• Journal of Ginseng Research
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• v.44 no.1
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• pp.79-85
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• 2020

Background: Helicobacter pylori increases reactive oxygen species (ROS) and induces oxidative DNA damage and apoptosis in gastric epithelial cells. DNA damage activates DNA damage response (DDR) which includes ataxia-telangiectasia-mutated (ATM) activation. ATM increases alternative reading frame (ARF) but decreases mouse double minute 2 (Mdm2). Because p53 interacts with Mdm2, H. pylori-induced loss of Mdm2 stabilizes p53 and induces apoptosis. Previous study showed that Korean Red Ginseng extract (KRG) reduces ROS and prevents cell death in H. pylori-infected gastric epithelial cells. Methods: We determined whether KRG inhibits apoptosis by suppressing DDRs and apoptotic indices in H. pylori-infected gastric epithelial AGS cells. The infected cells were treated with or without KRG or an ATM kinase inhibitor KU-55933. ROS levels, apoptotic indices (cell death, DNA fragmentation, Bax/Bcl-2 ratio, caspase-3 activity) and DDRs (activation and levels of ATM, checkpoint kinase 2, Mdm2, ARF, and p53) were determined. Results: H. pylori induced apoptosis by increasing apoptotic indices and ROS levels. H. pylori activated DDRs (increased p-ATM, p-checkpoint kinase 2, ARF, p-p53, and p53, but decreased Mdm2) in gastric epithelial cells. KRG reduced ROS and inhibited increase in apoptotic indices and DDRs in H. pylori-infected gastric epithelial cells. KU-55933 suppressed DDRs and apoptosis in H. pylori-infected gastric epithelial cells, similar to KRG. Conclusion: KRG suppressed ATM-mediated DDRs and apoptosis by reducing ROS in H. pylori-infected gastric epithelial cells. Supplementation with KRG may prevent the oxidative stress-mediated gastric impairment associated with H. pylori infection.

• Molecules and Cells
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• v.39 no.4
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• pp.322-329
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• 2016

Voltage-gated $Ca^{2+}$ ($Ca_V$) channels are dynamically modulated by Gprotein-coupled receptors (GPCR). The $M_1$ muscarinic receptor stimulation is known to enhance $Ca_V2.3$ channel gating through the activation of protein kinase C (PKC). Here, we found that $M_1$ receptors also inhibit $Ca_V2.3$ currents when the channels are fully activated by PKC. In whole-cell configuration, the application of phorbol 12-myristate 13-acetate (PMA), a PKC activator, potentiated $Ca_V2.3$ currents by ~two-fold. After the PMA-induced potentiation, stimulation of $M_1$ receptors decreased the $Ca_V2.3$ currents by $52{\pm}8%$. We examined whether the depletion of phosphatidylinositol 4,5-bisphosphate ($PI(4,5)P_2$) is responsible for the muscarinic suppression of $Ca_V2.3$ currents by using two methods: the Danio rerio voltage-sensing phosphatase (Dr-VSP) system and the rapamycin-induced translocatable pseudojanin (PJ) system. First, dephosphorylation of $PI(4,5)P_2$ to phosphatidylinositol 4-phosphate (PI(4)P) by Dr-VSP significantly suppressed $Ca_V2.3$ currents, by $53{\pm}3%$. Next, dephosphorylation of both PI(4)P and $PI(4,5)P_2$ to PI by PJ translocation further decreased the current by up to $66{\pm}3%$. The results suggest that $Ca_V2.3$ currents are modulated by the $M_1$ receptor in a dual mode-that is, potentiation through the activation of PKC and suppression by the depletion of membrane $PI(4,5)P_2$. Our results also suggest that there is rapid turnover between PI(4)P and $PI(4,5)P_2$ in the plasma membrane.

