Publications by authors named "Young Ho Seo"

81 Publications

New compression method for full-complex holograms using the modified zerotree algorithm with the adaptive discrete wavelet transform.

Opt Express 2020 Nov;28(24):36327-36345

In this paper, we propose a new method for coding a full complex hologram with random phase. Since holograms with random phase have very unique spatial and frequency characteristics, a new compression method suitable for such holograms is required. We analyze the frequency characteristics of holograms with random phases and propose a new adaptive discrete wavelet transform (aDWT). Next, we propose a new modified zerotree alogrithm (mZTA) suitable for the subband configuration generated by the modified wavelet transform method. The results of the compression using the proposed method showed higher efficiency than the previous method, and the reconstructed images showed visually superior results.
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http://dx.doi.org/10.1364/OE.406165DOI Listing
November 2020

Holographic augmented reality based on three-dimensional volumetric imaging for a photorealistic scene.

Opt Express 2020 Nov;28(24):35972-35985

In this paper, we propose a new system for a real-time holographic augmented reality (AR) video service based on a photorealistic three-dimensional (3D) object point for multiple users to use simultaneously at various locations and viewpoints. To observe the object from all viewpoints, a camera system capable of acquiring the 3D volume of a real object is developed and is used to generate a real object in real-time. Using the normal of the object point, the observable points are mapped to the viewpoint at which the user is located, and a hologram based on the object point is generated. The angle at which the reflected light from each point is incident on the hologram plane is calculated, and the intensity of the interference light is adjusted according to the angle to generate a hologram with a higher 3D effect. The generated hologram is transmitted to each user to provide a holographic AR service. The entire system consists of a camera system comprising eight RGB-D (depth) cameras and two workstations for photorealistic 3D volume and hologram generation. Using this technique, a realistic hologram was generated. Through experiments displaying holograms simultaneously from several different viewpoints, it is confirmed that multiple users can concurrently receive hologram AR.
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http://dx.doi.org/10.1364/OE.411141DOI Listing
November 2020

Structural Basis for Design of New Purine-Based Inhibitors Targeting the Hydrophobic Binding Pocket of Hsp90.

Int J Mol Sci 2020 Dec 9;21(24). Epub 2020 Dec 9.

Center for Neuro-Medicine, Brain Science Institute, KIST, Seoul 02792, Korea.

Inhibition of the molecular chaperone heat shock protein 90 (Hsp90) represents a promising approach for cancer treatment. BIIB021 is a highly potent Hsp90 inhibitor with remarkable anticancer activity; however, its clinical application is limited by lack of potency and response. In this study, we aimed to investigate the impact of replacing the hydrophobic moiety of BIIB021, 4-methoxy-3,5-dimethylpyridine, with various five-membered ring structures on the binding to Hsp90. A focused array of /-substituted purines, featuring aromatic and non-aromatic rings, was designed, considering the size of hydrophobic pocket B in Hsp90 to obtain insights into their binding modes within the ATP binding site of Hsp90 in terms of π-π stacking interactions in pocket B as well as outer α-helix 4 configurations. The target molecules were synthesized and evaluated for their Hsp90α inhibitory activity in cell-free assays. Among the tested compounds, the isoxazole derivatives and , and the sole six-membered derivative showed favorable Hsp90α inhibitory activity, with IC values of 1.76 µM, 0.203 µM, and 1.00 µM, respectively. Furthermore, compound 14 elicited promising anticancer activity against MCF-7, SK-BR-3, and HCT116 cell lines. The X-ray structures of compounds , , , , and bound to the -terminal domain of Hsp90 were determined in order to understand the obtained results and to acquire additional structural insights, which might enable further optimization of BIIB021.
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http://dx.doi.org/10.3390/ijms21249377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763603PMC
December 2020

MeBib Suppressed Methamphetamine Self-Administration Response via Inhibition of BDNF/ERK/CREB Signal Pathway in the Hippocampus.

Biomol Ther (Seoul) 2020 Nov;28(6):519-526

College of Pharmacy, Keimyung University, Daegu 42601, Republic of Korea.

