Publications by authors named "Su-Bin Lee"

26 Publications

  • Page 1 of 1

Porous Hybrids Structure between Silver Nanoparticle and Layered Double Hydroxide for Surface-Enhanced Raman Spectroscopy.

Nanomaterials (Basel) 2021 Feb 10;11(2). Epub 2021 Feb 10.

Department of Energy and Materials Engineering, Dongguk University-Seoul, Seoul 04620, Korea.

Silver nanoparticle (AgNP), in terms of antibacterial, catalytic, electronic, and optical applications, is an attractive material. Especially, when prepared to furnish sharp edge and systematic particle orientation on the substrate, AgNPs can take advantage of surface-enhanced Raman spectroscopy (SERS). In this research, we suggested a synthetic method to immobilize the AgNP on metal oxide by utilizing Ag-thiolate and layered double hydroxide (LDH) as precursor and template, respectively. The layer-by-layer structure of LDH and Ag-thiolate transformed through reductive calcination to metal oxide and AgNP array. Physicochemical characterization, including powder X-ray diffraction, N adsorption-desorption, microscopies, and X-ray photoelectron spectroscopy, revealed that the AgNP with sufficient crystallinity and particle gap was obtained at relatively high calcination temperature, ~600 °C. UV-vis diffusion reflectance spectroscopy showed that the calcination temperature affected particle size and electronic structure of AgNP. The prepared materials were subjected to SERS tests toward 4-nitrothiophenol (4-NTP). The sample obtained at 600 °C exhibited 50 times higher substrate enhancement factor (SEF) than the one obtained at 400 °C, suggesting that the calcination temperature was a determining parameter to enhance SERS activity in current synthetic condition.
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http://dx.doi.org/10.3390/nano11020447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916476PMC
February 2021

Molecular characterization of Hsf1 as a master regulator of heat shock response in the thermotolerant methylotrophic yeast Ogataea parapolymorpha.

J Microbiol 2021 Feb 1;59(2):151-163. Epub 2021 Feb 1.

Department of Life Science, College of Natural Science, Chung-Ang University, Seoul, 06974, Republic of Korea.

Ogataea parapolymorpha (Hansenula polymorpha DL-1) is a thermotolerant methylotrophic yeast with biotechnological applications. Here, O. parapolymorpha genes whose expression is induced in response to heat shock were identified by transcriptome analysis and shown to possess heat shock elements (HSEs) in their promoters. The function of O. parapolymorpha HSF1 encoding a putative heat shock transcription factor 1 (OpHsf1) was characterized in the context of heat stress response. Despite exhibiting low sequence identity (26%) to its Saccharomyces cerevisiae homolog, OpHsf1 harbors conserved domains including a DNA binding domain (DBD), domains involved in trimerization (TRI), transcriptional activation (AR1, AR2), transcriptional repression (CE2), and a C-terminal modulator (CTM) domain. OpHSF1 could complement the temperature sensitive (Ts) phenotype of a S. cerevisiae hsf1 mutant. An O. parapolymorpha strain with an H221R mutation in the DBD domain of OpHsf1 exhibited significantly retarded growth and a Ts phenotype. Intriguingly, the expression of heat-shock-protein-coding genes harboring HSEs was significantly decreased in the H221R mutant strain, even under non-stress conditions, indicating the importance of the DBD for the basal growth of O. parapolymorpha. Notably, even though the deletion of C-terminal domains (ΔCE2, ΔAR2, ΔCTM) of OpHsf1 destroyed complementation of the growth defect of the S. cerevisiae hsf1 strain, the C-terminal domains were shown to be dispensable in O. parapolymorpha. Overexpression of OpHsf1 in S. cerevisiae increased resistance to transient heat shock, supporting the idea that OpHsf1 could be useful in the development of heat-shock-resistant yeast host strains.
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http://dx.doi.org/10.1007/s12275-021-0646-2DOI Listing
February 2021

High-throughput analysis of high-molecular weight glutenin subunits in 665 wheat genotypes using an optimized MALDI-TOF-MS method.

3 Biotech 2021 Feb 24;11(2):92. Epub 2021 Jan 24.

National Institute of Agricultural Science, RDA, Jeonju, 54874 South Korea.

Gluten protein composition determines the rheological characteristics of wheat dough and is influenced by variable alleles with distinct effects on processing properties. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), we determined the high-molecular weight glutenin subunit (HMW-GS) composition of 665 wheat genotypes employed in breeding programs in South Korea. We identified 22 HMW-GS alleles, including 3 corresponding to the locus, 14 to , and 5 to . The Glu-1 quality score, which is an important criterion for high-quality wheat development, was found to be 10 for 105/665 (15.79%) of the studied genotypes, and included the following combinations of HMW-GS: 2*, 7 + 8, 5 + 10; 2*, 17 + 18, 5 + 10; 1, 7 + 8, 5 + 10; and 1, 17 + 18, 5 + 10. To select wheat lines with the 1Bx7 overexpression (1Bx7) subunit, which is known to have a positive effect on wheat quality, we used a combination of MALDI-TOF-MS and published genotyping markers and identified 6 lines carrying 1Bx7 out of the 217 showing a molecular weight of 83,400 Da, consistent with 1Bx7 and 1Bx7. This study demonstrates that the MALDI-TOF-MS method is fast, accurate, reliable, and effective in analyzing large numbers of wheat germplasms or breeding lines in a high-throughput manner.

Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-020-02637-z.
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http://dx.doi.org/10.1007/s13205-020-02637-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829314PMC
February 2021

Establishment of a genetically engineered chicken DF-1 cell line for efficient amplification of influenza viruses in the absence of trypsin.

BMC Biotechnol 2021 Jan 7;21(1). Epub 2021 Jan 7.

Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, College of Agriculture and Life Sciences, Seoul National University, Seoul, 08826, Korea.

Background: The initial step of influenza infection is binding of the virus to specific sialic acid receptors expressed by host cells. This is followed by cell entry via endocytosis. Cleavage of the influenza virus hemagglutinin (HA) protein is critical for infection; this is performed by host cell proteases during viral replication. In cell culture systems, HA is cleaved by trypsin added to the culture medium. The vast majority of established cell lines are mammalian.

Results: In the present study, we generated genetically engineered chicken DF-1 cell lines overexpressing transmembrane protease, serine 2 (TMPRSS2, which cleaves HA), ST3 beta-galactoside alpha-2,3-sialyltransferase 1 (ST3GAL1, which plays a role in synthesis of α-2,3 linked sialic acids to which avian-adapted viruses bind preferentially), or both. We found that overexpression of TMPRSS2 supports the virus life cycle by cleaving HA. Furthermore, we found that overexpression of ST3GAL1 increased the viral titer. Finally, we showed that overexpression of both TMPRSS2 and ST3GAL1 increased the final viral titer due to enhanced support of viral replication and prolonged viability of the cells. In addition, overexpression of these genes of interest had no effect on cell proliferation and viability.

Conclusions: Taken together, the results indicate that these engineered cells could be used as a cell-based system to propagate influenza virus efficiently in the absence of trypsin. Further studies on influenza virus interactions with chicken cell host factors could be studied without the effect of trypsin on cells.
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http://dx.doi.org/10.1186/s12896-020-00663-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792337PMC
January 2021

Comparison of MALDI-TOF-MS and RP-HPLC as Rapid Screening Methods for Wheat Lines With Altered Gliadin Compositions.

Front Plant Sci 2020 4;11:600489. Epub 2020 Dec 4.

National Institute of Agricultural Sciences, RDA, Jeonju, South Korea.

The wheat gliadins are a complex group of flour proteins that can trigger celiac disease and serious food allergies. As a result, mutation breeding and biotechnology approaches are being used to develop new wheat lines with reduced immunogenic potential. Key to these efforts is the development of rapid, high-throughput methods that can be used as a first step in selecting lines with altered gliadin contents. In this paper, we optimized matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and reversed-phase high-performance liquid chromatography (RP-HPLC) methods for the separation of gliadins from cv. Chinese Spring (CS). We evaluated the quality of the resulting profiles using the complete set of gliadin gene sequences recently obtained from this cultivar as well as a set of aneuploid lines in CS. The gliadins were resolved into 13 peaks by MALDI-TOF-MS. α- or γ-gliadins that contain abundant celiac disease epitopes and are likely targets for efforts to reduce the immunogenicity of flour were found in several peaks. However, other peaks contained multiple α- and γ-gliadins, including one peak with as many as 12 different gliadins. In comparison, separation of proteins by RP-HPLC yielded 28 gliadin peaks, including 13 peaks containing α-gliadins and eight peaks containing γ-gliadins. While the separation of α- and γ-gliadins gliadins achieved by RP-HPLC was better than that achieved by MALDI-TOF-MS, it was not possible to link peaks with individual protein sequences. Both MALDI-TOF-MS and RP-HPLC provided adequate separation of ω-gliadins. While MALDI-TOF-MS is faster and could prove useful in studies that target specific gliadins, RP-HPLC is an effective method that can be applied more broadly to detect changes in gliadin composition.
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http://dx.doi.org/10.3389/fpls.2020.600489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746642PMC
December 2020

Targeted Knockout of MDA5 and TLR3 in the DF-1 Chicken Fibroblast Cell Line Impairs Innate Immune Response Against RNA Ligands.

Front Immunol 2020 30;11:678. Epub 2020 Apr 30.

Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, College of Agriculture and Life Sciences, Seoul National University, Seoul, South Korea.

