• Title/Summary/Keyword: $LPA_{3}$

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Gintonin facilitates brain delivery of donepezil, a therapeutic drug for Alzheimer disease, through lysophosphatidic acid 1/3 and vascular endothelial growth factor receptors

  • Choi, Sun-Hye;Lee, Na-Eun;Cho, Hee-Jung;Lee, Ra Mi;Rhim, Hyewhon;Kim, Hyoung-Chun;Han, Mun;Lee, Eun-Hee;Park, Juyoung;Kim, Jeong Nam;Kim, Byung Joo;Nah, Seung-Yeol
    • Journal of Ginseng Research
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    • v.45 no.2
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    • pp.264-272
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    • 2021
  • Background: Gintonin is a ginseng-derived exogenous G-protein-coupled lysophosphatidic acid (LPA) receptor ligand, which exhibits in vitro and in vivo functions against Alzheimer disease (AD) through lysophosphatidic acid 1/3 receptors. A recent study demonstrated that systemic treatment with gintonin enhances paracellular permeability of the blood-brain barrier (BBB) through the LPA1/3 receptor. However, little is known about whether gintonin can enhance brain delivery of donepezil (DPZ) (Aricept), which is a representative cognition-improving drug used in AD clinics. In the present study, we examined whether systemic administration of gintonin can stimulate brain delivery of DPZ. Methods: We administered gintonin and DPZ alone or coadministered gintonin with DPZ intravenously or orally to rats. Then we collected the cerebral spinal fluid (CSF) and serum and determined the DPZ concentration through liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Results: Intravenous, but not oral, coadministration of gintonin with DPZ increased the CSF concentration of DPZ in a concentration- and time-dependent manner. Gintonin-mediated enhancement of brain delivery of DPZ was blocked by Ki16425, a LPA1/3 receptor antagonist. Coadministration of vascular endothelial growth factor (VEGF) + gintonin with DPZ similarly increased CSF DPZ concentration. However, gintonin-mediated enhancement of brain delivery of DPZ was blocked by axitinip, a VEGF receptor antagonist. Mannitol, a BBB disrupting agent that increases the BBB permeability, enhanced gintonin-mediated enhancement of brain delivery of DPZ. Conclusions: We found that intravenous, but not oral, coadministration of gintonin facilitates brain delivery of DPZ from plasma via LPA1/3 and VEGF receptors. Gintonin is a potential candidate as a ginseng-derived novel agent for the brain delivery of DPZ for treatment of patients with AD.

Gintonin, a Panax ginseng-derived LPA receptor ligand, attenuates kainic acid-induced seizures and neuronal cell death in the hippocampus via anti-inflammatory and anti-oxidant activities

  • Jong Hee Choi;Tae Woo Kwon;Hyo Sung Jo;Yujeong Ha;Ik-Hyun Cho
    • Journal of Ginseng Research
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    • v.47 no.3
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    • pp.390-399
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    • 2023
  • Background: Gintonin (GT), a Panax ginseng-derived lysophosphatidic acid receptor (LPAR) ligand, has positive effects in cultured or animal models for Parkinson's disease, Huntington's disease, and so on. However, the potential therapeutic value of GT in treating epilepsy has not yet been reported. Methods: Effects of GT on epileptic seizure (seizure) in kainic acid [KA, 55mg/kg, intraperitoneal (i.p.)]-induced model of mice, excitotoxic (hippocampal) cell death in KA [0.2 ㎍, intracerebroventricular (i.c.v.)]-induced model of mice, and levels of proinflammatory mediators in lipopolysaccharide (LPS)-induced BV2 cells were investigated. Results: An i.p. injection of KA into mice produced typical seizure. However, it was significantly alleviated by oral administration of GT in a dose-dependent manner. An i.c.v. injection of KA produced typical hippocampal cell death, whereas it was significantly ameliorated by administration of GT, which was related to reduced levels of neuroglial (microglia and astrocyte) activation and proinflammatory cytokines/enzymes expression as well as increased level of the Nrf2-antioxidant response via the upregulation of LPAR 1/3 in the hippocampus. However, these positive effects of GT were neutralized by an i.p. injection of Ki16425, an antagonist of LPA1-3. GT also reduced protein expression level of inducible nitric-oxide synthase, a representative proinflammatory enzyme, in LPS-induced BV2 cells. Treatment with conditioned medium clearly reduced cultured HT-22 cell death. Conclusion: Taken together, these results suggest that GT may suppress KA-induced seizures and excitotoxic events in the hippocampus through its anti-inflammatory and antioxidant activities by activating LPA signaling. Thus, GT has a therapeutic potential to treat epilepsy.

