Three-Dimensional Automated, Machine-Learning-Based Left Heart Chamber Metrics: Associations with Prevalent Vascular Risk Factors and Cardiovascular Diseases

Background. Three-dimensional transthoracic echocardiography (3DE) powered by artificial intelligence provides accurate left chamber quantification in good accordance with cardiac magnetic resonance and has the potential to revolutionize our clinical practice. Aims. To evaluate the association and the independent value of dynamic heart model (DHM)-derived left atrial (LA) and left ventricular (LV) metrics with prevalent vascular risk factors (VRFs) and cardiovascular diseases (CVDs) in a large, unselected population. Materials and Methods. We estimated the association of DHM metrics with VRFs (hypertension, diabetes) and CVDs (atrial fibrillation, stroke, ischemic heart disease, cardiomyopathies, >moderate valvular heart disease/prosthesis), stratified by prevalent disease status: participants without VRFs or CVDs (healthy), with at least one VRFs but without CVDs, and with at least one CVDs. Results. We retrospectively included 1069 subjects (median age 62 [IQR 49–74]; 50.6% women). When comparing VRFs with the healthy, significant difference in maximum and minimum indexed atrial volume (LAVi max and LAVi min), left atrial ejection fraction (LAEF), left ventricular mass/left ventricular end-diastolic volume ratio, and left ventricular global function index (LVGFI) were recorded (p < 0.05). In the adjusted logistic regression, LAVi min, LAEF, LV ejection fraction, and LVGFI showed the most robust association (OR 3.03 [95% CI 2.48–3.70], 0.45 [95% CI 0.39–0.51], 0.28 [95% CI 0.22–0.35], and 0.22 [95% CI 0.16–0.28], respectively, with CVDs. Conclusions. The present data suggested that novel 3DE left heart chamber metrics by DHM such as LAEF, LAVi min, and LVGFI can refine our echocardiographic disease discrimination capacity

Genotranscriptomic meta-analysis of the Polycomb gene CBX2 in human cancers: initial evidence of an oncogenic role

Background: Polycomb group (PcG) proteins are histone modifiers known to transcriptionally silence key tumour suppressor genes in multiple human cancers. The chromobox proteins (CBX2, 4, 6, 7, and 8) are critical components of PcG-mediated repression. Four of them have been associated with tumour biology, but the role of CBX2 in cancer remains largely uncharacterised. Methods: Addressing this issue, we conducted a comprehensive and unbiased genotranscriptomic meta-analysis of CBX2 in human cancers using the COSMIC and Oncomine databases. Results: We discovered changes in gene expression that are suggestive of a widespread oncogenic role for CBX2. Our genetic analysis of 8013 tumours spanning 29 tissue types revealed no inactivating chromosomal aberrations and only 40 point mutations at the CBX2 locus. In contrast, the overall rate of CBX2 amplification averaged 10% in all combined neoplasms but exceeded 30% in ovarian, breast, and lung tumours. In addition, transcriptomic analyses revealed a strong tendency for increased CBX2 mRNA levels in many cancers compared with normal tissues, independently of CDKN2A/B silencing. Furthermore, CBX2 upregulation and amplification significantly correlated with metastatic progression and lower overall survival in many cancer types, particularly those of the breast. Conclusions: Overall, we report that the molecular profile of CBX2 is suggestive of an oncogenic role. As CBX2 has never been studied in human neoplasms, our results provide the rationale to further investigate the function of CBX2 in the context of cancer cells

Tumor suppressor activity of CBX7 in lung carcinogenesis

The generation of knockout mice for the Cbx7 gene validates the tumor suppressor role of CBX7, whose expression is lost in several human malignancies. Indeed, these mice developed liver and lung adenomas and carcinomas. Cyclin E overexpression due to the lack of Cbx7-negative regulation of its expression likely accounts for the phenotype of the Cbx7-KO mice. A similar mechanism is likely involved in human lung carcinogenesis, since Cyclin E upregulation associated with the loss of CBX7 expression has been observed in most of human lung carcinomas analyze

Study on catalysts for the DeNOx-SCR with ammonia in thermoelectric power plants and gas turbines

Consiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7 , Rome / CNR - Consiglio Nazionale delle RichercheSIGLEITItal

Regulation of microRNA expression by HMGA1 proteins.

The High Mobility Group proteins HMGA1 are nuclear architectural factors that play a critical role in a wide range of biological processes. Since recent studies have identified the microRNAs (miRNAs) as important regulators of gene expression, modulating critical cellular functions such as proliferation, apoptosis and differentiation, the aim of our work was to identify the miRNAs that are physiologically regulated by HMGA1 proteins. To this purpose, we have analysed the miRNA expression profile of mouse embryonic fibroblasts (MEFs) carrying two, one or no Hmga1 functional alleles using a microarray (miRNA microarray). By this approach, we found a miRNA expression profile that differentiates Hmga1-null MEFs from the wild-type ones. In particular, a significant decrease in miR-196a-2, miR-101b, miR-331 and miR-29a was detected in homozygous Hmga1-knockout MEFs in comparison with wild-type cells. Consistently, these miRNAs are downregulated in most of the analysed tissues of Hmga1-null mice in comparison with the wild-type mice. ChIP assay shows that HMGA1 is able to bind regions upstream of these miRNAs. Moreover, we identified the HMGA2 gene product as a putative target of miR-196a-2, suggesting that HMGA1 proteins are able to downregulate the expression of the other member of the HMGA family through the regulation of the miR-196a-2 expression. Finally, ATXN1 and STC1 gene products have been identified as targets of miR-101b. Therefore, it is reasonable to hypothesize that HMGA1 proteins are involved in several functions by regulating miRNA expression.Oncogene advance online publication, 26 January 2009; doi:10.1038/onc.2008.495

HMGA1 pseudogenes as candidate proto-oncogenic competitive endogenous RNAs

The High Mobility Group A (HMGA) are nuclear proteins that participate in the organization of nucleoprotein complexes involved in chromatin structure, replication and gene transcription. HMGA overexpression is a feature of human cancer and plays a causal role in cell transformation. Since non-coding RNAs and pseudogenes are now recognized to be important in physiology and disease, we investigated HMGA1 pseudogenes in cancer settings using bioinformatics analysis. Here we report the identification and characterization of two HMGA1 non-coding pseudogenes, HMGA1P6 and HMGA1P7. We show that their overexpression increases the levels of HMGA1 and other cancer-related proteins by inhibiting the suppression of their synthesis mediated by microRNAs. Consistently, embryonic fibroblasts from HMGA1P7-overexpressing transgenic mice displayed a higher growth rate and reduced susceptibility to senescence. Moreover, HMGA1P6 and HMGA1P7 were overexpressed in human anaplastic thyroid carcinomas, which are highly aggressive, but not in differentiated papillary carcinomas, which are less aggressive. Lastly, the expression of the HMGA1 pseudogenes was significantly correlated with HMGA1 protein levels thereby implicating HMGA1P overexpression in cancer progression. In conclusion, HMGA1P6 and HMGA1P7 are potential proto-oncogenic competitive endogenous RNAs