• The Journal of Korean Obstetrics and Gynecology
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• v.23 no.3
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• pp.26-37
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• 2010

Purpose: This experiment is designed to find out anti-oxidant effects of Samultang-Gami which was composed of Rehmanniae Radix(RR), Angelicae Gigantis Radix, Cnidii Rhizoma(CR), Paeoniae Radix(PR), Cortex Moutan Radicis, Hedyotis Diffusa(HD) and Caesalpinia Sappan on MEF cells. Methods: In vitro antioxidant effects were measured by MTT assay, DPPH assay, cell cycle analysis, AnnexinV-FITC/PI assay and DAPI staining using MEF cells treated with various concentrations of 70% ethanol extract of Samultang-Gami. Results: 1. In the scavenging for DPPH radical, the each treated groups of PR, CR and HD showed positive effects. RR and CR increased the viability of oxidative damaged MEF cells in a dose-dependent manner. 2. 70% ethanol extract of Samultang-Gami was shown best antioxidative effect in the concentration of $0.5mg/m{\ell}$. 3. The treatment of Samultang-Gami in oxidative damaged MEF cells didn't have any effect on cell cycle restoration. but it could lower late apoptosis rate a little and be observed the protection of nucleus. Conclusion: It can be concluded that Samultang-Gami, RR and CR have antioxidant effects on MEF cells.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.4
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• pp.229-233
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• 2010

Amyloid precursor protein binding protein-1 (APP-BP1) binds to the carboxyl terminus of amyloid precursor protein and serves as a bipartite activation enzyme for the ubiquitin-like protein, NEDD8. Previously, it has been reported that APP-BP1 rescues the cell cycle S-M checkpoint defect in Ts41 hamster cells, that this rescue is dependent on the interaction of APP-BP1 with hUba3. The exogenous expression of APP-BP1 in neurons has been reported to cause DNA synthesis and apoptosis via a signaling pathway that is dependent on APP-BP1 binding to APP. These results suggest that APP-BP1 overexpression contributes to neurodegeneration. In the present study, we explored whether APP-BP1 expression was altered in the brains of Tg2576 mice, which is an animal model of Alzheimer's disease. APP-BP1 was found to be up-regulated in the hippocampus and cortex of 12 month-old Tg2576 mice compared to age-matched wild-type mice. In addition, APP-BP1 knockdown by siRNA treatment reduced cullin-1 neddylation in fetal neural stem cells, suggesting that APP-BP1 plays a role in cell cycle progression in the cells. Collectively, these results suggest that increased expression of APP-BP1, which has a role in cell cycle progression in neuronal cells, contributes to the pathogenesis of Alzheimer's disease.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.20 no.1 s.32
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• pp.201-208
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• 2007

RBL-2H3 cell line을 이용하여 백선피의 항알레르기 효과를 알아보기 위하여 PMA와 A23187로 자극한 후 RBL-2H3 내의 과립에 Histamine와 같이 존재하는 ${\beta}-hexosaminidase$의 유출량의 억제 정도 및 합성된 후 분비되는 $TNF-{\alpha}$, IL-4의 합성조절 정도를 살펴본 결과, 백선피는 세포생존율에는 영향을 미치지 않고 백선피의 농도가 증가함에 따라 ${\beta}-hexosaminidase$의 세포 위로의 유출을 억제하였으며, 또한 알레르기 반응과 밀접한 관련이 있는 사이토 카인 중에 하나인 $TNF-{\alpha}$, IL-4의 mRNA 수준에서의 발현의 조절을 통한 합성도 감소하였다. 이 결과로 보아 백선피는 알레르기와 관련된 질환에 응용이 가능할 것으로 사료된다.

