Olive pomace oil can improve blood lipid profile: a randomized, blind, crossover, controlled clinical trial in healthy and at-risk volunteers.

PURPOSE: This study aimed to assess the effect of dietary consumption of olive pomace oil (OPO) on blood lipids (primary outcome) and other cardiovascular disease (CVD) risk factors (blood pressure, inflammation and endothelial function as secondary outcomes). METHODS: A randomized, controlled, blind, crossover intervention was carried out in healthy and at-risk (hypercholesterolemic) subjects. Participants consumed daily 45 g of OPO or high-oleic acid sunflower oil (HOSO) as control oil during 4 weeks. RESULTS: OPO significantly reduced low-density lipoprotein cholesterol (LDL-C; P = 0.003) and apolipoprotein B (Apo B; P = 0.022) serum concentrations, and LDL/HDL ratio (P = 0.027) in healthy and at-risk volunteers. These effects were not observed with HOSO. Blood pressure, peripheral artery tonometry (PAT), endothelial function and inflammation biomarkers were not affected. CONCLUSIONS: Regular consumption of OPO in the diet could have hypolipidemic actions in subjects at cardiovascular risk as well as in healthy consumers, contributing to CVD prevention. CLINICAL TRIAL REGISTRY: NCT04997122, August 8, 2021, retrospectively registered.

Human prefoldin modulates co-transcriptional pre-mRNA splicing.

Prefoldin is a heterohexameric complex conserved from archaea to humans that plays a cochaperone role during the co-translational folding of actin and tubulin monomers. Additional functions of prefoldin have been described, including a positive contribution to transcription elongation and chromatin dynamics in yeast. Here we show that prefoldin perturbations provoked transcriptional alterations across the human genome. Severe pre-mRNA splicing defects were also detected, particularly after serum stimulation. We found impairment of co-transcriptional splicing during transcription elongation, which explains why the induction of long genes with a high number of introns was affected the most. We detected genome-wide prefoldin binding to transcribed genes and found that it correlated with the negative impact of prefoldin depletion on gene expression. Lack of prefoldin caused global decrease in Ser2 and Ser5 phosphorylation of the RNA polymerase II carboxy-terminal domain. It also reduced the recruitment of the CTD kinase CDK9 to transcribed genes, and the association of splicing factors PRP19 and U2AF65 to chromatin, which is known to depend on CTD phosphorylation. Altogether the reported results indicate that human prefoldin is able to act locally on the genome to modulate gene expression by influencing phosphorylation of elongating RNA polymerase II, and thereby regulating co-transcriptional splicing.

Main Colonic Metabolites from Coffee Chlorogenic Acid May Counteract Tumor Necrosis Factor-α-Induced Inflammation and Oxidative Stress in 3T3-L1 Cells.

Obesity is coupled with an altered redox state and low-level inflammation. Oxidative stress may increase pre-adipocyte proliferation, adipocyte differentiation and mature adipocyte size. Regarding inflammation, the dysregulation of cytokine production by adipose tissue takes place in obesity, which is promoted by oxidative stress. Polyphenols may exert a positive effect on obesity, not only by modulating the redox state, but also due to their anti-inflammatory activity. Coffee, which is one of the most consumed beverages, is very rich in phenolic compounds. Bioavailability studies on coffee phenols have shown that the most abundant group of metabolites in plasma and urine are dihydrocaffeic (DHCA), dihydroferulic (DHFA), and hydroxyhippuric (HHA) acids, the three acids of colonic origin. To better understand the antioxidant and anti-inflammatory properties of DHCA, DHFA, and HHA, an inflammation/oxidation model was set up in the pre-adipocyte 3T3-L1 cell line using tumor necrosis factor-α (TNF-α). After the exposure of 3T3-L1 cells to 0.5, 1, 5, and 10 µM of TNF-α at different times, the cell viability, interleukin (IL)-6 secretion, and the production of reactive oxygen species (ROS) and glutathione (GSH) were determined. Using the TNF-α prooxidant and proinflammatory conditions established (10 µM, 24 h), it was observed that the physiological concentrations (0.5, 1, 5, and 10 µM) of DHCA, DHFA, and HHA induced dose-dependent antioxidant effects according to the ROS, GSH, and antioxidant enzyme (glutathione peroxidase) results. In addition, reductions in the IL-1ß, IL-6, and monocyte chemoattractant protein-1 (MCP-1) concentrations were observed to different extents depending on the metabolite (DHFA, HHA, or DHCA) and the concentration used. In conclusion, the main colonic metabolites from coffee chlorogenic acids may counteract TNF-α-induced inflammation and oxidative stress in the 3T3-L1 cell line, and thus, they present antiobesity potential.

