• Asian Pacific Journal of Cancer Prevention
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• v.17 no.11
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• pp.4907-4911
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• 2016

Glioblastoma multiforme (GBM) is the most aggressive of the gliomas, a collection of tumors arising from glia in the central nervous system. Possible associations between the human cytomegalovirus (HCMV) and the JC virus with GBM are now attracting interest. Our present aim was to investigate the prevalence of the two viruses in Iranian patients from Kerman's cities in the south of Iran. In addition, the expression rates of pp65, large T antigen and p53 proteins were assessed and their relation with GBM evaluated using reverse transcription real time PCR (rReal Time PCR). A total of 199 patients with GBM cancer were enrolled, with $mean{\pm}SD$ ages of $50.0{\pm}19.5$ and $50.7{\pm}19.6$ years for males and females, respectively. The P53 rate was dramatically low suggesting an aetiological role,. Large T antigen expression was found in JC positive samples, while the PP65 antigen was observed in patients positive for CMV and JC. HCMV products and JC virus with oncogenic potential may induce the development of various tumors including glioblastomas. The JC virus produces an early gene product, T-antigen, which has the ability to associate with and functionally inactivate well-studied tumor suppressor proteins including p53 and pRB.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.4
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• pp.187-194
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• 2004

Middle cerebral artery occlusion (MCAO) results in cell death by activation of complex signal pathways for cell death and survival. Hypothermia is a robust neuroprotectant, and its effect has often been attributed to various mechanisms, but it is not yet clear. Upstream from the cell death promoters and executioners are several enzymes that may activate several transcription factors involved in cell death and survival. In this study, we immunohistochemically examined the phosphorylation of mitogen-activated protein kinase, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 kinase during early period of the ischemic injury, following 2 hours (h) of transient MCAO. Increased phosphorylation of ERK and p38 was observed in the vessels at 3 h, neuron-like cells at 6 and 12 h and glia-like cells at 12 h. Activation of JNK was not remarkable, and a few cells showed active JNK following ischemia. Phosphorylation of Elk-1, a transcription factor, was reduced by ischemic insult. Hypothermia attenuated the activation of ERK, p38 and JNK, and inhibited reduction of Elk-1. These data suggest that signals via different MAPK family members converge on the cell damage process and hypothermia protects the brain by interfering with these pathways.

• Korean Journal of Microbiology
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• v.42 no.1
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• pp.73-76
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• 2006

Neuronal precursor cells may provide for cell replacement or gene delivery vehicles in neurodegenerative disease therapy. One impediment to treating neuronal diseases is finding ways to introduce genes into neurons effectively. It is shown here that fiber-modified adenovirus vector delivered gene to neuronal precursor as well as differentiated neuronal cells more efficiently than first-generation adenoviral vector. Moreover, fiber-modified adenoviral vector transduced precursor cells retained the potential for differentiation into neurons and glia in vitro. These results show the potential of modified adenoviral vector in the improved gene delivery to neurons in direct gene therapy protocols. In addition it holds promise for the use of genetically manipulated stem cells for the therapy of neuronal diseases.

• Molecules and Cells
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• v.21 no.3
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• pp.436-442
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• 2006

Different proliferation of neuroblast 6-4 (NB6-4) in the thorax and abdomen produces segmental specific expression pattern of several neuroblast marker genes. NB6-4 is divided to form four medialmost cell body glia (MM-CBG) per segment in thorax and two MM-CBG per segment in abdomen. As homeotic genes determine the identities of embryonic segments along the A/P axis, we investigated if temporal and specific expression of homeotic genes affects MM-CBG patterns in thorax and abdomen. A Ubx loss-of-function mutation was found to hardly affect MM-CBG formation, whereas abd-A and Abd-B caused the transformation of abdominal MM-CBG to their thoracic counterparts. On the other hand, gain-of-function mutants of Ubx, abd-A and Abd-B genes reduced the number of thoracic MM-CBG, indicating that thoracic MM-CBG resembled abdominal MM-CBG. However, mutations in Polycomb group (PcG) genes, which are negative transregulators of homeotic genes, did not cause the thoracic to abdominal MM-CBG pattern transformation although the number of MM-CBG in a few percent of embryos were partially reduced or abnormally patterned. Our results indicate that temporal and spatial expression of the homeotic genes is important to determine segmental-specificity of NB6-4 daughter cells along the anterior-posterior (A/P) axis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.4
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• pp.1073-1077
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• 2005

