Immunocytochemistry-Based Detection of FOXO Isoforms in Human Cancer and Fibroblasts.

In mammals, the FOXO protein family consists of four distinct isoforms: FOXO1, FOXO3, FOXO4, and FOXO6. These isoforms are key players in a wide spectrum of physiological and pathological processes, including context-specific tumor suppression. FOXO3, in particular, has emerged as a gene associated with extraordinary human longevity.

Multiplexed Dual-Color Fluorescence-Based Distinction Between Nuclear Trapping and Translocation of FOXO3.

FOXO3 is a transcription factor that mainly exerts its functions in the cell nucleus. The amino acid sequence of FOXO3 contains a nuclear localization sequence (NLS) and a nuclear export sequence (NES) allowing for nuclear/cytoplasmic shuttling that plays an important role in regulating FOXO3 activity. Nuclear accumulation of FOXO3 proteins can be the result of translocation to the nucleus triggered by upstream regulatory input or trapping of FOXO3 within the nucleus through the inhibition of its nuclear export via the receptor CRM1.

Multiplexed cellular profiling identifies an organoselenium compound as an inhibitor of CRM1-mediated nuclear export.

Chromosomal region maintenance 1 (CRM1 also known as Xpo1 and exportin-1) is the receptor for the nuclear export controlling the intracellular localization and function of many cellular and viral proteins that play a crucial role in viral infections and cancer. The inhibition of CRM1 has emerged as a promising therapeutic approach to interfere with the lifecycle of many viruses, for the treatment of cancer, and to overcome therapy resistance. Recently, selinexor has been approved as the first CRM1 inhibitor for the treatment of multiple myeloma, providing proof of concept for this therapeutic option with a new mode of action.

mTORC2 Is the Major Second Layer Kinase Negatively Regulating FOXO3 Activity.

Forkhead box O (FOXO) proteins are transcription factors involved in cancer and aging and their pharmacological manipulation could be beneficial for the treatment of cancer and healthy aging. FOXO proteins are mainly regulated by post-translational modifications including phosphorylation, acetylation and ubiquitination. As these modifications are reversible, activation and inactivation of FOXO factors is attainable through pharmacological treatment.

P063 Prevalence in the Use of Complementary/Alternative Medicine in Patients With Inflammatory Bowel Disease from Centro Médico Nacional 20 de Noviembre.

Background: Frequently, existing therapies for inflammatory bowel disease (IBD) do not achieve complete remission of the disease and are commonly associated with adverse effects. Therefore, patients regularly turn to complementary or alternative medicine (CAM). International CAM use in IBD patients ranges from 21% to 60%.

[Iatrogenic ureteral injury].

Objectives: To determine the most frequent causes of ureteral injury, and the way to correct severe damage of the ureter.

Methods: We reviewed the medical records of 25 patients who suffered ureteral injuries during abdominal or pelvic surgery in a five-year period; endoscopic injuries were excluded.

Results: The most common presentation included pain, urinary incontinence and fever.