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Endogenous catalase delays high-fat diet-induced liver injury in mice

  • Piao, Lingjuan;Choi, Jiyeon;Kwon, Guideock;Ha, Hunjoo
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.3
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    • pp.317-325
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    • 2017
  • Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease in parallel with worldwide epidemic of obesity. Reactive oxygen species (ROS) contributes to the development and progression of NAFLD. Peroxisomes play an important role in fatty acid oxidation and ROS homeostasis, and catalase is an antioxidant exclusively expressed in peroxisome. The present study examined the role of endogenous catalase in early stage of NAFLD. 8-week-old male catalase knock-out (CKO) and age-matched C57BL/6J wild type (WT) mice were fed either a normal diet (ND: 18% of total calories from fat) or a high fat diet (HFD: 60% of total calories from fat) for 2 weeks. CKO mice gained body weight faster than WT mice at early period of HFD feeding. Plasma triglyceride and ALT, fasting plasma insulin, as well as liver lipid accumulation, inflammation (F4/80 staining), and oxidative stress (8-oxo-dG staining and nitrotyrosine level) were significantly increased in CKO but not in WT mice at 2 weeks of HFD feeding. While phosphorylation of Akt (Ser473) and $PGC1{\alpha}$ mRNA expression were decreased in both CKO and WT mice at HFD feeding, $GSK3{\beta}$ phosphorylation and Cox4-il mRNA expression in the liver were decreased only in CKO-HF mice. Taken together, the present data demonstrated that endogenous catalase exerted beneficial effects in protecting liver injury including lipid accumulation and inflammation through maintaining liver redox balance from the early stage of HFD-induced metabolic stress.

Selective Inhibition of Bicyclic Tetrapeptide Histone Deacetylase Inhibitor on HDAC4 and K562 Leukemia Cell

  • Li, Xiao-Hui;Huang, Mei-Ling;Wang, Shi-Miao;Wang, Qing
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7095-7100
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    • 2013
  • Histone deacetylase (HDAC) inhibitors of cyclic peptide have been proved to be the most complex but the most stable and relative efficient inhibitors because of their large cap region. In this paper, a series of studies were carried out to evaluate the efficacy of synthetic bicyclic tetrapeptide inhibitors 1-5 containing hydroxamic acid referring molecular docking, anti-proliferation, morphology and apoptosis. Docking analysis, together with enzyme inhibitory results, verified the selective capability of inhibitor 4 to HDAC4, which might closely related to haematological tumorigenesis, with Phe227, Asp115, Pro32, His198 and Ser114 participating into hydrophobic interactions and Van der Waals force which was familiar with former study. Moreover, inhibitor 4 inhibited K562 cell line at the $IC_{50}$ value of 1.22 ${\mu}M$ which was 51-67 times more efficient than that for U937 and HL60 cell lines. Inhibitor 4 exhibited the cell cycle-arrested capability to leukemia at S phase or G2/M phase as well as apoptosis-induced ability in different degrees. Finally, we considered that bicyclic tetrapeptide inhibitors were promising inhibitors used in cancer treatment and inhibitor 4 could prevent K562 cell line well from proliferation, arrest cell cycle and induce K562 towards apoptosis to achieve the goals of reversing cancer cells which could become a potential leukemia therapeutic agent in the future.

Channel Estimation in E-OCR for T-DMB System (T-DMB 시스템을 위한 E-OCR에서의 채널추정)

  • Park, Sung-Ik;Lim, Hyoung-Soo;Kim, Heung-Mook;Oh, Wang-Rok
    • Journal of Broadcast Engineering
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    • v.13 no.5
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    • pp.565-573
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    • 2008
  • This paper proposes noise reduction methods to improve the channel estimation performance in Equalization On-Channel Repeater (E-OCR) for Terrestrial-Digital Multimedia Broadcasting (T-DMB) system. In the E-OCR for T-DMB system, the channel estimation is performed by the pilot signal extraction and the channel coefficient estimation. Since the performance of the channel estimation highly depends on the estimated channel coefficients whose accuracy is associated with the received signal-to-noise ratio (SNR), it is important to reduce noise existing at the estimated channel coefficients. To reduce such noise components, various noise reduction methods of the estimated channel coefficients based on the M -point weighted moving average are proposed. Computer simulations show that the proposed methods improve the estimation performance by more than 2 to 3 dB in terms of the symbol error rate after equalization.

