McIntosh Glass (whorlbrandy6)

Transposable elements (TEs) have been shown to have important gene regulatory functions and their alteration could lead to disease phenotypes. Acute myeloid leukemia (AML) develops as a consequence of a series of genetic changes in hematopoietic precursor cells, including mutations in epigenetic factors. Here, we set out to study the gene regulatory role of TEs in AML. We first explored the epigenetic landscape of TEs in AML patients using ATAC-seq data. We show that a large number of TEs in general, and more specifically mammalian-wide interspersed repeats (MIRs), are more enriched in AML cells than in normal blood cells. We obtained a similar finding when analyzing histone modification data in AML patients. Gene Ontology enrichment analysis showed that genes near MIRs in open chromatin regions are involved in leukemogenesis. To functionally validate their regulatory role, we selected 19 MIR regions in AML cells, and tested them for enhancer activity in an AML cell line (Kasumi-1) and a chronic myeloid leukemia (CML) cell line (K562); the results revealed several MIRs to be functional enhancers. Taken together, our results suggest that TEs are potentially involved in myeloid leukemogenesis and highlight these sequences as potential candidates harboring AML-associated variation.Eggs are nutrient-dense while also loaded with abundant cholesterol, thus making the public hesitant about their consumption. We conducted the study to investigate if egg consumption is associated with incident cardiovascular disease (CVD) and all-cause mortality. Using the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China, we included 102,136 adults free of CVD and assessed their egg consumption with food-frequency questionnaires. CVD endpoints and all-cause mortality were confirmed during follow-ups by interviewing participants or their proxies and checking hospital records/death certificates. The HRs (95% CIs) were calculated using the cohort-stratified Cox regression models. During 777,163 person-years of follow-up, we identified 4,848 incident CVD and 5,511 deaths. U-shaped associations of egg consumption with incident CVD and all-cause mortality were observed. Compared with consumption of 3- less then 6/week, the multivariable-adjusted HRs (95% CIs) of less then 1/week and ≥10/week for incident CVD were 1.22 (1.11 to 1.35) and 1.39 (1.28 to 1.52), respectively. The corresponding HRs (95% CIs) for all-cause mortality were 1.29 (1.18 to 1.41) and 1.13 (1.04 to 1.24). Our findings identified that both low and high consumption were associated with increased risk of incident CVD and all-cause mortality, highlighting that moderate egg consumption of 3- less then 6/week should be recommended for CVD prevention in China.microRNAs (miRNAs), particularly the exosomal miRNAs have been widely used as biomarkers and promising therapeutic targets in cancer. However, a comprehensive analysis of miRNA-gene regulatory network with clinical significance remains scarce. The emergence of high-throughput multi-omics data over large, well-characterized patient cohorts provides an unprecedented opportunity to address this problem. Herein, we performed a clinic-centered analysis to identify cancer-associated miRNAs, miRNA-target axis. We first calculated the correlation among miRNA, mRNA and 75 unique clinico-pathological characteristics (CPCs) in 26 cancer types, and established an online resource (4CR). Interestingly, we found that the high expression of several DNA methylation-related enzymes was associated with adverse outcomes of cancer patients, and these genes were regulated by a cluster of miRNAs. Furthermore, by integrating exosomal miRNA and mRNA databases, we identified exosomal miRNA biomarkers for non-invasive cancer surveillance and therapy monitoring. Finally, we explored the role of CPC-related miRNAs for therapeutic effect prediction of drugs based on their shared targets.