RESUMO
Hepatitis B virus (HBV) infects approximately 300 million people worldwide, causing chronic infections. The HBV X protein (HBx) is crucial for viral replication and induces reactive oxygen species (ROS), leading to cellular damage. This study explores the relationship between HBx-induced ROS, p53 activation, and HBV replication. Using HepG2 and Hep3B cell lines that express the HBV receptor NTCP, we compared ROS generation and HBV replication relative to p53 status. Results indicated that HBV infection significantly increased ROS levels in p53-positive HepG2-NTCP cells compared to p53-deficient Hep3B-NTCP cells. Knockdown of p53 reduced ROS levels and enhanced HBV replication in HepG2-NTCP cells, whereas p53 overexpression increased ROS and inhibited HBV replication in Hep3B-NTCP cells. The ROS scavenger N-acetyl-L-cysteine (NAC) reversed these effects. The study also found that ROS-induced degradation of the HBx is mediated by the E3 ligase Siah-1, which is activated by p53. Mutations in p53 or inhibition of its transcriptional activity prevented ROS-mediated HBx degradation and HBV inhibition. These findings reveal a p53-dependent negative feedback loop where HBx-induced ROS increases p53 levels, leading to Siah-1-mediated HBx degradation and HBV replication inhibition. This study offers insights into the molecular mechanisms of HBV replication and identifies potential therapeutic targets involving ROS and p53 pathways.
Assuntos
Carcinoma Hepatocelular , Vírus da Hepatite B , Neoplasias Hepáticas , Espécies Reativas de Oxigênio , Transativadores , Proteína Supressora de Tumor p53 , Ubiquitina-Proteína Ligases , Proteínas Virais Reguladoras e Acessórias , Replicação Viral , Humanos , Proteína Supressora de Tumor p53/metabolismo , Vírus da Hepatite B/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Transativadores/metabolismo , Transativadores/genética , Células Hep G2 , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/virologia , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/virologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Linhagem Celular TumoralRESUMO
The tumour suppressor p53 has been implicated in the host defence system against hepatitis C virus (HCV) infection, although the detailed mechanism remains unknown. Here, we found that p53 inhibits HCV replication by downregulating HCV Core protein levels in human hepatoma cells. For this effect, p53 potentiated the role of E6-associated protein (E6AP) as an E3 ligase to induce ubiquitination and proteasomal degradation of HCV Core. Specifically, p53 facilitated the binding of E6AP to HCV Core through direct interactions with the two proteins. In addition, E6AP failed to induce ubiquitination of HCV Core in the absence of p53, suggesting that p53 increases the E3 ligase activity of E6AP in a triple complex consisting of p53, E6AP and HCV Core.
Assuntos
Hepatite C , Neoplasias , Proteínas Oncogênicas Virais , Hepacivirus/metabolismo , Humanos , Proteínas Oncogênicas Virais/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Proteínas do Core Viral/metabolismo , Replicação ViralRESUMO
This article presents a real-time bokeh rendering technique that splats pre-computed sprites but takes dynamic visibilities and intrinsic appearances into account at runtime. To attain alias-free looks without excessive sampling on a lens, the visibilities of strong highlights are densely sampled using rasterization, while regular objects are sparsely sampled using conventional defocus-blur rendering. The intrinsic appearance is dynamically transformed from a precomputed look-up table, which encodes radial aberrations against image distances in a compact 2D texture. Our solution can render complex bokeh effects without undersampling artifacts in real time, and greatly improve the photorealism of defocus-blur rendering.
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This study suggests a method to select core data that will be helpful for machine learning. Specifically, we form a two-dimensional distribution based on the similarity of the training data and compose grids with fixed ratios on the distribution. In each grid, we select data based on the distribution consistency (DC) of the target class data and examine how it affects the classifier. We use CIFAR-10 for the experiment and set various grid ratios from 0.5 to 0.005. The influences of these variables were analyzed with the use of different training data sizes selected based on high-DC, low-DC (inverse of high DC), and random (no criteria) selections. As a result, the average point accuracy at 0.95% (±0.65) and the point accuracy at 1.54% (±0.59) improved for the grid configurations of 0.008 and 0.005, respectively. These outcomes justify an improved performance compared with that of the existing approach (data distribution search). In this study, we confirmed that the learning performance improved when the training data were selected for very small grid and high-DC settings.
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While terrestrial organisms such as livestock are consumed regularly, studies of internal distribution and bioaccumulation of persistent organic pollutants (POPs) have been focused more on aquatic organisms. In this study, we have assessed the internal distribution and fate of legacy (PCDD/Fs and PCBs) and emerging POPs (HBCDs and PFASs), and TBBPA in 42 tissues of a Bos Taurus. PCDD/Fs, DL-PCBs, and HBCDs were found 3, 4, and 4-fold higher in the lipid-rich organs (subcutaneous fat, visceral fat, large intestine) compared to the remaining organs and muscles, owing to their hydrophobic properties. The TBBPA concentration in the excrement was 36-fold higher compared to the average tissues, suggesting a short internal half-life of TBBPA. Among PFASs, PFUnDA displayed 98% contribution from all ionic PFASs in the tissues due to its strong binding affinity, high exposure via feed and water, and increasing emergence of PFUnDA and its precursors in the Southeast Asian countries. While our study suggests that, at the moment, there is no significant health risks to the general Korean population, the future changes in environmental exposure as well as the internal dynamics and fate of various POPs species should be kept in mind when consuming various parts of livestock.
Assuntos
Poluentes Ambientais , Fluorocarbonos , Bifenilos Policlorados , Dibenzodioxinas Policloradas , Animais , Bovinos , Dibenzofuranos , Dibenzofuranos Policlorados/análise , Monitoramento Ambiental , Bifenilos Policlorados/análise , Dibenzodioxinas Policloradas/análiseRESUMO
BACKGROUND AND OBJECTIVES: The purpose of this study is to identify the prevalence of progressive dilation in patients with acute myocardial infarction (AMI) combined with heart failure (HF) and determine the prognostic significance and associated factors with a geometric change of an infarcted heart. SUBJECTS AND METHODS: A total of 1310 AMI patients with HF (63.9±12.5 years, 70% male) between November 2005 and April 2011 underwent echocardiography at admission and one year later. Left ventricular (LV) remodeling is defined as 20% progression, and left atria (LA) remodeling is 10% compared with the initial volume index. RESULTS: The prevalence of both LA and LV remodeling was 13.9%; LV only was 9.3%, LA only 22.8% and non-remodeling was 55.1%, respectively. In the non-remodeling group, Killip class II was more frequent (83.9%, p<0.001) whereas in other remodeling groups, Killip class III was more frequent. Initial wall motion score index, ejection fraction, maximal cardiac enzyme, high sensitive C-reactive protein, B type natriuretic peptide, and triglyceride serum levels were significantly associated with heart remodeling. All causes of death occurred in 168 cases (12.8%) during the follow-up period. Mortality was the highest in the LV and LA remodeling group (20.9%) and the lowest in the non-remodeling group (11.4%). During the period of follow-up, the cumulative survival rate was significantly lower in the groups of LA and LV remodeling than in others (log rank p=0.006). CONCLUSION: Total mortality was significantly increased in patients AMI with geometrically progressive LA and LV dilatation.