• Title/Summary/Keyword: glucose analog

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Effects of Nutrients on Quorum Signals and Secondary Metabolite Productions of Burkholderia sp. O33

  • Keum, Young-Soo;Lee, Young-Ju;Lee, Youn-Hyung;Kim, Jeong-Han
    • Journal of Microbiology and Biotechnology
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    • v.19 no.10
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    • pp.1142-1149
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    • 2009
  • Several bioactive metabolites, including pyrrolnitrin, N-acylhomoserine lactones, and polyhydroxyalkanoates were isolated from Burkholderia sp. O33. Effects of various nutrients, including sugars, gluconolactone, glycerol, tryptophan, chloride, and zinc were investigated in relation to the production of these metabolites. Logarithmic increase of pyrrolnitrin was observed between 2-5 days and reached a maximum at 7-10 days. Tryptophan concentration reached the maximum at 3 days, whereas 7-chlorotryptophan was gradually increased throughout the studies. Among various carbon sources, gluconolactone, trehalose, and glycerol enhanced pyrrolnitrin production, whereas strong inhibitory effects were found with glucose. Relative concentrations of pyrrolnitrin and its precursors were in the order of pyrrolnitrin$\gg$dechloroaminopyrrolnitrin or aminopyrrolnitrin throughout the experiments. Among three N-acylhomoserine lactones, the N-octanoyl analog was the most abundant quorum sensing signal, of which the concentrations reached the maximum in 2-3 days, followed by a rapid dissipation to trace level. No significant changes in pyrrolnitrin biosynthesis were observed by external addition of N-acylhomoserine lactones. Polyhydroxyalkanoates accumulated up to 3-4 days and decreased slowly thereafter. According to the kinetic analyses, no strong correlations were found between the levels of pyrrolnitrin, N-acylhomoserine lactones, and polyhydroxyalkanoates.

Studies of the Non-Mevalonate Pathway I. Biosynthesis of Menaquinone-7 in Bacillus subtilis II. Synthesis of Analogs of Fosmidomycin as Potential Antibacterial Agents

  • Kim, Dojung;Phillip J. Proteau
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1998.11a
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    • pp.158-158
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    • 1998
  • The non-mevalonate pathway is a newly discovered isoprenoid biosynthetic pathway in some bacteria, cyanobacteria, algae and plants. Because isoprenoid metabolites (ubiquinone, menaquinone, undecaprenol) are essential for bacterial growth, this pathway may represent a novel target for antibacterial agents. Antibiotics with a unique mechanism of action are needed to combat the risk of antibiotic resistance that is a current worldwide problem. In order to study this pathway as viable target, it was necessary to verify use of the pathway in our model system, the bacterium Bacillus subtilis. Incubation experiments with [6,6-$^2$H$_2$]-D-glucose and [l-$^2$H$_3$]-deoxy-D-xylulose were conducted to provide labeled menaquinone-7 (MK -7), the most abundant isoprenoid in B. subtilis. $^2$H-NMR analysis of the MK-7 revealed labeling patterns that strongly support utilization of the non-mevalonate pathway. Another approach to study the pathway is by structure activity relationships of proposed inhibitors of the pathway. Fosmidomycin is a phosphonic acid with antibacterial activity known to inhibit isoprenoid biosynthesis in susceptible bacteria and may act by inhibiting the non-mevalonate pathway. Fosmidomycin and an N-methyl analog were synthesized and tested for antibacterial activity. Fosmidomycin was active against Escherichia coli and B. subtilis, while N-formyl-N-methyl-3-amino-propylphosphonic acid was inactive.

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Imaging of Gastric Cancer Metabolism Using 18 F-FDG PET/CT

  • Yun, Mijin
    • Journal of Gastric Cancer
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    • v.14 no.1
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    • pp.1-6
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    • 2014
  • Aerobic glycolysis has been the most important hypothesis in cancer metabolism. It seems to be related to increased bioenergetic and biosynthetic needs in rapidly proliferating cancer cells. To this end, F-18 fluorodeoxyglucose (FDG), a glucose analog, became widely popular for the detection of malignancies combined with positron emission tomography/computed tomography (PET/CT). Although the potential roles of FDG PET/CT in primary tumor detection are not fully established, it seems to have a limited sensitivity in detecting early gastric cancer and mainly signet ring or non-solid types of advanced gastric cancer. In evaluating lymph node metastases, the location of lymph nodes and the degree of FDG uptake in primary tumors appear to be important factors affecting the diagnostic accuracy of PET/CT. In spite of the limited sensitivity, the high specificity of PET/CT for lymph node metastases may play an important role in changing the extent of lymphadenectomy or reducing futile laparotomies. For peritoneal metastases, PET/CT seems to have a poorer sensitivity but a better specificity than CT. The roles of PET/CT in the evaluation of other distant metastases are yet to be known. Studies including primary tumors with low FDG uptake or peritoneal recurrence seem suffer from poorer diagnostic performance for the detection of recurrent gastric cancer. There are only a few reports using FDG PET/CT to predict response to neoadjuvant or adjuvant chemotherapy. A complete metabolic response seems to be predictive of more favorable prognosis.

