Aire drives steroid hormone biosynthesis by medullary thymic epithelial cells.

Thymic epithelial cells (TECs) produce glucocorticoids, which antagonize negative selection of autoreactive thymocytes and promote a competent T cell antigen-specific repertoire. To characterize their source, we generated a knock-in reporter mouse in which endogenous Cyp11b1, the final enzyme in de novo production of active glucocorticoids, was fluorescently tagged with mScarlet. Here, we find that Cyp11b1 is expressed in medullary TECs (mTECs) but not cortical TECs or other cells in the thymus.

Tumors produce glucocorticoids by metabolite recycling, not synthesis, and activate Tregs to promote growth.

Glucocorticoids are steroid hormones with potent immunosuppressive properties. Their primary source is the adrenals, where they are generated via de novo synthesis from cholesterol. In addition, many tissues have a recycling pathway in which glucocorticoids are regenerated from inactive metabolites by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1, encoded by Hsd11b1).

Visualization of thalamic calcium influx with quantitative susceptibility mapping as a potential imaging biomarker for repeated mild traumatic brain injury.

A key event in the pathophysiology of traumatic brain injury (TBI) is the influx of substantial amounts of Ca into neurons, particularly in the thalamus. Detection of this calcium influx in vivo would provide a window into the biochemical mechanisms of TBI with potentially significant clinical implications. In the present work, our central hypothesis was that the Ca influx could be imaged in vivo with the relatively recent MRI technique of quantitative susceptibility mapping (QSM).

Circulating microRNAs as biomarkers in traumatic brain injury.

Preclinical and clinical studies can be greatly improved through the inclusion of diagnostic, prognostic, predictive or pharmacodynamics biomarkers. Circulating microRNAs (miRNAs) represent highly stable targets that respond to physiological and pathological changes. MicroRNA biomarkers can be detected by highly sensitive and absolutely quantitative methods currently available in most clinical laboratories.

Thymosin beta 4 induces significant changes in the plasma miRNA profile following severe traumatic brain injury in the rat lateral fluid percussion injury model.

Objectives: Thymosin beta 4 (Tβ4) has demonstrated neuroprotective potential in models of neurlogical injury. The neuroprotective potential of Tβ4 has been associated with increased miR-200a and miR-200b within the brain following stroke. Here we tested the hypothesis that Tβ4 treatment could also alter miRNA profiles within the plasma following severe traumatic brain injury (TBI).