The innate immune system, which senses invading pathogens, plays a critical role as the first line of host defense. After recognition of foreign RNA ligands (e.g., RNA viruses), host cells generate an innate immune or antiviral response the interferon-mediated signaling pathway. Retinoic acid-inducible gene I (RIG-1) acts as a major sensor that recognizes a broad range of RNA ligands in mammals; however, chickens lack a RIG-1 homolog, meaning that RNA ligands should be recognized by other cellular sensors such as melanoma differentiation-associated protein 5 (MDA5) and toll-like receptors (TLRs). However, it is unclear which of these cellular sensors compensates for the loss of RIG-1 to act as the major sensor for RNA ligands. Here, we show that chicken MDA5 (cMDA5), rather than chicken TLRs (cTLRs), plays a pivotal role in the recognition of RNA ligands, including poly I:C and influenza virus. First, we used a knockdown approach to show that both cMDA5 and cTLR3 play roles in inducing interferon-mediated innate immune responses against RNA ligands in chicken DF-1 cells. Furthermore, targeted knockout of cMDA5 or cTLR3 in chicken DF-1 cells revealed that loss of cMDA5 impaired the innate immune responses against RNA ligands; however, the responses against RNA ligands were retained after loss of cTLR3. In addition, double knockout of cMDA5 and cTLR3 in chicken DF-1 cells abolished the innate immune responses against RNA ligands, suggesting that cMDA5 is the major sensor whereas cTLR3 is a secondary sensor. Taken together, these findings provide an understanding of the functional role of cMDA5 in the recognition of RNA ligands in chicken DF-1 cells and may facilitate the development of an innate immune-deficient cell line or chicken model.
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http://dx.doi.org/10.3389/fimmu.2020.00678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204606PMC
March 2021

Core -Glycan Structures Are Critical for the Pathogenicity of Cryptococcus neoformans by Modulating Host Cell Death.

mBio 2020 05 12;11(3). Epub 2020 May 12.

Department of Life Science, Chung-Ang University, Seoul, South Korea

is a human-pathogenic fungal pathogen that causes life-threatening meningoencephalitis in immunocompromised individuals. To investigate the roles of -glycan core structure in cryptococcal pathogenicity, we constructed mutant strains of with defects in the assembly of lipid-linked -glycans in the luminal side of the endoplasmic reticulum (ER). Deletion of (Δ), which encodes dolichyl-phosphate-mannose (Dol-P-Man)-dependent α-1,3-mannosyltransferase, resulted in the production of truncated neutral -glycans carrying five mannose residues as a major species. Despite moderate or nondetectable defects in virulence-associated phenotypes , the Δ mutant was avirulent in a mouse model of systemic cryptococcosis. Notably, the mutant did not show defects in early stages of host cell interaction during infection, including attachment to lung epithelial cells, opsonic/nonopsonic phagocytosis, and manipulation of phagosome acidification. However, the ability to drive macrophage cell death was greatly decreased in this mutant, without loss of cell wall remodeling capacity. Furthermore, deletion of and , encoding Dol-P-Man-dependent α-1,2-mannosyltransferases and α-1,6-mannosyltransferases, generating truncated core -glycans with six and seven mannose residues, respectively, also displayed remarkably reduced macrophage cell death and virulence. However, secretion levels of interleukin-1β (IL-1β) were not reduced in the bone marrow-derived dendritic cells obtained from - and -deficient mice infected with the Δ mutant strain, excluding the possibility that pyroptosis is a main host cell death pathway dependent on intact core -glycans. Our results demonstrated -glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of We previously reported that the outer mannose chains of -glycans are dispensable for the virulence of , which is in stark contrast to findings for the other human-pathogenic yeast, Here, we present evidence that an intact core -glycan structure is required for pathogenicity by systematically analyzing , and strains that have defects in lipid-linked glycan assembly and in virulence. The null mutants producing truncated core -glycans were defective in inducing host cell death after phagocytosis, which is triggered as a mechanism of pulmonary escape and dissemination of , thus becoming inactive in causing fatal infection. The results clearly demonstrated the critical features of the -glycan structure in mediating the interaction with host cells during fungal infection. The delineation of the roles of protein glycosylation in fungal pathogenesis not only provides insight into the glycan-based fungal infection mechanism but also will aid in the development of novel antifungal agents.
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http://dx.doi.org/10.1128/mBio.00711-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218283PMC
May 2020

Host-Specific Restriction of Avian Influenza Virus Caused by Differential Dynamics of ANP32 Family Members.

J Infect Dis 2020 01;221(1):71-80

Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea.

Background: Influenza viruses must utilize host factors to complete their lifecycle. Species-specific differences in host factors between birds and mammals mean that avian influenza viruses (AIVs) replicate well in avian hosts but not in human hosts. Acidic nuclear phosphoprotein 32 family member A (ANP32A) has been identified as the host restriction factor for the viral polymerase (vPol) activity of AIVs. The ANP32A belongs to the conserved ANP32 family, the functional roles of which during viral replication remain unclear.

Methods: In this study, we targeted chicken ANP32A using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated genome editing to examine the functional roles of ANP32A and other members of the ANP32 family.

