• Title/Summary/Keyword: growth inhibition factor

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Protease Inhibitors in Porcine Colostrum: Potency Assessment and Initial Characterization

  • Zhou, Q.;He, R.G.;Li, X.;Liao, S.R.
    • Asian-Australasian Journal of Animal Sciences
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    • v.16 no.12
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    • pp.1822-1829
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    • 2003
  • Porcine colostrum and milk were separated into the acid-soluble and casein fractions by acidification followed by centrifuge. The acid-soluble fraction of porcine colostrum was further separated by liquid chromatography and anisotropic membrane filtration. Trypsin and chymotrypsin inhibitory capacity in porcine colostrum, milk and their components was determined by incubating bovine trypsin or chymotrypsin in a medium containing their corresponding substrates with or without addition of various amounts of porcine colostrum, porcine milk or their components. The inhibition of insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF) degradation in pig small intestinal contents by porcine colostrum was measured by incubating iodinated IGF-I or EGF with the intestinal contents with or without addition of porcine colostrum. Degradation of labeled IGF-I or EGF was determined by monitoring the generation of radioactivity soluble in 30% trichloroacetic acid (TCA). The results showed that porcine colostrum had high levels of trypsin and chymotrypsin inhibitory activity and increased the stability of IGF-I and EGF in pig intestinal contents. The inhibitory activity declined rapidly during lactation. It was also found that trypsin and chymotrypsin inhibitory activity and the inhibition on IGF-I and EGF degradation in the acid-soluble fraction were higher than that in the casein fraction. Heat-resistance study indicated that trypsin inhibitors in porcine colostrum survived heat treatments of $100^{\circ}C$ water bath for up to 10 min, but exposure to boiling water bath for 30 min significantly decreased the inhibitory activity. Compared with the trypsin inhibitors, the chymotrypsin inhibitors were more heatsensitive. Separation of the acid-soluble fraction of porcine colostrum by liquid chromatography and anisotropic membrane filtration revealed that the trypsin and chymotrypsin inhibitory capacity was mainly due to a group of small proteins with molecular weight of 10,000-50,000. In conclusion, the present study confirmed the existence of high levels of protease inhibitors in porcine colostrum, and the inhibition of porcine colostrum on degradation of milk-borne growth factors in the pig small intestinal tract was demonstrated for the first time.

Epidermal Growth Factor Decreases the Level of DNA Topoisomerase $II{\alpha}$ in Human Carcinoma A431 Cells

  • Chang, Jong-Soo
    • BMB Reports
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    • v.31 no.3
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    • pp.245-248
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    • 1998
  • Human epidermoid carcinoma A431 cells have an extraordinarily large number of epidermal growth factor (EGF) receptors, and their growth is inhibited by EGF, which results in growth arrest at the Gl phase. In order to investigate the EGF-mediated inhibition mechanism, the expression level of DNA topoisomerase (topo) II was analyzed after EGF treatment. As a result, it was shown that EGF treatment lowered the amount of 170 kDa topo II (topo $II{\alpha}$) but not 180 kDa (topo $II{\beta}$). However, the A431 cell variant resistant to EGF was not sensitive to EGF treatment. These results suggest that EGF-induced growth arrest of A431 cells may be closely related to the depletion of topo $II{\alpha}$.

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The WNT/Ca2+ pathway promotes atrial natriuretic peptide secretion by activating protein kinase C/transforming growth factor-β activated kinase 1/activating transcription factor 2 signaling in isolated beating rat atria

