70 research outputs found

    Anti-proliferative effect of main dietary phytosterols and \u3b2-cryptoxanthin alone or combined in human colon cancer Caco-2 cells through cytosolic Ca+2 \u2013 and oxidative stress induced apoptosis

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    \u3b2-cryptoxanthin (\u3b2-Cx) and phytosterols (Ps) have potential against different cancer types,including colon cancer. However, their combined action has not been reported so far. Human colon cancer Caco-2 cells were treated 24 h with \u3b2-Cx and/or main dietary Ps (\u3b2-sitosterol, campesterol and stigmasterol), alone or in combination, at concentrations compatible with physiological human serum levels. A decrease in cell viability due to apoptosis (rise in sub-G1 population and exposure of membrane phosphatidylserine) was accompanied with dephosphorylation of BAD, mitochondrial depolarization and caspase 3-dependent PARP cleavage, with intracellular Ca2+ influx and increase of RONS levels as initial triggers. Ps and \u3b2-Cx, alone or in combination showed anti-proliferative activity against human colon adenocarcinoma Caco-2 cells through the mitochondrial pathway of apoptosis. No additive or synergistic effects were observed.The importance of bioactivity-guided assays with mixtures of dietary bioactive compounds to determine their eventual interactions in the functional food context is demonstrated

    Antiproliferative and pro-apoptotic effects of the phytochemical Indicaxanthin on human intestinal (Caco-2) and hepatic (Ha 22T) cancer cell lines

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    In the present study antiproliferative effects of Indicaxanthin (Ind), a highly bioavailable pigment from the fruits of Opuntia ficus-indica (1), were investigated on a number of human cancer cell lines including hepatocarcinoma cells (HepG2, Ha22T, HUH 7), breast cancer cells (MCF7), cervix epithelial carcinoma (HeLa), and colorectal carcinoma cells (Caco-2). Cytotoxicity of Ind, in a concentration range between 25 to 100 \uf06dM, was evaluated by Trypan blue exclusion method and MTT assay. Ind caused a clear dose- and time-dependent decrease in the proliferation of Caco-2 and Ha 22T cells with an IC(50) of about 50 \uf06dM, with minor effect on the other cell lines. Flow cytometric analysis after Annexin V-FITC and propidium iodure double staining, at 24, 48 and 72 h of treatment with 100 \uf06dM Ind, showed a pro-apoptotic effect of the pigment at 48 and 72 h. Effect of Ind on DNA methylation investigated on DNA from Ha22T cells line and Caco2 cells line at 48 h of treatment with 10 \uf06dM Ind, using MESAP-PCR (Methylation-Sensitive Arbitrarily-Primed Polymerase Chain Reaction) (3) showed that Ind induces a slight global demethylation. While antiproliferative effects of indicaxanthin add further value to the nutritional characteristics of the fruits of O. ficus-indica (2), our results also are consistent with the emerging role of dietary phytochemicals on the epigenetic regulation of gene expression

    Influence of Interferon beta treatment on quality of life in multiple sclerosis patients

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    BACKGROUND: Interferon-beta (IFN-β) shows beneficial effect on the course of multiple sclerosis (MS), nevertheless its route and frequency of administration and side effects might impact negatively the quality of life (QoL) of MS patients. The objective of this study was to evaluate the influence of IFN-β on QoL in MS patients. METHODS: Seventy-seven disease modifying treatment (DMT) free and 41 IFN-β treated MS patients were evaluated. QoL, assessed by MSQoL-54, was related to IFN-β treatment and to clinical and demographic parameters at baseline and after two years. Multivariate hierarchical linear model for repeated measurements was used. RESULTS: Treated patients showed a younger age, a lower disease duration and a higher relapse rate in the two years preceding study entry. At inclusion time treated and untreated patients did not differ in relapse rate, expanded disability status scale (EDSS), fatigue, depression, physical and mental QoL. IFN-β did not influence QoL at inclusion time, but when QoL was evaluated after two years, treatment negatively affected mental QoL. Depression and fatigue negatively influenced physical and mental QoL both at baseline and after two years. EDSS correlated with a poor physical QoL only at baseline. CONCLUSION: IFN-β had a negative impact on QoL over the time in MS patients, influencing mainly mental QoL. The impairment of QoL in MS was strongly associated with increasing fatigue and depression, whereas clinical disability had a minor unfavourable role

    Circulating CD133+VEGFR2+ and CD34+VEGFR2+ cells and arterial function in patients with beta-thalassaemia major

