Identification of DNA methylation changes associated with human gastric cancer

<p>Abstract</p> <p>Background</p> <p>Epigenetic alteration of gene expression is a common event in human cancer. DNA methylation is a well-known epigenetic process, but verifying the exact nature of epigenetic changes associated with cancer remains difficult.</p> <p>Methods</p> <p>We profiled the methylome of human gastric cancer tissue at 50-bp resolution using a methylated DNA enrichment technique (methylated CpG island recovery assay) in combination with a genome analyzer and a new normalization algorithm.</p> <p>Results</p> <p>We were able to gain a comprehensive view of promoters with various CpG densities, including CpG Islands (CGIs), transcript bodies, and various repeat classes. We found that gastric cancer was associated with hypermethylation of 5' CGIs and the 5'-end of coding exons as well as hypomethylation of repeat elements, such as short interspersed nuclear elements and the composite element SVA. Hypermethylation of 5' CGIs was significantly correlated with downregulation of associated genes, such as those in the <it>HOX </it>and histone gene families. We also discovered long-range epigenetic silencing (LRES) regions in gastric cancer tissue and identified several hypermethylated genes (<it>MDM2</it>, <it>DYRK2</it>, and <it>LYZ</it>) within these regions. The methylation status of CGIs and gene annotation elements in metastatic lymph nodes was intermediate between normal and cancerous tissue, indicating that methylation of specific genes is gradually increased in cancerous tissue.</p> <p>Conclusions</p> <p>Our findings will provide valuable data for future analysis of CpG methylation patterns, useful markers for the diagnosis of stomach cancer, as well as a new analysis method for clinical epigenomics investigations.</p

Investigating Endocrine Disrupting Impacts of Nine Disinfection Byproducts on Human and Zebrafish Estrogen Receptor Alpha

Background: Disinfection byproducts (DBPs) cause endocrine disruption via estrogenic or anti-estrogenic effects on estrogen receptors. However, most studies have focused on human systems, with little experimental data being presented on aquatic biota. This study aimed to compare the effects of nine DBPs on zebrafish and human estrogen receptor alpha (zERα and hERα). Methods: In vitro enzyme response-based tests, including cytotoxicity and reporter gene assays, were performed. Additionally, statistical analysis and molecular docking studies were employed to compare ERα responses. Results: Iodoacetic acid (IAA), chloroacetonitrile (CAN), and bromoacetonitrile (BAN) showed robust estrogenic activity on hERα (maximal induction ratios of 108.7%, 50.3%, and 54.7%, respectively), while IAA strongly inhibited the estrogenic activity induced by 17β-estradiol (E2) in zERα (59.8% induction at the maximum concentration). Chloroacetamide (CAM) and bromoacetamide (BAM) also showed robust anti-estrogen effects in zERα (48.1% and 50.8% induction at the maximum concentration, respectively). These dissimilar endocrine disruption patterns were thoroughly assessed using Pearson correlation and distance-based analyses. Clear differences between the estrogenic responses of the two ERαs were observed, whereas no pattern of anti-estrogenic activities could be established. Some DBPs strongly induced estrogenic endocrine disruption as agonists of hERα, while others inhibited estrogenic activity as antagonists of zERα. Principal coordinate analysis (PCoA) showed similar correlation coefficients for estrogenic and anti-estrogenic responses. Reproducible results were obtained from computational analysis and the reporter gene assay. Conclusions: Overall, the effects of DBPs on both human and zebrafish highlight the importance of controlling their differences in responsiveness for estrogenic activities including the water quality monitoring and endocrine disruption, as DBPs have species-specific ligand-receptor interactions.Peer reviewe

LHC Signature of Mirage Mediation

We study LHC phenomenology of mirage mediation scenario in which anomaly and modulus contributions to soft SUSY breaking terms are comparable to each other. A Monte Carlo study of mirage mediation, with model parameters $\alpha=1$,$M_0=500$ GeV, $n_M=1/2$, $n_H=1$ and $\rm{tan}\beta=10$, is presented. It is shown that masses of supersymmetric particles can be measured in a model independent way, providing information on SUSY breaking sector. In particular, the mass ratio of gluino to the lightest neutralino for the benchmark scenario is determined to be 1.9 \lesssim m_{\tildeg}/m_{\tilde\chi_1^0} \lesssim 3.1, well reproducing theoretical input value of $m_{\tilde g}/m_{\tilde\chi_1^0} \simeq 2.5$ which is quite distinctive from the predictions $m_{\tilde g}/m_{\tilde\chi_1^0} \gtrsim 6$ of other SUSY scenarios in which gaugino masses are unified at the GUT scale. The model parameters of mirage mediation can be also determined from various kinematic distributions

