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Numerous studies support the protective role of bioactive peptides against cardiovascular diseases. Cereals represent the primary source of carbohydrates, but they also contain substantial amounts of proteins, therefore representing a potential dietary source of bioactive peptides with nutraceutical activities. The analysis of wheat extracts purified by chromatographic techniques by means of HPLC-UV/nanoLC-nanoESI-QTOF allowed the identification of a signal of about 7 kDa which, following data base searches, was ascribed to a nonspecific lipid-transfer protein (nsLTP) type 2 from Triticum aestivum (sequence coverage of 92%). For the first time nsLTP2 biological activities have been investigated. In particular, in experiments with human umbilical vein endothelial cells (HUVEC), nsLTP2 displayed antioxidant and cytoprotective activities, being able to significantly decrease reactive oxygen species (ROS) levels and to reduce lactate dehydrogenase (LDH) release, generated following oxidative (hydrogen peroxide) and inflammatory (tumor necrosis factor α, interleukin-1β, and lipopolysaccharide) stimulation. The obtained promising results suggest potential protective role of nsLTP2 in vascular diseases prevention. PRACTICAL APPLICATION: nsLTP 2 peptide is resistant to proteases throughout the gastrointestinal tract and exerts antioxidant and cytoprotective activities. These characteristics could be exploited in vascular diseases prevention.

Preventing oxidative damage in the heart is subject of considerable investigation and studies developing nutritional intervention methods to attenuate or prevent the resulting pathological state of free radical damage are now emerging. In this light, a dietary intervention directed to increase the daily intake of antioxidant molecules represents a fundamental step to achieve a beneficial result. In this minireview the attention is focused on the damage induced in cultured cardiac cells by the antitumoral doxorubicin, known for its cardiotoxicity, and by hypoxia/reoxygenation that occur in a wide variety of important clinical conditions. The identification of antioxidant molecules having specific effectiveness in a particular cell type may be useful for the development of a prevention strategy specific for free radical induced-diseases related to that cell type. Although the connection between consumption of foods rich in polyphenolic compounds and the decreased risk of cardiovascular disease has been reported, the role of different antioxidant molecules contained in foods is still to be elucidated. The protective effect of the polyphenolic components of green tea in the prevention/counteraction of cell damage induced in the heart by doxorubicin or hypoxia/reoxygenation has been discussed.

Background: This study evaluated whether demographics, pre-diagnosis lifestyle habits and clinical data are associated with the overall survival (OS) and head and neck cancer (HNC)-specific survival in patients with HNC. Patients and methods: We conducted a pooled analysis, including 4759 HNC patients from five studies within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. Cox proportional hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were estimated including terms reported significantly associated with the survival in the univariate analysis. Results: Five-year OS was 51.4% for all HNC sites combined: 50.3% for oral cavity, 41.1% for oropharynx, 35.0% for hypopharynx and 63.9% for larynx. When we considered HNC-specific survival, 5-year survival rates were 57.4% for all HNC combined: 54.6% for oral cavity, 45.4% for oropharynx, 37.1% for hypopharynx and 72.3% for larynx. Older ages at diagnosis and advanced tumour staging were unfavourable predictors of OS and HNC-specific survival. In laryngeal cancer, low educational level was an unfavourable prognostic factor for OS (HR=2.54, 95% CI 1.01-6.38, for high school or lower versus college graduate), and status and intensity of alcohol drinking were prognostic factors both of the OS (current drinkers HR=1.73, 95% CI 1.16-2.58) and HNC-specific survival (current drinkers HR=2.11, 95% CI 1.22-3.66). In oropharyngeal cancer, smoking status was an independent prognostic factors for OS. Smoking intensity ( > 20 cigarettes/day HR=1.41, 95% CI 1.03-1.92) was also an independent prognostic factor for OS in patients with cancer of the oral cavity. Conclusions: OS and HNC-specific survival differ among HNC sites. Pre-diagnosis cigarette smoking is a prognostic factor of the OS for patients with cancer of the oral cavity and oropharynx, whereas pre-diagnosis alcohol drinking is a prognostic factor of OS and HNC-specific survival for patients with cancer of the larynx. Low educational level is an unfavourable prognostic factor for OS in laryngeal cancer patients. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Cereals and legumes are key components of a healthy and balanced diet. Accordingly, many national nutritional guidelines emphasize their health promoting properties by placing them at the base of nutritional food pyramids. This concept is further validated by the observed correlation between a lower risk and occurrence of chronic diseases and the adherence to dietary patterns, like the Mediterranean diet, in which cereal grains, legumes and derived products represent a staple food. In the search for a dietary approach to control/prevent chronic degenerative diseases, protein derived bioactive peptides may represent one such source of health-enhancing components. These peptides may already be present in foods as natural components or may derive from hydrolysis by chemical or enzymatic treatments (digestion, hydrolysis or fermentation). Many reports are present in the literature regarding the bioactivity of peptides in vitro and a wide range of activities has been described, including antimicrobial properties, blood pressure-lowering (ACE inhibitory) effects, cholesterol-lowering ability, antithrombotic and antioxidant activities, enhancement of mineral absorption/bioavailability, cyto- or immunomodulatory effects, and opioid-like activities. However it is difficult to translate these observed effects to human. In fact, the active peptide may be degraded during digestion, or may not be absorbed or reach the target tissues at a concentration necessary to exert its function. This review will focus on bioactive peptides identified in cereals and legumes, from an agronomical and biochemical point of view, including considerations about requirements for the design of appropriate clinical trials necessary for the assessment of their nutraceutical effect in vivo.

