• Archives of Pharmacal Research
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• 제27권4호
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• pp.407-414
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• 2004

The expression of CYP3A4 gene is induced by a variety of structurally unrelated xenobiotics including the antibiotic rifampicin, pregnenolone 16-carbonitrile (PCN), and endogenous hormones, that might mediate through steroid and xenobiotic receptor (SXR) system. The molecular mechanisms underlying regulation of CYP3A4 gene expression have not been understood. In order to gain the insight of the molecular mechanism of CYP3A4 gene expression, study has been undertaken to investigate if the histone deacetylation is involved in the regulation of CYP3A4 gene expression by proximal promoter in human hepatoma HepG2 cells. Also we have investigated to see if SXR is involved in the regulation of CYP3A4 proximal promoter activity in human hepatoma HepG2 cells. HepG2 cells were transfected with a plasmid PCYP3A4-Luc containing ${\~}1kb$ of the CYP3A4 proximal promoter region (-863 to +64 bp) in front of a reporter gene, luciferase, in the presence or absence of pSAP-SXR. In HepG2 cells, CYP3A4 inducers, such as rifampicin, PCN and RU486 showed minimal stimulation of CYP3A4 proximal promoter activity in the absence of SXR and histone deacetylase (HDAC) inhibitors. 4-Dimethylamino-H-[4-(2-hydroxycarbamoylvinyl)benzyl]benzamide (IN2001), a new class HDAC inhibitor significantly increased CYP3A4 proximal promoter activity over untreated control cells and rifampicin concomitant treatment with IN2001 increased further CYP3A4 proximal promoter activity that was stimulated by IN2001 The results of this study demon-strated that both HDAC inhibitors and SXR are essential to increase of CYP3A4 proximal promoter activity by CYP3A4 inducers such as PCN, rifampicin, and RU486. Especially SXR seems to be important for the dose dependent response of CYP3A4 inducing chemicals to stimulate CYP3A4 proximal promoter activity. Also this data suggested that HDAC inhibitors seemed to facilitate the CYP3A4 proximal promoter to be activated by chemicals.

• 사상체질의학회지
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• 제18권1호
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• pp.30-40
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• 2006

1. Objectives The present study purposed to examine the contents and the principles of music therapy according to Oriental medicine theories in order to prove that music therapy is not a new research area but its principle is found in the long tradition of Oriental medicine. 2. Methods We investigate the possibility of music therapy based on Oriental medicine theories and examine the meanings of music therapy from the viewpoint of Oriental medicine. 3. Conclusions and discussions (1) The principles of music therapy are the principle of homogeneity, catharsis and balance. (2) When one’s mind changes, there are naturally occurred sounds, which are called Oseong (五聲: the oriental five voices exhalation, laughing, singing, wailing and groaning), and the notes defined by arranging the Oseong according to the principle of Ohaeng (五行: the oriental five phases wood, fire, earth, metal, water) are Oheum (五音: the oriental five musical notes Gakeum, Chieum, Gungeum, Sangeum and Wooeum.). If Eum (musical notes) is classified into Ohaeng, it can be divided into Gakeum, Chieum, Gungeum, Sangeum and Wooeum. (3) Change of Sinji (神志: consciousness) induces change of Gigi (氣機: function of Gi), which can change the character of voices. Oseong controls the functions of Ojang (五臟: the oriental five viscera) by ruling one’s Jeongji (情志: emotion). It can reduce the damage of the viscera caused by excessive vent of emotion resulted from unconscious expression of Oseong - Hoseong (呼聲: exhalation), Soseong (笑聲: laughing), Gaseong (歌聲: singing), Gokseong (哭聲: wailing) and Sinseong (呻聲: groaning). (4) Yijeongseungjeong (以情勝情: Control emotion with emotion) therapies, which suppresses an emotion by stimulating another, include Noseungsabeop (怒勝思法: Control anxiety with anger), Heeseungbibeop (喜勝悲法: Control sorrow with joyfulness), (思勝恐法: Control fear with anxiety), Biseungnobeop (悲勝愁法: Control anger with sorrow) and Gongseungheebeop (恐勝喜法: Control joyfulness with fear). (5) Seongeum (聲音: voices and musical notes) can be applied to a stimulation method that not only harmonizes the rhythm of living organs but also controls the occurrence of diseases caused by mutual Pyeonseongpyeonsoi (偏盛偏衰: relative preponderance and weakness) through direct induction of the strength and weakness of Gi function of the oriental five viscera in a human body according to the individual character. Sounds preferred by the patient, the material of an instrument selected by the patient, the character of rhythm and music expressed by the patient and the sound or voice uttered frequently by the patient can be considered in diagnosis and treatments for the patient’s body and mind.