Methamphetamine (MA) is one of the most commonly abused drugs in the world by illegal drug users. Addiction to MA is a serious public health problem and effective therapies do not exist to date. It has also been reported that behavior induced by psychostimulants such as MA is related to histone deacetylase (HDAC). MeBib is an HDAC6 inhibitor derived from a benzimidazole scaffold. Many benzimidazole-containing compounds exhibit a wide range of pharmacological activity. In this study, we investigated whether HDAC6 inhibitor MeBib modulates the behavioral response in MA self-administered rats. Our results demonstrated that the number of active lever presses in MA self-administered rats was reduced by pretreatment with MeBib. In the hippocampus of rats, we also found MA administration promotes GluN2B, an NMDA receptor subunit, expression, which results in sequential activation of ERK/CREB/BDNF pathway, however, MeBib abrogated it. Collectively, we suggest that MeBib prevents the MA seeking response induced by MA administration and therefore, represents a potent candidate as an MA addiction inhibitor.
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http://dx.doi.org/10.4062/biomolther.2020.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585641PMC
November 2020

Preparation and Characteristics of Wet-Spun Filament Made of Cellulose Nanofibrils with Different Chemical Compositions.

Polymers (Basel) 2020 Apr 19;12(4). Epub 2020 Apr 19.

College of Forest & Environmental Science, Kangwon National University, Chuncheon 24341, Korea.

In this study, wet-spun filaments were prepared using lignocellulose nanofibril (LCNF), with 6.0% and 13.0% of hemicellulose and lignin, respectively, holocellulose nanofibril (HCNF), with 37% hemicellulose, and nearly purified-cellulose nanofibril (NP-CNF) through wet-disk milling followed by high-pressure homogenization. The diameter was observed to increase in the order of NP-CNF ≤ HCNF < LCNF. The removal of lignin improved the defibrillation efficiency, thus increasing the specific surface area and filtration time. All samples showed the typical X-ray diffraction pattern of cellulose I. The orientation of CNFs in the wet-spun filaments was observed to increase at a low concentration of CNF suspensions and high spinning rate. The increase in the CNF orientation improved the tensile strength and elastic modulus of the wet-spun filaments. The tensile strength of the wet-spun filaments decreased in the order of HCNF > NP-CNF > LCNF.
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http://dx.doi.org/10.3390/polym12040949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240502PMC
April 2020

Hybrid inhibitors of DNA and HDACs remarkably enhance cytotoxicity in leukaemia cells.

J Enzyme Inhib Med Chem 2020 Dec;35(1):1069-1079

College of Pharmacy, Keimyung University, Daegu, Republic of Korea.

Chlorambucil is a nitrogen mustard-based DNA alkylating drug, which is widely used as a front-line treatment of chronic lymphocytic leukaemia (CLL). Despite its widespread application and success for the initial treatment of leukaemia, a majority of patients eventually develop acquired resistance to chlorambucil. In this regard, we have designed and synthesised a novel hybrid molecule, chloram-HDi that simultaneously impairs DNA and HDAC enzymes. Chloram-HDi efficiently inhibits the proliferation of HL-60 and U937 leukaemia cells with GI values of 1.24 µM and 1.75 µM, whereas chlorambucil exhibits GI values of 21.1 µM and 37.7 µM against HL-60 and U937 leukaemia cells, respectively. The mechanism behind its remarkably enhanced cytotoxicity is that chloram-HDi not only causes a significant DNA damage of leukaemia cells but also downregulates DNA repair protein, Rad52, resulting in the escalation of its DNA-damaging effect. Furthermore, chloram-HDi inhibits HDAC enzymes to induce the acetylation of -tubulin and histone H3.
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http://dx.doi.org/10.1080/14756366.2020.1754812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191901PMC
December 2020

Development of Thiazolidinedione-Based HDAC6 Inhibitors to Overcome Methamphetamine Addiction.

Int J Mol Sci 2019 Dec 9;20(24). Epub 2019 Dec 9.

College of Pharmacy, Keimyung University, Daegu 42601, Korea.

