The enhancer of zeste homologue 2 (EZH2) is a histone H3 lysine 27 methyltransferase that promotes tumorigenesis in a variety of human malignancies by altering the expression of tumour suppressor genes. To evaluate the prognostic value of EZH2 in glioma, we analysed gene expression data and corresponding clinicopathological information from the Chinese Glioma Genome Atlas, the Cancer Genome Atlas and GTEx. Increased expression of EZH2 was significantly associated with clinicopathologic characteristics and overall survival as evaluated by univariate and multivariate Cox regression. Gene Set Enrichment Analysis revealed an association of EZH2 expression with the cell cycle, DNA replication, mismatch repair, p53 signalling and pyrimidine metabolism. We constructed a nomogram for prognosis prediction with EZH2, clinicopathologic variables and significantly correlated genes. EZH2 was demonstrated to be significantly associated with several immune checkpoints and tumour‐infiltrating lymphocytes. Furthermore, the ESTIMATE and Timer Database scores indicated correlation of EZH2 expression with a more immunosuppressive microenvironment for glioblastoma than for low grade glioma. Overall, our study demonstrates that expression of EZH2 is a potential prognostic molecular marker of poor survival in glioma and identifies signalling pathways and immune checkpoints regulated by EHZ2, suggesting a direction for future application of immune therapy in glioma.
Systematic review and meta-analysis of the effect of using percutaneous pedicle screw internal fixation for thoracolumbar fractures Jiong Lu, Yinan Chen, Minwei Hu, Changhui Sun
Upper airway narrowing has been a concern of mandibular setback. The aims of this study were (1) to evaluate the effect of bimaxillary rotational setback surgery on upper airway structure in patients with skeletal class III deformities, and (2) to compare the preoperative and postoperative upper airways of class III patients with age- and sex-matched class I control subjects. The upper airways of 36 adults who consecutively underwent bimaxillary rotational setback surgery for skeletal class III deformities were assessed by means of cone-beam computed tomography before and at least 6 months after surgery. Results were compared with those of age- and sex-matched control subjects with skeletal class I structure. Before surgery, the class III patients had significantly larger velopharyngeal, oropharyngeal, and hypopharyngeal volumes than did the control subjects (all p < 0.01). The velopharyngeal, oropharyngeal, and hypopharynx volumes decreased significantly after surgery (all p < 0.01). The postoperative airways of class III patients were similar with regard to velopharyngeal, oropharyngeal, and hypopharyngeal volume (all p > 0.01) compared to control subjects. The postoperative velopharyngeal and oropharyngeal airway volumes were associated with the baseline airway volume (p < 0.001) and horizontal movement of the soft palate (p < 0.01). These results suggest that upper airway volume is decreased after bimaxillary rotational setback surgery for skeletal class III deformities, but is not smaller than in normal controls, and the postoperative upper airway volume is related to airway volume at baseline and changes in the surrounding structures. Therapeutic, III.
20 February 2024 in Journal of Molecular and Cellular Cardiology
Acute aortic dissection (AAD) progresses rapidly and is associated with high mortality; therefore, there remains an urgent need for pharmacological agents that can protect against AAD. Herein, we examined the therapeutic effects of cannabidiol (CBD) in AAD by establishing a suitable mouse model. In addition, we performed human AAD single-cell RNA sequencing and mouse AAD bulk RNA sequencing to elucidate the potential underlying mechanism of CBD. Pathological assays and in vitro studies were performed to verify the results of the bioinformatic analysis and explore the pharmacological function of CBD. In a β-aminopropionitrile (BAPN)-induced AAD mouse model, CBD reduced AAD-associated morbidity and mortality, alleviated abnormal enlargement of the ascending aorta and aortic arch, and suppressed macrophage infiltration and vascular smooth muscle cell (VSMC) apoptosis. Bioinformatic analysis revealed that the pro-apoptotic gene PMAIP1 was highly expressed in human and mouse AAD samples, and CBD could inhibit Pmaip1 expression in AAD mice. Using human aortic VSMCs (HAVSMCs) co-cultured with M1 macrophages, we revealed that CBD alleviated HAVSMCs mitochondrial-dependent apoptosis by suppressing the BAPN-induced overexpression of PMAIP1 in M1 macrophages. PMAIP1 potentially mediates HAVSMCs apoptosis by regulating Bax and Bcl2 expression. Accordingly, CBD reduced AAD-associated morbidity and mortality and mitigated the progression of AAD in a mouse model. The CBD-induced effects were potentially mediated by suppressing macrophage infiltration and PMAIP1 (primarily expressed in macrophages)-induced VSMC apoptosis. Our findings offer novel insights into M1 macrophages and HAVSMCs interaction during AAD progression, highlighting the potential of CBD as a therapeutic candidate for AAD treatment.