High prevalence of cardiac post-acute sequelae in patients recovered from Covid-19. Results from the ARCA post-COVID study.

Background: Many data were published about Long-Covid prevalence, very few about the findings of new cardiac alterations (NCA) in COVID-19-recovered people. is an observational study designed to investigate the prevalence of NCA in patients recovered from Covid-19.Methods: from June 2020 to December 2022, we enrolled 502 patients with a positive nasopharyngeal swab for SARS-CoV2 and a subsequent negative one.

I know how you'll say it: evidence of speaker-specific speech prediction.

Most models of language comprehension assume that the linguistic system is able to pre-activate phonological information. However, the evidence for phonological prediction is mixed and controversial. In this study, we implement a paradigm that capitalizes on the fact that foreign speakers usually make phonological errors.

FRA-1 as a Regulator of EMT and Metastasis in Breast Cancer.

Among FOS-related components of the dimeric AP-1 transcription factor, the oncoprotein FRA-1 (encoded by ) is a key regulator of invasion and metastasis. The well-established FRA-1 pro-invasive activity in breast cancer, in which is overexpressed in the TNBC (Triple Negative Breast Cancer)/basal subtypes, correlates with the FRA-1-dependent transcriptional regulation of EMT (Epithelial-to-Mesenchymal Transition). After summarizing the major findings on FRA-1 in breast cancer invasiveness, we discuss the FRA-1 mechanistic links with EMT and cancer cell stemness, mediated by transcriptional and posttranscriptional interactions between /FRA-1 and EMT-regulating transcription factors, miRNAs, RNA binding proteins and cytokines, along with other target genes involved in EMT.

Exogenous Players in Mitochondria-Related CNS Disorders: Viral Pathogens and Unbalanced Microbiota in the Gut-Brain Axis.

Billions of years of co-evolution has made mitochondria central to the eukaryotic cell and organism life playing the role of cellular power plants, as indeed they are involved in most, if not all, important regulatory pathways. Neurological disorders depending on impaired mitochondrial function or homeostasis can be caused by the misregulation of "endogenous players", such as nuclear or cytoplasmic regulators, which have been treated elsewhere. In this review, we focus on how exogenous agents, i.

The Fra-1/AP-1 Oncoprotein: From the "Undruggable" Transcription Factor to Therapeutic Targeting.

The genetic and epigenetic changes affecting transcription factors, coactivators, and chromatin modifiers are key determinants of the hallmarks of cancer. The acquired dependence on oncogenic transcriptional regulators, representing a major determinant of cancer cell vulnerability, points to transcription factors as ideal therapeutic targets. However, given the unavailability of catalytic activities or binding pockets for small-molecule inhibitors, transcription factors are generally regarded as undruggable proteins.

Multifaceted Roles of DNA Methylation in Neoplastic Transformation, from Tumor Suppressors to EMT and Metastasis.

Among the major mechanisms involved in tumorigenesis, DNA methylation is an important epigenetic modification impacting both genomic stability and gene expression. Methylation of promoter-proximal CpG islands (CGIs) and transcriptional silencing of tumor suppressors represent the best characterized epigenetic changes in neoplastic cells. The global cancer-associated effects of DNA hypomethylation influence chromatin architecture and reactivation of repetitive elements.

The nuclear oncoprotein Fra-1: a transcription factor knocking on therapeutic applications' door.

Among the FOS-related members of the AP-1 dimeric complex, the transcription factor Fra-1, encoded by FOSL1, is crucially involved in human tumor progression and metastasis, thus representing a promising therapeutic target. Here we review the state of the art and discuss the emerging topics and perspectives on FOSL1 and its gene product. First, we summarize the present knowledge on the FOSL1 transcriptional and epigenetic controls, driving Fra-1 accumulation in a variety of human solid tumors.

Collagen Prolyl Hydroxylation-Dependent Metabolic Perturbation Governs Epigenetic Remodeling and Mesenchymal Transition in Pluripotent and Cancer Cells.

Collagen prolyl hydroxylation (CPH), which is catalyzed by prolyl 4-hydroxylase (P4H), is the most prevalent posttranslational modification in humans and requires vitamin C (VitC). Here, we demonstrate that CPH acts as an epigenetic modulator of cell plasticity. Increased CPH induced global DNA/histone methylation in pluripotent stem and tumor cells and promoted cell state transition (CST).

Successful intravenous thrombolysis for ischemic stroke after reversal of dabigatran anticoagulation with idarucizumab: a case report.

Background: Non-vitamin K antagonist oral anticoagulants, including dabigatran, are currently widely used for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation. Recently, idarucizumab, a monoclonal antibody fragment for immediate reversal of dabigatran-induced anticoagulation, has been introduced into the market to be used in life-threatening bleeding or urgent surgery, allowing for rapid normalization of clotting parameters. The use of idarucizumab is not yet well established in patients presenting with acute ischemic stroke on dabigatran who are candidates for thrombolytic therapy.

One-year GH replacement therapy reduces early cardiac target organ damage (TOD) in adult GHD patients.

Hypopituitarism reduces life expectancy and increases the risk of cardiovascular and cerebrovascular diseases, as well as death. Abnormalities in the cardiovascular system may be independently related to GH deficiency (GHD). The aim of this study was to prospectively investigate coronary flow reserve and diastolic function in GHD adult patients at diagnosis and after 1 year of GH replacement therapy.