• Anxiety and mood
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• v.4 no.1
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• pp.3-10
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• 2008

The purpose of this review was to investigate the neurophysiological and neuroimaging characteristics of patients with depression and anxiety reported in previous studies. A literature search was conducted using Medline and psychiatric textbooks. "Electroencephalography (EEG)", "Event Related Potentials (ERP)", "functional neuroimaging", "heart rate variability (HRV)" and "depression or anxiety" were used as key words. A physiological finding indicated that there was a higher degree of relativity with regards to prefrontal dysfunction in patients with depression. Right prefrontal lobe hyperactivity and left prefrontal hypoactivity were consistently observed, and abnormalities were observed in other regions (ACC, hippocampus, amygdala, etc.). Therefore, dysfunctions in these areas are related to depressive symptoms. In patients with anxiety disorder, each emotional condition showed specific activation patterns in different brain regions, such as the prefrontal cortex, occipital lobe, temporal lobe, hippocampus, and limbic system, including the amygdala. However, in the majority of patients with anxiety disorder, the degree of activation was higher in the right hemisphere than in the left hemisphere. The current data supports that there is a difference in brain dysfunction characteristics between depression and anxiety and that the different activations of various brain regions would play a significant role in the pathophysiology of depression and anxiety disorder.

• The Journal of Korean Physical Therapy
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• v.15 no.3
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• pp.295-345
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• 2003

This study investigated activation of cerebral cortex in patients with hemiplegia that was caused by neural damage. Key-point control movement therapy of Bobath was performed for 9 weeks in 3 subjects with hemiplegia and fMRI was used to compare and analyze activated degree of cerebral cortex in these subjects. fMRI was conducted using the blood oxygen level-dependent(BOLD) technique at 3.0T MR scanner with a standard head coil. The motor activation task consisted of finger flexion-extension exercise in six cycles(one half-cycles = 8 scans = $3\;sec{\times}\;8\;=\;24\;sec$). Subjects performed this task according to visual stimulus that sign of right hand or left hand twinkled(500ms on, 500ms off). After mapping activation of cerebral motor cortex on hand motor function, below results were obtained. 1. Activation decreased in primary motor area, whereas it increased in supplementary motor area and visual association area(p<.001). 2. Activation was observed in bilateral medial frontal gyrus, middle frontal gyrus of left cerebrum, inferior frontal gyrus, inter-hemispheric, fusiform gyrus of right cerebrum, superior parietal lobule of parietal lobe and precuneus in subjedt 1, parahippocampal gyrus of limbic lobe and cingulate gyrus in subject 2, and inferior frontal gyrus of right frontal lobe, middle frontal gyrus, and inferior parietal lobule of left cerebrum in subject 3 (p<.001). 3. Activation cluster extended in declive of right cellebellum posterior lobe in subject 1, culmen of anterior lobe and declive of posterior lobe in subject 2, and dentate gyrus of anterior lobe, culmen and tuber of posterior lobe in subject 3 (p<.001). In conclusion, these data showed that Key-point control movement therapy of Bobath after stroke affect cerebral cortex activation by increasing efficiency of cortical networks. Therefore mapping of brain neural network activation is useful for plasticity and reorganization of cerebral cortex and cortico-spinal tract of motor recovery mechanisms after stroke.

• The Journal of Korean Physical Therapy
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• v.21 no.1
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• pp.81-87
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• 2009

Purpose: Human brain was lateralized to dominant or non-dominant hemisphere, and could be reorganized by the processing of the motor learning. We reported four cases which showed the changes of the cortical activation patterns resulting from two weeks of training with the serial reaction time task. Methods: Four right-handed healthy subjects were recruited, who was equally divided to two training conditions (right hand training or left hand training). They were assigned to train the serial reaction time task for two weeks, which should press the corresponding four colored buttons as fast as accurately as possible when visual stimulus was presented. Before and after two weeks of training, reaction time and function magnetic resonance image (fMRI) was acquired during the performance of the same serial reaction time task as the training. Results: The reaction time was significantly decreased in all of subjects after training. Our fMRI result showed that widespread bilateral activation at the pre scanning was shifted toward the focused activation on the contralateral hemisphere with progressive motor learning. However, the bilateral activation was still remained during the performance of the non-dominant hand. Conclusion: These findings showed that the repetitive practice of the serial reaction time task led to increase the movement speed and accuracy, as described by motor learning. Such motor learning induced to change the cortical activation pattern. And, the changed pattern of the cortical activation resulting from motor learning was different each other in accordance with the hand dominance.