Induced freezing tolerance and free amino acids perturbation of spinach by exogenous proline

  • Shin, Hyunsuk;Oh, Sewon;Kim, Daeil;Hong, Jeum Kyu;Yun, Jae Gil;Lee, Sang Woo;Son, Ki-Ho
    • Journal of Plant Biotechnology
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    • v.45 no.4
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    • pp.357-363
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    • 2018
  • The objective of this study was to investigate whether exogenous proline (Pro) could confer freezing tolerance of spinach and determine fluctuations of free amino acids in spinach leaf tissues under freeze-induced stress. Treatment with Pro (10 mM) resulted in more accumulation of Pro (~2.6-fold) in Pro-treated spinaches compared to untreated ones. These Pro-pretreated spinaches were more freezing-tolerant, showing more turgid leaves and petioles compared to untreated controls. However, when spinaches pre-treated with or without Pro were subjected to freezing, there was no significant difference in overall amino acid contents, emphasizing the role of Pro as an osmoprotectant. Freezing stress prompted intensification of total amino acid contents irrespective of pretreatment with Pro. Asp, Glu, Ala, and Val were the most abundant free amino acids due to increased protein degradation and nitrogen mobilization for plant survival under freezing stress. Arg, a precursor for the synthesis of polyamines in plants, was profoundly enhanced under freezing stress. This implies that Arg plays an important role in modulating freezing tolerance. Gly, Leu, and Ile were maintained at relatively low levels in all treatments. However, Ser, Tyr, and Lys as primary constituents of dehydrins were accumulated under freezing stress, suggesting that they might play a role in increasing cryoprotective activity under freezing stress.

Failure of Ciprofloxacin Therapy in the Treatment of Community-Acquired Acute Pyelonephritis caused by In-Vitro Susceptible Escherichia coli Strain Producing CTX-Type Extended-Spectrum β-Lactamase

  • Seok, Hyeri;Cha, Min Kyeong;Kang, Cheol-In;Cho, Sun Young;Kim, So Hyun;Ha, Young Eun;Chung, Doo Ryeon;Peck, Kyong Ran;Song, Jae-Hoon
    • Infection and chemotherapy
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    • v.50 no.4
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    • pp.357-361
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    • 2018
  • While carbapenems are the drug of choice to treat extended-spectrum-${\beta}$-lactamase (ESBL)-producing strains, some alternative carbapenem-sparing regimens are suggested for antibiotic stewardship. We experienced a case of ciprofloxacin treatment failure for acute pyelonephritis caused by an apparently susceptible Escherichia coli. A 71-year-old woman presented the emergency department with fever for 7 days and bilateral flank pain for 2 days. The laboratory results and abdominopelvic computed tomography finding were compatible with acute pyelonephritis. During 3-day ciprofloxacin therapy, the patient remained febrile with persistent bacteremia. After the change in antibiotics to ertapenem, the patient's clinical course started to improve. ESBL-producing E. coli isolates were identified in all three consecutive blood samples. Pulsed-field gel electrophoresis (PFGE) patterns, serotypes, and sequence types showed the three isolates were derived from the identical strain. The isolates produced CTX-M-14 type ESBL belonging to the ST69 clonal group. Despite in vitro susceptibility, the failure was attributed to a gyrA point mutation encoding Ser83Leu within quinolone resistance-determining regions. This case suggests that ciprofloxacin should be used cautiously in the treatment of serious infections caused by ciprofloxacin-susceptible, ESBL-producing E. coli, even in acute pyelonephritis because in-vitro susceptibility tests could fail to detect certain genetic mutations.

Chip Implementation of 830-Mb/s/pin Transceiver for LPDDR2 Memory Controller (LPDDR2 메모리 컨트롤러를 위한 830-Mb/s/pin 송수신기 칩 구현)

  • Jong-Hyeok, Lee;Chang-Min, Song;Young-Chan, Jang
    • Journal of IKEEE
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    • v.26 no.4
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    • pp.659-670
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    • 2022
  • An 830-Mb/s/pin transceiver for a controller supporting ×32 LPDDR2 memory is designed. The transmitter consists of eight unit circuits has an impedance in the range of 34Ω ∽ 240Ω, and its impedance is controlled by an impedance correction circuit. The transmitted DQS signal has a phase shifted by 90° compared to the DQ signals. In the receive operation, the read time calibration is performed by per-pin skew calibration and clock-domain crossing within a byte. The implemented transceiver for the LPDDR2 memory controller is designed by using a 55-nm process using a 1.2V supply voltage and has a maximum signal transmission rate of 830 Mb/s/pin. The area and power consumption of each lane are 0.664 mm2 and 22.3 mW, respectively.