  • Li, Zhi-yu;Liu, Ying;Han, Zhuo-na;Li, Xiang;Wang, Yue-ying;Cui, Xun;Zhang, Ying
    • The Korean Journal of Physiology and Pharmacology
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    • v.26 no.6
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    • pp.469-478
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    • 2022
  • WNT signaling plays an important role in cardiac development, but abnormal activity is often associated with cardiac hypertrophy, myocardial infarction, remodeling, and heart failure. The effect of WNT signaling on regulation of atrial natriuretic peptide (ANP) secretion is unclear. Therefore, the purpose of this study was to investigate the effect of Wnt agonist 1 (Wnta1) on ANP secretion and mechanical dynamics in beating rat atria. Wnta1 treatment significantly increased atrial ANP secretion and pulse pressure; these effects were blocked by U73122, an antagonist of phospholipase C. U73122 also abolished the effects of Wnta1-mediated upregulation of protein kinase C (PKC) β and γ expression, and the PKC antagonist Go 6983 eliminated Wnta1-induced secretion of ANP. In addition, Wnta1 upregulated levels of phospho-transforming growth factor-β activated kinase 1 (p-TAK1), TAK1 banding 1 (TAB1) and phospho-activating transcription factor 2 (p-ATF2); these effects were blocked by both U73122 and Go 6983. Wnta1-induced ATF2 was abrogated by inhibition of TAK1. Furthermore, Wnta1 upregulated the expression of T cell factor (TCF) 3, TCF4, and lymphoid enhancer factor 1 (LEF1), and these effects were blocked by U73122 and Go 6983. Tak1 inhibition abolished the Wnta1-induced expression of TCF3, TCF4, and LEF1 and Wnta1-mediated ANP secretion and changes in mechanical dynamics. These results suggest that Wnta1 increased the secretion of ANP and mechanical dynamics in beating rat atria by activation of PKC-TAK1-ATF2-TCF3/LEF1 and TCF4/LEF1 signaling mainly via the WNT/Ca2+ pathway. It is also suggested that WNT-ANP signaling is implicated in cardiac physiology and pathophysiology.

UV Effect on Plant Growth

  • Kondo, Noriaki;Tou, Seiji;Takahashi, Shinya;Nakajima, Nobuyoshi
    • Journal of Photoscience
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    • v.9 no.2
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    • pp.158-161
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    • 2002
  • UV-B radiation gives harmful effects on plants, such as production of several types of DNA lesions, and growth inhibition. On the other hand, plants have some protective mechanisms, including filtering effect due to accumulation of phenolic compounds in epidermal cells and reactivation of DNA lesions, which are enhanced by UV-B irradiation. We have investigated the mechanism of UV-B effects on plants using cucumber seedlings as plant materials. Cucumber plants were cultivated in an artificially lit growth chamber. Supplemental UV-B irradiation, of which intensity was almost equal to the level of natural sunlight, retarded the growth of first leaves. The growth retardation must result trom the inhibition of cell division and/or cell growth. Microscopical observation of leaf epidermis suggested that the growth retardation might be mainly caused by cell growth inhibition. The retardation was, however, restored within 2 or 3 days after the termination of UV-B irradiation. It is known that UV-B irradiation lowers the activity of photo system II (PS II). In the present experimental conditions, however, UV-B irradiation has little effect on PS II activity as estimated by chlorophyll fluorescence. The stomatal conductance, a major factor determining photosynthetic rate, of first leaves increased during the growth. The increase of stomatal conductance was suppressed by UV-B irradiation and restored by termination of the irradiation. It has not been clear, however, what mechanisms are involved in the suppression of increase of stomatal conductance.

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Activities of Antioxidation and AChE Inhibition of Extract from Hericium erinaceus

  • Lee, Jong-Seok;Hong, Eock-Kee
    • 한국생물공학회:학술대회논문집
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    • 2005.04a
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    • pp.103-107
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    • 2005
  • It has been known that the novel diterphenoids, hericenone and erinacine isolated from the fruiting body and cultured mycelia of Hericium erinaceus showed potent stimulating activity of nerve growth factor (NGF)-synthesis. To investigate the biological activities of extracts from fruiting body, cultured mycelium and cell-free broth of H. erinaceus, the activity experiments of antioxidation and AChE inhibition were carried out. Sephadex G-10 gel filtration followed by HPLC on a ${\mu}Bondapak$ $C_{18}$ column of EtOAc extract from cultured mycelium showed a biological activity.

