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To characterize the changes in global gene expression in the livers of H1/siRNAinsulin-CMV/hIDE transgenic (Tg) mice in response to the reduced bioavailability of insulin, total RNA extracted from the livers of 20-week-old Tg and non-Tg mice was converted to cDNA, labeled with biotin and hybridized to oligonucleotide microarrays. The microarray results were confirmed by a real-time reverse transcription-polymerase chain reaction. Two hundred and fifty-one and 73 genes were up- and down-regulated, respectively by insulin in H1/siRNAinsulin-CMV/hIDE Tg mice compared to the controls. Genes encoding for physiological processes, extracellular defense response and response to biotic stimuli were significantly over-represented in the up-regulated group. Among the down-regulated transcripts, those encoding for extracellular matrix proteins were dramatically over-represented, followed by those related to monooxygenase and oxidoreductase activities. The major genes in the up-regulated categories included Egr1, Saa2, Atf3, DNAJB1 and cCL2, whereas those in the down-regulated categories were Cyp17a1, Adn, Gadd45g, Eno3 and Moxd1. These results indicate that the microarray analysis identifies several gene functional groups and individual genes that respond to a sustained reduction in the insulin levels in the livers of Tg mice. These results also suggest that microarray testing is a useful tool for the better understanding of insulin-regulated diabetes-related diseases.

To investigate whether selenium (Sel) treatment would impact on the onset of diabetes,we examined serum biochemical components including glucose and insulin,endoplasmic reticulum (ER) stress and insulin signalling proteins, hepatic C/EBP-homologous protein (CHOP) expression and DNA fragmentation in diabetic and non- diabetic conditions of non-obese diabetic (NOD) mice. We conclude that (i) Sel treatment induced insulin-like effects in lowering serum glucose level in Sel-treated NOD mice, (ii) Sel-treated mice had significantly decreased serum biochemical components associated with liver damage and lipid metabolism, (iii) Sel treatment led to the activation of the ER stress signal through the phosphorylation of JNK and eIF2 protein and insulin signal mechanisms through the phosphorylation of Akt and PI3 kinase, and (iv) Sel-treated mice were significantly relieved apoptosis of liver tissues indicated by DNA fragmentation assay in the diabetic NOD group. These results suggest that Sel compounds not only serve as insulin-like molecules for the downregulation of glucose level and the incidence of liver damage, but may also have the potential for the development of new drugs for the relief of diabetes by activating the ER stress and insulin signalling pathways.

Background: Gliotoxin, a fungal metabolite, has been known to show strong immunosuppressive properties, although its mechanisms are not completely understood. In this report, the authors investigated the mechanism whereby gliotoxin has anti-inflammatory properties in vitro and in trinitrobenzene sulfonic acid-induced colitis., Materials and Methods: Body weight, histological scores, and myeloperoxidase activity were evaluated in trinitrobenzene sulfonic acid colitis. Nuclear factor-kappaB (NF-kappaB) p65, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-12, and intercellular adhesion molecule-1 were detected by immunohistochemical staining. IL-8 secretion was measured by an enzyme-linked immunosorbent assay. Heme oxygenase-1 (HO-1) expression and I-kappaB degradation were analyzed by Western blot., Results: Pretreatment of human epithelial HT-29 cells with gliotoxin significantly blocked the I-kappaB degradation and NF-kappaB p65 nuclear translocation induced by tumor necrosis factor-alpha or IL-1beta; these were parallel with the inhibition of IL-8 secretion and intercellular adhesion molecule-1 expression in the same cells. Interestingly, gliotoxin induced HO-1 in HT-29 cells and, in turn, inhibition of HO-1 activity by a zinc protoporphyrin IX reversed the effects of gliotoxin in terms of I-kappaB degradation, intercellular adhesion molecule-1 expression, and IL-8 production. In trinitrobenzene sulfonic acid colitis, gliotoxin administration significantly improved the clinical and histopathological symptoms. Notably, gliotoxin also induced HO-1 in the colonic mucosa and zinc protoporphyrin IX reversed the protective effects of gliotoxin in trinitrobenzene sulfonic acid colitis., Conclusions: These results demonstrate for the first time that the anti-inflammatory actions mediated by gliotoxin include HO-1 induction and the subsequent blockade of NF-kappaB-dependent signaling pathways in vitro and in vivo. The current results also demonstrate that gliotoxin may be an effective agent for the treatment of diseases characterized by mucosal inflammation.

