Validation of the inventory: lockdown and its impact on the university Community.

BACKGROUND: Significant consequences of COVID-19 within academic/professional life are, at the psychological level, related to worry, tension, stress; coping strategies and lifestyle changes. This study describes the process of design and validation of an inventory (QPIC), which aims to assess the psychological impact that a situation of confinement can produce among university students and teachers. METHODS: Design of the instrument and psychometric tests. A sample of 862 students and 229 professors affiliated to Spanish and Colombian universities was used. Data were collected in April 2020 with the request of the favourable Bioethics Committee IR/2020. RESULTS: Six experts carried out the content validation. A confirmatory factor analysis of the theoretical dimensions proposed for the scales was performed and the internal consistency of each of the three initial scales was confirmed (0.866, 0.813 and 0.834). CONCLUSION: A rigorous and reliable instrument is achieved, consisting of two final scales: (a) Worry, tension and stress scale (b) Coping scale, which helps to measure individual psychological effects in housebound situations. It is an instrument designed, constructed ad hoc to assess the impact of confinement and subjected to validation. The factor structure and reliability of the instrument are examined and good psychometric properties are obtained. The application of this inventory will make it possible to assess the impact on people's mental health during a period of confinement.

Inhibition of ALK3-mediated signalling pathway protects against acetaminophen-induced liver injury.

Acetaminophen (APAP)-induced liver injury is one of the most prevalent causes of acute liver failure (ALF). We assessed the role of the bone morphogenetic protein (BMP) type I receptors ALK2 and ALK3 in APAP-induced hepatotoxicity. The molecular mechanisms that regulate the balance between cell death and survival and the response to oxidative stress induced by APAP was assessed in cultured human hepatocyte-derived (Huh7) cells treated with pharmacological inhibitors of ALK receptors and with modulated expression of ALK2 or ALK3 by lentiviral infection, and in a mouse model of APAP-induced hepatotoxicity. Inhibition of ALK3 signalling with the pharmacological inhibitor DMH2, or by silencing of ALK3, showed a decreased cell death both by necrosis and apoptosis after APAP treatment. Also, upon APAP challenge, ROS generation was ameliorated and, thus, ROS-mediated JNK and P38 MAPK phosphorylation was reduced in ALK3-inhibited cells compared to control cells. These results were also observed in an experimental model of APAP-induced ALF in which post-treatment with DMH2 after APAP administration significantly reduced liver tissue damage, apoptosis and oxidative stress. This study shows the protective effect of ALK3 receptor inhibition against APAP-induced hepatotoxicity. Furthermore, findings obtained from the animal model suggest that BMP signalling might be a new pharmacological target for the treatment of ALF.

(-)-Epicatechin and colonic metabolite 2,3-dihydroxybenzoic acid, alone or in combination with metformin, protect cardiomyocytes from high glucose/high palmitic acid-induced damage by regulating redox status, apoptosis and autophagy.

(-)-Epicatechin (EC) and a main colonic phenolic acid derived from flavonoid intake, 2,3-dihydroxybenzoic acid (DHBA), display antioxidant and antidiabetic activities. Diabetic cardiomyopathy (DCM) is one of the main causes of mortality in patients with diabetes, lacking a suitable treatment. Hyperglycaemia and dyslipidaemia are mainly responsible for oxidative stress and altered apoptosis and autophagy in cardiomyocytes during DCM. In this context, phenolic compounds could be suitable candidates for alleviating DCM, but have scarcely been investigated or their use in combination with antidiabetic drugs. This study evaluates the effects of EC, DHBA and antidiabetic drug metformin (MET), alone or all combined (MIX), on redox status, autophagy and apoptosis in H9c2 cardiomyocytes challenged with high concentrations of glucose (HG) and palmitic acid (PA). Under HG + PA conditions, EC, DHBA, MET and MIX equally improved redox status, reduced apoptosis induction and ameliorated autophagy inhibition. Mechanistically, all treatments alleviated HG + PA-induced oxidative stress by reinforcing antioxidant defences (∼40% increase in glutathione, ∼30% diminution in GPx activity and ∼15% increase in SOD activity) and reducing ROS generation (∼20%), protein oxidation (∼35%) and JNK phosphorylation (∼200%). Additionally, all treatments mitigated HG + PA-induced apoptosis and activated autophagy by decreasing Bax (∼15-25%), caspase-3 (∼20-40%) and p62 (∼20-40%), and increasing Bcl-2, beclin-1 and LC3-II/LC3-I (∼40-60%, ∼15-20%, and ∼25-30%, respectively). JNK inhibition improved protective changes to redox status, apoptosis and autophagy that were observed in EC-, DHBA- and MIX-mediated protection. Despite no additive or synergistic effects being detected when phenolic compounds and MET were combined, these results provide the first evidence for the benefits of EC and DHBA, comparable to those of MET alone, to ameliorate cardiomyocyte damage, that involve an improvement in antioxidant competence, autophagy and apoptosis, these effects being mediated at least by targeting JNK.

