarding the biochemical parameters analysed, there is a lack of information on the tolerability and biochemical safety of noncommercial dilutions of inhaled antibiotics used to treat bronchiectasis.

Impact of Dietary Flavanols on Microbiota, Immunity and Inflammation in Metabolic Diseases.

Flavanols are natural occurring polyphenols abundant in fruits and vegetables to which have been attributed to beneficial effects on health, and also against metabolic diseases, such as diabetes, obesity and metabolic syndrome. These positive properties have been associated to the modulation of different molecular pathways, and importantly, to the regulation of immunological reactions (pro-inflammatory cytokines, chemokines, adhesion molecules, nuclear factor-κB [NF-κB], inducible enzymes), and the activity of cells of the immune system. In addition, flavanols can modulate the composition and function of gut microbiome in a prebiotic-like manner, resulting in the positive regulation of metabolic pathways and immune responses, and reduction of low-grade chronic inflammation. Moreover, the biotransformation of flavanols by gut bacteria increases their bioavailability generating a number of metabolites with potential to affect human metabolism, including during metabolic diseases. However, the exact mechanisms by which flavanols act on the microbiota and immune system to influence health and disease remain unclear, especially in humans where these connections have been scarcely explored. This review seeks to summarize recent advances on the complex interaction of flavanols with gut microbiota, immunity and inflammation focus on metabolic diseases.

Impact of cocoa flavanols on human health.

Cocoa is a source of flavanols, and these phenolic compounds exert beneficial effects on health and aging, and reduce the risk of suffering chronic diseases (cardiovascular diseases, metabolic disorders, cancer). An increasing body of evidence has emerged to suggest that cocoa flavanols potentially are important chemopreventive natural agents. This review summarizes human studies from the past two decades, providing data related to the effects derived from cocoa intake on health and disease. Most human studies have reported beneficial effects of cocoa consumption on health and chronic diseases; however, outcomes are not unequivocal. Review of human studies enable to identify different mechanisms of action for cocoa, although they are not fully understood at present. In addition, it remains unclear whether cocoa consumption should be recommended to healthy subjects or to patients and what is the appropriate dosage or duration of cocoa consumption. Elucidation of information regarding these crucial issues could lead to cocoa use as an approach for decreasing the risk of certain chronic diseases, as well as improving health and quality of life.

A new cyanine from oxidative coupling of chlorogenic acid with tryptophan: Assessment of the potential as red dye for food coloring.

A red pigment was prepared by reaction of chlorogenic acid (CGA) with tryptophan (TRP) in air at pH 9 (37% w/w yield) and evaluated as food dye. The main component of pigment was formulated as an unusual benzochromeno[2,3-b]indole linked to a TRP unit, featuring a cyanine type chromophore (λmax 542, 546 nm, 1% extinction coefficient of the sodium salt = 244 ± 2). The chromophore showed a minimal pH dependence and proved stable for at least 3 h at 90 °C, both at pH 3.6 or 7.0, whereas red wine anthocyanins showed a substantial (30%) and betanin a complete abatement after 1 h at the acidic pHs. An intense coloring of different food matrices was obtained with the pigment at 0.01 % w/w. No toxicity was observed up to 0.2 mg/mL on hepatic and colonic cell lines. These data make this dye a promising alternative for red coloring of food.

Effect of Cocoa and Cocoa Products on Cognitive Performance in Young Adults.

Increasing evidence support a beneficial role of cocoa and cocoa products on human cognition, particularly in aging populations and patients at risk. However, thorough reviews on the efficacy of cocoa on brain processes in young adults do not exist precisely due to the limited number of studies in the matter. Thus, the aim of this study was to summarize the findings on the acute and chronic effects of cocoa administration on cognitive functions and brain health in young adults. Web of Science and PubMed databases were used to search for relevant trials. Human randomized controlled studies were selected according to PRISMA guidelines. Eleven intervention studies that involved a total of 366 participants investigating the role of cocoa on cognitive performance in children and young adults (average age ≤ 25 years old) were finally selected. Findings from individual studies confirm that acute and chronic cocoa intake have a positive effect on several cognitive outcomes. After acute consumption, these beneficial effects seem to be accompanied with an increase in cerebral blood flow or cerebral blood oxygenation. After chronic intake of cocoa flavanols in young adults, a better cognitive performance was found together with increased levels of neurotrophins. This systematic review further supports the beneficial effect of cocoa flavanols on cognitive function and neuroplasticity and indicates that such benefits are possible in early adulthood.

Preventive effect of cocoa flavanols against glucotoxicity-induced vascular inflammation in the arteria of diabetic rats and on the inflammatory process in TNF-α-stimulated endothelial cells.