Early onset of immune-mediated diseases in minority ethnic groups in the UK.

BACKGROUND: The prevalence of some immune-mediated diseases (IMDs) shows distinct differences between populations of different ethnicities. The aim of this study was to determine if the age at diagnosis of common IMDs also differed between different ethnic groups in the UK, suggestive of distinct influences of ethnicity on disease pathogenesis. METHODS: This was a population-based retrospective primary care study. Linear regression provided unadjusted and adjusted estimates of age at diagnosis for common IMDs within the following ethnic groups: White, South Asian, African-Caribbean and Mixed-race/Other. Potential disease risk confounders in the association between ethnicity and diagnosis age including sex, smoking, body mass index and social deprivation (Townsend quintiles) were adjusted for. The analysis was replicated using data from UK Biobank (UKB). RESULTS: After adjusting for risk confounders, we observed that individuals from South Asian, African-Caribbean and Mixed-race/Other ethnicities were diagnosed with IMDs at a significantly younger age than their White counterparts for almost all IMDs. The difference in the diagnosis age (ranging from 2 to 30 years earlier) varied for each disease and by ethnicity. For example, rheumatoid arthritis was diagnosed at age 49, 48 and 47 years in individuals of African-Caribbean, South Asian and Mixed-race/Other ethnicities respectively, compared to 56 years in White ethnicities. The earlier diagnosis of most IMDs observed was validated in UKB although with a smaller effect size. CONCLUSION: Individuals from non-White ethnic groups in the UK had an earlier age at diagnosis for several IMDs than White adults.

Fractal Analysis: Prognostic Value of Left Ventricular Trabecular Complexity Cardiovascular MRI in Participants with Hypertrophic Cardiomyopathy.

Background The prognostic value of myocardial trabecular complexity in patients with hypertrophic cardiomyopathy (HCM) is unknown. Purpose To explore the prognostic value of myocardial trabecular complexity using fractal analysis in participants with HCM. Materials and Methods The authors prospectively enrolled participants with HCM who underwent 3.0-T cardiovascular MRI from August 2011 to October 2017. The authors also enrolled 100 age- and sex-matched healthy participants to form a comparison group. Trabeculae were quantified with fractal analysis of cine slices to estimate the fractal dimension (FD). Participants with HCM were divided into normal and high FD groups according to the upper limit of normal reference value from the healthy group. The primary end point was defined as all-cause mortality and aborted sudden cardiac death. The secondary end point was the composite of the primary end point and readmission to the hospital owing to heart failure. Internal validation was performed using the bootstrapping method. Results A total of 378 participants with HCM (median age, 50 years; age range, 40-61 years; 207 men) and 100 healthy participants (median age, 46 years; age range, 36-59 years; 55 women) were included in this study. During the median follow-up of 33 months ± 18 (standard deviation), the increased maximal apical FD (≥1.325) had a higher risk of the primary and secondary end points than those with a normal FD (<1.325) (P = .01 and P = .04, respectively). Furthermore, Cox analysis revealed that left ventricular maximal apical FD (hazard ratio range, 1.001-1.008; all P < .05) provided significant prognostic value to predict the primary and secondary end points after adjustment for the European Society of Cardiology predictors and late gadolinium enhancement. Internal validation showed that left ventricular maximal apical FD retained a good performance in predicting the primary end points with an area under the curve of 0.70 ± 0.03. Conclusion Left ventricular apical fractal dimension, which reflects myocardial trabecular complexity, was an independent predictor of the primary and secondary end points in patients with hypertrophic cardiomyopathy. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Captur and Moon in this issue.

Acid exposure disrupts mucus secretion and impairs mucociliary transport in neonatal piglet airways.

