• Title/Summary/Keyword: 억제유도치료

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Anti-Obesitic Effects of Cathepsin S Inhibitory Fraction Derived from Paecilomyces tenuipes in Mice Fed a High-Fat Diet (고지방식이를 섭취한 쥐에서 눈꽃동충하초 유래 cathepsin S 저해 분획의 비만 억제 효과)

  • Heo, Keon;Myoung, Kil-Sun;Lee, Jung-Hee;Huh, Chul-Sung
    • Korean Journal of Food Science and Technology
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    • v.41 no.4
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    • pp.446-451
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    • 2009
  • In this study, cathepsin S (CTSS) inhibitory fraction was isolated from Paecilomyces tenuipes and anti-obesitic effects of the fraction were evaluated in mice, fed a high-fat diet. Hot water extract of P. tenuipes (DHW) was divided into 2 fractions, water eluate fraction (DHP1) and methanol eluate fraction (DHP2) using Diaion HP-20. $IC_{50}$ values for DHW, DHP1 and DHP2 against CTSS were 108.7, 890.3 and 2.3 ${\mu}g$/mL, respectively. To evaluate anti-obesitic effects of the fractions, each fraction was administrated orally to C57BL/6 mice for 4 weeks with a high-fat diet. DHP2 had the highest inhibitory effect on CTSS activity, causing serious reduction in weight gain, a reduction in the amount of adipose tissue and in serum lipids levels. These results suggest that the inhibition of CTSS by compounds derived from P. tenuipes may be effective in preventing and in ameliorating obesity.

Bacterial Toxin-antitoxin Systems and Their Biotechnological Applications (박테리아의 toxin-antitoxin system과 생명공학기술 응용)

  • Kim, Yoonji;Hwang, Jihwan
    • Journal of Life Science
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    • v.26 no.2
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    • pp.265-274
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    • 2016
  • Toxin-antitoxin (TA) systems are ubiquitous genetic modules that are evolutionally conserved in bacteria and archaea. TA systems composed of an intracellular toxin and its antidote (antitoxin) are currently classified into five types. Commonly, activation of toxins under stress conditions inhibits diverse cellular processes and consequently induces cell death or reversible growth inhibition. These effects of toxins play various physiological roles in such as regulation of gene expression, growth control (stress response), programmed cell arrest, persister cells, programmed cell death, phage protection, stabilization of mobile genetic elements or postsegregational killing of plasmid-free cells. Accordingly, bacterial TA systems are commonly considered as stress-responsive genetic modules. However, molecule screening for activation of toxin in TA system is available as development of antimicrobial agents. In addition, cytotoxic effect induced by toxin is used as effective cloning method with antitoxic effect of antitoxin; consequently cells containing cloning vector inserted a target gene can survive and false-positive transformants are removed. Also, TA system is applicable to efficient single protein production in biotechnology industry because toxins that are site-specific ribonuclease inhibit protein synthesis except for target protein. Furthermore, some TA systems that induce apoptosis in eukaryotic cells such as cancer cells or virus-infected cells would have a wide range of applications in eukaryotes, and it will lead to new ways of treating human disease. In this review, we summarize the current knowledge on bacterial TA systems and their applications.

Protective Effects of Extracts of Protaetia brevitarsis on Carbon tetrachloride-induced Hepatotoxicity in the Mice (사염화탄소에 의해 유발된 흰쥐의 간독성에 미치는 흰점박이꽃무지 추출물의 간보호 효과)