Hyperglycaemia induces a vascular inflammatory process that is a critical event in cardiovascular disease in type 2 diabetes. Cocoa and its flavanols have been widely investigated for its antioxidant and anti-inflammatory properties, and several clinical and pre-clinical studies support their vascular benefits. However, the effects of cocoa flavanols on vascular inflammation in diabetes remains to be elucidated. Herein, we evaluated the anti-inflammatory effect of a cocoa-rich diet on the aortas of Zucker diabetic fatty (ZDF) rats. Moreover, the potential role of flavanol-derived colonic metabolites to modulate the adhesion and inflammatory processes were also evaluated using TNF-α-stimulated endothelial cells. Results demonstrate that cocoa attenuates the levels of phospho-p65-nuclear factor-kappaB (NF-κB) and the expression of inflammatory factors including intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1) and inducible nitric oxide synthase in the aortas of ZDF rats. Experiments with endothelial cells further confirm that a mix of flavanol-derived colonic metabolites effectively down-regulate the levels of p-p65-NF-κB and the cell adhesion molecules ICAM-1 and VCAM-1, preventing thus the increase of monocyte-endothelial adhesion induced by TNF-α. These novel data provide the first evidence of the relevant role of cocoa and their flavanol-derived metabolites to avoid the development of endothelial inflammation and diabetic complications.

(-)-Epicatechin and the colonic metabolite 2,3-dihydroxybenzoic acid protect against high glucose and lipopolysaccharide-induced inflammation in renal proximal tubular cells through NOX-4/p38 signalling.

Chronic hyperglycaemia and inflammation are present in diabetes and both processes have been related to the pathogenesis of diabetic kidney disease. Epicatechin (EC) and main colonic phenolic acids derived from flavonoid intake, such as 2,3-dihydroxybenzoic acid (DHBA), 3,4-dihydroxyphenylacetic acid (DHPAA) and 3-hydroxyphenylpropionic acid (HPPA), have been suggested to exert beneficial effects in diabetes. This study was aimed at investigating whether the mentioned compounds could prevent inflammation in renal proximal tubular NRK-52E cells induced by high glucose and lipopolysaccharide (LPS). Pre-treatment of cells with EC and DHBA (5 µM) reverted the enhanced levels of pro-inflammatory cytokines, such as tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemoattractant protein 1 (MCP-1), activated by high glucose and LPS. Additionally, EC and DHBA pre-incubation reduced the increased values of adhesion molecules, namely, intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), as well as those of mitogen-activated protein kinases (MAPKs) [extracellular signal-regulated kinase (ERK), -c-jun N-terminal kinase (JNK) and -p38 protein kinase (p38)] activated by the high glucose and LPS challenge. Thus, in EC and DHBA pre-treated cells ICAM-1, p-ERK and p-JNK were returned to control values, and VCAM-1 and p-p38 levels were reduced by ∼20 and 25%, respectively, when compared to high glucose plus LPS-stimulated cells. Likewise, pre-treatment with EC and DHBA protected against high glucose plus LPS-triggered oxidative stress by preventing increased ROS and NADPH oxidase 4 (NOX-4) levels (∼25 and 45% reduction, respectively). By using specific inhibitors of p38 and NOX-4, the participation of both proteins in EC- and DHBA-mediated protection against inflammation and associated oxidative stress was shown. Taken together, EC and DHBA exert beneficial effects in renal proximal tubular cells, as they contribute to preventing the inflammatory-induced milieu and the accompanying redox imbalance, playing NOX-4/p38 a crucial role.

Cocoa diet modulates gut microbiota composition and improves intestinal health in Zucker diabetic rats.

