• The Korean Journal of Physiology and Pharmacology
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• 제28권2호
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• pp.107-112
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• 2024

27-Hydroxycholesterol (27OHChol), a prominent cholesterol metabolite present in the bloodstream and peripheral tissues, is a kind of immune oxysterol that elicits immune response. Recent research indicates the involvement of 27OHChol in metabolic inflammation (meta-inflammation) characterized by chronic responses associated with metabolic irregularities. 27OHChol activates monocytic cells such that they secrete pro-inflammatory cytokines and chemokines, and increase the expression of cell surface molecules such as pattern-recognition receptors that play key roles in immune cell-cell communication and sensing metabolism-associated danger signals. Levels of 27OHChol increase when cholesterol metabolism is disrupted, and the resulting inflammatory responses can contribute to the development and complications of metabolic syndrome, including obesity, insulin resistance, and cardiovascular diseases. Since 27OHChol can induce chronic immune response by activating monocyte-macrophage lineage cells that play a crucial role in meta-inflammation, it is essential to understand the 27OHChol-induced inflammatory responses to unravel the roles and mechanisms of action of this cholesterol metabolite in chronic metabolic disorders.

• 생명과학회지
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• 제19권5호
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• pp.593-597
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• 2009

자궁은 임신에 필수불가결한 기관으로, 에스트로겐(E2)과 프로게스테론(P4)은 태아와 자궁 사이의 상호 신호전달을 적절하게 조절하여, 임신을 확립하게 하는 필수적 요소이다. 임신 초기 E2는 배아의 안정적인 착상을 위하여 자궁의 성장을 촉진하는 역할을 담당한다. 이 시기 자궁에서 분비되는 인슐린유사 성장인자-I(IGF-I)와 E2/P4 간의 상호 신호전달이 임신 확립에 있어서 매우 중요한 역할을 한다. E2는 에스트로겐 수용체(ER)에 의해 그 작용이 결정되어지는데, 임신 돼지 자궁에서는 ER-${\alpha}$만이 발현됨을 증명하였다. 자궁에서 ER-${\alpha}$의 발현은 임신 중기나 말기보다 임신 초기 단계에서 높게 발현됨이 관찰되었다. 이는 배아에서 분비되는 E2가 ER-${\alpha}$의 발현을 증가시키는 역할을 함을 보여주는 결과이다. IGF-I이 E2 표적 유전자임을 증명하기 위하여 난소를 제거한 쥐에 E2/P4를 처리한 후 IGF-I의 발현을 측정한 결과, E2를 처리한 샘플에서는 IGF-I의 발현이 크게 증가하였으나, P4를 처리한 샘플에서는 큰 영향을 받지 않는 것으로 나타났다. 이 결과는 E2가 자궁에서 IGF-I의 발현을 증가시키는 역할을 수행함을 직접적으로 증명하였다. 임신한 돼지의 자궁에서 임신 시기별로 IGF-I 유전자의 발현을 조사한 결과 임신 초기에 가장 높은 발현을 보였고, 이 양상은 ER-${\alpha}$의 발현 형태와 아주 유사한 패턴을 나타내었다. 이는 임신 자궁에서 ER-${\alpha}$와 IGF-I의 발현이 상호 연관되어 있으며 ER-${\alpha}$와 IGF-I은 E2에 의해서 조절되어지는 유전자이며, 임신초기 배아에서 분비되는 E2가 자궁에서 ER-${\alpha}$의 발현을 증진시키고, 나아가서 이 ER-${\alpha}$가 자궁에서 IGF-I 유전자의 발현을 증가시키는 역할을 함을 보여주는 결과이다.