  • Chon, Jeong-Woo;Kweon, HaeYong;Jo, You-Young;Yeo, Joo Hong;Lee, Heui Sam
    • Journal of Sericultural and Entomological Science
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    • v.50 no.2
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    • pp.93-100
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    • 2012
  • To investigate the effects of Protaetia. brevitarsis extracts on the protection against liver damage by carbon tetrachloride($CCl_4$) in rat, two kinds of experiment were performed, firstly by the primary hepatocyte culture and secondly by the animal feeding. The primary hepatocyte culture with the extracts of P.brevitarsis showed significantly low activities of GPT, bile acid, and bilirubin, indicating an excellent protective effect against liver damage by $CCl_4$. Especially, below molecular weight 1,000 blew the water to have 32.1% recovery degree. In the seconde experiment, serum GPT activity was significantly decreased in water fraction of P. brevitarsis compared to $CCl_4$ treatment by 98.2%. Serum concentration of bile acid and bilirubin were tended to increased by $CCl_4$ treatment, but water fraction of P. brevitarsis and silymarin recovered the level. These consistent results in vitro and in vivo suggest that the extracts of P. brevitarsis may have strong protective effects against liver damage induced by the potential toxicants such as $CCl_4$.

Anti-neuroinflammatory Effects of a Locusta migratoria Ethanol Extract in LPS-stimulated BV-2 Microglia (LPS로 자극된 미세아교세포에서 풀무치 에탄올 추출물의 신경염증 억제 효능)

  • Lee, Hwa Jeong;Seo, Minchul;Lee, Joon Ha;Kim, In-Woo;Kim, Sun Young;Hwang, Jae-Sam;Kim, Mi-Ae
    • Journal of Life Science
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    • v.28 no.11
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    • pp.1332-1338
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    • 2018
  • Activated microglia, induced by various pathogens, protect neurons and maintain homeostasis of the central nervous system (CNS). However, severe activation causes neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease because of the secretion of various neurotoxic molecules, such as nitric oxide (NO), prostaglandin (PG), and pro-inflammatory cytokines. Because chronic microglial activation endangers neuronal survival, negative regulators of microglial activation have been identified as potential therapeutic candidates for treatment of many neurological diseases. One potential source of these regulators is Locusta migratoria, a grasshopper of the Acrididae, usually 4-6 cm in size, belonging to the family of large insects in Acrididae. This grasshopper is an edible insect resource that can be consumed by humans as protein source or used for animal feed. The aim of the present study was to examine the inhibitory effects of a L. migratoria ethanol extract (LME) on the production of inflammatory mediators in LPS-stimulated BV-2 microglia cells. The extract significantly inhibited the NO, iNOS, COX-2, and pro-inflammatory cytokine ($TNF-{\alpha}$, IL-6 and $IL-1{\beta}$) levels in BV-2 microglia cell. Because the inhibition of microglial activation may be an effective solution for treating brain disorders like Alzheimer's and Parkinson's diseases, these results suggest that LME may be a potential therapeutic agent for the treatment of brain disorders induced by neuroinflammation.

Transplantation of Brain-Derived Neurotrophic Factor-Expressing Mesenchymal Stem Cells Improves Lower Urinary Tract Symptoms in a Rat Model (뇌유래신경영양인자 발현 중간엽 줄기세포의 하부요로증상 개선 효과)

  • Jeon, Seung Hwan;Park, Mi-Young
    • Korean Journal of Clinical Laboratory Science
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    • v.52 no.4
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    • pp.417-424
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    • 2020
  • This study aimed to explore the effects of brain-derived neurotrophic factor (BDNF), produced by engineered immortalized mesenchymal stem cells (imMSC), on lower urinary tract symptoms (LUTS) in a rat model with neurogenic bladder (NB). Forty-eight Sprague-Dawley (SD) rats were randomly divided into the following groups: Sham control, LUTS, LUTS+imMSC (treated with immortalized MSC), and LUTS+BDNF-eMSC (treated with BDNF-expressing MSC) groups. LUTS was induced by a crush injury to the major pelvic ganglion (MPG). Bladder function was tested under anesthesia, and bladder tissue strips were collected thereafter for contractility test and western blot analysis. Western blot results showed that the expression of both Angiopoietin 1 (Ang 1) and platelet-derived growth factor (PDGF) increased with MSC injection. The effect of treatment with BDNF-eMSC on LUTS was also evaluated, and the results were found to be better than those with imMSC (P<0.05). BDNF-eMSC prevented fibrosis in the bladder tissue and significantly reduced caspase-3 levels. In conclusion, high expression of BDNF in vivo resulted in recovery of bladder function and contractility, along with the inhibition of apoptosis in a rat model.

