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Effects of Adipokine Retnla on the Regulation of High-Density Lipoprotein Metabolism

  • Lee, Mi-Ran
    • Journal of the Korea Society of Computer and Information
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    • v.21 no.12
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    • pp.139-145
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    • 2016
  • In this paper, we propose to evaluate the effect of Resistin-like molecule alpha (Retnla) on the expression of transporters involved in modulating concentrations of peripheral cholesterol and plasma high-density lipoprotein (HDL) cholesterol. High levels of blood cholesterol are a well-recognized risk factor for atherosclerosis and are eliminated via the process of reverse cholesterol transport (RCT). We recently showed that Retnla ameliorates hypercholesterolemia and atherosclerosis by increasing biliary cholesterol secretion, the final step of the process, in low-density lipoprotein receptor-deficient mice. However, the role of Retnla in HDL-mediated cholesterol efflux, initial step of RCT pathway, is not yet clear. To identify cholesterol transport genes regulated by Retnla, we performed an extensive microarray-based gene expression screen using livers from Retnla-overexpressing (Tg) mice and control animals. The most significant change in Retnla-Tg mice was an upregulation of ATP-binding cassette sub-family G member 4 (Abcg4) transport and was validated using quantitative RT-PCR. The validated gene was also induced by treatment of purified Retnla protein in RAW 264.7 cells incubated with acetylated low-density lipoprotein and Hepa1c1c7 cells. Taken together, these results indicates that Retnla might also accelerate initial step of RCT pathway, suggesting therapeutic value of Retnla in the treatment of hypercholesterolemia and atherosclerosis.

Development of Digital Endoscopic Data Management System (디지탈 내시경 데이터 management system의 개발)

  • Song, C.G.;Lee, S.M.;Lee, Y.M.;Kim, W.K.
    • Proceedings of the KOSOMBE Conference
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    • v.1996 no.11
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    • pp.304-306
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    • 1996
  • Endoscopy has become a crucial diagnostic and theraputic procedure in clinical areas. Over the past three years, we have developed a computerized system to record and store clinical data pertaining to endoscopic surgery of laparascopic cholesystectomy, peviscopic endometriosis, and surgical arthroscopy. In this study, we are developed computer system, which is composed of frame grabber, sound board, VCR control board, LAN card and EDMS(endoscopic data management software). Also, computer system has controled over peripheral instruments as a color video printer, video cassette recorder, and endoscopic input/output signals(image and doctor's speech). Also, we are developed one body system of camels control unit including an endoscopic miniature camera and light source. Our system offer unsurpassed image quality in terms of resolution and color fidelity. Digital endoscopic data management system is based on open architecture and a set of widely available industry standards, namely: windows 3.1 as a operating system, TCP/IP as a network protocol and a time sequence based database that handles both an image and drctor's speech synchronized with endoscopic image.

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X-linked adrenoleukodystrophy; Recent Advances in Classification, Diagnosis and Management (X 연관 부신백질이영양증의 분류, 진단 및 치료의 최신 지견)

  • Jung, Eul Sik;Ko, Ara;Kang, Hoon-Chul
    • Journal of the Korean Child Neurology Society
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    • v.24 no.3
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    • pp.71-83
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    • 2016
  • X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ATP binding cassette subfamily D member 1 (ABCD1), a gene that encodes peroxisomal membrane located on ABC half-transporter named adrenoleukodystrophy protein (ALDP). X-ALD is characterized by a highly variable clinical spectrum, including progressive cerebral type, adrenomyeloneuropathy, and addison-only phenotype. No genotype/phenotype correlation has been established. Thus, unidentified modifier genes and other co-factors are speculated to modulate the phenotypic variation and disease severity. Recent advanced sequencing methods and reprogramming technologies not only offer an affordable and applicable approach to investigate the pathophysiological mechanisms of adrenoleukodystrophy, but also provide means to develop therapy. A causal therapy of X-ALD is lacking. Lorenzo's oil therapy is recommended for asymptomatic boys, but the longest study found that the oil was not beneficial at all to symptomatic X-ALD patients. Hematopoietic stem cell therapy has a relevant chance of success when performed during this early stage of cerebral type X-ALD. Recently, it has been insisted that lentiviral-mediated gene therapy of hematopoietic stem cells can provide clinical benefits in X-ALD. This review describes current knowledge on the clinical presentation, pathogenesis, diagnosis and management of X- ALD.

