Dietary flavonoids: Nano delivery and nanoparticles for cancer therapy.

Application of nanotechnologies to cancer therapy might increase solubility and/or bioavailability of bioactive compounds of natural or synthetic origin and offers other potential benefits in cancer therapy, including selective targeting. In the present review we aim to evaluate in vivo studies on the anticancer activity of nanoparticles (NPs) obtained from food-derived flavonoids. From a systematic search a total of 60 studies were identified. Most of the studies involved the flavanol epigallocatechin-3-O-gallate and the flavonol quercetin, in both delivery and co-delivery (with anti-cancer drugs) systems. Moreover, some studies investigated the effects of other flavonoids, such as anthocyanins aglycones anthocyanidins, flavanones, flavones and isoflavonoids. NPs inhibited tumor growth in both xenograft and chemical-induced animal models of cancerogenesis. Encapsulation improved bioavailability and/or reduced toxicity of both flavonoids and/or co-delivered drugs, such as doxorubicin, docetaxel, paclitaxel, honokiol and vincristine. Moreover, flavonoids have been successfully applied in molecular targeted nanosystems. Selectivity for cancer cells involves pH- and/or reactive oxygen species-mediated mechanisms. Furthermore, flavonoids are good candidates as drug delivery for anticancer drugs in green synthesis systems. In conclusion, although human studies are needed, NPs obtained from food-derived flavonoids have promising anticancer effects in vivo.

Supplementation with dairy matrices impacts on homocysteine levels and gut microbiota composition of hyperhomocysteinemic mice.

PURPOSE: Several studies highlighted a correlation between folic acid deficiency and high plasma homocysteine concentration, considered a risk factor for multifactorial diseases. Natural folates represent an emerging alternative strategy to supplementation with synthetic folic acid, whose effects are controversial. The present work was, therefore, performed in hyperhomocysteinemic mice to study the impact of supplementation with dairy matrices containing natural folates on plasma homocysteine levels and faecal microbiota composition. METHODS: Forty mice were divided into six groups, two of which fed control or folic acid deficient (FD) diets for 10 weeks. The remaining four groups were fed FD diet for the first 5 weeks and then shifted to a standard control diet containing synthetic folic acid (R) or a FD diet supplemented with folate-enriched fermented milk (FFM) produced by selected lactic acid bacteria, fermented milk (FM), or milk (M), for additional 5 weeks. RESULTS: Supplementation with dairy matrices restored homocysteine levels in FD mice, although impacting differently on hepatic S-adenosyl-methionine levels. In particular, FFM restored both homocysteine and S-adenosyl-methionine levels to the control conditions, in comparison with FM and M. Next generation sequencing analysis revealed that faecal microbiota of mice supplemented with FFM, FM and M were characterised by a higher richness of bacterial species in comparison with C, FD and R groups. Analysis of beta diversity highlighted that the three dairy matrices determined specific, significant variations of faecal microbiota composition, while hyperhomocysteinemia was not associated with significant changes. CONCLUSIONS: Overall, the results represent a promising starting point for the applicability of food matrices enriched in natural folates to manage hyperhomocysteinemia.

The Potential Role of Naringin and Naringenin as Nutraceuticals Against Metabolic Syndrome.

Metabolic syndrome, an increasing problem in western society, is a cluster of conditions that affect cardiovascular health, lipid and glucose management, increasing the risk of heart diseases, stroke and diabetes. Bioactive flavonoids are a great resource of compounds with proven antiinflammatory activities. Naringin, a natural flavanone found in citrus fruits, and its aglycone have demonstrated to ameliorate obesity, dyslipidemia, and insulin resistance in animal models. The principal mechanisms by which these flavonoids exert their action involve AMPK and PPARα up-regulation and the down-regulation of genes involved in lipid metabolism. Although different studies have been carried out to define the pharmacological effects of these flavonoids, their therapeutic use is still limited.

Alcohol Consumption by Italian and Spanish University Students in Relation to Adherence to the Mediterranean Diet and to the Food Neophobia: A Pilot Study.