Synergistic Effect of a Flavonoid-Rich Cocoa-Carob Blend and Metformin in Preserving Pancreatic Beta Cells in Zucker Diabetic Fatty Rats.

The loss of functional beta-cell mass in diabetes is directly linked to the development of diabetic complications. Although dietary flavonoids have demonstrated antidiabetic properties, their potential effects on pancreatic beta-cell preservation and their synergistic benefits with antidiabetic drugs remain underexplored. We have developed a potential functional food enriched in flavonoids by combining cocoa powder and carob flour (CCB), which has shown antidiabetic effects. Here, we investigated the ability of the CCB, alone or in combination with metformin, to preserve pancreatic beta cells in an established diabetic context and their potential synergistic effect. Zucker diabetic fatty rats (ZDF) were fed a CCB-rich diet or a control diet, with or without metformin, for 12 weeks. Markers of pancreatic oxidative stress and inflammation, as well as relative beta-cell mass and beta-cell apoptosis, were analyzed. Results demonstrated that CCB feeding counteracted pancreatic oxidative stress by enhancing the antioxidant defense and reducing reactive oxygen species. Moreover, the CCB suppressed islet inflammation by preventing macrophage infiltration into islets and overproduction of pro-inflammatory cytokines, along with the inactivation of nuclear factor kappa B (NFκB). As a result, the CCB supplementation prevented beta-cell apoptosis and the loss of beta cells in ZDF diabetic animals. The observed additive effect when combining the CCB with metformin underscores its potential as an adjuvant therapy to delay the progression of type 2 diabetes.

Maternal Diet Determines Milk Microbiome Composition and Offspring Gut Colonization in Wistar Rats.

Mother's milk contains a unique microbiome that plays a relevant role in offspring health. We hypothesize that maternal malnutrition during lactation might impact the microbial composition of milk and affect adequate offspring gut colonization, increasing the risk for later onset diseases. Then, Wistar rats were fed ad libitum (Control, C) food restriction (Undernourished, U) during gestation and lactation. After birth, offspring feces and milk stomach content were collected at lactating day (L)4, L14 and L18. The V3-V4 region of the bacterial 16S rRNA gene was sequenced to characterize bacterial communities. An analysis of beta diversity revealed significant disparities in microbial composition between groups of diet at L4 and L18 in both milk, and fecal samples. In total, 24 phyla were identified in milk and 18 were identified in feces, with Firmicutes, Proteobacteria, Actinobacteroidota and Bacteroidota collectively representing 96.1% and 97.4% of those identified, respectively. A higher abundance of Pasteurellaceae and Porphyromonas at L4, and of Gemella and Enterococcus at L18 were registered in milk samples from the U group. Lactobacillus was also significantly more abundant in fecal samples of the U group at L4. These microbial changes compromised the number and variety of milk-feces or feces-feces bacterial correlations. Moreover, increased offspring gut permeability and an altered expression of goblet cell markers TFF3 and KLF3 were observed in U pups. Our results suggest that altered microbial communication between mother and offspring through breastfeeding may explain, in part, the detrimental consequences of maternal malnutrition on offspring programming.

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.

Sociodemographic Variables and Body Mass Index Associated with the Risk of Eating Disorders in Spanish University Students.

