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European sea bass ( Dicentrarchus labrax) is a widely consumed marine fish in Mediterranean areas, and different farming techniques are applied for fish culturing to satisfy the growing demand for seafood. The aim of this study was to investigate the effects of conventional and organic feed on the quality of cultured European sea bass ( Dicentrarchus labrax) collected during the growth period. The concentrations of ash, moisture, essential macro-elements (Ca, K, Mg, Na and P), micro-elements (Co, Cr, Cu, Fe, Mn, Ni and Zn) and toxic elements (As, Cd, and Pb) were determined in feeds and in fillets of cultured fish. The results were compared to those obtained from wild sea bass. Results showed that the differences between organic diet-fed and conventional diet-fed sea basses varied in relation to the specific element measured and the growth period. The former showed higher concentration of Fe, Mg and Cr, and lower Na content. The amount of P, Na, Fe, Cu and Cr in wild sea bass was significantly ( P ≤ 0.05) higher than that found in farmed fish. The levels of toxic elements in cultured sea bass were always within the allowed limit for fishery products. Wild samples had significantly ( P ≤ 0.05) higher content of arsenic and lead than farmed sea bass. Cultured fish represent a valuable dietary source of essential macro- and micro-elements. Controlled rearing systems and feedings were related to a decrease in the presence of some toxic metals in cultured fish compared with wild fish. [ABSTRACT FROM AUTHOR]

Experimental and clinical studies evidenced the health effects of moderate consumption of beer, mainly due to the presence of bioactive compounds, such as polyphenols, vitamins, or fibers. To exploit the potential beneficial effect on health and in disease prevention of these compounds, a new beverage based on barley malts and hops named Aliophen ® has been designed, through a patented production process, with a high total polyphenolic amount compared to alcohol-free beer and similar to the one present in light and dark beers. In the present study, the antioxidant activity of Aliophen ® against low-density lipoprotein (LDL) oxidation and its ability to protect erythrocytes from hemolysis have been characterized. Moreover, the chemopreventive effect of Aliophen ® against colon cancer has been assessed, employing a mouse model of chemically induced carcinogenesis using azoxymethane (AOM). Data obtained showed that Aliophen at a low dose (3 mg/kg) inhibited the formation of preneoplastic lesions, polyps, and tumors. At higher doses (300 mg/kg) the protective effect was measured in the first phase of the onset of cancer. The antioxidant properties of Aliophen ® were also observed in AOM-treated mice where it increased the serum antioxidant capacity. Based on the data presented, Aliophen ® can exert promising health effects, including an anticancer capacity presumably associated with its antioxidant properties.

Carotenoids, including β -carotene, lycopene, and derivatives, such as retinoic acid, have been studied for their significant antiproliferative and differentiating activity on cancer cells in experimental models and in clinics. We are presenting here data on the mechanism of action of a carotenoid-enriched extract obtained from the pumpkin Cucurbita moschata , variety "long of Naples," on two malignant human cell lines, Caco-2 and SAOs, derived from a colon adenocarcinoma and an osteosarcoma, respectively. The carotenoid extract has been obtained from pumpkin pulp and seeds by supercritical CO 2 extraction and employed to prepare oil-in-water nanoemulsions. The nanoemulsions, applied at a final carotenoid concentration of 200-400  μ g/ml, were not cytotoxic, but induced a delay in cell growth of about 40% in both SAOs and Caco-2 cell lines. This effect was associated with the activation of a "nonprotective" form of autophagy and, in SAOs cells, to the induction of cell differentiation via a mechanism that involved AMPK activation. Our data suggest the presence of a pool of bioactive compounds in the carotenoid-enriched extract, acting additively, or synergistically, to delay cell growth in cancer cells.