• Journal of Acupuncture Research
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• v.25 no.5
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• pp.151-165
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• 2008

Objectives : To evaluate the effects of Head Acupuncture versus Upper and Lower Limbs Acupuncture on signal activation of Blood Oxygen Level Dependent(BOLD) fMRI on the Brain and Somatosensory Cortex. Subjects and Methods : 10 healthy normal right-handed female volunteer were recruited. The average age of the 10 subjects was 30 years old. The BOLD functional MRI(fMRI) signal characteristics were determined during tactile stimulation was conducted by rubbing 4 acu-points in the right upper and lower limbs($LI_1$, $LI_{10}$, $LV_3$, $ST_{36}$). After stimulation of Head Acupuncture in Sishencong($HN_1$), $GB_{18}$, $GB_9$, $TH_{20}$ of Left versus Upper and Lower Limbs Acupuncture($LI_1$, $LI_{10}$, $LV_3$, $ST_{36}$ of Right) and took off needles. Then the BOLD fMRI signal characteristics were determined at the same manner. Results : 1. When touched with cotton buds(sensory stimulation), left Parietal Lobe, Post-central Gyrus, primary somatosensory cortex(BA 1, 2, 3), and primary motor cortex(BA 4) were mainly activated. When $ST_{36}$ was stimulated, Frontal Lobe, Parietal Lobe, Cerebellum, and Posterior Lobe as well as Inter-Hemispheric displaying a variety of regions. 2. In signal activation before and after Head Acupuncture reaction, it showed signal activation after removing the acupuncture needle and right Somatosensory Association Cortex, Postcentral Gyrus, and Parietal Lobe were more activated. 3. In reactions of before and after Upper and Lower Limb Acupuncture, it also showed signal activation after removing the acupuncture needle and bilateral Occipital Lobe, Lingual Gyrus, visual association cortex, and Cerebellum were activated. 4. After acupuncture stimulation, In Upper and Lower Limb Acupuncture Group, left frontal Lobe, Precentral Gyrus and Bilateral parietal lobe, Postcentral Gyrus and Primary Somatosensory Cortex(BA 2) were activated. In Head Acupuncture Group, which has most similar activation regions, but especially right Pre-Post central Gyrus, Primary Somatosensory Cortex(BA 3), Primary Motor Cortex, frontal Lobe and Parietal Lobe were activated. Conclusions : When sensory stimulation was done with cotton buds on four acup-points($LI_1$, $LI_{10}4, $LV_3$, $ST_{36}$), while bilaterally activated, contralateral sense was more dominant. It showed consistency with cerebral cortex function. When $ST_{36}$ was stimulated Frontal Lobe, Parietal Lobe, Cerebellum, Posterior Lobe as well as Inter-Hemispheric were stimulated. In Head Acupuncture, it showed more contralateral activation after acupuncture. In Upper and Lower Limb Acupuncture, it showed typically contralateral activation and deactivation of limbic system after acupuncture stimulation. Therefore, there were different fMRI BOLD signal activation reaction before and after Head Acupuncture vs Upper and Lower Limb Acupuncture which might be thought to be caused by acu-points' sensitivity and different sensory receptor to response acupuncture stimulation.

• IMMUNE NETWORK
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• v.5 no.1
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• pp.45-49
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• 2005

Background: Inflammation in the brain has known to be associated with the development of a various neurological diseases. The hallmark of neuro-inflammation is the activation of microglia, brain macrophage. Pro-inflammatory compounds including nitric oxide (NO) are the main cause of neuro-degenerative disease such as Alzheimer's disease (AD) which is resulted in cell death. Among those pro-inflammatory compounds, NO contributes to the cell death by directly or indirectly. Methods: In the study, we examined whether ursodeoxycholic acid (UDCA), a non-toxic hydrophilic bile acid, inhibits the NO production by a direct method using Griess reagent and by RT-PCR in the gene expression of inducible nitric oxide synthase (iNOS). In signal transduction, we also examined the NF-${\kappa}B$ (p65/p50), IKK, and I ${\kappa}B$, which are associated with the expression of iNOS gene using western blots. Results: In the present study, we found that UDCA effectively inhibited NO production in BV-2 microglial cell, and NF-${\kappa}B$ activation was reduced by suppressing IKK gene expression and by increasing the I${\kappa}B$ in cytosol comparing those to the positive control LPS. Conclusion: Taken together, these data suggested that UDCA may playa crucial role in inhibiting the NO production and the results imply that UDCA suppresses a cue signal of the microglial activation via stimulators, such as ${\beta}$-amyloid peptides which are known to stimulate microglia in AD pathogenesis.