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Inhibitory Effects of Paeonia suffruticosa Andrews Extracts on VEGF Binding to VEGF Receptor

  • Lee, Hak-Kyo;Lee, Sung-Jin
    • Natural Product Sciences
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    • v.13 no.2
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    • pp.128-131
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    • 2007
  • Tumor angiogenesis is a critical step f3r the growth and metastasis of solid tumors. Vascular endothelial growth factor (VEGF) is the most important angiogenic molecule associated with tumor-induced neovascularization. VEGF exerts its activity through binding to its receptor tyrosine kinase, KDR/Flk-1, expressed on the surface of endothelial cells. This study was carried out to investigate inhibitory effect of extracts from root cortex of Paeonia suffruticosa Andrews on VEGF binding to VEGF receptor. The MeOH extract from P. suffrutiocosa Andr. inhibited the binding of KDR/Flk-1-Fc to immobilized VEGF$_{165}$ more than 45% at the concentration of 100 ${\mu}$g/mL. The MeOH extract was further fractionated into n-hexane, ethyl acetate, n-BuOH, and aqueous fractions. Among the four fractions, the ethyl acetate fraction from the root cortex of P. suffruticosa Andr. exhibited highly effective inhibition (${\approx}$ 79% inhibition) and then n-BuOH fraction (${\approx}$ 45% inhibition) on the binding of KDR/Flk-1-Fc to immobilized VEGF$_{165}$ at the concentration of 100 ${\mu}$g/mL. The ethyl acetate fraction from the root cortex of P. suffruticosa Andr. more efficiently blocked VEGF-induced human umbilical vein endothelial cell proliferation, than the growth of HT1080 human fibrosarcoma. Our results suggest that P. suffruticosa Andr. may be used as a candidate fur developing anti-angiogenic agent.

Growth Stimulation and Inhibition of Differentiation of the Human Colon Carcinoma Cell Line Caco-2 with an Anti-Sense Insulin-Like Growth Factor Binding Protein-3 Construct

  • YoonPark, Jung-Han
    • BMB Reports
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    • v.32 no.3
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    • pp.266-272
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    • 1999
  • The insulin-like growth factor (IGF) system consisting of IGF-I, IGF-II, IGF-receptors, and IGF-binding proteins (IGFBP) regulates the proliferation of a variety of cancer cell types. To examine whether a decrease in endogenous IGFBP-3 stimulates proliferation or inhibits differentiation, Caco-2 cells, a human colon adenocarcinoma cell line, were stably transfected with an anti-sense IGFBP-3 expression construct or pcDNA3 vector as control. Accumulation of IGFBP-3 mRNA and secretion of IGFBP-3 into serum-free conditioned medium, 9 days after plating, were significantly lower in Caco-2 cell clones transfected with anti-sense IGFBP-3 cDNA compared to the controls. The anti-sense clones grew at a similar rate to the controls for 8 days after plating, but achieved a higher final density between days 10 and 12. The levels of sucrase-isomaltase mRNA, a marker of enterocyte differentiation of Caco-2 cells, were lower in the anti-sense clones examined on day 9. In conclusion, proliferation of Caco-2 cells can be stimulated by lowering endogenously-produced IGFBP-3.

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The Experimental Study on the Effect of Herbal Exrtacts on Hair Growth and Acnes (복분자(覆盆子), 석창포(石菖蒲), 상침자 및 숙지황(熟地黃)이 모발성장(毛髮成長)과 면포에 미치는 실험적(實驗的) 연구(硏究))

  • Oh, Young-Sun;Roh, Sek-Seun;Oh, Min-Suck
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.19 no.3 s.31
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    • pp.34-54
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    • 2006
  • The effects of four extracts of medicinal herbs, Rubus coreanum, Acorus calamus, Morus alba and Rehmannia glutinosa on hair growth activity and acnes control were investigated. In the course of screening natural extracts for hair growth, we found that the extract of dried root of Rubus coreanum has the hair growth promoting effect. After topical application of these extracts to the back of C57BL/6 mice, the earlier conversion of telogen-to-anagen phase was induced. The growth of dermal papilla cells and mouse vibrissae hair follicle cultured in vitro, however, was not affected by treatment of these extracts. Furthermore these extracts do not possesspotent inhibitory effect on $5{\alpha}-reductase$ I and II activity and anti-bacterial effect on Escherichia coli , Propionibacterium acnes, Pityrosporum ovale, Staphylococcus aureus, Staphylococcus epidemidis, and Candida albicans. RT-PCR analysis showed that these extracts did notinduce mRNA levels of growth factors such as insulin-like growth factor-I, keratinocyte growth factor, hepatocyte growth factor and vascular endothelial growth factor in dermal papilla cells. These results suggest that Rubus coreanum has hair growth promoting effect. However, the effects of these materials on the hair growth promotion are not mediated through inhibition of $5{\alpha}-reductase$ I and II activity, stimulation of hair follicle cells and expression of growth factors in the dermal papilla cells.

