Alvarezsahl0774

Carcinogenesis is a complicated process that involves the deregulation of epigenetics, resulting in cellular transformational events, such as proliferation, differentiation, and metastasis. Most chromatin-modifying enzymes utilize metabolites as co-factors or substrates and thus are directly dependent on such metabolites as acetyl-coenzyme A, S-adenosylmethionine, and NAD+. Here, we show that using specific siRNA to deplete a tumor of VDAC1 not only led to reprograming of the cancer cell metabolism but also altered several epigenetic-related enzymes and factors. VDAC1, in the outer mitochondrial membrane, controls metabolic cross-talk between the mitochondria and the rest of the cell, thus regulating the metabolic and energetic functions of mitochondria, and has been implicated in apoptotic-relevant events. We previously demonstrated that silencing VDAC1 expression in glioblastoma (GBM) U-87MG cell-derived tumors, resulted in reprogramed metabolism leading to inhibited tumor growth, angiogenesis, epithelial-mesenchymal transition and invasiveness, and elimination of cancer stem cells, while promoting the differentiation of residual tumor cells into neuronal-like cells. These VDAC1 depletion-mediated effects involved alterations in transcription factors regulating signaling pathways associated with cancer hallmarks. As the epigenome is sensitive to cellular metabolism, this study was designed to assess whether depleting VDAC1 affects the metabolism-epigenetics axis. Using DNA microarrays, q-PCR, and specific antibodies, we analyzed the effects of si-VDAC1 treatment of U-87MG-derived tumors on histone modifications and epigenetic-related enzyme expression levels, as well as the methylation and acetylation state, to uncover any alterations in epigenetic properties. Our results demonstrate that metabolic rewiring of GBM via VDAC1 depletion affects epigenetic modifications, and strongly support the presence of an interplay between metabolism and epigenetics.OBJECTIVE This study aimed to explore the influence of social support on the survival outcomes of patients with nasopharyngeal carcinoma (NPC). We examined whether the combined proxy influenced whether patients were more likely to receive radiotherapy. METHODOLOGY data were collected from the 18 registries of the National Cancer Institute's Surveillance, Epidemiology, and End Results database. The association between both insurance status and marital status and disease-specific survival rates were evaluated with a multivariate Cox proportional-hazards regression model to calculate the hazard ratios and associated confidence intervals. Odds ratio (OR) computed by logistic regression was also used to examine the relationship between the receipt of radiotherapy and insurance and marital status. RESULTS insured and uninsured patients differed significantly in T-stage, N-stage, M-stage, radiotherapy use, race, and marital status. The uninsured-non-married patients showed the lowest 5-year disease-specific survival rates. We further found unmarried patients with either Medicaid (OR, 0.40), or no insurance (OR, 0.24) had lower odds of receiving radiotherapy than those with insurance at diagnosis. CONCLUSIONS uninsured-unmarried NPC patients had a significantly higher risk of distant metastasis at diagnosis, poorer 5-year disease-specific survival, and were less likely to receive radiotherapy than insured-married patients.The prediction of the viscosity of suspensions is of fundamental importance in several fields. Most of the available studies have been focused on particles with simple shapes, for example, spheres or spheroids. In this work, we study the viscosity of a dilute suspension of fractal-shape aggregates suspended in a shear-thinning fluid by direct numerical simulations. The suspending fluid is modeled by the power-law constitutive equation. For each morphology, a map of particle angular velocities is obtained by solving the governing equations for several particle orientations. The map is used to integrate the kinematic equation for the orientation vectors and reconstruct the aggregate orientational dynamics. The intrinsic viscosity is computed by a homogenization procedure along the particle orbits. In agreement with previous results on Newtonian suspensions, the intrinsic viscosity, averaged over different initial orientations and aggregate morphologies characterized by the same fractal parameters, decreases by increasing the fractal dimension, that is, from rod-like to spherical-like aggregates. Shear-thinning further reduces the intrinsic viscosity showing a linear dependence with the flow index in the investigated range. The intrinsic viscosity can be properly scaled with respect to the number of primary particles and the flow index to obtain a single curve as a function of the fractal dimension.In this work, we measured the intensities of Q-branches of the ν1, ν2 and ν3 bands in the polarized and depolarized methane Raman spectra in the pressure range of 1-60 atm. It was established that the pressure dependence of depolarization ratios of the ν2 and ν3 bands are negligible. In turn, the depolarization ratio of the ν1 band increases with increasing pressure and reaches approximately 0.0045 at 60 atm. These data are more precise than previously published ones because ν1 band intensities were determined taking into account the contribution of overlapping lines of ν3 band. The presented data will be useful in calculating the methane polarizabilities at high pressure, as well as in calculating methane Raman spectra for measuring the natural gas composition using Raman spectroscopy.The aim of this study was to prepare pure trans-resveratrol nanoparticles without additives (surfactants, polymers, and sugars) using a supercritical antisolvent (SAS) process with alcohol (methanol or ethanol) and dichloromethane mixtures. In addition, in order to investigate the effect of particle size on the dissolution and oral bioavailability