Cocoa supplementation improves glucose metabolism in Zucker diabetic fatty (ZDF) rats via multiple mechanisms. Furthermore, cocoa rich-diets modify the intestinal microbiota composition both in humans and rats in healthy conditions. Accordingly, we hypothesized that cocoa could interact with the gut microbiota (GM) in ZDF rats, contributing to their antidiabetic effects. Therefore, here we investigate the effect of cocoa intake on gut health and GM in ZDF diabetic rats. Male ZDF rats were fed with standard (ZDF-C) or 10% cocoa-rich diet (ZDF-Co) during 10 weeks. Zucker Lean animals (ZL) received the standard diet. Colon tissues were obtained to determine the barrier integrity and the inflammatory status of the intestine and faeces were analysed for microbial composition, short-chain fatty acids (SCFA) and lactate levels. We found that cocoa supplementation up-regulated the levels of the tight junction protein Zonula occludens-1 (ZO-1) and the mucin glycoprotein and reduced the expression of pro-inflammatory cytokines such as tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemoattractant protein 1 (MCP-1) in the colon of ZDF diabetic animals. Additionally, cocoa modulated the microbial composition of the ZDF rats to values similar to those of the lean group. Importantly, cocoa treatment increased the relative abundance of acetate-producing bacteria such as Blautia and prevented the increase in the relative amount of lactate-producing bacteria (mainly Enterococcus and Lactobacillus genera) in ZDF diabetic animals. Accordingly, the total levels of SCFA (mainly acetate) increased significantly in the faeces of ZDF-Co diabetic rats. Finally, modified GM was closely associated with improved biochemical parameters related to glucose homeostasis and intestinal integrity and inflammation. These findings demonstrate for the first time that cocoa intake modifies intestinal bacteria composition towards a healthier microbial profile in diabetic animals and suggest that these changes could be associated with the improved glucose homeostasis and gut health induced by cocoa in ZDF diabetic rats.

Cocoa Flavanols Protect Human Endothelial Cells from Oxidative Stress.

Oxidative stress may cause functional disorders of vascular endothelia which can lead to endothelial apoptosis and thus alter the function and structure of the vascular tissues. Plant antioxidants protect the endothelium against oxidative stress and then become an effective option to treat vascular diseases. Cocoa flavanols have been proven to protect against oxidative stress in cell culture and animal models. In addition, epidemiological and interventional studies strongly suggest that cocoa consumption has numerous beneficial effects on cardiovascular health. The objective of this study was to test the chemo-protective effect of realistic concentrations of a cocoa phenolic extract and its main monomeric flavanol epicatechin on cultured human endothelial cells submitted to an oxidative challenge. Both products efficiently restrained stress-induced reactive oxygen species and biomarkers of oxidative stress such as carbonyl groups and malondialdehyde, and recovered depleted glutathione, antioxidant defences and cell viability. Our results demonstrate for the first time that a polyphenolic extract from cocoa and its main flavonoid protect human endothelial cells against an oxidative insult by modulating oxygen radical generation and antioxidant enzyme and non-enzyme defences.

Ansiedad e insatisfacción corporal en universitarios / Ansiedade e insatisfação corporal em universitários / Anxiety and body dissatisfaction in university students

Resumen La ansiedad y la insatisfacción corporal son factores de riesgo para los trastornos de conducta alimentaria y de la ingesta de alimentos. La presente investigación busca analizar los niveles de ansiedad e insatisfacción corporal, y su relación con las diferencias en función del género, curso y centro de estudios en 516 universitarios de Burgos, España -el 42.8 % fueron varones y el 57.2 %, mujeres; M = 21.7 años (DT = 4.1)-, utilizando un muestreo aleatorio estratificado. Para ello, se realizó un estudio descriptivo transversal en el que se aplicó el Cuestionario de Ansiedad Estado-Rasgo y la subescala Insatisfacción Corporal del Inventario de Trastornos de Conducta Alimentaria. Como resultados, alrededor del 20 % de los participantes presentó niveles altos de ansiedad, aunque no se encontraron diferencias por género, curso o centro; adicionalmente, el 61.4 % presentó alta o moderada insatisfacción corporal, principalmente si eran mujeres, personas ansiosas, o de segundo curso en la universidad. También se encontró interrelación entre estos factores, por lo cual en algunos universitarios se pudo identificar determinado riesgo para la aparición de trastornos de la conducta alimentaria y de la ingesta de alimentos.

Resumo A ansiedade e a insatisfação corporal são fatores de risco dos transtornos de comportamento alimentar e da ingestão de alimentos. Esta pesquisa procura analisar os níveis de ansiedade e de insatisfação corporal, bem como sua relação com as diferenças em função do gênero, do curso e do centro de estudos em 516 universitários de Burgos, Espanha - 42.8 % homens e 57.2 %, mulheres; M = 21.7 anos (DP = 4.1) -, utilizando uma amostra aleatória estratificada. Para isso, foi realizado um estudo descritivo transversal, no qual foi aplicado o Inventário de Ansiedade Traço-Estado e a subescala Insatisfação Corporal do Inventário de Transtornos de Comportamento Alimentar. Como resultados, ao redor de 20 % dos participantes apresentaram níveis altos de ansiedade, embora não se tenham encontrado diferenças por gênero, curso ou centro de estudos; além disso, 61.4 % apresentaram alta ou moderada insatisfação corporal, principalmente mulheres, pessoas ansiosas ou de segundo curso na universidade. Também foi encontrada inter-relação entre esses fatores, razão pela qual, em alguns universitários, pôde ser verificado determinado risco para o surgimento de transtorno de comportamento alimentar e da ingestão de alimentos.

