• Title/Summary/Keyword: $NAD^+$

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Increased Cellular NAD+ Level through NQO1 Enzymatic Action Has Protective Effects on Bleomycin-Induced Lung Fibrosis in Mice

  • Oh, Gi-Su;Lee, Su-Bin;Karna, Anjani;Kim, Hyung-Jin;Shen, AiHua;Pandit, Arpana;Lee, SeungHoon;Yang, Sei-Hoon;So, Hong-Seob
    • Tuberculosis and Respiratory Diseases
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    • v.79 no.4
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    • pp.257-266
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    • 2016
  • Background: Idiopathic pulmonary fibrosis is a common interstitial lung disease; it is a chronic, progressive, and fatal lung disease of unknown etiology. Over the last two decades, knowledge about the underlying mechanisms of pulmonary fibrosis has improved markedly and facilitated the identification of potential targets for novel therapies. However, despite the large number of antifibrotic drugs being described in experimental pre-clinical studies, the translation of these findings into clinical practices has not been accomplished yet. NADH:quinone oxidoreductase 1 (NQO1) is a homodimeric enzyme that catalyzes the oxidation of NADH to $NAD^+$ by various quinones and thereby elevates the intracellular $NAD^+$ levels. In this study, we examined the effect of increase in cellular $NAD^+$ levels on bleomycin-induced lung fibrosis in mice. Methods: C57BL/6 mice were treated with intratracheal instillation of bleomycin. The mice were orally administered with ${\beta}$-lapachone from 3 days before exposure to bleomycin to 1-3 weeks after exposure to bleomycin. Bronchoalveolar lavage fluid (BALF) was collected for analyzing the infiltration of immune cells. In vitro, A549 cells were treated with transforming growth factor ${\beta}1$ (TGF-${\beta}1$) and ${\beta}$-lapachone to analyze the extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT). Results: ${\beta}$-Lapachone strongly attenuated bleomycin-induced lung inflammation and fibrosis, characterized by histological staining, infiltrated immune cells in BALF, inflammatory cytokines, fibrotic score, and TGF-${\beta}1$, ${\alpha}$-smooth muscle actin accumulation. In addition, ${\beta}$-lapachone showed a protective role in TGF-${\beta}1$-induced ECM expression and EMT in A549 cells. Conclusion: Our results suggest that ${\beta}$-lapachone can protect against bleomycin-induced lung inflammation and fibrosis in mice and TGF-${\beta}1$-induced EMT in vitro, by elevating the $NAD^+$/NADH ratio through NQO1 activation.

Network Anomaly Detection Technologies Using Unsupervised Learning AutoEncoders (비지도학습 오토 엔코더를 활용한 네트워크 이상 검출 기술)

  • Kang, Koohong
    • Journal of the Korea Institute of Information Security & Cryptology
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    • v.30 no.4
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    • pp.617-629
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    • 2020
  • In order to overcome the limitations of the rule-based intrusion detection system due to changes in Internet computing environments, the emergence of new services, and creativity of attackers, network anomaly detection (NAD) using machine learning and deep learning technologies has received much attention. Most of these existing machine learning and deep learning technologies for NAD use supervised learning methods to learn a set of training data set labeled 'normal' and 'attack'. This paper presents the feasibility of the unsupervised learning AutoEncoder(AE) to NAD from data sets collecting of secured network traffic without labeled responses. To verify the performance of the proposed AE mode, we present the experimental results in terms of accuracy, precision, recall, f1-score, and ROC AUC value on the NSL-KDD training and test data sets. In particular, we model a reference AE through the deep analysis of diverse AEs varying hyper-parameters such as the number of layers as well as considering the regularization and denoising effects. The reference model shows the f1-scores 90.4% and 89% of binary classification on the KDDTest+ and KDDTest-21 test data sets based on the threshold of the 82-th percentile of the AE reconstruction error of the training data set.

Molecular Cloning and Gene Expression of Sinorhizobium meliloti Mannitol Dehydrogenase in Escherichia coli, and Its Enzymatic Characterization (Sinorhizobium meliloti 유래 Mannitol Dehydrogenase 유전자의 클로닝 및 대장균 내 발현과 효소특성 규명)

  • Jang, Myoung-Uoon;Park, Jung-Mi;Kim, Min-Jeong;Lee, So-Won;Kang, Jung-Hyun;Kim, Tae-Jip
    • Microbiology and Biotechnology Letters
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    • v.41 no.2
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    • pp.153-159
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    • 2013
  • A mannitol dehydrogenase (MDH; EC 1.1.1.67) gene was cloned from the Sinorhizobium meliloti 1021 (KCTC 2353) genome and expressed in Escherichia coli. It was seen to have an open reading frame consisting of 1,485 bp encoding 494 amino acids (about 54 kDa), which shares approximately 35-55% of amino acid sequence identity with some known long-chain dehydrogenase/ reductase family enzymes. The recombinant S. meliloti MDH (SmMDH) showed the highest activity at $40^{\circ}C$, and pH 7.0 (D-fructose reduction) and pH 9.0 (D-mannitol oxidation), respectively. SmMDH could catalyze the oxidative/reductive reactions between D-mannitol and D-fructose in the presence of $NAD^+/NADH$ as a coenzyme, but not with NADP+/NADPH. These results indicate that SmMDH is a typical $NAD^+/NADH$-dependent mannitol dehydrogenase.

