Markussen Cowan (guideuse76)

BRD4 is an epigenome reader known to exert key roles at the interface between chromatin remodeling and transcriptional regulation, and is primarily known for its role in promoting gene expression. In selective contexts, however, BRD4 may work as negative regulator of transcription. Here, we reported that BRD4 binds several long noncoding RNAs (lncRNA). Among these, the lncRNA NEAT1 was found to interfere with BRD4 transcriptional activity. Mechanistically, lncNEAT1 forms a complex with BRD4 and WDR5 and maintains them in a low-activity state. Treatment with Bromodomains and Extraterminal (BET) inhibitor caused the lncRNA NEAT1 to dissociate from the BRD4/WDR5 complex, restored the acetyl-transferase capacity of BRD4, and restored the availability of WDR5 to promote histone trimethylation, thereby promoting BRD4/WDR5 transcriptional activity and activation of target gene expression. In addition, the lncRNA NEAT1 then became available to bind and to inhibit EZH2, cooperatively increasing transcriptional activation. IMPLICATIONS Our results revealed an epigenetic program that involves the interaction between the lncRNA NEAT1 and BRD4, functioning as a molecular switch between BRD4's activator and repressor chromatin complexes. Approximately 15%-45% of patients with unruptured intracranial aneurysms have multiple intracranial aneurysms (MIAs). Determining which one is most likely to rupture is extremely important for treatment decision making for MIAs patients. This study aimed to develop and validate a nomogram to evaluate the per-aneurysm rupture risk of MIAs patients. A total of 1671 IAs from 700 patients with MIAs were randomly dichotomised into derivation and validation sets. Multivariate logistic regression analysis was used to select predictors and construct a nomogram model for aneurysm rupture risk assessment in the derivation set. The discriminative accuracy, calibration performance and clinical usefulness of this nomogram were assessed. We also developed a multivariate model for a subgroup of 158 subarachnoid haemorrhage (SAH) patients and compared its performance with the nomogram model. Multivariate analyses identified seven variables that were significantly associated with IA rupture (history of SAH, alcohol consumption, female sex, aspect ratio >1.5, posterior circulation, irregular shape and bifurcation location). The clinical and morphological-based MIAs (CMB-MIAs) nomogram model showed good calibration and discrimination (derivation set area under the curve (AUC)=0.740 validation set AUC=0.772). Decision curve analysis demonstrated that the nomogram was clinically useful. Compared with the nomogram model, the AUC of multivariate model developed from SAH patients had lower value of 0.730. This CMB-MIAs nomogram for MIAs rupture risk is the first to be developed and validated in a large multi-institutional cohort. This nomogram could be used in decision-making and risk stratification in MIAs patients. This CMB-MIAs nomogram for MIAs rupture risk is the first to be developed and validated in a large multi-institutional cohort. This nomogram could be used in decision-making and risk stratification in MIAs patients. SLE is a strong risk factor for premature cardiovascular (CV) disease and mortality. We investigated which factors could explain poor prognosis in SLE compared with controls. Patients with SLE and population controls without history of clinical CV events who performed carotid ultrasound examination were recruited for this study. The outcome was incident CV event and death. Event-free survival rates were compared using Kaplan-Meier curves. Relative HR (95% CI) was used to estimate risk of outcome. Patients (n=99, 87% female), aged 47 (13) years and with a disease duration of 12 (9) years, had mild disease at inclusion, Systemic Lupus Erythematosus Diseases Activity Index score of 3 (1-6) and Systemic Lupus International Collab