• Journal of Nutrition and Health
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• v.50 no.1
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• pp.25-31
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• 2017

Purpose: Neuroinflammation is mediated by activation of microglia implicated in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Inhibition of neuroinflammation may be an effective solution to treat these brain disorders. Petalonia binghamiae is known as a traditional food, based on multiple biological activities such as anti-oxidant and anti-obesity. In present study, the anti-neuroinflammatory potential of Petalonia binghamiae was investigated in LPS-stimulated BV2 microglial cells. Methods: Cell viability was measured by MTT assay. Production of nitric oxide (NO) was examined using Griess reagent. Expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) was detected by Western blot analysis. Activation of nuclear factor ${\kappa}B$ ($NF-{\kappa}B$) signaling was examined by nuclear translocation of $NF-{\kappa}B$ p65 subunit and phosphorylation of $I{\kappa}B$. Results: Extract of Petalonia binghamiae significantly inhibited LPS-stimulated NO production and iNOS/COX-2 protein expression in a dose-dependent manner without cytotoxicity. Pretreatment with Petalonia binghamiae suppressed LPS-induced $NF-{\kappa}B$ p65 nuclear translocation and phosphorylation of $I{\kappa}B$. Co-treatment with Petalonia binghamiae and pyrrolidine duthiocarbamate (PDTC), an $NF-{\kappa}B$ inhibitor, reduced LPS-stimulated NO release compared to that in PB-treated or PDTC-treated cells. Conclusion: The present results indicate that extract of Petalonia binghamiae exerts anti-neuroinflammation activities, partly through inhibition of $NF-{\kappa}B$ signaling. These findings suggest that Petalonia binghamiae might have therapeutic potential in relation to neuroinflammation and neurodegenerative diseases.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.4
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• pp.1082-1091
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• 2003

To elucidate the neuroprotective effect of Kamijihwang-hwan(KSH) on nerve cells damaged by hypoxia, the cytotoxic effects of exposure to hypoxia were determined by XTT, NR, MTT and SRB asssay. The activity of catalase and SOD was measured by spectrophometry, and TNF-α and PKC activity was measured after exposure to hypoxia and treatment of Kamijihwang-hwan(KSH) water extract(KJHWE). Also the neuroprotective effect of KJHWE was researched for the elucidation of neuroprotective mechanism. The results were as follows ; Hypoxia decreased cell viability measured by XTT, NR assay when cultured cerebral neurons were exposed to 95% N2/5% CO₂ for 2～26 minutes in these cultures and KJHWE inhibited the decrease of cell viability. H₂O₂ treatment decreased cell viability measured by MTT, and SRB assay when cultured cerebral neurons were exposed to 1-80 uM for 6 hours, but KJHWE inhibited the decrease of cell viability. Hypoxia decreased catalase and SOD activity, and also TNF-α and PKC activity in these cultured cerebral neurons, but KJHWE inhibited the decrease of the catalase and SOD activity in these cultures. Hypoxia triggered the apoptosis via caspase activation and internucleosomal DNA fragmentation. Also hypoxia stimulate the release of cytochrome c form mitochondria. KJHWE inhibited the apoptosis via caspase activation induced by hypoxia. From these results, it can be suggested that brain ischemia model induced hypoxia showed neurotoxity on cultured mouse cerebral neurons, and the KJHWE has the neuroprotective effect in blocking the neurotoxity induced by hypoxia in cultured mouse cerebral neurons.

• BMB Reports
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• v.56 no.4
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• pp.234-239
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• 2023

Thioredoxin-like protein 1 (TXNL1), one of the thioredoxin superfamily known as redox-regulator, plays an essential in maintaining cell survival via various antioxidant and anti-apoptotic mechanisms. It is well known that relationship between ischemia and oxidative stress, however, the role of TXNL1 protein in ischemic damage has not been fully investigated. In the present study, we aimed to determine the protective role of TXNL1 against on ischemic injury in vitro and in vivo using cell permeable Tat-TXNL1 fusion protein. Transduced Tat-TXNL1 inhibited ROS production and cell death in H₂O₂-exposed hippocampal neuronal (HT-22) cells and modulated MAPKs and Akt activation, and pro-apoptotic protein expression levels in the cells. In an ischemia animal model, Tat-TXNL1 markedly decreased hippocampal neuronal cell death and the activation of astrocytes and microglia. These findings indicate that cell permeable Tat-TXNL1 protects against oxidative stress in vitro and in vivo ischemic animal model. Therefore, we suggest Tat-TXNL1 can be a potential therapeutic protein for ischemic injury.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.17 no.4
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• pp.351-360
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• 2016

