Comparison of Grenz ray and photodynamic therapy for field treatment of actinic keratoses on the forearm: A case series.

BACKGROUND: Actinic Keratosis is an intraepidermal neoplasm that represents the second most common reason for dermatologic visits in the United States. Sustained clearance with existing therapies is highly variable. OBJECTIVE: To assess the effects of combination and monotherapy with photodynamic therapy (PDT), grenz ray therapy, and PDT with microneedling (microchannel skin system) for actinic damage of the dorsal forearms and hands. METHODS: Full ethics approval was obtained through a Human Subjects Committee. Four patients with diffuse actinic field damage on their forearms and hands were recruited for the study. The dorsal forearm and hand from the elbow to the metacarpophalangeal joint were divided into four equal sections. Section 1 was treated with PDT. Section 2 was treated with grenz ray. Section 3 was treated with PDT plus microneedling. Section 4 was treated with grenz ray and PDT with microneedling. Lesion counts were recorded with transparent grids, photographed and evaluated by the same investigator at baseline, 1, 2, 3 and 6 months. RESULTS: At month 6 post treatment, lesion counts, as a per cent reduction from baseline, were 91.7% in section 1 (PDT); 97.3% in section 2 (grenz ray); 92.9% in section 3 (PDT + microneedle); and 93.9% in section 4 (grenz ray + PDT + microneedle). CONCLUSION: The greatest reduction occurred in the grenz ray monotherapy section and the second greatest reduction in the grenz ray, PDT, microneedling section. Further research on the efficacy of grenz ray therapy for field treatment of actinic keratosis of the forearms and hands is needed.

A Global Map of Lipid-Binding Proteins and Their Ligandability in Cells.

Lipids play central roles in physiology and disease, where their structural, metabolic, and signaling functions often arise from interactions with proteins. Here, we describe a set of lipid-based chemical proteomic probes and their global interaction map in mammalian cells. These interactions involve hundreds of proteins from diverse functional classes and frequently occur at sites of drug action. We determine the target profiles for several drugs across the lipid-interaction proteome, revealing that its ligandable content extends far beyond traditionally defined categories of druggable proteins. In further support of this finding, we describe a selective ligand for the lipid-binding protein nucleobindin-1 (NUCB1) and show that this compound perturbs the hydrolytic and oxidative metabolism of endocannabinoids in cells. The described chemical proteomic platform thus provides an integrated path to both discover and pharmacologically characterize a wide range of proteins that participate in lipid pathways in cells.

Evaluation of NHS carbamates as a potent and selective class of endocannabinoid hydrolase inhibitors.

Monoacylglycerol lipase (MAGL) is a principal metabolic enzyme responsible for hydrolyzing the endogenous cannabinoid (endocannabinoid) 2-arachidonoylglycerol (2-AG). Selective inhibitors of MAGL offer valuable probes to further understand the enzyme's function in biological systems and may lead to drugs for treating a variety of diseases, including psychiatric disorders, neuroinflammation, and pain. N-Hydroxysuccinimidyl (NHS) carbamates have recently been identified as a promising class of serine hydrolase inhibitors that shows minimal cross-reactivity with other proteins in the proteome. Here, we explore NHS carbamates more broadly and demonstrate their potential as inhibitors of endocannabinoid hydrolases and additional enzymes from the serine hydrolase class. We extensively characterize an NHS carbamate 1a (MJN110) as a potent, selective, and in-vivo-active MAGL inhibitor. Finally, we demonstrate that MJN110 alleviates mechanical allodynia in a rat model of diabetic neuropathy, marking NHS carbamates as a promising class of MAGL inhibitors.