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Identification of the IL-1$\beta$ inhibitor in the febrile patient urine by anti-IL-1$\beta$ monoclonal antibody (Anti-IL-1$\beta$ 단일클론 항체를 이용해서 발열환자의 뇨중 IL-1$\beta$ inhibitor의 확인)

  • 남경수;배윤수;남명수;오은숙;박순희;최인성;정태화
    • YAKHAK HOEJI
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    • v.37 no.4
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    • pp.420-426
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    • 1993
  • To effectively purify of IL-1 inhibitor from human febrile urine, we have established monoclonal antibody that reacts with human recombinant interleukin l$\beta$(IL-1$\beta$). The antibody, designated ON-1, was highly specific to IL-1$\beta$ and no cross-reaction with other cytokines(IL-l$\alpha$ and IL-4) was observed. As the results of ELISA inhibition assay and Western blotting method, it was further identified that ON-1 had high binding specificity with IL-1$\beta$. IL-1 receptor binding material from febrile patient urine was effectively purified with affinity column chromatography which conjugated with ON-1. This urinary material inhibited the thymocyte proliferation in a dosedependent manner. IL-l$\beta$ induced thymocyte proliferation activity was inhibited to 67.3% at 6 $\mu\textrm{g}$ of the purified urinary material. The result may suggest that this urinary material the purified urinary material. The result may suggest that this urinary material will have antagonic effect on IL-1 action mechanism and act IL-l$\beta$ inhibitor.

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Induction of Steroid 11 $\beta$-hydroxylase in Pellicularia fillamentosa (Pellicularia fillamentosa로부터 Steroid 11$\beta$-hydroxylase의 유도)

  • 김말남;김영숙
    • Korean Journal of Microbiology
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    • v.27 no.4
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    • pp.366-372
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    • 1989
  • Twenty-one strains were tested for 11$\beta$-hydroxylation of Reichstein's substance S. Four fungi exhibited ability for the reaction, among which Pellicularia fillamentosa showed the highest activity. The 11$\beta$-hydroxylase of this fungus was proved to be induced by the substrate, cycloheximide reducing significantly the activity of the enzyme. Range of optimum pH for the 11$\beta$-hydroxylation was broad and found to be 2.0-8.0. Test of the enzyme activity at different growing stages, from spore to mycelia, showed that the branching stage of hyphae and the mature mycelial stage were the most effective for the Reichstein's substance S transformation. However, 11$\beta$-hydroxylase in the intact spore was turned out to be uninducible with the substrate.

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Mechanisms of Amyloid-β Peptide Clearance: Potential Therapeutic Targets for Alzheimer's Disease

  • Yoon, Sang-Sun;AhnJo, Sang-Mee
    • Biomolecules & Therapeutics
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    • v.20 no.3
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    • pp.245-255
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    • 2012
  • Amyloid-${\beta}$ peptide ($A{\beta}$) is still best known as a molecule to cause Alzheimer's disease (AD) through accumulation and deposition within the frontal cortex and hippocampus in the brain. Thus, strategies on developing AD drugs have been focused on the reduction of $A{\beta}$ in the brain. Since accumulation of $A{\beta}$ depends on the rate of its synthesis and clearance, the metabolic pathway of $A{\beta}$ in the brain and the whole body should be carefully explored for AD research. Although the synthetic pathway of $A{\beta}$ is equally important, we summarize primarily the clearance pathway in this paper because the former has been extensively reviewed in previous studies. The clearance of $A{\beta}$ from the brain is accomplished by several mechanisms which include non-enzymatic and enzymatic pathways. Nonenzymatic pathway includes interstitial fluid drainage, uptake by microglial phagocytosis, and transport across the blood vessel walls into the circulation. Multiple $A{\beta}$-degrading enzymes (ADE) implicated in the clearance process have been identified, which include neprilysin, insulin-degrading enzyme, matrix metalloproteinase-9, glutamate carboxypeptidase II and others. A series of studies on $A{\beta}$ clearance mechanism provide new insight into the pathogenesis of AD at the molecular level and suggest a new target for the development of novel therapeutics.

Optimal Extracting Conditions Dimethyl-$\beta$-propiothetin from Ulva pertusa (구멍갈파래(Ulva pertusa)로부터 Dimethyl-$\beta$-propiothetin 최적추출조건)

  • 배태진;강동수;최옥수
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.29 no.5
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    • pp.783-789
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    • 2000
  • This study was focused on the optimal extracting conditions of dimethyl-$\beta$-propiothetin as bioactive substance from green seaweed. Identification and quantification of dimethyl-$\beta$-propiothetin were measured by headspace gas chromatography after conversion to dimethyl sulfide by treatment with saturated NaOH solution. Dimethyl-$\beta$-propiothetin was extracted through various processes (solvent extraction, ultrasonication, boiling and autoclaving) from Ulva pertusa. The content of dimethyl-$\beta$-propiothetin extracted by autoclaving treatment showed higher than that of various extraction methods. Dimethyl-$\beta$-propiothetin content in extract of Ulva pertusa was 325,800 ng/g after autoclaving 121$^{\circ}C$ for 45 min. Dimethyl-$\beta$-propiothetin in exract of Ulva pertusa was comparative stable under low temperature. The retentions of dimethyl-$\beta$-propiothetin content in extract of Ulva pertusa were 76.6~99.8% by incubation at 10~6$0^{\circ}C$ for 2 hours. Chemical decomposition of dimethyl-$\beta$-propiothetin was observed under laboratory conditions at pH values higher than 9.5.