Tenacious mucus produced by tracheal and bronchial submucosal glands is a defining feature of several airway diseases, including cystic fibrosis (CF). Airway acidification as a driving force of CF airway pathology has been controversial. Here we tested the hypothesis that transient airway acidification produces pathologic mucus and impairs mucociliary transport. We studied pigs challenged with intra-airway acid. Acid had a minimal effect on mucus properties under basal conditions. However, cholinergic stimulation in acid-challenged pigs revealed retention of mucin 5B (MUC5B) in the submucosal glands, decreased concentrations of MUC5B in the lung lavage fluid, and airway obstruction. To more closely mimic a CF-like environment, we also examined mucus secretion and transport following cholinergic stimulation under diminished bicarbonate and chloride transport conditions ex vivo. Under these conditions, airways from acid-challenged pigs displayed extensive mucus films and decreased mucociliary transport. Pretreatment with diminazene aceturate, a small molecule with ability to inhibit acid detection through blockade of the acid-sensing ion channel (ASIC) at the doses provided, did not prevent acid-induced pathologic mucus or transport defects but did mitigate airway obstruction. These findings suggest that transient airway acidification early in life has significant impacts on mucus secretion and transport properties. Furthermore, they highlight diminazene aceturate as an agent that might be beneficial in alleviating airway obstruction.

Airway cholinergic history modifies mucus secretion properties to subsequent cholinergic challenge in diminished chloride and bicarbonate conditions.

NEW FINDINGS: What is the central question of this study? What is the impact of airway cholinergic history on the properties of airway mucus secretion in a cystic fibrosis-like environment? What is the main finding and its importance? Prior cholinergic challenge slightly modifies the characteristics of mucus secretion in response to a second cholinergic challenge in a diminished bicarbonate and chloride transport environment. Such modifications might lead to retention of mucus on the airway surface, thereby potentiating exacerbations of airway disease. ABSTRACT: Viral infections precipitate exacerbations in many airway diseases, including asthma and cystic fibrosis. Although viral infections increase cholinergic transmission, few studies have examined how cholinergic history modifies subsequent cholinergic responses in the airway. In our previous work, we found that airway resistance in response to a second cholinergic challenge was increased in young pigs with a history of airway cholinergic stimulation. Given that mucus secretion is regulated by the cholinergic nervous system and that abnormal airway mucus contributes to exacerbations of airway disease, we hypothesized that prior cholinergic challenge would also modify subsequent mucus responses to a secondary cholinergic challenge. Using our established cholinergic challenge-rechallenge model in pigs, we atomized the cholinergic agonist bethanechol or saline control to pig airways. Forty-eight hours later, we removed tracheas and measured mucus secretion properties in response to a second cholinergic stimulation. The second cholinergic stimulation was conducted in conditions of diminished chloride and bicarbonate transport to mimic a cystic fibrosis-like environment. In pigs previously challenged with bethanechol, a second cholinergic stimulation produced a mild increase in sheet-like mucus films; these films were scarcely observed in animals originally challenged with saline control. The subtle increase in mucus films was not associated with changes in mucociliary transport. These data suggest that prior cholinergic history might modify mucus secretion characteristics with subsequent stimulation in certain environmental conditions or disease states. Such modifications and/or more repetitive stimulation might lead to retention of mucus on the airway surface, thereby potentiating exacerbations of airway disease.

Nutritional and other health properties of olive pomace oil.

Olive-pomace oil is rich in oleic acid, and thus it can be an interesting dietary fat alternative as it can allow reaching the recommendation of consuming 20% of total diet energy in the form of monounsaturated fatty acids. In addition, olive-pomace oil also contains a wide range of minor components that may contribute to its healthy properties. The major components identified with healthy properties are triterpenic dialcohols and acids, squalene, tocopherols, sterols, fatty alcohols and phenolic compounds. The refining process, that the crude pomace-oil must undergo for commercial purposes, significantly reduces the content of phenolic compounds, while the other minor components remain at concentrations which can induce positive health effects, especially on cardiovascular health, outstanding pentacyclic triterpenes and aliphatic fatty alcohols in olive-pomace oil. Numerous in vitro and preclinical studies support that mainly the pure compounds, or extracts isolated from plant sources, play an important role in preventing cardiovascular disease and risk factors. Likewise, tocopherols, squalene and phytosterols, in addition to the minor fraction of phenolic compounds, have shown high biological activity with particular association to the cardiovascular function. In the light of the foregoing, and taking into consideration the absence of clinical studies with olive-pomace oil, it would be of great interest to develop randomized, crossover, controlled, double-blind studies to extend the knowledge and understanding on the health effects of olive-pomace olive.