• IMMUNE NETWORK
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• 제7권1호
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• pp.39-47
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• 2007

Background: Stromal cell-derived factor (SDF)-1 is a potent chemoattractant for activated T cells into the inflamed Rheumatoid arthritis (RA) synovium. To determine the effect of macrophage migration inhibitory factor (MIF) on the production of SDF-1 in the inflamed RA synovium. Methods: The expression of SDF-1 and MIF in RA and Osteoarthritis (OA) synovium was examined by immunohistochemical staining. The SDF-1 was quantified by RT-PCR and ELISA after RA fibroblast like synoviocyte (FLS) were treated with MIF in the presence and absence of inhibitors of intracellular signal molecules. The synovial fluid (SF) and serum levels of MIF and SDF-1 in RA, OA and healthy control were measured by ELISA. Results: Expression of SDF-1 and MIF in synovium was higher in RA patients than in OA patients. The production of SDF-1 was enhanced in RA FLS by MIF stimulation. Such effect of MIF was blocked by the inhibitors of NF-${\kappa}B$. Concentrations of SDF-1 in the serum and SF were higher in RA patients than in OA patients and healthy control. SDF-1 and MIF was overexpressed in RA FLS, and MIF could up-regulate the production of SDF-1 in RA FLS via NF-${\kappa}B$-mediated pathways. Conclusion: These results suggest that an inhibition of interaction between MIF from T cells and SDF-1 of FLS may provide a new therapeutic approach in the treatment of RA.

• 생명과학회지
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• 제28권9호
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• pp.1100-1117
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• 2018

Ras superfamily에 속하는 monomeric small GTPase는 현재까지 170여 종이 알려져 있으며 이들은 세포 신호전달에 있어서 분자 스위치(molecular switch)로 작용하고 있다. Ras GTPase는 guanosine diphosphate (GDP)와 결합하여 불활성화 되거나 혹은 guanosine triphosphate (GTP)와 결합하여 활성화되는 guanosine nucleotide 결합단백질로서 세포내의 수많은 생리작용을 조절하고 있다. 즉, 쉬고 있던 불활성화 상태의 Ras-GDP는 외부 신호에 반응하여 활성화 된 guanine nucleotide exchange factor (GEF)에 의하여 활성형인 Ras-GTP상태로 전환되어 그 하류로 신호를 전달하는 효과기로 작용하게 된다. 신호전달을 마친 Ras-GTP는 다시 불활성형인 Ras-GDP로 전환되어야 하는데 Ras 자체의 GTPase 활성이 미약하여 RasGTPase activating protein (RasGAP)의 도움을 받아야만 한다. 이와 같이 Ras GTPase는 GEF와 GAP의 활성으로 세포 안의 스위치를 켜고 끄게 된다. 현재까지 알려진 인간 암(cancer)의 30% 이상이 돌연변이를 포함하는 Ras switch의 비정상적인 작동에 기인한다는 점이 밝혀져 있으므로 Ras GTPase의 구조와 생리적 기능에 대한 최근의 연구결과들을 요약하였다. 나아가 GTPase activating protein으로서의 기능을 상실한 RasGAP분자의 돌연변이는 세포 안의 Ras 스위치를 계속 켜 두는 상태인 Ras-GTP 상태를 유발함으로서 종국에는 암의 발생을 촉발하게 된다. 이에, 본고에서는 최근에 와서 tumor suppressor로서 알려지면서 암의 치료 표적단백질로 떠오르게 된 RasGAP의 인체생리학적 기능을 고찰하였다. 인간 게놈 안에는 RASA1, NF1, GAP1 family 및 SynGAP family 등에 속하는 14종의 RasGAP 분자들이 존재하는데 이들 GAP분자들의 이상과 인간 질병의 연관성에 대한 최근의 연구결과들에 대해 고찰하였다.

• 한국융합학회논문지
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• 제11권4호
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• pp.95-108
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• 2020

신종 코로나 바이러스(COVID-19)가 세계적으로 대유행하고 있다. 정부는 세계적인 전염병 확산에 대응할 수 있는 국가적 기술 역량 확보에 필요한 연구개발(R&D) 투자를 통해 향후 성장 동력을 확보하고 단기 경기 부양을 추진하고 있다. 따라서 코로나 바이러스에 대한 R&D 투자 및 연구현황을 종합적으로 파악하여 향후 R&D 기획의 방향성을 정립하기 위한 지식정보가 필요한 시점이다. 주요 해외 국가(미국, EU 등) R&D 과제를 기반으로 4개(세부 5개) R&D 영역을 도출하고, 국내 R&D 과제와의 비교분석을 통해 차별화된 2개 R&D 영역을 추가하였다. 제시된 6(세부 7개)개의 R&D 연구영역별 국내외 연구기관-연구과제명-과제규모-과제기간을 제시하였다. 동시에 학제 간 융합적 특징을 나타내는 R&D 과제를 제시하였다. 본 연구는 코로나 바이러스 관련 국내 경쟁 우위 영역과 차별화된 연구영역을 도출하여 현재 세계적으로 조명받고 있는 코로나 바이러스 검출 및 현장진단 역량의 우수성을 입증하고, 향후 집중 투자 영역을 제시하였다.