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    Arterial dysfunction has been documented in patients with beta-thalassaemia major. This study aimed to determine the quantity and proliferative capacity of circulating CD133+VEGFR2+ and CD34+VEGFR2+ cells in patients with beta-thalassaemia major and those after haematopoietic stem cell transplantation (HSCT), and their relationships with arterial function. Brachial arterial flow-mediated dilation (FMD), carotid arterial stiffness, the quantity of these circulating cells and their number of colony-forming units (CFUs) were determined in 17 transfusion-dependent thalassaemia patients, 14 patients after HSCT and 11 controls. Compared with controls, both patient groups had significantly lower FMD and greater arterial stiffness. Despite having increased CD133+VEGFR2+ and CD34+VEGFR2+ cells, transfusion-dependent patients had significantly reduced CFUs compared with controls (p = 0.002). There was a trend of increasing CFUs across the three groups with decreasing iron load (p = 0.011). The CFUs correlated with brachial FMD (p = 0.029) and arterial stiffness (p = 0.02), but not with serum ferritin level. Multiple linear regression showed that CFU was a significant determinant of FMD (p = 0.043) and arterial stiffness (p = 0.02) after adjustment of age, sex, body mass index, blood pressure and serum ferritin level. In conclusion, arterial dysfunction found in patients with beta-thalassaemia major before and after HSCT may be related to impaired proliferation of CD133+VEGFR2+ and CD34+VEGFR2+ cells

    CDK5 Is Essential for Soluble Amyloid β-Induced Degradation of GKAP and Remodeling of the Synaptic Actin Cytoskeleton

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    The early stages of Alzheimer's disease are marked by synaptic dysfunction and loss. This process results from the disassembly and degradation of synaptic components, in particular of scaffolding proteins that compose the post-synaptic density (PSD), namely PSD95, Homer and Shank. Here we investigated in rat frontal cortex dissociated culture the mechanisms involved in the downregulation of GKAP (SAPAP1), which links the PSD95 complex to the Shank complex and cytoskeletal structures within the PSD. We show that Aβ causes the rapid loss of GKAP from synapses through a pathway that critically requires cdk5 activity, and is set in motion by NMDAR activity and Ca2+ influx. We show that GKAP is a direct substrate of cdk5 and that its phosphorylation results in polyubiquitination and proteasomal degradation of GKAP and remodeling (collapse) of the synaptic actin cytoskeleton; the latter effect is abolished in neurons expressing GKAP mutants that are resistant to phosphorylation by cdk5. Given that cdk5 also regulates degradation of PSD95, these results underscore the central position of cdk5 in mediating Aβ-induced PSD disassembly and synapse loss

    Sicilian pistachio (Pistacia vera L.) nut inhibits expression and release of inflammatory mediators and reverts the increase of paracellular permeability in IL-1b-exposed human intestinal epithelial cells

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    Background Dietary approaches to control inflammatory bowel diseases (IBD) may include proanthocyanidin-rich foods. Our previous research showed that a hydrophilic extract from Sicilian pistachio nut (HPE) contains sub- stantial amounts of proanthocyanidins and possesses anti- inflammatory activities. Purpose We studied the effects of HPE and of its poly- meric proanthocyanidin fraction (PPF) in a cell model that simulated some conditions of IBD, consisting of interleukin (IL)-1b-stimulated Caco-2 cells. Methods HPE was prepared by Pistacia vera L. nuts, and PPF was isolated from HPE by adsorbance chromatogra- phy. Proanthocyanidins were quantified as anthocyanidins after acidic hydrolysis. Differentiated Caco-2 cells were pre-incubated with HPE or PPF and then were exposed to IL-1b. Cell viability and parameters associated with nuclear factor-kB (NF-kB) activation were assayed. Adsorption of polymeric proanthocyanidins to the cell membrane was investigated by transepithelial electrical resistance (TEER) measurements. Results HPE decreased prostaglandin (PG)E2 production, IL-6 and IL-8 release, and cyclooxygenase (COX)-2 expression. HPE also inhibited the increase in paracellular permeability and reduced NF-kB activation. Polymeric proanthocyanidins, tested at a concentration comparable with their content in HPE, produced effects comparable HPE. Finally, cell exposure to PPF increases TEER of the epithelial monolayers. Conclusion Our results provide evidence that pistachio nut components inhibit inflammatory response of intestinal epithelial cells in vitro and indicate polymeric proanthocyanidins as the major bioactive nut components. The protection implies inhibition of NF-jB activation and occurs in parallel with the adsorption of polymeric pro- anthocyanidins to cell membrane. Our findings suggest that intake of small amounts of pistachio nut can exert benefi- cial effects to gastrointestinal pathophysiology
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