Functional Contributions of Prefoldin to Gene Expression.

Prefoldin is a co-chaperone that evolutionarily originates in archaea, is universally present in all eukaryotes and acts as a co-chaperone by facilitating the supply of unfolded or partially folded substrates to class II chaperonins. Eukaryotic prefoldin is known mainly for its functional relevance in the cytoplasmic folding of actin and tubulin monomers during cytoskeleton assembly. However, the role of prefoldin in chaperonin-mediated folding is not restricted to cytoskeleton components, but extends to both the assembly of other cytoplasmic complexes and the maintenance of functional proteins by avoiding protein aggregation and facilitating proteolytic degradation. Evolution has favoured the diversification of prefoldin subunits, and has allowed the so-called prefoldin-like complex, with specialised functions, to appear. Subunits of both canonical and prefoldin-like complexes have also been found in the nucleus of yeast and metazoan cells, where they have been functionally connected with different gene expression steps. Plant prefoldin has also been detected in the nucleus and is physically associated with a gene regulator. Here we summarise information available on the functional involvement of prefoldin in gene expression, and discuss the implications of these results for the relationship between prefoldin structure and function.

Defective histone supply causes changes in RNA polymerase II elongation rate and cotranscriptional pre-mRNA splicing.

RNA polymerase II (RNAPII) transcription elongation is a highly regulated process that greatly influences mRNA levels as well as pre-mRNA splicing. Despite many studies in vitro, how chromatin modulates RNAPII elongation in vivo is still unclear. Here, we show that a decrease in the level of available canonical histones leads to more accessible chromatin with decreased levels of canonical histones and variants H2A.X and H2A.Z and increased levels of H3.3. With this altered chromatin structure, the RNAPII elongation rate increases, and the kinetics of pre-mRNA splicing is delayed with respect to RNAPII elongation. Consistent with the kinetic model of cotranscriptional splicing, the rapid RNAPII elongation induced by histone depletion promotes the skipping of variable exons in the CD44 gene. Indeed, a slowly elongating mutant of RNAPII was able to rescue this defect, indicating that the defective splicing induced by histone depletion is a direct consequence of the increased elongation rate. In addition, genome-wide analysis evidenced that histone reduction promotes widespread alterations in pre-mRNA processing, including intron retention and changes in alternative splicing. Our data demonstrate that pre-mRNA splicing may be regulated by chromatin structure through the modulation of the RNAPII elongation rate.

A Comprehensive Characterisation of Rosemary tea Obtained from Rosmarinus officinalis L. Collected in a sub-Humid Area of Tunisia.

INTRODUCTION: Rosemary (Rosmarinus officinalis L.) is an aromatic plant common in Tunisia and it is widely consumed as a tea in traditional cuisine and in folk medicine to treat various illnesses. Currently, most research efforts have been focused on rosemary essential oil, alcoholic and aqueous extracts, however, little is reported on rosemary infusion composition. OBJECTIVE: To investigate compounds present in rosemary tea obtained from Rosmarinus officinalis L. collected in a sub-humid area of Tunisia in order to assess whether the traditional rosemary tea preparation method could be considered as a reference method for rosemary's compounds extraction. METHODOLOGY: Qualitative characterisation of Rosmarinus officinalis tea obtained after rosemary infusion in boiled water was determined by high performance liquid chromatography coupled with electrospray ionisation quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF-MS). Quantitative analysis relies on high performance liquid chromatography with diode array detector (HPLC-DAD). RESULTS: Forty-nine compounds belonging to six families, namely flavonoids, phenolic acids, phenolic terpenes, jasmonate, phenolic glycosides, and lignans were identified. To the best of the authors' knowledge eucommin A is characterised for the first time in rosemary. Rosmarinic acid (158.13 µg/g dried rosemary) was the main compound followed then by feruloylnepitrin (100.87 µg/g) and luteolin-3'-O-(2″-O-acetyl)-ß-d-glucuronide (44.04 µg/g). Among quantified compounds, luteolin-7-O-rutinoside was the compound with the lowest concentration. CONCLUSION: The infusion method allows several polyphenols present in rosemary tea to be extracted, therefore it could be a reference method for rosemary's compounds extraction. Moreover, traditional Tunisian Rosmarinus officinalis tea consumption is of interest for its rich phenolic content. Copyright © 2017 John Wiley & Sons, Ltd.

