Chronic Hormonal Imbalance and Adipose Redistribution Is Associated with Hypothalamic Neuropathology following Blast Exposure.

Endocrine disorders have been shown to be a consequence of blast traumatic brain injury in soldiers returning from military conflicts. Hormone deficiency and adrenocorticotropic hormone (ACTH) dysfunction can lead to symptoms such as fatigue, anxiety, irritability, insomnia, sexual dysfunction, and decreased quality of life. Given these changes following blast exposure, the current study focused on investigating chronic pathology within the hypothalamus following blast, in addition to systemic effects.

Adamantyl Retinoid-Related Molecules Induce Apoptosis in Pancreatic Cancer Cells by Inhibiting IGF-1R and Wnt/β-Catenin Pathways.

Pancreatic carcinoma has a dismal prognosis as it often presents as locally advanced or metastatic. We have found that exposure to adamantyl-substituted retinoid-related (ARR) compounds 3-Cl-AHPC and AHP3 resulted in growth inhibition and apoptosis induction in PANC-1, Capan-2, and MiaPaCa-2 pancreatic cancer cell lines. In addition, AHP3 and 3-Cl-AHPC inhibited growth and induced apoptosis in spheres derived from the CD44(+)/CD24(+) (CD133(+)/EpCAM(+)) stem-like cell population isolated from the pancreatic cancer cell lines.

Akt, FoxO and regulation of apoptosis.

Forkhead box O (FoxO) transcription factors are downstream targets of the serine/threonine protein kinase B (PKB)/Akt. The Akt kinase regulates processes of cellular proliferation and survival. Phosphorylation of FoxOs by Akt inhibits transcriptional functions of FoxOs and contributes to cell survival, growth and proliferation.

CAAT/enhancer binding protein activates an enhancer in the glutamine synthetase distal 5'-flanking sequence.

The glutamine synthetase (GS) gene is expressed at high levels in several cell types, including astrocytes, pericentral hepatocytes, and adipocytes. During hormone-mediated adipocyte differentiation of 3T3-L1 cells, GS gene expression increases several hundred fold. We previously reported that elements in the distal 5'-flanking sequence and intron-1 participate in establishing the temporal pattern of GS transcription during adipocyte differentiation.