• IMMUNE NETWORK
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• v.13 no.6
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• pp.289-294
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• 2013

Lipocalin-2 (LCN2) is an acute-phase protein induced by injury, infection, or other inflammatory stimuli. LCN2 binds small hydrophobic ligands and interacts with cell surface receptor to regulate diverse cellular processes. The role of LCN2 as a chemokine inducer in the central nervous system (CNS) has been previously reported. Based on the previous participation of LCN2 in neuroinflammation, we investigated the role of LCN2 in formalin-induced nociception and pathological pain. Formalin-induced nociceptive behaviors (licking/biting) and spinal microglial activation were significantly reduced in the second or late phase of the formalin test in Lcn2 knockout mice. Likewise, antibody-mediated neutralization of spinal LCN2 attenuated the mechanical hypersensitivity induced by peripheral nerve injury in mice. Taken together, our results suggest that LCN2 can be therapeutically targeted, presumably for both prevention and reversal of acute inflammatory pain as well as pathological pain.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.6
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• pp.415-425
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• 2022

Memory formation in the hippocampus is formed and maintained by circadian clock genes during sleep. Sleep deprivation (SD) can lead to memory impairment and neuroinflammation, and there remains no effective pharmacological treatment for these effects. Myricetin (MYR) is a common natural flavonoid that has various pharmacological activities. In this study, we investigated the effects of MYR on memory impairment, neuroinflammation, and neurotrophic factors in sleep-deprived rats. We analyzed SD-induced cognitive and spatial memory, as well as pro-inflammatory cytokine levels during SD. SD model rats were intraperitoneally injected with 10 and 20 mg/kg/day MYR for 14 days. MYR administration significantly ameliorated SD-induced cognitive and spatial memory deficits; it also attenuated the SD-induced inflammatory response associated with nuclear factor kappa B activation in the hippocampus. In addition, MYR enhanced the mRNA expression of brain-derived neurotropic factor (BDNF) in the hippocampus. Our results showed that MYR improved memory impairment by means of anti-inflammatory activity and appropriate regulation of BDNF expression. Our findings suggest that MYR is a potential functional ingredient that protects cognitive function from SD.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4849-4852
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• 2015

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been investigated as an effective agent to treat various cancers. Cancer stem cells are resistant to TRAIL treatment, but the mechanism of TRAIL resistance remains unknown. In this study, brain cancer stem cells were isolated by CD133 magnetic sorting, and the number of CD133 positive cells detected by flow cytometry. The self-renewing capacity of brain cancer stem cells was examined by a neurosphere formation assay, and the percentage of cell death after TRAIL treatment was examined by an MTS assay. Expression of DR5, FADD, caspase 8 and BCL2 proteins was detected by western blot. The amount of CD133 positive cells was enriched to 71% after CD133 magnetic sorting. Brain cancer stem cell neurosphere formation was significantly increased after TRAIL treatment. TRAIL treatment also reduced the amount of viable cells and this decrease was inhibited by a caspase 8 inhibitor or by the pan-caspase inhibitor z-VAD (P<0.05). Brain cancer stem cells expressed lower levels caspase 8 protein and higher levels of BCL2 protein when compared with CD133 negative cells (P<0.05). Our data suggest that TRAIL resistance is related to overexpression of BCL2 and low expression of caspase 8 which limit activation of caspase 8 in brain cancer stem cells.

• The Korea Journal of Herbology
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• v.30 no.1
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• pp.77-84
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• 2015

