• Title/Summary/Keyword: Drug transfer

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Effects of 3-Phenyl-1-isoquinolinamine on the Metabolism of ${\beta}$-Amyloid Precursor Protein in Neuroblastoma Cells (3-페닐-1-이소퀴놀린아민이 신경세포에서 베타 아밀로이드 전구단백질의 대사에 미치는 영향)

  • Leem, Jae-Yoon;Cho, Won-Jea
    • YAKHAK HOEJI
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    • v.54 no.6
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    • pp.529-534
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    • 2010
  • Alzheimer's disease (AD) is characterized pathologically by the presence of intracellular neurofibrillary tangles and deposition of ${\beta}$-amyloid ($A{\beta}$) peptides, which are generated by processing of amyloid precursor protein (APP). It is urgent to develop effective therapies for the treatment of AD, since our society rapidly accelerate aging. $A{\beta}$ peptides have been believed to be neurotoxic and now are also considered to have effects on the mechanism of memory formation. Recently, we investigated that a quinoline compound from natural product reduced the secretion of $A{\beta}$ from the neuroblastoma N2a cells (NL/N cell line) overexpressing APPswe. In this study, 3-phenyl-1-isoquinolinamine, a synthetic isoquinoline compound was analyzed to determine its effects on the metabolism of APP. It inhibited the secretion of $A{\beta}$ peptides from the N2a NL/N cell line. Beta-site APP cleaving enzyme (BACE) fluorescence resonance energy transfer (FRET) assay revealed that it inhibited BACE activity in a dose dependent manner. Immunoblotting study showed that it inhibited APP stabilization and expression and it slightly increased the stablization and the expression of ${\gamma}$-secreatase component from the N2a NL/N cell line. We suggest that 3-phenyl-1-isoquinolinamine inhibits APP metabolism and $A{\beta}$ generation by the means of BACE inhibitory mechanism. This is the first report that 3-phenyl-1-isoquinolinamine inhibits the secretion of $A{\beta}$ peptides from neuroblastoma cells.

Measuring Efficiency of National R&D Programs within Nanotechnology Field Using DEA Model (DEA모형을 활용한 나노기술 분야 국가 R&D 과제의 효율성 분석)

  • Bae, Seoung-Hun;Kim, Jun-Hyun;Yoon, Jin-Seon;Kang, Sang-Kyu;Shin, Kwang-Min;Cho, Su-Ji;Lee, Ki-Kwang
    • Journal of Korean Society of Industrial and Systems Engineering
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    • v.39 no.2
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    • pp.64-71
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    • 2016
  • Recently, nanotechnology has grown as one of the leading science technology along with other converging technologies such as biology, information, medicine etc., bringing the continuous investment of the government in nano-related field. However, it is difficult to measure and evaluate the performance of the national research and development programs because of the multidimensional character of the expected outcomes. This study aims to measuring efficiency of the national nanotechnology research and development programs using DEA model. The decision making units are nine nano-related ministries including the Ministry of Science, ICT and Future Planning. The input variables are total expenditure, number of the programs and average expenditure per program. The output variables are science, technology and economic indicator, and the combination of these outputs are respectively measured as seven different DEA cases. The Ministry of Science, ICT and Future was the first efficient ministry in total technical efficiency. Ministry of Agriculture, Food and Rural Affairs and the Ministry of Food and Drug Safety were efficient in pure technical efficiency, when the Ministry of Commerce Industry and Energy took the first in the scale efficiency. The program efficiency was affected by organizational characteristics such as the institution's scale, the concentration of the research paper or the patent, technology transfer or the commercialization. The result of this study could be utilized in development of the policy in the nanotechnology and the related field. Furthermore, it could be applied for the modification of expenditure management or the adjustment of the research and development programs' input and output scale for each ministry.

Molecular epidemiologic analysis of pathogenic Escherichia coli isolated from poultry in Korea (국내 가금 유래 병원성 대장균의 분자역학적 분석)

