Histone deacetylase regulates high mobility group A2-targeting microRNAs in human cord blood-derived multipotent stem cell aging

Cellular senescence involves a reduction in adult stem cell self-renewal, and epigenetic regulation of gene expression is one of the main underlying mechanisms. Here, we observed that the cellular senescence of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs) caused by inhibition of histone deacetylase (HDAC) activity leads to down-regulation of high mobility group A2 (HMGA2) and, on the contrary, to up-regulation of p16INK4A, p21CIP1/WAF1 and p27KIP1. We found that let-7a1, let-7d, let-7f1, miR-23a, miR-26a and miR-30a were increased during replicative and HDAC inhibitor-mediated senescence of hUCB-MSCs by microRNA microarray and real-time quantitative PCR. Furthermore, the configurations of chromatins beading on these miRNAs were prone to transcriptional activation during HDAC inhibitor-mediated senescence. We confirmed that miR-23a, miR-26a and miR-30a inhibit HMGA2 to accelerate the progress of senescence. These findings suggest that HDACs may play important roles in cellular senescence by regulating the expression of miRNAs that target HMGA2 through histone modification

Alcohol use behaviors and risk of metabolic syndrome in South Korean middle-aged men

<p>Abstract</p> <p>Background</p> <p>It is thought that small volumes of alcohol may have positive effects on health. However, excessive drinking results in serious health problems. An accurate method to determine individual alcohol use behaviors are needed to assess objectively the extent to which drinking affects health. This study investigated the association between risk of metabolic syndrome (MetS) and alcohol use behaviors in middle-aged South Korean men using the Alcohol Use Disorders Identification Test.</p> <p>Methods</p> <p>This study used data from the South Korea National Health and Nutrition Examination (KNHANES) IV (2008), which extracted the standard survey household by using the proportional systematic sampling method. Data of 714 participants from KNHANES IV, 2008 were analyzed using Surveyfreq and Surveylogistic regression to investigate the association between MetS and alcohol use behaviors in middle-aged South Korean men.</p> <p>Results</p> <p>After adjustment for education, smoking, and physical activity, alcohol use behaviors were significantly associated with an increased risk of hypertension [odds ratio (OR) = 2.54, 95% confidence interval (CI) = 1.5-4.06 in the hazardous group; OR = 2.99, 95% CI = 1.84-4.92 in the problem group]; impaired fasting glucose (OR = 2.15, 95% CI = 1.16-3.99 in the hazardous group; OR = 2.48, 95% CI = 1.42-4.33 in the problem group); dyslipidemia (OR = 2.19, 95% CI = 1.38-3.47 in the problem group); abdominal obesity (OR = 1.93, 95% CI = 1.17-3.19 in the hazardous group; OR = 1.85, 95% CI = 1.17-2.92 in the problem group); and MetS (OR = 2.16, 95% CI = 1.24-3.77 in the hazardous group; OR = 2.54, 95% CI = 1.41-4.58 in problem group).</p> <p>Conclusions</p> <p>This study found that excessive alcohol use behaviors increased the risk of hypertension, diabetes, dyslipidemia, abdominal obesity, and MetS. Considering the rising rate of alcohol consumption and heavy drinking at single sittings, a culture of less risky alcohol consumption must be established to promote health among middle-aged men.</p

Epigenomic analysis of aberrantly methylated genes in colorectal cancer identifies genes commonly affected by epigenetic alterations.

Methylation profiling based on bead-chip arrays is an effective method for screening aberrantly methylated genes in CRC. In addition, we identified novel methylated genes that are candidate diagnostic or prognostic markers for CRC

Structural and functional analyses of minimal phosphopeptides targeting the polo-box domain of polo-like kinase 1

Polo-like kinase-1 (Plk1) has a pivotal role in cell proliferation and is considered a potential target for anticancer therapy. The noncatalytic polo-box domain (PBD) of Plk1 forms a phosphoepitope binding module for protein-protein interaction. Here, we report the identification of minimal phosphopeptides that specifically interact with the PBD of human PLK1, but not those of the closely related PLK2 and PLK3. Comparative binding studies and analyses of crystal structures of the PLK1 PBD in complex with the minimal phosphopeptides revealed that the C-terminal SpT dipeptide functions as a high-affinity anchor, whereas the N-terminal residues are crucial for providing specificity and affinity to the interaction. Inhibition of the PLK1 PBD by phosphothreonine mimetic peptides was sufficient to induce mitotic arrest and apoptotic cell death. The mode of interaction between the minimal peptide and PBD may provide a template for designing therapeutic agents that target PLK1.National Institutes of Health (U.S.) (Grant R01 GM60594)National Cancer Institute (U.S.)National Institutes of Health (U.S.) (Contract N01-CO-12400)National Institutes of Health (U.S.) (HHSN261200800001E

Protective Effect of Ginseng Polysaccharides on Influenza Viral Infection

Ginseng polysaccharide has been known to have multiple immunomodulatory effects. In this study, we investigated whether Panax ginseng polysaccharide (GP) would have a preventive effect on influenza infection. Administration of mice with GP prior to infection was found to confer a survival benefit against infection with H1N1 (A/PR/8/34) and H3N2 (A/Philippines/82) influenza viruses. Mice infected with the 2009 H1N1 virus suspended in GP solution showed moderately enhanced survival rates and lower levels of lung viral titers and the inflammatory cytokine (IL-6). Daily treatment of vaccinated mice with GP improved their survival against heterosubtypic lethal challenge. This study demonstrates the first evidence that GP can be used as a remedy against influenza viral infection