This work aimed to relate alcohol consumption with adherence to the Mediterranean diet (MD) and with food neophobia (FN) among Italian and Spanish university students. Volunteers (n = 194, 108 Italian and 86 Spanish), recruited at the La Sapienza University of Rome and the Catholic University of Murcia, filled in standardized questionnaires to evaluate alcohol consumption (AUDIT), FN (FN Scale: FNS), and adherence to the MD (MDS-14, MED-55, QueMD). In addition to the previously reported QueMD sub-score (aMED), a sub-score for non-typical MD foods (ntMED, carbonated and/or sugar-sweetened beverages (soft drinks), butter, margarine, or cooking cream, and manufactured sweets, pastries, and cakes) was evaluated. Italian females had higher MED-55 and FNS scores, and a lower AUDIT score than Spaniards (p < 0.01). Students who stayed with their family (resident) were more adherent to MD than those who moved away from home. Resident Italians consumed less beer, hard liquors, and cocktails than Spaniards on Saturday nights (p < 0.01). There were negative correlations between AUDIT and QueMD (R squared: 0.137, p < 0.05), and AUDIT and ntMED (R squared: 0.201, p < 0.01) in Spaniards, however, there was no relationship between AUDIT and other MD scores. In conclusion, this pilot study suggests that non-typical MD foods and Saturday night consumptions, related to being far from home, have a great impact on alcohol consumption.

Overlap of orthorexia, eating attitude and psychological distress in some Italian and Spanish university students.

BACKGROUND: Orthorexia nervosa (ON) is the persistent concern of maintaining the self-imposed diet to improve one's health. Many factors have been associated to ON in univ-ersity students. AIM: To assess the prevalence of ON in Italian and Spanish university students in relation to eating attitude and psychological distress, and the possible overlaps between ON (evaluated with different scored questionnaires from the originally proposed ORTO-15), distress and risk of eating disorders. METHODS: This study was carried out on 160 students recruited at La Sapienza University of Rome and at the Catholic University of Murcia. Questionnaires were administered to evaluate ON (ORTO-15 and sub-scores), body concerns (Multidimensional Body-Self Relations Questionnaire, MBSRQ, and Body Uneasiness test, BUT), psychological distress (Kessler Psychological Distress Scale, K10), physical activity (International Physical Activity Questionnaire, IPAQ), eating attitude (Eating Attitudes Test, EAT-26) and malnutrition (Starvation Symptom Inventory, SSI). Sex differences, within the same country, and differences between Italian and Spanish students, within the same sex, were evaluated. RESULTS: The ORTO-15 positive subjects, assessed with the originally proposed cut-off, were above 70% in both Italian and Spanish students, with a higher prevalence in the Spanish sample (Italian females 76.3%, Italian males 70.7%; Spanish females 97.0%, Spanish males 96.3%). According to ORTO-7, about 30% of Italian and 48% of Spanish students were positive to ON with no significant sex differences. When excluding students underweight (UW), overweight (OW) or obese (OB), as well as those potentially at risk of eating disorders or presenting mild, moderate and severe distress, in the resultant normal weight (NW)-K10neg-EAT-26neg subgroup, we did not find many correlations observed in the whole sample, including those between ORTO scores and BUT, SSI, Total MBSRQ and some of its components. Moreover, ORTO-7 resulted in the only ON score unrelated with Body Mass Index, MBSRQ components and IPAQ-assessed intense activity, in the NW-K10neg-EAT-26neg subgroup. After this sort of "exclusion diagnosis", the prevalence of ON of these students on the overall sample resulted in 16.9%, 12.2%, 15.2% and 25.9% for Italian females, Italian males, Spanish females and Spanish males, respectively. CONCLUSION: In some university students ON could be a symptom of other conditions related to body image concerns and distress, as well as to high physical activity and appearance, fitness, health or illness orientation (from MBSRQ). However, ORTO-7 became independent from these confounding variables, after the exclusion of UW, OW, OB and students positive to EAT-26 and K10, suggesting the possibility of identifying orthorexic subjects with this specific questionnaire.

Body Composition and Metabolic Status of Italian and Spanish University Students: Relationship with Fruit and Vegetable Consumption.

Most university students do not follow recommendations for fruit and vegetable intake, with a consequent increase in the prevalence of cardiovascular disease (CVD) risk factors. The aim of this study was to compare obesity prevalence and biomarkers of metabolic status between Italian and Spanish university students, in relation with the consumption of fruits and vegetables. Food consumption, adherence to a Mediterranean diet (MD), level of physical activity (PA), blood glucose, total cholesterol, triglycerides and ketones, blood pressure, and body composition were evaluated. Among CVD risk factors, only glucose was significantly higher in Spaniards (SP), and only 3.1% of SP presented ketosis. SP had a higher percentage of energy from fat. Although adherence to MD and fruit and vegetable consumption did not differ between Italians and SP, students who consumed at least four servings of fruit and vegetables (FV group) showed better values for pressure and metabolic parameters than the no FV group. We observed an association between consumption of fruit and PA. Students who consumed more vegetables than fruit reported a better body composition profile and lower glucose concentrations. As previously suggested, in addition to PA, two servings of fruit and three servings of vegetables per day should be recommended.

Entomophagy: A Narrative Review on Nutritional Value, Safety, Cultural Acceptance and A Focus on the Role of Food Neophobia in Italy.

