• Title/Summary/Keyword: LPA

검색결과 159건 처리시간 0.038초

Gintonin regulates inflammation in human IL-1β-stimulated fibroblast-like synoviocytes and carrageenan/kaolin-induced arthritis in rats through LPAR2

  • Kim, Mijin;Sur, Bongjun;Villa, Thea;Yun, Jaesuk;Nah, Seung Yeol;Oh, Seikwan
    • Journal of Ginseng Research
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    • 제45권5호
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    • pp.575-582
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    • 2021
  • Background: In ginseng, there exists a glycolipoprotein complex with a special form of lipid LPAs called Gintonin. The purpose of this study is to show that Gintonin has a therapeutic effect on rheumatoid arthritis through LPA2 receptors. Methods: Fibroblast-like synoviocytes (FLS) were treated with Gintonin and stimulated with interleukin (IL)-1β. The antioxidant effect of Gintonin was measured using MitoSOX and H2DCFDA experiments. The anti-arthritic efficacy of Gintonin was examined by analyzing the expression levels of inflammatory mediators, phosphorylation of mitogen-activated protein kinase (MAPK) pathways, and translocation of nuclear factor kappa B (NF-κB)/p65 into the nucleus through western blot. Next, after treatment with LPAR2 antagonist, western blot analysis was performed to measure inflammatory mediator expression levels, and NF-κB signaling pathway. Carrageenan/kaolin-induced arthritis rat model was used. Rats were orally administered with Gintonin (25, 50, and 100 mg/kg) every day for 6 days. The knee joint thickness, squeaking score, and weight distribution ratio (WDR) were measured as the behavioral parameters. After sacrifice, H&E staining was performed for histological analysis. Results: Gintonin significantly inhibited the expression of iNOS, TNF-α, IL-6 and COX-2. Gintonin prevented NF-κB/p65 from moving into the nucleus through the JNK and ERK MAPK phosphorylation in FLS cells. However, pretreatment with an LPA2 antagonist significantly reversed these effects of Gintonin. In the arthritis rat model, Gintonin suppressed all parameters that were measured. Conclusion: This study suggests that LPA2 receptor plays a key role in mediating the anti-arthritic effects of Gintonin by modulating inflammatory mediators, the MAPK and NF-κB signaling pathways.

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.

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.

초등학교 교사의 학교도서관 역할 인식유형이 이용행태에 미치는 영향에 관한 연구 (A Study on the Impact of Elementary School Teachers' Perceptions of the School Library Roles on Their Library Use Behaviors)

  • 이승연;김기영
    • 정보관리학회지
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    • 제40권4호
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    • pp.375-401
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    • 2023
  • 학교도서관은 학생들에게 미래의 불확실성에 대응할 수 있는 능력을 기를 수 있는 장소로, 다양한 정보를 활용하여 기본 역량과 변화 대응력을 키울 수 있는 곳이다. 학교도서관의 활용은 교사의 지도가 필수적이므로 교사의 인식은 매우 중요하다. 그러나 대부분의 연구는 교사의 인식을 외부환경으로 간주하여 그 중요성을 계량적인 척도로 측정하는 데 초점을 맞추고 있다. 본 연구에서는 초등학교 교사들의 학교도서관 인식을 구체적으로 알아보고자, 사람 중심적인 접근 방법인 잠재프로파일 분석기법(Latent Profile Analysis, 이하 LPA)을 사용하여 기존 연구에서 검토하기 어려웠던 교사의 학교도서관의 역할과 중요성에 대한 복합적인 인식과 그 인식의 대표적인 유형을 확인하였다. 이를 토대로 교사의 인식유형에 따라 학교도서관의 운영과 활성화 방안을 맞춤형으로 제안하였다.

Atypical formations of gintonin lysophosphatidic acids as new materials and their beneficial effects on degenerative diseases

  • Ji-Hun Kim;Ra Mi Lee;Hyo-Bin Oh;Tae-Young Kim;Hyewhon Rhim;Yoon Kyung Choi;Jong-Hoon Kim;Seikwan Oh;Do-Geun Kim;Ik-Hyun Cho;Seung-Yeol Nah
    • Journal of Ginseng Research
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    • 제48권1호
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    • pp.1-11
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    • 2024
  • Fresh ginseng is prone to spoilage due to its high moisture content. For long-term storage, most fresh ginsengs are dried to white ginseng (WG) or steamed for hours at high temperature/pressure and dried to form Korean Red ginseng (KRG). They are further processed for ginseng products when subjected to hot water extraction/concentration under pressure. These WG or KRG preparation processes affect ginsenoside compositions and also other ginseng components, probably during treatments like steaming and drying, to form diverse bioactive phospholipids. It is known that ginseng contains high amounts of gintonin lysophosphatidic acids (LPAs). LPAs are simple lipid-derived growth factors in animals and humans and act as exogenous ligands of six GTP-binding-protein coupled LPA receptor subtypes. LPAs play diverse roles ranging from brain development to hair growth in animals and humans. LPA-mediated signaling pathways involve various GTP-binding proteins to regulate downstream pathways like [Ca2+]i transient induction. Recent studies have shown that gintonin exhibits anti-Alzheimer's disease and antiarthritis effects in vitro and in vivo mediated by gintonin LPAs, the active ingredients of gintonin, a ginseng-derived neurotrophin. However, little is known about how gintonin LPAs are formed in high amounts in ginseng compared to other herbs. This review introduces atypical or non-enzymatic pathways under the conversion of ginseng phospholipids into gintonin LPAs during steaming and extraction/concentration processes, which exert beneficial effects against degenerative diseases, including Alzheimer's disease and arthritis in animals and humans via LPA receptors.

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.

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.

지역 거주 노인의 활동 체력과 신체 활동수준의 관련성 (Effects of physical activity level on functional fitness in community-residing older adults)

  • 신소희;김용안;김현수
    • 한국융합학회논문지
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    • 제13권4호
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    • pp.625-634
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    • 2022
  • 이 연구의 목적은 지역에 거주하는 65세 이상 노인의 신체 활동(physical activity; PA) 수준과 활동 체력(functional fitness; FF) 변인 사이의 관계를 조사하는 것이었다. 피검자(남성:1,645명; 여성:2,394명)의 PA 수준은 설문지를 이용하여 조사하였고, FF는 상·하지 근력, 민첩성 및 동적 평형성, 유연성, 유산소성 능력, 협응력, 그리고 신체 구성 등 체력 영역을 대표하는 6항목으로 측정, 평가하였다. 피검자는 신체 활동 권장기준에 따라 권장량보다 낮은 그룹(low physical activity; LPA)과 권장량 기준을 충족하는 그룹(PA)으로 나누었고, PA 그룹은 다시 강도 수준에 따라 중강도 그룹(MIPA)과 고강도 그룹(HIPA)으로 분류하였다. 권장량 수준을 충족하는 피검자는 48%였고, 이들은 모든 항목에서 LPA보다 성적이 높았다(p<.001). HIPA 그룹은 MIPA 그룹보다 민첩성 및 동적 평형성, 협응력, 그리고 하지 근력(여성)이 유의하게 높았다(p<.001). 결론적으로 지역에 거주하고 있는 노인이 활동 체력을 유지하고 개선하기 위해서는 건강을 위해 권장하고 있는 신체 활동량을 충족시켜야 하며, 특히 낙상 관련 체력을 개선하기 위해서는 강도가 높은 신체 활동을 할 필요가 있다.

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.