Thiazolidinedione is a five-membered heterocycle that is widely used in drug discovery endeavors. In this study, we report the design, synthesis, and biological evaluation of a series of thiazolidinedione-based HDAC6 inhibitors. In particular, compound exerts an excellent inhibitory activity against HDAC6 with an IC value of 21 nM, displaying a good HDAC6 selectivity over HDAC1. Compound dose-dependently induces the acetylation level of -tubulin via inhibition of HDAC6 in human neuroblastoma SH-SY5Y cell line. Moreover, compound efficiently reverses methamphetamine-induced morphology changes of SH-SY5Y cells via regulating acetylation landscape of -tubulin. Collectively, compound represents a novel HDAC6-isoform selective inhibitor and demonstrates promising therapeutic potential for the treatment of methamphetamine addiction.
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http://dx.doi.org/10.3390/ijms20246213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940941PMC
December 2019

Ultra-thin ion exchange film on the ceramic supporter for output power improvement of reverse electrodialysis.

Sci Rep 2019 11 25;9(1):17440. Epub 2019 Nov 25.

Advanced Mechanical Engineering, Kangwon National University, 1 Gangwondaehak-gil, Chuncheon, 24341, South Korea.

In this study, ultra-thin ion exchange film on the ceramic supporter (UTFCS) composed of thin polymer layer and nanoporous ceramic layer with low electrical resistance was developed. The electrical properties and permselectivity of UTFCSs were evaluated and the properties of UTFCSs were compared with other ion exchange membranes. Fabricated UTFCSs were applied to a reverse electrodialysis (RED) system to evaluate the output characteristics and compared with other ion exchange membranes. The power density of RED using UTFCS was 36.6 mW/m, which was 8% higher than that of a commercial anion exchange membrane. In addition, possibility as power source was experimentally verified by driving LEDs. The proposed UTFCS can be applied not only to RED but also to energy development such as fuel cells and microbial cells.
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http://dx.doi.org/10.1038/s41598-019-54002-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6877634PMC
November 2019

Design, synthesis and biological evaluation of a series of CNS penetrant HDAC inhibitors structurally derived from amyloid-β probes.

Sci Rep 2019 Sep 12;9(1):13187. Epub 2019 Sep 12.

College of Pharmacy, Keimyung University, Daegu, 42601, South Korea.

To develop novel CNS penetrant HDAC inhibitors, a new series of HDAC inhibitors having benzoheterocycle were designed, synthesized, and biologically evaluated. Among the synthesized compounds, benzothiazole derivative 9b exhibited a remarkable anti-proliferative activity (GI = 2.01 μM) against SH-SY5Y cancer cell line in a dose and time-dependent manner, better than the reference drug SAHA (GI = 2.90 μM). Moreover, compound 9b effectively promoted the accumulation of acetylated Histone H3 and α-tubulin through inhibition of HDAC1 and HDAC6 enzymes, respectively. HDAC enzyme assay also confirmed that compound 9b efficiently inhibited HDAC1 and HDAC6 isoforms with IC values of 84.9 nM and 95.9 nM. Furthermore, compound 9b inhibited colony formation capacity of SH-SY5Y cells, which is considered a hallmark of cell carcinogenesis and metastatic potential. The theoretical prediction, in vitro PAMPA-BBB assay, and in vivo brain pharmacokinetic studies confirmed that compound 9b had much higher BBB permeability than SAHA. In silico docking study demonstrated that compound 9b fitted in the substrate binding pocket of HDAC1 and HDAC6. Taken together, compound 9b provided a novel scaffold for developing CNS penetrant HDAC inhibitors and therapeutic potential for CNS-related diseases.
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http://dx.doi.org/10.1038/s41598-019-49784-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6742641PMC
September 2019

Hair Metabolomics in Animal Studies and Clinical Settings.

Molecules 2019 Jun 12;24(12). Epub 2019 Jun 12.

College of Pharmacy, Keimyung University, 1095 Dalgubeoldaero, Dalseo-gu, Daegu 42601, Korea.

