Advanced CMR Techniques in Anderson-Fabry Disease: State of the Art

Anderson-Fabry disease (AFD) is a rare multisystem X-linked lysosomal storage disorder caused by α-galactosidase A enzyme deficiency. Long-term cardiac involvement in AFD results in left ventricular hypertrophy and myocardial fibrosis, inducing several complications, mainly arrhythmias, valvular dysfunction, and coronary artery disease. Cardiac magnetic resonance (CMR) represents the predominant noninvasive imaging modality for the assessment of cardiac involvement in the AFD, being able to comprehensively assess cardiac regional anatomy, ventricular function as well as to provide tissue characterization. This review aims to explore the role of the most advanced CMR techniques, such as myocardial strain, T1 and T2 mapping, perfusion and hybrid imaging, as diagnostic and prognostic biomarkers

CBX2 shapes chromatin accessibility promoting AML via p38 MAPK signaling pathway

Abstract Background: The dynamic epigenome and proteins specialized in the interpretation of epigenetic marks critically contribute to leukemic pathogenesis but also offer alternative therapeutic avenues. Targeting newly discovered chromatin readers involved in leukemogenesis may thus provide new anticancer strategies. Accumulating evidence suggests that the PRC1 complex member CBX2 is overexpressed in solid tumors and promotes cancer cell survival. However, its role in leukemia is still unclear. Methods: We exploited reverse genetic approaches to investigate the role of CBX2 in human leukemic cell lines and ex vivo samples. We also analyzed phenotypic effects following CBX2 silencing using cellular and molecular assays and related functional mechanisms by ATAC-seq and RNA-seq. We then performed bioinformatic analysis of ChIPseq data to explore the influence of histone modifications in CBX2-mediated open chromatin sites. Lastly, we used molecular assays to determine the contribution of CBX2-regulated pathways to leukemic phenotype. Results: We found CBX2 overexpressed in leukemia both in vitro and ex vivo samples compared to CD34+ cells. Decreased CBX2 RNA levels prompted a robust reduction in cell proliferation and induction of apoptosis. Similarly, sensitivity to CBX2 silencing was observed in primary acute myeloid leukemia samples. CBX2 suppression increased genome-wide chromatin accessibility followed by alteration of leukemic cell transcriptional programs, resulting in enrichment of cell death pathways and downregulation of survival genes. Intriguingly, CBX2 silencing induced epigenetic reprogramming at p38 MAPK-associated regulatory sites with consequent deregulation of gene expression. Conclusions: Our results identify CBX2 as a crucial player in leukemia progression and highlight a potential druggable CBX2-p38 MAPK network in AML

First validation of the technical and administrative staff quality of life at work tool (TASQ@work) in academia

IntroductionBased on the job demands-resources (JD-R) model, the present study aimed to validate “The Technical and Administrative Staff Quality of Life At Work” (TASQ@work), a new tool to assess the quality of life at work in academia focused on technical and administrative staff.MethodsThis tool was developed by the QoL@Work research team, a group of expert academics in the field of work and organizational psychology affiliated with the Italian Association of Psychologists. The TASQ@work was elaborated in different steps. The first phase was aimed at the identification of the dimensions of the tool. The second phase was aimed to assess the psychometric properties of the tool. The validation process involved confirmatory analysis and measurement invariance of the various constructs selected. The analyses were performed in a convenience sample of two Italian universities in different regions (one in the Northwest and the second in Central Italy).ResultsThe sample was composed of 1820 Administrative Staff, comprising 69.4% from University 1 (N = 1,263) and 30.6% from University 2 (N = 557). The TASQ@work presented satisfactory psychometric properties (normality of the items, reliability and content, construct and nomological validity) and measurement invariance across gender, seniority, and Athenaeum.DiscussionThe results indicate that the tool can be considered a reliable and valid instrument to assess job demands, job resources, and outcomes in the working life of technical and administrative academic staff. In this perspective, the present study represents the first contribution to the debate on the psychosocial risks in academic contexts by presenting a new tool, the TASQ@work, aimed at contextualizing the JD-R model to understand the role played by psychosocial aspects in affecting the well-being of the academic employees

MicroRNA Expression Profiling Using Agilent One-Color Microarray

MicroRNA (miRNA) expression profiling is an important tool to identify miRNA regulation in physiological or pathological states. This technique has a large number of molecular diagnostic applications, including cancer, cardiovascular and autoimmune diseases, and forensics. To date, a multitude of high-throughput genomic approaches have been developed. Here, we focus on miRNA expression profiling by microarray using SurePrint technology, providing a description of both the workflow and methods for expression profiling by Agilent One-Color Microarray

Cancer Therapy Resistance: Choosing Kinase Inhibitors

Recent advances in comprehending the essential molecular mechanisms that govern cancer signaling have revealed the pivotal involvement of kinases in the development and progression of various cancer types [...