Phylogenic Analysis of Locusta migratoria (Orthoptera: Acridae) in Haenam-gun and Muan-gun, Jeollanam-do, Korea Using Mitochondrial NADH dehydrogenase subunits (전라남도 해남과 무안의 풀무치 개체군에 대한 마이토콘드리아 NADH dehydrogenase subunit 들을 이용한 계통분석)

  • Lee, Gwan Seok;Kim, Young Ha;Jung, Jin Kyo;Koh, Young Ho
    • Korean journal of applied entomology
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    • v.56 no.4
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    • pp.371-376
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    • 2017
  • In a nationwide survey of the occurrence and density of the migratory locust (Locusta migratoria), high density was continuously observed in the reclaimed areas of Mangun-myeon in Muan-gun, Jeollanam-do, and Sanye-myeon in Haenam-gun, Jeollanam-do, Korea. We have analyzed the nucleotide sequences of NADH dehydrogenase subunit (NAD) 2, NAD4, and NAD5 genes in order to determine the origins of the migratory locusts at two sites. According to the analysis, the migratory locusts in Haenam-gun were closely related with those in Liaoning Province and Heilongjiang Province in the northeast China. In contrast, the migratory locusts in Muan-gun were most similar to those in Japan. Because Korean migratory locusts were not included in the previous global study on the evolution and migration of migratory locusts, we did not know the origin of Korean migratory locusts, earlier. Phylogenetic analyses this study suggested that the migratory locusts from the northeast Chinese population might have migrated and settled in Haenam-gun in Korea. Moreover, another northeast Chinese population might have migrated to Muan-gun in Korea though Sakhalin, Russia and Hokkaido, Japan. However, the possibility that the migratory locusts moved from northeast China might be isolated from each other in Korea, and that the Muan population might migrate to Japan cannot be excluded.

Effeds of Malathion on the Development of the Chick Embryo Cerebrum (계배의 대뇌의 발생에 미치는 Malathion의 영향)

  • 김완종;등용건;최임순
    • The Korean Journal of Zoology
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    • v.31 no.3
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    • pp.191-206
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    • 1988
  • Chick embryos which have received a single injection of the organophosphate compound,malathion (0.1 mg, 0.5 mg, 1.0 mg or 2.0 mg in 0.05 ml of corn oil) via the yolk sac at certain times (2 daya, 4 days or 6 days after incubation) have been investigated. After 9 days of incubation, chick embryos were harvested to investigate the effects of malathion on the development of cerebrum morphologically and biochemically. The effects of simultaneous injection of malathion and nicotinamide were also compared. On ultrastructural examination, neurons in cerebral cortex showed to be inhibited in their differentiation by malathion; nuclear irregularity, swelling of endoplasmic reticulum, and cytoplasmic vacuoles were observed. On cytochemical study of acetylcholinesterase(AChE) by electron microscope, the positive reaction products of this enryme were localized at the membrane of nucleus and endoplasmic reticulum of neurons. Inhibition of AChE activty was severe in groups treated with relatively low doses, which was consistent with the results of spectrophotometric analysis. The activity of lactate dehydrogenase(LDH) of cerebrum in groups treated with malathion was higher than that of the control group. The nicotinamide adenine dinucleotide(NAD) content of chick embruo treated with malathioti decreased significantly, and nicotinamide coinjection raised the NAD level as compared with the control group, thus preventing malathion-induced momhological alteration. In conclusion, it is suggested that malathion changes the ultrastructure of differentiating neurons and alters some enzyme activities in chick embryo cerebrum, and the severity of which is consistently dose-or age-dependent.

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자외선 조사 Escherichia coli B의 세포분열회복활성물질

  • 송방호
    • Proceedings of the Korean Society for Applied Microbiology Conference
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    • 1976.10a
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    • pp.188.2-188
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    • 1976
  • E. coli B 및 E. coli K-12의 Ion 변리주는 저중의 UV 조사에 의해 확산 및 단백질 합성은 그대로 지속되나 세포분열능은 상실되어 격막이 없는 다핵의 filament를 형성하므로 한무배지상에서 colony가 형성되지 않는다. 이와같은 균에 동일균 또는 타의 균체추출액을 가하어 주므로써 세포분열은 재개되며 그 활성물질중 $\beta-NAD가$ 중요한 인자로 작용함은 이미 발표되었으며 본보에서는 NAD 이외의 고분자활성물질에 대해 보고코저 한다.(중략)