Objectives : Brain inflammation early activates the microglia and activated microglia secrete a variety of pro-inflammatory cytokines. Kaempferol, which is a flavonoid in Cuscutae Semen, shows a wide range of physiological activities, including neurons protection and anti-inflammatory actions through inhibition of pro-inflammatory mediators. The present study examined the modulatory effect of kaempferol on cytokines [tumor necrosis factor- alpha ($TNF-{\alpha}$), interleukin-1beta ($IL-1{\beta}$) and interleukin-6 (IL-6)] and cyclooxygenase-2 (COX-2) mRNA expression and microglia activation in the brain tissue of the mouse. Methods : Kaempferol was administered orally three doses of 10, 20 and 30 mg/kg respectively, once 1 hour before the lippolysaccharide(LPS) (3 mg/kg, i.p.) injection. Brain tissue was removed at 4 hours after LPS injection. Cytokines and COX-2 mRNA expression in the brain tissue was measured by the quantitative real-time polymerase chain reaction (PCR) method. Iba1 expression was calculated by western blotting method. Microglia was observed with immunohistochemistry. Immunohistochemistry stained microglia was analyzed by using ImageJ software. Results : Kaempferol 20 and 30 mg/kg was significantly attenuated the expression of $TNF-{\alpha}$, $IL-1{\beta}$ and IL-6 mRNA. Kaempfrol 10, 20 and 30 mg/kg significantly attenuated COX-2 mRNA expression in the brain tissue. Kaempferol 30 mg/kg significantly suppressed the increase of Iba1 protein expression by LPS. Kaempferol 30 mg/kg significantly decreased the number of microglia in the cerebral cortex and the number and cell size of microglia in the hypothalamic region and the area percentage of ionized calcium binding adaptor molecule 1(Iba1)-expressed microglia in the hippocampus. Conclusions : This results indicate that kaempferol plays an anti-inflammatory role in the brain.

• Development and Reproduction
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• v.13 no.3
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• pp.199-205
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• 2009

HSP70 has widely been induced in in vivo hyperthermia conditions in various organisms to study gene regulation and recently neuroprotectve roles of the induced gene expression under varying conditions. We investigated different responses among various tissues in zebrafish under heat shock to evaluate whether spatial and temporal expression pattern of zebrafish (z) hsp70 in transcriptional and translational level under heat shock stress in different brain regions. Heat shock groups were given for 1 h at $37^{\circ}C$ after recovery by transferring the treated animals back to $28^{\circ}C$ for 1, 2 and 24 h for recovery, respectively. Control (CTRL) group was kept at $28^{\circ}C$. At the end of treatments, five animals were collected and used for isolation of total RNAs and peptides from the corresponding tissues. Expression of zhsp70 mRNA showed different patterns in recovery periods in the tissues including the brain, eye, intestines, muscles, heart and testis by RT-PCR. Unlike the RT-PCR analysis, Northern blot analysis demonstrated nearly 30-fold increase in zhsp70 at 1 h heat shock, suggesting that RT-PCR may not be appropriate in unmasking regulation of the time-dependent zhsp70 expression. In the experiment involving different brain regions, the cerebellum showed gradual activation at 1 h to R1h and decreases in R2h and R24h, while the medulla oblongata and optic tectum showed gradual increase at R1h and decrease at R24h, indicating that different brain tissues respond specifically to heat shock in inducing zhsp70 and recovering from the heat shock status. Western blot analysis also demonstrated that the intracellular levels of zHSP70 in three different brain regions including the cerebellum, medulla oblongata and optic tectum are differently induced and recovered to normal state. These results clearly demonstrate that different regions of the body and the brain tissues are responding differently to heat shock in the aspects of its level of expression and speed of recovery.

• Journal of Ginseng Research
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• v.46 no.1
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• pp.79-90
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• 2022

Background: Herbal medicines are popular approaches to capably prevent and treat obesity and its related diseases. Excessive exposure to dietary lipids causes oxidative stress and inflammation, which possibly induces cellular senescence and contribute the damaging effects in brain. The potential roles of selective enhanced ginsenoside in regulating high fat diet (HFD)-induced brain damage remain unknown. Methods: The protection function of Ginsenoside F1-enhanced mixture (SGB121) was evaluated by in vivo and in vitro experiments. Human primary astrocytes and SH-SY5Y cells were treated with palmitic acid conjugated Bovine Serum Albumin, and the effects of SGB121 were determined by MTT and lipid uptake assays. For in vivo tests, C57BL/6J mice were fed with high fat diet for 3 months with or without SGB121 administration. Thereafter, immunohistochemistry, western blot, PCR and ELISA assays were conducted with brain tissues. Results and conclusion: SGB121 selectively suppressed HFD-induced oxidative stress and cellular senescence in brain, and reduced subsequent inflammation responses manifested by abrogated secretion of IL-6, IL-1β and TNFα via NF-κB signaling pathway. Interestingly, SGB121 protects against HFD-induced damage by improving mitophagy and endoplasmic reticulum-stress associated autophagy flux and inhibiting apoptosis. In addition, SGB121 regulates lipid uptake and accumulation by FATP4 and PPARα. SGB121 significantly abates excessively phosphorylated tau protein in the cortex and GFAP activation in corpus callosum. Together, our results suggest that SGB121 is able to favor the resistance of brain to HFD-induced damage, therefore provide explicit evidence of the potential to be a functional food.