Metabolomics is a powerful tool used to understand comprehensive changes in the metabolic response and to study the phenotype of an organism by instrumental analysis. It most commonly involves mass spectrometry followed by data mining and metabolite assignment. For the last few decades, hair has been used as a valuable analytical sample to investigate retrospective xenobiotic exposure as it provides a wider window of detection than other biological samples such as saliva, plasma, and urine. Hair contains functional metabolomes such as amino acids and lipids. Moreover, segmental analysis of hair based on its growth rate can provide information on metabolic changes over time. Therefore, it has great potential as a metabolomics sample to monitor chronic diseases, including drug addiction or abnormal conditions. In the current review, the latest applications of hair metabolomics in animal studies and clinical settings are highlighted. For this purpose, we review and discuss the characteristics of hair as a metabolomics sample, the analytical techniques employed in hair metabolomics and the consequence of hair metabolome alterations in recent studies. Through this, the value of hair as an alternative biological sample in metabolomics is highlighted.
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http://dx.doi.org/10.3390/molecules24122195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630908PMC
June 2019

Evaluation of the Inhibitory Effects of (E)-1-(2-hydroxy-4,6-dimethoxyphenyl)-3-(naphthalen-1-yl)prop-2-en-1-one (DiNap), a Natural Product Analog, on the Replication of Type 2 PRRSV In Vitro and In Vivo.

Molecules 2019 Mar 3;24(5). Epub 2019 Mar 3.

College of Veterinary Medicine, Chonbuk National University, Iksan 54596, Korea.

DiNap [()-1-(2-hydroxy-4,6-dimethoxyphenyl)-3-(naphthalen-1-yl)prop-2-en-1-one], an analog of a natural product (the chalcone flavokawain), was synthesized and characterized in this study. Porcine reproductive and respiratory syndrome virus (PRRSV) is the most challenging threat to the swine industry worldwide. Currently, commercially available vaccines are ineffective for controlling porcine reproductive and respiratory syndrome (PRRS) in pigs. Therefore, a pharmacological intervention may represent an alternative control measure for PRRSV infection. Hence, the present study evaluated the effects of DiNap on the replication of VR2332 (a prototype strain of type 2 PRRSV). Initially, in vitro antiviral assays against VR2332 were performed in MARC-145 cells and porcine alveolar macrophages (PAMs). Following this, a pilot study was conducted in a pig model to demonstrate the effects of DiNap following VR2332 infection. DiNap inhibited VR2332 replication in both cell lines in a dose-dependent manner, and viral growth was completely suppressed at concentrations ≥0.06 mM, without significant cytotoxicity. Consistent with these findings, in the pig study, DiNap also reduced viral loads in the serum and lungs and enhanced the weight gain of pigs following VR2332 infection, as indicated by comparison of the DiNap-treated groups to the untreated control (NC) group. In addition, DiNap-treated pigs had fewer gross and microscopic lesions in their lungs than NC pigs. Notably, virus transmission was also delayed by approximately 1 week in uninfected contact pigs within the same group after treatment with DiNap. Taken together, these results suggest that DiNap has potential anti-PRRSV activity and could be useful as a prophylactic or post-exposure treatment drug to control PRRSV infection in pigs.
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http://dx.doi.org/10.3390/molecules24050887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429065PMC
March 2019

Correction to: Development of a column-switching LC-MS/MS method of tramadol and its metabolites in hair and application to a pharmacogenetic study.

Arch Pharm Res 2019 04;42(4):372

College of Pharmacy, Keimyung University, 1095 Dalgubeoldaero, Dalseo-gu, Daegu, 42601, Republic of Korea.

In the original version of the article titled "Development of a column-switching LC-MS/MS method of tramadol and its metabolites in hair and application to a pharmacogenetic study", published in 41(5):554-563 (https://doi.org/10.1007/s12272-018-1013-7), unfortunately an important statement was missing in the Clinical study section by the author.
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http://dx.doi.org/10.1007/s12272-018-01105-wDOI Listing
April 2019

A novel class of anthraquinone-based HDAC6 inhibitors.

