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Rockville, MD, United States

Li H.,Uniformed Services University of the Health Sciences | Li X.,Georgetown University | Smerin S.E.,Uniformed Services University of the Health Sciences | Zhang L.,Uniformed Services University of the Health Sciences | And 6 more authors.
Frontiers in Neurology | Year: 2014

The metabolic mechanisms underlying the development of exaggerated fear in posttraumatic stress disorder (PTSD) are not well defined. In the present study, alteration in the expression of genes associated with mitochondrial function in the amygdala of an animal model of PTSD was determined. Amygdala tissue samples were excised from 10 nonstressed control rats and10 stressed rats, 14 days post stress treatment.. Total RNA was isolated, cDNA was synthesized, and gene expression levels were determined using a cDNA microarray. During the development of the exaggerated fear associated with PTSD, 48 genes were found to be significantly upregulated and 37 were significantly downregulated in the amygdala complex based on stringent criteria (p<0.01). Ingenuity Pathway Analysis (IPA) revealed up or down regulation in the amygdala complex of four signaling networks - one associated with inflammatory and apoptotic pathways, one with immune mediators and metabolism, one with transcriptional factors, and one with chromatin remodeling. Thus, informatics of a neuronal gene array allowed us to determine the expression profile of mitochondrial genes in the amygdala complex of an animal model of PTSD. The result is a further understanding of the metabolic and neuronal signaling mechanisms associated with delayed and exaggerated fear. © 2014 Li, Li, Smerin, Zhang, Jia, Xing, Su, Wen, Benedek and Ursano.

Hsiao Y.-H.,Chung Shan Medical University | Hsiao Y.-H.,Changhua Christian Hospital | Su Y.A.,GenProMarkers, Inc. | Tsai H.-D.,Changhua Christian Hospital | And 3 more authors.
International Journal of Biological Sciences | Year: 2010

Our previous studies revealed that pregnancy associated breast cancer (PABC) had significantly reduced nuclear p63 expression in myoepithelia, while intense cytoplasmic p63 expression in associated epithelia. Our current study assessed these epithelia using immunohistochemistry with a panel of aggressiveness and invasiveness related markers and comparative genomic hybridization (array-CGH) with over 30,000 DNA probes. These epithelia showed several unique alterations, including (1) immunohistochemical and morphological resemblance to invasive cancer, (2) significant gain in copy numbers of DNA coding genes for morphogenesis, angiogenesis, and metastasis, and (3) significant loss in copy numbers of DNA coding genes for tumor suppressors, cell adhesion, and macromolecular complex assembly or intra-cellular trafficking. Detected array-CGH alterations correlated well with in vivo expression of a number of corresponding proteins tested. These findings suggest that aberrant sub-cellular localization of p63 expression in normal or hyperplastic appearing epithelial cells may significant contribute to increased invasiveness and aggressiveness of these cells. © Ivyspring International Publisher. All rights reserved.

China M.,Forestry and Fisheries Promotion Center | Nakamura H.,Okinawa Prefectural Sea Farming Center | Hamakawa K.,Okinawa Prefectural Fisheries Research and Extension Center | Tamaki E.,Okinawa Prefectural Sea Farming Center | And 4 more authors.
Fish Pathology | Year: 2013

In 2008, the myxosporean emaciation disease was found in cultured Malabar grouper Epinephelus malabaricus in a fish farm in Okinawa Prefecture, Japan. The disease occurred in winter when water temperature ranged from 21 to 26°C, and the cumulative mortality reached 20-50% among culture tanks. In affected fish, cranial bones were externally apparent due to severe emaciation. The intestinal wall was very thin and the liver exhibited conspicuous green color. Morphological and molecular analyses demonstrated that the causative myxosporean was Enteromyxum leei. Histopathological examinations revealed that the epithelia of the intestine and bile duct of diseased fish were heavily infected with E. leei. The common bile duct was often obstructed by severe inflammation with degenerated tissues and bacteria, suggesting that the abnormal color of the liver was caused by cholestasis. Some diseased fish recovered in a laboratory when water temperature increased naturally to 27-30°C in summer months, and the parasite was not detected in those fish. Experimental transmission of E. leei to naive Malabar grouper was successfully achieved by cohabitation with infected grouper or by feeding with the feces of infected fish. This is a new host and locality record for E. leei.

Hu T.,Kunming Medical University | Zhang C.,Kunming Medical University | Tang Q.,Kunming Medical University | Su Y.,GenProMarkers, Inc. | And 5 more authors.
BMC Cancer | Year: 2013

Background: Glucose-6-phosphate dehydrogenase (G6PD), elevated in tumor cells, catalyzes the first reaction in the pentose-phosphate pathway. The regulation mechanism of G6PD and pathological change in human melanoma growth remains unknown.Methods: HEM (human epidermal melanocyte) cells and human melanoma cells with the wild-type G6PD gene (A375-WT), G6PD deficiency (A375-G6PD{increment}), G6PD cDNA overexpression (A375-G6PD{increment}-G6PD-WT), and mutant G6PD cDNA (A375-G6PD{increment}-G6PD-G487A) were subcutaneously injected into 5 groups of nude mice. Expressions of G6PD, STAT3, STAT5, cell cycle-related proteins, and apoptotic proteins as well as mechanistic exploration of STAT3/STAT5 were determined by quantitative real-time PCR (qRT-PCR), immunohistochemistry and western blot.Results: Delayed formation and slowed growth were apparent in A375-G6PD{increment} cells, compared to A375-WT cells. Significantly decreased G6PD expression and activity were observed in tumor tissues induced by A375-G6PD{increment}, along with down-regulated cell cycle proteins cyclin D1, cyclin E, p53, and S100A4. Apoptosis-inhibited factors Bcl-2 and Bcl-xl were up-regulated; however, apoptosis factor Fas was down-regulated, compared to A375-WT cells. Moderate protein expressions were observed in A375-G6PD{increment}-G6PD-WT and A375-G6PD{increment}-G6PD-G487A cells.Conclusions: G6PD may regulate apoptosis and expression of cell cycle-related proteins through phosphorylation of transcription factors STAT3 and STAT5, thus mediating formation and growth of human melanoma cells. Further study will, however, be required to determine potential clinical applications. © 2013 Hu et al.; licensee BioMed Central Ltd.

Agency: Department of Defense | Branch: Army | Program: SBIR | Phase: Phase I | Award Amount: 100.00K | Year: 2012

Our pilot study demonstrates that a novel proprietary biological dry powder/pellet (BDP) is useful for long-term preservation of nucleic acids in blood and bone marrow at room temperature (15"22 degree C). The concept of the BDP approach includes to dissolve the interested biological samples into nucleic acid protecting reagents and then to lyophilize mixture into BDP for preservation of nucleic acids at room temperature or 4 degree C for many years. To make BDP useful, we have also developed specific methods for efficient purification of high quality and quantity of RNA from BDP derived from small amount samples, for example, as low as 500 microliters of peripheral blood or 200 microliters of bone marrow. To our knowledge, BDP represents a paradigm shift in archiving biological samples for preservation of RNA and DNA at room temperature for years potentially as long as a human life span. We now apply for the DoD SBIR Phase I support to optimize the BDP methods, specifically, i) to determine preferable tissue for nucleic acid archiving, ii) to investigate sample collection protocol, processing, of the selected tissue, and iii) to initially define key potential aspects of storage conditions for preservation of nucleic acids.

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