Phytochemical indicaxanthin suppresses 7-ketocholesterol-induced THP-1 cell apoptosis by preventing cytosolic Ca++ increase and oxidative stress

7-Ketocholesterol (7-KC)-induced apoptosis of macrophages is considered a key event in the development of human atheromas. In the present study, the effect of indicaxanthin (Ind), a bioactive pigment from cactus pear fruit, on 7-KC-induced apoptosis of human monocyte/macrophage THP-1 cells was investigated. A pathophysiological condition was simulated by using amounts of 7-KC that can be reached in human atheromatous plaque. Ind was assayed within a micromolar concentration range, consistent with its plasma level after dietary supplementation with cactus pear fruit. Pro-apoptotic effects of 7-KC were assessed by cell cycle arrest, exposure of phosphatidylserine at the plasma membrane, variation of nuclear morphology, decrease of mitochondrial trans-membrane potential, activation of Bcl-2 antagonist of cell death and poly(ADP-ribose) polymerase-1 cleavage. Kinetic measurements within 24 h showed early formation of intracellular reactive oxygen species over basal levels, preceding NADPH oxidase-4 (NOX-4) over-expression and elevation of cytosolic Ca2þ, with progressive depletion of total thiols. 7-KC-dependent activation of the redox-sensitive NF-kB was observed. Co-incubation of 2·5mM of Ind completely prevented 7-KC-induced pro-apoptotic events. The effects of Ind may be ascribed to inhibition of NOX-4 basal activity and over-expression, inhibition of NF-kB activation, maintaining cell redox balance and Ca homeostasis, with prevention of mitochondrial damage and consequently apoptosis. The findings suggest that Ind, a highly bioavailable dietary phytochemical, may exert protective effects against atherogenetic toxicity of 7-KC at a concentration of nutritional interest

Insight into halloysite nanotubes-loaded gellan gum hydrogels for soft tissue engineering applications

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Prospective open-label study on the efficacy and tolerability of a combination of nutritional supplements in primary infertile patients with idiopathic astenoteratozoospermia

Aim of the study: To evaluate with an open-label study the efficacy and safety of a complex of nutritional supplements with antioxidant activity (L-carnitine, acetyl-L-carnitine, fructose, citric acid, selenium, coenzyme Q10, zinc, ascorbic acid, cyanocobalamin, folic acid) in primary infertile patients with idiopathic astenoteratozoospermia. Methods: The study was conducted in a population of 114 infertile men (96 completed the study) diagnosed with idiopathic astenoteratozoospermia since at least 18 months. Patients orally received a formulation (Proxeed - Sigma-Tau) containing L-carnitine 145 mg, acetyl-L-carnitine 64 mg, fructose 250 mg, citric acid 50 mg, selenium 50 mcg, coenzyme Q10 20 mg, zinc 10 mg, ascorbic acid 90 mg, cyanocobalamin 1.5 mcg, folic acid 200 mcg in combination once a day for 4 months. Results: At the end of study, the mean sperm progressive motility showed a statistically significant increase from 18.3 ± 3.8 to 42.1 ± 5.5. Sixteen patients achieved pregnancy during the study. No significant improvement were observed for sperm density and rate of morphologically normal forms. The treatment was well tolerated. Conclusions: Carnitines in association with others functional substances can improve the most important parameters of sperm quality

Trans-epithelial transport of the betalain pigments indicaxanthin and betanin across Caco-2 cell monolayers and influence of food matrix

Purpose: This study investigated the absorption mechanism of the phytochemicals indicaxanthin and betanin and the influence of their food matrix (cactus pear and red beet) on the intestinal transport. Methods: Trans-epithelial transport of dietary-consistent amounts of indicaxanthin and betanin in Caco-2 cell monolayers seeded on TranswellR inserts was measured in apical to basolateral (AP-BL) and basolateral to apical (BL-AP) direction, under an inwardly directed pH gradient (pH 6.0/7.4, AP/BL) mimicking luminal and serosal sides of human intestinal epithelium. The effect of inhibitors of membrane transporters on the absorption was also evaluated. Contribution of the paracellular route was investigated after EDTA treatment of the cell monolayer. In vitro digestion of betalainic food was performed to provide a post-intestinal fraction containing bioaccessible pigments. Results: Apparent permeability coefficients (P app) in the absorptive direction were (4.4 ± 0.4) × 10-6 and (3.2 ± 0.3) × 10-6 cm s-1 for indicaxanthin and betanin, respectively. Transport of indicaxanthin was non-polarized, linear as a function of time and concentration, and unaffected by inhibitors of membrane transporters. Betanin exhibited significantly different bidirectional P app values and non-linear efflux kinetics. The concentration- dependent betanin efflux was described by a kinetic model including one non-saturable (K d = 0.042 μL cm-2 min-1) and one saturable component identified as the apical multidrug resistance-associated protein 2 (MRP2; K m = 275 μM; J max = 42 pmol min-1 cm-2). Permeation of both betalains increased remarkably after EDTA treatment of the cell monolayer. Neither indicaxanthin nor betanin underwent metabolic transformation. Food matrix did not affect trans-epithelial transfer of indicaxanthin, but reduced the absorption rate of betanin, red beet more than cactus pear. Conclusions: Dietary indicaxanthin and betanin can substantially be absorbed through paracellular junctions of intestinal epithelial cells. Additional trans-membrane permeation can be considered for betanin, whose absorption is limited by a MRP2-mediated efflux and negatively affected by its food matrix. Present findings are consistent with the quite higher bioavailability of indicaxanthin over betanin established in humans. © 2012 Springer-Verlag

