Ezzat, Shereen

Abstract Adrenal infections are considered clinically important but often go unrecognized, with a significant number of cases only diagnosed post-mortem. The limited evidence regarding imaging findings in the literature emphasizes the need to detect and diagnose these infections early in disease course to improve patient outcomes. A range of microorganisms, including fungi, viruses, parasites, and bacteria, can directly or indirectly affect the morphology and function of the adrenal glands. When evaluating a patient with adrenal infection, several immunological and hormonal factors should be considered, such as the status of the hypothalamic-pituitary-adreno cortical axis and the serum cortisol level. Moreover, certain microorganisms specifically target one of the zones of the adrenal glands or vascular supply, resulting in distinct imaging manifestations. The purpose of this article is to describe the fundamental clinical features and imaging manifestations associated with adrenal infections, enabling radiologists to make informed interpretations and contribute to accurate diagnostic assessments.

AbstractThe oncogene c-maf is frequently overexpressed in multiple myeloma cell lines and patient samples and contributes to increased cellular proliferation in part by inducing cyclin D2 expression. To identify regulators of c-maf, we developed a chemical screen in NIH3T3 cells stably overexpressing c-maf and the cyclin D2 promoter driving luciferase. From a screen of 2400 off-patent drugs and chemicals, we identified glucocorticoids as c-maf–dependent inhibitors of cyclin D2 transactivation. In multiple myeloma cell lines, glucocorticoids reduced levels of c-maf protein without influencing corresponding mRNA levels. Subsequent studies demonstrated that glucocorticoids increased ubiquitination-dependent degradation of c-maf and up-regulated ubiquitin C mRNA. Moreover, ectopic expression of ubiquitin C recapitulated the effects of glucocorticoids, demonstrating regulation of c-maf protein through the abundance of the ubiquitin substrate. Thus, using a chemical biology approach, we identified a novel mechanism of action of glucocorticoids and a novel mechanism by which levels of c-maf protein are regulated by the abundance of the ubiquitin substrate.