A Study on Implementation and Performance Evaluation of Error Amplifier for the Feedforward Linear Power Amplifier (Feedforward 선형 전력증폭기를 위한 에러증폭기의 구현 및 성능평가에 관한 연구)

  • Jeon, Joong-Sung;Cho, Hee-Jea;Kim, Seon-Keun;Kim, Ki-Moon
    • Journal of Navigation and Port Research
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    • v.27 no.2
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    • pp.209-215
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    • 2003
  • In this paper. We tested and fabricated the error amplifier for the 15 Watt linear power amplifier for the IMT-2000 baseband station. The error amplifier was comprised of subtractor for detecting intermodulation distortion, variable attenuator for control amplitude, variable phase shifter for control phase, low power amplifier and high power amplifier. This component was designed on the RO4350 substrate and integrated the aluminum case with active biasing circuit. For suppression of spurious, the through capacitance was used. The characteristics of error amplifier measured up to 45 dB gain, $\pm$0.66 dB gain flatness and -15 dB input return loss. Results of application to the 15 Watt feedforward Linear Power Amplifier, the error amplifier improved with 27 dB cancellation from 34 dBc to 61 dBc IM$_3$.

Dual-band Predistortion Linear Power Amplifier for Base-station Application (기지국용 이중 대역 전치 왜곡 선형 전력 증폭기)

  • Choi, Heung-Jae;Jeong, Yong-Chae;Kim, Chul-Dong
    • The Journal of Korean Institute of Electromagnetic Engineering and Science
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    • v.17 no.10 s.113
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    • pp.959-966
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    • 2006
  • This paper proposes a new concept about dual band predistortion linear power amplifier(PD LPA) using diplexer for digital cellular ($f_o$=880 MHz) and IMT-2000($f_o$=2,140 MHz) base stations. The diplexer is composed of low pass filter having defected ground structure(BGS) microstrip line and high pass filter having high-Q lumped capacitors and distributed elements. The proposed predistorter adopts a reflection type intermodulation signal generator with 3 dB hybrid coupler for good reflection characteristic. for a forward link one carrier CDMA IS-95A 1FA and WCDMA 1FA signal, the proposed dual band PD LPA shows the adjacent channel leakage ratio(ACLR) improvement about 10 dB and 9.36 dB for digital cellular and IMT-2000 band, respectively.

Effect of Diltiazem Cardioplegia on the Myocardial Protection and Functional Recovery of the Isolated Perfused Rat Heart (적출된 작업성 쥐심장에서 Diltiazem 심정지액이 심근보호 및 심근기능 회복에 미치는 영향)

  • 최종범
    • Journal of Chest Surgery
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    • v.21 no.6
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    • pp.970-978
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    • 1988
  • There is tendency of increasing number and decreasing age of patients who are indicated for Rastelli operation for their cyanotic congenital heart disease. So there is the need to find the criterion which saves the patients from early postoperative hemodynamic disturbances. We reviewed the 26 patients who had been performed Rastelli operation at Seoul national University Hospital from January 1981 to June 1988. mean age of the patients was 7.8*3.4 years[range 2.5-15years], mean body surface area[BSA] 0.79*0.25m2[range 0.49-1.51m2] and mean hematocrit 57.95*12%[range 48-80%]. We divided these patients into survived group and died group before postoperative 72 hours, and analyzed preoperative arterial oxygen saturation[SaO2], the ratio of diameter of right pulmonary artery to ascending aorta[RPA/AA], the ratio of both right and left pulmonary artery diameter to descending thoracic aorta[RPA+LPA/DTA], pulmonary artery index[PA index], cardiopulmonary bypass time, aorta cross-clamping time, postoperative perfusion state and total amount of dopamine infused postoperatively. The results showed that RPA+LPA/DTA and PA index were statistically significant factors to influence early postoperative cardiac death rate[P< 0.05]. Especially there were good linear correlations between PA index[X] and peripheral perfusion index[Y][Y= - 1.15+0.02 X, r=0.86, P<0.01]and between PA index[X] and total amount of dopamine infused before postoperative 72 hours[mg/kg, Y][Y=61.94 - 0.15 X, r=-0.80, P < 0.01]. Also there were tendencies that the higher RPA+LPA/DTA[Y], the better peripheral perfusion [X] and the lower need of dopamine[X], but no statistical significance.[Y=0.78+1.60 X, r =0. 49, P >0.05] And the discriminate analysis showed that patients with PA index over 221 mm2/BSA could undergo correction with 25 per cent of error rate. In conclusion, early postoperative hemodynamic states could be predicted by preoperatively measured PA index, and which can be used as a criterion for Rastelli operation performed on cyanotic congenital heart disease.

