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The oxidative stress results from a change in the physiological balancebetween oxidant and antioxidant species. This condition induces an chemical change in the redox state of cells.. The function of t-PMET is to cooperate with intracellular redox pairs, like piruvate and lactate, to maintain thecytoplasmatic NAD+/NADH balance. The t-PMET is correlated with the modulation of internal pH and redox homeostasis, as it is able to activate proton release. Thus, t-PMET causes external and internal pH modification, as well as development of an inside negative membrane potential. The aim of this work was evaluate the erythrocytes redox status in a group of health volunteers and then to study whether some of flavonoids, enclosed in sub-class of flavonols (Quercetin and Kaempferol), are able to modify the erythrocytes redox homeostasis.Our attention has been focused on red blood cells (RBC) because a close link between t-PMET and metabolic status of erythrocytes has been reported. The RBCs act as antioxidants to themselves and, inaddition, their mobility carries their antioxidant capabilities to all the plasma accessible parts of the body.The subjects that participating at this work attested no supplement intake or some other substance that could interfere with our tests. Human venous blood from twenty healthy volunteers of both sexes between the ages of 25-50 years were obtained by venipuncture in heparin after an over-night fast and centrifuged.The antioxidant capacity of plasma was analyzed by crocin bleaching assay and FRAP. On the other hand, the reducing activity in erythrocytes that represents the body redox state of the last 120 days was evaluated by FRAP method. After centrifugation at 3000 rpm for 10 minutes at 4°C, plasma was separate from red blood cells. The resultant plasma was transferred to microcentrifuge tubes and used at least in part for ferric-reducing activity power (FRAP) and for Crocin Bleaching Assay (CBA) and the others aliquots was stored -80°C before to use for further analysis. Red blood cells, after removal of buffy coat and upper 15% of the packed red blood cells, were washed two times with cold PBS. A stock solution (20mM) of each flavonoid was prepared in dimethyl sulfoxide and then diluted 1:2 with PBS. Packed RBC (10%v/v) were incubatedin PBS containing 5mM glucose at 37°C for 10. minutes with a 50 μM concentration of each flavonoids. After this time the suspensions was centrifuged, the RBC were washed and then analyzed. The percentage of hemolysis was evaluated in the same sample by measuring the haemoglobin contents.The extent of lysis was not different than the controls and never higher than 0.5%.All the values confirm the data of literature about the antioxidant status of human being in physiological condition. All compounds were taken up by the erythrocytes and displaying significant FIC-reducing activity. Both the analysed compounds (Quercetin and Kaempferol) are able to increase the reducing activity of the erythrocytes of 15% and 13% respectively respect to the value recorded for the control. On the other hand, only the quercetin was able to increment the activity of the tPMET system; not any significant difference has been recorded between the Kaempferol and the control group .This study shows that the flavonoids are able to form stable complexeswith the erythrocytes and to influence the intracellular redox homeostasis.Therefore, it could affirm that the polyphenols are able to increase the defence of erythrocytes against ROS. This work underlines that the RBC plays a pivotal role in the distribution and bioavailability of circulating polyphenols which contribute to the defence against injury induced by ROS in various clinical disorders.

The aim of our study was to evaluate the capability of a crude extract of phenols from extra virgin olive oil of Moraiolo cultivar to induce apoptosis and/or differentiation in sensitive and resistant HL60 cell lines to anticancer drugs (Typical Multidrug Resistance). Our data highlight that the crude extract is able to induce apoptosis on both sensitive and resistant cells, whereas the exposure to a number of anticancer drugs does not induce apoptosis in resistant cells. In differentiation experiments we investigated the capability of crude extract of phenols to induce the expression of CD11 granulocytic or CD14 monocytic cell surface antigen in sensitive and resistant HL60 cell lines. At IC50 dose level (17 µg/ml and 32 µg/ml respectively for sensitive and resistant cell lines), the crude extract induced differentiation associated with the expression of CD14 monocytic cell surface antigen either in sensitive or resistant cell lines but not that of CD11 granulocityc cell surface antigen. Further investigations are in progress to better clarify the mechanism by which olive oil phenols induce differentiation differentiation on this cell line.

Oleuropein (Ole) is the main bioactive phenolic compound present in olive leaves, fruits and olive oil. This molecule has been shown to exert beneficial effects on several human pathological conditions. In particular, recent preclinical and observational studies have provided evidence that Ole exhibits chemo-preventive effects on different types of human tumors. Studies undertaken to elucidate the specific mechanisms underlying these effects have shown that this molecule may thwart several key steps of malignant progression, including tumor cell proliferation, survival, angiogenesis, invasion and metastasis, by modulating the expression and activity of several growth factors, cytokines, adhesion molecules and enzymes involved in these processes. Interestingly, experimental observations have highlighted the fact that most of these signalling molecules also appear to be actively involved in the homing and growth of disseminating cancer cells in bones and, ultimately, in the development of metastatic bone diseases. These findings, and the experimental and clinical data reporting the preventive activity of Ole on various pathological conditions associated with a bone loss, are indicative of a potential therapeutic role of this molecule in the prevention and treatment of cancer-related bone diseases. This paper provides a current overview regarding the molecular mechanisms and the experimental findings underpinning a possible clinical role of Ole in the prevention and development of cancer-related bone diseases.

Cystatin C (Cyst C) is an endogenous inhibitor of lysosomal cysteine proteinases, which has been shown to play a role in several normal and pathological processes. Interestingly, a growing number of experimental and clinical studies suggest that this inhibitor also appears to be implicated in the malignant progression of various human tumors. However, the role of Cyst C in malignant diseases is still controversial as these studies have highlighted that this protein may function either as tumor suppressor or tumor promoter. The specific mechanisms underlying these opposing effects at present remain murky and are the subject of many current investigations. On the other hand, a complete knowledge of these mechanisms is of clinical interest in order to develop new, effective antitumor treatments based on the appropriate use of natural and/or synthetic cysteine proteinase inhibitors. This paper discusses the current findings regarding the role of Cyst C in cancer progression and the clinical implications emerging from these studies.

Leptin is involved in the lung epithelial homeostasis. Its role in the nasal tract is largely unknown. Allergic rhinitis (AR) is induced by the allergen exposure leading to a consequential structural abnormalities in the nasal epithelium. Topical corticosteroids are recommended as first-line therapy in AR. Parietaria pollen is one of the most important allergenic sources in the southern Europe. In vitro on human nasal epithelial cell line RPMI 2650, we aimed to determine whether allergen stimulation acts on leptin/leptin receptor pathway and how Fluticasone Furoate (FF) influences this pathway. The effects of the major allergen rPar j 1, of FF, of leptin and of TGFβ1 on cell proliferation and on leptin/leptin receptor expression and modulation (by clonogenic test, by RT-q-RT-PCR, by immunocytochemistry and by flow-cytometry, respectively) and on STAT-3 activation (assessing nuclear translocation by western blot analysis) were assessed. We found that rPaj1 and TGFβ1 significantly decreased cell proliferation and down-regulated the leptin/leptin receptor pathway whereas leptin and FF reverted them, alone and together combined. Furthermore, rPar j 1 reduces while leptin and FF increases STAT-3 activation. In conclusion, leptin and FF are able to preserve nasal epithelial homeostasis restoring the leptin/leptin receptor pathway altered by rParj 1 exposure.