• Journal of Life Science
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• v.19 no.5
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• pp.593-597
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• 2009

The uterus plays a critical role in pregnancy and steroid hormones, and both estrogen (E2) and progesterone (P4) especially play important roles in the cross-talk between embryos and uterus to support the pregnancy. E2 stimulates uterine growth during early pregnancy to prepare for implantation of embryos. This cross-talk during the implantation period involves hormones (E2 and P4) and growth factors, including insulin-like growth factor-I (IGF-I). In the uterus of a pregnant pig, the action of E2 is mediated by estrogen receptor-${\beta}$ (ER-${\beta}$). The expression of ER-a was much higher in early pregnancy than in mid- and late- pregnancy, suggesting E2 secretion from embryos enhances transcription of ER-a during early pregnancy. In order to prove whether IGF-I is an E2 target gene, quantitative real-time PCR was performed on ovariectomized murine uterus with E2 and/or P4 treatment(s). Increased IGF-I mRNA expression was observed with E2 treatment, however, it was not significantly induced by P4 treatment, which clearly demonstrates that, in mice, E2 depends on the activation of uterine IGF-I gene expression. The expression of IGF-I in the uterus of pigs was much higher in early pregnancy than in mid- and late- pregnancy and these data exhibited the same expression pattern with the ER-${\beta}$ gene expression in the uterus. It suggests that a positive co-relationship between IGF-I and ER-${\beta}$ expression exists in the uterus, and that both gene expressions of IGF-I and ER-${\beta}$ are regulated by E2. It further suggests that uterine the IGF-I gene expression might be initiated by E2 secreted from embryos to increase ER-${\beta}$ gene expression, and that this increased ER-${\beta}$ further stimulates the expression of IGF-I in the uterus during early pregnancy.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.3
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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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• v.26 no.3
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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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• v.24 no.3
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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.

• Journal of Life Science
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• v.22 no.10
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• pp.1428-1433
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• 2012

Longevity is an exciting but difficult subject to study because it is determined by complex processes that require the coordinated action of several genetic factors as well as physiological and environmental influences. Genetic approaches have been applied to animal models to identify the molecular mechanism responsible for longevity. Several experimental model organisms obtained over the last decades suggest that the complete deletion of a single gene by gene targeting has proven to be an invaluable tool for the discovery of the mechanisms underlying longevity. The first discovery of long-lived mutants came from Caenorhabditis elegans research, which identified the insulin/IGF-1 pathway as responsible for longevity in this worm. IGF-1 is a multifunctional polypeptide that has sequence similarity to insulin and is involved in normal growth and development of cells. Several factors in the IGF-1 system have since been studied by gene targeting in the control of longevity in lower species, including nematode and fruit fly. In addition, significant progress has been made using mice models to extend the lifespan by targeted mutations that interfere with growth hormone/IGF-1 and IGF-1 signaling cascades. A recent finding that IGF-1 is involved in aging in mice was achieved by using liver-specific knockout mutant mice, and this clearly demonstrated that the IGF-1 signal pathway can extend the lifespan in both invertebrates and vertebrate models. Although the underlying molecular mechanisms for the control of longevity are not fully understood, it is widely accepted that reduced IGF-1 signaling plays an important role in the control of aging and longevity. Several genes involved in the IGF-1 signaling system are reviewed in relation to longevity in genetically modified mice models.

• Journal of Life Science
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• v.32 no.10
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• pp.762-770
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• 2022

Hyperglycemia in type 2 diabetes can be alleviated by promoting cellular glucose uptake. Betulinic acid (3β,-3-hydroxy-lup-20(29)-en-28-oic acid) is a pentacyclic lupane-type triterpenoid compound. Although there have been studies on the antidiabetic activity of betulinic acid, studies on cellular glucose uptake are lacking. We investigated the effects of betulinic acid on glucose uptake and its mechanism of action in 3T3-L1 adipocytes. Betulinic acid significantly stimulated glucose uptake in 3T3-L1 adipocytes by increasing the phosphorylation of the insulin receptor substrate 1-tyrosine (IRS-1tyr) in the insulin signaling pathway, which in turn stimulated the activation of phosphoinositide 3-kinase (PI3K) and the phosphorylation of protein kinase B (Akt). The activation of PI3K and Akt by betulinic acid translocated glucose transporter 4 to the plasma membrane (PM-GLUT4), thereby increasing the expression of PM-GLUT4 and thus stimulating cellular glucose uptake. Betulinic acid also significantly increased the phosphorylation/activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase. The activation of PI3K and AMPK by betulinic acid was confirmed using the PI3K inhibitor wortmannin and the AMPK inhibitor compound C. The increase in glucose uptake induced by betulinic acid was significantly decreased by wortmannin and compound C in the 3T3-L1 adipocytes. These results suggest that betulinic acid stimulates glucose uptake by activating PI3K and AMPK in 3T3-L1 adipocytes.

• Journal of Applied Biological Chemistry
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• v.53 no.1
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• pp.44-50
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• 2010

Tae-Um-Jo-wee-Tang (TUJWT) and Do-Dam-Tang (DDT) have been used as an anti-obesity herbal medicine but their effect and mechanism of action have not been studied. We investigated the effects of TUJWT and DDT on energy and glucose homeostasis using Sprague Dawley female rats with diet-induced obesity. The mechanisms of action of TUJWT and DDT were studied whether they had anti-obesity effects. Rats fed a high-fat diet were divided into 3 groups: rats in each group received 2 g water extracts of modified TUJWT and DDT, or 2 g cellulose per kg body weight (a negative control) on a daily basis. A further group was fed a low-fat diet as a positive control. We found that DDT significantly decreased body weight and body fat (mesenteric fat and retroperitoneal fat) more than the control. This decrease was due to the reduction in energy intake but no changes of energy expenditure. However, DDT increased fat oxidation as a major energy source than the control. In addition, modified TUJWT and DDT improved glucose tolerance without changing serum insulin levels during an oral glucose tolerance test. In conclusion, DDT have a better anti-obesity effect than TUJWT by decreasing energy intake in female rats with diet-induced obesity. It also improves glucose tolerance.

• Journal of Korean Physical Therapy Science
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• v.8 no.1
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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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• v.44 no.6
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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.

• Journal of Veterinary Science
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• v.25 no.2
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• pp.23.1-23.15
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• 2024

The widespread use of antimicrobials causes antibiotic resistance in bacteria. The use of butyric acid and its derivatives is an alternative tactic. This review summarizes the literature on the role of butyric acid in the body and provides further prospects for the clinical use of its derivatives and delivery methods to the animal body. Thus far, there is evidence confirming the vital role of butyric acid in the body and the effectiveness of its derivatives when used as animal medicines and growth stimulants. Butyric acid salts stimulate immunomodulatory activity by reducing microbial colonization of the intestine and suppressing inflammation. Extraintestinal effects occur against the background of hemoglobinopathy, hypercholesterolemia, insulin resistance, and cerebral ischemia. Butyric acid derivatives inhibit histone deacetylase. Aberrant histone deacetylase activity is associated with the development of certain types of cancer in humans. Feed additives containing butyric acid salts or tributyrin are used widely in animal husbandry. They improve the functional status of the intestine and accelerate animal growth and development. On the other hand, high concentrations of butyric acid stimulate the apoptosis of epithelial cells and disrupt the intestinal barrier function. This review highlights the biological activity and the mechanism of action of butyric acid, its salts, and esters, revealing their role in the treatment of various animal and human diseases. This paper also discussed the possibility of using butyric acid and its derivatives as surface modifiers of enterosorbents to obtain new drugs with bifunctional action.