• Clinical and Experimental Pediatrics
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• v.45 no.9
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• pp.1106-1113
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• 2002

Purpose : Nuclear ($factor-{\kappa}BNF-{\kappa}B$) is now recognized as playing a potential role in programmed cell death and the adaptive response to various stress. Cellular hypoxia is a primary manifestation of many cardiovascular diseases. It seems that vascular endothelial growth factor (VEGF) and insulin like growth factor-I(IGF-I) have a function as a protective molecule in the heart against several stress including hypoxia. In this study, the role of $NF-{\kappa}B$ to the cellular response and regulation of protective molecules against the acute hypoxia in the heart was studied. Methods : To cause acute hypoxic stress to the heart, Sprague Dawley rats were exposed to hypoxic chamer($N_2$ 92% and $O_2$ 8%). After the hypoxic exposure, nuclear proteins, total proteins and mRNA were isolated from heart. Translocation of the transcription factors $NF-{\kappa}B$, NF-ATc, AP-1 and NKX-2.5 were evaluated by electrophoretic mobility shift assay(EMSA). The expression of IGF-I and VEGF were studied before and after the hypoxic stress by competitive-PCR, Northern hybridization and Western hybridization. To confirm the role of the $NF-{\kappa}B$ in the heart, the rats also were pretreated with diethyl-dithiocarbamic acid(DDTC) into peritoneal cavity to block $NF-{\kappa}B$ translocation into nucleus. Results : The expression of $NF-{\kappa}B$, AP-1 and NF-ATc were increased by the hypoxic stress. Increased expression of the VEGF and IGF-I were also observed by the hypoxic stress. However, the blocking of the $NF-{\kappa}B$ translocation reduced those expressions of VEGF and IGF-I. Conclusion : These results suggest that $NF-{\kappa}B$ has a protective role against the acute hypoxia through several gene expression, especially VEGF and IGF-I in heart muscle.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3667-3671
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• 2015

Invasion and metastasis is the major cause of tumor recurrence, difficulty for cure and low survival rate. Excavating key transcription factors, which can regulate tumor invasion and metastasis, are crucial to the development of therapeutic strategies for cancers. PU.1 is a master hematopoietic transcription factor and a vital regulator in life. Here, we report that, compared to adjacent non-cancerous tissues, expression of PU.1 mRNA in metastatic hepatocellular carcinoma (HCC), but not primary HCC, was significantly down-regulated. In addition, levels of PU.1 mRNA in metastatic hepatoma cell lines MHCC97L and MHCC97H were much lower than in non-metastatic Hep3B cells. Transwell invasion assays after PU.1 siRNA transfection showed that the invasion of hepatoma cell lines was increased markedly by PU.1 knockdown. Oppositely, overexpression of PU.1 suppressed the invasion of these cells. However, knockdown and overexpression of PU.1 did not influence proliferation. Finally, we tried to explore the potential mechanism of PU.1 suppressing hepatoma cell invasion. ChIP-qPCR analysis showed that PU.1 exhibited a high binding capacity with miR-615-5p promoter sequence. Overexpression of PU.1 caused a dramatic increase of pri-, pre- and mature miR-615-5p, as well as a marked decrease of miR-615-5p target gene IGF2. These data indicate that PU.1 inhibits invasion of human HCC through promoting miR-615-5p and suppressing IGF2. These findings improve our understanding of PU.1 regulatory roles and provided a potential target for metastatic HCC diagnosis and therapy.

