Circulating miRNA in functional tricuspid regurgitation. Unveiling novel links to heart failure: A pilot study.

Aim: Severe functional tricuspid regurgitation (FTR) is associated with high risk of cardiovascular events, particularly heart failure (HF) and mortality. MicroRNAs (miRNAs) have been recently identified as novel biomarkers in different cardiovascular conditions, but no studies have focused on FTR. We sought to (1) to identify and validate circulating miRNAs as regulators of FTR and (2) to test association of miRNA with heart failure and mortality in FTR.

Dependence of Induced Biological Damage on the Energy Distribution and Intensity of Clinical Intra-Operative Radiotherapy Electron Beams.

The survival fraction of epithelial HaCaT cells was analysed to assess the biological damage caused by intraoperative radiotherapy electron beams with varying energy spectra and intensities. These conditions were achieved by irradiating the cells at different depths in water using nominal 6 MeV electron beams while consistently delivering a dose of 5 Gy to the cell layer. Furthermore, a Monte Carlo simulation of the entire irradiation procedure was performed to evaluate the molecular damage in terms of molecular dissociations induced by the radiation.

Selective miRNA inhibition in CD8 cytotoxic T lymphocytes enhances HIV-1 specific cytotoxic responses.

miRNAs dictate relevant virus-host interactions, offering new avenues for interventions to achieve an HIV remission. We aimed to enhance HIV-specific cytotoxic responses-a hallmark of natural HIV control- by miRNA modulation in T cells. We recruited 12 participants six elite controllers and six patients with chronic HIV infection on long-term antiretroviral therapy ("progressors").

Serum microRNAs are key predictors of long-term heart failure and cardiovascular death after myocardial infarction.

Background: Patients with acute myocardial infarction (MI) are at high risk of upcoming events, in particular heart failure (HF), but reliable stratification methods are lacking. Our goal was to evaluate the potential role of circulating miRNAs as prognostic biomarkers in patients presenting with MI.

Methods And Results: We conducted a prospective study among 311 consecutive patients hospitalized with MI (65% ST-segment elevation MI & median age of 55 years) with long-term follow-up.

Cyclooxygenase 2 Effector Genes as Potential Inflammation-Related Biomarkers for Colorectal Cancer Circulating Tumor Cells Detection by Liquid Biopsy.

Cyclooxygenase 2 (COX2) has been implicated in cancer development and metastasis. We have identified several COX2-regulated inflammation-related genes in human colorectal cancer cells and shown that some of them play important roles in tumor progression. In this work, we have studied the COX2-regulated genes in the mouse colorectal cancer cell line CT26, to find that many are also regulated by COX2 over-expression.

Consensus guidelines for the validation of qRT-PCR assays in clinical research by the CardioRNA consortium.

Despite promising findings, quantitative PCR (qPCR)-based tests for RNA quantification have experienced serious limitations in their clinical application. The noticeable lack of technical standardization remains a huge obstacle in the translation of qPCR-based tests. The incorporation of qPCR-based tests into the clinic will benefit from guidelines for clinical research assay validation.

Serum miR-181b-5p predicts ascites onset in patients with compensated cirrhosis.

Background & Aims: Treatment with non-selective beta-blockers (NSBBs) reduces the risk of ascites, which is the most common decompensating event in cirrhosis. This study aimed to assess the ability of a serum microRNA (miRNA) signature to predict ascites formation and the hemodynamic response to NSBBs in compensated cirrhosis.

Methods: Serum levels of miR-452-5p, miR-429, miR-885-5p, miR-181b-5p, and miR-122-5p were analyzed in patients with compensated cirrhosis (N = 105).

Circulating Extracellular Vesicle Proteins and MicroRNA Profiles in Subcortical and Cortical-Subcortical Ischaemic Stroke.

In order to investigate the role of circulating extracellular vesicles (EVs), proteins, and microRNAs as damage and repair markers in ischaemic stroke depending on its topography, subcortical (SC), and cortical-subcortical (CSC) involvement, we quantified the total amount of EVs using an enzyme-linked immunosorbent assay technique and analysed their global protein content using proteomics. We also employed a polymerase chain reaction to evaluate the circulating microRNA profile. The study included 81 patients with ischaemic stroke (26 SC and 55 CSC) and 22 healthy controls (HCs).

Biomarkers Associated with Regorafenib First-Line Treatment Benefits in Metastatic Colorectal Cancer Patients: REFRAME Molecular Study.

First-line treatment with regorafenib in frail metastatic colorectal cancer (mCRC) patients has shown some benefit. To accurately identify such patients before treatment, we studied blood biomarkers and primary tumor molecules. We unveiled serum microRNAs (miRNAs), single-nucleotide polymorphisms (SNPs) in angiogenic-related genes, and Notch 1 expression as biomarkers associated with response or toxicity.

Similarities and Differences in Extracellular Vesicle Profiles between Ischaemic Stroke and Myocardial Infarction.

Extracellular vesicles (EVs) are involved in intercellular signalling through the transfer of molecules during physiological and pathological conditions, such as ischaemic disease. EVs might therefore play a role in ischaemic stroke (IS) and myocardial infarction (MI). In the present study, we analysed the similarities and differences in the content of circulating EVs in patients with IS and MI.

BRAF Mutated Colorectal Cancer: New Treatment Approaches.

Colon cancer is one of the most frequently diagnosed malignancies in adults, considering both its incidence and prevalence. Anatomically, the right colon is considered as being from the cecum to the splenic flexure, and the left colon is from the splenic flexure to the rectum. Sidedness is a surrogate of a wide spectrum of colorectal cancer (CRC) biology features (embryology, microbiome, methylation, microsatellite instability (MSI), BRAF, aging, KRAS, consensus molecular subtypes (CMS), etc.