• 동의생리병리학회지
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• 제24권3호
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• pp.504-511
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• 2010

Diabetes is a disease that contains a high concentration of glucose in blood and due to defects in either insulin secretion or insulin action. Although the distinctive causes and factors of diabetes have not been clarified, the genetic factors are suggested as a main susceptibility until now. SNP (Single Nucleotide Polymorphism), as the most common genetic variation, has an influence on personal susceptibility for diseases. A nonsynonymous SNP, which changes the amino acid of the protein and its function, is especially important. Therefore, this study hypothesized that there are associations between specific SNPs of the targeted genes. Transcription factor 7-like 2 (TCF7L2) and fat mass and obesity associated (FTO) genes were selected as target genes from the results of genome-wide association and other related research studies. Second, four nonsynonymous SNPs (three in TCF7L2 and one in FTO gene) were selected as target SNPs by using public database of NCBI (National Center for Biotechnology Information). The recruited personnel was classified into three subgroups of diabetes, impaired fasting glucose (IFG) and normal groups. The individual genotypes of each group were analyzed by resequencing. None of genetic variations at four targeted SNP sites was revealed in all samples of this study. However, this study found two new SNPs that were not reported in TCF7L2 gene. One is synonymous SNP, which is heterozygous of C/T and no amino acid change of asparagine/asparagines, was located at c1641 and found in one normal person. Another is nonsynonymous SNP, which is heterozygous of G/A, was located at c1501 and found in two samples. This new discovered nonsynonymous SNP induce the amino acid change from alanine to threonine. Moreover, this new nonsynonymous SNP was found among two persons, one of whom was a diabetes patient and the other one was a person at boundary between IFG and normal, suggesting that this variant might be associated with IFG or diabetes. Even if there is a limitation of sample number for statistical power, this study has an importance due to the discovery of new SNPs. In the future study, a large sample number of diabetes cohort will be needed to investigate the frequency and association with new discovered SNP.

• Clinical and Experimental Reproductive Medicine
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• 제26권3호
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• pp.483-490
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• 1999

Objectives: Polycystic ovary syndrome (PCOS) has the feature of excessive LH, hyperandrogenism and disturbance of folliculogenesis. Also, insulin, IGF-I and IGFBP-l are involved in the pathogenesis of PCOS. Various surgical and medical therapies have been used and the action mechanisms are related to the endocrine effect. Laparoscopic ovarian electrocautery or laser vaporization is effective in the restoration of ovulation and normal menstrual cycle with minimal invasive procedure especially in the patients resistant to medical therapy. Clomiphen citrate (CC) is used for the ovulation induction in pcas and the resistance is known to be related to insulin, IGF-I, IGFBP-l levels. This study was performed to evaluate the effect of the laparoscopic laser vaporization on the levels of LH, FSH, testosterone, IGF-I and IGFBP-l and on the ovarian response to clomiphen citrate in patients with CC-resistant PCOS. Materials and Methods: The fasting basal serum LH, FSH, testosterone, IGF-I and IGFBP-l level were measured in 10 PCOS patients with CC-resistance and 7 normal controls with regular menstrual cycle. In PCOS, after laparoscopic $CO_2$ laser vaporization, endocrine levels were measured in 1 week interval for 4 weeks and then compared with preoperative levels. Results: In PCOS group, mean serum LH/FSH ratio, testosterone, IGF-I levels were higher and IGFBP-l level was lower than control. LH/FSH ratio decreased from $2.51{\pm}0.67$ to $1.7{\pm}0.6$ (p<0.05) in 2 weeks, to $0.56{\pm}0.2$ (p<0.01) in 3 weeks and to $1.41{\pm}0.3$ (p<0.01) in 4 weeks after operation. Testosterone level decreased from $1.51{\pm}0.82ng/ml$ to $0.65{\pm}0.34ng/ml$ (p<0.05) in 2 weeks, to $0.56{\pm}0.67ng/ml $(p<0.01) in 3 weeks after operation. IGF-I level also decreased from $436{\pm}47.5{\mu}g/l$ to $187{\pm}38{\mu}g/l$ (p<0.0l) in 1 week, to $167{\pm}42{\mu}g/l$ (p<0.01) in 2 weeks, $179{\pm}55{\mu}g/l$ (p<0.01) in 3 weeks and to $120{\pm}43{\mu}g/l$ (p<0.01) in 4 weeks after operation. IGFBP-l level showed no significant change. In 8 of 10 PCOS patients, ovulation was induced with low dose clomiphen citrate. Conclusion: Laparoscopic $CO_2$ laser vaporization restores normal menstrual cycle and ovulation through endocrine effect of decreasing LH/FSH ratio, testosterone and IGF-I level and increases the response to CC. Therefore it is useful for restoration of normal menstruation and induction of ovulation in CC resistant PCOS patients.