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Quantitative Analysis of Lysophosphatidic Acid in Human Plasma by Tandem Mass Spectrometry

  • Kim, Ho-Hyun;Yoon, Hye-Ran;Pyo, Dong-Jin
    • Bulletin of the Korean Chemical Society
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    • v.23 no.8
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    • pp.1139-1143
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    • 2002
  • Analysis of lysophosphatidic acids (LPAs) is of clinical importance as they can serve a potential marker for ovarian and other gynecological cancers and obesity. It is critically important to develop a highly sensitive and specific method for the early detection of gynecological cancers to improve the overall outcome of this disease. We have established a novel quantification method of LPAs in human plasma by negative ionization tandem mass spectrometry (MS-MS) using multiple reaction monitoring (MRM) mode without the conventional TLC step. Protein-bound lipids, LPAs in plasma were extracted with methanol : chloroform (2:1) containing LPA C14:0 as an internal standard under acidic condition. Following back extraction with chloroform and water, the centrifuged lower phase was evaporated and reconstituted in methanol. The reconstituted solution was directly injected into electrospray source of MS/MS. For MRM mode, Q1 ions selected were m/z 409, 433, 435, 437 and 457 which corresponds to molecular mass [M-H]- of C16:0, C18:2, C18:1, C18:0 and C20:4 LPA, respectively. Q2 ions selected for MRM were m/z 79, phosphoryl product. Using MS/MS with MRM mode, all the species of LPAs were completely separated from plasma matrix without severe interferences. This method allowed simultaneous detection and quantification of different species of LPAs in a plasma over a linear dynamic range of 0.01-25 ㎛olL-1 . The detection limit of the method was 0.3 pmol/mL, with a correlation coefficient of 0.9983 in most LPAs analyzed. When applied to the plasmas of normal and gynecological cancer patients, this new method differentiated two different groups by way of total LPA level.

HeLa E-Box Binding Protein, HEB, Inhibits Promoter Activity of the Lysophosphatidic Acid Receptor Gene Lpar1 in Neocortical Neuroblast Cells

  • Kim, Nam-Ho;Sadra, Ali;Park, Hee-Young;Oh, Sung-Min;Chun, Jerold;Yoon, Jeong Kyo;Huh, Sung-Oh
    • Molecules and Cells
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    • v.42 no.2
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    • pp.123-134
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    • 2019
  • Lysophosphatidic acid (LPA) is an endogenous lysophospholipid with signaling properties outside of the cell and it signals through specific G protein-coupled receptors, known as $LPA_{1-6}$. For one of its receptors, $LPA_1$ (gene name Lpar1), details on the cis-acting elements for transcriptional control have not been defined. Using 5'RACE analysis, we report the identification of an alternative transcription start site of mouse Lpar1 and characterize approximately 3,500 bp of non-coding flanking sequence 5' of mouse Lpar1 gene for promoter activity. Transient transfection of cells derived from mouse neocortical neuroblasts with constructs from the 5' regions of mouse Lpar1 gene revealed the region between -248 to +225 serving as the basal promoter for Lpar1. This region also lacks a TATA box. For the region between -761 to -248, a negative regulatory element affected the basal expression of Lpar1. This region has three E-box sequences and mutagenesis of these E-boxes, followed by transient expression, demonstrated that two of the E-boxes act as negative modulators of Lpar1. One of these E-box sequences bound the HeLa E-box binding protein (HEB), and modulation of HEB levels in the transfected cells regulated the transcription of the reporter gene. Based on our data, we propose that HEB may be required for a proper regulation of Lpar1 expression in the embryonic neocortical neuroblast cells and to affect its function in both normal brain development and disease settings.