Eur J Med Chem 2019 Feb 24;164:263-272. Epub 2018 Dec 24.

College of Pharmacy, Keimyung University, Daegu, 42601, Republic of Korea. Electronic address:

Histone deacetylase 6 (HDAC6) is an important target for the treatment of diverse diseases including cancer, neurodegenerative diseases, autoimmune disorders, inflammation, drug addiction, and viral infection. Therefore, the discovery of HDAC6-isoform selective inhibitors is of high importance for clinical applications. Here, we present an approach to discover HDAC6-isoform selective inhibitors. To our best knowledge, we for the first time perform a virtual screening campaign in the surface and channel region of HDAC6 enzyme, followed by rational installation of zinc binding group for the development of HDAC6-isoform selective inhibitors. Consequently, this approach establishes the proof of principle for the discovery of HDAC6-isoform selective inhibitors and successfully provides our lead compound 3. In particular, compound 3 inhibits HDAC6 enzyme with an IC value of 56 nM and displays an excellent HDAC6 selectivity over other HDAC isoforms in HDAC enzyme assay. Furthermore, the exposure of SH-SY5Y cells with compound 3 significantly promotes the acetylation of α-tubulin at the low concentration of 0.5 μM, but not the acetylation of Histone H3 up to 20 μM. Thus, our lead compound 3 represents a novel HDAC6-isoform selective inhibitor and warrants further studies for therapeutic evaluation.
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http://dx.doi.org/10.1016/j.ejmech.2018.12.056DOI Listing
February 2019

Epicatechin Prevents Methamphetamine-Induced Neuronal Cell Death via Inhibition of ER Stress.

Biomol Ther (Seoul) 2019 Mar;27(2):145-151

College of Pharmacy, Keimyung University, Daegu 42601, Republic of Korea.

Methamphetamine (METH) acts strongly on the nervous system and damages neurons and is known to cause neurodegenerative diseases such as Alzheimer's and Parkinson's. Flavonoids, polyphenolic compounds present in green tea, red wine and several fruits exhibit antioxidant properties that protect neurons from oxidative damage and promote neuronal survival. Especially, epicatechin (EC) is a powerful flavonoid with antibacterial, antiviral, antitumor and antimutagenic effects as well as antioxidant effects. We therefore investigated whether EC could prevent METH-induced neurotoxicity using HT22 hippocampal neuronal cells. EC reduced METH-induced cell death of HT22 cells. In addition, we observed that EC abrogated the activation of ERK, p38 and inhibited the expression of CHOP and DR4. EC also reduced METH-induced ROS accumulation and MMP. These results suggest that EC may protect HT22 hippocampal neurons against METH-induced cell death by reducing ER stress and mitochondrial damage.
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http://dx.doi.org/10.4062/biomolther.2018.092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430228PMC
March 2019

Small Molecule Inhibitors of HSF1-Activated Pathways as Potential Next-Generation Anticancer Therapeutics.

Molecules 2018 Oct 24;23(11). Epub 2018 Oct 24.

College of Pharmacy, Keimyung University, Daegu 42601, Korea.

Targeted therapy is an emerging paradigm in the development of next-generation anticancer drugs. Heat shock factor 1 (HSF1) has been identified as a promising drug target because it regulates several pathways responsible for cancer cell growth, metastasis, and survival. Studies have clearly demonstrated that HSF1 is an effective drug target. Herein, we provide a concise yet comprehensive and integrated overview of progress in developing small molecule inhibitors of HSF1 as next-generation anticancer chemotherapeutics while critically evaluating their potential and challenges. We believe that this review will provide a better understanding of important concepts helpful for outlining the strategy to develop new chemotherapeutic agents with promising anticancer activities by targeting HSF1.
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http://dx.doi.org/10.3390/molecules23112757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278446PMC
October 2018

Erosive Arthritis Resembling Osteomyelitis in Behcet's Disease.

J Coll Physicians Surg Pak 2018 Sep;28(9):719-720

Korea University College of Medicine, Seoul, Korea.

