Translational research : the journal of laboratory and clinical medicine
-
Lipid and lipoprotein metabolism in zebrafish and in humans are remarkably similar. Zebrafish express all major nuclear receptors, lipid transporters, apolipoproteins and enzymes involved in lipoprotein metabolism. Unlike mice, zebrafish express cetp and the Cetp activity is detected in zebrafish plasma. ⋯ In this review article, we discuss recent advances in using dyslipidemic zebrafish in atherosclerosis-related studies. We also summarize recent work connecting lipid metabolism with regulation of angiogenesis, the work that considerably benefited from using the zebrafish model. These studies uncovered the role of aibp, abca1, abcg1, mtp, apoB, and apoC2 in regulation of angiogenesis in zebrafish and paved the way for future studies in mammals, which may suggest new therapeutic approaches to modulation of excessive or diminished angiogenesis contributing to the pathogenesis of human disease.
-
Individuals with type 2 diabetes are significantly more susceptible to pneumococcal infections than healthy individuals of the same age. Increased susceptibility is the result of impairments in both innate and adaptive immune systems. Given the central role of T-helper 17 (Th17) and T-regulatory (Treg) cells in pneumococcal infection and their altered phenotype in diabetes, this study was designed to analyze the Th17 and Treg cell responses to a whole heat-killed capsular type 2 strain of Streptococcus pneumoniae. ⋯ However, stratification of data by obesity indicated a significant increase in frequency of CD4+ and Th17 cells in obese individuals with diabetes compared with nonobese individual with diabetes. The memory CD+T-cell response was associated inversely with both fasting blood glucose and percent glycated hemoglobin A1c. This study demonstrated that those with type 2 diabetes have a diminished pathogen-specific memory CD4+ and Th17 response, and low percentages of CD+T-cells in response to S. pneumoniae stimulation.
-
The purpose of this review is to highlight the importance of telomeres, the mechanisms implicated in their maintenance, and their role in the etiology as well as the treatment of human esophageal cancer. We will also discuss the role of telomeres in the maintenance and preservation of genomic integrity, the consequences of telomere dysfunction, and the various factors that may affect telomere health in esophageal tissue predisposing it to oncogenesis. There has been growing evidence that telomeres, which can be affected by various intrinsic and extrinsic factors, contribute to genomic instability, oncogenesis, as well as proliferation of cancer cells. ⋯ This indicates that telomere maintenance mechanisms may potentially be targeted to make esophageal cancer cells static. The rate at which telomeres in healthy cells shorten is determined by a number of intrinsic and extrinsic factors, including those associated with lifestyle. Avoidance of factors that may directly or indirectly injure esophageal tissue including its telomeric and other genomic DNA can not only reduce the risk of development of esophageal cancer but may also have positive impact on overall health and lifespan.
-
Telomeres are DNA-protein structures that form a protective cap on chromosome ends. As such, they prevent the natural ends of linear chromosomes from being subjected to DNA repair activities that would result in telomere fusion, degradation, or recombination. Both the DNA and protein components of the telomere are required for this essential function, because insufficient telomeric DNA length, loss of the terminal telomeric DNA structure, or deficiency of key telomere-associated factors may elicit a DNA damage response and result in cellular senescence or apoptosis. ⋯ We provide an overview of basic telomere structure and maintenance. We outline the telomere biology defects observed in dyskeratosis congenita, focusing on recent discoveries in this field. Last, we review the evidence of how telomere biology may impact sporadic aplastic anemia and the risk for various cancers.