• 대한치과교정학회지
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• 제25권6호
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• pp.715-722
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• 1995

Orthodontic tooth movement in response to orthodontic force results from actions of osteoclasts and osteeoblasts in the cell level. Convincing evidence has now been provided to support the view that osteoclasts are derived from mononuclear cells that originate in the bone marrow or other hematopoietic organs and they migrate to the bones via vascular routes. Nitric oxide(NO), which accounts for the biological properties of endothelium-derived relaxing factor(EDRF), is the endogenous stimulator of soluble guanylate cylase. The discovery of the formation of nitric oxide(NO) from L-arginine in mammalian tissues and its biological roles has, in the last 7 years, thrown new light onto many areas of research. Data from experiments in vitro showed that N-metyl-L-arginine(L-NMA) and L-nitro-L- arginine(L-NAME) are competitive inhibitors of nitric oxide synthase. This study suggest that the multinucleated cells in our culture have characteristics of osteoclasts and that the potential bone cell activity of nitric oxide in vitro may be mediated in part by stimulation of marrow mononuclear cells to form osteoclast-like cells. Bone marrow cells were obtaineed from tibia of 19-days old chick embryo. After sacrifice, tibia was quickly dissected and the bone were then split to expose the medullary bone. The cells were attached for 4 hours and the nonadherent cells were collected. Marrow cells weere cultured in 96-well plate in medium 199. To examine the number of TRAP-positive multinucleated cells(MNCs), $10^{-8}\;M\;Vit=D_3$ and various concentration of L-NMA and L-NAME weere added at the beginning of cultures and with each medium change. After 7 days of culture. tartrate-resistant acid phosphatase(TRAP) staining was performed for microscopic evaluation. Cells haying more than three nuclei per cell were counted as MNCs. The obsrved results were as follows;1. 1,25-dihydroxyvitamine $D_3$ stimulated the osteoclast-like multinucleated cells in cultures of chick embryo bone marrow. 2. Nitric oxide synthase inhibitors(NOSI ; N-NMA, N-NAME) stimulated the osteoclast-like cells in cultures of chick embry bone marrow. 3. 1,25-dihydroxyvitamine$D_3$ and nitric oxide synthase inhibitors did not appear to have additive effect on the generation of TRAP-positive MNCs. These results suggest that nitric oxide synthase inhibitors may stimulate the osteoclast-like multinucleated cell formation and fusion in cultures of chick bone marrow.

• Journal of Periodontal and Implant Science
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• 제28권4호
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• pp.545-559
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• 1998

Magnoliae cortex has been used as a drug for treatment of fractures in Chinese medicine and safflower(Carthamus tinctorius $Linn{\acute{e}}$) has been traditionally used for treatment of blood stasis. The purpose of present study was to examine the biologic effects of magnoliae cortex extract and safflower extract mixture(MSM) on human periodontal ligament cells and fetal rat calvarial osteoblasts and on healing of rat calvarial defects. The ethanolic extracts of magnoliae cortex(MCE), safflower seed(SSE), Zea May L(ZML) were prepared as positive control group. MSM mixed to the ratios of 1 : 1, 1 : 2, 1 : 5 and 1 : 10 were used as test group. The effects of each agents on the growth and survival, ALPase activity, cell proliferation and tissue regenerative effect of each extracts was evaluated by histomorphometric measuring of newly formed bone on the 8 mm defect in rat calvaria after oral administration of 2 ratio groups(1 : 5 and 1 : 10) at 3 different doses (0.1, 0.25 and 0.5g/kg per day). MSM stimulated the growth and survival rate of osteoblasts and PDL cells more than any other agents. The growth and survival rate were increased as the proportion of safflower seed extract was increased. MCE, SSE, ZML stimulated the ALPase activity of osteoblast and PDL cell in comparison to the negative control group. But all groups of MSM regardless of ratio of safflower seed extract stimulated the ALPase activity than any other agent. The ALPase activity was also increased as the proportion of safflower seed extract was increased. Although MCE, SSE, ZML stimulated the proliferation of osteoblasts. 1 : 5 and 1 : 10 ratio MSM showed significant increase in stimulation of proliferation of osteoblasts. No agent significantly increased proliferation of PDL cells. Significant new bone formation were seen where 1 : 5 ratio, 0.5g/kg group and 1 : 10 ratio, 0.25, 0.5g/kg groups were used. These results show that magnoliae cortex extract and safflower seed extract mixture can potentially increase bone regeneration ability.