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Anti-Helicobacter pylori Effect of Costunolide Isolated from the Stem Bark of Mgnolia Sieboldii

  • Park, Jong-Beak;Lee, Chong-Kyo;Park, Hee-Juhn
    • Archives of Pharmacal Research
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    • v.20 no.3
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    • pp.275-279
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    • 1997
  • Helicobacter pylori (H. pylorl) infection is now established as the major pathogenic factor in chronic gastritis and peptic ulcer disease. in addition, there is accumulating evidence that H. pylori plays an important role in the process of gastric carcinogenesis. On the other hand, oriental traditional medicines have been used for stomach disease for thousands of years. In the present study, methanol extract from the stem bark of Magnolia sieboldii (M. sieboldii) and its components were investigated on their inhibitory effects against urease activity and growth of H. pylori in vitro. The methanol extract of M. sieboldii significantly inhibited the growth of H. pylori ATCC 43504 at 5 mg/ml. From the further fractionation, the chloroform fraction inhibited the bacterial growth dose-dependently. Among four fractions separated from the chloroform fraction by silica gel column chromatography, MS-C-2 was the most potent. Costunolide was isolated from the MS-C-2 subtraction by preparative TLC and recrystallization using n-hexane. Anti-H. pylori effect of costunolide was investigated using one commercial strain (H. pylori ATCC 43504) and three clinical strains (H. pylon 4, 43, 82548). Costunolide exhibited potent anti-H. pylori activity, and the MIC was around $100-200{\mu}g/ml$. However, costunolide had no inhibitory effect of H. pylori urease activity at the concentration used for the growth inhibition assay. From these results, we conclude that costunolide inhibits the, growth of H. pylori by the independent manner of H. pylori urease inhibition.

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Low-dose metronomic doxorubicin inhibits mobilization and differentiation of endothelial progenitor cells through REDD1-mediated VEGFR-2 downregulation

  • Park, Minsik;Kim, Ji Yoon;Kim, Joohwan;Lee, Jeong-Hyung;Kwon, Young-Guen;Kim, Young-Myeong
    • BMB Reports
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    • v.54 no.9
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    • pp.470-475
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    • 2021
  • Low-dose metronomic chemotherapy has been introduced as a less toxic and effective strategy to inhibit tumor angiogenesis, but its anti-angiogenic mechanism on endothelial progenitor cells (EPCs) has not been fully elucidated. Here, we investigated the functional role of regulated in development and DNA damage response 1 (REDD1), an endogenous inhibitor of mTORC1, in low-dose doxorubicin (DOX)-mediated dysregulation of EPC functions. DOX treatment induced REDD1 expression in bone marrow mononuclear cells (BMMNCs) and subsequently reduced mTORC1-dependent translation of endothelial growth factor (VEGF) receptor (Vegfr)-2 mRNA, but not that of the mRNA transcripts for Vegfr-1, epidermal growth factor receptor, and insulin-like growth factor-1 receptor. This selective event was a risk factor for the inhibition of BMMNC differentiation into EPCs and their angiogenic responses to VEGF-A, but was not observed in Redd1-deficient BMMNCs. Low-dose metronomic DOX treatment reduced the mobilization of circulating EPCs in B16 melanoma-bearing wild-type but not Redd1-deficient mice. However, REDD1 overexpression inhibited the differentiation and mobilization of EPCs in both wild-type and Redd1-deficient mice. These data suggest that REDD1 is crucial for metronomic DOX-mediated EPC dysfunction through the translational repression of Vegfr-2 transcript, providing REDD1 as a potential therapeutic target for the inhibition of tumor angiogenesis and tumor progression.