• Molecules and Cells
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• v.38 no.9
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• pp.796-805
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• 2015

Gintonin is a novel ginseng-derived lysophosphatidic acid (LPA) receptor ligand. Oral administration of gintonin ameliorates learning and memory dysfunctions in Alzheimer's disease (AD) animal models. The brain cholinergic system plays a key role in cognitive functions. The brains of AD patients show a reduction in acetylcholine concentration caused by cholinergic system impairments. However, little is known about the role of LPA in the cholinergic system. In this study, we used gintonin to investigate the effect of LPA receptor activation on the cholinergic system in vitro and in vivo using wild-type and AD animal models. Gintonin induced $[Ca^{2+}]_i $ transient in cultured mouse hippocampal neural progenitor cells (NPCs). Gintonin-mediated $[Ca^{2+}]_i $ transients were linked to stimulation of acetylcholine release through LPA receptor activation. Oral administration of gintonin-enriched fraction (25, 50, or 100 mg/kg, 3 weeks) significantly attenuated scopolamine-induced memory impairment. Oral administration of gintonin (25 or 50 mg/kg, 1 2 weeks) also significantly attenuated amyloid-${\beta}$ protein ($A{\beta}$)-induced cholinergic dysfunctions, such as decreased acetylcholine concentration, decreased choline acetyltransferase (ChAT) activity and immunoreactivity, and increased acetylcholine esterase (AChE) activity. In a transgenic AD mouse model, long-term oral administration of gintonin (25 or 50 mg/kg, 3 months) also attenuated AD-related cholinergic impairments. In this study, we showed that activation of G protein-coupled LPA receptors by gintonin is coupled to the regulation of cholinergic functions. Furthermore, this study showed that gintonin could be a novel agent for the restoration of cholinergic system damages due to $A{\beta}$ and could be utilized for AD prevention or therapy.

• Journal of Life Science
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• v.30 no.9
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• pp.826-833
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• 2020

Phospholipase C gamma (PLCγ) has critical roles in receptor tyrosine kinase- and non-receptor tyrosine kinase-mediated cellular signaling relating to the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P₂] to produce inositol 1,4,5 trisphosphate (IP₃) and diacylglycerol (DAG), which promote protein kinase C (PKC) and Ca²⁺ signaling to their downstream cellular targets. PLCγ has two isozymes called PLCγ1 and PLCγ2, which control cell growth and differentiation. In addition to catalytically active X- and Y-domains, both isotypes contain two Src homology 2 (SH2) domains and an SH3 domain for protein-protein interaction when the cells are activated by ligand stimulation. PLCγ also contains two pleckstrin homology (PH) domains for membrane-associated phosphoinositide binding and protein-protein interactions. While PLCγ1 is widely expressed and appears to regulate intracellular signaling in many tissues, PLCγ2 expression is restricted to cells of hematopoietic systems and seems to play a role in the regulation of immune response. A distinct mechanism for PLCγ activation is linked to an increase in phosphorylation of specific tyrosine residue, Y783. Recent studies have demonstrated that PLCγ mutations are closely related to cancer, immune disease, and brain disorders. Our review focused on the physiological roles of PLCγ by means of its structure and enzyme activity and the pathological functions of PLCγ via mutational analysis obtained from various human diseases and PLCγ knockout mice.

• Parasites, Hosts and Diseases
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• v.47 no.3
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• pp.205-212
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• 2009

Trichomonas vaginalis commonly causes vaginitis and perhaps cervicitis in women and urethritis in men and women. Macrophages are important immune cells in response to T. vaginalis infection. In this study, we investigated whether human macrophages could be involved in inflammation induced by T. vaginalis. Human monocyte-derived macrophages (HMDM) were co-cultured with T. vaginalis. Live, opsonized-live trichomonads, and T. vaginalis Iysates increased proinflammatory cytokines, such as TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 by HMDM. The involvement of nuclear factor (NF)-${\kappa}B$ signaling pathway in cytokine production induced by T. vaginalis was confirmed by phosphorylation and nuclear translocation of p65 NF-${\kappa}B$. In addition, stimulation with live T. vaginalis induced marked augmentation of nitric oxide (NO) production and expression of inducible NO synthase (iNOS) levels in HMDM. However, trichomonad-induced NF-${\kappa}B$ activation and TNF-${\alpha}$ production in macrophages were significantly inhibited by inhibition of iNOS levels with L-NMMA (NO synthase inhibitor). Moreover, pretreatment with NF-${\kappa}B$ inhibitors (PDTC or Bay11-7082) caused human macrophages to produce less TNF-${\alpha}$. These results suggest that T. vaginalis stimulates human macrophages to produce proinflammatory cytokines, such as IL-1, IL-6, and TNF-${\alpha}$, and NO. In particular, we showed that T. vaginalis induced TNF-${\alpha}$ production in macrophages through NO-dependent activation of NF-${\kappa}B$, which might be closely involved in inflammation caused by T. vaginalis.