• Korean Journal of Cognitive Science
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• v.18 no.2
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• pp.139-157
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• 2007

We compared brain activation areas during participants drawn from contrasting two college majors performed intentionality detection (known as the basic mechanism of theory of mind) task using fMRI. The main purpose of this study was to identify whether individual differences are present in intentionality detection or not. In psychology major, the left inferior frontal gyrus, the fusiform gyrus, the superior temporal gyrus and the right fusiform gyrus, the supramarginal gyrus were activated. In engineering major, the inferior parietal lobule and the superior parietal lobule were found. This result suggests that according to participants' major, different brain areas were activated. The relations between performance of the intentionality detection task and the individual variants of participants were discussed.

• Journal of The Korean Association For Science Education
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• v.32 no.3
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• pp.524-531
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• 2012

Categorization is an important human function used to process different stimuli. It is also one of the most important factors affecting measurement of a person's classification ability. Explicit categorization, the representative system by which categorization ability is measured, can verbally describe the categorization rule. The purpose of this study was to develop a prediction model for categorization ability as it relates to the classification process of living organisms using fMRI. Fifty-five participants were divided into two groups: a model generation group, comprised of twenty-seven subjects, and a model verification group, made up of twenty-eight subjects. During prediction model generation, functional connectivity was used to analyze temporal correlations between brain activation regions. A classification ability quotient (CQ) was calculated to identify the verbal categorization ability distribution of each subject. Additionally, the connectivity coefficient (CC) was calculated to quantify the functional connectivity for each subject. Hence, it was possible to generate a prediction model through regression analysis based on participants' CQ and CC values. The resultant categorization ability regression model predictor was statistically significant; however, researchers proceeded to verify its predictive ability power. In order to verify the predictive power of the developed regression model, researchers used the regression model and subjects' CC values to predict CQ values for twenty-eight subjects. Correlation between the predicted CQ values and the observed CQ values was confirmed. Results of this study suggested that explicit categorization ability differs at the brain network level of individuals. Also, the finding suggested that differences in functional connectivity between individuals reflect differences in categorization ability. Last, researchers have provided a new method for predicting an individual's categorization ability by measuring brain activation.

• The Journal of Internal Korean Medicine
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• v.21 no.4
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• pp.535-542
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• 2000

The water extracts of Samul-tang(SMT) has been used for treatment of ischemic brain damage in Oriental traditional medicine. However, little is known about the mechanism by which the water extracts of SMT rescues brain cells from ischemic damages. To elucidate the protective mechanism on ischemic induced cytotoxicity, I investigate the regulation of LPS and PMA induced iNOS expression in C6 glial cells. LPS and PMA treatment for 72 h in C6 glial cells markedly induce nitric oxide(NO), but treatment of the cells with the water extracts of SMT decrease. dose dependently nitrite formation. In addition, LPS and PMA treatment for 72 h induce severe cell death and LDH release in C6 glial cells. However treatment of the cells with the water extracts of SMT dose not induce significant changes compare to control cells. Furthermore, the protective effects of the water extracts of SMT is mimicked by treatment of $N^{G}MMA$, a specific inhibitor of NOS. LPS and PMA induced iNOS activation in C6 glial cells cause chromosomal condensation and fragmentation of nuclei by caspase activation. The treatment of the cells with the water extracts of SMT may suppress apoptosis via caspase inhibition by regulation of iNOS expression. Taken together, I suggest that the protective effects of the water extracts of SMT against ischemic brain damages may be mediated by regulation of iNOS during ischemic condition.

• Korean Journal of Cognitive Science
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• v.19 no.4
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• pp.397-417
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• 2008

We applied fMRI to examine brain activation during false-belief task in Korean healthy adults. In the first experiment, brain areas including bilateral precuneus, temoporo-parietal junction, left inferior parietal lobule, posterior cingulate, middle frontal gyrus were found during first -order false-belief task. In the second experiment, the left middle frontal gyrus, medial frontal gyrus and right precuneus, middle frontal gyrus, temoporo-parietal junction were activated during second-order false-belief task. These results are compatible with the suggestions that the ways in which adults understand theory of mind stories are universal.