Overexpression of TNFα in TNF∆ARE+/- mice increases hepatic periportal inflammation and alters bile acid signaling in mice.

Background: Intestinal inflammation is a common factor in ~70% of patients diagnosed with primary sclerosing cholangitis. The TNF∆ARE+/- mouse overexpresses TNFα and spontaneously develops ileitis after weaning. The aim of this study was to examine the influence of ileitis and TNFα overexpression on hepatic injury, fibrosis, inflammation, and bile acid homeostasis.

Effect of apremilast on hand and whole-body MRI assessments of inflammation in patients with psoriatic arthritis (MOSAIC): a phase 4, multicentre, single-arm, open-label study.

Background: The Psoriatic Arthritis Magnetic Resonance Imaging Scoring System (PsAMRIS) and MRI Whole-Body Scoring System for Inflammation in Peripheral Joints and Entheses in Inflammatory Arthritis (MRI-WIPE) have not been used together to assess treatment of psoriatic arthritis in a clinical trial. We aimed to assess the effect of apremilast treatment on inflammation, with outcomes measured by PsAMRIS and MRI-WIPE.

Methods: MOSAIC was a phase 4, multicentre, single-arm, open-label study conducted at 29 sites across ten countries (Belgium, Canada, Denmark, Germany, Italy, Russia, Spain, Switzerland, the UK, and the USA).

Physiologic hypoxia in the intestinal mucosa: a central role for short-chain fatty acids.

The intestinal mucosa is a dynamic surface that facilitates interactions between the host and an outside world that includes trillions of microbes, collectively termed the microbiota. This fine balance is regulated by an energetically demanding physical and biochemical barrier that is formed by the intestinal epithelial cells. In addition, this homeostasis exists at an interface between the anaerobic colonic lumen and a highly oxygenated, vascularized lamina propria.

Chlorination of epithelial tight junction proteins by neutrophil myeloperoxidase promotes barrier dysfunction and mucosal inflammation.

Neutrophils (polymorphonuclear leukocytes, PMNs) comprise a major component of the immune cell infiltrate during acute mucosal inflammation and have an important role in molding the inflammatory tissue environment. While PMNs are essential to clearance of invading microbes, the major PMN antimicrobial enzyme myeloperoxidase (MPO) can also promote bystander tissue damage. We hypothesized that blocking MPO would attenuate acute colitis and prevent the development of chronic colitis by limiting bystander tissue damage.

Diabetes and obesity burden and improvements in cardiometabolic parameters in patients with psoriasis or psoriatic arthritis receiving apremilast in a real-world setting.

Introduction: Patients with psoriasis and psoriatic arthritis have a higher prevalence of cardiometabolic comorbidities compared to the general population. Clinical data suggest apremilast may reduce weight and glycated hemoglobin (HbA1c).

Objective: To describe changes in cardiometabolic parameters among patients with psoriasis and psoriatic arthritis newly treated with apremilast by prediabetes/diabetes or obesity status.