The Roles of Study Habits and Emotional-behavioral Problems in Predicting School Adjustment Classification Among 3rdGraders (초등학교 3학년 아동의 학교적응 유형을 예측하는 학습습관과 정서행동문제의 역할)

  • Sung, Miyoung;Chang, Young Eun;Seo, Byungtae
    • Korean Journal of Childcare and Education
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    • v.12 no.6
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    • pp.79-102
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    • 2016
  • The purpose of this study was to identify school adjustment groups by applying a Latent Profile Analysis(LPA) and to investigate the effects of children's emotional problems and study habits on determining the membership of these groups. LPA and multiple logistic regression were conducted using the data of 2,200 third-graders from the Korean Children and Youth Panel Study. The results are listed as follows. First, four school adjustment groups were identified: adjustment, approach to adjustment, maladjustment risk, and maladjustment group. Second, accomplishment value and mastery goal orientation were relatively strong predictors of membership of the school adjustment groups. Time management was also a significant variable that predicted the membership of maladjustment or the maladjustment-risk group. Third, attention problems and depression were the most consistent predictors of membership of maladjustment or the maladjustment-risk group. Physical symptoms and social withdrawal were also significant. Based on the results, implications for intervention to promote early school adjustment were discussed.

Regional Profiling by Considering Educational Facilities - Centered on Gwangjin-gu, Seoul - (교육 시설 생활인프라 특성을 고려한 지역 프로파일링 연구 - 서울시 광진구 중심으로 -)

  • Kang, Woo-Seok;Lee, Hee-Chung
    • Journal of the Korean Institute of Educational Facilities
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    • v.26 no.5
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    • pp.3-10
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    • 2019
  • This study has a purpose to profile local sectors into meaningful groups by using facilities rates of Social Overhead Capital(SOC) for daily life. Comparing SOC for daily life among the meaningful groups, the profiling and comparison results bring the comprehensive understanding about the educational facilities in local sectors. For the research purpose, this study utilized Latent Profile Analysis(LPA) by using variables such as population, road information, SOC for daily life, usage of land, possession of land, and appraised value of land from the 2018 Geographic Information System(GIS) dataset of Gwangjin-gu, where is one of the administrative district of Seoul City. Results showed that there are four latent groups of sectors among 904 local sectors(100 squared-meters sector per each) in Gwangjin-gu. By comparing the four latent groups by using LPA, the results diagnose each sector's status and help to improve the policy about educational facilities. Specifically, by using dataset for SOC of daily life, there are four groups of local sectors and each group has different features. Based on the different features of local sector groups, there can be improved management of educational facilities matching with each group's features.

The Effect of Baby-boomer Retirees' Consumption Patterns on Depression in Later Life (은퇴 베이비부머의 소비패턴과 우울에 관한 연구)

  • Park, Seo-Young;Hong, Song-Iee
    • 한국노년학
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    • v.37 no.2
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    • pp.349-368
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    • 2017
  • The purpose of this study is to empirically structure the patterns of baby boomer retirees'consumption and their effects on depression in later life. Using the 5th wave of Korea Retirement and Income Study(KReIS) in 2013, of baby boomers born in 1955 to 1963, we analyzed those who were completely retired(n=420). The Latent Profile Analysis(LPA) classified the empirical patterns of consumption and then a multiple regression analyzed the effect of consumption patterns on depression among these baby boomer retirees. The LPA results showed that the consumption patterns consist of five groups: (1) Basic life-oriented class(26.9%), (2) Balanced consumption class(29.3%), (3) Social life-oriented class(18.3%), (4) Leisure-oriented class(18.5%), and (5) Education-oriented class(7.0%). Baby boomer retirees' depression was associated with their consumption patterns. Specifically, the basic life-oriented class showed significantly lower depression than the education-oriented class. Other correlates such as higher education, having no spouse, lower subjective health, greater limitations in physical functions, having a diagnosed disability, having fewer children, higher dissatisfaction with leisure activities, and lower self-perceived economic status were associated with higher levels of depression in this study. These findings suggest meaningful implications for gerontological policy and practice for baby boomer retirees in Korea. In light of vulnerable retirement preparation, social services specialized for baby boomers should consider financial education for revamping consumption scale beyond asset management and long-term case management of pre and post retirement cases.