• Journal of Ginseng Research
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• v.46 no.4
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• pp.526-535
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• 2022

Background: During the pathogenesis of tendinopathy, the chronic inflammation caused by the injury and apoptosis leads to the generation of scars. Ginsenoside Rg1 (Rg1) is extracted from ginseng and has anti-inflammatory effects. Rg1 is a unique phytoestrogen that can activate the estrogen response element. This research aimed to explore whether Rg1 can function in the process of tendon repair through the estrogen receptor. Methods: In this research, the effects of Rg1 were evaluated in tenocytes and in a rat model of Achilles tendinitis (AT). Protein levels were shown by western blotting. qRT-PCR was employed for evaluating mRNA levels. Cell proliferation was evaluated through EdU assay and cell migration was evaluated by transwell assay and scratch test assay. Results: Rg1 up-regulated the expression of matrix-related factors and function of tendon in AT rat model. Rg1 reduced early inflammatory response and apoptosis in the tendon tissue of AT rat model. Rg1 promoted tenocyte migration and proliferation. The effects of Rg1 on tenocytes were inhibited by ICI182780. Rg1 activates the insulin-like growth factor-I receptor (IGF1R) and MAPK signaling pathway. Conclusion: Rg1 promotes injured tendon healing in AT rat model through IGF1R and MAPK signaling pathway activation.

• Animal Bioscience
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• v.35 no.7
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• pp.989-998
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• 2022

Objective: This study investigated the effects of intrauterine growth restriction (IUGR) during late pregnancy on the cell growth, proliferation, and differentiation in ovine fetal thymuses. Methods: Eighteen time-mated Mongolian ewes with singleton fetuses were allocated to three groups at d 90 of pregnancy: restricted group 1 (RG1, 0.18 MJ ME/body weight [BW]^0.75/d, n = 6), restricted group 2 (RG2, 0.33 MJ ME/BW^0.75/d, n = 6) and control group (CG, ad libitum, 0.67 MJ ME/BW^0.75/d, n = 6). Fetuses were recovered at slaughter on d 140. Results: The G0/G1 phase cell number in fetal thymus of the RG1 group was increased but the proliferation index and the expression of proliferating cell nuclear antigen (PCNA) were reduced compared with the CG group (p<0.05). Fetuses in the RG1 group exhibited decreased growth hormone receptor (GHR), insulin-like growth factor 2 receptor (IGF-2R), and their mRNA expressions (p<0.05). For the RG2 fetuses, there were no differences in the proliferation index and PCNA expression (p>0.05), but growth hormone (GH) and the mRNA expression of GHR were lower than those of the CG group (p<0.05). The thymic mRNA expressions of cyclin-dependent protein kinases (CDKs including CDK1, CDK2, and CDK4), CCNE, E2-factors (E2F1, E2F2, and E2F5) were reduced in the RG1 and RG2 groups (p<0.05), and decreased mRNA expressions of E2F4, CCNA, CCNB, and CCND were occurred in the RG1 fetuses (p<0.05). The decreased E-cadherin (E-cad) as a marker for epithelial-mesenchymal transition (EMT) was found in the RG1 and RG2 groups (p<0.05), but the OB-cadherin which is a marker for activated fibroblasts was increased in fetal thymus of the RG1 group (p<0.05). Conclusion: These results indicate that weakened GH/IGF signaling system repressed the cell cycle progression in G0/G1 phase in IUGR fetal thymus, but the switch from reduced E-cad to increased OB-cadherin suggests that transdifferentiation process of EMT associated with fibrogenesis was strengthened. The impaired cell growth, retarded proliferation and modified differentiation were responsible for impaired maturation of IUGR fetal thymus.

• Asian-Australasian Journal of Animal Sciences
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• v.25 no.8
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• pp.1055-1062
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• 2012