Abstract Anxiety and body dissatisfaction are risk factors for eating behavior disorders (ACT). This research analyzes the levels of anxiety and body dissatisfaction, the relationship between these variables, and the differences according to gender, course and center in 516 university students of Burgos (Spain), using a stratified random sampling. 42.8 % were males and 57.2 % females, M = 21.7 years (SD = 4.1). Was carried descriptive study a cross-sectional. The State-Trait Anxiety Inventory and the subscale Body Dissatisfaction of the Eating Disorders Inventory are applied. About 20 % of participants have high levels of anxiety, not finding differences by gender, course and center. 61.4 % present high and median body dissatisfaction, mainly women, the more anxious and those of 2nd. In addition, there is an interrelation between factors. Therefore, in some students there are conditioning factors that are risk factors for the appearance of eating behavior disorders.

Dietary Cocoa Prevents Aortic Remodeling and Vascular Oxidative Stress in Diabetic Rats.

SCOPE: The aim of the present study is to investigate the potential protective effect of a cocoa-rich diet on functional and structural vascular alterations in diabetes and the mechanism involved. METHODS AND RESULTS: Male Zucker diabetic fatty (ZDF) rats are fed on a standard (ZDF-C) or cocoa-rich diet (ZDF-Co) from week 10 to 20 of life. Diabetic ZDF-C rats showed increased blood pressure and enhanced aortic stiffness, as demonstrated by the increased pulse pressure and the augmented aortic medial thickness with loss and disruption of elastic fibres. Interestingly, cocoa intake strongly avoided all these adverse effects and reduced aortic oxidative stress. Mechanistically, cocoa diet prevented sirtuin-1 (SIRT-1) depletion and increased NADPH oxidases (NOXs) and reactive oxygen species production as well as reduced active nuclear factor E2 related factor 2 (Nrf2) and their antioxidant products. CONCLUSION: The results demonstrate for the first time that a cocoa-rich diet strongly prevents aortic stiffening and remodeling in diabetic animals and avoids aortic oxidative stress. It is suggested that this effect could be mediated via its effects on SIRT-1, NOXs, and Nrf2.

Protective effects of (-)-epicatechin and the colonic metabolite 3,4-dihydroxyphenylacetic acid against glucotoxicity-induced insulin signalling blockade and altered glucose uptake and production in renal tubular NRK-52E cells.

Glucotoxicity (high levels of glucose) is a major cause in the pathogenesis of diabetes. Evidences indicate that (-)-epicatechin (EC) and colonic metabolites derived from flavonoid intake could possess antidiabetic effects, but the mechanisms for their preventive activities related to glucose homeostasis and insulin signalling in the kidney remain largely unknown. This work is aimed to investigate the effect of EC and main colonic phenolic acids derived from flavonoid intake, i.e. 2,3-dihydroxybenzoic-acid, 3,4-dihydroxyphenylacetic-acid (DHPAA) and 3-hydroxyphenylpropionic-acid, on insulin signalling, and glucose production and uptake in renal tubular proximal NRK-52E cells treated with high glucose. Pre-treatment with EC or DHPAA prevented the decreased tyrosine-phosphorylated and total levels of IR caused by high glucose. EC and DHPAA pre-treatment also avoided the inactivation of the PI3K/AKT pathway and AMPK, and the elevation of PEPCK levels induced by high glucose. Additionally, EC and DHPAA pre-treatment alleviated the altered glucose uptake and production caused by high glucose, although this protective effect was abrogated when AKT and AMPK were inhibited. These results suggest EC and DHPAA prevent or delay a potential dysfunction of NRK-52E cells treated with high glucose through the attenuation of the insulin signalling blockade and the modulation of glucose homeostasis via AKT and AMPK.

Colonic metabolites from flavanols stimulate nitric oxide production in human endothelial cells and protect against oxidative stress-induced toxicity and endothelial dysfunction.

Oxidative stress is involved in endothelial dysfunction, the key player in the development of vascular events. Flavanols, the major antioxidants in cocoa have been related to vascular protection and lower cardiovascular risk. However, the bioavailability of cocoa flavanols is very low and their bioactivity in vivo seems to be greatly mediated by the derived phenolic metabolites formed by intestinal microbiota. Hence, we investigated whether microbial-derived flavanol metabolites 3,4-dihydroxyphenylacetic acid (DHPAA), 2,3-dihydroxybenzoic acid (DHBA), 3-hydroxyphenylpropionic acid (HPPA) and a mix of them could influence endothelial function and prevent oxidative stress in human endothelial cells (Ea.hy926). Our results revealed that a mixture of flavanol colonic metabolites significantly increased phosphorylation of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) production. By using specific inhibitors, we also established the participation of the adenosine monophosphate-activated protein kinase (AMPK) and protein kinase B (AKT) in eNOS activation. Likewise, flavanol metabolite mix protected against oxidative stress-induced endothelial dysfunction and cell death by preventing increased ROS generation and activation of signaling pathways related to oxidative stress. We concluded that flavanol colonic metabolites could exert beneficial effects in endothelial cells and prevent oxidative stress-induced vascular dysfunction.

