Intake of fruits and vegetables and polymorphisms in DNA repair genes in bladder cancer

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Light dependent redox catalysis by Photosystem I complexes encapsulated in organic nanoparticles

Photosystem I (PSI) is a pigment binding multi-subunit protein complexes involved in photosynthesis. PSI is localized in the thylakoid membranes and catalyze the electron transfer reaction from plastocyanin to ferredoxin, as one of the main steps involved in conversion of light energy into chemical energy. PSI is highly efficiency with a photochemical efficiency close to one. Several attempts have doing in the past in order to exploit the high efficiency and high stability of PSI in an extra-cellular context in order to catalyze electron transfer reactions: in this work we present an innovative solution for exploiting the photochemical properties of PSI, by encapsulation of PSI complexes in organic nanoparticles. Nanoparticles offer a protected environment to the encapsulated molecule, giving it the possibility of preserving its functional properties and studying how they change over time. In this work the complete characterization, both morphological and functional, of nanostructures obtained by encapsulation of PSI complexes purified from higher plants with PLGA (poly lactic-co-glycolic acid) polymer is presented. The results obtained by transient absorption and time-resolved fluorescence demonstrate that encapsulated PSI were characterized by an higher photochemcial activity compared to PSI complexes in detergent solution. Moreover, encapsulated PSI maintained the high efficiency observed for several weeks even if exposed to very strong light, being more stable compared to PSI in detergent solution. Finally, the nanostructures obtained by encapsulated PSI were able to catalyze light dependent redox reactions with electron acceptors and donors outside the nanostructures Potential application of these PLGA encapsulated PSI in different fields are thus presented and discussed

HDL cholesterol protects from liver injury in mice with intestinal specific LXRα activation

Background and aims: Liver X receptors (LXRs) exert anti-inflammatory effects even though their hepatic activation is associated with hypertriglyceridemia and hepatic steatosis. Selective induction of LXRs in the gut might provide protective signal(s) in the aberrant wound healing response that induces fibrosis during chronic liver injury, without hypertriglyceridemic and steatogenic effects. Methods: Mice with intestinal constitutive LXRα activation (iVP16-LXRα) were exposed to intraperitoneal injection of carbon tetrachloride (CCl4) for 8 weeks, and in vitro cell models were used to evaluate the beneficial effect of high-density lipoproteins (HDL). Results: After CCl4 treatment, the iVP16-LXRα phenotype showed reduced M1 macrophage infiltration, increased expression M2 macrophage markers, and lower expression of hepatic pro-inflammatory genes. This anti-inflammatory effect in the liver was also associated with decreased expression of hepatic oxidative stress genes and reduced expression of fibrosis markers. iVP16-LXRα exhibited increased reverse cholesterol transport in the gut by ABCA1 expression and consequent enhancement of the levels of circulating HDL and their receptor SRB1 in the liver. No hepatic steatosis development was observed in iVP16-LXRα. In vitro, HDL induced a shift from M1 to M2 phenotype of LPS-stimulated Kupffer cells, decreased TNFα-induced oxidative stress in hepatocytes and reduced NF-kB activity in both cells. SRB1 silencing reduced TNFα gene expression in LPS-stimulated KCs, and NOX-1 and IL-6 in HepG2. Conclusions: Intestinal activation of LXRα modulates hepatic response to injury by increasing circulating HDL levels and SRB1 expression in the liver, thus suggesting this circuit as potential actionable pathway for therapy

Engineered mucoperiosteal scaffold for cleft palate regeneration towards the non-immunogenic transplantation

Cleft lip and palate (CL/P) is the most prevalent craniofacial birth defect in humans. None of the surgical procedures currently used for CL/P repair lead to definitive correction of hard palate bone interruption. Advances in tissue engineering and regenerative medicine aim to develop new strategies to restore palatal bone interruption by using tissue or organ-decellularized bioscaffolds seeded with host cells. Aim of this study was to set up a new natural scaffold deriving from a decellularized porcine mucoperiosteum, engineered by an innovative micro-perforation procedure based on Quantum Molecular Resonance (QMR) and then subjected to in vitro recellularization with human bone marrow-derived mesenchymal stem cells (hBM-MSCs). Our results demonstrated the efficiency of decellularization treatment gaining a natural, non-immunogenic scaffold with preserved collagen microenvironment that displays a favorable support to hMSC engraftment, spreading and differentiation. Ultrastructural analysis showed that the micro-perforation procedure preserved the collagen mesh, increasing the osteoinductive potential for mesenchymal precursor cells. In conclusion, we developed a novel tissue engineering protocol to obtain a non-immunogenic mucoperiosteal scaffold suitable for allogenic transplantation and CL/P repair. The innovative micro-perforation procedure improving hMSC osteogenic differentiation potentially impacts for enhanced palatal bone regeneration leading to future clinical applications in humans

