Lindemerson1407

Collectively, our study provided novel evidence that MTA2 plays an aggressive role in ESCC metastasis by a novel EIF4E-Twist positive feedback loop, which may provide a potential therapeutic target for the management of ESCC.Recently, advances in genomic technology such as RNA sequencing and genome-wide profiling have enabled the identification of considerable numbers of non-coding RNAs (ncRNAs). MicroRNAs have been studied for decades, leading to the identification of those with disease-causing and/or protective effects in vascular disease. Although other ncRNAs such as long ncRNAs have not been fully described yet, recent studies have indicated their important functions in the development of vascular diseases. Here, we summarize the current understanding of the mechanisms and functions of ncRNAs, focusing on microRNAs, circular RNAs and long ncRNAs in vascular diseases.Cancer stem-like cells (CSCs) induce drug resistance and recurrence of tumors when they experience DNA replication stress. However, the mechanisms underlying DNA replication stress in CSCs and its compensation remain unclear. Here, we demonstrate that upregulated c-Myc expression induces stronger DNA replication stress in patient-derived breast CSCs than in differentiated cancer cells. Our results suggest critical roles for mini-chromosome maintenance protein 10 (MCM10), a firing (activating) factor of DNA replication origins, to compensate for DNA replication stress in CSCs. MCM10 expression is upregulated in CSCs and is maintained by c-Myc. c-Myc-dependent collisions between RNA transcription and DNA replication machinery may occur in nuclei, thereby causing DNA replication stress. MCM10 may activate dormant replication origins close to these collisions to ensure the progression of replication. Moreover, patient-derived breast CSCs were found to be dependent on MCM10 for their maintenance, even after enrichment for CSCs that were resistant to paclitaxel, the standard chemotherapeutic agent. Further, MCM10 depletion decreased the growth of cancer cells, but not of normal cells. Therefore, MCM10 may robustly compensate for DNA replication stress and facilitate genome duplication in cancer cells in the S-phase, which is more pronounced in CSCs. Overall, we provide a preclinical rationale to target the c-Myc-MCM10 axis for preventing drug resistance and recurrence of tumors.

Intravenous amiodarone infusion is effective and widely used treatment for pharmacological cardioversion of recent-onset atrial fibrillation (Af). Although amiodarone may trigger various alterations in cardiac electrophysiology and electrocardiography (ECG), the impact of amiodarone treatment on frontal plane QRS-T angle remains unclear. Frontal plane QRS-T angle is the angle between the depolarization and repolarization axes and indicates instability in the cardiac cellular electrophysiology. Therefore, the present study aimed to investigate whether intravenous amiodarone infusion has effect on frontal plane QRS-T angle in patients with acute Af.

A total of 179 patients with acute-onset Af who underwent pharmacological cardioversion with intravenous amiodarone infusion were included into the study. Patients with successful and failed pharmacological cardioversion were compared regarding pre- and post-treatment frontal plane QRS-T angle.

At the end of the amiodarone infusion, sinus rhythm was restored iordings, frontal plane QRS-T angle may be useful in the monitoring of intravenous amiodarone treatment.

Comparisons of second-line anti-tumour necrosis factor (TNF) agents and vedolizumab are sparse.

To evaluate the effectiveness of anti-TNF agents compared to vedolizumab as second-line biologics in inflammatory bowel disease (IBD).

A propensity score-matched cohort was created using Swedish nationwide registers. Patients with Crohn's disease or ulcerative colitis, exposed to first-line anti-TNF treatment, who initiated a second anti-TNF agent or vedolizumab in 2014-2016 (N=1363) were included. The primary outcome was drug survival at 12months. Secondarily, we assessed survival without IBD-related hospitalisation, IBD-related surgery, antibiotics, or hospitalisation because of infection, and also corticosteroid exposure.

After 11 propensity score matching, 400 patients (Crohn's disease, N=198; ulcerative colitis, N=202) remained. For Crohn's disease, drug survival was 73% in the vedolizumab group vs 74% in the anti-TNF group (difference 1 percentage point; 95% confidence interval [CI]-11-13; P=0.87). Survival without IBD-related hospitalisation (82% vs 88%), surgery (82% vs 89%), antibiotics (65% vs 71%), hospitalisation due to infection (95% vs 88%) and corticosteroids (58% vs 48%) were not statistically significantly different between groups. For ulcerative colitis, drug survival was 69% in the vedolizumab group vs 62% in the anti-TNF group (difference -7 percentage points; 95% CI -20 to 6; P=0.30). Vedolizumab-treated patients had lower survival without IBD-related hospitalisation (82% vs 93%, P=0.02). Survival without colectomy (93% vs 97%), antibiotics (81% vs 70%), hospitalisation due to infection (92% vs 92%) and corticosteroids (58% vs 48%) were not statistically significantly different.

Based on Swedish clinical practice, the effectiveness and safety of second-line anti-TNF and vedolizumab at 12 months appeared largely similar.

Based on Swedish clinical practice, the effectiveness and safety of second-line anti-TNF and vedolizumab at 12 months appeared largely similar.Phosphodiesterase 4 (PDE4) inhibitors have been shown to present beneficial effects in cerebral ischemic injury because of their ability to improve cognition and target different phases and mechanisms of cerebral ischemia, including apoptosis, neurogenesis, angiogenesis, and inflammation. The present study investigated whether repeated treatment with the PDE4 inhibitor roflumilast rescued memory loss and attenuated neuroinflammation in rats following transient global cerebral ischemia (TGCI). TGCI caused memory impairments, neuronal loss (reflected by Neuronal nuclei (NeuN) immunoreactivity), and compensatory neurogenesis (reflected by doublecortin (DCX) immunoreactivity) in the hippocampus. 2-MeOE2 Also, increases in the protein expression of the phosphorylated response element-binding protein (pCREB) and inflammatory markers such as the glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule 1 (Iba-1), were detected in the hippocampus in TGCI rats. Repeated treatment with roflumilast (0.