(-)-Epicatechin and the Colonic 2,3-Dihydroxybenzoic Acid Metabolite Regulate Glucose Uptake, Glucose Production, and Improve Insulin Signaling in Renal NRK-52E Cells.

SCOPE: (-)-Epicatechin (EC) and main colonic phenolic acids derived from flavonoid intake, such as 2,3-dihydroxybenzoic acid (DHBA), 3,4-dihydroxyphenylacetic acid (DHPAA), 3-hydroxyphenylpropionic acid (HPPA), and vanillic acid (VA), have been suggested to exert beneficial effects in diabetes, although the mechanism for their actions remains unknown. In this study, the modulation of glucose homeostasis and insulin signaling by the mentioned compounds on renal proximal tubular NRK-52E cells is investigated. METHODS AND RESULTS: Levels of the glucose transporters SGLT-2 and GLUT-2, as well as glucose uptake, glucose production, and key proteins of the insulin pathways, namely insulin receptor (IR), insulin receptor substrate-1 (IRS-1), and PI3K/AKT pathway are analyzed. EC (5-20 µm) and DHBA (20 µm) reduced both renal glucose uptake and production. Interestingly, EC and DHBA did not modify the levels of SGLT-2 and GLUT-2, and modulated the expression of phosphoenolpyruvate carboxykinase via AKT leading to a diminished glucose production. EC and DHBA also enhanced the tyrosine phosphorylation and total IR and IRS-1 levels, and activated the PI3K/AKT pathway in NRK-52E cells. CONCLUSION: EC and DHBA regulate the renal glucose homeostasis by modulating both glucose uptake and production, and strengthen the insulin signaling by activating key proteins of that pathway in NRK-52E cells.

Factores de riesgo de trastornos de la conducta alimentaria entre universitarios: Estimación de vulnerabilidad por sexo y edad / Risk factors of eating disorders in university students: Estimation of vulnerability by sex and age

Resumen Los trastornos de la conducta alimentaria (TCA) constituyen un problema de salud pública que ha venido incrementando. El objetivo de este estudio fue estimar la vulnerabilidad de los estudiantes universitarios a presentar un TCA. Se trabajó con una muestra probabilística de 561 estudiantes (M edad = 21.7; DE =4.1), 42.8% varones y 57.2% mujeres. Los datos fueron recabados con base al Inventario de Trastornos de la Conducta Alimentaria-Criterio de Remisión (EDI-3-RF), además de registrar algunos indicadores antropométricos. Destacan los siguientes resultados: las mujeres presentaron mayor obsesión por la delgadez e insatisfacción corporal que los varones; las conductas bulímicas estuvieron más presentes en estudiantes menores de 20 años; los varones recurren en mayor medida al ejercicio físico como forma de control del peso; 7.7% presentaron bajo peso y preocupación excesiva por la comida y el peso, condición que amerita remisión a atención especializada. Resulta apremiante reforzar los esfuerzos encaminados a la implementación de estrategias de prevención e intervención dirigidas específicamente a los estudiantes universitarios, a través del diseño de programas destinados a promover hábitos de alimentación saludables, mejorar la percepción de la imagen corporal y disminuir la preocupación obsesiva por la delgadez.

Abstract Eating disorders (ED) are a public health problem which it has been increasing. The aim of this study was to estimate the vulnerability of university students to an ED. We worked with a probabilistic sample of 561 students (M age = 21.7; SD = 4.1), 42.8% men and 57.2% women. They completed the Inventory Eating Disorder-Reference criterion (EDI-3-RF), also we took anthropometric measures. The results show that: women have a significantly more obsession with thinness and body dissatisfaction; the students under 20years old showed significant more bulimic behaviors; men prefer to do physical exercise as a way to control their weight; about 7.7% should be referred to a specialized center for having low weight along with excessive concern about food and weight. It is concluded that it is necessary to implement preventive programs and intervention measures aimed towards to the university students who promote healthy eating habits, improve the perception of their body image and diminish the obsessive preoccupation with thinness.