• 제목/요약/키워드: $LPA_{3}$

검색결과 98건 처리시간 0.028초

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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    • 제45권2호
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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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    • 제47권3호
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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.

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

  • 전중성;조희제;김선근;김기문
    • 한국항해항만학회지
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    • 제27권2호
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    • pp.209-215
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    • 2003
  • 본 논문은 IMT-2000 기지국용 15 Watt Feedforward 선형전력증폭기(Linear Power Amplifier; LPA)의 구현을 위한 에러증폭기를 설계 및 제작하여, 그 성능을 평가하였다. 에러증폭기는 상호 변조 왜곡 신호(Intermodulation Distortion: IMD)만을 검출하기 위한 빼기회로, RF 신호의 세기 및 위상을 제어하기 위한 가변 감쇠기, 가변 위상변환기, 그리고 신호의 증폭을 위한 저전력증폭기, 대전력증폭기로 구성되었다. 이들 구성요소는 RO4350 기판 위에 구현되어, 틴 도금한 알루미늄 기구물 안에 바이어스 회로와 함께 집적하였다. 제작시 RF 회로부의 바이어스 회로에 전원을 공급하기 위하여 내벽에 관통형 커패시터를 삽입하여 DC 전원에 의한 스퓨리어스 성분이 제거되도록 하였다. 제작된 에러증폭기는 45 dB 이상의 이득, $\pm$ 0.66 dB의 이득평탄도, -15 dB 이하의 입력반사 손실 특성을 나타내었다. 또한 성능을 평가하기 위해 Feedforward 방식의 LPA에 적용한 결과 주증폭기의 IM3 성분이 34 dBc에서 61 dBc,개선되었다. 이때 오차루프의 상쇄지수는 약 27 dB, 최종 출력 전력은 15 W로 나타났다.

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

  • 최흥재;정용채;김철동
    • 한국전자파학회논문지
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    • 제17권10호
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    • pp.959-966
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    • 2006
  • 본 논문은 다이플렉서를 이용하여 디지털 셀룰라 대역($f_o$=880 MHz)과 IMT-2000 대역($f_o$=2,140 MHz) 기지국에서 동시에 사용 가능한 이중 대역 전치 왜곡 선형 전력 증폭기(Predistortion Linear Power Amplifier: PD LPA)의 설계 방법을 제시하였다. 입 출력단에 사용된 다이플렉서는 결함 접지 구조(Defected Ground Structure: DGS)를 이용한 저역 통과 여파기와 높은 Q값을 갖는 캐패시터와 마이크로 스트립 스터브를 이용한 고역 통과 여파기로 이루어져 있다. 입출력 반사 계수 특성을 좋게 하기 위하여 3 dB 하이브리드 결합기를 이용한 반사형 타입의 전치 왜곡 선형화기를 설계하였다. IS-95 CDMA IFA 신호와 WCDMA IFA 신호를 이용하여 각 대역에서 제작된 이중 대역 전치 왜곡 선형 전력 증폭기의 인접 채널 누설비(Adjacent Channel Leakage Ratio: ACLR) 개선 정도를 측정한 결과 880 MHz 대역에서 약 10 dB, 2,140 MHz 대역에서 약 9.36 dB 개선되었다.

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

  • 최종범
    • Journal of Chest Surgery
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    • 제21권6호
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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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    • 제23권8호
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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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    • 제42권2호
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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.

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

  • 성미영;장영은;서병태
    • 한국보육지원학회지
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    • 제12권6호
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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.

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

  • 강우석;이희정
    • 교육시설 논문지
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    • 제26권5호
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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.

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

  • 박서영;홍송이
    • 한국노년학
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    • 제37권2호
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    • pp.349-368
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    • 2017
  • 본 연구는 우리나라 은퇴 베이비부머의 소비패턴을 실증적으로 탐색하고, 소비패턴이 우울에 미치는 영향을 검증하는 데 목적을 두고 있다. 이를 위해 국민노후보장패널 5차 자료를 활용하여 은퇴 베이비부머 420명을 대상으로 잠재프로파일분석과 다중회귀분석을 실시하였다. 은퇴 베이비부머의 소비패턴을 분석한 결과, 기초생활중심형(26.9%), 균형소비생활형(29.3%), 사회생활중심형(18.3%), 여가생활중심형(18.5%), 교육비중심형(7.0%)의 5가지 유형이 실증적으로 구조화되었다. 그리고 우울과 관련된 인구사회적 요인, 건강상태, 가족관계, 사회관계, 경제상태를 통제한 상태에서 소비패턴과 우울의 관계를 분석한 결과, 소비패턴과 우울 사이의 유의미한 상관관계가 증명되었다. 구체적으로 교육비중심형 소비패턴보다 기초생활중심형 소비패턴의 우울수준이 유의하게 낮았다. 또한 교육수준이 높을수록, 배우자가 없는 경우, 주관적 건강상태가 나쁠수록, 신체기능에 제한이 있는 경우, 장애진단을 받은 경우, 자녀의 수가 적을수록, 여가활동에 만족하지 않을수록, 주관적 경제상태가 부정적일수록 우울수준이 높은 것으로 나타났다. 본 연구결과는 베이비부머를 표적집단으로 한 사회복지정책과 서비스 기획 실효성을 제고함과 동시에 은퇴 후 바람직한 소비패턴을 유지할 수 있는 은퇴 전 소비교육의 필요성 및 사례관리 현장에서의 노후 소비관리 프로그램의 필요성을 제언한다.