• Physical Therapy Korea
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• v.12 no.2
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• pp.73-80
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• 2005

We investigated the activation of the cerebral cortex during active movement, passive movement, and functional electrical stimulation (FES), which was provided on wrist extensor muscles. A functional magnetic resonance imaging study was performed on 5 healthy volunteers. Tasks were the extension of right wrist by active movement, passive movement, and FES at the rate of .5 Hz. The regions of interest were measured in primary motor cortex (M1), primary somatosensory cortex (SI), secondary somatosensory cortex (SII), and supplementary motor area (SMA). We found that the contralateral SI and SII were significantly activated by all of three tasks. The additional activation was shown in the areas of ipsilateral S1 (n=2), and contralateral (n=1) or ipsilateral (n=2) SII, and bilateral SMA (n=3) by FES. Ipsilateral M1 (n=1), and contralateral (n=1) or ipsilateral SII (n=1), and contralateral SMA (n=1) were activated by active movement. Also, Contralateral SMA (n=3) was activated by passive movement. The number of activated pixels on SM1 by FES ($12{\pm}4$ pixels) was smaller than that by active movement ($18{\pm}4$ pixels) and nearly the same as that by passive movement ($13{\pm}4$ pixels). Findings reveal that active movement, passive movement, and FES had a direct effect on cerebral cortex. It suggests that above modalities may have the potential to facilitate brain plasticity, if applied with the refined-specific therapeutic intervention for brain-injured patients.

• Investigative Magnetic Resonance Imaging
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• v.3 no.1
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• pp.41-46
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• 1999

Purpose : To investigate the difference of total activation in visual area, motor area, and cerebellum according to the stimulation paradigm. Materials and Methods : Functional MR imaging was performed in 5 healthy volunteers with visual and motor activity using EPI technique. LED and Checker-Board stimulation were performed for visual activity. Thumb motion and Finger Tapping were performed for motor and cerebellum activity. Stimulus timing was 60sec. off, 120sec. on, 60sec. off. Data processing was carried out by using the cross-correlation method for each pixel. Each pixel was then selected and assumed activated if the correlation coefficient was equal or larger than a threshold value. Time course data was obtained by calculating the total activation which was defined as the number of activated pixel x averaged pixel intensity. Results : In the case of visual activity with LED stimulation, we found increased total activity of more than 100% compared with Checker-Board stimulation. In the case of motor area and cerebellum with Finger tapping stimulation, we found increased total activity of more than 10% and 150%, respectively compared with Thumb motion stimulation.

• Nutrition Research and Practice
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• v.11 no.5
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• pp.381-387
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• 2017

BACKGROUND/OBJECTIVES: Vascular dementia (VaD) caused by reduced blood supply to the brain manifests as white matter lesions accompanying demyelination and glial activation. We previously showed that arabinoxylan consisting of arabinose and xylose, and arabinose itself attenuated white matter injury in a rat model of VaD. Here, we investigated whether larch arabinogalactan (LAG) consisting of arabinose and galactose could also reduce white matter injury. MATERIALS/METHODS: We used a rat model of bilateral common carotid artery occlusion (BCCAO), in which the bilateral common carotid arteries were exposed and ligated permanently with silk sutures. The rats were fed a modified AIN-93G diet supplemented with LAG (100 mg/kg/day) for 5 days before and 4 weeks after being subjected to BCCAO. Four weeks after BCCAO, the pupillary light reflex (PLR) was measured to assess functional consequences of injury in the corpus callosum (cc). Additionally, Luxol fast blue staining and immunohistochemical staining were conducted to assess white matter injury, and astrocytic and microglial activation, respectively. RESULTS: We showed that white matter injury in the the cc and optic tract (opt) was attenuated in rats fed diet supplemented with LAG. Functional consequences of injury reduction in the opt manifested as improved PLR. Overall, these findings indicate that LAG intake protects against white matter injury through inhibition of glial activation. CONCLUSIONS: The results of this study support our hypothesis that cell wall polysaccharides consisting of arabinose are effective at protecting white matter injury, regardless of their origin. Moreover, LAG has the potential for development as a functional food to prevent vascular dementia.