Erosive arthritis in Behcet's disease (BD) is rare and confused with infectious diseases such as osteomyelitis. Clinical course and imaging may be similar in BD-related arthritis and osteomyelitis. A 48-year woman diagnosed with BD developed recurrent pain in both feet. Magnetic resonance imaging of her feet showed bony erosions and suggested osteomyelitis with myositis or septic arthritis, but the response to antibiotics was equivocal. We diagnosed BD-related arthritis and started treatment with methotrexate, and increased azathioprine and sulfasalazine, and her joint symptoms improved. BD-related arthritis should be considered in the differential diagnosis of BD patients with articular manifestations that may mimic septic arthritis.
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http://dx.doi.org/10.29271/jcpsp.2018.09.719DOI Listing
September 2018

Transcriptome profiling of whisker follicles in methamphetamine self-administered rats.

Sci Rep 2018 07 30;8(1):11420. Epub 2018 Jul 30.

College of Pharmacy, Keimyung University, Daegu, 42601, Republic of Korea.

Methamphetamine (MA) is a highly addictive psychostimulant that disturbs the central nervous system; therefore, diagnosis of MA addiction is important in clinical and forensic toxicology. In this study, a MA self-administration rat model was used to illustrate the gene expression profiling of the rewarding effect caused by MA. RNA-sequencing was performed to examine changes in gene expression in rat whisker follicles collected before self-administration, after MA self-administration, and after withdrawal sessions. We identified six distinct groups of genes, with statistically significant expression patterns. By constructing the functional association network of these genes and performing the subsequent topological analysis, we identified 43 genes, which have the potential to regulate MA reward and addiction. The gene pathways were then analysed using the Reactome and Knowledgebase for Addiction-Related Gene database, and it was found that genes and pathways associated with Alzheimer's disease and the heparan sulfate biosynthesis were enriched in MA self-administration rats. The findings suggest that changes of the genes identified in rat whisker follicles may be useful indicators of the rewarding effect of MA. Further studies are needed to provide a comprehensive understanding of MA addiction.
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http://dx.doi.org/10.1038/s41598-018-29772-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065325PMC
July 2018

Aspirin-inspired acetyl-donating HDACs inhibitors.

Arch Pharm Res 2018 Oct 20;41(10):967-976. Epub 2018 Jun 20.

College of Pharmacy, Keimyung University, Daegu, 42601, Republic of Korea.

Aspirin is one of the oldest drugs for the treatment of inflammation, fever, and pain. It is reported to covalently modify COX-2 enzyme by acetylating a serine amino acid residue. By virtue of aspirin's acetylating potential, we for the first time developed novel acetyl-donating HDAC inhibitors. In this study, we report the design, synthesis, in silico docking study, and biological evaluation of acetyl-donating HDAC inhibitors. The exposure of MDA-MB-231 cells with compound 4c significantly promotes the acetylation of α-tubulin and histone H3, which are substrates of HDAC6 and HDAC1, respectively. In silico docking simulation also indicates that compound 4c tightly binds to the deep substrate-binding pocket of HDAC6 by coordinating the active zinc ion in a bidentate manner and forming hydrogen bond interactions with Ser531 and His573 amino acid residues. In particular, compound 4c (GI = 147 μM) affords the significant enhancement of anti-proliferative effect on MDA-MB-231 cells, compared with its parent compound 2c (GI > 1000 μM) and acetyl-donating group deficient compound 6 (GI = 554 μM). Overall, compound 4c presents a novel strategy for developing acetyl-donating HDAC inhibitors.
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http://dx.doi.org/10.1007/s12272-018-1045-zDOI Listing
October 2018

High-speed computer-generated hologram based on resource optimization for block-based parallel processing: publisher's note.

Appl Opt 2018 Jun;57(16):4569

This publisher's note corrects the author affiliations in Appl. Opt.57, 3511 (2018)APOPAI0003-693510.1364/AO.57.003511.
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http://dx.doi.org/10.1364/AO.57.004569DOI Listing
June 2018

A technique for a nano-textured gapless microlens array using self-formation characteristics of anodic alumina.