• Journal of the Korean Society of Radiology
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• v.13 no.7
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• pp.901-907
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• 2019

The aim of this study is to evaluate the ability of target localizations of Leksell GammaPlan(LGP) in Gamma Knife Subthalamotomy(or Pallidotomy, Thalamotomy) of functional diseases. To evaluate the accuracy of LGP's location settings, the difference Δr of the target coordinates calculated by LGP (or LSP) and author's algorithm was reviewed for 10 patients who underwent Deep Brain Stimulation(DBS) surgery. Δr ranged from 0.0244663 mm to 0.107961 mm. The average of Δr was 0.054398 mm. Transformation matrix between stereotactic space and brain atlas space was calculated using PseudoInverse or Singular Value Decomposition of Mathematica to determine the positional relationship between two coordinate systems. Despite the precise frame positioning, the misalignment of yaw from -3.44739 degree to 1.82243 degree, pitch from -4.57212 degree to 0.692063 degree, and rolls from -6.38239 degree to 7.21426 degree appeared. In conclusion, a simple in-house algorithm was used to test the accuracy for location settings of LGP(or LSP) in Gamma Knife platform and the possibility for Gamma Knife Subthalamotomy. The functional diseases can be treated with Gamma Knife Radiosurgery with safety and efficacy. In the future, the proposed algorithm for target localizations' QA will be a great contributor to movement disorders' treatment of several Gamma Knife Centers.

• Development and Reproduction
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• v.13 no.2
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• pp.79-87
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• 2009

Due to its well-known function in parturition and milk ejection, oxytocin (OT) has been considered as a 'female neurohypophyseal hormone'. Recent studies, however, clearly indicate that OT has some local roles in male reproduction via both central and peripheral routes. In experimental rodents, OT is released within distinct brain regions in response to social stimuli, and the brain OT receptor (OTR) mediated actions were strongly involved in the regulation of a variety of male behaviors such as mating-associated behaviors. In particular, OT and/or OTR knockout mice provide important clues about the molecular regulatory mechanism of the socio-sexual behaviors. Several lines of evidence also show that OT is synthesized within rodents testis, epididymis and prostate, and the presence of OTRs in these organs. In rodent testes, OT might have a role in the modulation of steroidogenesis via stimulation of the conversion of testosterone (T) to dihydrotestosterone (DHT) by 5alpha-reductase. Similar effects of OT on this androgen conversion were observed in epididymis and prostate suggesting the OT's modulatory role, such as contractility induction, in these androgen-dependent organs. In this context, further investigations on the OT's role in male CNS and reproductive organs are likely to provide better understanding on the complex socio-sexual behaviors and a platform for development of therapeutics to treat some psychological and/or andrological problems.

• Journal of the Institute of Electronics and Information Engineers
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• v.51 no.10
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• pp.213-220
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• 2014

Korean magnetoencephalography (MEG) system had been developed and installed to hospital. The Korean MEG system contains helmet-shaped arrays of 152 first-order double relaxation oscillation SQUID (DROS) sensor. As a clinical application we have measured and analyzed evoked responses in patients with functional brain disease by outer stimulation as follows; 1) auditory evoked field in patients with hemifacial spasm, 2) somatosensory evoked fields in patients with tumor. We confirm that neuromagnetic data by Korean MEG system can provide useful information for pre-surgical planning or functional brain research.

• The Journal of Korean Medicine
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• v.30 no.4
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• pp.13-27
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• 2009

Objectives: Trans-cinnamaldehyde (TCA) is the main component of Cinnamomi Ramulus and it has been reported that TCA inhibits inflammatory responses in various cell types. Inflammation-mediated neurological disorders induce the activation of macrophages such as microglia in brain, and these activated macrophages release various inflammation-related molecules, which can be neurotoxic if overproduced. In this study, we evaluated gene expression profiles using gene chip microarrays in lipopolysaccharide (LPS)-stimulated BV-2 cells to investigate the antiinflammatory effect of TCA on inflammatory responses in brain microglia. Methods: A negative control group was cultured in normal medium and a positive control group was stimulated with $1{\mu}g/ml$ in the absence of TCA. TCA group was pretreated with $10{\mu}g/ml$ before $1{\mu}g/ml$ LPS stimulation. The oligonucleotide microarray analysis was performed to obtain the expression profiles of 28,853 genes using gene chip mouse gene 1.0 ST array in this study. Results: In positive control group, 1522 probe sets were up-regulated in the condition of the cutoff value of 1.5-fold change and 341 genes with Unigene ID were retrieved. In TCA group, 590 probe sets were down-regulated from among 1522 probe sets and 33 genes with Unigene ID were retrieved, which included 6 inflammation-related genes. We found out that Id3 gene is associated with transforming growth factor-${\beta}$ (TGF-${\beta}$) signaling pathway and Klra8 gene is related to natural killer cell-mediated cytotoxicity pathway. Conclusions: The results mean that TCA inhibits inflammatory responses through down-regulating the expressions of inflammation-related genes in LPS-stimulated BV-2 cells.

