Molecular Pathways of Rosmarinic Acid Anticancer Activity in Triple-Negative Breast Cancer Cells: A Literature Review.

Breast cancer is the most frequent type of cancer in women. Oncogenic transcription factors promote the overproduction of cellular adhesion molecules and inflammatory cytokines during cancer development. Cancer cells exhibit significant upregulation of antiapoptotic proteins, resulting in increased cell survival, tumor growth, and metastasis. Research on the cell cycle-mediated apoptosis pathway for drug discovery and therapy has shown promising results. In fact, dietary phytoconstituents have been extensively researched for anticancer activity, providing indirect protection by activating endogenous defense systems. The role of polyphenols in key cancer signaling pathways could shed light on the underlying mechanisms of action. For instance, Rosmarinic Acid, a polyphenol constituent of many culinary herbs, has shown potent chemoprotective properties. In this review, we present recent progress in the investigation of natural products as potent anticancer agents, with a focus on the effect of Rosmarinic Acid on triple-negative BC cell lines resistant to hormone therapy. We highlight a variety of integrated chemical biology approaches aimed at utilizing relevant mechanisms of action that could lead to significant clinical advances in BC treatment.

Postprandial Bioactivity of a Spread Cheese Enriched with Mountain Tea and Orange Peel Extract in Plasma Oxidative Stress Status, Serum Lipids and Glucose Levels: An Interventional Study in Healthy Adults.

Postprandial lipemia, glycemia and oxidative stress may affect the occurrence of cardiovascular disease. The purpose of the present intervention study was to investigate the effect of a spread cheese enriched with mountain tea (Sideritis sp.) and orange peel (Citrus sinensis) extract on postprandial metabolic biomarkers in healthy volunteers. In a cross-over design, 14 healthy subjects 20-30 years old were consumed either a meal rich in fat and carbohydrates (80 g white bread, 40 g butter and 30 g full fat spread cheese) or a meal with the spread cheese enriched with 6% mountain tea-orange peel extract. Differences in postprandial total plasma antioxidant capacity, resistance of plasma to oxidation, serum lipids, glucose and uric acid levels were evaluated at 0, 1.5 and 3 h after consumption. Plasma total antioxidant capacity was significantly increased 3 h after the consumption of the meal in the presence of the extract-enriched cheese, compared to the conventional cheese (p = 0.05). Plasma resistance to oxidation was increased at 30 min in the Functional meal compared with the Control meal. A tendency to decrease the postprandial rise in glucose and triglyceride levels, 1.5 h and 3 h, respectively, after the intake of the meal with the extract-enriched cheese was observed (p = 0.062). No significant changes in the concentrations of the remaining biomarkers studied were observed (p > 0.05). Further studies with a larger sample are needed in both healthy adults and patients with cardiovascular disease to draw safer conclusions about the postprandial effect of the extracts on metabolic biomarkers that predict cardiovascular risk.

Micronutrient dietary intakes and their food sources in adults: the Hellenic National Nutrition and Health Survey (HNNHS).

BACKGROUND: The present study aimed to assess micronutrient intake among Greek adults and to identify the main food sources that contribute to it. METHODS: Food consumption data from 2389 participants in the Hellenic National Nutrition and Health Survey (HNNHS), collected with 24-h recalls, was used to calculate micronutrient intakes. Usual nutrient intake was estimated according to the National Cancer Institute method. Nutrient adequacy was estimated using the estimated average requirement (EAR) cut-point method, when available, or adequate intake otherwise. The probability approach was used to determine iron intake adequacy in females of reproductive age. Food group contribution for each nutrient assessed was derived to identify their main food sources. RESULTS: Almost all individuals had vitamin D intake below EAR, whereas vitamins A, E, K and C, as well as potassium intake, were also insufficient in a considerable percentage of the population (>70% in most age groups). Calcium intake was substantially below the EAR for females aged >50 years and males >70 years; the same for magnesium in males >70 years. Furthermore, 50% of females, including those of reproductive age, had intake of folate below EAR. More than 50% of the population (to 79%) exceeded the upper tolerable limit for sodium (2300 mg day-1 ). Food contribution analysis revealed that most vitamins were derived from low-quality foods (i.e. fast-food). CONCLUSIONS: A significant proportion of adults residing in Greece have low nutrient intake and poor food selections. These results provide guidance to public health policy makers for developing strategies to improve the dietary quality in Greece.