• Herbal Formula Science
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• v.27 no.2
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• pp.121-136
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• 2019

Objective : To investigate the effect of sihogayonggolmoryeotang (SY) on Single Prolonged Stress(SPS)-induced Post Traumatic Stress Disorder(PTSD). Method : To confirm the effects of SY on SPS-induced PTSD, Changes in body weight, sucrose intake open field test(OFT) and forced swimming test(FST)were observed. After behavioral tests, the plasma corticosterone(CORT) from the abdominal aorta, serotonin(5-HT) from prefrontal cortex, hippocampus, amygdala and striatum, norepinephrine(NE) and dopamine(DA) from hippocampus was measured by ELISA. mRNA expression of brain-derived neurotrophic factor(BDNF) and cAMP response element-binding protein(CREB) in hippocampus was measured by RT-PCR. Result : Weight change and sucrose intakes of rats in 14th day after the administration of SY were significantly increased in the SPS + SY450 group compared to the SPS group (p<0.05). Numbers of crossing in the central zone in the OFT were significantly increased in the SPS + SY450 group (p<0.05) compared with the SPS group. The immobility time of FST was significantly decreased in SPS + SY450 group compared with SPS group (p<0.05). The change of plasma CORT concentration was significantly decreased in SPS + SY450 group compared with that in SPS group (p<0.05). The change of 5-HT concentration was significantly increased in the SPS + SY450 group at hippocampus and amygdala compared with the SPS group (p<0.05). The concentration of DA was significantly increased in the SPS + SY450 group compared with the SPS group (p<0.05). The expression of BDNF and CREB were significantly increased in SPS + SY450 group compared with the SPS group (p<0.05). Conclusion : SY administration lowered the increase of CORT caused by PTSD and increases the 5-HT concentration and reversed the decreased expression of NE and DA and BDNF and CREB by PTSD. It is postulated that SY is effective in treating PTSD by restoring cognitive function, memory impairment, unstable emotional disturbances.

• Molecules and Cells
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• v.45 no.8
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• pp.588-602
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• 2022

Various RNA-binding proteins (RBPs) are key components in RNA metabolism and contribute to several neurodevelopmental disorders. To date, only a few of such RBPs have been characterized for their roles in neocortex development. Here, we show that the RBP, Rbms1, is required for radial migration, polarization and differentiation of neuronal progenitors to neurons in the neocortex development. Rbms1 expression is highest in the early development in the developing cortex, with its expression gradually diminishing from embryonic day 13.5 (E13.5) to postnatal day 0 (P0). From in utero electroporation (IUE) experiments when Rbms1 levels are knocked down in neuronal progenitors, their transition from multipolar to bipolar state is delayed and this is accompanied by a delay in radial migration of these cells. Reduced Rbms1 levels in vivo also reduces differentiation as evidenced by a decrease in levels of several differentiation markers, meanwhile having no significant effects on proliferation and cell cycle rates of these cells. As an RNA binding protein, we profiled the RNA binders of Rbms1 by a cross-linked-RIP sequencing assay, followed by quantitative real-time polymerase chain reaction verification and showed that Rbms1 binds and stabilizes the mRNA for Efr3a, a signaling adapter protein. We also demonstrate that ectopic Efr3a can recover the cells from the migration defects due to loss of Rbms1, both in vivo and in vitro migration assays with cultured cells. These imply that one of the functions of Rbms1 involves the stabilization of Efr3a RNA message, required for migration and maturation of neuronal progenitors in radial migration in the developing neocortex.

• Journal of Oriental Neuropsychiatry
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• v.33 no.3
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• pp.277-285
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• 2022

Objectives: Gastrodia elata (GE) has been used to treat cognition impairment, including Alzheimer's disease (AD) in Korea. The purpose of this study was to investigate the effects of GE water extracts (GEE) on the lipopolysaccharide (LPS)-induced AD model in mice. (Aβ). Methods: We classified six groups as follow; group 1: control (CON), group 2: LPS (0.5 mg/kg/day, four times), group 3: 4 mg/kg donepezil (DP), group 4: 100 mg/kg GEE+LPS, group 5: 200 mg/kg GEE+LPS, group 6: 500 mg/kg GEE+LPS. Results: We found that GEE has an effect that inhibits decrease of discrimination index in object recognition test, as well as spontaneous alteration in the Y-maze test by LPS. Treatment with LPS increased amlyloid-β (Aβ) concentration, and decreased brain-derived neurotrophic factor (BDNF) in cerebral cortex of mice. However, GEE significantly protected against LPS-induced Aβ and BDNF changes. Our findings also showed that the inflammatory cytokines [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β)] mRNA and protein were up-regulated by the LPS injection. But GEE significantly suppressed LPS-induced inflammatory cytokines increase in a dose-dependent manner. Conclusions: This study suggests that the GEE may be an effective AD therapeutic agent, in treating neurodegenerative diseases including AD.