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Intestinal Bacterial ${\beta}-Glucuronidase$ Activity of Patients with Colon Cancer

  • Kim, Dong-Hyun;Jin, Young-Ho
    • Archives of Pharmacal Research
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    • v.24 no.6
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    • pp.564-567
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    • 2001
  • The fecal ${\beta}-glucuronidase$ activity of patients with colon cancer and healthy controls were measured to determine the relationship between the fluctuation of intestinal bacterial ${\beta}-glucuronidase$ and colon cancer. The fecal ${\beta}-glucuronidase$ activity of patients with colon cancer was 1.7 times higher than that of the healthy controls. However, when these fecal specimens were sonicated, the enzyme activity of patients with colon cancer was 12.1 times higher than that of the healthy controls. The fecal ${\beta}-glucuronidase$ activity of human Intestinal bacteria was drastically induced by its substrate or the bile secreted after a subcutaneous injection of 1,2-dimethylhydrazine (DMH) and benzo[a]pyrene into rats. DMH-and benzo[a]pyrene-treated biles induced ${\beta}-glucuronidase$ activity in the human intestinal microflora by approximately 1.5- and 2.3-fold, respectively. They also induced ${\beta}-glucuronidase$ in E. coli HGU-3, which is a ${\beta}-glucuronidase$-producing bacterium from the human intestine. D-saccharic acid 1,4-lactone similarly inhibited fecal ${\beta}-glucuronidase$ in several patients with colon cancer in addition to the healthy controls. This suggests that potent ${\beta}-glucuronidase$ activity is a prime factor in the etiology of colon cancer.

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Justicidin A Reduces β-Amyloid via Inhibiting Endocytosis of β-Amyloid Precursor Protein

  • Chun, Yoon Sun;Kwon, Oh-Hoon;Oh, Hyun Geun;Cho, Yoon Young;Yang, Hyun Ok;Chung, Sungkwon
    • Biomolecules & Therapeutics
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    • v.27 no.3
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    • pp.276-282
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    • 2019
  • ${\beta}$-amyloid precursor protein (APP) can be cleaved by ${\alpha}$-, and ${\gamma}$-secretase at plasma membrane producing soluble ectodomain fragment ($sAPP{\alpha}$). Alternatively, following endocytosis, APP is cleaved by ${\beta}$-, and ${\gamma}$-secretase at early endosomes generating ${\beta}$-amyloid ($A{\beta}$), the main culprit in Alzheimer's disease (AD). Thus, APP endocytosis is critical for $A{\beta}$ production. Recently, we reported that Monsonia angustifolia, the indigenous vegetables consumed in Tanzania, improved cognitive function and decreased $A{\beta}$ production. In this study, we examined the underlying mechanism of justicidin A, the active compound of M. angustifolia, on $A{\beta}$ production. We found that justicidin A reduced endocytosis of APP, increasing $sAPP{\alpha}$ level, while decreasing $A{\beta}$ level in HeLa cells overexpressing human APP with the Swedish mutation. The effect of justicidin A on $A{\beta}$ production was blocked by endocytosis inhibitors, indicating that the decreased APP endocytosis by justicidin A is the underlying mechanism. Thus, justicidin A, the active compound of M. angustifolia, may be a novel agent for AD treatment.

Loss of βPix Causes Defects in Early Embryonic Development, and Cell Spreading and Platelet-Derived Growth Factor-Induced Chemotaxis in Mouse Embryonic Fibroblasts

  • Kang, TaeIn;Lee, Seung Joon;Kwon, Younghee;Park, Dongeun
    • Molecules and Cells
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    • v.42 no.8
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    • pp.589-596
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    • 2019
  • ${\beta}Pix$ is a guanine nucleotide exchange factor for the Rho family small GTPases, Rac1 and Cdc42. It is known to regulate focal adhesion dynamics and cell migration. However, the in vivo role of ${\beta}Pix$ is currently not well understood. Here, we report the production and characterization of ${\beta}Pix$-KO mice. Loss of ${\beta}Pix$ results in embryonic lethality accompanied by abnormal developmental features, such as incomplete neural tube closure, impaired axial rotation, and failure of allantois-chorion fusion. We also generated ${\beta}Pix$-KO mouse embryonic fibroblasts (MEFs) to examine ${\beta}Pix$ function in mouse fibroblasts. ${\beta}Pix$-KO MEFs exhibit decreased Rac1 activity, and defects in cell spreading and platelet-derived growth factor (PDGF)-induced ruffle formation and chemotaxis. The average size of focal adhesions is increased in ${\beta}Pix$-KO MEFs. Interestingly, ${\beta}Pix$-KO MEFs showed increased motility in random migration and rapid wound healing with elevated levels of MLC2 phosphorylation. Taken together, our data demonstrate that ${\beta}Pix$ plays essential roles in early embryonic development, cell spreading, and cell migration in fibroblasts.