Microbial Diversity of Fermented Greek Table Olives of Halkidiki and Konservolia Varieties from Different Regions as Revealed by Metagenomic Analysis.

Current information from conventional microbiological methods on the microbial diversity of table olives is insufficient. Next-generation sequencing (NGS) technologies allow comprehensive analysis of their microbial community, providing microbial identity of table olive varieties and their designation of origin. The purpose of this study was to evaluate the bacterial and yeast diversity of fermented olives of two main Greek varieties collected from different regions-green olives, cv. Halkidiki, from Kavala and Halkidiki and black olives, cv. Konservolia, from Magnesia and Fthiotida-via conventional microbiological methods and NGS. Total viable counts (TVC), lactic acid bacteria (LAB), yeast and molds, and Enterobacteriaceae were enumerated. Microbial genomic DNA was directly extracted from the olives' surface and subjected to NGS for the identification of bacteria and yeast communities. Lactobacillaceae was the most abundant family in all samples. In relation to yeast diversity, Phaffomycetaceae was the most abundant yeast family in Konservolia olives from the Magnesia region, while Pichiaceae dominated the yeast microbiota in Konservolia olives from Fthiotida and in Halkidiki olives from both regions. Further analysis of the data employing multivariate analysis allowed for the first time the discrimination of cv. Konservolia and cv. Halkidiki table olives according to their geographical origin.

Micronutrient intakes and their food sources among Greek children and adolescents.

OBJECTIVE: To assess the usual dietary intake of twenty micronutrients and to identify their food sources in a representative sample of Greek children and adolescents. DESIGN: Cross-sectional data from the Hellenic National Nutrition and Health Survey (HNNHS). Vitamin and mineral intakes were estimated from two 24 h dietary recalls by sex and age groups. Estimates were calculated using the National Research Council method and the statistical software package Stata13 to account for within- and between-person variations. The prevalence of nutrients' inadequacy among sample was estimated using the estimated average requirement (EAR) cut-point method. The contribution of food groups to nutrient intake was estimated to identify micronutrients food sources. SETTING: Greece. PARTICIPANTS: Children and adolescents aged 1-19 years (n 577) who provided sufficient and plausible 24-h recalls. RESULTS: A substantial percentage of children and adolescents had insufficient intakes of numerous micronutrients. Usual intake of vitamins D, K and potassium was inadequate in practically all individuals. Vitamin A, folate, Ca and Mg were also insufficient to a considerable percentage, especially in girls aged 14-18 years. Pantothenic acid was highlighted as nutrient of interest since only one out of ten boys 9-13 years and girls 14-19 years had intake above the EAR. Data demonstrated that food groups highly ranked in energy contribution were not necessarily important sources of micronutrients. CONCLUSIONS: Results suggest that micronutrient density of Greek children and adolescents' diet should be improved. These findings might be used by public health policy-makers to help young people optimise their food choices in Greece.

Dietary patterns and cardiovascular disease in Greek adults: The Hellenic National Nutrition and Health Survey (HNNHS).