C-terminal truncated HBx reduces doxorubicin cytotoxicity via ABCB1 upregulation in Huh-7 hepatocellular carcinoma cells

  • Jegal, Myeong-Eun;Jung, Seung-Youn;Han, Yu-Seon;Kim, Yung-Jin
    • BMB Reports
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    • v.52 no.5
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    • pp.330-335
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    • 2019
  • Hepatitis B virus (HBV) encoding the HBV x protein (HBx) is a known causative agent of hepatocellular carcinoma (HCC). Its pathogenic activities in HCC include interference with several signaling pathways associated with cell proliferation and apoptosis. Mutant C-terminal-truncated HBx isoforms are frequently found in human HCC and have been shown to enhance proliferation and invasiveness leading to HCC malignancy. We investigated the molecular mechanism of the reduced doxorubicin cytotoxicity by C-terminal truncated HBx. Cells transfected with C-terminal truncated HBx exhibited reduced cytotoxicity to doxorubicin compared to those transfected with full-length HBx. The doxorubicin resistance of cells expressing C-terminal truncated HBx correlated with upregulation of the ATP binding cassette subfamily B member 1(ABCB1) transporter, resulting in the enhanced efflux of doxorubicin. Inhibiting the activity of ABCB1 and silencing ABCB1 expression by small interfering ribonucleic acid (siRNA) increased the cytotoxicity of doxorubicin. These results indicate that elevated ABCB1 expression induced by C-terminal truncation of HBx was responsible for doxorubicin resistance in HCC. Hence, co-treatment with an ABCB1 inhibitor and an anticancer agent may be effective for the treatment of patients with liver cancer containing the C-terminal truncated HBx.

Production of virus-like particles of nervous necrosis virus displaying partial VHSV's glycoprotein at surface and encapsulating DNA vaccine plasmids

  • Yang, Jeong In;Bessaid, Mariem;Kim, Ki Hong
    • Journal of fish pathology
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    • v.33 no.2
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    • pp.103-109
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    • 2020
  • In order to use nervous necrosis virus (NNV) virus-like particles (VLPs) as a delivery tool for heterologous antigens or plasmids, we attempted to produce red-spotted grouper nervous necrosis virus (RGNNV) VLPs displaying a partial region of viral hemorrhagic septicemia virus (VHSV) glycoprotein at the surface and VLPs that are harboring DNA vaccine plasmids within the VLP. A peptide encoding 105 amino acids of VHSV glycoprotein was genetically inserted in the loop region of NNV capsid gene, and VLPs expressing the partial part of VHSV glycoprotein were successfully produced. However, in the transmission electron microscope analysis, the shape and size of the partial VHSV glycoprotein-expressing NNV VLPs were irregular and variable, respectively, indicating that the normal assembly of capsid proteins was inhibited by the relatively long foreign peptide (105 aa) on the loop region. To encapsulate by simultaneous transformation with both NNV capsid gene expressing plasmids and DNA vaccine plasmids (having an eGFP expressing cassette under the CMV promoter), NNV VLPs containing plasmids were produced. The encapsulation of plasmids in the NNV VLPs was demonstrated by PCR and cells exposed to the VLPs encapsulating DNA vaccine plasmids showed fluorescence. These results suggest that the encapsulation of plasmids in NNV VLPs can be done with a simple one-step process, excluding the process of disassembly-reassembly of VLPs, and NNV VLPs can be used as a delivery tool for DNA vaccine vectors.

Effect of extraction conditions on radical scavenging and cholesterol metabolism regulating capacity of silkworm larvae

  • Kim, Soo Hyun;Jo, You-Young;Kweon, HaeYong;Lee, Ji Hae
    • International Journal of Industrial Entomology and Biomaterials
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    • v.43 no.2
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    • pp.45-51
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    • 2021
  • High blood cholesterol levels and oxidized cholesterol are risk factors for cardiovascular disease, which displays high annual incidence. Although studies on sericulture products, including pupae, silk protein, and blood lymph, as hypocholesterolemic substances have been reported, insufficient research in this field has been focused on silkworm larvae. Six larval extracts (Low temperature distilled water, LW; hot temperature distilled water, HW; and 30-100% ethanol, E30-E100) were prepared, and their effects on cholesterol metabolism were examined. LW most potently reduced the risk of cholesterol-related disorders. Polyphenols were highly represented in LW, corresponding with its increased antioxidant potency. The cholesterol biosynthesis enzyme, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) was strongly inhibited by LW. Hepatocytes over-expressed LDL receptor (LDLR) after LW stimulation, promoting cholesterol elimination from plasma. LW also increased ATP binding cassette transporter 1 (ABCA1) gene expression, upregulating HDL biogenesis. In conclusion, LW exhibited strong antioxidant activity, suppressed cholesterol biosynthesis, improved LDL uptake from plasma, and upregulated HDL biosynthesis. In aggregate, these activities could reduce blood cholesterol levels and prevent cardiovascular disease.

Impact of ABCB1 C3435T Polymorphism on Treatment Response of Vitamin K Antagonists: A Systematic Review and Meta-analysis

  • Lee, So Yeon;An, Sook Hee
    • Korean Journal of Clinical Pharmacy
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    • v.32 no.3
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    • pp.238-250
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    • 2022
  • Objective: The aim of this study was to examine the impact of ATP-binding cassette subfamily B member 1 (ABCB1) C3435T polymorphism on the treatment response of patients to vitamin K antagonists (VKAs). Methods: In this systematic review and meta-analysis, the PubMed/Medline, Embase, and Cochrane Library databases were searched for eligible articles for the period up to November 2020. Articles that reported treatment response to VKAs according to the ABCB1 C3435T polymorphism were included in this study. Results: A total of 13 and 9 articles were included in the systematic review and meta-analysis, respectively. The weekly maintenance dose of warfarin was significantly lower in patients with the ABCB1 3435CT or TT polymorphism type than in those with the ABCB1 3435CC type (weighted mean difference [WMD], -2.53 mg/week; 95% confidence interval [CI], -3.64 to -1.43, p<0.001). However, the weekly maintenance dose of acenocoumarol was not significantly associated with the ABCB1 C3435T polymorphism (WMD, 1.02; 95% CI, -0.61 to 2.65, p=0.22). Conclusion: The ABCB1 C3435T polymorphism was significantly associated with the weekly maintenance dose of warfarin. Further research is needed to confirm the association between the ABCB1 C3435T polymorphism and the incidence rate of bleeding events.