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On the Root Rot of Ginseng(I) (인삼근부병에 관한 연구 1)

  • 김종희;이민웅
    • Korean Journal of Microbiology
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    • v.12 no.2
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    • pp.94-98
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    • 1974
  • This study was conducted from April 1 to September 31, 1973. Ten strains of Fusarium spp. were isolated from the diseased ginseng in two local areas at Kangwha-Gun nad Kumsan-Gun in Korea. Among of them, 2 strains ($G_1$, $G_4$) did not have virulence to ginseng in reinoculation. Their cultural, morphological characteristic and hose virulence to pea seedling were examined. Taxonomical identification of 8 isolates followed by the method of Wollenweber, Snyder nad Toussoun, Booth, Matuo and Snyder. All of eight strains were identified as the Fusarium solani f.sp.pisi(Jones) Synd. et Hans.

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Synthesis of Antithypertensive Agents via Couping Reaction of Benzothiazepinone and 1,4-Dihydropyridine Derivatives

  • Ham, Won-Hun;Yang, Jae-Gwon;Lim, Tae-Gyun;Jung, Yun-Ho;Chung, Yun-Sung
    • Archives of Pharmacal Research
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    • v.17 no.2
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    • pp.119-123
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    • 1994
  • The synthesis of 3a, 3b, 7a fro Benzpthiazepinone and 1,4-dihyropyridine derivatives is described. Benzothiazepinone nad 1,4-dihydropyridine derivatives were prepared according to literature procedure. The key reactions involve esterification and amidation of benzothize-pinone nad 1,4-dihydropyridine derivatives.

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Molecular Authentication of Morus Folium Using Mitochondrial nad7 Intron 2 Region

  • Jin, Chi-Gyu;Kim, Min-Kyeung;Kim, Jin-Young;Sun, Myung-Suk;Kwon, Woo-Saeng;Yang, Deok-Chun
    • Korean Journal of Plant Resources
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    • v.26 no.3
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    • pp.397-402
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    • 2013
  • Morus Folium (Sang-yeop in Korean) is one of the most important Oriental medicinal plants. In Korea, both M. alba and M. cathayana are regarded as the botanical sources for Morus Folium. In order to discriminate M. alba and M. cathayana from their adulterant, M. tricuspidata, mitochondrial NADH dehydrogenase subunit 7 (nad7) intron 2 region was targeted for molecular analysis with universal primers. DNA polymorphisms, including SNP sites, insertions, and deletions, were detected among these three species sequencing data. Based on these DNA polymorphisms, specific primers were designed for the three species respectively. Multiplex PCR was conducted for molecular authentication of M. alba, M. cathayana, and M. tricuspidata with specific primers. The present results indicate that it is possible to identify Morus Folium from its adulterant using mitochondrial nad7 intron 2 region. The established multiplex-PCR system was proved to be effective for identification of Morus Folium. The results indicate that mitochondrial introns can be used for inter-specific polymorphic study, and the described method can be applied for molecular identification of medicinal materials.

Enhanced Expression of Cell Adhesion Molecules in the Aorta of Diabetic Mice is Mediated by gp91phox-derived Superoxide

  • Yun, Mi-Ran;Kim, Jong-Jae;Lee, Sun-Mi;Heo, Hye-Jin;Bae, Sun-Sik;Kim, Chi-Dae
    • The Korean Journal of Physiology and Pharmacology
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    • v.9 no.2
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    • pp.109-115
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    • 2005
  • Endothelial activation and subsequent recruitment of inflammatory cells are important steps in atherogenesis. The increased levels of cell adhesion molecules (CAM) have been identified in diabetic vasculatures, but the underlying mechanisms remain unclear. To determine the relationship among vascular production of superoxide, expression of CAM and diabetes, superoxide generation and expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E- and P-selectin in the aorta from control (C57BL/6J) and diabetic mice (ob/ob) were measured. In situ staining for superoxide using dihydroethidium showed an increased superoxide production in diabetic aorta, accompanied with an enhanced NAD(P)H oxidase activity. Immunohistochemical analysis revealed that the endothelial expression of ICAM-1 ($3.5{\pm}0.4$) and VCAM-1 ($3.8{\pm}0.3$) in diabetic aorta was significantly higher than those in control aorta ($0.9{\pm}0.5$ and $1.6{\pm}0.3$, respectively), accompanied with the enhanced expression of gp91phox, a membrane subunit of NAD(P)H oixdase. Furthermore, there was a strong positive correlation (r=0.89, P<0.01 in ICAM-1 and r=0.88, P<0.01 in VCAM-1) between ICAM-1/VCAM-1 expression and vascular production of superoxide. The present data indicate that the increased production of superoxide via NAD(P)H oxidase may explain the enhanced expression of CAM in diabetic vasculatures.