In Vitro and In Vivo Effects of Piceatannol and Resveratrol on Glucose Control and TLR4-NF-κB Pathway (피세아테놀과 레스베라트롤의 혈당조절 및 TLR4-NF-κB 경로 조절 작용)

  • Lee, Hee Jae;Lee, Hae-Jeung;Yang, Soo Jin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.2
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    • pp.267-272
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    • 2017
  • Piceatannol (PIC) is a natural hydroxylated analog of resveratrol (RSV), which is a polyphenol known to extend lifespan by stimulating sirtuins. The aim of this study was to investigate the effects of PIC and RSV on the toll-like receptor 4 (TLR4)-nuclear factor kappa B ($NF-{\kappa}B$) pathway in mouse hepatocytes and an obese/diabetic KK/HlJ mouse model. AML12 mouse hepatocytes in the absence or presence of palmitic acids (PA) were treated with PIC ($50{\mu}M$) or RSV ($50{\mu}M$). Male KK/HlJ mice at 20 weeks of age were divided into three subgroups as follows: 1) obese and diabetic control (KK), 2) KK_PIC, and 3) KK_RSV. PIC and RSV were administered orally at a dose of 10 mg/kg/d for 4 weeks. Four weeks of PIC and RSV treatment did not affect body weight or food intake in KK mice. Serum fasting blood glucose was significantly reduced in KK_PIC, and 2 h oral glucose tolerance test area under the curve was significantly reduced by PIC and RSV treatment in KK mice. PIC tended to improve homeostasis model assessment of the insulin resistance index (HOMA-IR) and HOMA beta-cells in diabetic KK mice. TLR4 and $NF-{\kappa}B$ were down-regulated by PIC and RSV treatments in hepatocytes in the absence or presence of PA. Insulin receptor, AMP-activated protein kinase, peroxisome proliferator-activated receptor gamma, nucleotide oligomerization domain-like receptor family pyrin domain-containing 3, interleukin-1, and $NF-{\kappa}B$ were altered in PIC-treated livers. Collectively, PIC and RSV inhibited the $TLR4-NF-{\kappa}B$ pathway, and PIC seems to be more effective than RSV in the regulation of analyzed targets, which are involved in insulin signaling and inflammation in vivo.

Role of Nitric Oxide in Ischemia-evoked Release of Norepinephrine from Rat Cortex Slices (흰쥐 대뇌피질 절편에서 허혈에 의한 Norepinephrine 유리에 있어서 Nitric Oxide의 영향)

  • Eun, Young-Ah;Kim, Dong-Chan;Cho, Kyu-Park;Kim, Kee-Won
    • The Korean Journal of Physiology and Pharmacology
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    • v.1 no.6
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    • pp.673-679
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    • 1997
  • It has been generally accepted that glutamate mediates the ischemic brain damage, excitotoxicity, and induces release of neurotransmitters, including norepinephrine(NE), in ischemic milieu. In the present study, the role of nitric oxide(NO) in the ischemia-induced $[^3H]norepinephrine([^3H]NE)$ release from cortex slices of the rat was examined. Ischemia, deprivation of oxygen and glucose from $Mg^{2+}-free$ artificial cerebrospinal fluid, induced significant release of $[^3H]NE$ from cortex slices. This ischemia-induced $[^3H]NE$ release was significantly attenuated by glutamatergic neurotransmission modifiers. $N^G-nitro-L-arginine$ methyl ester(L-NAME), $N^G-monomethyl-L-arginine$ (L-NMMA) or 7-nitroindazole, nitric oxide synthase inhibitors attenuated the ischemia-evoked $[^3H]NE$ release. Hemoglobin, a NO chelator, and 5, 5- dimethyl-L-pyrroline-N-oxide(DMPO), an electron spin trap, inhibited $[^3H]NE$ release dose-dependently. Ischemia-evoked $[^3H]NE$ release was inhibited by methylene blue, a soluble guanylate cyclase inhibitor, and potentiated by 8-bromo-cGMP, a cell permeable cGMP analog, zaprinast, a cGMP phosphodiesterase inhibitor, and S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide generator. These results suggest that the ischemia-evoked $[^3H]NE$ release is mediated by NMDA receptors, and activation of NO system is involved.