BackgroundThe human X-ray repair cross-complementing protein 1 ( XRCC1) gene encodes for one of the major repair factors involved in base excision repair (BER), which is reported to be associated with the risk of several cancers. A few studies have explored the association between risk of hepatocellular carcinoma (HCC) and single-nucleotide polymorphisms (SNPs) in different DNA repair genes, with contradictory results. The purpose of this study was to evaluate the association between XRCC1 Arg399Gln polymorphism and susceptibility to HCC.MethodsA total of 89 HCC patients and 99 randomly selected healthy controls were enrolled. Genotyping of XRCC1 rs25487 was performed by high-resolution melting analysis and Sanger sequencing.ResultsOn univariate analysis, a statistically significant association was found between risk of HCC and XRCC1 399Arg/Gln genotype (odd ratio [OR] = 1.88; 95% CI, 1.04-3.43), which was confirmed after adjusting by sex (OR = 1.94; 95% CI, 1.04-3.63). Although not significant, Kaplan-Meier analysis showed a decreased median survival in Arg/Gln genotype carriers in comparison with Arg/Arg carriers.ConclusionsTo our knowledge, this is the first study reporting an association between BER SNP and HCC risk in a population of central-southern Italy.

L’endotelio svolge un ruolo chiave nel mantenimento dell’omeostasi vascolare e la sua funzionalità può essere considerata un marker predittivo della salute cardiovascolare. Stress ossidativo e infiammazione sono associati ad uno stato di attivazione/disfunzione endoteliale, che rappresenta un meccanismo patogenetico comune dell’azione dei fattori di rischio cardiovascolare. Quindi, il mantenimento della funzionalità dell’endotelio rappresenta un target fondamentale di strategie dietetiche preventive. Studi epidemiologici hanno evidenziato che il consumo di cereali integrali può rappresentare un fattore protettivo nei confronti di numerose patologie cronico-degenerative. Questo effetto è stato oggi attribuito non solo all’abbondanza di fibra e micronutrienti, ma anche allo specifico profilo polifenolico dei diversi cultivar (1). L’interesse della ricerca in ambito nutrizionale si è recentemente focalizzato sulla caratterizzazione delle proprietà salutistiche di peptidi bioattivi che, mediante diversi meccanismi, (azione antiipertensiva, antiossidante, antitrombotica e ipocolesterolemizzante), potrebbero concorrere al mantenimento della salute vascolare (2). I cereali, nell’ambito della dieta mediterranea, possono contribuire significativamente al fabbisogno proteico giornaliero, rappresentando una potenziale fonte dietetica di peptidi bioattivi. Lo studio, effettuato nell'ambito del progetto EU FPVII BACCHUS, ha indagato le attività protettive nei confronti dell’endotelio vascolare esercitate dal peptide appartenente alla famiglia delle “non specific lipid transfer protein type 2” (nsLTP2) di fumento, di cui non sono presenti in letteratura dati riguardanti l’attività biologica in cellule di mammifero. In un sistema modello rappresentato da cellule HUVEC sottoposte a stress infiammatorio indotto da TNF-α, il trattamento con nsLTP2 ha diminuito significativamente i livelli intracellulari di specie reattive dell’ossigeno ed il danno cellulare indotto da TNF-α, valutato misurando l’attività di lattico deidrogenasi rilasciata nel mezzo di coltura. Inoltre, nsLTP2 ha aumentato l’espressione di eme-ossigenasi e contrastato significativamente l’aumento dell’espressione di molecole di adesione (VCAM-1, ICAM-1, E-Selectin) indotte dall’infiammazione. Gli effetti antiossidante e citoprotettivo, corroborati dalla modulazione di proteine chiave del processo infiammatorio, rappresentano meccanismi alla base del potenziale ruolo nutraceutico di nsLTP2 nel mantenimento della salute vascolare.