The purpose of this study is to predict visual-spatial working memory performance through the characteristics of an electroencephalogram (EEG) in the resting state. The 31 study participants, middle school students with various to academic performance, were underwent visual-spatial working memory test in the Comprehensive Attention Test (CAT) on December in 2014. Each 7 and 6 participants were divided into an Excellent Working Memory (EWM) group and Poor Working Memory (PWM) group depending on the forward/backward working memory scores. The EEG measurements and analysis of the data from a Brain Function Tester were performed by the two groups. A Mann-Whitney Test was used to examine the statistical differences between them. The activation of high beta (${\beta}H$) at the Fp1 and Fp2 sites in the left and right hemisphere, and that of the low beta (${\beta}L$) in the right hemisphere in the EWM group was significantly higher than that in the PWM group. In conclusion, there is a correlation between the visual-spatial working memory performance and the activation of ${\beta}H$ and ${\beta}L$ in the resting state and a close correlation that of ${\beta}L$ in the right hemisphere in terms of mental activity and faculty. Therefore, the visual-spatial working memory performance can be predicted by the activation of ${\beta}H$ and ${\beta}L$ in the resting state. The activation of EEG can be applied as an assessment tool and provide basis data for visual-spatial working memory performance.

• Archives of Pharmacal Research
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• v.28 no.3
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• pp.249-268
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• 2005

Drug metabolizing enzymes (DMEs) play central roles in the metabolism, elimination and detoxification of xenobiotics and drugs introduced into the human body. Most of the tissues and organs in our body are well equipped with diverse and various DMEs including phase I, phase II metabolizing enzymes and phase III transporters, which are present in abundance either at the basal unstimulated level, and/or are inducible at elevated level after exposure to xenobiotics. Recently, many important advances have been made in the mechanisms that regulate the expression of these drug metabolism genes. Various nuclear receptors including the aryl hydrocarbon receptor (AhR), orphan nuclear receptors, and nuclear factor-erythoroid 2 p45-related factor 2 (Nrf2) have been shown to be the key mediators of drug-induced changes in phase I, phase II metabolizing enzymes as well as phase III transporters involved in efflux mechanisms. For instance, the expression of CYP1 genes can be induced by AhR, which dimerizes with the AhR nuclear translocator (Arnt) , in response to many polycyclic aromatic hydrocarbon (PAHs). Similarly, the steroid family of orphan nuclear receptors, the constitutive androstane receptor (CAR) and pregnane X receptor (PXR), both heterodimerize with the ret-inoid X receptor (RXR), are shown to transcriptionally activate the promoters of CYP2B and CYP3A gene expression by xenobiotics such as phenobarbital-like compounds (CAR) and dexamethasone and rifampin-type of agents (PXR). The peroxisome proliferator activated receptor (PPAR), which is one of the first characterized members of the nuclear hormone receptor, also dimerizes with RXR and has been shown to be activated by lipid lowering agent fib rate-type of compounds leading to transcriptional activation of the promoters on CYP4A gene. CYP7A was recognized as the first target gene of the liver X receptor (LXR), in which the elimination of cholesterol depends on CYP7A. Farnesoid X receptor (FXR) was identified as a bile acid receptor, and its activation results in the inhibition of hepatic acid biosynthesis and increased transport of bile acids from intestinal lumen to the liver, and CYP7A is one of its target genes. The transcriptional activation by these receptors upon binding to the promoters located at the 5-flanking region of these GYP genes generally leads to the induction of their mRNA gene expression. The physiological and the pharmacological implications of common partner of RXR for CAR, PXR, PPAR, LXR and FXR receptors largely remain unknown and are under intense investigations. For the phase II DMEs, phase II gene inducers such as the phenolic compounds butylated hydroxyanisol (BHA), tert-butylhydroquinone (tBHQ), green tea polyphenol (GTP), (-)-epigallocatechin-3-gallate (EGCG) and the isothiocyanates (PEITC, sul­foraphane) generally appear to be electrophiles. They generally possess electrophilic-medi­ated stress response, resulting in the activation of bZIP transcription factors Nrf2 which dimerizes with Mafs and binds to the antioxidant/electrophile response element (ARE/EpRE) promoter, which is located in many phase II DMEs as well as many cellular defensive enzymes such as heme oxygenase-1 (HO-1), with the subsequent induction of the expression of these genes. Phase III transporters, for example, P-glycoprotein (P-gp), multidrug resistance-associated proteins (MRPs), and organic anion transporting polypeptide 2 (OATP2) are expressed in many tissues such as the liver, intestine, kidney, and brain, and play crucial roles in drug absorption, distribution, and excretion. The orphan nuclear receptors PXR and GAR have been shown to be involved in the regulation of these transporters. Along with phase I and phase II enzyme induction, pretreatment with several kinds of inducers has been shown to alter the expression of phase III transporters, and alter the excretion of xenobiotics, which implies that phase III transporters may also be similarly regulated in a coordinated fashion, and provides an important mean to protect the body from xenobiotics insults. It appears that in general, exposure to phase I, phase II and phase III gene inducers may trigger cellular 'stress' response leading to the increase in their gene expression, which ultimately enhance the elimination and clearance of these xenobiotics and/or other 'cellular stresses' including harmful reactive intermediates such as reactive oxygen species (ROS), so that the body will remove the 'stress' expeditiously. Consequently, this homeostatic response of the body plays a central role in the protection of the body against 'environmental' insults such as those elicited by exposure to xenobiotics.