A CFD model for biomass flame-combustion analysis

The present work addresses the study of the combustion of individual biomass particle surrounded by a gas stream of N2/O2 under the operating conditions encountered in a drop tube reactor. The aim of this analysis is to give a better insight into the chemical and physical processes that occur both at particle and reactor scale where the volatiles, generated by the biomass pyrolysis, burn in a fuel particle enveloped flame. A comprehensive CFD model was developed within the open-source OpenFOAM® framework in order to properly handle the computational mesh and the discretization of the characteristic governing equations. At the reactor scale, the reactive flow was described by the equations for continuous, multicomponent, compressible and thermally-perfect mixtures of gases. At the particle scale, instead, the solid particle was considered as a porous media with isotropic and uniform morphological properties

Association of USF1 and APOA5 polymorphisms with familial combined hyperlipidemia in an Italian population.

Familial combined hyperlipidemia (FCH) is a polygenic and multifactorial disease characterized by a variable phenotype showing increased levels of triglycerides and/or cholesterol. The aim of this study was to identify single nucleotides (SNPs) in lipid-related genes associated with FCH. METHODS AND RESULTS: Twenty SNPs in lipid-related genes were studied in 142 control subjects and 165 FCH patients after excluding patients with mutations in the LDLR gene and patients with the E2/E2 genotype of APOE. In particular, we studied the 9996G > A (rs2073658) and 11235C > T (rs3737787) variants in the Upstream Stimulatory Factor 1 gene (USF1), and the -1131T > C (rs662799) and S19W (rs3135506) variants in the Apolipoprotein A-V gene (APOA5). We found that the frequencies of these variants differed between patients and controls and that are associated with different lipid profiles. At multivariate logistic regression SNP S19W in APOA5 remained significantly associated with FCH independently of age, sex, BMI, cholesterol and triglycerides. CONCLUSIONS: Our results show that the USF1 and APOA5 polymorphisms are associated with FCH and that the S19W SNP in the APOA5 gene is associated to the disease independently of total cholesterol, triglycerides and BMI. However, more extensive studies including other SNPs such as rs2516839 in USF1, are required

Histological, histochemical and immunohistochemical study on the growing oocytes of the abyssal teleost Hoplostethus mediterraneus (V).

The oocytes of the abyssal Teleost, Hoplostethus mediterraneus were studied. Four stages of growth were observed and the oocytes of all the stages were surrounded by follicular cells and had several nucleoli in the nucleus. In the oocytes of the II degrees stage, vacuoles without contents, in oocytes of the III degrees stage several vacuoles with a basophilic contents and small yolk globules were identified. General and basic proteins, ribonucleoproteins, acid proteoglycans with -COOH groups were recognized in the cytoplasm, in the nucleoli of oocytes in the II degrees stage and in the vacuolar contents of oocytes in the III degrees stage. In the follicular cells, in the pellucid zone, in the yolk globules, from their beginning, glycoproteins were present. Positivity, for all lectins used, was revealed in the follicular cells and in the four stages of oocytes growth. alpha-D-glucose and alpha-D-mannose binding sites were in the pellucid zone and in the initial yolk globules. In the lather galactose and beta-N-acetyl glucosamine were present too. nNOS and VIP immunopositivity revealed at the periphery of the cytoplasm and at network of nerve fibres between oocytes, suggests NO is involved in a mechanism of regulation of the gametogenesis and of the spawning

Long lasting octreotide LAR therapy in non functioning pancreatic neuroendocrine carcinoma

Non functioning endocrine pancreatic tumors (NF-PETs) have absent or low hormone secretion without symptoms and constitue ~60% of PETs. At diagnosis more than 50% of patients have liver metastases and almost 40% are not candidates for radical surgery because of either locally advanced disease or unresectable metastases. We described the case of a 47-year-old woman with a pancreatic carcinoma with secondarism in the liver not suitable for radical surgery. Histological test of liver metastases showed positivity for endocrine well-differentiated non functioning carcinoma expressing receptors for somatostatin with very low proliferation index (Ki67 < 2%). After this diagnosis she started a specific treatment with octreotide analogues which achieved durable stabilization of the disease