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L-Phenylalanine Production by Regulatory Mutants of Excherichia coli K-12 (Escherichia coli K-12 대사조절 변이주에 의한 L-페닐알라닌 생산)

  • Lee, Sae-Bae;Park, Chung;Won, Chan-Hee;Choi, Duk-Ho;Lim, Bun-San
    • Korean Journal of Microbiology
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    • v.28 no.2
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    • pp.174-179
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    • 1990
  • In order to overproduce L-phenylalanine, various kind of regulatory mutants were isolated from parental Escherichia coli K-12. MWEC 83 Producing 7.4g/l of L-phenylalanine has been derived as a tyrosine and tryptophan double auxotrophic mutant. To produce L-phenylalanine without adding L-tyrosine and L-tryptophan, revertant strain MWEC 101 was isolated from MWEC 83. Further various analogues and valine resistant mutants were isolated from MWEC 101. MWEC 101-5 was the most excellent strain that produced 17.9g/l of L-phenylalanine after having been cultivated for 54 hours in 15% glucose medium. It was disclosed that activities of rate-limiting enzymes including chorismate mutase and prephenate dehydratase in MWEC 101-5 were desensitized to 2mM L-phenylalanine in the enzyme reaction mixture and that activities level of 3-deoxy-D-arabino-heptulosonic acid-7-phosphate synthase and prephenate dehydratase were increased more than 20 times over those of the parental strain.

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Recombinant Glargine Insulin Production Process Using Escherichia coli

  • Hwang, Hae-Gwang;Kim, Kwang-Jin;Lee, Se-Hoon;Kim, Chang-Kyu;Min, Cheol-Ki;Yun, Jung-Mi;Lee, Su Ui;Son, Young-Jin
    • Journal of Microbiology and Biotechnology
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    • v.26 no.10
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    • pp.1781-1789
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    • 2016
  • Glargine insulin is a long-acting insulin analog that helps blood glucose maintenance in patients with diabetes. We constructed the pPT-GI vector to express prepeptide glargine insulin when transformed into Escherichia coli JM109. The transformed E. coli cells were cultured by fed-batch fermentation. The final dry cell mass was 18 g/l. The prepeptide glargine insulin was 38.52% of the total protein. It was expressed as an inclusion body and then refolded to recover the biological activity. To convert the prepeptide into glargine insulin, citraconylation and trypsin cleavage were performed. Using citraconylation, the yield of enzymatic conversion for glargine insulin increased by 3.2-fold compared with that without citraconylation. After the enzyme reaction, active glargine insulin was purified by two types of chromatography (ion-exchange chromatography and reverse-phase chromatography). We obtained recombinant human glargine insulin at 98.11% purity and verified that it is equal to the standard of human glargine insulin, based on High-performance liquid chromatography analysis and Matrix-assisted laser desorption/ionization Time-of-Flight Mass Spectrometry. We thus established a production process for high-purity recombinant human glargine insulin and a method to block Arg (B31)-insulin formation. This established process for recombinant human glargine insulin may be a model process for the production of other human insulin analogs.

Nuclear Imaging of Cellular Proliferation (핵의학적 세포증식 영상)