Results: We showed that chicken ANP32A only, not ANP32B and ANP32E, plays a pivotal role in supporting vPol activity of AIVs. Furthermore, we found that the human ANP32C, ANP32D, and ANP32E have suppressive effects on vPol activity in contrast to human ANP32A and ANP32B.

Conclusions: Chicken and human ANP32 family members had different effects on vPol activity, suggesting that species-specific vPol activity of AIVs could be caused by the differential functions and overall competency of ANP32 family members.
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http://dx.doi.org/10.1093/infdis/jiz506DOI Listing
January 2020

Extract (ZOE) Incorporated with Layered Double Hydroxide Hybrid through Reconstruction to Preserve Antioxidant Activity of ZOE against Ultrasound and Microwave Irradiation.

Nanomaterials (Basel) 2019 Sep 8;9(9). Epub 2019 Sep 8.

Department of Energy and Materials Engineering, Dongguk University-Seoul, Seoul 04620, Korea.

We prepared extract (ZOE) incorporated in a layered double hydroxide (LDH) hybrid through a reconstruction method in order to preserve the antioxidant activity of ZOE from ultrasound and microwave irradiation. X-ray patterns, infrared spectroscopy, and scanning electron microscopy suggested that ZOE moieties were encapsulated in the interparticle space of reconstructed LDH, thus preserving its intact structure. Dynamic light scattering and zeta-potential measurement also supported the hypothesis that ZOE moieties were located in the interparticle pore of LDH rather than at the surface of LDH particles. Thermogravimetry analysis revealed that thermal stability of encapsulated ZOE could be enhanced by LDH encapsulation. Radical scavenging assay showed that antioxidant activity of ZOE-LDH hybrid was increased after ultrasound and microwave irradiation, while ZOE itself dramatically lost its antioxidant activity upon ultrasound and microwave treatment.
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http://dx.doi.org/10.3390/nano9091281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781092PMC
September 2019

Augmentation of cellular NAD by NQO1 enzymatic action improves age-related hearing impairment.

Aging Cell 2019 10 28;18(5):e13016. Epub 2019 Jul 28.

Center for Metabolic Function Regulation (CMFR) and Department of Microbiology, Wonkwang University School of Medicine, Jeonbuk, Korea.

Age-related hearing loss (ARHL) is a major neurodegenerative disorder and the leading cause of communication deficit in the elderly population, which remains largely untreated. The development of ARHL is a multifactorial event that includes both intrinsic and extrinsic factors. Recent studies suggest that NAD /NADH ratio may play a critical role in cellular senescence by regulating sirtuins, PARP-1, and PGC-1α. Nonetheless, the beneficial effect of direct modulation of cellular NAD levels on aging and age-related diseases has not been studied, and the underlying mechanisms remain obscure. Herein, we investigated the effect of β-lapachone (β-lap), a known plant-derived metabolite that modulates cellular NAD by conversion of NADH to NAD via the enzymatic action of NADH: quinone oxidoreductase 1 (NQO1) on ARHL in C57BL/6 mice. We elucidated that the reduction of cellular NAD during the aging process was an important contributor for ARHL; it facilitated oxidative stress and pro-inflammatory responses in the cochlear tissue through regulating sirtuins that alter various signaling pathways, such as NF-κB, p53, and IDH2. However, augmentation of NAD by β-lap effectively prevented ARHL and accompanying deleterious effects through reducing inflammation and oxidative stress, sustaining mitochondrial function, and promoting mitochondrial biogenesis in rodents. These results suggest that direct regulation of cellular NAD levels by pharmacological agents may be a tangible therapeutic option for treating various age-related diseases, including ARHL.
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http://dx.doi.org/10.1111/acel.13016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718544PMC
October 2019

Hierarchical Ag Nanostructures Fabricated from Silver Coordination Polymers for Antibacterial Surface.

Polymers (Basel) 2019 Jan 17;11(1). Epub 2019 Jan 17.

Department of Chemistry and Medical Chemistry, College of Science and Technology, Yonsei University, Wonju, Gangwondo 26493, Korea.

A hierarchical silver nanostructure with improved antibacterial property was fabricated utilizing silver coordination polymer. Octadecanethiolate⁻silver polymer was synthesized to have a layered structure and was coated on silicon wafer by drop-casting method utilizing hydrophobic⁻hydrophobic interaction. Thus, the silver coordination polymer was calcined under reductive condition to produce zero-valent silver with a hierarchical nanostructure. X-ray diffraction patterns revealed that layered silver coordination polymer successfully transformed to hexagonal silver upon calcination. According to scanning electron and atomic force microscopy, silver coordination polymer with ~145.5 nm size was homogeneously coated on the surface before calcination, and it evolved micrometer-sized lumps and grooves which were composed of ~58.8 nm sized Ag nanoparticles. The hierarchical structure-micrometer lump/groove consisting of Ag nanoparticles-would be advantageous to kill bacteria; micrometer-grooves provide physical condition (pocket for bacteria capture) and the Ag nanoparticles from the neighboring lump endow chemical condition (antibacterial property of released Ag⁺). The antibacterial activity test on via colony forming inhibitory assay indeed exhibited an improved antibacterial activity of hierarchical Ag nanostructure compared with the surface simply coated with Ag nanoparticles. From the line profile of atomic force microscopy, the bacterium trapped in the hierarchical Ag nanostructure was shown to interact intimately with Ag surface.
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http://dx.doi.org/10.3390/polym11010155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401719PMC
January 2019

Pharmacological stimulation of NQO1 decreases NADPH levels and ameliorates acute pancreatitis in mice.