In the present study, we report that polyphenols present in red wine obtained by a controlled microvinification process are able to protect human erythrocytes from oxidative stress and to activate Plasma Membrane Redox System (PMRS). Human plasma obtained from healthy subjects was incubated in the presence of whole red wine at a concentration corresponding to 9.13-73 μg/ml gallic acid equivalents to verify the capacity to protect against hypochlorous acid (HOCl)-induced plasma oxidation and to minimize chloramine formation. Red wine reduced hemolysis and chloramine formation induced by HOCl of 40 and 35%, respectively. PMRS present on human erythrocytes transfers electrons from intracellular molecules to extracellular electron acceptors. We demonstrated that whole red wine activated PMRS activity in human erythrocytes isolated from donors in a dose-dependent manner with a maximum at about 70-100 μg/ml gallic acid equivalents. We also showed that red wine increased glutathione (GSH) levels and erythrocytic antioxidant capacity, measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) quenching assay. Furthermore, we reported that GSH played a crucial role in regulating PMRS activity in erythrocytes. In fact, the effect of iodoacetamide, an alkylating agent that induces depletion of intracellular GSH, was completely counteracted by red wine. Bioactive compounds present in red wine, such as gallic acid, resveratrol, catechin, and quercetin were unable to activate PMRS when tested at the concentrations normally present in aged red wines. On the contrary, the increase of PMRS activity was associated with the anthocyanin fraction, suggesting the capacity of this class of compounds to positively modulate PMRS enzymatic activity.

Over the past decades, extensive studies have addressed the therapeutic effects of omega-3 polyunsaturated fatty acids (omega-3 FAs) against different human diseases such as cardiovascular and neurodegenerative diseases, cancer, etc. A growing body of scientific research shows the pharmacokinetic information and safety of these natural occurring substances. Moreover, during recent years, a plethora of studies has demonstrated that omega-3 FAs possess therapeutic role against certain types of cancer. It is also known that omega-3 FAs can improve efficacy and tolerability of chemotherapy. Previous reports showed that suppression of nuclear factor-κB, activation of AMPK/SIRT1, modulation of cyclooxygenase (COX) activity, and up-regulation of novel anti-inflammatory lipid mediators such as protectins, maresins, and resolvins, are the main mechanisms of antineoplastic effect of omega-3 FAs. In this review, we have collected the available clinical data on the therapeutic role of omega-3 FAs against breast cancer, colorectal cancer, leukemia, gastric cancer, pancreatic cancer, esophageal cancer, prostate cancer, lung cancer, head and neck cancer, as well as cancer cachexia. We also discussed the chemistry, dietary source, and bioavailability of omega-3 FAs, and the potential molecular mechanisms of anticancer and adverse effects.

Increased consumption of fruits and vegetables can represent an easy strategy to significantly reduce the incidence of cancer. From this observation, derived mostly from epidemiological data, the new field of chemoprevention has emerged in the primary and secondary prevention of cancer. Chemoprevention is defined as the use of natural or synthetic compounds able to stop, reverse, or delay the process of tumorigenesis in its early stages. A large number of phytochemicals are potentially capable of simultaneously inhibiting and modulating several key factors regulating cell proliferation in cancer cells. Quercetin is a flavonoid possessing potential chemopreventive properties. It is a functionally pleiotropic molecule, possessing multiple intracellular targets, affecting different cell signaling processes usually altered in cancer cells, with limited toxicity on normal cells. Simultaneously targeting multiple pathways may help to kill malignant cells and slow down the onset of drug resistance. Among the different substrates triggered by quercetin, we have reviewed the ability of the molecule to inhibit protein kinases involved in deregulated cell growth in cancer cells.