• Proceedings of the Ginseng society Conference
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• 1998.06a
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• pp.1-11
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• 1998

Ameliorating mechanisms of red ginseng on learning deficits were investigated in the following 3 experiments; its effects on 1) place learning deficits in aged rats and in young rats with selective hippocampal lesions (behavioral study), 2) long-term potentiation in the hippocampal formation (neuro- physiological study), and 3) ChAT (choline acetyl transferase) activity in various brain regions of aged rats (pharmacological study). In the behavioral study, first, performance in the place learning tasks were compared among 3 groups of young and aged rats; control young intact rats (10-12 week old) treated with water, aged rats (28-32 month old) treated with water, and aged rats (28-32 month old) treated with red ginseng (100 mghglday) suspended in water. Second, performance in the place learning tasks was compared among 3 groups of young rats; control intact rats treated with water, rats with bilateral hippocampal lesions treated with water, and rats with bilateral hippocampal lesions treated with red ginseng (100 mg/kg/day). Each rat in these 2 behavioral experiments was tested with the 3 types of the place learning tasks in a circular open field using intracranial self-stimulation (ICSS) as reward. The ICSS reward was delivered if the rat (1) moved distance of 100-160 cm (DMT): (2) entered an experiment-determined reward place within the open field, and this place was randomly varied in sequential trials (RRPST); or (3) entered 2 specific places, and did a shuttle behavior between the 2 places (PLT). Performance of the aged rats in the ginseng group was not significantly different from that of control young rats in ICSS (current intensity, bar press rates), DMT and RRPST. However, treatment with red ginseng significantly ameliorated place-navigation learning deficits in aged rats in the PLT. Similarly, red ginseng ameliorated learning and memory deficits in young rats with hippocampal lesions in the same tasks. In the neurophysiological study using young rats, perfusion of hippocampal slices with non-sapon in fraction of red ginseng significantly enhanced magnitudes of the long-term potentiation (LfP) in the CA3 subfield. In the pharmacological study, treatment with red ginseng did not affect ChAT activity in aged rat brain including the hippocampal formation. These results strongly suggest that red ginseng ameliorates learning and memory deficits in aged rats through actions on the CA3 subfield of the hippocampal formation, which were independent of the presynaptic components of the cholinergic system

• Journal of Korea Entertainment Industry Association
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• v.14 no.7
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• pp.539-548
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• 2020

TTH(tension-type headache) is the most common primary headache among adults. Long-term headaches cause chronic headaches and have a better impact on daily life. The purpose of this study is to compare the contributions to TTH through AVE(audio-visual entertainment) and STM(soft tissue mobilization) suitable for management of pathogenic and psychogenic factors of TTH. The participants of this study were from 30 people who complained of intermittent or persistent headaches for more than 6 months, and 10 participants each in the AVE group, STM group, and AVE plus STM group. In the assigned group, a total of 12 sessions were performed three times a week for 4 weeks after the baseline, followed by post-test. Outcome measures measured PPTs(pressure pain thresholds), psychophysiological parameters, and EEG(electroencephalogram). The measured results were analyzed for interaction between time and group through a two way rmANOVA(repeated measurement variance analysis). As a result of the PPTs, interaction was found in the results of the right trapezius (p<.05), and the more improvement was observed in the AVE group. Therefore, through AVE based on psychological factors rather than direct access to the muscles of pathogenic factors, a positive impact on the PPTs was shown, but the average value of the psychophysiological parameters and brain waves that were not statistically significant. The amount of change was observed. Through this, it is suggested that audio-visual stimulation could be considered in the management of TTH.

• Proceedings of the Korean Society of Computer Information Conference
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• 2016.07a
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• pp.295-296
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• 2016

본 연구에서는 LED 광 자극이 뇌의 어느 영역을 자극하여 신경신호를 전달하는지에 관해서 관찰하고자 연구를 진행하였다. 광 자극에 의한 뇌 영역의 활성변화를 관찰하기 위하여 실험용 소동물과 영상장비인 9.4T MRI를 이용하여 연구를 수행 하였다. 실험용 소동물은 Balb/c 마우스를 이용하였으며 기능적 자기공명영상 획득 방법 중 하나인 에코평면영상 기법을 이용하여 뇌 영상을 획득 하였다. 획득한 영상을 바탕으로 뇌 영역의 자극 정도를 확인해보기 위해 영상처리기법인 재편성(realignment), 일치(co-registration), 표준화(normalization), 평활화(smoothing) 방법으로 영상을 전처리 하고, statistical parametric map (SPM12)을 사용하여 분석하였다. 본 연구에서는 광자극이 소동물 뇌 영역 중 하나인 상구(Superior colliculus)영역과 대뇌의 시각피질 (visual cortex, V1) 영역에서 자극을 일으키는 것을 확인할 수 있었다.