Oxidative stressand glia-associated chronic inflammation have been linked to the pathophysiology of Alzheimer's disease. Rhei rhizoma has been commonly used as a purgative and a haemostatic agent in traditional oriental medicine. Recently, the methanol extract from a dried root of Rheum undulatumhas been shown to have anti-allergic and anti-inflammatory effects. In this study, we tested the potential of the extract of Rheum undulatum for neuroprotective agent. The aqueous extract of Rheum undulatum reduced cell death and p53 phosphorylation in neuronal cells and attenuated levels of cyclooxygenase-2 and inducible nitric oxide synthase mRNAs in BV2 microglial cells treated with $amyloid-\beta$

• Molecules and Cells
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• v.37 no.3
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• pp.248-256
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• 2014

N-acetylglucosamine kinase (GlcNAc kinase or NAGK; EC 2.7.1.59) is a N-acetylhexosamine kinase that belong to the sugar kinase/heat shock protein 70/actin superfamily. In this study, we investigated both the expression and function of NAGK in neurons. Immunohistochemistry of rat brain sections showed that NAGK was expressed at high levels in neurons but at low levels in astrocytes. Immunocytochemistry of rat hippocampal dissociate cultures confirmed these findings and showed that NAGK was also expressed at low levels in oligodendrocytes. Furthermore, several NAGK clusters were observed in the nucleoplasm of both neuron and glia. The overexpression of EGFP- or RFP (DsRed2)-tagged NAGK in rat hippocampal neurons (DIV 5-9) increased the complexity of dendritic architecture by increasing the numbers of primary dendrites and dendritic branches. In contrast, knockdown of NAGK by shRNA resulted in dendrite degeneration, and this was prevented by the co-expression of RFP-tagged NAGK. These results suggest that the upregulation of dendritic complexity is a non-canonical function of NAGK.

• Preventive Nutrition and Food Science
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• v.4 no.3
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• pp.209-214
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• 1999

In this study, the effectof ethanol and acetaldehyde on DNA binding activities of NF-$textsc{k}$B and AP-1 were evaluated in C6 rat glial cells. Both NF-$textsc{k}$B and AP-1 are important transcription factors for the expression of various cytokines in glial cells. Our data showed that neither ethanol nor acetaldehyde induced conspicuous cell death of C6 cells at clinically realistic concentrations. When the DNA binding activities of nuclear NF-$textsc{k}$B and AP-1 were estimated using electrophoretic mobility shift assay (EMSA), ethanol(0.3%) or acetaldehyde(1mM) induced transient activation of these transcription factors, which attained peak levels at 4~8 hours and declined to basal levels at 12 hours after treatement . The supershift analysis showed that the increased activities of NF-$textsc{k}$B in ethanol/acetaldehyde-treated C6 cells were due to the preferential induction of p65/p50 heterodimer complex. The DNA binding activities of these transcriptional factors decreased below basal levels when cells were cultured with either ethanol or acetaldehyde for 24 hours, and showed the inhibitory effect of chronic ehtanol /acetaldehyde treatment on the activities of these transsriptional factors. Our data indicate that either ethanol or acetaldehyde can induce functional changes of glial cells throught bi-directional modulation of NF-$textsc{k}$B and AP-1 DNA binding activities.