BACKGROUND: The passage through university is a complex experience that can heighten personal susceptibility to eating disorders. The objective of this research is to determine how gender, age, course, educational faculty, and body mass index (BMI) can influence the risk of eating disorders among university students. METHOD: A transversal and descriptive study is conducted with a sample of 516 Spanish students (57.2% female, 42.8% male; Mage = 21.7, SDage = 4.1) following 26 university degrees. The Inventory Eating Disorder-Reference criterion (EDI-3-RF) was administered to the students. Contingency tables were used between categorical variables with the chi-squared statistic, at a significance level of p < 0.05. The Student t-test was used for two independent samples and a one-way ANOVA test with the post hoc Bonferroni test for more than two groups. Pearson's correlation and a simple linear regression analysis were used to analyze the relationship between the variables in its quantitative version. RESULTS: It was found that the female students enrolled in the second year presented a greater obsession with thinness and body dissatisfaction (p = 0.029; d = 0.338); the male students practiced more physical exercise to control their weight (p = 0.003); and that students under the age of twenty (p < 0.010; d = 0.584) and students from both the Health (p = 0.0.13) and Law (p = 0.021) educational faculties showed greater bulimic behavior (d = 0.070). More females are underweight (z = 2.8), and more men are overweight (z = 2.4). Normal-weight students scored significantly higher in thinness obsession (p = 0.033). Overweight students scored significantly higher on thinness obsession (p < 0.001) and body dissatisfaction (p < 0.001). Obese students scored significantly higher on body dissatisfaction (p = 0.04). CONCLUSIONS: The data obtained in this study, reinforce the hypothesis that the female gender, at an age within the limits of early adolescence, in the first year of the degree courses, with specific university qualifications, and a high BMI constituted factors that could provoke an eating disorder. Consequently, it is necessary to implement preventive measures adapted to the circumstances of each university student.

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.

Supplementation with a Cocoa-Carob Blend, Alone or in Combination with Metformin, Attenuates Diabetic Cardiomyopathy, Cardiac Oxidative Stress and Inflammation in Zucker Diabetic Rats.

Diabetic cardiomyopathy (DCM) is one of the main causes of mortality among diabetic patients, with oxidative stress and inflammation major contributors to its development. Dietary flavonoids show strong antioxidant and anti-inflammatory activities, although their potential additive outcomes in combination with antidiabetic drugs have been scarcely explored. The present study investigates the cardioprotective effects of a cocoa-carob blend (CCB) diet, rich in flavonoids, alone or in combination with metformin, in the development of DCM. Zucker diabetic fatty rats (ZDF) were fed with a CCB rich-diet or a control diet, with or without metformin for 12 weeks. Glucose homeostasis, cardiac structure and function, and oxidative and inflammatory biomarkers were analysed. CCB improved glucose homeostasis, and mitigated cardiac dysfunction, hypertrophy, and fibrosis in ZDF rats. Mechanistically, CCB counteracted oxidative stress in diabetic hearts by down-regulating NADPH oxidases, reducing reactive oxygen species (ROS) generation and modulating the sirtuin-1 (SIRT1)/ nuclear factor E2-related factor 2 (Nrf2) signalling pathway, overall improving antioxidant defence. Moreover, CCB suppressed inflammatory and fibrotic reactions by inhibiting nuclear factor kappa B (NFκB) and pro-inflammatory and pro-fibrotic cytokines. Noteworthy, several of these effects were further improved in combination with metformin. Our results demonstrate that CCB strongly prevents the cardiac remodelling and dysfunction observed in diabetic animals, highlighting its potential, alone or in adjuvant therapy, for treating DCM.

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.

Dietary Flavonoids and Insulin Signaling in Diabetes and Obesity.

Type 2 diabetes (T2D) and obesity are relevant worldwide chronic diseases. A common complication in both pathologies is the dysregulation of the insulin-signaling pathway that is crucial to maintain an accurate glucose homeostasis. Flavonoids are naturally occurring phenolic compounds abundant in fruits, vegetables and seeds. Rising evidence supports a role for the flavonoids against T2D and obesity, and at present, these compounds are considered as important potential chemopreventive agents. This review summarizes in vitro and in vivo studies providing data related to the effects of flavonoids and flavonoid-rich foods on the modulation of the insulin route during T2D and obesity. Notably, few human studies have evaluated the regulatory effect of these phenolic compounds at molecular level on the insulin pathway. In this context, it is also important to note that the mechanism of action for the flavonoids is not fully characterized and that a proper dosage to obtain a beneficial effect on health has not been defined yet. Further investigations will contribute to solve all these critical challenges and will enable the use of flavonoids to prevent, delay or support the treatment of T2D and obesity.

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.