• Journal of Korean Neurosurgical Society
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• v.66 no.4
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• pp.400-408
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• 2023

Objective : Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is a crucial factor for the survival of neuron. The role of NMNAT2 in damage following traumatic brain injury (TBI) remains unknown. This study was designed to investigate the role of NMNAT2 in TBI-induced neuronal degeneration and neurological deficits in rats. Methods : The TBI model was established in Sprague-Dawley rats by a weight-dropping method. Real-time polymerase chain reaction, western blot, immunofluorescence, Fluoro-Jade C staining, and neurological score analyses were carried out. Results : NMNAT2 mRNA and protein levels were increased in the injured-side cortex at 6 hours and peaked 12 hours after TBI. Knocking down NMNAT2 with an injection of small interfering RNA in lateral ventricle significantly exacerbated neuronal degeneration and neurological deficits after TBI, which were accompanied by increased expression of BCL-2-associated X protein (Bax). Conclusion : NMNAT2 expression is increased and NMNAT2 exhibits neuroprotective activity in the early stages after TBI, and Bax signaling pathway may be involved in the process. Thus, NMNAT2 is likely to be an important target to prevent secondary damage following TBI.

• The Korean Journal of Nuclear Medicine Technology
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• v.16 no.1
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• pp.27-33
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• 2012

Purpose: Most of diagnosis in the pediatric hydronephrosis patients have been performed $^{99m}Tc$-DMSA renal scan. Then the region of interest (ROI) is set for comparative analysis of uptake ratio in left-right kidney after acquiring the image. But if the equipment set an automatic ROI, the ROI could include expanded renal pelvis due to hydronephrosis and the uptake ratio of left-right kidney will be incorrect result. Therefore this study compared both ROIs including expanded renal pelvis and excluding renal pelvis through experiment using normal kidney phantom and expanded renal pelvis phantom and suggested setting method of improved ROI. In addition, this study have been helped by readout doctor for investigate distinction radiopharmaceutical uptake between renal cortex and remained urine by expanded renal pelvis. Materials and Methods: The both of renal phantoms were filled with water and shacked with $^{99m}TcO_4$ 111 MBq. In order to describe the expanded renal pelvis, the five latex balloon were all filled with 10 mL water and each of balloon was mixed with $^{99m}TcO_4$ 18.5, 37, 55.5, 74, 92.5 MBq. And we made phantom with fixed $^{99m}TcO_4$activity of 37 MBq and mixed water 5, 10, 15, 20, 25 mL in each balloon. The left kidney was fixed its shape and the right kidney was modified like as hydronephrosis kidney by attached the latex balloons. And the acquiring counts were 2 million. After acquisition, we compared the image of ROI with Expanded renal pelvis and the image of ROI without renal pelvis for analyzing difference in the uptake ratio of left-right kidney and for reproducibility, set the ROI 5 times in the same images. Patients were injected $^{99m}Tc$-DMSA 1.5~1.9 MBq/kg and scanned 3 to 4 hours after injection. The each of 3 skillful radio technologists performed the comparing estimation by setting ROI. To determine statistical significance between two data, SPSS (ver. 17) Wilcoxon Signed Ranks Test was used. Results: As a result of renal phantom's experiment, we compared with average of counts Background (BKG) ratios in the setting of ROI including expanded renal pelvis and setting of excluding expanded renal pelvis. Therefore, they can obtain changed counts and changed ratios. Patient also can obtain same results. In addition, the radiopharmaceutical uptake in expanded renal pelvis was come out the remained urine that couldn't descend to ureter by the help of readout doctor. Conclusion: As above results, the case of setting ROI including expanded renal pelvis was more abnormally increasing uptake ratio than the case of setting ROI excluding expanded renal pelvis in analysis the uptake ratio in left-right kidney of hydronephrosis. Because of the work convenience and prompted analysis, the automatic ROI is generally used. But in case of the hydronephrosis study, we should set the manual ROI without expanded renal pelvis for an accurate observation of the uptake ratio of left-right kidney since the radiopharmaceutical uptake in expanded renal pelvis is the remained urine.