• 한국양식학회지
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• 제8권4호
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• pp.307-316
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• 1995

최근 비단가리비가 새로운 양식품종으로 관심이 높다. 자연에서의 치패는 절대 부족하므로 인공종묘 생산이 필수적이다. 1993년 7월부터 1994년 5월까지 거제군 장목면 실전리 지선과 통영해역에서 수집한 모패로 인공종묘 생산을 시도했다. 산란은 수온이 상승하는 3월부터 고수온기에 걸쳐 간헐적으로 일어났고 산란성기는 7월로 간주되었다 간출자극, 온도자극, 화학자극을 단독 또는 병행실시하여도 성숙상태만 좋으면 어느 경우에도 산란유발에는 어렵지 않았다. 그 중, serotonin 주사에 의한 화학자극에다 간출, 온도자극을 병행한 방법이 가장 효과가 있었다. 수정난의 수용밀도는 부화율에 많은 영향을 미쳤는데 정상적인 발생을 위 한 밀도는 1ml 당 $30\~40$개이었다. 부착기 유생의 평균각장은 $155{\mu}m$ 였으며, 수정에서 부착기유생까지는 수온 11.5\~13.0^{\circ}C$에서 27일이 소요되었다. 먹이생물은 Isochrysis galvana와 Chaetoceros calcitrans 이었다. 사육시의 유생의 적정밀도는 10 마리/ml이었다.

• 생물정신의학
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• 제8권1호
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• pp.20-36
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• 2001

우울증으로 고통받는 많은 환자들에서 보이는 다양항 양상과 다양한 경과를 자주 접하면서 분류를 어떻게 하여야 임상적으로 유용한가 의문을 가지게 된다. 이에 저자들은 우울증의 아형 평가의 필요성과 평가도구들을 문헌을 통하여 고찰하였다. 원래부터 이들이 이질적인 집단으로 구성되어 있는지, 하나의 유전적 소인이 있어 개인에 따라서 병의 진행 시기에 따라서 여러 우울증의 spectrum으로 표현되는 것인지 문제가 제기되어 왔지만, 현재로서는 분명히 알 수 없다. 저자들은 먼저 "우울증 스펙트럼" "양극성 우울과 단극성 우울이 공통의 하나의 유전적 인자를 가지는가" "양극성 스펙트럼 장애"등 강한 주장들이 있어 문헌 고찰을 통해서 알아보았다. 그리고, 최근 생물학적인 연구로부터 나온 세로토닌 관련 우울증 가설을 알아보았다. 이 우울증 가설(SeCA depression)은 조기 모성 분리 혹은 모성 박탈 같은 유년시절의 부정적 경험, 불안, 공격성, co-rtisol 증가, cortisol flattening, DST 양성, 스트레스 사건, CRF 상승, 5HIAA저하 등을 연결하여 우울증의 역동을 쉽게 설명하였고 생물-심리-사회적 접근을 가능하게끔 하는 우울증의 모델이다. 둘째로 고전적인 생물학적 지표 즉 DST, TRH 자극 검사, 및 뇨 MHPG 검사 결과에 따르는 우울증 아형을 구분하고 특징을 살펴보았고 이들의 역사적이고 임상적인 의미를 알아보았다. 그밖에 APOE epsilon 4 allele, 기질-성격이론(Temperament Character Inventory : TCI) 심박동 변이도(heart rate variability : HRV) 같은 요인들을 비롯하여 잘 알려진 증상이나 진단으로 분류된 아형들을 조사하여 임상적인 의미를 찾아보았다.

• 대한약리학회지
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• 제27권2호
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• pp.135-144
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• 1991

흰쥐 말초혈액에서 얻은 T 림프구를 아드레날린성 ${\beta}-$수용체 효현제 및 concanavalin A(Con-A)로 자극해 다음과 같은 결과를 얻었다. 자극이 없는 상태에서의 주 인산화 단백은 분자량 44kD, 등전점 6.8의 단백이었으며 효현제로 자극시키면 분자량 44kD, 등전점 6.3의 단백이 새로이 인산화되어 나타났다. 이 분자량 44kD, 등전점 6.3의 단백은 forskolin에 의해 역시 인산화되며 A-kinase 억제제인 H-8을 전처치하면 인산화의 억제가 나타났다. 또한 Con-A로 자극시키면 44 kD/pI 6.3 단백의 인산화가 증가되었으며 이 인산화의 증가는 CaM kinase 억제제인 W-7 전처치에 의해 억제되었다. H-7은 분자량 44 kD, 등전점 6.8 단백의 인산화를 감소 시켰다. 이상의 결과로 분자량 44 kD 등전점 6.3의 단백은 A-kinase와 CaM kinase 모두에 의해 인산화 되는 기질단백으로서 tryptic peptide map상에서 44 kD/pI 6.8 단백과 44 kD/pI 6.3 단백은 서로 다른 단백임을 알 수 있었다.