The relevance of K calculation for bi-substrate enzymes illustrated by kinetic evaluation of a novel lysine (K) acetyltransferase 8 inhibitor.

Histone acetyltransferases (HATs) are important mediators of epigenetic post-translational modifications of histones that play important roles in health and disease. A disturbance of these modifications can result in disease states, such as cancer or inflammatory diseases. Inhibitors of HATs (HATi) such as lysine (K) acetyltransferase 8 (KAT8), could be used to study the epigenetic processes in diseases related to these enzymes or to investigate HATs as therapeutic targets.

HDAC1-3 inhibitor MS-275 enhances IL10 expression in RAW264.7 macrophages and reduces cigarette smoke-induced airway inflammation in mice.

Chronic obstructive pulmonary disease (COPD) constitutes a major health burden. Studying underlying molecular mechanisms could lead to new therapeutic targets. Macrophages are orchestrators of COPD, by releasing pro-inflammatory cytokines.

A 6-alkylsalicylate histone acetyltransferase inhibitor inhibits histone acetylation and pro-inflammatory gene expression in murine precision-cut lung slices.

Lysine acetylations are post-translational modifications of cellular proteins, that are crucial in the regulation of many cellular processes. Lysine acetylations on histone proteins are part of the epigenetic code regulating gene expression and are installed by histone acetyltransferases. Observations that inflammatory lung diseases, such as asthma and chronic obstructive pulmonary disease, are characterized by increased histone acetyltransferase activity indicate that development of small molecule inhibitors for these enzymes might be a valuable approach towards new therapies for these diseases.

An evaluation of our experience in position verification of catheters used for interstitial high-dose-rate brachytherapy of solitary bladder tumors.

Purpose: The goal of this study was to verify the position of catheters used over 4 days for brachytherapy of solitary bladder tumors.

Methods And Materials: The study covered three phases. Shifting of catheters was studied using daily position verification CT scans of 20 patients.

Activity-Based Probes for 15-Lipoxygenase-1.

Human 15-lipoxygenase-1 (15-LOX-1) plays an important role in several inflammatory lung diseases, such as asthma, COPD, and chronic bronchitis, as well as various CNS diseases, such as Alzheimer's disease, Parkinson's disease, and stroke. Activity-based probes of 15-LOX-1 are required to explore the role of this enzyme further and to enable drug discovery. In this study, we developed a 15-LOX-1 activity-based probe for the efficient activity-based labeling of recombinant 15-LOX-1.