BACKGROUND AND AIMS: Empirically-derived dietary patterns have been shown to have both positive and adverse associations with cardiovascular disease (CVD). Yet, such associations remain unclear in the Greek population. The aim of this study was to investigate the association between empirically-derived dietary patterns and the presence of CVD and CVD-related medical conditions in a nationally representative sample of Greek adults. METHODS AND RESULTS: Adult participants (≥20 years old) of the Hellenic National Nutrition and Health Survey (HNNHS) were included (N = 3552; 41.2% men; 43.7 years, SD: 18.1). Dietary patterns were derived by principal component analysis using 24-h recall data. The presence of dyslipidemia (elevated cholesterol and/or triglycerides), hypertension, coronary heart disease, and total CVD, was defined according to the International Clinical Diagnosis (ICD)-10 codes. Odds ratios of CVD outcomes were estimated across dietary patterns using multivariable logistic regression analysis. Three dietary patterns -Traditional (proxy Mediterranean), Western, and Prudent-were identified explaining 16.5% of the total variance in consumption. Logistic regression analysis, adjusted for age, sex, total caloric intake, sociodemographic characteristics, and other CVD risk factors, showed an inverse association between the Traditional dietary pattern and CVD presence (OR: 0.53; 95% CI: 0.30-0.95), and a positive association between the Western pattern and dyslipidemia (1.52; 1.02-2.26). No association was found between the Prudent pattern and CVD outcomes. CONCLUSION: The variability of food intake combinations in the Greek population seem to be associated with the presence of CVD and CVD related conditions. Such findings are imperative for national monitoring and informed priority setting.

Association of serum vitamin D status with dietary intake and sun exposure in adults.

BACKGROUND & AIMS: Serum 25(OH)D deficiency is becoming an epidemic. The aim was to assess vitamin D status of the adult Greek population in relation to intake, sun exposure and other factors, using data from the Hellenic National Nutrition and Health Survey (HNNHS). METHODS: Data from 1084 adult participants (37.8% males) were analyzed. Vitamin D intake was assessed using 24-h recalls. Serum 25(OH)D concentration was evaluated and related to anthropometric measurements and other covariates including supplements used, by sex. Variables significantly associated with 25(OH)D < 20 ng/ml were assessed using simple and multiple logistic regression. RESULTS: Median vitamin D intake from food was 1.23 mcg/day (0.60, 2.44), with 9.1% consuming supplements. Median serum 25(OH)D was 16.72 ng/ml, with no sex differences (P = 0.923). The odds of having 25(OH)D < 20 ng/ml significantly decreased with being very active (OR 0.55, 95% CI 0.35, 0.98), increasing length of sun exposure [1-3 h/day (OR 0.59, 95% CI 0.44, 0.80), >3 h/day (OR 0.36, 95% CI 0.24, 0.55)], and skin colour [light to medium skin (OR 0.47, 95% CI 0.24, 0.91), fairly dark skin colour (OR 0.34, 95% CI 0.17, 0.67) and dark or very dark skin colour (OR 0.34, 95% CI 0.15, 0.75)], compared to respective baseline levels. The odds significantly increased with obesity (OR 1.95, 95% CI 1.24, 3.08), and spring season of blood sample collection (OR 1.75, 95% CI 1.22, 2.50). CONCLUSIONS: Vitamin D deficiency is highly prevalent in Greek adults. Relevant public health policies are highly recommended, which could include vitamin D fortification. and suggestion for increased but safe sun exposure.

Bioactivity of Epigallocatechin Gallate Nanoemulsions Evaluated in Mice Model.

The hypothesis that incorporation of epigallocatechin gallate (EGCG) into nanoemulsions may increase its bioactivity compared with EGCG aqueous solutions was examined in mice. After an in vitro study in a model system with stimulated gastrointestinal conditions, the following EGCG nanoemulsions were used in a mice experiment: Emulsion I: emulsion water in oil (W/O), which contained 0.23 mg/mL EGCG in aqueous phase; Emulsion II: emulsion oil in water (O/W), which contained 10% olive oil and 0.23 mg/mL esterified EGCG in fatty phase; and Emulsion III: emulsion O/W in water (W1/O/W2; 8:32:60), which contained 32% olive oil and 0.23 mg/mL EGCG in aqueous phase. After 2 h of mice administration by gavage with 0.1 mL of EGCG nanoemulsions, total antioxidant capacity (TAC) of plasma and some tissues (especially colon, jejunum, heart, spleen) was measured with Ferric-Reducing Antioxidant Power (FRAP) and Oxygen Radical Absorbance Capacity (ORAC) assays. No toxic effects were observed after administration of 0.23 mg/mL esterified EGCG in CD1 mouse strain. The study concluded that administration of mice with the three EGCG nanoemulsions did not increase their TAC in specific tissues, compared with an aqueous EGCG solution at the same concentration. Nevertheless, the esterified EGCG emulsion (Emulsion II) exerted an increase in mice plasma compared with aqueous EGCG and showed higher values of TAC in several tissues, compared with Emulsions I and III. EGCG nanoemulsions could be considered a useful method in plethora functional food applications, but further research is required for safer results.