Two SNPs, i.e. L127V and T172M, of bovine growth hormone (GH) causing the presence of GH gene haplotypes A, B, and C was previously shown to alter intramuscular fatty acid (FA) composition in Japanese Black (JB) heifers. To determine the SNP effect on somatotropic hormone concentration and lipogenesis, we measured plasma GH, insulin, and insulin-like growth factor-1 (IGF-1) concentrations. We also measured mRNA levels of fatty acid synthase (FASN), stearoyl-coA desaturase (SCD), and sterol regulatory element binding proteins-1 (SREBP-1) and FA composition in diaphragm tissues. Heifers with genotype CC had the lowest plasma insulin concentration and FASN and SCD mRNA levels among genotypes. FASN mRNA levels in haplotype A tended to positively correlate with saturated FA (SFA) content and negatively correlated with C18:2 and unsaturated FA (USFA) contents. SCD mRNA levels in haplotype A positively correlated with monounsaturated FA (MUFA) contents and negatively correlated with C18:0 content. They also tended to positively correlate with C16:1, C18:1, and USFA contents and USFA/SFA ratio and negatively correlate with SFA content. Taken together, GH gene polymorphism affects the lipogenic genes expression levels and their relationships with fatty acid compositions in diaphragm tissues of JB heifers at 31 months of age.

• Development and Reproduction
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• v.11 no.3
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• pp.205-217
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• 2007

As an initial step toward better understanding of the molecular mechanism of estrogen-dependent growth in myoma, an optimal primary cell culture condition has been developed and examined by this study. Myoma and myometrium were cultured by two different methods. Culture stability and $E_2$-responsiveness in stable culture were studied. The culture of digested tissue pieces(Method 2) was found to be a stable culture method for the myoma and myometrium showing a favorable response to estrogen. mRNA expression of PR, IGF-1 and IGF-1 receptor genes was enhanced by $E_2$. The gene responses to $E_2$ were higher in myoma compared with myometrium. Moreover, these responses were more expressive in tissues than in the surrounding cells in primary culture of normal myometrium and myoma, implying a vital role of cell communication through the extracellular matrix in maintaining the estrogen-responsiveness. The development of an improved cell culture system for myoma provides an in vitro tool to further investigate the basis of the tumor formation.

• Animal Bioscience
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• v.36 no.6
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• pp.920-928
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• 2023

Objective: Angora rabbits fed a low-protein diet exhibit decreased hair production performance. This study was set out to evaluate the effects of methionine on hair properties and nitrogen metabolism in Angora rabbits fed a low-protein diet and to investigate the gene expression related to hair follicle development to determine the possible molecular mechanism of methionine effects on hair follicle development. Methods: An experiment was conducted to investigate the effects of DL-methionine addition on a low-protein diet on hair development in Angora rabbits. Angora rabbits were divided into 5 groups: fed a normal diet (control), fed a low-protein diet (LP), or fed an LP supplemented with 0.2%, 0.4%, or 0.6% DL-methionine (Met). Results: The results showed that rabbits in the LP group had lower wool yield than the control rabbits, but the addition of 0.4% to 0.6% Met to LP attenuated these effects (p<0.05). Dietary addition of 0.4% to 0.6% Met to LP increased the apparent nitrogen digestibility, nitrogen utilization rate, and feed efficiency (p<0.05). Feeding LP decreased the insulin-like growth factor 1 (IGF1), keratin-associated protein (KAP) 3.1, and KAP 6.1 mRNA levels compared with the control, but the addition of 0.4% Met in LP attenuated these effects (p<0.05). Relative to the LP or control group, dietary addition of 0.4% Met increased versican mRNA levels. Conclusion: In conclusion, the addition of Met to LP could improves wool production performance and feed efficiency and reduce nitrogen emissions in Angora rabbits. Met can promote hair follicle development, which may be associated with IGF1, KAP, and the versican signaling.

• Journal of Acupuncture Research
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• v.20 no.6
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• pp.45-62
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• 2003