New Evidence of Alleles (V199I and G52S) at the PRKAG3 (RN) Locus Affecting Pork Meat Quality

  • Chen, J.F.;Dai, L.H.;Peng, J.;Li, J.L.;Zheng, R.;Zuo, B.;Li, F.E.;Liu, M.;Yue, K.;Lei, M.G.;Xiong, Y.Z.;Deng, C.Y.;Jiang, S.W.
    • Asian-Australasian Journal of Animal Sciences
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    • v.21 no.4
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    • pp.471-477
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    • 2008
  • The porcine PRKAG3 (RN) gene encodes the regulatory gamma subunit of adenosine monophosphate-activated protein kinase (AMPK), which is a good candidate gene affecting meat quality. In this study, the effects of two missense mutations A595G (Ile199Val) and G154A (Gly52Ser) in porcine PRKAG3 gene on meat quality traits were studied in M. Longissimus dorsi (LD), M. Semispinalis capitis (SC) and M. Biceps femoris (BF) from different populations of 326 pigs. The PRKAG3 alleles 199I, 199IV, 52S and 52G were identified with PCR-RFLPs and all genotypes - 199I/199I, 199I/199V, 199V/199V, 52S/52S, 52S/52G and 52G/52G - were found. The frequency of V allele was larger than that of I allele in all populations. I allele frequency was zero in Chinese Meishan pigs (population D) especially. G allele frequency was larger than that of S allele in all populations except Large White (population A). Both variations at the PRKAG3 locus significantly affected these meat quality traits. The pork meat quality has not previously been established in Meishan or crosses thereof. The results suggested that generally pH of LD, SC and BF was higher in Meishan pigs than that in other populations. Moreover, Meishan pigs showed higher water-holding capacity and intramuscular fat (IMF), lower water content and water loss percentage compared to other populations in terms of the two variations. The results present here supply new evidence that alleles V199I and G52S at the PRKAG3 locus affect pork meat quality and provide useful information on pork production.

gyrA Mutations Found Among Ofloxacin-resistant Mycobacterium tuberculosis is Isolated from Korea

  • Kim Junho;Kim Yeun;Bae Kiho;Song Taek-Sun;Cho Sang-Nae;Lee Hyeyoung
    • Biomedical Science Letters
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    • v.11 no.4
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    • pp.465-471
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    • 2005
  • Ofloxacin has antimycobacterial activity that possibly contributes a pivotal role in the second-line drug regimens that are used for the treatment of multidrug-resistant tuberculosis. However, in some communities, the resistance rate of Mycobacterium tuberculosis to this agent is surging. Therefore, a rapid and accurate method that can be used to determine the resistance of M tuberculosis to the ofloxacin can be very useful for effective treatment of the patients. As an effort to develop such a method, this study was set up to reveal general types of mutations that are related to ofloxacin resistance of M tuberculosis. From previous studies, it has been well known that ofloxacin resistance is associated with mutations in a gene encoding the gyrase A subunit protein. In this study, we obtained 43 ofloxacin-resistant and 50 ofloxacin-susceptible M tuberculosis clinical isolates from Masan National TB Hospital, and sequences of DNA fragment of 320 bp, region of gyrA corresponding to the ofloxacin resistance-determining region were analyzed. In brief, the results showed that a total of seven mutation types were found at gyrA. Theses mutations were all clustered within nucleotides 2574 to 2586 of the gyrA gene (codons 88 to 94). Codon 94 was the most frequently substituted site. Twenty-four of the 43 isolates had mutations at this position resulting in a total of five different types of amino acid changes $(Asp{\to}Ala,\;Asp{\to}Gly,\;Asp{\to}His,\;Asp{\to}Tyr,\;and\;Asp{\to}Asn)$. Five isolates contained a mutation at codon 90 resulting $Ala{\to}Val$ change. Four isolates had mutations at codon 91 causing a $Ser{\to}Pro$ change at this site. Two isolates contained a mutation at codon 88 and each of them resulted in different types of amino acid changes $(Gly{\to}Cys,\;Gly{\to}Ala)$. On the other hand, polymorphic site at codon 95 was found in both ofloxacin-resistant and ofloxacin-susceptible isolates. From these results, we concluded that the rate of mutations present in gyrA among ofloxacin-resistant M. tuberculosis in Korea is similar to the general rates of mutations found throughout the world. Subsequently, an oligonucleotide probe was designed based on the results of sequence analysis and was used to develop a dot blot hybridization assay system to determine ofloxacin-resistance of M tuberculosis. To evaluate this probe, dot-blot hybridization was carried out using other 57 clinical isolates, and the results showed that the dot-blot hybridization assay is good for detecting sequence alterations atgyrA gene.