Cell Death Dis 2018 12 18;10(1). Epub 2018 Dec 18.

Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University School of Medicine, Iksan, Jeonbuk, 54538, Republic of Korea.

Reactive oxygen species (ROS) regulates the activation of inflammatory cascades and tissue damage in acute pancreatitis. NADPH oxidase (NOX) is upregulated in pancreatitis and is one of the major enzymes involved in ROS production using NADPH as a general rate-limiting substrate. Dunnione, a well-known substrate of NAD(P)H:quinone oxidoreductase 1 (NQO1), reduces the ratio of cellular NADPH/NADP through the enzymatic action of NQO1. This study assessed whether a reduction in cellular NADPH/NADP ratio can be used to regulate caerulein-induced pancreatic damage associated with NOX-induced ROS production in animal models. Dunnione treatment significantly reduced the cellular NADPH/NADP ratio and NOX activity through the enzymatic action of NQO1 in the pancreas of the caerulein-injection group. Similar to these results, total ROS production and expressions of mRNA and protein for NOX subunits Nox1, p27, p47, and p67 also decreased in the dunnione-treated group. In addition, caerulein-induced pancreatic inflammation and acinar cell injury were significantly reduced by dunnione treatment. This study is the first to demonstrate that modulation of the cellular NADPH:NADP ratio by enzymatic action of NQO1 protects acute pancreatitis through the regulation of NOX activity. Furthermore, these results suggest that modulation of the NADPH:NADP ratio in cells by NQO1 may be a novel therapeutic strategy for acute pancreatitis.
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http://dx.doi.org/10.1038/s41419-018-1252-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315021PMC
December 2018

Augmentation of NAD levels by enzymatic action of NAD(P)H quinone oxidoreductase 1 attenuates adriamycin-induced cardiac dysfunction in mice.

J Mol Cell Cardiol 2018 11 3;124:45-57. Epub 2018 Oct 3.

Center for Metabolic Function Regulation, & Department of Microbiology, Republic of Korea.. Electronic address:

Background: Adriamycin (ADR) is a powerful chemotherapeutic agent extensively used to treat various human neoplasms. However, its clinical utility is hampered due to severe adverse side effects i.e. cardiotoxicity and heart failure. ADR-induced cardiomyopathy (AIC) has been reported to be caused by myocardial damage and dysfunction through oxidative stress, DNA damage, and inflammatory responses. Nonetheless, the remedies for AIC are even not established. Therefore, we illustrate the role of NAD/NADH modulation by NAD(P)H quinone oxidoreductase 1 (NQO1) enzymatic action on AIC.

Methods And Results: AIC was established by intraperitoneal injection of ADR in C57BL/6 wild-type (WT) and NQO1 knockout (NQO1) mice. All Mice were orally administered dunnione (named NQO1 substrate) before and after exposure to ADR. Cardiac biomarker levels in the plasma, cardiac dysfunction, oxidative biomarkers, and mRNA and protein levels of pro-inflammatory mediators were determined compared the cardiac toxicity of each experimental group. All biomarkers of Cardiac damage and oxidative stress, and mRNA levels of pro-inflammatory cytokines including cardiac dysfunction were increased in ADR-treated both WT and NQO1 mice. However, this increase was significantly reduced by dunnione in WT, but not in NQO1 mice. In addition, a decrease in SIRT1 activity due to a reduction in the NAD/NADH ratio by PARP-1 hyperactivation was associated with AIC through increased nuclear factor (NF)-κB p65 and p53 acetylation in both WT and NQO1 mice. While an elevation in NAD/NADH ratio via NQO1 enzymatic action using dunnione recovered SIRT1 activity and subsequently deacetylated NF-κB p65 and p53, however not in NQO1 mice, thereby attenuating AIC.

Conclusion: Thus, modulation of NAD/NADH by NQO1 may be a novel therapeutic approach to prevent chemotherapy-associated heart failure, including AIC.
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http://dx.doi.org/10.1016/j.yjmcc.2018.10.001DOI Listing
November 2018

Direct Oxidation of Aldehydes to Methyl Esters with Urea Hydrogen Peroxide and -Toluenesulfonyl Chloride.

Lett Org Chem 2017 Dec;14(10):725-728

Department of Chemistry, Chung-Ang University, Seoul06974, Korea.