Epigenetic Landscape in Pancreatic Ductal Adenocarcinoma: On the Way to Overcoming Drug Resistance?

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid malignancies due to the rapid rate of metastasis and high resistance to currently applied cancer therapies. The complex mechanism underlying the development and progression of PDAC includes interactions between genomic, epigenomic, and signaling pathway alterations. In this review, we summarize the current research findings on the deregulation of epigenetic mechanisms in PDAC and the influence of the epigenome on the dynamics of the gene expression changes underlying epithelial-mesenchymal transition (EMT), which is responsible for the invasive phenotype of cancer cells and, therefore, their metastatic potential.

Low dose of extracellular vesicles identified that promote recovery after ischemic stroke.

Background: Mesenchymal stem cell-derived extracellular vesicles (EVs) are one of the most promising therapeutics in protective and/or regenerative therapy in animal models of stroke using a dose of 100 μg. However, whether EVs dose is related to outcomes is not known. This study aimed to identify the optimal effective dose of EVs from adipose tissue-derived mesenchymal stem cells that promote functional recovery in subcortical stroke.

Prostaglandin F-induced Prostate Transmembrane Protein, Androgen Induced 1 mediates ovarian cancer progression increasing epithelial plasticity.

The role of prostaglandin (PG) F has been scarcely studied in cancer. We have identified a new function for PGF in ovarian cancer, stimulating the production of Prostate Transmembrane Protein, Androgen Induced 1 (PMEPA1). We show that this induction increases cell plasticity and proliferation, enhancing tumor growth through PMEPA1.

A genetic risk score predicts recurrent events after myocardial infarction in young adults.

Introduction And Objectives: To evaluate whether a genetic risk score (GRS) improves prediction of recurrent events in young nondiabetic patients presenting with an acute myocardial infarction (AMI) and identifies a more aggressive form of atherosclerosis.

Methods: We conducted a prospective study with consecutive nondiabetic patients aged <55 years presenting with AMI. We performed a genetic test, cardiac computed tomography, and analyzed several biomarkers.

Intracellular Delivery of an Antibody Targeting Gasdermin-B Reduces HER2 Breast Cancer Aggressiveness.

Purpose: Gasdermin B (GSDMB) overexpression/amplification occurs in about 60% of HER2 breast cancers, where it promotes cell migration, resistance to anti-HER2 therapies, and poor clinical outcome. Thus, we tackle GSDMB cytoplasmic overexpression as a new therapeutic target in HER2 breast cancers.

Experimental Design: We have developed a new targeted nanomedicine based on hyaluronic acid-biocompatible nanocapsules, which allow the intracellular delivery of a specific anti-GSDMB antibody into HER2 breast cancer cells both and .

Targeting Tyrosine kinases in Renal Cell Carcinoma: "New Bullets against Old Guys".

Clear cell renal cell carcinoma (ccRCC) is the seventh most frequently diagnosed tumor in adults in Europe and represents approximately 2.5% of cancer deaths. The molecular biology underlying renal cell carcinoma (RCC) development and progression has been a key milestone in the management of this type of tumor.

Novel Molecular Characterization of Colorectal Primary Tumors Based on miRNAs.

microRNAs (miRNA) expression in colorectal (CR) primary tumours can facilitate a more precise molecular characterization. We identified and validated a miRNA profile associated with clinical and histopathological features that might be useful for patient stratification. In situ hybridization array using paraffin-embedded biopsies of CR primary tumours were used to screen 1436 miRNAs.

Maraviroc Is Associated with Latent HIV-1 Reactivation through NF-κB Activation in Resting CD4 T Cells from HIV-Infected Individuals on Suppressive Antiretroviral Therapy.

Maraviroc is a CCR5 antagonist used in the treatment of HIV-1 infection. We and others have suggested that maraviroc could reactivate latent HIV-1. To test the latency-reversing potential of maraviroc and the mechanisms involved, we performed a phase II, single-center, open-label study in which maraviroc was administered for 10 days to 20 HIV-1-infected individuals on suppressive antiretroviral therapy (EudraCT registration no.

VHL promotes immune response against renal cell carcinoma via NF-κB-dependent regulation of VCAM-1.

Vascular cell adhesion molecule 1 (VCAM-1) is an adhesion molecule assigned to the activated endothelium mediating immune cells adhesion and extravasation. However, its expression in renal carcinomas inversely correlates with tumor malignancy. Our experiments in clear cell renal cell carcinoma (ccRCC) cell lines demonstrated that von Hippel Lindau (VHL) loss, hypoxia, or PHD (for prolyl hydroxylase domain-containing proteins) inactivation decreased VCAM-1 levels through a transcriptional mechanism that was independent of the hypoxia-inducible factor and dependent on the nuclear factor κB signaling pathway.

HIF-1α induction during reperfusion avoids maladaptive repair after renal ischemia/reperfusion involving miR127-3p.

Ischemia/reperfusion (I/R) leads to Acute Kidney Injury. HIF-1α is a key factor during organ response to I/R. We previously demonstrated that HIF-1α is induced during renal reperfusion, after ischemia.

A double-blind, randomized, cross-over, placebo-controlled, pilot trial with Sativex in Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disease for which there is no curative treatment available. Given that the endocannabinoid system is involved in the pathogenesis of HD mouse models, stimulation of specific targets within this signaling system has been investigated as a promising therapeutic agent in HD. We conducted a double-blind, randomized, placebo-controlled, cross-over pilot clinical trial with Sativex(®), a botanical extract with an equimolecular combination of delta-9-tetrahydrocannabinol and cannabidiol.