Comparative study of antioxidant and anti-neuroinflammatory activity of leaf extracts of three different species of Bamboos in different extraction solvents containing caffeic acid, p-coumaric acid and tricin (왕대, 조릿대, 오죽의 추출 용매에 따른 항산화, 신경염증제어 활성 및 지표성분 caffeic acid, p-coumaric acid, tricin의 함량 비교)

  • Kim, Yon-Suk;Cho, Duk-Yeon;Kim, Mikyung;Choi, Dong-Kug
    • Korean Journal of Food Science and Technology
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    • v.53 no.3
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    • pp.296-303
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    • 2021
  • The antioxidant and anti-neuroinflammatory activities of water, 30, 70, and 100% ethanol extracts of leaves of three different species of bamboo (Phyllostachys nigra, P. bambusoides, and Sasa borealis) were investigated. The levels of total polyphenol and flavonoid were measured, and antioxidant activity was evaluated using various antioxidant assays (DPPH, ABTS, and FRAP). Lipopolysaccharide (LPS)-induced BV2 microglial cell activation was used to evaluate the anti-neuroinflammatory properties of the bamboo leaf extracts. Treatment with both aqueous and ethanolic extracts showed no cytotoxicity in BV-2 microglial cells. Pre-treatment of BV-2 cells with bamboo leaf extracts significantly inhibited LPS-induced excessive production of nitric oxide in a dose-dependent manner. Moreover, phytochemical analysis based on the extraction solvent showed that caffeic acid, p-coumaric acid, and tricin are the principal constituents of all three bamboo leaf extracts. Therefore, our findings suggest that bamboo leaf extract contains potent antioxidants and anti-neuroinflammatory compounds that can be used as potential therapeutic agents for the treat neuroinflammatory diseases.

Caulerpa okamurae ethanol extract improves the glucose metabolism and insulin sensitivity in vitro and in vivo (옥덩굴 에탄올 추출물의 당 대사 및 인슐린 민감성 개선효과)

  • Park, Chul-Min;Thakuri, Laxmi Sen;Rhyu, Dong-Young
    • Journal of Applied Biological Chemistry
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    • v.64 no.1
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    • pp.89-96
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    • 2021
  • The aim of this study is to examine the effect of Caulerpa okamurae ethanol extract (COE) on glucose metabolism and insulin sensitivity as one of the drug targets for treatment of type2 diabetes. COE significantly inhibited protein tyrosine phosphatase (PTP1B) and dipeptidyl peptidase-IV (DPP-IV) enzyme activities in vitro assay. Also, COE significantly enhanced the glucose uptake and the expression of insulin receptor substrate-1 (IRS-1) and glucose transporter4 (GLUT4) proteins in 3T3-L1 adipocytes or zebrafish larvae compared with control. In dexamethasone-induced resistance model of L6 myotubes, the protein expression of insulin signaling and glucose uptake was effectively increased by the treatment of COE. In contrast, the elevated phosphorylation of IRS-1 Ser307 was normally suppressed by treatment of COE. However, COE had no effect on insulin secretion in pancreatic beta cells. Thus, our results suggest that COE improves the glucose metabolism and insulin sensitivity through the regulation of insulin signaling and GLUT4 protein in insulin's target cells and zebrafish larvae.

Anti-inflammatory Effect of Berchemia berchemiaefolia Leaves through Inhibition of NF-κB and MAPK Signaling Activation in LPS-stimulated RAW264.7 Cells (망개나무 추출물의 NF-κB 및 MAPK 신호전달 억제를 통한 항염증 효과)