In recent years, the consumption of insects, or entomophagy, has produced an increasing interest amongst scientists and ecologists as a potential source of animal protein. Eating insects is also interesting in terms of low greenhouse gas emissions and low land use. In contrast to tropical countries, where most of the 2000 edible insect species are traditionally consumed, the concept of eating insects is still new to Western culture and diet. Culture and eating habits exert a great influence on what is considered edible in the Mediterranean area, especially in Italy, where the preservation of culinary traditions is a predominant factor affecting dietary behaviour. The purpose of this narrative paper is to provide an overview of the main topics related to entomophagy. The introduction presents some information about the nutrient content and safety aspects, the second part summarises the cultural acceptance of insect in the world, while the role of food neophobia on the intention to consume insects in Italy is focused on in part three. The discussion displays important viewpoints of previously published studies and based on these perspectives it can be concluded that the Italian diet is still clearly influenced by local tradition. In conclusion, in order to introduce insects into the Italian diet, psychological motivation has to be enhanced.

Neutrophil-to-Lymphocyte Ratio, Mediterranean Diet, and Bone Health in Coeliac Disease Patients: A Pilot Study.

Neutrophil-to-lymphocyte ratio (NLR) has been proposed as a bone loss index in postmenopausal women and as a marker of inflammation in coeliac patients. The aims of this work were to evaluate the effect of gluten-free diet (GFD) on NLR retrospectively and study the relationship between NLR and Mediterranean diet adherence and selected food groups (fruits, vegetables, red meat, potatoes, and unrefined and refined cereals). Adult individuals (n = 50), who had been on a strict GFD by at least 6 months, were recruited. The degree of adherence to the Mediterranean diet was calculated with two different scores: the Mediterranean Diet Score (MDS-14), assessed through the validated 14-item questionnaire of the PREDIMED study, and the MEDScore (Score-55) proposed by Panagiotakos. The latter includes the consumption of unrefined cereals (UC). High percentages of osteopenia and osteoporosis were found within the recruited subjects, who furnished the reports of bone mineral density (BMD), in particular in postmenopausal (Post-M) women. Recent NLR was higher in subjects with osteoporosis compared to osteopenia and normal BMD. However, retrospective analysis showed both increase and decrease in NLR after GFD, with no significant differences between Marsh grade, anemia, and BMD status. Moreover, premenopausal previous pregnancy (Pre-MPP) and Post-M had higher NLR at diagnosis compared to Men and premenopausal (Pre-M), but higher differences were observed in recent NLR between Pre-MPP and Men only. Chocolate consumption was associated with lower recent NLR, whereas the latter was correlated with Score-55, but not with MDS-14. Moreover, refined cereal consumption was correlated with recent NLR. Although large prospective studies are needed in order to clarify the relationship between UC and NLR in coeliac patients, in this pilot study, we have investigated for the first time the relationship between NLR, dietary habit, and osteoporosis in coeliac disease.

Anti-Inflammatory and Immunomodulatory Effects of Barberry (Berberis vulgaris) and Its Main Compounds.

Berberis vulgaris is a well-known herb in Iran that is widely used as a medicinal plant and a food additive. The aim of this study was to investigate the anti-inflammatory and immunomodulatory effects of Barberry and its main compounds. This narrative review was conducted by searching keywords such as B. vulgaris, Barberry, immunomodulatory, anti-inflammatory, medicinal herbs, plants, and extract, separately or combined in various databases, such as Web of Sciences, PubMed, and Scopus. According to the inclusion and exclusion criteria, just English language articles, which reported effective whole plants or herbal compounds, were included. 21 articles were reviewed in this study. In the in vivo models (mice, rats, and human cells) and in the in vitro models (some organ cells such as the spleen, kidney, blood, and brain), B. vulgaris and its main components showed anti-inflammatory effects in both models. The main mechanisms were the shift of cell immune response to Th2, T reg induction, inhibition of inflammatory cytokines (IL-1, TNF, and IFN-γ), and stimulation of IL-4 and IL-10. The induction of apoptosis in APCs and other effector cells was another important mechanism.

Medicinal Plants in the Prevention and Treatment of Colon Cancer.

