Vedolizumab to prevent postoperative recurrence of Crohn's disease (REPREVIO): a multicentre, double-blind, randomised, placebo-controlled trial.

Background: Approximately half of patients with Crohn's disease require ileocolonic resection. Of these, 50% will subsequently have endoscopic disease recurrence within 1 year. We aimed to evaluate the efficacy and safety of vedolizumab to prevent postoperative recurrence of Crohn's disease.

Loss of tet methyl cytosine dioxygenase 3 (TET3) enhances cardiac fibrosis via modulating the DNA damage repair response.

Background: Cardiac fibrosis is the hallmark of all forms of chronic heart disease. Activation and proliferation of cardiac fibroblasts are the prime mediators of cardiac fibrosis. Existing studies show that ROS and inflammatory cytokines produced during fibrosis not only signal proliferative stimuli but also contribute to DNA damage.

Early Versus Late Use of Vedolizumab in Ulcerative Colitis: Clinical, Endoscopic, and Histological Outcomes.

Background And Aims: We explored the potential for differential efficacy of vedolizumab between early and late ulcerative colitis [UC] with evaluation of clinical, endoscopic, and histological endpoints.

Methods: This was a multicentre, multinational, open-label study in patients with moderately-to-severely active UC, defining early UC by a disease duration <4 years and bio-naïve and late UC by a disease duration > 4 years and additional exposure to tumour necrosis factor antagonists. Patients received standard treatment with intravenous vedolizumab for 52 weeks [300 mg Weeks 0, 2, 6, every 8 weeks thereafter without escalation].

Efficacious dosing regimens for anti-TNF therapies in inflammatory bowel disease: where do we stand?

Introduction: During the last decades, biologics have revolutionized the treatment of Crohn's disease and ulcerative colitis. Even though the inflammatory bowel disease (IBD) armamentarium is rapidly expanding with novel biologics, anti-tumor necrosis factor (TNF) antibodies remain the first-line biologic therapy in most areas of the world. However, anti-TNF therapy is not effective in all patients (primary non-response) and patients can lose effect over time (secondary loss of response).

miR-132-3p and KLF7 as novel regulators of aortic stiffening-associated EndMT in type 2 diabetes mellitus.

Background: The prevalence of diabetes mellitus has risen considerably and currently affects more than 422 million people worldwide. Cardiovascular diseases including myocardial infarction and heart failure represent the major cause of death in type 2 diabetes (T2D). Diabetes patients exhibit accelerated aortic stiffening which is an independent predictor of cardiovascular disease and mortality.

CRISPR/Cas Derivatives as Novel Gene Modulating Tools: Possibilities and In Vivo Applications.

The field of genome editing started with the discovery of meganucleases (e.g., the LAGLIDADG family of homing endonucleases) in yeast.

Serelaxin alleviates cardiac fibrosis through inhibiting endothelial-to-mesenchymal transition via RXFP1.

: Cardiac fibrosis is an integral constituent of every form of chronic heart disease, and persistence of fibrosis reduces tissue compliance and accelerates the progression to heart failure. Relaxin-2 is a human hormone, which has various physiological functions such as mediating renal vasodilation in pregnancy. Its recombinant form Serelaxin has recently been tested in clinical trials as a therapy for acute heart failure but did not meet its primary endpoints.

Non-coding RNA in endothelial-to-mesenchymal transition.

Endothelial-to-mesenchymal transition (EndMT) is the process wherein endothelial cells lose their typical endothelial cell markers and functions and adopt a mesenchymal-like phenotype. EndMT is required for development of the cardiac valves, the pulmonary and dorsal aorta, and arterial maturation, but activation of the EndMT programme during adulthood is believed to contribute to several pathologies including organ fibrosis, cardiovascular disease, and cancer. Non-coding RNAs, including microRNAs, long non-coding RNAs, and circular RNAs, modulate EndMT during development and disease.

Causal Connections From Chronic Kidney Disease to Cardiac Fibrosis.

Cardiovascular disease and heart failure are the primary cause of morbidity and mortality in patients with chronic kidney disease. Because impairment of kidney function correlates with heart failure and cardiac fibrosis, a kidney-heart axis is suspected. Although our understanding of the underlying mechanisms still is evolving, the possibility that kidney-heart messengers could be intercepted offers ample reason to focus on this clinically highly relevant problem.

Epigenetic Regulation of Endothelial-to-Mesenchymal Transition in Chronic Heart Disease.

Endothelial-to-mesenchymal transition (EndMT) is a process in which endothelial cells lose their properties and transform into fibroblast-like cells. This transition process contributes to cardiac fibrosis, a common feature of patients with chronic heart failure. To date, no specific therapies to halt or reverse cardiac fibrosis are available, so knowledge of the underlying mechanisms of cardiac fibrosis is urgently needed.

High-fidelity CRISPR/Cas9- based gene-specific hydroxymethylation rescues gene expression and attenuates renal fibrosis.

While suppression of specific genes through aberrant promoter methylation contributes to different diseases including organ fibrosis, gene-specific reactivation technology is not yet available for therapy. TET enzymes catalyze hydroxymethylation of methylated DNA, reactivating gene expression. We here report generation of a high-fidelity CRISPR/Cas9-based gene-specific dioxygenase by fusing an endonuclease deactivated high-fidelity Cas9 (dHFCas9) to TET3 catalytic domain (TET3CD), targeted to specific genes by guiding RNAs (sgRNA).

Hypoxia-induced endothelial-mesenchymal transition is associated with RASAL1 promoter hypermethylation in human coronary endothelial cells.

Cardiac fibrosis is integral in chronic heart disease, and one of the cellular processes contributing to cardiac fibrosis is endothelial-to-mesenchymal transition (EndMT). We recently found that hypoxia efficiently induces human coronary artery endothelial cells (HCAEC) to undergo EndMT through a hypoxia inducible factor-1α (HIF1α)-dependent pathway. Promoter hypermethylation of Ras-Gap-like protein 1 (RASAL1) has also been recently associated with EndMT progression and cardiac fibrosis.