The effect of iron and fat in a diet containing green tea extract (Camellia sinensis) on the antioxidant capacity of some organs and the mRNA expression of specific genes in mice.

The hypothesis that iron and fat in the diet may affect green tea extract (GTE) bioactivity, in particular antioxidant capacity and gene expression, was proposed and tested in mice. Thirty mice were randomly assigned to have for 37 days free access to standard or high-fat diets with or without GTE and ferrous lactate. Mice were euthanized and specific organs were removed. Total antioxidant capacity (TAC) was measured using the ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity assays. Polymerase chain reaction was performed on liver and heart mRNA extracts. The FRAP assay showed that GTE from the standard diet did not affect plasma TAC but increased TAC of heart, aorta, and duodenum. GTE from diets enriched with iron resulted to lower TAC of liver and heart than diets with GTE alone. GTE from the fatty diet did not have any effect on TAC compared with fatty control diet, but increased TAC in heart and aorta compared with standard control diet. An effect on expression of the mapk-1 and NF-kB genes in heart was observed in the presence of GTE. These results suggest that GTE may exhibit bioactivity in some organs affected by dietary fat and iron. The findings of this study contribute to the elucidation of the role of dietary components on tea bioactivity.

Dessert formulation using sucralose and dextrin affects favorably postprandial response to glucose, insulin, and C-peptide in type 2 diabetic patients.

BACKGROUND: Dessert compositions may conform to diabetic diet when it contains low sugar or artificial sweetener to replace sugar. However, it is still questionable whether glycemic control in type 2 diabetes patients is improved by the use of diet-conforming dessert compositions. OBJECTIVE: To compare, in type 2 diabetes patients, the glycemic, insulin, and C-peptide responses to seven modified dessert compositions for diabetics (D-dessert) with the response to seven similar desserts of non-modified composition, used as control desserts (C-dessert). METHODS: Seventy type 2 diabetes patients were allocated to seven groups of ten. On three occasions, each patient received either the meal which consisted of bread and cheese, or the meal and D-dessert, or the meal and the respective C-dessert. Differences in postprandial glucose, insulin, and C-peptide were evaluated using analysis of repeated measures at 0, 30, 60, 90, and 120 min after consumption. RESULTS: D-cake and D-pastry cream resulted in lower glucose levels (8.81 ± 0.32 mmol/l and 8.67 ± 0.36 mmol/l, respectively) and D-strawberry jelly in lower insulin levels (16.46 ± 2.66 µU/ml) than the respective C-desserts (9.99 ± 0.32 mmol/l for C-cake, 9.28 ± 0.36 mmol/l for C-pastry cream, and 27.42 ± 2.66 µU/ml for C-strawberry jelly) (p < 0.05). Compared with the meal, D-cake did not increase glucose or insulin levels (p < 0.05), while C-cake did (p < 0.05). D-pastry cream increased glucose to a lesser extent than C-pastry cream (p < 0.05). Similar effects were reported for D-milk dessert, D-millefeuille, and D-chocolate on glucose, insulin, and C-peptide at specific timepoints. D-crème caramel showed no effect. CONCLUSIONS: Some desserts formulated with sugar substitutes and soluble fiber may have a favorable effect on postprandial levels of glucose, insulin, and C-peptide in type 2 diabetic patients.

Milk peptides increase iron dialyzability in water but do not affect DMT-1 expression in Caco-2 cells.

