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51.
Manar Aoun Ilaria Passerini Pietro Chiurazzi Marianthi Karali Irene De Rienzo Giovanna Sartor Vittoria Murro Natalia Filimonova Marco Seri Sandro Banfi 《International journal of molecular sciences》2021,22(13)
Inherited retinal diseases (IRDs) are a heterogeneous group of conditions that include retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) and early-onset severe retinal dystrophy (EO[S]RD), which differ in severity and age of onset. IRDs are caused by mutations in >250 genes. Variants in the RPE65 gene account for 0.6–6% of RP and 3–16% of LCA/EORD cases. Voretigene neparvovec is a gene therapy approved for the treatment of patients with an autosomal recessive retinal dystrophy due to confirmed biallelic RPE65 variants (RPE65-IRDs). Therefore, the accurate molecular diagnosis of RPE65-IRDs is crucial to identify ‘actionable’ genotypes—i.e., genotypes that may benefit from the treatment—and is an integral part of patient management. To date, hundreds of RPE65 variants have been identified, some of which are classified as pathogenic or likely pathogenic, while the significance of others is yet to be established. In this review, we provide an overview of the genetic diagnostic workup needed to select patients that could be eligible for voretigene neparvovec treatment. Careful clinical characterization of patients by multidisciplinary teams of experts, combined with the availability of next-generation sequencing approaches, can accelerate patients’ access to available therapeutic options. 相似文献
52.
Giulio Verna Marina Liso Elisabetta Cavalcanti Giusy Bianco Veronica Di Sarno Angelo Santino Pietro Campiglia Marcello Chieppa 《International journal of molecular sciences》2021,22(15)
Dendritic cells (DCs) can be divided by lineage into myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs). They both are present in mucosal tissues and regulate the immune response by secreting chemokines and cytokines. Inflammatory bowel diseases (IBDs) are characterized by a leaky intestinal barrier and the consequent translocation of bacterial lipopolysaccharide (LPS) to the basolateral side. This results in DCs activation, but the response of pDCs is still poorly characterized. In the present study, we compared mDCs and pDCs responses to LPS administration. We present a broad panel of DCs secreted factors, including cytokines, chemokines, and growth factors. Our recent studies demonstrated the anti-inflammatory effects of quercetin administration, but to date, there is no evidence about quercetin’s effects on pDCs. The results of the present study demonstrate that pDCs can respond to LPS and that quercetin exposure modulates soluble factors release through the same molecular pathway used by mDCs (Slpi, Hmox1, and AP-1). 相似文献
53.
Margaret Ottaviano Emilio Francesco Giunta Marianna Tortora Marcello Curvietto Laura Attademo Davide Bosso Cinzia Cardalesi Mario Rosanova Pietro De Placido Erica Pietroluongo Vittorio Riccio Brigitta Mucci Sara Parola Maria Grazia Vitale Giovannella Palmieri Bruno Daniele Ester Simeone 《International journal of molecular sciences》2021,22(7)
As widely acknowledged, 40–50% of all melanoma patients harbour an activating BRAF mutation (mostly BRAF V600E). The identification of the RAS–RAF–MEK–ERK (MAP kinase) signalling pathway and its targeting has represented a valuable milestone for the advanced and, more recently, for the completely resected stage III and IV melanoma therapy management. However, despite progress in BRAF-mutant melanoma treatment, the two different approaches approved so far for metastatic disease, immunotherapy and BRAF+MEK inhibitors, allow a 5-year survival of no more than 60%, and most patients relapse during treatment due to acquired mechanisms of resistance. Deep insight into BRAF gene biology is fundamental to describe the acquired resistance mechanisms (primary and secondary) and to understand the molecular pathways that are now being investigated in preclinical and clinical studies with the aim of improving outcomes in BRAF-mutant patients. 相似文献
54.
