• Journal of Yeungnam Medical Science
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• v.30 no.1
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• pp.4-9
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• 2013

Leptin, a 16-kDa cytokine, is secreted by adipose tissue in response to the surplus of fat store. Thereby, the brain is informed about the body's energy status. In the hypothalamus, leptin triggers specific neuronal subpopulations (e.g., POMC and NPY neurons) and activates several intracellular signaling events, including the JAK/STAT, MAPK, PI3K, and mTOR pathway, which eventually translates into decreased food intake and increased energy expenditure. Leptin signal is inhibited by a feedback inhibitory pathway mediated by SOCS3. PTP1B involves another inhibitory pathway of leptin. Leptin potently promotes fat mass loss and body weight reduction in lean subjects. However, it is not widely used in the clinical field because of leptin resistance, which is a common feature of obesity characterized by hyperleptinemia and the failure of exogenous leptin administration to provide therapeutic benefit in rodents and humans. The potential mechanisms of leptin resistance include the following: 1) increases in circulating leptin-binding proteins, 2) reduced transport of leptin across the blood-brain barrier, 3) decreased leptin receptor-B (LRB), and/or 4) the provocation of processes that diminish cellular leptin signaling (inflammation, endoplasmic reticulum stress, feedback inhibition, etc.). Thus, interference of the cellular mechanisms that attenuate leptin signaling improves leptin action in cells and animal models, suggesting the potential utility of these processes as points of therapeutic intervention. Various experimental trials and compounds that improve leptin resistance are introduced in this paper.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3359-3362
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• 2014

Increasing attention is being devoted to the mechanisms by which cells receive signals and then translate these into decisions for growth, death, or migration. Recent findings have presented significant breakthroughs in developing a deeper understanding of the activation or repression of target genes and proteins in response to various stimuli and of how they are assembled during signal transduction in cancer cells. Detailed mechanistic insights have unveiled new maps of linear and integrated signal transduction cascades, but the multifaceted nature of the pathways remains unclear. Although new layers of information are being added regarding mechanisms underlying ovarian cancer and how polymorphisms in VDR gene influence its development, the findings of this research must be sequentially collected and re-interpreted. We divide this multi-component review into different segments: how vitamin D modulates molecular network in ovarian cancer cells, how ovarian cancer is controlled by tumor suppressors and oncogenic miRNAs and finally how vitamin D signaling regulates miRNA expression. Intra/inter-population variability is insufficiently studied and a better understanding of genetics of population will be helpful in getting a step closer to personalized medicine.

• PNF and Movement
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• v.6 no.2
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• pp.51-57
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• 2008

Purpose : Mechanical stress activates signaling cascades and leading to a specific response of a network of signaling pathways. The purpose of this study is to review the effect of mechanical stress-induced adaptation in skeletal muscle involves a biological mechanisms. Methods : This is literature study with Pubmed, Medline and books. Results : Skeletal muscle tissue demonstrates a malleability and may adjust its metabilic response, vascularization and neuromuscular characteristic makeup in response to alteration in functional demands. The adaptation in skeletal muscle involoves a multitude of signalling mechanisms related with insuline-like growth factor, vascular endothelial growth factor, neurotrophins. Conclusions : The identification of the basic relationships underlying the malleability of skeletal muscle tissue is likely to be of relevance for our understanding with PNF technique.

• Journal of Microbiology and Biotechnology
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• v.27 no.10
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• pp.1727-1735
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• 2017

Hepatitis E virus (HEV) infections cause epidemic or sporadic acute hepatitis, which are mostly self-limiting. However, viral infection in immunocompromised patients and pregnant women may result in serious consequences, such as chronic hepatitis and liver damage, mortality of the latter of which reaches up to 20-30%. Type I interferon (IFN)-induced antiviral immunity is known to be the first-line defense against virus infection. Upon HEV infection in the cell, the virus genome is recognized by pathogen recognition receptors, leading to rapid activation of intracellular signaling cascades. Expression of type I IFN triggers induction of a barrage of IFN-stimulated genes, helping the cells cope with viral infection. Interestingly, some of the HEV-encoded genes seem to be involved in disrupting signaling cascades for antiviral immune responses, and thus crippling cytokine/chemokine production. Antagonistic mechanisms of type I IFN responses by HEV have only recently begun to emerge, and in this review, we summarize known HEV evasion strategies and compare them with those of other hepatitis viruses.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.4
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• pp.645-653
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• 2003

Taste receptor cells respond to gustatory stimuli using a complex arrangement of receptor molecules, signaling cascades and ion channels. When stimulated, these cells produce action potentials that result in the release of neurotransmitter onto an afferent nerve fiber that in turn relays the identity and intensity of the gustatory stimuli to tie brain. A variety of mechanisms are used in transducing the four primary tastes. Direct interaction of the stimuli with ion channels appears to be of particular importance in transducing stimuli reported as salty or sour, whereas tile second messenger systems cyclic AMP and inositol trisphosphate are important in transducing bitter and sweet stimuli. In addition to the four basic tastes, specific mechanisms exist for the amino acid glutamate, which is sometimes termed the fifth primary taste. The emerging picture is that not only do individual taste qualities use more than one mechanism, but multiple pathways are available for individual tastants as well.