In vitro digestion of milk produces peptide fractions that enhance iron uptake by Caco-2 cells. The objectives of this study were to investigate whether these fractions (a) exert their effect by increasing relative gene expression of DMT-1 in Caco-2 cells and (b) enhance iron dialyzability when added in meals. Two milk peptide fractions that solubilize iron were isolated by Sephadex G-25 gel filtration of a milk digest. These peptide fractions did not affect relative gene expression of DMT-1 when incubated with Caco-2 cells for 2 or 48 h. Dialyzability was measured after in vitro simulated gastric and pancreatic digestion. Both peptide fractions enhanced the dialyzability of iron from ferric chloride added to PIPES buffer, but had no effect on dialyzability from milk or a vegetable or fruit meal after in vitro simulated gastric and pancreatic digestion. However, dialyzability from milk was enhanced by the addition of a more concentrated lyophilized peptide fraction.

Green tea, white tea, and Pelargonium purpureum increase the antioxidant capacity of plasma and some organs in mice.

OBJECTIVE: We tested in mice the hypothesis that ingestion of infusions of green tea, white tea, or the aromatic plant Pelargonium purpureum increases total antioxidant capacity (TAC) of plasma and organs. METHODS: Twenty-five mice were randomly assigned to five groups, each of which received by gavage 0.1 mL of infusion from green tea, white tea, or P. purpureum (8 g/100 mL of water) or catechin (0.01 g/100 mL) or water for 5 consecutive days. On the fifth day the animals were euthanized. Blood was taken by heart puncture and the heart, lungs, liver, spleen, kidney, and brain were removed. TAC was measured in plasma and in all organ homogenates with the ferric reducing antioxidant power assay and in selected organ homogenates by the total radical-trapping antioxidant parameter assay. RESULTS: Green tea and P. purpureum increased TAC in the plasma and lungs, whereas green tea, white tea, and catechin increased TAC in heart homogenates. No effect was observed on the liver, brain, spleen, and kidney homogenates in comparison with the water control with the ferric reducing antioxidant power assay or the total radical-trapping antioxidant parameter assay. CONCLUSION: These results suggest that green tea, white tea, and P. purpureum exhibit antioxidant effects in vivo that may be observed not only in plasma but also in some organs.

Peptides isolated from in vitro digests of milk enhance iron uptake by caco-2 cells.

Milk proteins, during digestion, produce a range of biologically active peptides. Among those are peptides that may enhance iron absorption. The objective of this project was to investigate the effect of isolated milk peptides on iron uptake. Cow's milk, 0% fat, was subjected to a modified in vitro digestion process. The milk digest was further fractionated by gel filtration. All eluted fractions as well as beta-casein synthetic peptides (a tripeptide and a hexapeptide) were subsequently tested for effects on iron uptake with Caco-2 cell monolayers. Fractions of milk digests obtained through Sephadex G-25 gel filtration had a significant enhancing effect on iron uptake in Caco-2 cells compared to nonfractionated milk digests. Two fractions (P = 0) and the hexapeptide (P < 0.0001) enhanced iron uptake by up to 3-fold, whereas others and the tripeptide had no effect. These results suggest that selected peptides produced during the in vitro digestion of milk may enhance iron absorption; however, it remains to be demonstrated whether this effect may be nutritionally significant.

Phenolic compounds in red wine digested in vitro in the presence of iron and other dietary factors.

Quantitative and qualitative changes in the phenolic composition of red wine may occur during digestion in the lumen, particularly when other dietary components are present. In this study, mixtures of red wine, iron, and ascorbic acid, meat or casein were subjected to a simulated gastrointestinal digestion. This process involves incubation of samples for 4.5 h at 37 degrees C, at different pH values, in the presence of peptic enzymes and fractionation of digests through a dialysis membrane with a molecular weight cut-off of 6000-8000. Selected phenolic compounds were determined in undigested samples and in their dialysable digests by reversed-phase high-performance liquid chromatography. A dramatic decrease in the concentration of the selected phenolic compounds was observed in all samples after they were digested in vitro. Moreover, when iron and/or protein were added to red wine samples, changes in the phenolic profile of the undigested and of the in vitro digested samples were detected. These results suggest that interactions between red wine phenolic compounds and iron, protein and/or digestion components are important determinants of the physicochemical properties and the concentration of these phenolic compounds in the lumen. The in vitro methodology employed herein offers a tool for the study of phenolic compounds under conditions of simulated gastrointestinal digestion, incorporating lumenal events that may affect phenolic compounds.