• Clinical and Experimental Reproductive Medicine
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• 제24권3호
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• pp.355-359
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• 1997

Leiomyomas, which are the commonest pelvic tumors in women, are originated from myometrial cells. Although the exact initial pathophysiologic event of the leiomyoma is not known, recent evidences suggested that the effects of sex steroid hormones in the process of tumor growth are mediated by local production of growth factors including epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I) and insulin-like growth factor-II (IGF-II). If we look at the effects of other cytokines, it was suggested that basic fibroblast growth factor (bFGF) may stimulate the proliferation of myometrial and leiomyomas cells. And it was reported that interferon-${\alpha}$ inhibit the action of bFGF. Therefore, we examined the effect of bFGF and interferon-${\alpha}$ on the proliferation of leiomyoma and myometrial cells. bFGF stimulated the myometrial and leiomyoma cells significantly at the concentration of 1ng/ml (p<0.05) and 5ng/ml (p<0.05). However, Interferon-${\alpha}$ inhibited the cell proliferation of myometrial and leiomyoma cells significantly at the concentration of 100U/ml (p<0.05) and 1000U/ml (p<0.05). And the stimulated effects of bFGF with the various concentration on the myometrial and leiomyoma cells ware inhibited by interferon-${\alpha}$ with 100U/ml. Therefore, we concluded that bFGF may stimulate the myometrial and leiomyoma cell proliferation and interferon-${\alpha}$ may inhibit the myometrial and leiomyoma cell proliferation through blocking the effect of basic fibroblast growth factor.

• 생명과학회지
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• 제22권10호
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• pp.1428-1433
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• 2012

장수 또는 노화에 관한 연구는 여러 가지 유전적 요인과 생리학적 및 환경 요인들의 복잡한 조합에 의해 결정되므로, 이와 관련된 연구는 매우 흥미로운 분야이나 또한 어려운 주제이다. 지난 수십 년 동안 장수 또는 노화에 관여하는 분자 메커니즘을 찾기 위하여 동물 모델을 사용한 유전학적 접근법으로, 특이적 유전자를 결손 시키는 연구는 귀중한 도구임이 입증되었다. 장수에 관한 첫 번째 연구는 꼬마선충의 돌연변이체에서 발견되었으며, 이 선충의 인슐린/인슐린유사 성장인자-1 회로가 장수에 관여함이 밝혀졌다. 인슐린유사 성장인자-1은 인슐린과 유사한 아미노산 서열을 가진 폴리펩타이드로, 세포의 정상적인 성장과 발달에 관여한다. 이 발견 이후 인슐린/인슐린유사 성장인자-1 회로에 관여하는 많은 인자들이 선충과 초파리 연구에서 장수에 관여함이 밝혀졌다. 또한 특이적 유전자를 결손 시킨 생쥐 모델을 이용한 연구에서도 인슐린/인슐린유사 성장인자-1 회로뿐 아니라 성장호르몬/인슐린유사 성장인자 회로도 장수에 관여함이 지난 수십 년 동안의 연구결과로 밝혀졌다. 간 조직 특이적으로 인슐린유사 성장인자-1 유전자를 결손 시킨 생쥐모델을 이용한 최근의 연구 결과에 의하면 인슐린유사 성장인자-1 자체도 장수에 관여함이 최초로 밝혀졌으며, 이는 인슐린유사 성장인자-1 회로가 무척추동물뿐 아니라 척추동물에서도 장수에 관여함을 명백하게 보여주는 결과이다. 장수를 조절하는 분자 메커니즘은 아직 완전하게 설명되지 않지만, 감소되어진 인슐린유사 성장인자-1의 신호가 장수와 노화의 조절에 중요한 역할을 하며, 인슐린유사 성장인자-1 회로에 관여하는 여러 가지 유전자들의 장수에서의 역할을 유전자 조작된 생쥐모델을 이용하여 집중적으로 검토하려 한다.

