Background and Aims
Mutations in TERT (telomerase reverse transcriptase) promoter are established gatekeepers in early hepatocarcinogenesis, but little is known about other molecular alterations ...driving this process. Epigenetic deregulation is a critical event in early malignancies. Thus, we aimed to (1) analyze DNA methylation changes during the transition from preneoplastic lesions to early HCC (eHCC) and identify candidate epigenetic gatekeepers, and to (2) assess the prognostic potential of methylation changes in cirrhotic tissue.
Approach and Results
Methylome profiling was performed using Illumina HumanMethylation450 (485,000 cytosine‐phosphateguanine, 96% of known cytosine‐phosphateguanine islands), with data available for a total of 390 samples: 16 healthy liver, 139 cirrhotic tissue, 8 dysplastic nodules, and 227 HCC samples, including 40 eHCC below 2cm. A phylo‐epigenetic tree derived from the Euclidean distances between differentially DNA‐methylated sites (n = 421,997) revealed a gradient of methylation changes spanning healthy liver, cirrhotic tissue, dysplastic nodules, and HCC with closest proximity of dysplasia to HCC. Focusing on promoter regions, we identified epigenetic gatekeeper candidates with an increasing proportion of hypermethylated samples (beta value > 0.5) from cirrhotic tissue (<1%), to dysplastic nodules (≥25%), to eHCC (≥50%), and confirmed inverse correlation between DNA methylation and gene expression for TSPYL5 (testis‐specific Y‐encoded‐like protein 5), KCNA3 (potassium voltage‐gated channel, shaker‐related subfamily, member 3), LDHB (lactate dehydrogenase B), and SPINT2 (serine peptidase inhibitor, Kunitz type 2) (all P < 0.001). Unsupervised clustering of genome‐wide methylation profiles of cirrhotic tissue identified two clusters, M1 and M2, with 42% and 58% of patients, respectively, which correlates with survival (P < 0.05), independent of etiology.
Conclusions
Genome‐wide DNA‐methylation profiles accurately discriminate the different histological stages of human hepatocarcinogenesis. We report on epigenetic gatekeepers in the transition between dysplastic nodules and eHCC. DNA‐methylation changes in cirrhotic tissue correlate with clinical outcomes.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Transfusion of packed red blood cells (PRBC) to patients in critical states is often accompanied by post-transfusion complications. This may be related with disturbance of properties of PRBC and ...their membranes during long-term storage in the hemopreservative solution. The purpose of our work is the study of transformation of morphology, membranes stiffness and nanostructure for assessment of PRBC quality, in vitro. By atomic force microscopy we studied the transformation of cell morphology, the appearance of topological nanodefects of membranes and by atomic force spectroscopy studied the change of membrane stiffness during 40 days of storage of PRBC. It was shown that there is a transition period (20-26 days), in which we observed an increase in the Young's modulus of the membranes 1.6-2 times and transition of cells into irreversible forms. This process was preceded by the appearance of topological nanodefects of membranes. These parameters can be used for quality assessment of PRBC and for improvement of transfusion rules.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Using a FDTD-method implemented in the FullWAVE (RSoft) software, a process of generating optical vortices during the propagation of a left- or right-hand circularly polarized Gaussian pulse through ...a phase and amplitude spiral zone plate with topological charge 2, a diameter of 8 μm, and a focal length of 532 nm is numerically modeled. An investigation of the amplitude and phase distributions in the focal plane shows the presence of optical vortices with topological charge 2. Analysis of the longitudinal component of the Umov-Poynting vector shows the presence of an inverse energy flow in the focal plane. In the case of using an amplitude spiral zone plate, the magnitude of the reverse flow decreases sharply until it disappears completely for the left circularly polarized incident beams.