• Molecules and Cells
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• v.26 no.2
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• pp.113-120
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• 2008

Laser light microscopy enables observation of various simultaneously occurring events in living cells. This capability is important for monitoring the spatiotemporal patterns of the molecular interactions underlying such events. Two-photon excited fluorescence microscopy (two-photon microscopy), a technology based on multiphoton excitation, is one of the most promising candidates for such imaging. The advantages of two-photon microscopy have spurred wider adoption of the method, especially in neurological studies. Multicolor excitation capability, one advantage of two-photon microscopy, has enabled the quantification of spatiotemporal patterns of $[Ca^{2+}]_i$ and single episodes of fusion pore openings during exocytosis. In pancreatic acinar cells, we have successfully demonstrated the existence of "sequential compound exocytosis" for the first time, a process which has subsequently been identified in a wide variety of secretory cells including exocrine, endocrine and blood cells. Our newly developed method, the two-photon extracellular polar-tracer imaging-based quantification (TEPIQ) method, can be used for determining fusion pores and the diameters of vesicles smaller than the diffraction-limited resolution. Furthermore, two-photon microscopy has the demonstrated capability of obtaining cross-sectional images from deep layers within nearly intact tissue samples over long observation times with excellent spatial resolution. Recently, we have successfully observed a neuron located deeper than 0.9 mm from the brain cortex surface in an anesthetized mouse. This microscopy also enables the monitoring of long-term changes in neural or glial cells in a living mouse. This minireview describes both the current and anticipated capabilities of two-photon microscopy, based on a discussion of previous publications and recently obtained data.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.5
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• pp.881-886
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• 2011

AMPA receptor (AMPAR)s are heterotetrameric structures made up from 4 units (GluR1-4) and are thought to underlie perception of persistent inflammatory pain. Complete Freund's adjuvant (CFA)-evoked inflammation induces synaptic GluR2 internalization, which is initiated by GluR2 phosphorylation, in dorsal horn neurons during the maintenance of CFA-induced hypersensitivity. The present study investigated whether electroacupuncture (EA) stimulation has any effect on GluR2 trafficking by using immunoblot and immunohistochemistry. We examined that CFA-induced dorsal horn GluR2 internalization was attenuated by EA treatment. EA treatment could also decrease the level of pGluR2 regardless of whether CFA injection was administrated or not. In addition, previous studies suggest that microglial cells are increased without morphological change in CFA injected animal. In our study, increases in microglial cells in CFA group were observed, whereas EA with or without CFA-injected group showed similar aspects with normal group. In conclusion, our results indicate that EA might blunt CFA-evoked inflammation by coordinating mechanisms at the upstream step of neuron activation and GluR2 phosphorylation.

• The Korea Journal of Herbology
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• v.25 no.4
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• pp.85-93
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• 2010

Objectives : This study aimed at evaluation of the effects of Gastrodiae Rhizoma on brain edema and aquaporin water channel expressions in the brain. Methods : Brain edema following intracerebral hemorrhage (ICH) was induced by the stereotaxic intrastriatal injection of bacterial collagenase type VII in Sprague-Dawley rats. Then ethanol extract of Gastrodiae rhizoma was treated once a day for 3 days. Brain edema % and water contents, and cell size of neurons in the cerebral cortex were examined. Immuno-histochemistry was processed for AQP4, AQP1, and AQP9 expressions in the brain sections and area % of immuno-labeling was analyzed with image analysis. Results : 1. Ethanol extract of Gastrodiae Rhizoma reduced brain edema of ICH induced rats significantly. 2. Ethanol extract of Gastrodiae Rhizoma reduced excessive brain tissue water contents of ICH induced rats significantly. 3. Ethanol extract of Gastrodiae Rhizoma reduced cellular edema of neurons in cerebral cortex of ICH induced rats significantly. 4. Ethanol extract of Gastrodiae Rhizoma reduced AQP4 immuno-positive area % in cerebral cortex and external capsule of ICH induced rat brain significantly. 5. Ethanol extract of Gastrodiae Rhizoma reduced AQP9 immuno-positive area % in glia limitans externa of ICH induced rat brain significantly. Conclusions : These results suggest that Gastrodiae Rhizoma reveals protective effects against brain edema and cytotoxic edema of neurons by means of down-regulation of AQP4 expression in the brain.