Metabolic Engineering of Saccharomyces cerevisiae to Improve Glucan Biosynthesis

  • Zhou, Xing;He, Jing;Wang, Lingling;Wang, Yang;Du, Guocheng;Kang, Zhen
    • Journal of Microbiology and Biotechnology
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    • v.29 no.5
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    • pp.758-764
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    • 2019
  • ${\beta}$-Glucan is a chief structural polymer in the cell wall of yeast. ${\beta}$-Glucan has attracted intensive attention because of its wide applications in health protection and cosmetic areas. In the present study, the ${\beta}$-glucan biosynthesis pathway in S. Cerevisiae was engineered to enhance ${\beta}$-glucan accumulation. A newly identified bacterial ${\beta}-1$, 6-glucan synthase GsmA from Mycoplasma agalactiae was expressed, and increased ${\beta}$-glucan content by 43%. In addition, other pathway enzymes were investigated to direct more metabolic flux towards the building of ${\beta}$-glucan chains. We found that overexpression of Pgm2 (phosphoglucomutase) and Rho1 (a GTPase for activating glucan synthesis) significantly increased ${\beta}$-glucan accumulation. After further optimization of culture conditions, the ${\beta}$-glucan content was increased by 53.1%. This study provides a new approach to enhance ${\beta}$-glucan biosynthesis in Saccharomyces cerevisiae.

Anti-cancer Activity of the Leave Extracts of Rodgersia podophylla through β-catenin Proteasomal Degradation in Human Cancer Cells

  • Kim, Jeong Dong;Park, Su Bin;Kim, Ha Na;Jeong, Jin Boo
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2019.10a
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    • pp.68-68
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    • 2019
  • In this study, we evaluated the effect of Rodgersia podophylla leave extracts (RPL) on ${\beta}$-catenin level in human cancer cells. RPL dose-dependently inhibited cell proliferation in SW480, A549, MDA-MB-231, PC-3 and AsPC-1 cells. RPL dramatically decreased ${\beta}$-catenin protein level in all cancer cells. However, decreased level of ${\beta}$-catenin mRNA expression was observed in A549 and AsPC-1 cells. In addition, RPL dramatically attenuated cyclin D1 mRNA expression in all cancer cells. MG132 decreased the downregulation of ${\beta}$-catenin protein level induced by RPL in all cancer cells, while RPL-induced downregulation of ${\beta}$-catenin was inhibited by the inhibition of $GSK-3{\beta}$ by LiCl in MDA-MB-231 cells. RPL phosphorylated ${\beta}$-catenin and $GSK-3{\beta}$. In addition, the inhibition of $GSK-3{\beta}$ by LiCl attenuated RPL-induced ${\beta}$-catenin phosphorylation. Based on these findings, RPL may be a potential candidate for the development of chemopreventive or therapeutic agents for human cancer.

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Effect of Mycelial Extract of Clavicorona pyxidata on the Production of Amyloid $\beta$-Peptide and the Inhibition of Endogenous $\beta$-Secretase Activity in vitro

  • Lee, Tae-Hee;Park, Young-Il;Han, Yeong-Hwan
    • Journal of Microbiology
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    • v.44 no.6
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    • pp.665-670
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    • 2006
  • Amyloid $\beta$-peptide (A$\beta$), which is a product of the proteolytic effect of $\beta$-secretase (BACE) on an amyloid precursor protein, is closely associated with Alzheimer's disease (AD) pathogenesis. There is sufficient evidence to suggest that a BACE inhibitor may reduce A$\beta$ levels, thus decreasing the risk of AD. In a previous study, an extract of Clavicorona pyxidata DGUM 29005 mycelia was found to inhibit the production of a soluble $\beta$-amyloid precursor protein (s$\beta$APP), A$\beta$, and BACE in neuronal cell lines. We sought to determine whether this mycelial extract exerts the same effect in human rhabdomyosarcoma A-204 and rat pheochromocytoma PC-12 cells. We found that the production of A$\beta$ decreased in a dose-dependent manner in the presence of the mycelial extract and that the concentration of A$\beta$ never exceeded $50{\mu}g/ml$. The presence of sAPP was detected in every culture medium to which the mycelial extract had been added and its concentration remained the same, regardless of the concentration of the extract used. Endogenous $\beta$-secretase activity in A-204 and PC-12 cellular homogenates also decreased in the presence of this extract. These cells, in culture, were not susceptible to the cytotoxic activity of the mycelial extract.