The impact of non-pharmaceutical interventions on premature births during the COVID-19 pandemic: a nationwide observational study in Korea

BackgroundNon-pharmaceutical interventions (NPIs), such as social distancing and hand washing, have been associated with a decline in the preterm birth rate worldwide. We aimed to evaluate whether the preterm birth rate in Korea during the coronavirus disease 2019 lockdown has changed compared to that in previous years.MethodA birth registry from the Korea Statistical Information Service, which is a nationwide official database, was used to include all births claimed to have occurred between 2011 and 2020. Newborns with gestational age (GA) less than 22 weeks and birth weight less than 220 g were excluded. The pre-NPI period was designated as January 2011 to January 2020, and the NPI period was defined as February 2020 to December 2020. We assessed the effect of NPI on the incidence of prematurity per 100 births using an interrupted time-series quasi-experimental design and implementing an autoregressive integrated moving average (ARIMA) model.ResultsFrom 2011 to 2020, a total of 3,931,974 live births were registered, among which 11,416 were excluded. Consequently, the final study population included 3,920,558 live births (both singleton and multiple births) among which 275,009 (7.0%) were preterm. The preterm birth rate was significantly higher during the NPI period (8.68%) compared to that in the pre-NPI period (6.92%) (P &lt; 0.001). The ARIMA model showed that in all singleton and multiple births, except those in July (observed 9.24, expected 8.54, [95% prediction interval {PI} 8.13–8.96], percent difference 7.81%), September (observed 7.89, expected 8.35, [95% PI 7.93–8.76], percent difference −5.66%), and December (observed 9.90, expected 9.40, [95% PI 8.98–9.82], percent difference 5.2%), most observed values were within the 95% PI of the expected values and showed an increasing trend.ConclusionIn this nationwide observational study, the trend in premature birth rate did not significantly change due to NPI implementation in Korea, as it had been increasing since 2011. The trend of Korea's birth rate appears to be unaffected by the implementation of NPIs; however, further studies with a longer follow-up period are needed

Transient receptor potential channel TRPV4 mediates TGF-β1-induced differentiation of human ventricular fibroblasts

Background: Cardiac fibroblasts (CFs) are principal extracellular matrix-producing cells. In response to injury, CFs transdifferentiate into myofibroblasts. Intracellular calcium (Ca2+) signaling, involved in fibroblast proliferation and differentiation, is activated in fibroblasts through transient receptor potential (TRP) channels, but the function of these channels has not been investigated in human ventricular CFs. Under evaluation in this study, was the role of TRP channels in the differentiation of human ventricular CFs induced by transforming the growth factor beta (TGF-β), a pro-fibrotic cytokine. Methods: Human ventricular CFs were used in this study. The differentiation of CFs into myofibroblast was induced with TGF-β and was identified by the expression of smooth muscle actin. Results: Results indicate that Ca2+ signaling was an essential component of ventricular CF dif­ferentiation. CFs treated with TGF-β demonstrated increased expression of a TRP channel, TRPV4, both at the mRNA and protein levels, which corresponded with CF-myofibroblast trans-differentiation, as evidenced by the upregulation of α-smooth muscle actin, a myofibroblast marker, and plasminogen activator inhibitor-1, which are fibrogenesis markers. An agonist of TRPV4 induced the conversion of CFs into myofibroblasts, whereas it’s antagonist as well a Ca2+ chelating agent reduced it, indicating that the Ca2+ influx throughTRPV4 is required for CF trans-differentiation. Overall, these results dem­onstrate that TRPV4-mediated Ca2+ influx participates in regulating the differentiation of human ventricular CFs into myofibroblasts through the MAPK/ERK pathway. Conclusions: Overall, these results demonstrate that TRPV4-mediated Ca2+ influx participates in regulating the differentiation of human ventricular CFs into myofibroblasts through the MAPK/ERK pathway