• BMB Reports
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• v.44 no.7
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• pp.423-434
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• 2011

A female hormone, estrogen, is linked to breast cancer incidence. Estrogens undergo phase I and II metabolism by which they are biotransformed into genotoxic catechol estrogen metabolites and conjugate metabolites are produced for excretion or accumulation. The molecular mechanisms underlying estrogen-mediated mammary carcinogenesis remain unclear. Cell proliferation through activation of estrogen receptor (ER) by its agonist ligands and is clearly considered as one of carcinogenic mechanisms. Recent studies have proposed that reactive oxygen species generated from estrogen or estrogen metabolites are attributed to genotoxic effects and signal transduction through influencing redox sensitive transcription factors resulting in cell transformation, cell cycle, migration, and invasion of the breast cancer. Conjuguation metabolic pathway is thought to protect cells from genotoxic and cytotoxic effects by catechol estrogen metabolites. However, methoxylated catechol estrogens have been shown to induce ER-mediated signaling pathways, implying that conjugation is not a simply detoxification pathway. Dual action of catechol estrogen metabolites in mammary carcinogenesis as the ER-signaling molecules and chemical carcinogen will be discussed in this review.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3119-3121
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• 2012

Non-small-cell lung cancer (NSCLC) is a leading cause of cancer deaths worldwide. Crizotinib has been approved by the U.S. Food and Drug Administration for the treatment of patients with advanced NSCLC. However, understanding of mechanisms of action is still limited. In our studies, we confirmed crizotinib-induced apoptosis in A549 lung cancer cells. In order to assess mechanisms, small molecular docking technology was used as a preliminary simulation of signaling pathways. Interesting, our results of experiments were consistent with the results of computer simulation. This indicates that small molecular docking technology should find wide use for its reliability and convenience.

• Molecules and Cells
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• v.25 no.3
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• pp.397-406
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• 2008

Computational modeling of signal transduction is currently attracting much attention as it can promote the understanding of complex signal transduction mechanisms. Although several mathematical models have been used to examine signaling pathways, little attention has been given to crosstalk mechanisms. In this study, an attempt was made to develop a computational model for the pathways involving growth-factor-mediated mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3'-kinase/protein kinase B (PI3K/Akt). In addition, the dynamics of the protein activities were analyzed based on a set of kinetic data. The simulation approach integrates the information on several levels and predicts systems behavior. The in-silico analysis conducted revealed that the Raf and Akt pathways act independently.

• The Plant Pathology Journal
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• v.26 no.2
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• pp.101-109
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• 2010

Protein phosphorylation is one of the major mechanisms for controlling many cellular processes in all living organisms. Mitogen-activated protein kinase (MAPK) cascades are known to transducer extracellular stimuli to several cellular processes, including cell division, differentiation as well as responses to various stresses. In plants, several studies have revealed that MAPK cascade pathways play an important role in responses against biotic and abiotic stresses, including wounding, pathogen infection, temperature, drought, salinity and plant hormones. It is also known that MAPK cascades-mediated signaling is an essential process in the resistance step to pathogens by regulating the activity of transcription factors. Here, the insights into the functions of MAPK cascade pathways in plant defense response signaling from Arabidopsis, tobacco and rice are described.

• Journal of Korean Neurosurgical Society
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• v.42 no.6
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• pp.470-474
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• 2007

Objective : The brain is dependent on glucose as an energy source. Intricate homeostatic mechanisms have been implicated in maintaining the blood glucose concentration in the brain. The aim of this study is to find the way to identify the metabolic proteins regulating the glucose in rat hypothalamus. Methods : In this study, we analysed the secretome from rat hypothalamus in vivo. We introduced 500 nM of insulin into the rat hypothalamus. The chromatographic patterns of the secretome were identified, after which Mass Spectrometry-Mass Spectrometry (MS-MS) analysis was performed. Results : In Liquid Chromatography-Mass Spectrometry (LC-MS) analysis, 60 proteins were identified in the secretome. Among them, 8 novel proteins were unveiled and were associated with the energy metabolism of insulin signaling in mitochondria of rat hypothalamic neuron. Nineteen other proteins have unknown functions. These ligands were confirmed to be secreting from the rat hypothalmus on insulin signaling by western blotting. Conclusion : The hypothalamus is the master endocrine gland responsible for the regulation of various physiological and metabolic processes. Proteomics using LC-MS analysis offer a efficient means for generating a comprehensive analysis of hypothalamic protein expression by insulin signaling.