• Molecules and Cells
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• v.26 no.5
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• pp.454-458
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• 2008

Sex steroid hormone receptors play a central role in modulating telomerase activity, especially in cancer cells. However, information on the regulation of steroid hormone receptors and their distinct functions on telomerase activity within the mesenchymal stem cell are largely unavailable due to low telomerase activity in the cell. In this study, the effects of estrogen ($E_2$) treatment and function of estrogen receptor alpha ($ER{\alpha}$) and estrogen receptor beta ($ER{\beta}$) on telomerase activity were investigated in human mesenchymal stem cells (hMSCs). Telomerase activity and mRNA expression of the catalytic subunit of telomerase (hTERT) were upregulated by treatment of the cells with $E_2$. The protein concentration of $ER{\alpha}$ was also increased by $E_2$ treatment, and enhancement of $ER{\alpha}$ accumulation in the nucleus was clearly detected with immunocytochemistry. When $ER{\alpha}$ expression was reduced by siRNA transfection into hMSCs, the effect of $E_2$ on the induction of hTERT expression and telomerase activity was diminished. In contrast, the transient overexpression of $ER{\alpha}$ increased the effect of $E_2$ on the expression of hTERT mRNA. These findings indicate that the activation of hTERT expression and telomerase activity by $E_2$ in hMSCs depends on $ER{\alpha}$, but not on $ER{\beta}$.

• Journal of Korean Neurosurgical Society
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• v.46 no.1
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• pp.1-4
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• 2009

Objective: To report an unsuspected adaptive plasticity of single upper motor neurons and of primary motor cortex found after microsurgical connection of the spinal cord with peripheral nerve via grafts in paraplegics and focussed discussion of the reviewed literature. Methods: The research aimed at making paraplegics walk again, after 20 years of experimental surgery in animals. Amongst other things, animal experiments demonstrated the alteration of the motor endplates receptors from cholinergic to glutamatergic induced by connection with upper motor neurons. The same paradigm was successfully performed in paraplegic humans. The nerve grafts were put into the ventral-lateral spinal tract randomly, with out possibility of choosing the axons coming from different areas of the motor cortex. Results: The patient became able to selectively activate the re-innervated muscles she wanted without concurrent activities of other muscles connected with the same cortical areas. Conclusion: Authors believe that unlike in nerve or tendon transfers, where the whole cortical area corresponding to the transfer changes its function a phenomenon that we call "brain plasticity by areas". in our paradigm due to the direct connection of upper motor neurons with different peripheral nerves and muscles via nerve grafts motor learning occurs based on adaptive neuronal plasticity so that simultaneous contractions of other muscles are prevented. We propose to call it adaptive functional "plasticity by single neurons". We speculate that this phenomenon is due to the simultaneous activation of neurons spread in different cortical areas for a given specific movement, whilst the other neurons of the same areas connected with peripheral nerves of different muscles are not activated at the same time. Why different neurons of the same area fire at different times according to different voluntary demands remains to be discovered. We are committed to solve this enigma hereafter.