Background: The use of music as a method of relieving anxiety has been studied extensively by researchers from varying disciplines. The abundance of these reports focused on which genre of music best aided in the relief of stress. Little work has been performed in the area of auditory preference in an attempt to ascertain whether an individual's preferred music type aids in their anxiety reduction at levels greater than music that they have little or no propensity for., Material/methods: In the present report we seek to determine whether naive human subjects exposed to music of their preference show a decrease in anxiety, as measured by systolic and diastolic blood pressure values. We furthermore contrast these values to those obtained during non-preferred music listening., Results: We found statistically significant reduction of anxiety levels only when subjects were exposed to their preferred musical selections., Conclusions: Students participating in the study already had knowledge of what genre of music would best relax them. It is our belief, that within the general population, many people do not have this self understanding. We conclude that music therapy may provide a mechanism for this self-understanding and subsequently help alleviate anxiety and stress.

Capsaicin (8-methyl-n-vanillyl-6-nonenamide), a pungent component found in red pepper can induce body heat and possibly enhance blood flow as well as increase energy expenditure, and prevent oxidative stress. Male Wistar rats were divided into vehicle, 1 mg/kg body weight capsaicin and 3 mg/kg body weight capsaicin groups. Samples were taken from the animals on day 1 of i.p. treatment with capsaicin and on 3 consecutive days of i.p. treatment with capsaicin. Our investigation demonstrated that blood flow measurements in rats was negatively correlated with LDL after treatment with capsaicin. Although capsaicin did not show a noticeable effect on the serum total cholesterol level, LDL decreased while HDL and triglyceride increased in rats treated with 3 mg/kg capsaicin for 3 days. The antioxidant effect of capsaicin was not shown when the rats were treated with 1 mg/kg body weight capsaicin. However, rats treated with 3 mg/kg body weight capsaicin for 3 days showed a reduction of oxidative stress measured as malondialdehyde in the liver, lung, kidney and muscle. Liver glycogen was found to decrease after 3 days treatment with 3 mg/kg body weight capsaicin. From this study, it is hypothesized that capsaicin can be a potent antioxidant and aid in lowering LDL even when consumed for a short period., (Copyright 2003 John Wiley & Sons, Ltd.)

The use of music as a means of inducing positive emotions and subsequent relaxation has been studied extensively by researchers. A great deal of this research has centered on the use of music as a means of reducing feelings of anxiety and stress as well as aiding in the relief of numerous pathologies. The precise mechanism responsible for these mediated effects has never been truly determined. In the current report we propose that nitric oxide (NO) is the molecule chiefly responsible for these physiological and psychological relaxing effects. Furthermore this molecules importance extends beyond the mechanistic, and is required for the development of the very process that it mediates. Nitric oxide has been determined to aid in the development of the auditory system and participate in cochlear blood flow. We show that NO is additionally responsible for the induced exhibited physiological effects. We proceed to outline the precise neurochemical pathway leading to these effects. Furthermore we explore the interrelationship between the varying emotion centers within the central nervous system and explain how the introduction of music can mediate its effects via NO coupled to these complex pathways.

The development of the social self has been a topic of interest to developmental psychologists for some time. With the recent emphasis placed on the effect of the nuclear family and its increasing paucity, researchers have been even more pressed to develop alternate means to aid in the social effects of family and subsequently enhance a child's assertion of independence. In our paper we explore some of the possible ways by which developmental learning occurs, most notably by implicit or unconscious acquisition. We further provide some historical background explaining the emergence of this unconscious learning. Once we understand the process by which this learning occurs and the historical context in which it operates we can put forth our hypothesis. We suggest that an effective way of aiding or supplementing the role of the family is by providing a theoretical family unit. Specifically we propose that participation in musical or band related activities aids in the emergence of adolescence independence and a healthy self concept.