Neuroblastoma-secreted exosomes carrying miR‐375 promote osteogenic differentiation of bone-marrow mesenchymal stromal cells

Bone marrow (BM) is the major target organ for neuroblastoma (NB) metastasis and its involvement is associated with poor outcome. Yet, the mechanism by which NB cells invade BM is largely unknown. Tumour microenvironment represents a key element in tumour progression and mesenchymal stromal cells (MSCs) have been recognized as a fundamental part of the associated tumour stroma. Here, we show that BM-MSCs isolated from NB patients with BM involvement exhibit a greater osteogenic potential than MSCs from non-infiltrated BM. We show that BM metastasis-derived NB-cell lines secrete higher levels of exosomal miR-375, which promotes osteogenic differentiation in MSCs. Of note, clinical data demonstrate that high level of miR-375 correlates with BM metastasis in NB patients. Our findings suggest, indeed, a potential role for exosomal miR-375 in determining a favourable microenvironment in BM to promote metastatic progression. MiR-375 may, thus, represent a novel biomarker and a potential target for NB patients with BM involvement

The η′g∗g∗\eta^\prime g^* g^* vertex with arbitrary gluon virtualities in the perturbative QCD hard scattering approach

We study the $\eta^\prime g^* g^*$ vertex for arbitrary gluon virtualities in the time-like and space-like regions, using the perturbative QCD hard scattering approach and an input wave-function of the $\eta^\prime$-meson consistent with the measured $\eta^\prime \gamma^* \gamma$ transition form factor. The contribution of the gluonic content of the $\eta^\prime$-meson is taken into account, enhancing the form factor over the entire virtuality considered. However, data on the electromagnetic transition form factor of the $\eta^\prime$-meson is not sufficient to quantify the gluonic enhancement. We also study the effect of the transverse momenta of the partons in the $\eta^\prime$-meson on the $\eta^\prime g^* g^*$ vertex, using the modified hard scattering approach based on Sudakov formalism. Analytic expressions for the $\eta^\prime g^* g^*$ vertex are presented in limiting kinematic regions and parametrizations are given satisfying the QCD anomaly, for real gluons, and perturbative QCD behavior for large gluon virtualities, in both the time-like and space-like regions. Our results have implications for the inclusive decay $B \to \eta^\prime X$ and exclusive decays, such as $B \to \eta^\prime (K,K^*)$, and in hadronic production processes $N + N (\bar N) \to \eta^\prime X$.Comment: 23 pages, 19 figures (requires revtex4, amssymb, epsf); several typos corrected, this version now identical to the one accepted for publication in Phys. Rev.

Interaction between SNAI2 and MYOD enhances oncogenesis and suppresses differentiation in Fusion Negative Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is an aggressive pediatric malignancy of the muscle, that includes Fusion Positive (FP)-RMS harboring PAX3/7-FOXO1 and Fusion Negative (FN)-RMS commonly with RAS pathway mutations. RMS express myogenic master transcription factors MYOD and MYOG yet are unable to terminally differentiate. Here, we report that SNAI2 is highly expressed in FN-RMS, is oncogenic, blocks myogenic differentiation, and promotes growth. MYOD activates SNAI2 transcription via super enhancers with striped 3D contact architecture. Genome wide chromatin binding analysis demonstrates that SNAI2 preferentially binds enhancer elements and competes with MYOD at a subset of myogenic enhancers required for terminal differentiation. SNAI2 also suppresses expression of a muscle differentiation program modulated by MYOG, MEF2, and CDKN1A. Further, RAS/MEK-signaling modulates SNAI2 levels and binding to chromatin, suggesting that the differentiation blockade by oncogenic RAS is mediated in part by SNAI2. Thus, an interplay between SNAI2, MYOD, and RAS prevents myogenic differentiation and promotes tumorigenesis

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012