Luisa Siculella Laura Giannotti Benedetta Di Chiara Stanca Matteo Calcagnile Alessio Rochira Eleonora Stanca Pietro Alifano Fabrizio Damiano 《International journal of molecular sciences》2021,22(8)
Reactive intermediate deaminase (Rid) proteins are enzymes conserved in all domains of life. UK114, a mammalian member of RidA subfamily, has been firstly identified as a component of liver perchloric acid-soluble proteins (L-PSP). Although still poorly defined, several functions have been attributed to the mammalian protein UK114/RIDA, including the reactive intermediate deamination activity. The expression of UK114/RIDA has been observed in some tumors, arousing interest in this protein as an evaluable tumor marker. However, other studies reported a negative correlation between UK114/RIDA expression, tumor differentiation degree and cell proliferation. This work addressed the question of UK114/RIDA expression in human non-tumor HEK293 cell lines and in some human tumor cell lines. Here we reported that human RIDA (hRIDA) was expressed in all the analyzed cell line and subjected to lysine (K-)succinylation. In HEK293, hRIDA K-succinylation was negatively correlated to the cell proliferation rate and was under the control of SIRT5. Moreover, K-succinylation clearly altered hRIDA quantification by immunoblotting, explaining, at least in part, some discrepancies about RIDA expression reported in previous studies. We found that hRIDA was able to deaminate reactive enamine-imine intermediates and that K-succinylation drastically reduced deaminase activity. As predicted by in silico analysis, the observed reduction of deaminase activity has been related to the drastic alterations of hRIDA structure inferred by K-succinylation. The role of hRIDA and the importance of its K-succinylation in cell metabolism, especially in cancer biology, have been discussed. 相似文献
55.
Maria Stella Simonetti Francesca BlasiAncilla Bosi Angela MauriziLina Cossignani Pietro Damiani 《Food chemistry》2008
The fatty acid compositions and the positional distributions of fatty acid in triacylglycerol (TAGs) and phospholipid (PLs) fractions of four cultured freshwater fish species (Salmo trutta, Ictalurus punctatus, Ictalurus melas and Micropterus salmoides) were investigated. As regards the TAGs fraction, the S. trutta (trout) and I. punctatus (channel catfish) species had the highest % content in n3 polyunsaturated fatty acids (PUFAs) and the lowest n6/n3 ratio; this ratio resulted always lower than 1 in all the considered fish species. The PLs fraction of the considered fish was very interesting because of the high percentage of PUFAs, both in phosphatidylcholines and in phosphatidylethanolamines. The fatty acid distribution among the three sn-positions of the glycerol backbone was non-random; generally, both n6 and n3 PUFAs were mainly distributed between sn-2- and sn-3-positions of TAGs while the contents in sn-1-position were generally lower; in PLs fraction these fatty acids preferred the sn-2-position. 相似文献
56.
Accumulation parameters and seasonal trends for PCBs in temperate and boreal forest plant species 总被引:1,自引:0,他引:1
Nizzetto L Pastore C Liu X Camporini P Stroppiana D Herbert B Boschetti M Zhang G Brivio PA Jones KC Di Guardo A 《Environmental science & technology》2008,42(16):5911-5916
The concentration of polychlorinated biphenyls (PCBs) in the air and vegetation was measured periodically in two alpine forests, during the growing season. Foliage samples from nine plant species typical of the temperate and boreal environment were collected and analyzed. Leaf concentrations of tri- and tetra-CBs showed fast response times with changing temperature and gas-phase concentrations, suggesting that a partitioning equilibrium is approached relatively rapidly (few days) in the field. Heavier compounds showed kinetically limited accumulation trends, not reaching equilibrium during the growing season. Results were used to estimate the bioconcentration factors or equilibrium plant/air partition coefficient (KPA) for each species. Values of log KPA (calculated on a mass/volume basis) ranged between 0.78 and 1.96 and were correlated to the log KOA. Uptake trends of the higher chlorinated compounds showed intraspecific differences which were partially explained by the specific leaf area (SLA). 相似文献
57.
Isolation of red wine components with anti-adhesion and anti-biofilm activity against Streptococcus mutans 总被引:1,自引:0,他引:1
Maria Daglia Monica Stauder Adele Papetti Caterina Signoretto Giovanni Giusto Pietro Canepari Carla Pruzzo Gabriella Gazzani 《Food chemistry》2010
Red wine is a widely consumed beverage with multiple beneficial effects on human health. In the present paper, the anticaries properties of red wine were studied in vitro and ex vivo. Our in vitro findings shows that dealcoholised red wine, besides exerting antibacterial activity, strongly interferes with Streptococcus mutans adhesion to saliva-coated hydroxyapatite (sHA) beads, promotes its detachment from sHA, and powerfully inhibits in vitro biofilm formation. The main components responsible for such activities were found to be proanthocyanidins. The ability of red wine to inhibit ex vivoS. mutans biofilm formation on the occlusal surface of natural human teeth also was demonstrated. 相似文献
58.
