Oxidative stress is a common mediator in pathogenicity of established cardiovascular risk factors. Furthermore, it likely mediates effects of emerging, less well-defined variables that contribute to residual risk not explained by traditional factors. Functional oxidative modifications of cellular proteins, both reversible and irreversible, are a causal step in cellular dysfunction. Identifying markers of oxidative stress has been the focus of many researchers as they have the potential to act as an “integrator” of a multitude of processes that drive cardiovascular pathobiology. One of the major challenges is the accurate quantification of reactive oxygen species with very short half-life. Redox-sensitive proteins with important cellular functions are confined to signalling microdomains in cardiovascular cells and are not readily available for quantification. A popular approach is the measurement of stable by-products modified under conditions of oxidative stress that have entered the circulation. However, these may not accurately reflect redox stress at the cell/tissue level. Many of these modifications are “functionally silent”. Functional significance of the oxidative modifications enhances their validity as a proposed biological marker of cardiovascular disease, and is the strength of the redox cysteine modifications such as glutathionylation. We review selected biomarkers of oxidative stress that show promise in cardiovascular medicine, as well as new methodologies for high-throughput measurement in research and clinical settings. Although associated with disease severity, further studies are required to examine the utility of the most promising oxidative biomarkers to predict prognosis or response to treatment.

No abstract

No abstract

No abstract

No abstract

No abstract

BackgroundHepatocellular carcinoma (HCC) guidelines recommend ultrasound screening in high-risk patients. However, in some patients, ultrasound image quality is suboptimal due to factors such as hepatic steatosis, cirrhosis, and confounding lesions. Our aim was to investigate an abbreviated non-contrast magnetic resonance imaging (aNC-MRI) protocol as a potential alternative screening method.MethodsA retrospective study was performed using consecutive liver MRI studies performed over 3 years, with set exclusion criteria. The unenhanced T2-weighted, T1-weighted Dixon, and diffusion-weighted sequences were extracted from MRI studies with a known diagnosis. Each anonymised aNC-MRI study was read by three radiologists who stratified each study into either return to 6 monthly screening or investigate with a full contrast-enhanced MRI study.ResultsA total of 188 patients were assessed; 28 of them had 42 malignant lesions, classified as Liver Imaging Reporting and Data System 4, 5, or M. On a per-patient basis, aNC-MRI had a negative predictive value (NPV) of 97% (95% confidence interval [CI] 95–98%), not significantly different in patients with steatosis (99%, 95% CI 93–100%) and no steatosis (97%, 95% CI 94–98%). Per-patient sensitivity and specificity were 85% (95% CI 75–91%) and 93% (95% CI 90–95%).ConclusionOur aNC-MRI HCC screening protocol demonstrated high specificity (93%) and NPV (97%), with a sensitivity (85%) comparable to that of ultrasound and gadoxetic acid contrast-enhanced MRI. This screening method was robust to hepatic steatosis and may be considered an alternative in the case of suboptimal ultrasound image quality.

To understand the biology of the interactome, the covisualization of protein interactions and other protein-related data is required. In this study, we have adapted a 3-D network visualization platform, GEOMI, to allow the coanalysis of protein-protein interaction networks with proteomic parameters such as protein localization, abundance, physicochemical parameters, post-translational modifications, and gene ontology classification. Working with Saccharomyces cerevisiae data, we show that rich and interactive visualizations, constructed from multidimensional orthogonal data, provide insights on the complexity of the interactome and its role in biological processes and the architecture of the cell. We present the first organelle-specific interaction networks, that provide subinteractomes of high biological interest. We further present some of the first views of the interactome built from a new combination of yeast two-hybrid data and stable protein complexes, which are likely to approximate the true workings of stable and transient aspects of the interactome. The GEOMI tool and all interactome data are freely available by contacting the authors.