none 13 no Objectives: Oxidized LDL (oxLDL) or pro-inflammatory stimuli lead to increased oxidative stress linked to endothelial dysfunction and atherosclerosis. The oxLDL receptor-1 (LOX1) is elevated within atheromas and cholesterol-lowering statins also inhibit LOX1 expression. Berberine (BBR), an alkaloid extracted from plants of gender Berberis, has lipid-lowering and anti-inflammatory activity. However, its role in regulating LOX1- mediated signalling is still unknown. The aim of this study was to compare the effects of BBR and lovastatin (LOVA) on oxLDL- and TNFa-induced endothelial dysfunction in human umbilical vein endothelial cells (HUVECs). Methods: Cytotoxicity was determined by LDH assay. Antioxidant capacity was measured with chemiluminescent and ORAC method and intracellular ROS levels in HUVECs through a fluorescent dye. Gene and protein expression levels were assayed by qRT-PCR and western blot, respectively. Results: HUVECs exposure to oxLDL (30mg/ml) or TNFa (10ng/ml) for 24h led to a significant increase in LOX1 expression, effect abrogated by BBR (5mM) and LOVA (1mM). BBR but not LOVA treatment abolished the TNFa induced cytotoxicity and restored the activation of Akt signalling. Although both compounds reduced intracellular ROS levels induced by H2O2 (100mM) or TNFa, only BBR inhibited NOX2 expression, MAPK/Erk signalling and subsequent NF-kB e related genes VCAM and ICAM expression, induced by TNFa. Conclusions: These findings demonstrated for the first time that BBR could prevent the oxLDL and TNFa - induced LOX1 expression and oxidative stress, key events that lead to NOX2, MAPK/Erk and NF-kB activation linked to endothelial dysfunction. Cicero, A; Caliceti, C; Rizzo, P; Ferrari, R; Fortini, F; Aquila, G; Shehu, J; Leoncini, E; Zambonin, L; Rizzo, B; Guardigli, M; Roda, A; Hrelia, S Cicero, A; Caliceti, C; Rizzo, P; Ferrari, R; Fortini, F; Aquila, G; Shehu, J; Leoncini, E; Zambonin, L; Rizzo, B; Guardigli, M; Roda, A; Hrelia, S

Il lavoro ricostruisce l'intero sistema di tela penale dell'ambiente, allargando una precedente ricostruzione con le importanti e numerose modifiche al settore introdotte con la L. 68/2015. Viene risistemata la catalogazione delle fattispecie, con il loro contenuto e le prassi giurisprudenziali, trattate le problematiche 'trasversali' ai diversi settori ed analizzata la parte sanzionatoria, compresa quella amministrativo-punitiva.