  • Kim, Da Som;Eo, Hyun Ji;Kang, Yeongyeong;Park, Gwang Hun
    • Korean Journal of Plant Resources
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    • v.34 no.1
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    • pp.31-36
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    • 2021
  • Berchemia berchemiaefolia (Makino) Koidz. is found not only in korea, but also in japan and is known as a rare plant all over the world. In this study, we evaluated anti-inflammatory effect of B. berchemiaefolia (Makino) Koidz. leaves (BBK-L) in LPS-stimulated RAW264.7 cells. BBK-L inhibited the generation of NO through the suppression of iNOS experession. BBK-L attenuated the expression of iNOS, COX-2, TNF-α, IL-1β, IL-6 induced by LPS. BBK-L decreased LPS-mediated IκB-α degradation inhibite which resulted in the inhibition of NF-κB activation in RAW264.7 cells. In addition, BBK-L suppressed ERK1/2, JNK phosphorylation induced by LPS. BBK-L showed anti-inflammatory effect through blocking the generation of the inflammatory mediators such as NO, iNOS, COX-2, TNF-α, IL-1β, IL-6 via the inhibiting of NF-κB and MAPK signaling activation. These results suggests that BBK-L may have great potential for the development of anti-inflammatory drug to treat acute and chronic inflammatory disorders.

Anti-inflammatory effect of soil blue-green algae Nostoc commune isolated from Daejeon National Cemetery (국립대전현충원에서 분리한 남조류 구슬말(Nostoc commune)의 항염증 효과)

  • Hong, Hyehyun;Bae, Eun Hee;Park, Tae-Jin;Kang, Min-Sung;Kang, Jae Shin;Chi, Won-Jae;Kim, Seung-Young
    • Journal of Applied Biological Chemistry
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    • v.65 no.2
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    • pp.113-120
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    • 2022
  • We examined the anti-inflammatory properties of Nostoc commune HCW0811 in lipopolysaccharide-stimulated RAW264.7 macrophage cells. The anti-inflammatory activity of HCW0811 on viability of treated cells was assessed by measuring the level of expression of NO, prostaglandin E2 and pro-inflammatory cytokines, namely interleukin-1β, interleukin-6, and tumor necrosis factor-α in HCW0811 treated RAW 264.7 macrophages. HCW0811 was non-toxic to cells and inhibited the production of cytokines in a concentration-dependent manner. In addition its treatment suppressed the production of pro-inflammatory cytokines in a dose-dependent manner, and concomitantly decreased the protein expressions of inducible NO synthase and cyclooxygenase-2. Moreover, the levels of the phosphorylation of mitogen-activated protein kinase family proteins such as extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, and nuclear factor kappa B were reduced by HCW0811. These findings suggest that the HCW0811 collected from Daejeon National Cemetery have anti-inflammatory effects, and demonstrated its efficacy in cell-based in vitro assays.

Pathophysiological Functions of Deubiquitinating Enzymes in Obesity and Related Metabolic Diseases (탈유비퀴틴화 효소 DUBs의 비만 및 대사 관련 질환에서 병태생리학적 기능)

  • Lee, Seul Gi;Kwon, Taeg Kyu
    • Journal of Life Science
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    • v.32 no.6
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    • pp.476-481
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    • 2022
  • Ubiquitin signaling regulates virtually all aspects of eukaryotic biology and dynamic processes in which protein substrates are modified by ubiquitin. To regulate these processes, deubiquitinating enzymes (DUBs) cleave ubiquitin or ubiquitin-like proteins from these substrates. DUBs have been implicated in the pathogenesis of cancer, leading to the development of increasing numbers of small-molecule DUB inhibitors. On the other hand, recent studies have focused on the function of DUBs in metabolic diseases such as obesity, diabetes, and fatty liver diseases. DUBs play a positive or negative role in the progression and development of metabolic diseases. Their involvement in cell pathology and regulation of major transcription factors in metabolic syndrome has been examined in vitro and in animal and human biopsies. UCH, USP7, and USP19 were linked to adipocyte differentiation, body weight gain, and insulin resistance in genetic or diet-induced obesity. CYLD, USP4, and USP18 were found to be closely associated with fatty liver diseases. In addition, these liver diseases were accompanied by body weight change in certain cases. Collectively, in this review, we discuss the current understanding of DUBs in metabolic diseases with a particular focus on obesity. We also provide basic knowledge and regulatory mechanisms of DUBs and suggest these enzymes as therapeutic targets for metabolic diseases.