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Pharmacologic Inhibition of Autophagy Sensitizes Human Acute Leukemia Jurkat T Cells to Acacetin-Induced Apoptosis

  • Lee, Ji Young;Jun, Do Youn;Kim, Ki Yun;Ha, Eun Ji;Woo, Mi Hee;Ko, Jee Youn;Yun, Young Ho;Oh, In-Seok;Kim, Young Ho
    • Journal of Microbiology and Biotechnology
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    • v.27 no.1
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    • pp.197-205
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    • 2017
  • Exposure of Jurkat T cell clone (J/Neo cells) to acacetin (5,7-dihydroxy-4'-methoxyflavone), which is present in barnyard millet (Echinochloa esculenta (A. Braun)) grains, caused cytotoxicity, enhancement of apoptotic $sub-G_1$ rate, Bak activation, loss of mitochondrial membrane potential (${\Delta}{\Psi}m$), activation of caspase-9 and caspase-3, degradation of poly(ADP-ribose) polymerase, and FITC-Annexin V-stainable phosphatidylserine exposure on the external surface of the cytoplasmic membrane without accompanying necrosis. These apoptotic responses were abrogated in Jurkat T cell clone (J/Bcl-xL) overexpressing Bcl-xL. Under the same conditions, cellular autophagic responses, including suppression of the Akt-mTOR pathway and p62/SQSTM1 down-regulation, were commonly detected in J/Neo and J/Bcl-xL cells; however, formation of acridine orange-stainable acidic vascular organelles, LC3-I/II conversion, and Beclin-1 phosphorylation (Ser-15) were detected only in J/Neo cells. Correspondingly, concomitant treatment with the autophagy inhibitor (3-methyladenine or LY294002) appeared to enhance acacetin-induced apoptotic responses, such as Bak activation, ${\Delta}{\Psi}m$ loss, activation of caspase-9 and caspase-3, and apoptotic $sub-G_1$ accumulation. This indicated that acacetin could induce apoptosis and cytoprotective autophagy in Jurkat T cells simultaneously. Together, these results demonstrate that acacetin induces not only apoptotic cell death via activation of Bak, loss of ${\Delta}{\Psi}m$, and activation of the mitochondrial caspase cascade, but also cytoprotective autophagy resulting from suppression of the Akt-mTOR pathway. Furthermore, pharmacologic inhibition of the autophagy pathway augments the activation of Bak and resultant mitochondrial damage-mediated apoptosis in Jurkat T cells.

Purification and Characterization of a Novel Extracellular Thermostable Alkaline Protease from Streptomyces sp. M30

  • Xin, Yan;Sun, Zhibin;Chen, Qiongzhen;Wang, Jue;Wang, Yicheng;Luogong, Linfeng;Li, Shuhuan;Dong, Weiliang;Cui, Zhongli;Huang, Yan
    • Journal of Microbiology and Biotechnology
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    • v.25 no.11
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    • pp.1944-1953
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    • 2015
  • A novel alkaline protease from Streptomyces sp. M30, SapHM, was purified by ammonium sulfate precipitation, hydrophobic interaction chromatography, and DEAE-Sepharose chromatography, with a yield of 15.5% and a specific activity of 29,070 U/mg. Tryptic fragments of the purified SapHM were obtained by electrospray ionization quadrupole time-of-flight mass spectrometry. Nucleotide sequence analysis revealed that the gene sapHM contained 1,179 bp, corresponding to 392 amino acids with conserved Asp156, His187, and Ser339 residues of alkaline protease. The first 24 amino acid residues were predicted to be a signal peptide, and the molecular mass of the mature peptide was 37.1 kDa based on amino acid sequences and mass spectrometry. Pure SapHM was optimally active at 80℃ in 50 mM glycine-NaOH buffer (pH 9.0), and was broadly stable at 0-50℃ and pH 4.0-9.0. The protease relative activity was increased in the presence of Ni2+, Mn2+, and Cu2+ to 112%, 113%, and 147% of control, respectively. Pure SapHM was also activated by dimethylformamide, dimethyl sulfoxide, Tween 80, and urea. The activity of the purified enzyme was completely inhibited by phenylmethylsulfonyl fluoride, indicating that it is a serine-type protease. The Km and Vmax values were estimated to be 35.7 mg/ml, and 5 × 104 U/mg for casein. Substrate specificity analysis showed that SapH was active on casein, bovine serum albumin, and bovine serum fibrin.