The formation of an optical vortex by a silver spiral zone plate was presented by using the finite-difference time-domain method implemented in FullWVE (RSoft). Both the left and right circularly ...polarized Gaussian beams at the wavelength of 532 nm have been used as an incident light. Spiral zone plate with the topological charge of 2 μm the diameter of 8 μm and the focal length of 532 nm made in 100 nm silver film produces an optical vortex with the maximum intensity of 55 a.u. at the focal plane.
The formation of a narrow nanojet by polyester microcylinder with metall shell was presented by using the finite element method implemented in COMSOL Myltiphysics. Linear polarized light at a ...wavelength of 532 nm was used as incident light. The presence of a metal layer allows to increase the focal depth.
The acute phase of spinal cord injury is characterized by excitotoxic and inflammatory events that mediate extensive neuronal loss in the gray matter. Neural crest stem cells (NCSCs) can exert ...neuroprotective and anti-inflammatory effects that may be mediated by soluble factors. We therefore hypothesize that transplantation of NCSCs to acutely injured spinal cord slice cultures (SCSCs) can prevent neuronal loss after excitotoxic injury. NCSCs were applied onto SCSCs previously subjected to
N
-methyl-
d
-aspartate (NMDA)-induced injury. Immunohistochemistry and TUNEL staining were used to quantitatively study cell populations and apoptosis. Concentrations of neurotrophic factors were measured by ELISA. Migration and differentiation properties of NCSCs on SCSCs, laminin, or hyaluronic acid hydrogel were separately studied. NCSCs counteracted the loss of NeuN-positive neurons that was otherwise observed after NMDA-induced excitotoxicity, partly by inhibiting neuronal apoptosis. They also reduced activation of both microglial cells and astrocytes. The concentration of brain-derived neurotrophic factor (BDNF) was increased in supernatants from SCSCs cultured with NCSCs compared to SCSCs alone and BDNF alone mimicked the effects of NCSC application on SCSCs. NCSCs migrated superficially across the surface of SCSCs and showed no signs of neuronal or glial differentiation but preserved their expression of SOX2 and Krox20. In conclusion, NCSCs exert neuroprotective, anti-apoptotic and glia-inhibitory effects on excitotoxically injured spinal cord tissue, some of these effects mediated by secretion of BDNF. However, the investigated NCSCs seem not to undergo neuronal or glial differentiation in the short term since markers indicative of an undifferentiated state were expressed during the entire observation period.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The catalytic activity of nanotubular titanium dioxide films formed during the oxidation of acetone to carbon dioxide under the action of visible light with a wavelength of 450 nm was found to be ...approximately 2 times higher compared to standard titanium dioxide (Degussa P25). The nanotubular films were grown by the anodization of titanium foil using an original technique. Diffuse reflectance spectra of the films are attributed to enhanced activity in the visible spectrum by the nonstoichiometry of titanium dioxide near the interface between the nanotubular film and the titanium foil substrate.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
In this paper, the design of a plasmonic lens in gold and silver thin films for focusing the light with radial polarization is presented. Using the finite difference time domain method the ...optimal parameters of the plasmonic lens design are found. It was shown that the silver plasmonic lens produces a tight focal spot with a full width at half maximum of 0.38 of the incident light wavelength.
Using near-field scanning microscopy, we demonstrate that a 15-µm zone plate fabricated in a 70-nm chromium film sputtered on a glass substrate and having a focal length and outermost zone's width ...equal to the incident wavelength λ = 532 nm, focuses a circularly polarized Gaussian beam into a circular subwavelength focal spot whose diameter at the full-width of half-maximum intensity is FWHM = 0.47λ. This value is in near-accurate agreement with the FDTD-aided numerical estimate of FWHM = 0.46λ. When focusing a Gaussian beam linearly polarized along the y-axis, an elliptic subwavelength focal spot is experimentally found to measure FWHMx = 0.42λ (estimated value FWHMx = 0.40λ) and FWHMy = 0.64λ. The subwavelength focal spots presented here are the tightest among all attained so far for homogeneously polarized beams by use of non-immersion amplitude zone plates.
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