Characterization of a novel non-steroidal glucocorticoid receptor agonist optimized for topical treatment.

Glucocorticoids (GCs) are commonly used topical treatments for skin diseases but are associated with both local and systemic side effects. In this study, we describe a selective non-steroidal glucocorticoid receptor (GR) agonist for topical use, LEO 134310, which is rapidly deactivated in the blood resulting in low systemic exposure and a higher therapeutic index in the TPA-induced skin inflammation mouse model compared with betamethasone valerate (BMV) and clobetasol propionate (CP). Selectivity of LEO 134310 for GR was confirmed within a panel of nuclear receptors, including the mineralocorticoid receptor (MR), which has been associated with induction of skin atrophy.

Label-Free Quantification of Pharmacokinetics in Skin with Stimulated Raman Scattering Microscopy and Deep Learning.

The treatment of inflammatory skin conditions relies on a deep understanding of how drugs and tissue behave and interact. Although numerous methods have been developed that aim to follow and quantify topical drug pharmacokinetics, these tools can come with limitations, assumptions, and trade-offs that do not allow for real-time tracking of drug flow and flux on the cellular level in situ. We have developed a quantitative imaging toolkit that makes use of stimulated Raman scattering microscopy and deep learning-based computational image analysis to quantify the uptake of specific drug molecules in skin without the need for labels.

Kinetics of gene expression and bone remodelling in the clinical phase of collagen-induced arthritis.

Introduction: Pathological bone changes differ considerably between inflammatory arthritic diseases and most studies have focused on bone erosion. Collagen-induced arthritis (CIA) is a model for rheumatoid arthritis, which, in addition to bone erosion, demonstrates bone formation at the time of clinical manifestations. The objective of this study was to use this model to characterise the histological and molecular changes in bone remodelling, and relate these to the clinical disease development.

MicroRNA expression in early mycosis fungoides is distinctly different from atopic dermatitis and advanced cutaneous T-cell lymphoma.

Mycosis fungoides (MF) is the most common variant of cutaneous T-cell lymphoma (CTCL). MF is characterized by chronic inflammation dominated by cluster of differentiation 4-positive (CD4(+)) T-cells and T helper 2 cytokines, and as the malignant T-cell clone is initially elusive, early diagnosis is often impossible. MF usually takes an indolent course, but for unknown reasons may turn into an aggressive disease with a poor prognosis.

Calcipotriol counteracts betamethasone-induced decrease in extracellular matrix components related to skin atrophy.

The calcipotriol/betamethasone dipropionate fixed-combination gel is widely used for topical treatment of psoriasis vulgaris. It has been hypothesized that calcipotriol counteracts glucocorticoid-induced skin atrophy which is associated with changes in the extracellular matrix (ECM). To elucidate the combined effects of calcipotriol and betamethasone on key ECM components, a comparative study to the respective mono-treatments was carried out.