Combination of urea hydrogen peroxide and p-toluenesulfonyl chloride in methanol was proved to be facile and highly efficient for the oxidative methyl esterification of various aldehydes to the corresponding carboxylic methyl esters.
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http://dx.doi.org/10.2174/1570178614666170918121035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5791350PMC
December 2017

Erratum to: Ganglioside GM1 influences the proliferation rate of mouse induced pluripotent stem cells.

BMB Rep 2017 Jun;50(6):341

Department of Biological Science, College of Natural Sciences, Wonkwang University, Iksan 570-749, Korea

The BMB Reports would like to correct in the ACKNOWLEDGEMENTS of BMB Rep. 45(12), 713-718 titled "Ganglioside GM1 influences the proliferation rate of mouse induced pluripotent stem cells".
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June 2017

NAD augmentation ameliorates acute pancreatitis through regulation of inflammasome signalling.

Sci Rep 2017 06 7;7(1):3006. Epub 2017 Jun 7.

Center for Metabolic Function Regulation & Department of Microbiology, Daejeon, Republic of Korea.

Acute pancreatitis (AP) is a complicated disease without specific drug therapy. The cofactor nicotinamide adenine dinucleotide (NAD) is an important regulator of cellular metabolism and homeostasis. However, it remains unclear whether modulation of NAD levels has an impact on caerulein-induced AP. Therefore, in this study, we investigated the effect of increased cellular NAD levels on caerulein-induced AP. We demonstrated for the first time that the activities and expression of SIRT1 were suppressed by reduction of intracellular NAD levels and the p53-microRNA-34a pathway in caerulein-induced AP. Moreover, we confirmed that the increase of cellular NAD by NQO1 enzymatic action using the substrate β-Lapachone suppressed caerulein-induced AP with down-regulating TLR4-mediated inflammasome signalling, and thereby reducing the inflammatory responses and pancreatic cell death. These results suggest that pharmacological stimulation of NQO1 could be a promising therapeutic strategy to protect against pathological tissue damage in AP.
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http://dx.doi.org/10.1038/s41598-017-03418-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5462749PMC
June 2017

A Nonpregnant Woman with Group B Streptococcal Meningitis and Multifocal Embolic Infarctions.

J Clin Neurol 2016 Oct;12(4):517-518

Department of Neurology, Seonam University College of Medicine, Myongji Hospital, Goyang, Korea.

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http://dx.doi.org/10.3988/jcn.2016.12.4.517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063885PMC
October 2016

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

Tuberc Respir Dis (Seoul) 2016 Oct 5;79(4):257-266. Epub 2016 Oct 5.

Department of Microbiology, Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan, Korea.

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 β-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 β1 (TGF-β1) and β-lapachone to analyze the extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT).

Results: β-Lapachone strongly attenuated bleomycin-induced lung inflammation and fibrosis, characterized by histological staining, infiltrated immune cells in BALF, inflammatory cytokines, fibrotic score, and TGF-β1, α-smooth muscle actin accumulation. In addition, β-lapachone showed a protective role in TGF-β1-induced ECM expression and EMT in A549 cells.

Conclusion: Our results suggest that β-lapachone can protect against bleomycin-induced lung inflammation and fibrosis in mice and TGF-β1-induced EMT in vitro, by elevating the NAD/NADH ratio through NQO1 activation.
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http://dx.doi.org/10.4046/trd.2016.79.4.257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5077729PMC
October 2016

New Therapeutic Concept of NAD Redox Balance for Cisplatin Nephrotoxicity.

Biomed Res Int 2016 5;2016:4048390. Epub 2016 Jan 5.

Center for Metabolic Function Regulation, Department of Microbiology, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.

Cisplatin is a widely used chemotherapeutic agent for the treatment of various tumors. In addition to its antitumor activity, cisplatin affects normal cells and may induce adverse effects such as ototoxicity, nephrotoxicity, and peripheral neuropathy. Various mechanisms such as DNA adduct formation, mitochondrial dysfunction, oxidative stress, and inflammatory responses are closely associated with cisplatin-induced nephrotoxicity; however, the precise mechanism remains unclear. The cofactor nicotinamide adenine dinucleotide (NAD(+)) has emerged as a key regulator of cellular energy metabolism and homeostasis. Recent studies have demonstrated associations between disturbance in intracellular NAD(+) levels and clinical progression of various diseases through the production of reactive oxygen species and inflammation. Furthermore, we demonstrated that reduction of the intracellular NAD(+)/NADH ratio is critically involved in cisplatin-induced kidney damage through inflammation and oxidative stress and that increase of the cellular NAD(+)/NADH ratio suppresses cisplatin-induced kidney damage by modulation of potential damage mediators such as oxidative stress and inflammatory responses. In this review, we describe the role of NAD(+) metabolism in cisplatin-induced nephrotoxicity and discuss a potential strategy for the prevention or treatment of cisplatin-induced adverse effects with a particular focus on NAD(+)-dependent cellular pathways.
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http://dx.doi.org/10.1155/2016/4048390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4736397PMC
November 2016

Dunnione ameliorates cisplatin-induced small intestinal damage by modulating NAD(+) metabolism.