Nanoengineered surfaces for focal adhesion guidance trigger mesenchymal stem cell self-organization and tenogenesis.

The initial conditions for morphogenesis trigger a cascade of events that ultimately dictate structure and functions of tissues and organs. Here we report that surface nanopatterning can control the initial assembly of focal adhesions, hence guiding human mesenchymal stem cells (hMSCs) through the process of self-organization and differentiation. This process self-sustains, leading to the development of macroscopic tissues with molecular profiles and microarchitecture reminiscent of embryonic tendons.

The class I-specific HDAC inhibitor MS-275 modulates the differentiation potential of mouse embryonic stem cells.

Exploitation of embryonic stem cells (ESC) for therapeutic use and biomedical applications is severely hampered by the risk of teratocarcinoma formation. Here, we performed a screen of selected epi-modulating compounds and demonstrate that a transient exposure of mouse ESC to MS-275 (Entinostat), a class I histone deacetylase inhibitor (HDAC), modulates differentiation and prevents teratocarcinoma formation. Morphological and molecular data indicate that MS-275-primed ESCs are committed towards neural differentiation, which is supported by transcriptome analyses.

Citalopram and levosulpiride: a dangerous drug combination for QT prolongation.

We report the case of an 89-year-old female patient who presented to the emergency department after out-of-hospital cardiac arrest due to polymorphic ventricular tachycardia treated by public access defibrillation. The admission electrocardiogram (ECG) showed extreme QT prolongation (650 milliseconds) with recurrent episodes of nonsustained polymorphic ventricular tachycardia. Intravenous magnesium sulfate therapy was instituted.

An automated high throughput screening-compatible assay to identify regulators of stem cell neural differentiation.

The use of Embryonic Stem Cells (ESCs) holds considerable promise both for drug discovery programs and the treatment of degenerative disorders in regenerative medicine approaches. Nevertheless, the successful use of ESCs is still limited by the lack of efficient control of ESC self-renewal and differentiation capabilities. In this context, the possibility to modulate ESC biological properties and to obtain homogenous populations of correctly specified cells will help developing physiologically relevant screens, designed for the identification of stem cell modulators.

Osteopontin plasma levels and accelerated atherosclerosis in patients with CAD undergoing PCI: a prospective clinical study.

Objectives: Growing evidence supports the role played by inflammation in atherosclerosis. Identifying sensitive biomarkers is useful in predicting accelerated atherosclerosis. We investigated prospectively the relationship between plasma levels of inflammatory biomarkers [osteopontin, C-reactive protein (CRP), interleukin-6 (IL-6)] and instent restenosis, and rapid coronary plaque progression in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI).

Control of embryonic stem cell metastability by L-proline catabolism.

The molecular mechanisms controlling mouse embryonic stem cell (ESC) metastability, i.e. their capacity to fluctuate between different states of pluripotency, are not fully resolved.

A dangerous fruit juice.

We report the case of a female patient presenting to the emergency department with postprandial syncope and atrial fibrillation. After amiodarone administration, the electrocardiogram showed marked QT prolongation associated with ventricular arrhythmias, including an episode of torsade de pointes requiring immediate electrical cardioversion. During history taking, the patient reported that she had been drinking large amounts of grapefruit juice regularly.

[Atrial myxoma presenting during pregnancy].

We report a case of left atrial myxoma presenting as acute respiratory failure following surgical intervention for voluntary interruption of pregnancy. After cardiac surgery T-wave changes were observed on the ECG, most likely due to coronary embolism.

Percutaneous closure of patent foramen ovale in patients with presumed paradoxical embolism: periprocedural results and midterm risk of recurrent neurologic events.

Objective: To report our data on selected patients with previous paradoxical embolism who underwent transcatheter patent foramen ovale (PFO) closure.

Methods: Between July 2001 and July 2007, percutaneous PFO closure was performed on 128 patients (65 women, mean age: 46 +/- 12.8 years).

Deciphering AP-1 function in tumorigenesis: fra-ternizing on target promoters.

Multi-gene families of transcription factors pose a formidable challenge to molecular and functional analysis. Dissecting distinct functions for individual family members requires a combination of approaches in different cellular and animal models. The AP-1 transcription factor complex serves as a paradigm for understanding the dynamics of transcriptional regulation.

Fra-1 promotes growth and survival in RAS-transformed thyroid cells by controlling cyclin A transcription.

Fra-1 is frequently overexpressed in epithelial cancers and implicated in invasiveness. We previously showed that Fra-1 plays crucial roles in RAS transformation in rat thyroid cells and mouse fibroblasts. Here, we report a novel role for Fra-1 as a regulator of mitotic progression in RAS-transformed thyroid cells.

Accumulation of Fra-1 in ras-transformed cells depends on both transcriptional autoregulation and MEK-dependent posttranslational stabilization.

The AP-1 transcription factor plays an essential role in cell proliferation and tumorigenesis. It was previously shown that the fra-1 gene product is upregulated by various oncogenes and is involved in the in vitro and in vivo transformation of thyroid cells. Here we show that the ras oncogene-dependent accumulation of Fra-1 is mediated by a positive feedback mechanism which requires both transcriptional autoregulation and posttranslational stabilization of the protein.