Subhash C. Mishra Himanshu Poonia Arup K. Das Pietro Asinari R. Borchiellini 《Numerical Heat Transfer, Part A: Applications》2013,63(6):669-688
Application of the lattice Boltzmann method (LBM) recently extended by Pietro et al. [P. Asinari, S. C. Mishra, and R. Borchiellini, A Lattice Boltzmann Formulation to the Analysis of Radiative Heat Transfer Problems in a Participating Medium, Numer. Heat Transfer B, 57(2), 126–146, 2010] for calculation of volumetric radiative information is extended for the analysis of a combined mode transient conduction and radiation heat transfer in a 2D rectangular enclosure containing an absorbing, emitting and scattering medium. Unlike all previous studies, with volumetric radiative information computed using the proposed LBM, the energy equation is formulated and solved using the LBM. In the combined mode conduction–radiation problem, to assess the computational advantage of computing the radiative information too using the LBM, the same problem is also solved using the LBM–finite volume method (FVM) formulation. In this LBM–FVM formulation, the FVM is used to calculate the volumetric radiative information needed for the energy equation, and the energy equation is solved using the LBM. Comparisons are made for the effects of the extinction coefficient, the scattering albedo and the conduction–radiation parameter on the temperature distributions in the medium. Although the number of iterations for the converged solution in LBM–LBM is much more than that of the LBM–FVM, computationally, the LBM–LBM is faster than the LBM–FVM. 相似文献
59.
A 2D vortex panel model with a viscous boundary layer formulation has been developed for the numerical simulation of a vertical axis wind turbine (VAWT), including the operation in dynamic stall. The model uses the ‘double wake’ concept to reproduce the main features of the unsteady separated flow, including the formation and shedding of strong vortical structures and the wake–blade interaction. The potential flow equations are solved together with the integral boundary layer equations by using a semi‐inverse iterative algorithm. A new criterion for the reattachment of the boundary layer during the downstroke of a dynamically stalled aerofoil is implemented. The model has been validated against experimental data of steady aerofoils and pitching aerofoils in dynamic stall at high and low Reynolds numbers (Re = 1.5 × 106 and Re = 5 × 104). For the low Reynolds number case, time‐resolved 2D particle image velocimetry (PIV) measurements have been performed on a pitching NACA 0012 aerofoil in dynamic stall. The PIV vorticity fields past the oscillating aerofoil are used to test the model capability of capturing the formation, growth and release of the strong leading edge vortex that characterizes the dynamic stall. Furthermore, the forces extracted from the PIV velocity fields are compared with the predicted ones for a quantitative validation of the model. Finally, the model is applied to the computation of the wake flow past a VAWT in dynamic stall; the predicted vorticity fields and forces are in good agreement with phase‐locked PIV data and CFD‐DES available in the literature. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
60.
Mariapaola Parisi Alberto GiaconiaSalvatore Sau Annarita SpadoniGiampaolo Caputo Pietro Tarquini 《International Journal of Hydrogen Energy》2011,36(3):2007-2013
This paper reports an investigation on the Bunsen reaction. An experimental campaign was conducted by means of a stirred reactor. Runs were carried out at a constant temperature in the 30-120 °C range, following a semi-batch procedure by feeding gaseous sulfur dioxide in an iodine/hydriodic acid/water solution. A specific analytical procedure to measure the hydriodic phase composition was implemented. It was observed that both the amount of absorbed SO2 and its conversion lowered as the temperature increased. Secondary reactions were beyond the detection limit in the reactor, even at low temperature and low iodine content. The purification of the produced hydriodic phase was also investigated. It was possible to satisfactorily reduce the impurities content without the occurrence of secondary reactions only when high temperature and high iodine content were applied. 相似文献