The standard treatment for cancer is generally based on using cytotoxic drugs, radiotherapy, chemotherapy, and surgery. However, the use of traditional treatments has received attention in recent years. The aim of the present work was to provide an overview of medicinal plants effective on colon cancer with special emphasis on bioactive components and underlying mechanisms of action. Various literature databases, including Web of Science, PubMed, and Scopus, were used and English language articles were considered. Based on literature search, 172 experimental studies and 71 clinical cases on 190 plants were included. The results indicate that grape, soybean, green tea, garlic, olive, and pomegranate are the most effective plants against colon cancer. In these studies, fruits, seeds, leaves, and plant roots were used for in vitro and in vivo models. Various anticolon cancer mechanisms of these medicinal plants include induction of superoxide dismutase, reduction of DNA oxidation, induction of apoptosis by inducing a cell cycle arrest in S phase, reducing the expression of PI3K, P-Akt protein, and MMP as well; reduction of antiapoptotic Bcl-2 and Bcl-xL proteins, and decrease of proliferating cell nuclear antigen (PCNA), cyclin A, cyclin D1, cyclin B1 and cyclin E. Plant compounds also increase both the expression of the cell cycle inhibitors p53, p21, and p27, and the BAD, Bax, caspase 3, caspase 7, caspase 8, and caspase 9 proteins levels. In fact, purification of herbal compounds and demonstration of their efficacy in appropriate in vivo models, as well as clinical studies, may lead to alternative and effective ways of controlling and treating colon cancer.

Cardiovascular Risk Factors and Haematological Indexes of Inflammation in Paralympic Athletes with Different Motor Impairments.

Haematological indexes of both inflammation and platelet activation have been suggested as predictive markers of cardiovascular disease (CVD), which has high prevalence in Paralympic athletes (PA). Different mechanisms could play a role in increasing CVD risk in PA with spinal cord injury (PA-SCI), lower limb amputation (PA-LLA), or upper limb impairment (PA-ULI). We compared, in 4 groups of PA competing in power, intermittent (mixed metabolism), and endurance sports, Framingham Risk Score (FRS), metabolic syndrome criteria (MetS-C), inflammation (INFLA) Score, 5 haematological indexes of platelet activation (mean platelet volume (MPV), platelet distribution width (PDW), and the ratios between MPV and platelet (MPVPR), between MPV and lymphocyte (MPVLR), and between PDW and lymphocyte (PDWLR)) and the endogenous antioxidants uric acid (UA) and bilirubin (BR). A retrospective chart review of PA from preparticipation examinations' records (London 2012 and Sochi 2014 Paralympics) was performed. We included 25 PA-SCI (13 with high and 12 with low lesion, PA-SCI-H and PA-SCI-L), 15 PA-LLA, and 10 PA-ULI. FRS and INFLA Score did not differ among groups, but PA-SCI-H had lower HDL, compared to PA-SCI-L and PA-ULI. PA-LLA had more MetS diagnostic criteria with significant higher glucose levels than other groups. PA-SCI-H had significantly lower lymphocytes' count compared to PA-LLA and higher MPV, PDW, MPVPR, MPVLR, and PDWLR. SCI-H had lower BR, haemoglobin, haematocrit, proteins, and creatinine. No interaction was found between the 3 kinds of sitting sports and the 2 groups of health conditions (PA-SCI and PA-LLA). In conclusion, PA-LLA had a higher cardiometabolic risk, whereas PA-SCI-H had a higher platelet-derived cardiovascular risk. Further larger studies are needed to investigate the relationship between indexes of inflammation/oxidation and dietary habit, body composition, and physical fitness/performance in PA with motor impairments.

Nutraceutical-based Integrative Medicine: Adopting a Mediterranean Diet Pyramid for Attaining Healthy Ageing in Veterans with Disabilities.

Veterans with disability represent a big burden worldwide and often require long-term rehabilitation. Unhealthy dietary and lifestyle habits, including smoke and alcohol abuse, are common in veterans. In the context of integrative medicine approaches, the "complementary and alternative medicine" has been suggested for the management of chronic diseases. However, the potential risk of interaction between herbal products, dietary supplements and drugs must be considered in veterans. The Mediterranean diet has been suggested as a natural, non-pharmacological nutraceutical for healthy ageing. Although there is a broad consensus on the positive effect of plant foods consumption, the presence of glucosinolates, flavonoids and furanocoumarins in some plant foods and beverages must be taken into consideration owing to their potential interfering with drugs metabolism and bioavailability. Albeit seasonality could ensure the maintenance of the single dose of phytochemical below that at which adverse effects in some individuals genetically predisposed or unpleasant drug interactions in diseased subjects can occur, a personalized nutrition is recommended in veterans who are under treatment for comorbidities. Furthermore, sports practice can lead veterans with motor disabilities and mental impairments to excel in some disciplines, giving rise to the phenomenon of the Paralympics and the development of "recreational therapy". Moreover, outdoor lifestyle, through vitamin D synthesis, and conviviality, improving socialization, could account for the Mediterranean lifestyle health benefits. In this work, we propose for veterans a Mediterranean Pyramid, which could be the basis for integrative medicine for veterans with disabilities, patient-centered approaches and interprofessional (including physical medicine and rehabilitation clinicians, pharmacists and nutritionists) interventions.