  • Yeo, Jeong-Seok
    • The Korean Journal of Nuclear Medicine
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    • v.38 no.2
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    • pp.198-204
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    • 2004
  • Tumor cell proliferation is considered to be a useful prognostic indicator of tumor aggressiveness and tumor response to therapy but in vitro measurement of individual proliferation is complex and tedious work. PET imaging provides a noninvasive approach to measure tumor growth rate in situ. Early approaches have used $^{18}F$-FDG or methionine to monitor proliferation status. These 2 tracers detect changes in glucose and amino acid metabolism, respectively, and therefore provide only an indirect measure of proliferation status. More recent studies have focused on DNA synthesis itself as a marker of cell proliferation. Cell lines and tissues with a high proliferation rate require high rates of DNA synthesis. $[^{11}C]Thymidine$ was the first radiotracer for noninvasive imaging of tumor proliferation. The short half-life of $^{11}C$ and rapid metabolism of $[^{11}C]Thymidine$ in vivo make the radiotracer less suitable for routing use. Halogenated thymidine analogs such as 5-iodo-2-deoxyuridine (IUdR) can be successfully used as cell proliferation markers for in vitro studies because these compounds are rapidly incorporated into newly synthesized DNA. IUdR has been evaluated as a potential in vivo tracer in nuclear medicing but the image qualify and the calculation of proliferation rates are impaired by its rapid in vivo degradation. Hence, the thymidine analog $3'-deoxy-3'-^{18}F-fluorothymidine$ (FLT) was recently introduced as a stable proliferation marker with a suitable nuclide half-life and stable in vivo. $[^{18}F]FLT$ is phosphorylated to 3-fluorothymidine monophosphate by thymidine kinase 1 and reflects thymidine kinase 1 activity in proliferating cell. $[^{18}F]FLT$ PET is feasible in clincal use and well correlates with cellular proliferation. Choline is a precursor for the biosynthesis of phospholipids (in particular, phosphatidylcholine), which is the essential component of all eukaryotic cell membranes and $[^{11}C]choline$, which is a new marker for cellular proliferation.

Prediction of Prognosis to Concurrent Chemo-Radiotherapy by Standardized Uptake Value of $2-[18^F]$ Fluovo-2-Deoxy-D-Glucose for Nasopharyngeal Carcinomas (비인강암 환자의 예후에서 $2-[18^F]$ Fluoro-2-Deoxy-D-Glucose PET 영상에서 계산되는 Standardized Uptake Value의 의의)

  • Lee Sang-wook;Im Ki Chun;Nam Soon Yuhl;Kim Jae Seung;Choi Eun Kyung;Ahn Seung Do;Shin Seong Soo;Ryu Jin Sook;Kim Sang Yoon;Lee Bong-Jae;Choi Seung-Ho;Kim Sung-Bae;Moon Dae Hyuk
    • Radiation Oncology Journal
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    • v.23 no.1
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    • pp.9-16
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    • 2005
  • Purpose : To prospectively evaluate the use of positron emission tomography with the glucose analog fluoro-deoxyglucose (FDG-PET) to deoxyglucose (FDG-PET) to predict disease-free survival (DFS) after concurrent chemo-radiotherapy (CCRT) in patients with non-disseminated nasopharyngeal carcinoma (NPC). Materials and Methods : We studied 41 patients with non-disseminated NPC scheduled to undergo platinum-based CCRT were eligible for this study. Patients were studied by FDG-PET prior to the CCRT. FDG uptake of tumors were measured with the maximal standardized uptake value (SUV). Results : Complete response rate was $100\%$. In ten patients who presented with any component of treatment failure, the median $SUV_{max}$ was 8.55 (range: $2.49\~14.81$) in any component of failure and the median $SUV_{max}$ was 5.48 (range: $2.31\~26.07$) In the remaining patients without any such failure. Patients having tumors with high FDG uptake had a significantly lower 3-year DFS ($51\%\;{\nu}91\%$, p=0.0070) compared with patients having low uptake tumors. Conclusion : FDG uptake, as measured by the SUV, has potential value in predicting DFS in NPC treated by CCRT, High FDG uptake may be a useful parameter for Identifying patients requiring more aggressive treatment approaches.

A Design and Implementation of NFC Bridge Chip (NFC 브릿지 칩 설계 및 구현)

  • Lee, Pyeong-Han;Ryu, Chang-Ho;Chun, Sung-Hun;Kim, Sung-Wan
    • Journal of the Institute of Electronics and Information Engineers
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    • v.52 no.3
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    • pp.96-101
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    • 2015
  • This paper describes a design and implementation of the NFC bridge chip which performs interface between kinds of devices and mobile phones including NFC controller through NFC communication. The NFC bridge chip consists of the digital part and the analog part which are based on NFC Forum standard. Therefore the chip treats RF signals and then transforms the signal to digital data, so it can interface kinds of devices with the digital data. Especially the chip is able to detect RF signals and then wake up the host processor of a device. The wakeup function dramatically decreases the power consumption of the device. The carrier frequency is 13.56MHz, and the data rate is up to 424kbps. The chip has been fabricated with SMIC 180nm mixed-mode technology. Additionally an NFC bridge chip application to the blood glucose measurement system is described for an application example.