  • Sung, Myung-Suk;Kim, Jin-Hyun;Kim, Ki-Seuk
    • Korean Journal of Veterinary Research
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    • v.50 no.3
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    • pp.239-246
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    • 2010
  • Among 203 avian pathogenic Escherichia coli (APEC) isolated from poultry with colibacillosis in korea, 14 isolates were selected from total 68 isolates transferred R plasmid and classified into 5 groups on the basis of antimicrobial minimal inhibitory concentration (MIC) pattern, farm source and O serotype. An association between clonal origin and R plasmid of them was investigated by R plasmid profile, restriction endonuclease analysis and pulsed-field gel electrophoresis (PFGE). The strains that showed the same or very similar antimicrobial MIC pattern, but different farm source and O serotype, revealed different PFGE pattern, which seemed to be different clonal origin. And the strains that showed the same MIC pattern and O serotype, revealed different PFGE pattern, seemed to be originated from different clone. Also the strains showing the same MIC pattern and farm source, but different O serotype, revealed to be different clonal origin. The strains that showed the same or similar MIC pattern, farm source, and O serotype, revealed identical or similar PFGE pattern, which seemed to belong to be one clone. Meanwhile, horizontal transfer of R plasmid seems to be common in APEC with regardless of O serotype and clone of the strains. These results indicate that rapid and accurate epidemiological survey of APEC can be possible by the combination of O serotyping, plasmid profiling and PFGE analysis following the classification of them into groups of antimicrobial drug resistance pattern.

Binding model for eriodictyol to Jun-N terminal kinase and its anti-inflammatory signaling pathway

  • Lee, Eunjung;Jeong, Ki-Woong;Shin, Areum;Jin, Bonghwan;Jnawali, Hum Nath;Jun, Bong-Hyun;Lee, Jee-Young;Heo, Yong-Seok;Kim, Yangmee
    • BMB Reports
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    • v.46 no.12
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    • pp.594-599
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    • 2013
  • The anti-inflammatory activity of eriodictyol and its mode of action were investigated. Eriodictyol suppressed tumor necrosis factor (mTNF)-${\alpha}$, inducible nitric oxide synthase (miNOS), interleukin (mIL)-6, macrophage inflammatory protein (mMIP)-1, and mMIP-2 cytokine release in LPS-stimulated macrophages. We found that the anti-inflammatory cascade of eriodictyol is mediated through the Toll-like Receptor (TLR)4/CD14, p38 mitogen-activated protein kinases (MAPK), extracellular-signal-regulated kinase (ERK), Jun-N terminal kinase (JNK), and cyclooxygenase (COX)-2 pathway. Fluorescence quenching and saturation-transfer difference (STD) NMR experiments showed that eriodictyol exhibits good binding affinity to JNK, $8.79{\times}10^5M^{-1}$. Based on a docking study, we propose a model of eriodictyol and JNK binding, in which eriodictyol forms 3 hydrogen bonds with the side chains of Lys55, Met111, and Asp169 in JNK, and in which the hydroxyl groups of the B ring play key roles in binding interactions with JNK. Therefore, eriodictyol may be a potent anti-inflammatory inhibitor of JNK.

Virulence, Resistance Genes, and Transformation Amongst Environmental Isolates of Escherichia coli and Acinetobacter spp.

  • Doughari, Hamuel James;Ndakidemi, Patrick Alois;Human, Izanne Susan;Benade, Spinney
    • Journal of Microbiology and Biotechnology
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    • v.22 no.1
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    • pp.25-33
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    • 2012
  • The association of verotoxic E. coli and Acinetobacter spp. with various antibiotic-resistant, diarrhogenic, and nosocomial infections has been a cause for concern worldwide. E. coli and A. haemolyticus isolated on a number of selective media were screened for virulence factors, antibiotic resistance, and transformation of resistance genes. Out of 69 E. coli isolates obtained, 25 (35.23%), 14 (20.30%), and 28 (40.58%) were positive for Vtx1&2, Vtx1, and Vtx2, respectively, 49 (71.015%) for extendedspectrum beta-lactamases (ESBLs), 34 (49.28%) for serum resistance, 57 (82.61%) for cell surface hydrophobicity, 48 (69.57%) for gelatinase production, and 37 (53.62%) for hemolysin production. For the 14 A. haemolyticus isolates, only 2 (14.29%) in each case from all the samples investigated were positive for Vtx1, Vtx2 and Vtx1&2 respectively, 8 (57.14%) for ESBLs, 7 (50.00%) for serum resistance, 11 (78.57%) for cell surface hydrophobicity, 4 (28.57%) for gelatinase production, and 8 (57.14%) for hemolysin production. Although transformation occurred among the E. coli and Acinetobacter isolates (transformation frequency: $13.3{\times}10^{-7}-53.4^{-7}$), there was poor curing of the plasmid genes, a confirmation of the presence of stable antibiotic-resistant genes (DNA concentration between 42.7 and 123.8 ${\mu}g$) and intragenetic transfer of multidrug-resistant genes among the isolates. The isolates were potentially virulent and contained potentially transferable antibiotic resistance genes. Detection of virulence factors, antibiotic resistance genes, and transformation among these isolates is a very significant outcome that will influence approaches to proactive preventive and control measures and future investigations. However, continued surveillance for drug resistance among these bacteria and further investigation of the mechanism of action of their virulence factors are a necessity.