Polyphenol content, in vitro bioaccessibility and antioxidant capacity of widely consumed beverages.

BACKGROUND: Beverages prepared from antioxidant-rich plants are sources of polyphenols, the bioactivity of which depends on bioaccessibility in the gastrointestinal tract. This work evaluated the polyphenol content and antioxidant capacity of widely consumed beverages such as chamomile tea, yerba mate, a coffee blend (65% roasted: 35% green), and coffee-like substitutes such as chicory, malt and a soluble cereal mixture. Additionally, the bioaccessibility of the two beverages with the highest antioxidant capacity was evaluated using an in vitro digestion model. RESULTS: Total phenolic content ranged from 11.15 mg 200 mL-1 in chamomile tea, up to 154.53 mg 200 mL-1 in mate or 215.05 mg 200 mL-1 in the blend. These results correlated with the antioxidant capacity analysed by ferric reducing antioxidant power, oxygen radical scavenging capacity and 2,2'-azinobis-3-ethylbenzothiazoline-6-sulphonic acid methods. Yerba mate and the coffee blend showed an average polyphenol recovery after in vitro gastrointestinal digestion of 57% and 78%, respectively. Although both beverages showed similar phenolic composition, polyphenols in coffee were more stable than in yerba mate. Alkaline pH in the intestinal digestion stage was responsible for the observed reduction in polyphenol stability. CONCLUSION: Regular consumption of the studied beverages provides considerable amounts of antioxidants which are relatively stable after simulated digestion, and thus have the potential to prevent oxidative stress-related disorders. © 2017 Society of Chemical Industry.

Bioavailability and metabolism of rosemary infusion polyphenols using Caco-2 and HepG2 cell model systems.

BACKGROUND: Rosmarinus officinalis is an aromatic plant used in folk medicine as a result of the therapeutic properties associated with its phenolic composition, being rich in rosmarinic acid (RA) and caffeic acid (CA). To better understand the bioactivity of these compounds, their absorption and metabolism were assessed in human Caco-2 and HepG2 cells, as small intestine and liver models, respectively, using RA and CA standards, as well as a rosemary infusion and ferulic acid (FA). RESULTS: Test compounds were partially up-taken and metabolized by Caco-2 and HepG2 cells, although a higher metabolization rate was observed after hepatic incubation compared to intestinal incubation. CA was the compound best absorbed followed by RA and FA, showing metabolites percentages of 30.4%, 11.8% and 4.4% in Caco-2 and 34.3%, 10.3% and 3.2% in HepG2 cells, respectively. RA in the rosemary infusion showed improved bioavailability compared to pure RA. Methyl derivatives were the main metabolites detected for CA and RA after intestinal and hepatic metabolism, followed by methyl-glucuronidates and glucuronidates. RA was also minimally hydrolyzed into CA, whereas FA only was glucuronidated. Rosemary polyphenols followed the same biotransformation pathways as the standards. In addition, phase II derivatives of luteolin were observed. CONCLUSION: Rosemary polyphenols are partially metabolized in both the intestine and liver. © 2018 Society of Chemical Industry.

Effects of in vitro digestion and storage on the phenolic content and antioxidant capacity of a red grape pomace.

Red grape pomace (RGP) is a major winery by-product with interesting applications due to its high phenolic content and antioxidant capacity. Effects of in vitro gastrointestinal digestion and storage on the phenolic content and antioxidant capacity of RGP were studied. RGP polyphenols were stable under stomach-mimicking conditions and more sensitive to small intestine conditions, reducing anthocyanins and flavonols. After 3- and 6-month storage, at either 4 or 25 °C, there were no changes in the total phenolic and condensed tannin content, or antioxidant capacity (evaluated by ABTS, FRAP, ORAC assays); however, after 9 months these parameters decreased. Contrarily, chromatic b* values were higher, thus the samples had more intense red color, which may be related to the increased condensed tannin content. Storage time or temperature induced no changes in microbiological load. RGP preserves high antioxidant capacity after storage and in vitro digestion and thus presents potential as a functional ingredient or nutraceutical.

Synthesis and Antioxidant Activity of Alkyl Nitroderivatives of Hydroxytyrosol.