Despite extensive studies, the fundamental mechanisms responsible for the development and progression of cardiovascular diseases have not yet been fully elucidated. Recent experimental and clinical studies have suggested that reactive oxygen species play a major pathological role. Oxidative stress reduction induced by flavonoids has been regarded by many as the most likely mechanism in the protective effects of these compounds; however, there is an emerging view that flavonoids may also exert modulatory actions on protein kinase and lipid kinase signaling pathways. Quercetin, a major flavonoid present in the human diet, has been widely studied, and its biological properties are consistent with its protective role in the cardiovascular system. However, it remains unknown whether the cardioprotective effects of quercetin may also occur through the modulation of genes involved in cell survival. The main goal of this study was to examine the gene expression profiling of cultured rat primary cardiomyocytes treated with quercetin using DNA microarrays and to relate these data to functional effects. Results showed distinct temporal changes in gene expression induced by quercetin and a strong upregulation of phase 2 enzymes, highlighting quercetin ability to act also with an indirect antioxidant mechanism.

Background: The purpose of this study is to evaluate whether demographics, lifestyle habits, clinical data and alcohol dehydrogenase polymorphisms rs1229984 and rs1573496 associated with first primary head and neck (HNC) are associated with overall survival, recurrence, and second primary cancer (SPC). Methods: We conducted a follow-up study in five centres including 801 cases. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for overall survival, recurrence and SPC. Results: Five-years overall survival was 62% for HNC cases, 55% for oral cavity, 53% for oropharynx, 41% for hypopharynx, and 71% for larynx. Predictors of survival were older ages (HR. =. 1.18 for 5 years increase; CI: 1.07-1.30), higher tumour stage (HR. =. 4.16; CI: 2.49-6.96), and high alcohol consumption (HR. =. 3.93; CI: 1.79-8.63). A combined therapy (HR. =. 3.29; CI: 1.18-9.13) was associated with a worst prognosis for oral cavity cancer. The only predictor was higher tumour stage (HR. =. 2.25; CI: 1.26-4.03) for recurrence, and duration of smoking (HR. =. 1.91; CI: 1.00-3.68) for SPC. ADH1B rs1229984 polymorphism HRs for HNC and oesophageal cancer death and for alcohol related cancer death were 0.67 (95% CI: 0.42-1.08), and 0.64 (95% CI: 0.40-1.03), respectively. Conclusions: The survival expectation differs among HNC sites. Increasing age and stage, and high alcohol consumption were unfavourable predictors of HNC survival overall. Duration of tobacco consumption before the first primary tumour was a risk factor for SPC.

Food and nutrition play an important role in head and neck cancer (HNC) etiology; however, the role of carotenoids remains largely undefined. We explored the relation of HNC risk with the intake of carotenoids within the International Head and Neck Cancer Epidemiology Consortium. We pooled individual-level data from 10 case-control studies conducted in Europe, North America, and Japan. The analysis included 18,207 subjects (4414 with oral and pharyngeal cancer, 1545 with laryngeal cancer, and 12,248 controls), categorized by quintiles of carotenoid intake from natural sources. Comparing the highest with the lowest quintile, the risk reduction associated with total carotenoid intake was 39% (95% CI 29-47%) for oral/pharyngeal cancer and 39% (95% CI 24-50%) for laryngeal cancer. Intakes of β-carotene equivalents, β-cryptoxanthin, lycopene, and lutein plus zeaxanthin were associated with at least 18% reduction in the rate of oral and pharyngeal cancer (95% CI 6-29%) and 17% reduction in the rate of laryngeal cancer (95% CI 0-32%). The overall protective effect of carotenoids on HNC was stronger for subjects reporting greater alcohol consumption (p&nbsp

Hypoxia/reoxygenation (H/R) is one of the causes of the increased expression of inducible nitric oxide synthase (iNOS) in cardiomyocytes. Since an aberrant NOS induction has detrimental consequences, we evaluated the effect of a green tea extract (GTE) on the NOS induction and activity in H/R-cardiomyocytes to define a nutritional strategy. Cultured rat cardiomyocytes were exposed to H/R in the presence of two concentrations of a green tea extract (GTE), which is reported to inhibit NOS expression and activity in different cells. In cultured cardiomyocytes two NOS isoforms were constitutively expressed, but only iNOS was induced by H/R. GTE supplementation at the lowest concentration, comparable to that in human plasma after dietary consumption, was ineffective, while the highest, comparable to that achievable by dietary supplements, counteracted the effect of H/R on iNOS induction and activity. It is necessary to verify in humans the relationship between the modulation of NO production and green tea dietary consumption.