Mitochondrial Genome Sequences of Spirometra erinaceieuropaei and S. decipiens (Cestoidea: Diphyllobothriidae)

  • Eom, Keeseon S.;Park, Hansol;Lee, Dongmin;Choe, Seongjun;Kim, Kyu-Heon;Jeon, Hyeong-Kyu
    • Parasites, Hosts and Diseases
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    • v.53 no.4
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    • pp.455-463
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    • 2015
  • The present study was performed to compare the mitochondrial genomes between 2 Spirometra tapeworms, Spirometra erinaceieuropaei and Spirometra decipiens (Cestoidea: Diphyllobothriidae), which larval stages are important etiological agents of sparganosis in humans. For each species, the full mitochondrial genome was amplified in 8 overlapping fragments using total genomic DNA purified from a single worm as the template. The mitochondrial genomes were 13,643 bp (S. erinaceieuropaei) and 13,641 bp (S. decipiens) in length and contained 36 genes; 12 protein-coding genes, 2 ribosomal RNA (rRNA, small and large subunits), and 22 transfer RNAs (tRNAs). The 12 protein-coding genes constituted 10,083 bp (S. erinaceieuropaei) and 10,086 bp (S. decipiens) of their respective mitochondrial genomes. The tRNA genes, ranging in length from 56 to 70 bp, were identified based on putative secondary structures such as the typical cloverleaf shape. A total of 23 intergenic sequences, varying from 1 to 204 bp in size, were interspersed in S. erinaceieuropaei (total, 504 bp) and S. decipiens (total, 496 bp) mtDNA. The 12 protein-coding genes of S. erinaceieuropaei and S. decipiens differed by 12.4%, whereas the overall difference in mtDNA sequence between S. erinaceieuropaei and S. decipiens was 12.9%. Thus, from the standpoint of the mitochondrial genome, S. decipiens represents a valid species that can be distinguished from S. erinaceieuropaei.

Egg Antibody Farming and IgY Technology for Food and Biomedical Applications

  • Sim, J.S.;Sunwoo, H.H.
    • Korean Journal of Poultry Science
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    • v.31 no.1
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    • pp.37-44
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    • 2004
  • It has been recognized that the hen, like its mammalian counterparts, provides young chicks with antibodies as protection against hostile invaders. This system facilitates the transfer of specific antibodies from serum to egg yolk, and provides a supply of antibodies called immunoglobulin Y(IgY) to the developing embryo and the hatched chick. The protection against pathogens that the relatively immune-incompetent newly hatched chick has, is through transmission of antibodies from the mother via the egg. Egg yolk, therefore, can be loaded with a large amount of IgY against pathogens which can immobilize the existing or invading pathogens during the embryo development or in day-old chicks. Thus, the immunization of laying hens to various pathogens results in production of different antigen-specific IgY in eggs. Egg yolk contains 8∼20 mg of jmmunoglobulins (IgY) per ml or 136∼340 mg per yolk suggesting that more than 30 g of IgY can be obtained from one immunized hen in a year. By immunizing laying hens with antigens and collecting IgY from egg yolk, low cost antibodies at less than $10 per g compared to more than $20,000 per g of mammalian IgG can be obtained. This IgY technology opens new potential market applications in medicine, public health, veterinary medicine and food safety. A broader use of IgY technology could be applied as biological or diagnostic tool, nutraceutical or functional food development, oral-supplementation for prophylaxis, and as pathogen-specific antimicrobial agents for infectious disease control. This paper has emphasized that when IgY-loaded chicken eggs are produced and consumed, the specific antibody binds, immobilizes and consequently reduces or inhibits the growth or colony forming abilities of microbial pathogens. This concept could serve as an alternative agent to replace the use of antibiotics, since today, more and more antibiotics are less effective in the treatment of infections, due to the emergence of drug-resistant bacteria.