Chronic lymphocytic leukemia (CLL) is the most frequent form of leukemia in adult population and despite numerous studies, it is considered an incurable disease. Since CLL is characterized by overexpression of pro-survival Bcl-2 family members, treatments with their antagonists, such as ABT-737, represent a promising new therapeutic strategy. ABT-737 is a BH3 mimetic agent which binds Bcl-2, Bcl-XL and Bcl-w with high affinity, while weakly interacts with Mcl-1 and Bfl-1. Previous studies demonstrated that quercetin, a flavonoid naturally present in food and beverages, was able to sensitize B-cells isolated from CLL patients to apoptosis when associated with death ligands or fludarabine, through a mechanism involving Mcl-1 down-regulation. Here, we report that the association between ABT-737 and quercetin synergistically induces apoptosis in B-cells and in five leukemic cell lines (Combination Index <1). Peripheral blood mononuclear cell from healthy donors were not affected by quercetin treatment. The molecular pathways triggered by quercetin have been investigated in HPB-ALL cells, characterized by the highest resistance to both ABT-737 and quercetin when applied as single molecules, but highly sensitivity to the co-treatment. In this cell line, quercetin down-regulated Mcl-1 through the inhibition of PI3K/Akt signaling pathway, leading to Mcl-1 instability. The same mechanism was confirmed in B-cells. These results may open new clinical perspectives based on a translational approach in CLL therapy., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Increased consumption of fruit and vegetables can represent an easy strategy to significantly reduce the incidence of cancer. We recently demonstrated that the flavonoid quercetin, naturally present in the diet and belonging to the class of phytochemicals, is able to sensitize several leukemia cell lines and B cells isolated from patients affected by chronic lymphocytic leukemia (B-CLL), in addition to apoptotic inducers (anti-CD95 and rTRAIL). Further, it potentiates the effect of fludarabine, a first-line chemotherapeutic drug used against CLL. The proapoptotic activity of quercetin in cell lines and B-CLL is related to the expression and activity of Mcl-1-antiapoptotic proteins belonging to the Bcl-2 family. Quercetin downregulates Mcl-1 mRNA and protein levels acting on mRNA stability and protein degradation. Considering the low toxicity of the flavonoids toward normal peripheral blood cells, our experimental results are in favor of a potential use of quercetin in adjuvant chemotherapy in CLL or other types of cancer., (© 2012 New York Academy of Sciences.)

The eukaryotic Initiation Factor 2 (eIF2) is a key regulator of protein synthesis in eukaryotic cells, implicated in the initiation step of translation. Fertilization of the sea urchin eggs triggers a rapid increase in protein synthesis activity, which is necessary for the progress into embryonic cell cycles. Here we demonstrate that fertilization triggers eIF2α dephosphorylation, concomitant with an increase in protein synthesis and that induction of the eIF2α phosphorylation is intimately linked with an inhibition of protein synthesis and cell cycle arrest. Using a phospho-mimetic protein microinjected into sea urchin eggs, we showed that dephosphorylation of eIF2α is necessary for protein synthesis activity and cell division progression following fertilization. Our results demonstrate that regulation of eIF2α plays an important role in the protein synthesis rise that occurs during early development following fertilization., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Biochemical and genetic studies on cellular and animal models on the mechanism(s) of action of phytochemicals provide a functional explanation of how and why a diet rich in fruits and vegetables is considered healthy. It is not unusual to find molecules that protect against diseases, which greatly differ from a physiopathological point of view, such as cancer and cardiovascular disorders. Quercetin falls into this category and possesses a broad range of biological properties. Uptake, metabolism and circulating concentrations of quercetin and its metabolites suggest that a regular diet provides amounts of quercetin (<1 μM) not compatible with its chemopreventive and/or cardioprotective effects. However, it appears relatively easy to increase total quercetin concentrations in plasma (>10 μM) by supplementation with quercetin-enriched foods or supplements. Multiple lines of experimental evidence suggest a positive association between quercetin intake and improved outcomes of inflammatory cardiovascular risk. The ameliorating effect of quercetin administration can be extended to other chronic inflammatory disorders but only if supplementation occurs in patients. Quercetin can be considered the prototype of a naturally-occurring chemopreventive agent because of its key roles in triggering the "hallmarks of cancer". However, several critical points must be taken into account when considering the potential therapeutic use of this molecule: (1) pharmacological versus nutraceutical doses applied, (2) specificity of its mechanism of action compared to other phytochemicals, and (3) identification of "direct" cellular targets. The design of specific clinical trials is extremely warranted to depict possible applications of quercetin in adjuvant cancer therapy., (Copyright © 2011 Elsevier Inc. All rights reserved.)

