CDK4/6 inhibition confers protection of normal gut epithelia against gemcitabine and the active metabolite of irinotecan.

Cancer chemotherapy relies on a high ratio of toxicity toward cancer cells vs. nonmalignant cells, making it desirable to protect normal cells. Among the nonmalignant cells, epithelia of the gut belong to the most vulnerable ones toward chemotherapeutics.

Preparation and Cultivation of Colonic and Small Intestinal Murine Organoids Including Analysis of Gene Expression and Organoid Viability.

Organoids are complex three-dimensional structures, which contain different cell types and help to overcome many limitations of conventional 2D cell culture techniques. Here, we present a protocol for the cultivation of murine matched-pairs of small intestinal and colonic epithelial organoids, and colonic tumor organoids derived from the chemical colorectal cancer (CRC) AOM/DSS mouse model. Therefore, intestinal crypts or tumor tissue containing stem cells are isolated from the same donor mouse and cultivated in Matrigel.

The glucocorticoid antagonist RU-486 suppresses HIV infectivity and replication.

The effects of RU-486, a glucocorticoid antagonist, on HIV infection and replication in depressed and nondepressed women were studied using ex vivo models of HIV infection. RU-486 treatment of cells decreased HIV reverse transcriptase activity of monocyte-derived macrophages in a model of acute infectivity. RU-486 also decreased HIV viral replication in the chronically-infected T-cell line ACH-2, but not in the promonocyte cell line U1.

Immune suppression and immune activation in depression.

Depression has been characterized as a disorder of both immune suppression and immune activation. Markers of impaired cellular immunity (decreased natural killer cell cytotoxicity) and inflammation (elevated IL-6, TNFα, and CRP) have been associated with depression. These immunological markers have been associated with other medical illnesses, suggesting that immune dysregulation may be a central feature common to both depression and to its frequent medical comorbidities.

Selective serotonin reuptake inhibitor suppression of HIV infectivity and replication.

Objective: To test the hypothesis that the selective serotonin reuptake inhibitor (SSRI) citalopram would down-regulate human immunodeficiency virus (HIV) infectivity and that the greatest effects would be seen in people with depression. Depression is a risk factor for morbidity and mortality in HIV/acquired immune deficiency syndrome. Serotonin (5-HT) neurotransmission has been implicated in the pathobiology of depression, and pharmacologic therapies for depression target this system.