Soluble Expression and Purification of the Catalytic Domain of Human Vascular Endothelial Growth Factor Receptor 2 in Escherichia coli

  • Wei, Jia;Cao, Xiaodan;Zhou, Shengmin;Chen, Chao;Yu, Haijun;Zhou, Yao;Wang, Ping
    • Journal of Microbiology and Biotechnology
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    • v.25 no.8
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    • pp.1227-1233
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    • 2015
  • Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis through binding to its specific receptors, which mainly occurs to VEGF receptor 2 (VEGFR-2), a kinase insert domain-containing receptor. Therefore, the disruption of VEGFR-2 signaling provides a promising therapeutic approach for the treatment of cancer by inhibiting abnormal or tumorinduced angiogenesis. To explore this potential, we expressed the catalytic domain of VEGFR-2 (VEGFR-2-CD) as a soluble active kinase in Escherichia coli. The recombinant protein was purified and the VEGFR-2-CD activity was investigated. The obtained VEGFR-2-CD showed autophosphorylation activity and phosphate transfer activity comparable to the commercial enzyme. Furthermore, the IC50 value of known VEGFR-2 inhibitor was determined using the purified VEGFR-2-CD. These results indicated a possibility for functional and economical VEGFR-2-CD expression in E. coli to use for inhibitor screening.

Genetic Relatedness within Streptococcus pneumoniae Serotype 19F and 23F Isolates in Korea by Pulsed-Field Gel Electrophoresis

  • Lee, Kwang-Jun;Bae, Song-Mee;Hwang, Kyu-Jam;Lee, Young-Hee;Kim, Ki-Sang
    • Journal of Microbiology
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    • v.41 no.1
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    • pp.1-6
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    • 2003
  • The genetic relatedness of multidrug-resistant pneumococcal isolates of serotypes 19F and 23F was investigated. The DNA fragments digested with Sma I were resolved by pulsed-field gel electrophoresis (PFGE). PFGE analysis of 365. pneumoniae isolates showed 13 different patterns. Among 22 isolates of serotype 19F, 9 different PFGE patterns were present and 14 isolates of serotype 23F isolates represented 5 distinct PFGE patterns. Two isolates of serotype 19F and six isolates of serotype 23F shared the same PFGE pattern (Pattern I). Based on the genetic relatedness within the strains (one genetic cluster was defined as having more than 85% homology), we divided the pneumococcal strains into genefic clusters (Ⅰ, II, III, IV, V, and VI). The 22 strains of serotype 19F belonged to five distinct genetic clusters (I, II, III, IV, V and VI) and 14 strains of serotype 23F represented two genetic clusters (I and II ). These results showed that strains of serotype 19F are genetically more diverse than those of serotype 23F, Serotype 19F isolates with PFGE patterns H and I appeared to be less related to those of the remaining PFCE patterns (A to G) (less than 60% genetic relatedness), but those strains were genetically closely related with serotype 23f. These results suggest that the latter isolates originated from horizontal transfer of the capsular type 19F gene locus to 23F pneumococcal genotypes. In conclusion, the multidrug-resistant pneumococcal isolates of serotype 19f and 23F isolated in Korea are the result of the spread of a limited number of resistant clones.

Clinical efficacy of chloroquine versus artemether-lumefantrine for Plasmodium vivax treatment in Thailand

  • Krudsood, Srivicha;Tangpukdee, Noppadon;Muangnoicharoen, Sant;Thangchartwet, Vipa;Luplertlop, Nutthanej;Srivilarit, Siripan;Wilairatana, Polrat;Kano, Shigeyuki;Ringwald, Pascal;Looareesuwan, Sornchai
    • Parasites, Hosts and Diseases
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    • v.45 no.2 s.142
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    • pp.111-114
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    • 2007
  • Chloroquine remains the drug of choice for the treatment of vivax malaria in Thailand. Mixed infections of falciparum and vivax malaria are also common in South-East Asia. Laboratory confirmation of malaria species is not generally available. This study aimed to find alternative regimens for treating both malaria species by using falciparum antimalarial drugs. From June 2004 to May 2005, 98 patients with Plasmodium vivax were randomly treated with either artemether-lumefantrine (n = 47) or chloroquine (n = 51). Both treatments were followed by 15 mg of primaquine over 14 days. Adverse events and clinical and parasitological outcomes were recorded and revealed similar in both groups. The cure rate was 97.4% for the artemether-lumefantrine treated group and 100% for the chloroquine treated group. We concluded that the combination of artemether-lumefantrine and primaquine was well tolerated, as effective as chloroquine and primaquine, and can be an alternative regimen for treatment of vivax malaria especially in the event that a mixed infection of falciparum and vivax malaria could not be ruled out.