of the trans-resveratrol, two microparticles with different sizes (1.94 μm and 18.75 μm) were prepared using two different milling processes, and compared to trans-resveratrol nanoparticles prepared by the SAS process. The solid-state properties of pure trans-resveratrol particles were characterized. By increasing the percentage of dichloromethane in the solvent mixtures, the mean particle size of trans-resveratrol was decreased, whereas its specific surface area was increased. The particle size could thus be controlled by solvent composition. Trans-resveratrol nanoparticle with a mean particle size of 0.17 μm was prepared by the SAS process using the ethanol/dichloromethane mixture at a ratio of 25/75 (w/w). The in vitro dissolution rate of trans-resveratrol in fasted state-simulated gastric fluid was significantly improved by the reduction of particle size, resulting in enhanced oral bioavailability in rats. The absolute bioavailability of trans-resveratrol nanoparticles was 25.2%. The maximum plasma concentration values were well correlated with the in vitro dissolution rate. These findings clearly indicate that the oral bioavailability of trans-resveratrol can be enhanced by preparing pure trans-resveratrol nanoparticles without additives (surfactants, polymers, and sugars) by the SAS process. These pure trans-resveratrol nanoparticles can be applied as an active ingredient for the development of health supplements, pharmaceutical products, and cosmetic products.BACKGROUND Dietary supplements purported to increase circulating nitric oxide are very popular among consumers. We determined the acute impact of two novel dietary supplements on plasma nitrate/nitrite (NOx) and nitrite alone. METHODS 20 men and women (age 24 ± 5 years) ingested two different nitrate-rich supplements (Resync Recovery Blend at 7.5 g and 15 g; Resync Collagen Blend at 21 g), or placebo, on four different days. Fasting blood samples were obtained before and 75 min following ingestion and analyzed for NOx and nitrite. RESULTS Nitrite was not differently impacted by treatment (p > 0.05). The NOx response for men and women was very similar, with no sex interactions noted (p > 0.05). Condition (p less then 0.0001), time (p less then 0.0001), and condition x time (p less then 0.0001) effects were noted for NOx. Values increased from baseline to post-ingestion for the Resync Recovery Blend at 7.5 g (11 ± 9 to 101 ± 48 µM) and at 15 g (9 ± 5 to 176 ± 91µM), as well as for the Resync Collagen Blend (9 ± 9 to 46 ± 21µM), while values for placebo remained stable (9 ± 7 to 8 ± 5µM). CONCLUSION While nitrite alone was not impacted by treatment, both Resync products result in an increase in plasma NOx, with the increase proportionate to the quantity of "nitric oxide blend" ingredients contained within each product. Future studies are needed to determine the physiological implications of the increased NOx, as pertaining to exercise performance and recovery, in addition to other aspects of human health.BACKGROUND Combining resistance exercise (RE) with nutrient intake stimulates muscle protein net balance. However, it is still unclear whether the optimal timing of nutrient intake is before or after RE, especially on muscle protein breakdown (MPB) for an augmented muscle anabolic response. The aim of this study was to investigate the effect of a substantial mixed meal (i.e., nutrient- and protein-dense whole foods) before or after RE, compared with RE without a meal on the acute response of MPB in a crossover-design study. METHODS Eight healthy young men performed three trials (1) meal intake before RE (Pre), (2) meal intake after RE (Post), and (3) RE without meal intake (No). Plasma insulin and 3-methylhistidine (3-MH), an MPB marker, were measured. RESULTS Time course change in plasma insulin level after RE was significantly higher in the Post condition than in the Pre and No conditions. The area under the curve of 3-MH concentration was significantly lower in the Post condition than in the Pre and No conditions. CONCLUSIONS These results suggest that a substantial mixed meal immediately after RE may effectively suppress MPB in the morning.BACKGROUND Metabolic Syndrome (MetS), a major worldwide concern for the public health system, refers to a cluster of key metabolic components, and represents a risk factor for diabetes and cardiovascular diseases. As oxidative stress (OxS) and inflammation are the major triggers of insulin sensitivity (IS), a cardinal MetS feature, the principal aim of the present work is to determine whether glycomacropeptide (GMP), a milk-derived bioactive peptide, exerts beneficial effects on their expression. METHODS Fully differentiated intestinal Caco-2/15 cells are used to evaluate the preventive action of 2 mg/mL GMP against OxS and inflammation induced by the mixture iron-ascorbate (Fe/Asc) (200 μM2 mM). The potency of GMP of decreasing the production of lipoproteins, including chylomicrons (CM), very-low-density lipoproteins (VLDL) and low-density lipoproteins (LDL) is also assessed. RESULTS The administration of GMP significantly reduces malondialdehyde, a biomarker of lipid peroxidation, and raises superoxide dismutase 2 and glutathione peroxidase via the induction of the nuclear factor erythroid 2-related factor 2, a transcription factor, which orchestrates cellular antioxidant defenses. Similarly, GMP markedly lowers the inflammatory agents tumor necrosis factor-α and cyclooxygenase-2 via abrogation of the nuclear transcription factor-kB. GSK343 Moreover, GMP-treated cells show a down-regulation of Fe/Asc-induced mitogen activated protein kinase pathway, suggesting greater IS. Finally, GMP decreases the production of CM, VLDL, and LDL. CONCLUSIONS Our results highlight the effectiveness of GMP in attenuating OxS, inflammation and lipoprotein biogenesis, as well as improving IS, the key components of MetS. Further investigation is needed to elucidate the mechanisms mediating the preventive action of GMP.