Biochem Biophys Res Commun 2015 Nov 21;467(4):697-703. Epub 2015 Oct 21.

Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea. Electronic address:

Although cisplatin is a widely used anticancer drug for the treatment of a variety of tumors, its use is critically limited because of adverse effects such as ototoxicity, nephrotoxicity, neuropathy, and gastrointestinal damage. Cisplatin treatment increases oxidative stress biomarkers in the small intestine, which may induce apoptosis of epithelial cells and thereby elicit damage to the small intestine. Nicotinamide adenine dinucleotide (NAD(+)) is a cofactor for various enzymes associated with cellular homeostasis. In the present study, we demonstrated that the hyper-activation of poly(ADP-ribose) polymerase-1 (PARP-1) is closely associated with the depletion of NAD(+) in the small intestine after cisplatin treatment, which results in downregulation of sirtuin1 (SIRT1) activity. Furthermore, a decrease in SIRT1 activity was found to play an important role in cisplatin-mediated small intestinal damage through nuclear factor (NF)-κB p65 activation, facilitated by its acetylation increase. However, use of dunnione as a strong substrate for the NADH:quinone oxidoreductase 1 (NQO1) enzyme led to an increase in intracellular NAD(+) levels and prevented the cisplatin-induced small intestinal damage correlating with the modulation of PARP-1, SIRT1, and NF-κB. These results suggest that direct modulation of cellular NAD(+) levels by pharmacological NQO1 substrates could be a promising therapeutic approach for protecting against cisplatin-induced small intestinal damage.
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http://dx.doi.org/10.1016/j.bbrc.2015.10.081DOI Listing
November 2015

Dunnione ameliorates cisplatin ototoxicity through modulation of NAD(+) metabolism.

Hear Res 2016 Mar 1;333:235-246. Epub 2015 Sep 1.

Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University School of Medicine, Iksan, Jeonbuk, 570-749, Republic of Korea. Electronic address:

Ototoxicity is an important issue in patients receiving cisplatin chemotherapy. Numerous studies have demonstrated that cisplatin-induced ototoxicity is related to oxidative stress and DNA damage. However, the precise mechanism underlying cisplatin-associated ototoxicity is still unclear. The cofactor nicotinamide adenine dinucleotide (NAD(+)) has emerged as an important regulator of energy metabolism and cellular homeostasis. Here, we demonstrate that the levels and activities of sirtuin-1 (SIRT1) are suppressed by the reduction of intracellular NAD(+) levels in cisplatin-mediated ototoxicity. We provide evidence that the decreases in SIRT1 activity and expression facilitated by increasing poly(ADP-ribose) polymerase-1 (PARP-1) activation and microRNA-34a levels through cisplatin-mediated p53 activation aggravate the associated ototoxicity. Furthermore, we show that the induction of cellular NAD(+) levels using dunnione, which targets intracellular NQO1, prevents the toxic effects of cisplatin through the regulation of PARP-1 and SIRT1 activity. These results suggest that direct modulation of cellular NAD(+) levels by pharmacological agents could be a promising therapeutic approach for protection from cisplatin-induced ototoxicity.
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http://dx.doi.org/10.1016/j.heares.2015.08.017DOI Listing
March 2016

Nicotinamide adenine dinucleotide: An essential factor in preserving hearing in cisplatin-induced ototoxicity.

Hear Res 2015 Aug 17;326:30-9. Epub 2015 Apr 17.

Center for Metabolic Function Regulation & Department of Microbiology, School of Medicine, Wonkwang University, Iksan, Jeonbuk, 570-749, Republic of Korea. Electronic address:

Ototoxicity is an important issue in patients receiving cisplatin chemotherapy. Numerous studies have demonstrated that several mechanisms, including oxidative stress, DNA damage, and inflammatory responses, are closely associated with cisplatin-induced ototoxicity. Although much attention has been directed at identifying ways to protect the inner ear from cisplatin-induced damage, the precise underlying mechanisms have not yet been elucidated. The cofactor nicotinamide adenine dinucleotide (NAD(+)) has emerged as an important regulator of cellular energy metabolism and homeostasis. NAD(+) acts as a cofactor for various enzymes including sirtuins (SIRTs) and poly(ADP-ribose) polymerases (PARPs), and therefore, maintaining adequate NAD(+) levels has therapeutic benefits because of its effect on NAD(+)-dependent enzymes. Recent studies demonstrated that disturbance in intracellular NAD(+) levels is critically involved in cisplatin-induced cochlear damage associated with oxidative stress, DNA damage, and inflammatory responses. In this review, we describe the importance of NAD(+) in cisplatin-induced ototoxicity and discuss potential strategies for the prevention or treatment of cisplatin-induced ototoxicity with a particular focus on NAD(+)-dependent cellular pathways.
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http://dx.doi.org/10.1016/j.heares.2015.04.002DOI Listing
August 2015

Cisplatin-induced Kidney Dysfunction and Perspectives on Improving Treatment Strategies.