Objective: This study was designed to investigate effects of Nokyongsageunhwan and Nokyongsageunhwan aquapuncuture on body weight, body length, intellectual development Methods: We observed body weight, body length, intellectual development after feeding Nokyongsageunhwan and Nokyongsageunhwan aquapuncuture for thirty three days, and mRNA expressions of GHRF, Somatostatin, IGF-1, NPY were analyzed by RT-PCR method. Results: The results were summarized as follows. 1. Body length was significantly increased in Nokyongsageunhwan herbal acupuncture group compared to normal group and normal saline injection group on 4th week, 2. Lower part of hind leg length was significantly increased in Nokyongsageunhwan oral administration group compared to normal group on 3rd week, and it was significantly increased in Nokyongsageunhwan herbal acupuncture group and Nokyongsageunhwan oral administration group compared to that of normal group on 4th week. 3. As results of observing memory aquisition using Morris water maze system, there was significantly difference in Nokyongsageunhwan oral administration group compared to that of normal group on 4th week. 4. As results of observing retention using Morris water maze system, staying time was significantly increased in Nokyongsageunhwan herbal acupuncture group compared to that of normal group. 5. The somatostatin mRNA expression in the hypothalamus was significantly decreased in Nokyongsageunhwan oral administration group compared to that of normal group. 6. The IGF-1 mRNA expression in the hypothalamus is significantly increased in Nokyongsageunhwan herbal acupuncture group and Nokyongsageunhwan oral administration group compared to that of normal group. 7. The NPY mRNA expression in the hypothalamus was significantly increased in Nokyongsageunhwan oral administration group compared to that of normal group, and it was increased in Nokyongsageunhwan herbal acupuncture group compared to that of normal group, but there was no significant difference. Conclusions: According to the above results, it appears that Nokyongsageunhwan oral administration and Nokyongsageunhwan herbal acupuncture on acupoint GB34 and GB39 showed effects on the growth and the intellectual development of rats.

• Proceedings of the Korea Society of Poultry Science Conference
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• 2006.11a
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• pp.17-27
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• 2006

The effects of dietary betaine on performance, blood compositions, hepatic amino acid concentrations and hormonal secretions were examined in laying hens. Egg production was significantly higher in birds fed the 16.5 % protein diet compared to those fed 14.5 % protein diet(p<0.05), whereas dietary supplementation of betaine did not show any significant effect. The high level of protein and betaine supplementation significantly improved egg weight, egg mass and feed conversion(p<0.05), while eggshell breaking strength, eggshell thickness and Haugh unit were not influenced by betaine and dietary protein levels. Supplemental betaine did not affect serum total protein, albumin and BUN concentration. However, uric acid concentration significantly increased in 600 ppm betaine-fed groups(p<0.05). Concentrations of most hepatic amino acid were influenced by increased protein feeding and dietary betaine supplementation. Hormone studies recorded significantly higher serum and hepatocyte IGF-I concentration in 600 and 1,200 ppm betaine treatments(p<0.05) compared to those of control group. IGF-I mRNA gene expression of hepatocytes revealed statistically correlated increase in 600 and 1,200 ppm betaine-fed groups compared to the controls(p<0.05). Serum IGFBP-3 concentration was significantly elevated in 600 ppm betaine treatments. However, the secretion of IGFBP-1 in hepatocyte of laying hens fed with 600 and 1,200 ppm of betaine showed a significant decrease compared to the control group(p<0.05). Results of these study show that dietary betaine supplementation affects protein and hormone metabolism in laying hens.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.3
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• pp.557-562
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• 2006

Hypoxia induced angiogenesis and inflammation are essential processes for metastasis and progress of solid tumors. We examined the anti-angiogenic and inflammation related activity of Kochiae Fructus (KF) extract. To investigate the roles of the KF extract, we performed MTS assay, western blots using HaCaT cells and $HepG_2$ cells. The results are as follows. The protein level of $HIF-1{\alpha}$ was reduced when induced by $CoCl_2$ in $HepG_2$ cells treated with KF extract and induced by IGF-11 in HaCaT cells treated with KF extract. KF extract reduced the mRNA level of VEGF in HaCaT cells and KF extract reduced the protein level of iNOS in HaCaT cells. These results suggest that KF extract contributes to the anti-angiogenic and anti-inflammatory activities and also we could assume that KF extract act as antioxidant or anti-inflammatory agents via reduction of $HIF-1{\alpha}$.