• 생명과학회지
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• 제32권10호
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• pp.762-770
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• 2022

제 2형 당뇨병은 고혈당을 특징으로 하는 만성 대사성 질환으로 인슐린 민감성및 저항성을 개선하여 세포속으로 포도당 흡수를 촉진시킴으로서 완화될 수 있다. 본 연구는 triterpenoid 화합물인 betulinic acid가 3T3-L1 지방세포에서 인슐린 신호전달체계를 개선하여 포도당 흡수를 촉진시키는지를 조사하고 그 작용기전을 규명하였다. Betulinic acid는 3T3-L1 지방세포에서 농도의존적으로 포도당 흡수를 유의하게 증가시켰으며, 이는 PM-GLUT4의 발현 증가와 관련이 있음을 관찰하였다. Betulinic acid는 인슐린 신호전달 경로에서 PI3K의 활성화 및 IRS-1tyr, Akt의 인산화를 대조군에 비해 유의하게 증가시켰다. 또한 AMPK의 활성화를 나타내는 pAMPK와 AMPK 하위인자인 pACC의 수준을 유의하게 증가시켰다. Betulinic acid에 의한 PI3K 및 AMPK 경로의 활성화를 증명하기 위해, PI3K 억제제(Wortmannin)와 AMPK의 억제제(Compound C)를 사용하여 이들 처리에 의한 포도당 흡수능과 PM-GLUT4의 발현을 측정한 결과 이들의 발현이 유의하게 저해되었다. 본 연구에서 betulinic acid는 3T3-L1 지방세포에서 PI3K 및 AMPK 경로의 활성화를 통해 세포막으로 포도당 수송체인 GLUT4 전위를 촉진시키고 포도당 흡수를 증가시킬 수 있음을 나타내었다. 이러한 결과는 betulinic acid가 인슐린 민감성을 증진시키고 고혈당을 완화하는데 도움이 될 수 있음을 시사한다.

• Journal of Applied Biological Chemistry
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• 제53권1호
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• pp.44-50
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• 2010

본 연구에서는 고지방식이로 비만을 유도한 암컷 백서에게 태음조위탕과 도담탕을 8주 동안 경구 투여하였을 때 에너지와 포도당 대사에 미치는 영향을 조사하였다. 태음조위탕은 체중과 복부지방에 지방 축적을 나타내는 mesenteric fat과 retroperitoneal fat 양을 감소시키는 경향은 있었지만 통계적으로 유의한 차이를 나타내지는 않았다. 태음조위탕은 대조군에 비해 식이섭취량을 감소시키는 경향을 나타내었다. 반면에 도담탕은 대조군에 비해 체중과 복부지방을 통계적으로 유의하게 감소시켰으며 이것은 식이 섭취량의 감소에 기인하였다. 에너지 소모량은 고지방식이군과 저지방식이군에 차이가 없었고 태음조위탕과 도담탕도 에너지 소모량에 영향을 미치지 않았다. 그러나 에너지원으로 지방을 사용하는 것은 도담탕이 대조군에 비해 높았다. 고지방식이에서는 체내 인슐린 저항성을 나타내는 $HOMA_{IR}$의 값이 높았고, 도담탕은 이것을 통계적으로 유의적으로 낮추었다. 또한, 간에 저장된 글리코겐양도 도담탕을 섭취한 백서에서 가장 많았고, 반면에 간에 저장된 중성 지방 함량은 가장 낮았다. 결론적으로 고지방을 장기간 투여한 암컷 백서에서 체내 에너지와 포도당 대사에 장애가 나타났으며, 태음조위탕과 도담탕이 모두 이러한 장애를 해소하는 경향이 있었으나 도담탕이 효과적으로 에너지와 포도당 대사를 정상화시켰다. 그러므로 비만인 사람에게서 효과적으로 에너지와 포도당 대사를 정상화시킬 수 있는 지에 대한 인체 실험을 하는 것이 필요할 것으로 사료된다.