A series of alkyl nitrohydroxytyrosyl ether derivatives has been synthesized from free hydroxytyrosol (HT), the natural olive oil phenol, in order to increase the assortment of compounds with potential neuroprotective activity in Parkinson's disease. In this work, the antioxidant activity of these novel compounds has been evaluated using Ferric Reducing Antioxidant Power (FRAP), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), and Oxygen Radical Scavenging Capacity (ORAC) assays compared to that of nitrohydroxytyrosol (NO2HT) and free HT. New compounds showed variable antioxidant activity depending on the alkyl side chain length; compounds with short chains (2-4 carbon atoms) maintained or even improved the antioxidant activity compared to NO2HT and/or HT, whereas those with longer side chains (6-8 carbon atoms) showed lower activity than NO2HT but higher than HT.

Regular consumption of a cocoa product improves the cardiometabolic profile in healthy and moderately hypercholesterolaemic adults.

Cocoa products present great health potential due to their high content of polyphenols, mainly of flavanols. However, the antioxidant, anti-inflammatory and other health effects of regularly consuming cocoa products seem to depend on the intake and health status of the consumer, etc. and need to be further clarified. A randomised, controlled, cross-over, free-living study was carried out in healthy (n 24) and moderately hypercholesterolaemic (>2000 mg/l, n 20) subjects to assess the influence of regularly consuming (4 weeks) two servings (15 g each) of a cocoa product rich in fibre (containing 33·9 % of total dietary fibre (TDF) and 13·9 mg/g of soluble polyphenols) in milk v. consuming only milk (control) on (1) serum lipid and lipoprotein profile, (2) serum malondialdehyde levels, carbonyl groups, ferric reducing/antioxidant power, oxygen radical absorbance capacity and free radical-scavenging capacity, (3) IL-1ß, IL-6, TNF-α, IL-10, IL-8, monocyte chemoattractant protein-1, and vascular and intracellular cell adhesion molecule levels, and (4) systolic and diastolic blood pressure and heart rate. Throughout the study, the diet and physical activity of the volunteers, as well as any possible changes in weight or other anthropometric parameters, were also evaluated. The intake of TDF increased (P< 0·001) to the recommended levels. Serum HDL-cholesterol (HDL-C) levels were increased (P< 0·001), whereas glucose (P= 0·029), IL-1ß (P= 0·001) and IL-10 (P= 0·001) levels were decreased. The rest of the studied cardiovascular parameters, as well as the anthropometric ones, remained similar. In conclusion, regularly consuming a cocoa product with milk improves cardiovascular health by increasing HDL-C levels and inducing hypoglycaemic and anti-inflammatory effects in healthy and hypercholesterolaemic individuals without causing weight gain.

An aqueous pomegranate seed extract ameliorates oxidative stress of human hepatoma HepG2 cells.

BACKGROUND: Aqueous pomegranate seed extract (PSE), a by-product of the pomegranate juice industry, was recently identified as a potential antiglycative ingredient. Ellagic acid was proposed as the major polyphenol responsible for the antiglycative activity as exerted in in vitro models. However, there is no information on safety aspects of this extract in biological systems before its application as ingredient. The cytotoxicity of PSE (1-100 µg mL(-1) ) was evaluated by determining its effect on cell viability and redox status of cultured HepG2 cells. The protective effect of the PSE against oxidative stress induced by tert-butyl hydroperoxide (t-BOOH) was also investigated. RESULTS: No changes in cell integrity or intrinsic antioxidant status resulted from a direct treatment with aqueous PSE, even at high dosage. In addition, reactive oxygen species (ROS) induced by t-BOOH were reduced by 21% when cells were pretreated with 100 µg mL(-1) of aqueous PSE at 180 min. The range of concentrations investigated was effective in decreasing the ROS formation but not in a dose-dependent manner. CONCLUSION: Aqueous pomegranate seed extract enhances human hepatoma cells integrity and resistance to cope with a stressful situation at concentration up to 100 µg mL(-1) .

Characterizing Factors Associated with Excess Body Weight: A Descriptive Study Using Principal Component Analysis in a Population with Overweight and Obesity.

