BackgroundTraditional risk factors are insufficient to explain all cases of coronary artery disease (CAD) in patients with diabetes mellitus (DM). Advanced glycation end-products (AGEs) and their receptors may play important roles in the development and progression of CAD.BodyHyperglycemia is the hallmark feature of DM. An increase in the incidence of both micro-and macrovascular complications of diabetes has been observed with increased duration of hyperglycemia. This association persists even after glycemic control has been achieved, suggesting an innate mechanism of “metabolic memory.” AGEs are glycated proteins that may serve as mediators of metabolic memory due to their increased production in the setting of hyperglycemia and generally slow turnover. Elevated AGE levels can lead to abnormal cross linking of extracellular and intracellular proteins disrupting their normal structure and function. Furthermore, activation of AGE receptors can induce complex signaling pathways leading to increased inflammation, oxidative stress, enhanced calcium deposition, and increased vascular smooth muscle apoptosis, contributing to the development of atherosclerosis. Through these mechanisms, AGEs may be important mediators of the development of CAD. However, clinical studies regarding the role of AGEs and their receptors in advancing CAD are limited, with contradictory results.ConclusionAGEs and their receptors may be useful biomarkers for the presence and severity of CAD. Further studies are needed to evaluate the utility of circulating and tissue AGE levels in identifying asymptomatic patients at risk for CAD or to identify patients who may benefit from invasive intervention.

This study introduces novel methods for assessing RNA from postmortem samples. It increases the reported cases of HCV in the brain, provides the first E1 sequences from the brain, and contributes to the growing evidence that HCV replicates and evolves within the brain.

Purpose Hepatitis C virus (HCV) infection can promote the development of hepatocellular carcinoma (HCC). Published data implicate the HCV core gene in oncogenesis. We tested the hypothesis that core gene sequences from HCC patients differ from those of patients without cirrhosis/HCC. Experimental Design Full-length HCV sequences from HCC patients and controls were obtained from the investigators and GenBank and compared to each other. A logistic regression model was developed to predict the HCC risk of individual point mutations and other sequence features. Mutations in partial sequences (bases 36–288) from HCC patients and controls were also analyzed. The first base of the AUG start codon was designated position 1. Results A logistic regression model developed through analysis of full-length core gene sequences identified seven polymorphisms significantly associated with increased HCC risk (36G/C, 209A, 271U/C, 309A/C, 435A/C, 481A, 546A/C) and an interaction term (for 209A-271U/C) that had an odds ratio < 1.0. Three of these polymorphisms could be analyzed in the partial sequences. Two of them, 36G/C and 209A, were again associated with increased HCC risk, but 271U/C, was not. The odds ratio of 209A-271U/C was not significant. Conclusions HCV core genes from patients with and without HCC differ at several positions. Of interest, 209A has been associated with interferon resistance and HCC in previous studies. Our findings suggest that HCV core gene sequence data might provide useful information about HCC risk. Prospective investigation is needed to establish the temporal relationship between the appearance of the viral mutations and development of HCC.

Many RNA viruses exist as a cloud of closely related sequence variants called a quasispecies, rather than as a population of identical clones. In this article, we explain the quasispecies nature of RNA viral genomes, and briefly review the principles of quasispecies dynamics and the differences with classical population genetics. We then discuss the current methods for quasispecies analysis and conclude with the biological implications of this phenomenon, focusing on the hepatitis C virus.