Breast Cancer Vaccines: New Insights

Breast cancer (BC) is a persistent global challenge for its high frequency in women (although it seldom occurs in men), due to the large diffusion of risk factors and gene mutations, and for its peculiar biology and microenvironment. To date, BC can benefit from different therapeutic strategies involving surgery, ablation, chemotherapy, radiotherapy, and more specific approaches such as hormone therapy and the administration of various substances impairing cancer growth, aggressivity, and recurrence with different modalities. Despite these relatively wide chances, also used in combinatory protocols, relevant mortality and relapse rates, often associated with resistant phenotypes, stress the need for a personalized-medicine based on prompting the patient’s immune system (IS) against cancer cells. BC immunogenicity was latterly proven, so the whole immunotherapy field for BC is still at a very early stage. This immunotherapeutic approach exploits both the high specificity of adaptive immune response and the immunological memory. This review is focused on some of the majorly relevant BC vaccines available (NeuVax, AVX901, and INO-1400), providing a description of the more promising clinical trials. The efficacy of cancer vaccines highly depends on the patient’s IS, and a wide optimization is needed in terms of targets’ selection, drug design and combinations, dose finding, protocol structuring, and patients’ recruitment; moreover, new standards are being discussed for the outcome evaluation. However, early-phases excellent results suggest that the manipulation of the IS via specific vaccines is a highly attractive approach for BC

HDAC2-dependent miRNA signature in acute myeloid leukemia

Acute myeloid leukemia (AML) is a multifactorial and highly heterogeneous malignancy, whose incidence rises with age. Among the many epigenetic regulators, histone deacetylases are tightly involved in AML etiology. Notably, HDAC2 is highly overexpressed in solid and haematological cancers, including AML. HDAC2 silencing by enzymatic inhibition has a substantial impact on leukemia cell proliferation and immune regulation, as described in our previous work (Conte M. et al. doi:10.18632/oncotarget.2816). Altered miRNAs in AML are known to play a critical role in a broad range of key molecular processes via sophisticated regulation of distinct targets, orchestrating a molecular intracellular balance of gene expression. Recently, the potential use of circulating miRNAs as biomarkers for AML diagnosis/prognosis and as therapeutic targets has been widely explored, and many miRNAs were found to be associated with HDAC2 dysfunction in leukemia. Here, we identified a cluster of common up- and downregulated miRNAs in both SAHA-treated and HDAC2-downregulated cells. By miRNA target network computational analysis, we defined an HDAC2mediated miRNA signatures in AML by genetic and enzymatic HDAC2 deficiency in a U937 leukemic cell line. We propose a crucial role of miR-96-5p and miR92a-3p and related target genes and their relationship with HDAC2 in AML. This HDAC2-dependent miRNA signature in AML highlights the potentially beneficial effects of treatment with epigenetic drugs alone or in combination with other therapies

Extracellular vesicle-based nucleic acid delivery: Current advances and future perspectives in cancer therapeutic strategies

Extracellular vesicles (EVs) are sophisticated and sensitive messengers released by cells to communicate with and influence distant and neighboring cells via selective transfer of bioactive content, including protein lipids and nucleic acids. EVs have therefore attracted broad interest as new and refined potential therapeutic systems in many diseases, including cancer, due to their low immunogenicity, non-toxicity, and elevated bioavailability. They might serve as safe and effective vehicles for the transport of therapeutic molecules to specific tissues and cells. In this review, we focus on EVs as a vehicle for gene therapy in cancer. We describe recent developments in EV engineering to achieve efficient intracellular delivery of cancer therapeutics and avoid off-target effects, to provide an overview of the potential applications of EV-mediated gene therapy and the most promising biomedical advances