Obesity is a worldwide epidemic, making it crucial to understand how it can be effectively prevented/treated. Considering that obesity is a multifactorial condition, this article carried out a baseline cross-sectional study of the variables involved in the disorder. Eighty-four subjects with overweight/obesity were recruited. Dietary baseline information was obtained by analysing three 24 h recalls. Resting metabolic rate was measured using indirect calorimetry, physical activity was measured through accelerometry, cardiometabolic parameters were determined in blood samples and body composition via anthropometry and bioimpedance. A univariant and multivariate exploratory approach was carried out using principal component analysis (PCA). Large inter-individual variability was observed in dietetic, biochemical, and physical activity measurements (coefficient of variation ≥ 30%), but body composition was more uniform. Volunteers had an unbalanced diet and low levels of physical activity. PCA reduced the 26 analysed variables to 4 factors, accounting for 65.4% of the total data variance. The main factor was the "dietetic factor", responsible for 24.0% of the total variance and mainly related to energy intake, lipids, and saturated fatty acids. The second was the "cardiometabolic factor" (explaining 16.8% of the variability), the third was the "adiposity factor" (15.2%), and the last was the "serum cholesterol factor" (9.4%).

Epicatechin gallate induces cell death via p53 activation and stimulation of p38 and JNK in human colon cancer SW480 cells.

The tea flavonoid epicatechin gallate (ECG) exhibits a wide range of biological activities. In this study, the in vitro anticancer effects of ECG on SW480 colon cancer cell line was investigated by analyzing the cell cycle, apoptosis, key proteins involved in cellular survival/proliferation, namely AKT/phosphatidylinositol-3-kinase (PI3K) and mitogen-activated protein kinases (MAPKs), and the role of p53 in these processes. ECG induced cell cycle arrest at the G0/G1-S phase border associated with the stimulation of p21, p-p53, and p53 and the suppression of cyclins D1 and B1. Exposure of SW480 cells to ECG also led to apoptosis as determined by time-dependent changes in caspase-3 activity, MAPKs [extracellular regulated kinase (ERK), p38, and c-jun amino-terminal kinase (JNK)], p21 and p53 activation, and AKT inhibition. The presence of pifithrin, an inhibitor of p53 function, blocked ECG-induced apoptosis as was manifested by restored cell viability and caspase-3 activity to control values and reestablished the balance among Bcl-2 anti- and proapoptotic protein levels. Interestingly, ECG also inhibited p53 protein and RNA degradation, contributing to the stabilization of p53. In addition, JNK and p38 have been identified as necessary for ECG-induced apoptosis, upon activation by p53. The results suggest that the activation of the p53-p38/JNK cascade is required for ECG-induced cell death in SW480 cells.

Cocoa polyphenols prevent inflammation in the colon of azoxymethane-treated rats and in TNF-α-stimulated Caco-2 cells.

Numerous lines of evidence support a relationship between intestinal inflammation and cancer. Therefore, much attention has recently been focused on the identification of natural compounds with anti-inflammatory activities as a strategy to suppress the early stages of colorectal cancer. Because cocoa is a rich source of bioactive compounds, the present study investigated its anti-inflammatory properties in a rat model of azoxymethane (AOM)-induced colon carcinogenesis and in TNF-α-stimulated Caco-2 cells. A total of forty male rats were fed with control or cocoa-enriched diets (12 %) during 8 weeks and injected with saline or AOM (20 mg/kg body weight) during the third and fourth week (n 10 rats/group). At the end of the experiment, colon samples were evaluated for markers of inflammation. The anti-inflammatory activity of a cocoa polyphenolic extract (10 µg/ml) was examined in TNF-α-stimulated Caco-2 cells, an in vitro model of experimentally induced intestinal inflammation. The signalling pathways involved, including NF-κB and the mitogen-activated protein kinase family such as c-Jun NH2-terminal kinases (JNK), extracellular signal-regulated kinases and p38, were also evaluated. The results show that the cocoa-rich diet decreases the nuclear levels of NF-κB and the expression of pro-inflammatory enzymes such as cyclo-oxygenase-2 and inducible NO synthase induced by AOM in the colon. Additionally, the experiments in Caco-2 cells confirm that cocoa polyphenols effectively down-regulate the levels of inflammatory markers induced by TNF-α by inhibiting NF-κB translocation and JNK phosphorylation. We conclude that cocoa polyphenols suppress inflammation-related colon carcinogenesis and could be promising in the dietary prevention of intestinal inflammation and related cancer development.