• Journal of Life Science
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• v.20 no.4
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• pp.496-502
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• 2010

The acidic saline animal model of pain has been suggested to mimic fibromyalgia (FM). Oligomeric proanthocyanidin complexes (OPC) from grape seeds are known to act as an antioxidant. We studied the effects of OPC on the pain threshold in the acidic saline animal model of pain. The left gastrocnemius muscle was injected with $100\;{\mu}l$ of saline at pH 4.0 under brief isoflurane anesthesia on days 0 and 5. Control rats (n=5) received identical injections of physiological saline (pH 7.2) on the same schedule. Rats (n=10) with acidic saline injection were separated into two study subgroups. After measurement of pre-drug pain thresholds, rats were injected intraperitoneally with either saline or OPC 300 mg/kg. Paw withdrawal thresholds to pressure were again measured 60 min after intraperitoneal injection. Nociceptive thresholds were measured with a Dynamic Plantar Aesthesiometer by applying an increasing pressure to right or left hind paw until the rat withdrew the paw. Compared to baseline (day 0), acid injections produced mechanical hyper-responsiveness on day 7 (pre-drug) in these rats [p<0.05]. A potent antihyperalgesic effect was observed when rats were injected intraperitoneally with OPC 300 mg/kg [injected paw, p=0.001; contralateral paw, p=0.002]. OPC treatment decreased the expression of acid sensing ion channel 3 in the brain motor cortex area on immunohistochemical staining when OPC 300 mg/kg was administered intraperitoneally in the animal model of FM pain [p<0.05]. Further research is required to determine the efficacy of OPC treatments in FM pain in humans.

• Toxicological Research
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• v.24 no.1
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• pp.51-58
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• 2008

The present study was designed to explore the immunotoxic effects of orally administered aluminum (AI) on pregnant rats (n = 60) and their growing fetuses and consequently on the animal wealth. The animals were randomly allocated into three equal groups of 20 rats each. The first group has no treatment and kept as a control (G1). The second and third groups of pregnant rats were treated orally with aluminum chloride at 345 mg/Kg b.wt. The second group (G2) received the tested compound from the $6^{th}$ day of gestation to the end of weaning, whereas the third group (G3) received the tested compound from the $15^{th}$h day of gestation to the end of weaning. Control and treated animals (dams and offspring) were immunized ip with (0.5 ml) 20% sheep red blood cell (SRBC) suspension seven days before the end of experiments. At the end of exposure, ten dams and ten offspring from each group were used for assessment of cell-mediated immunity and a similar number of animals were sacrificed for evaluating the humoral immune response and serum protein profile. Aluminum chloride exposure of dams ($G_2&G_3$) caused significant suppression of both cell mediated and humoral immune responses in the obtained offsprings compared to the control group ($G_1$) without any significant effect on the immune responses of these dams. Moreover, the serum total globulins, albumin/ globulin (A/G) ratio and gamma globulin fraction were significantly decreased in the treated dam's offsprings compared to the corresponding controls while the serum total protein and all serum protein fractions showed non significant difference between the control and treated dams and between the two treated dam groups themselves. There were no histopathological changes observed in thymus, spleen and liver of the control and treated dams. Thymus of treated dam's offsprings (G2) showed lymphoid depletion in both cortex and medulla. Their spleens showed lymphoid depletion in the white pulps and congestion with hemosiderosis in the red pulps. Liver of treated dam's offsprings showed dilation and congestion of its central vein with degenerative changes in the hepatocytes. These histopathological changes were more severe in G2 than in G3 offsprings. It can be concluded that gestational and/ or lactation exposure of pregnant dams to AI chloride caused suppression of both cellular and humoral immune responses of their offsprings.