• Journal of Acupuncture Research
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• v.20 no.5
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• pp.133-150
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• 2003

Objective: Recently. many studies have showed the evidences of the effect of the Electro-acupuncture treatment through scientific. Methods : One of these methods is functional MRI. We performed electro-acupuncture on Zusanli(St36) and observed the change of brain activation using fMRI. Zusanli(St36) is located on the lateral side of the lower leg. 3 cun(寸) inferior to the Patella of the lower border. Theoretically and clinically. this point has been considered very important for gynecological disorders. spleen and stomach disorders. and psychological disorders. To see the effects of electro-acupuncture stimulation on Zusanli(St36). the experiment was carried out on twelve healthy volunteers. using the gradient echo sequence with the 3.0T whole-body fMRI system(ISOL). After the needle insertion on right Zusanli(St36). 2 Hz of electric stimulation was given for 30 seconds. repeated five times. with 30 seconds' intervals. The Image analysis including motion correction. talairach transformation, and smoothing was done with SPM99. Results ad conclusion : The electro-acupuncture stimulation on Zusanli(St36) activates Brodmann Area 6, 13, 2, 19, 21, 22, 39, 40, 38, 3which indicates the pathways of the electro-acupuncture stimulation on Zusanli(St36) and the possibility of the relationship of the electro-acupuncture stimulation on Zusanli(St36) with autonomic nervous system, internal organic system.

• Journal of Acupuncture Research
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• v.33 no.2
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• pp.109-116
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• 2016

Objectives : Our primary objective lies in understanding the current landscape of translational research on acupuncture, moxibustion and pharmacopuncture. Methods : We searched our own selection of keywords of acupuncture, moxibustion and pharmacopuncture and translational research from three overseas databases (Pubmed, Scopus, Medicine) and four domestic databases (DBpia, KISS, Riss4u, Korea Med). Results : We have chosen 41 articles in total-40 articles on acupunture, 6 article on moxibustion(5 articles were duplicated in use in each category). Origin-wise, 48.8 %/24.8 %/17.0 % of our articles pool came from USA/China/Korea, respectively. UK, Austria, Thailand and Italy contributed the rest of our article pool. For those articles written in USA and China, review articles were the most common type. For the US articles, all 10 review articles were non-systematic reviews, while, for China's contribution, one out of 4 review articles were systematic review. Type-wise, our research pool's breakdown is as follows ; 17 review articles, 11 experimental research, 2 randomized controlled trials(RCT), 1 clinical trial, 4 conference reports, 1 letter, 1 study protocol and 4 uncategorized. Topic-wise, brain-neurology was most frequently referred with 8 articles, followed by parkinson's disease (3 articles) and epilepsy (2 articles). Conclusion : 1. In terms of research submission articles, Korea appears to be lacking translational research on acupuncture, moxibustion and pharmacopuncture, compared to USA and China, in our view. 2. Unlike the cases of USA and China, most of Korean translational research is limited to doing a T1 level of translational research. In order to bring bench-to-bedside to light. we believe, there should be more studies, and thereby a certain level of activation, to the T2 level of translational research in Korea. 3. Further, in our view there should be more efforts to improve article quality at the T1 level of translational research, which eventually becomes the fundamentals of the next level of research (i.e. T2 research), as well as to increase the number of research submissions, going forward.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.6
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• pp.673-679
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• 1997

It has been generally accepted that glutamate mediates the ischemic brain damage, excitotoxicity, and induces release of neurotransmitters, including norepinephrine(NE), in ischemic milieu. In the present study, the role of nitric oxide(NO) in the ischemia-induced $[^3H]norepinephrine([^3H]NE)$ release from cortex slices of the rat was examined. Ischemia, deprivation of oxygen and glucose from $Mg^{2+}-free$ artificial cerebrospinal fluid, induced significant release of $[^3H]NE$ from cortex slices. This ischemia-induced $[^3H]NE$ release was significantly attenuated by glutamatergic neurotransmission modifiers. $N^G-nitro-L-arginine$ methyl ester(L-NAME), $N^G-monomethyl-L-arginine$ (L-NMMA) or 7-nitroindazole, nitric oxide synthase inhibitors attenuated the ischemia-evoked $[^3H]NE$ release. Hemoglobin, a NO chelator, and 5, 5- dimethyl-L-pyrroline-N-oxide(DMPO), an electron spin trap, inhibited $[^3H]NE$ release dose-dependently. Ischemia-evoked $[^3H]NE$ release was inhibited by methylene blue, a soluble guanylate cyclase inhibitor, and potentiated by 8-bromo-cGMP, a cell permeable cGMP analog, zaprinast, a cGMP phosphodiesterase inhibitor, and S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide generator. These results suggest that the ischemia-evoked $[^3H]NE$ release is mediated by NMDA receptors, and activation of NO system is involved.