Electrolyte Blood Press 2014 Dec 31;12(2):55-65. Epub 2014 Dec 31.

Center for Metabolic Function Regulation, Department of Microbiology, Wonkwang University School of Medicine, Iksan, Jeonbuk, Korea.

Cisplatin is one of the most widely used and highly effective drug for the treatment of various solid tumors; however, it has dose-dependent side effects on the kidney, cochlear, and nerves. Nephrotoxicity is the most well-known and clinically important toxicity. Numerous studies have demonstrated that several mechanisms, including oxidative stress, DNA damage, and inflammatory responses, are closely associated with cisplatin-induced nephrotoxicity. Even though the establishment of cisplatin-induced nephrotoxicity can be alleviated by diuretics and pre-hydration of patients, the prevalence of cisplatin nephrotoxicity is still high, occurring in approximately one-third of patients who have undergone cisplatin therapy. Therefore it is imperative to develop treatments that will ameliorate cisplatin-nephrotoxicity. In this review, we discuss the mechanisms of cisplatin-induced renal toxicity and the new strategies for protecting the kidneys from the toxic effects without lowering the tumoricidal activity.
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http://dx.doi.org/10.5049/EBP.2014.12.2.55DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297704PMC
December 2014

Phenotype difference between familial and sporadic ankylosing spondylitis in Korean patients.

J Korean Med Sci 2014 Jun 30;29(6):782-7. Epub 2014 May 30.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

Clustered occurrences of ankylosing spondylitis (AS) in family have been noticed. We evaluated patients with AS confirmed by the modified New York criteria for familial history of AS (one or more first to third degree relatives). The clinical characteristics and the recurrence risks (number of AS patients/number of familial members) of the familial AS compared to sporadic AS were investigated. Out of a total of 204 AS patients, 38 patients (18.6%) reported that they had a familial history of AS. The recurrence risks in the familial AS patients for first, second and third degree family members were 14.5%, 5.2%, and 4.4% respectively. Erythrocyte sedimentation rate (ESR) (22.6 ± 22.2 vs 35.4 ± 34.4, P=0.029) and C-reactive protein (CRP) (1.24 ± 1.7 vs 2.43 ± 3.3, P=0.003) at diagnosis, body mass index (21.9 ± 2.7 vs 23.7 ± 3.3, P=0.002) and frequency of oligoarthritis (13.2% vs 33.7%, P=0.021) were significantly lower in the familial form. The presence of HLA-B27 (97.4% vs 83.1%, P=0.044) was significantly higher in familial AS. In conclusion, Korean familial AS patients show a lower frequency of oligoarthritis, lower BMI, lower ESR and CRP at diagnosis and higher presence of HLA-B27.
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http://dx.doi.org/10.3346/jkms.2014.29.6.782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055810PMC
June 2014

Ganglioside GM1 influences the proliferation rate of mouse induced pluripotent stem cells.

BMB Rep 2012 Dec;45(12):713-8

Department of Biological Science, College of Natural Sciences, Wonkwang University, Iksan 570-749, Korea.

Gangliosides play important roles in the control of several biological processes, including proliferation and transmembrane signaling. In this study, we demonstrate the effect of ganglioside GM1 on the proliferation of mouse induced pluripotent stem cells (miPSCs). The proliferation rate of miPSCs was lower than in mouse embryonic stem cells (mESCs). Fluorescence activated cell sorting analysis showed that the percentage of cells in the G2/M phase in miPSCs was lower than that in mESCs. GM1 was expressed in mESCs, but not miPSCs. To confirm the role of GM1 in miPSC proliferation, miPSCs were treated with GM1. GM1-treated miPSCs exhibited increased cell proliferation and a larger number of cells in the G2/M phase. Furthermore, phosphorylation of mitogen-activated protein kinases was increased in GM1- treated miPSCs.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133816PMC
http://dx.doi.org/10.5483/bmbrep.2012.45.12.138DOI Listing
December 2012

Synthesis, characterization, and photovoltaic properties of soluble TiOPc derivatives.

Int J Mol Sci 2008 Dec 19;9(12):2745-56. Epub 2008 Dec 19.

Department of Polymer Science and Engineering, Pusan National University, Busan, South Korea.

We have synthesized soluble TiOPc derivatives containing alkoxy groups for use as additives in dye-sensitized solar cells (DSSCs). The DSSC devices containing these TiOPc derivatives exhibited short-circuit current densities of 8.49~10.04 mA/cm(2) and power conversion efficiencies of 2.73~3.62 % under AM 1.5 illumination and 100 mW/cm(2) irradiation.
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http://dx.doi.org/10.3390/ijms9122745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2635652PMC
December 2008