• 대한물리치료과학회지
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• 제8권1호
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• pp.745-758
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• 2001

The purpose of study to phenomenological examine and the mechanism regarding the gene(DNA, RNA, Protein) and sports to studied, analyzed. and evaluated. This review considers the evidence for genetic effects in several determinants of endurance performance and resistance performance, namely: body measurements and physique, body fat pulmonary functions, cardiac and circulatory functions, muscle characteristics. substrate utilization, maximal aerobic power and other. Moreover, the response to aerobic training of indicators aerobic work metabolism and endurance performance is reviewed, with emphasis on the specificity of the response and the individual differences observed in training ability. This study indicate that improvement of 'Enhancer Action' in RNA genes changed by exercise or sports. Moreover exercise was effect on Central Dogma with DNA makes RNA makes Protein. and think that occurred with exercise influence on skeletal muscle into cell have to Myosin Heavy Chain (MHC) changed was after exercise performance, which accompanied into skeletal muscle that were exercise-induces gene-modulation that is, take gene mutations. This study known that existed hormone(epinephrine)-immune system with interaction. Exercise were altered insulin binding and MAP Kinase signaling increased into immune cells. This review suggested that the high rate of glutamine utilization by cells of the immune system serves to maintain a high intra cellular concentration of the intermediates of biosynthetic pathways such that optimal rates of DNA, RNA and protein synthesis can be maintained. In the absence of glutamine, lymphocytes do not proliferate in vitro: proliferation increase greatly as the glutamine concentration increase. Glutamine is synthesized in skeletal muscle. Skeletal muscle and plasma glutamine levels are lowered by sepsis, injury, bums, surgery and endurance exercise and in the overtrained athlete. The study of result show that production of ET-1 is markedly increased tissue specifically in the heart by exercise without appreciable changes in endothelin-converting enzyme and endothelial receptor expressions, suggest that myocardial ET-1 may participate in modulation of cardiac function during exercise. Conclusionally, this study indicate that improvement of 'Enhancer Action' in RNA genes changed by exercise or sports. Moreover exercise was effect on Central Dogma with DNA makes RNA makes Protein. This study is expected to contribute the area of sports science, medicine, hereafter more effort is required to establish the relation between gene alters and exercise amount.

• Journal of Korean Neurosurgical Society
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• 제44권6호
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• pp.375-381
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• 2008

Objective : The effects on neural proliferation and differentiation of neural stem cells (NSC) of basic fibroblast growth factor-2 (bFGF). insulin growth factor-I (IGF-I). brain-derived neurotrophic factor (BDNF). and nerve growth factor (NGF) were assessed. Also, following combinations of various factors were investigated : bFGF+IGF-I, bFGF+BDNF, bFGF+NGF, IGF-I+BDNF, IGF-I+NGF, and BDNF+NGF. Methods : Isolated NSC of Fisher 344 rats were cultured with individual growth factors, combinations of factors, and no growth factor (control) for 14 days. A proportion of neurons was analyzed using $\beta$-tubulin III and NeuN as neural markers. Results : Neural differentiations in the presence of individual growth factors for $\beta$-tubulin III-positive cells were : BDNF, 35.3%; IGF-I, 30.9%; bFGF, 18.1%; and NGF, 15.1%, and for NeuN-positive cells was : BDNF, 34.3%; bFGF, 32.2%; IGF-I, 26.6%; and NGF, 24.9%. However, neural differentiations in the absence of growth factor was only 2.6% for $\beta$-tubulin III and 3.1% for NeuN. For $\beta$-tubulin III-positive cells, neural differentiations were evident for the growth factor combinations as follows : bFGF+IGF-I, 73.1 %; bFGF+NGF, 65.4%; bFGF+BDNF, 58.7%; BDNF+IGF-I, 52.2%; NGF+IGF-I, 40.6%; and BDNF+NGF, 40.0%. For NeuN-positive cells : bFGF+IGF-I, 81.9%; bFGF+NGF, 63.5%; bFGF+BDNF, 62.8%; NGF+IGF-I, 62.3%; BDNF+NGF, 56.3%; and BDNF+IGF-I, 46.0%. Significant differences in neural differentiation were evident for single growth factor and combination of growth factors respectively (p<0.05). Conclusion : Combinations of growth factors have an additive effect on neural differentiation. The most prominent neural differentiation results from growth factor combinations involving bFGF and IGF-I. These findings suggest that the combination of a mitogenic action of bFGF and post-mitotic differentiation action of IGF-I synergistically affects neural proliferation and NSC differentiation.