The aim of this study was to find estrogen receptor (ER) binding sites of estradiol (E2)-treated and control groups and discuss the roles of ER activation in the tumorigenesis and progression of various human cancers. The ER ChIP-seq data GSE19013 was downloaded from Gene Expression Omnibus database, including E2-treated data GSM470419 and control data GSM470418. MACS software was utilized to identify ER binding sites in two groups. R's ChIPpeakAnno was used to detect ER-regulated target genes. Motif finding was employed to analyze ER concordant transcription factors (TFs) in MCF7 cell. The Gene Ontology (GO) was used to conduct functional enrichment analysis. We identified 9,134 ER binding sites in E2 stimulation group and 1,969 in control group. GO enrichment analysis of target genes showed that ER-regulated target genes mainly participated in mRNA catabolic process, protein complex disassembly, and protein localization to organelle-related biology process; while in E2 stimulation group, the function of ER-regulated target genes sharply changed. The effect of E2 in MCF7 cell suggested that activated ER probably reacted with several TFs and then co-regulated related genes expression. Furthermore, several TFs, such as PAX6, SMAD3, and ESR2, had multiply cellular regulation function. Our results showed that E2 stimulates breast cancer cell growth through ER. This may infer the function of ER in occurrence and development of breast cancer. Together, our study would pave ways for discussing ER concordant TFs and studying other ER-recruited TFs.
Background
Dexmedetomidine has controversial influence on cardiac electrophysiology. The aim of this study was to explore the effects of dexmedetomidine on perioperative cardiac electrophysiology in patients undergoing general anesthesia.
Methods
Eighty-one patients were randomly divided into four groups: groups D1, D2, D3 receiving dexmedetomidine 1, 1, 0.5 μg/kg over 10 min and 1, 0.5, 0.5 μg/kg/h continuous infusion respectively, and control group (group C) receiving normal saline. Twelve-lead electrocardiograms were recorded at the time before dexmedetomidine/normal saline infusion (T1), loading dose finish (T2), surgery ending (T6), 1 h (T7) after entering PACU, 24 h (T8), 48 h (T9), 72 h (T10) and 1 month (T11) postoperatively. Cardiac circulation efficiency (CCE) were also recorded.
Results
Compared with group C, QTc were significantly increased at T2 in groups D1 and D2 while decreased at T7 and T8 in group D3 (P < 0.05), iCEB were decreased at T8 (P < 0.05). Compared with group D1, QTc at T2, T6, T7, T9 and T10 and iCEB at T8 were decreased, and CCE at T2-T4 were increased in group D3 significantly (P < 0.05). Compared with group D2, QTc at T2 and iCEB at T8 were decreased and CCE at T2 and T3 were increased in group D3 significantly (P < 0.05).
Conclusions
Dexmedetomidine at a loading dose of 0.5 μg/kg and a maintenance dose of 0.5 μg/kg/h can maintain stability of cardiac electrophysiology during perioperative period and has no significant adverse effects on CCE.
Trial registration
ClinicalTrials.gov NCT04577430 (Date of registration: 06/10/2020).
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