In all vertebrates, mature oocytes arrest at the metaphase of the II meiotic division, while some invertebrates arrest at metaphase-I, others at prophase-I. Fertilization induces completion of meiosis and entry into the first mitotic division. Several experimental models have been considered from both vertebrates and invertebrates in order to shed light on the peculiar aspects of meiotic division, such as the regulation of the cytostatic factor (CSF) and the maturation promoting factor (MPF) in metaphase I or II. Recently, we proposed the oocytes of ascidian Ciona intestinalis as a new model to study the meiotic division. Here, taking advantage of the recent publication of the C. intestinalis genome, we presented a phylogenetic analysis of key molecular components of the CSF-related machinery. We showed that the Mos/MAP kinase pathway is perfectly conserved in ascidians. We demonstrated the presence of a CSF-like activity in metaphase-I arrested C. intestinalis oocytes able to block cell division in two-cell embryos. We further investigated the regulation of CSF by demonstrating that both CSF and MPF inactivation, at the exit of metaphase-I, are independent from protein synthesis, indicating the absence of short-lived factors that regulate metaphase stability, as in other invertebrate species. The results obtained suggest that meiotic regulation in C. intestinalis resembles that of vertebrates, such as Xenopus accordingly to the position of this organism in the evolutionary tree.

In recent years, the impact of sperm DNA damage on fertility has become an important issue. The different technologies developed to check sperm DNA fragmentation lead to the same conclusion: DNA damage negatively impacts upon reproductive processes. Oocyte DNA repair capacity is one of the cues to understanding embryo developmental arrest. APEX/Ref-1 (apurinic/apyrimidic endonuclease) is an enzyme involved in the DNA base excision repair pathway removing the abasic sites, the most common DNA decays. In humans, APEX has a multifunctional role, including the control of the redox status of transcription factors. RT-PCR allowed us to detect human APEX transcripts in oocytes, spermatozoa and preimplantation blocked embryos. In parallel, a comparative study on sea squirt Ciona intestinalis (ascidian) indicated that APEX transcripts are clearly detectable in oocytes and embryos until the larva stage, but not in spermatozoa, suggesting the appearance of the paternal contribution to DNA repair during development having arisen only late in Vertebrate evolution. Of additional phylogenetic significance is the observation that sea squirt APEX appears to lack redox transcriptional activity.

The new bubble Oxybel oxygenator (Bellco Laboratories) has been used for routine clinical perfusions in this Institution. A comparison has been made between two groups of 51 patients each, one group perfused with on Oxybel oxygenator (OXY) and the other with the Harvey H 1000 oxygenator (H-H). Among these patients a wide range of acquired and congenital cardiac lesions have been encountered. Both series were comparable for patients' age, sex distribution, body weight, procedures performed, perfusion time and preoperative values of hematocrit, serum creatinine, platelet count, plasma hemoglobin. The gas/blood flow ratio was 2.09 +/- 0.07 (+/- SE) for the H-H oxygenator and 1.38 +/- 0.06 for the OXY series (P < 0.001). Serum-creatinine 24-hrs postoperative values (mg/100 ml) were 1.58 +/- 0.17 for the H-H and 1.30 +/- 0.06 for the OXY series (NS); 48-hrs postoperative values were 1.28 +/- 0.11 for the H-H and 1.20 +/- 0.11 for the OXY (NS). The 60 minutes postoperative platelet count was 127.9 +/- 7 X 10(3) for the H-H and 120.9 +/- 6 X 10(3) for the OXY series (NS). Fourtyeight-hrs postoperative platelet count was 153.0 +/- 5 X 10(3) for the H-H and 151.8 +/- 6 X 10(3) for the OXY series (NS). Postoperative plasma hemoglobin values (mg/100 ml) were 91.55 +/- 7.18 for H-H and 117 +/- 17.8 for the OXY series (NS). Total postoperative bleeding was 1037.9 +/- 94 ml in the H-H and 1056.7 +/- 98.9 ml in the OXY series (NS). The more favorable gas/blood flow ratio observed with the Oxybel oxygenator did not affect clinical and haematologic results. These were comparable in both series.