Carriage of the V279F Null Allele within the Gene Encoding Lp-PLA2 Is Protective from Coronary Artery Disease in South Korean Males

The Asia-specific PLA2G7 994G-T transversion leads to V279F substitution within the lipoprotein-associated phospholipase-A2 (Lp-PLA₂) and to absence of enzyme activity in plasma. This variant offers a unique natural experiment to assess the role of Lp-PLA₂ in the pathogenesis of coronary artery disease (CAD) in humans. Given conflicting results from mostly small studies, a large two-stage case-control study was warranted.PLA2G7 V279F genotypes were initially compared in 2890 male cases diagnosed with CAD before age 60 with 3128 male controls without CAD at age 50 and above and subsequently in a second independent male dataset of 877 CAD cases and 1230 controls. In the first dataset, the prevalence of the 279F null allele was 11.5% in cases and 12.8% in controls. After adjustment for age, body mass index, diabetes, smoking, glucose and lipid levels, the OR (95% CI) for CAD for this allele was 0.80 (0.66-0.97, p = 0.02). The results were very similar in the second dataset, despite lower power, with an allele frequency of 11.2% in cases and 12.5% in controls, leading to a combined OR of 0.80 (0.69-0.92), p = 0.002. The magnitude and direction of this genetic effect were fully consistent with large epidemiological studies on plasma Lp-PLA₂ activity and CAD risk.Natural deficiency in Lp-PLA₂ activity due to carriage of PLA2G7 279F allele protects from CAD in Korean men. These results provide evidence for a causal relationship between Lp-PLA₂ and CAD, and support pharmacological inhibition of this enzyme as an innovative way to prevent CAD

Carriage of the V279F Null Allele within the Gene Encoding Lp-PLA2 Is Protective from Coronary Artery Disease in South Korean Males

The Asia-specific PLA2G7 994G-T transversion leads to V279F substitution within the lipoprotein-associated phospholipase-A2 (Lp-PLA₂) and to absence of enzyme activity in plasma. This variant offers a unique natural experiment to assess the role of Lp-PLA₂ in the pathogenesis of coronary artery disease (CAD) in humans. Given conflicting results from mostly small studies, a large two-stage case-control study was warranted.PLA2G7 V279F genotypes were initially compared in 2890 male cases diagnosed with CAD before age 60 with 3128 male controls without CAD at age 50 and above and subsequently in a second independent male dataset of 877 CAD cases and 1230 controls. In the first dataset, the prevalence of the 279F null allele was 11.5% in cases and 12.8% in controls. After adjustment for age, body mass index, diabetes, smoking, glucose and lipid levels, the OR (95% CI) for CAD for this allele was 0.80 (0.66-0.97, p = 0.02). The results were very similar in the second dataset, despite lower power, with an allele frequency of 11.2% in cases and 12.5% in controls, leading to a combined OR of 0.80 (0.69-0.92), p = 0.002. The magnitude and direction of this genetic effect were fully consistent with large epidemiological studies on plasma Lp-PLA₂ activity and CAD risk.Natural deficiency in Lp-PLA₂ activity due to carriage of PLA2G7 279F allele protects from CAD in Korean men. These results provide evidence for a causal relationship between Lp-PLA₂ and CAD, and support pharmacological inhibition of this enzyme as an innovative way to prevent CAD

Improvement in survival among HIV-infected individuals in the Republic of Korea: Need for an early HIV diagnosis

<p>Abstract</p> <p>Background</p> <p>There is little information describing survival in HIV-infected patients after primary diagnosis in Korea, and changes in survival over time. This study investigated survival times, survival characteristics, and changes in survival after initial HIV diagnosis. Survival was characterized by evaluation of the immune status at primary HIV diagnosis nationwide.</p> <p>Methods</p> <p>A total of 5,323 HIV-infected individuals were registered with the government and followed until the end of 2007. Survival following HIV diagnosis was estimated based on epidemiological characteristics. We examined 3,369 individuals with available initial CD4+ T-cell counts within 6 months of HIV diagnosis to estimate survival based on immune status at diagnosis. The association between epidemiological variables and survival times was analyzed with univariate and multivariate Cox's proportional hazards model.</p> <p>Results</p> <p>Individuals died during the study period (n = 980), and 45% of the individuals died within 6 months of HIV diagnosis. The median survival following HIV diagnosis was 16.7 years. Survival were longer in women, in younger persons, in individuals diagnosed at blood centers, and in individuals diagnosed later in the study period. Survival were shortest in individuals with CD4+ T-cell counts <200 cells/mm³at HIV diagnosis. These results suggest that early HIV diagnosis in Korea is imperative to increase survival and to promote the quality of life for HIV-infected individuals with governmental support.</p> <p>Conclusion</p> <p>The median survival time of HIV-infected individuals following HIV diagnosis was 16.7 years in Korea. The survival was significantly lower in individuals with CD4+ T-cell counts <200 cells/mm³at HIV diagnosis and higher by introduction of drugs and development of therapy.</p