Recent progress in using Drosophila as a platform for human genetic disease research

  • Wan Hee Yoon
    • Journal of Genetic Medicine
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    • v.20 no.2
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    • pp.39-45
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    • 2023
  • As advanced sequencing technologies continue to uncover an increasing number of variants in genes associated with human genetic diseases, there is a growing demand for systematic approaches to assess the impact of these variants on human development, health, and disease. While in silico analyses have provided valuable insights, it is essential to complement these findings with model organism studies to determine the functional consequences of genetic variants in vivo. Drosophila melanogaster is an excellent genetic model for such functional studies due to its efficient genetic technologies, high gene conservation with humans, accessibility to mutant fly resources, short life cycles, and cost-effectiveness. The traditional GAL4-UAS system, allowing precise control of gene expression through binary regulation, is frequently employed to assess the effects of monoallelic variants. Recombinase medicated cassette exchange or CRISPR-Cas9-mediated GAL4 insertion within coding introns or substitution of gene body with Kozak-Gal4 result in the loss-of-function of the target gene. This GAL4 insertion strategy also enables the expression of reference complementary DNA (cDNA) or cDNA carrying genetic variants under the control of endogenous regulatory cis elements. Furthermore, the CRISPR-Cas9-directed tissue-specific knockout and cDNA rescue system provides the flexibility to investigate candidate variants in a tissue-specific and/or developmental-timing dependent manner. In this review, we will delve into the diverse genetic techniques available in Drosophila and their applications in diagnosing and studying numerous undiagnosed diseases over the past decade.

Exposure Assessment of Airborne Hexavalent Chromium in the South Korea Plating Industry (도금사업장에서 발생하는 공기 중 6가 크롬의 노출평가)

  • Ji-hyun An;Young Gyu Phee
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.34 no.1
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    • pp.98-105
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    • 2024
  • Objectives: The purpose of this study was to identify the exposure level of airborne hexavalent chromium in the plating industry and the exposure level compared to domestic and international occupational exposure limits. Methods: A total 92 samples were collected from ten industrial plating sites. Hexavalent chromium samples were collected using a three-stage cassette equipped with a 37 mm, 5 ㎛ pore size PVC filter. The analysis was performed by ion chromatography. Results: The geometric mean of hexavalent chromium concentration in the plating industry was 0.052 ㎍/m2, and it was found that the average exposure level was 0.8 times the South Korean exposure limit. When applying the US ACGIH TLV, however, the average concentration was more than twice as high. Conclusions: The South Korean exposure limit for hexavalent chromium needs to be strengthened due to significant differences in exposure levels according to domestic and international occupational exposure limits. Furthermore, respiratory and dermal sensitization should be labeled.

Detection of Nitrate/Nitrite Bioavailability in Wastewater Using a luxCDABE-Based Klebsiella oxytoca Bioluminescent Bioreporter

  • Abd-El-Haleem, Desouky;Ripp, Steven;Zaki, Sahar;Sayler, Gary S.
    • Journal of Microbiology and Biotechnology
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    • v.17 no.8
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    • pp.1254-1261
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    • 2007
  • In the present study, we have constructed a bioluminescent bioreporter for the assessment of nitrate/nitrite bioavailability in wastewater. Specifically, an approximately 500-bp DNA fragment containing a nitrate/nitrite-activated nasR-like promoter (regulating expression of genes encoding nitrite reductase in the genus Klebsiella) was fused upstream of the Vibrio fischeri luxCDABE gene cassette in a modified mini-Tn5 vector. Characterization of this strain, designated W6-1, yielded dose-dependent increased bioluminescence coincident with increased nitrate, nitrite, and ammonium added to the growth medium from 1 to 11 ppm. Bioluminescence in response to nitrogen species addition was light dependent up to 10, 7, and 8 ppm with nitrate, nitrite, and ammonium, respectively. This response was linear in the range from 1 to 8 ppm for nitrate ($R^2=0.98$), 1 to 6 ppm for nitrite ($R^2=0.99$), and 1 to 7 ppm for ammonium ($R^2=0.99$). A significant bioluminescent response was also recorded when strain W6-1 was incubated with slurries from aged, nitrate/nitrite contaminated wastewater. Thus, bioreporter strain W6-1 can be used to elucidate factors that constrain the use of nitrate/nitrite in wastewaters.