Nanoscale 2018 May;10(21):10137-10147

Department of Advance Mechanical Engineering, Kangwon National University, Gangwondaehak-gil, Chuncheon, Gangwon-do 24341, South Korea.

This paper presents a method to utilize the growth properties of anodic alumina possessing self-formation characteristics to fabricate a nano-textured microstructure and also introduces an application technique of the proposed method. The growth rate of anodic alumina, fabricated on aluminum surfaces, has a strong dependence on the intensity of the applied current density or electric field. The uniformity of the thickness of anodic alumina is determined by its electrical distribution characteristics. Accordingly, microscale structures can be fabricated using the growth rate deviation of anodic alumina. A patterned insulative layer is an important factor that determines the current density distribution property of a local region. A computational analysis and a verification experiment can verify this characteristic through the correlation between structural dimensional conditions and a cross-section of the fabricated anodic alumina. The anodic alumina fabricated by the verification experiment in this study had a swollen shape and a nano & micro complex structure, in which a nanoscale base pattern was formed on all bottom surface due to the process characteristics. Based on the advantages of the proposed process, evidenced by the reliability evaluation results, gapless microlens array (MLA) replication molds with nanostructured surfaces were fabricated to verify the applicability of the proposed technique to other fields. A patterned insulative layer with a cylindrical cavity and dimensional conditions was designed to induce the fabrication of lens-shaped anodic alumina. The anodic alumina fabricated by the long process was selectively etched out, and an additional process was conducted to fabricate a nanoporous structure having controlled dimensional conditions on the engraved gapless MLA surface. The textured aluminum surface was used as a replication mold for the imprinting process. The analysis of the fabrication results showed that the gapless MLA surface had a nanopillar structure. In addition, we investigated the reflection characteristics of the fabricated gapless N-MLA structure according to the incident light and verified the low reflectance of the gapless microlens. The results of this study affirmed that the proposed technique is applicable to various fields including those concerning optical devices.
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http://dx.doi.org/10.1039/c7nr07440aDOI Listing
May 2018

High-speed computer-generated hologram based on resource optimization for block-based parallel processing.

Appl Opt 2018 May;57(13):3511-3518

A huge amount of computation is required to generate a hologram using a computer. In order to speed up the computer-generated-hologram (CGH) operation, we use a parallel programming technique using a general purpose graphic processing unit (GPGPU). In this paper, we propose three techniques to improve CGH performance in the condition using GPU. The first is to remove the memory bottleneck by allocating shared memory and a dedicated thread for this process, and the second is to optimize the block allocation within the GPU using a hologram pixel-based method. The third is to increase the computation time by minimizing the idle region by using multiple threads of host processor and device. When these three techniques were implemented in the GTX 1080Ti GPU, it took 25.05 ms to generate the HD digital hologram with 10 K object points, and compared to the previous research, the performance improvement was at least 1.56 times up to 216.71 times.
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http://dx.doi.org/10.1364/AO.57.003511DOI Listing
May 2018

Development of a column-switching LC-MS/MS method of tramadol and its metabolites in hair and application to a pharmacogenetic study.

Arch Pharm Res 2018 May 9;41(5):554-563. Epub 2018 Mar 9.

College of Pharmacy, Keimyung University, 1095 Dalgubeoldaero, Dalseo-gu, Daegu, 42601, Republic of Korea.

Hair is a valuable specimen for monitoring long-term drug use. Tramadol is an effective opioid analgesic but is associated with risks such as drug dependence and unexpected toxicity arising from genetic differences in metabolism. However, few studies have been performed on the distribution of tramadol and its metabolites in hair. In the present study, a column-switching LC-MS/MS method was developed and fully validated for the simultaneous determination of tramadol and its phase I and II metabolites in hair. Furthermore, the distribution of tramadol and its metabolites in hair was investigated in a pharmacogenetic study. Tramadol and its metabolites were extracted from hair using methanol and injected onto LC-MS/MS. The validation results of selectivity, matrix effect, linearity, precision and accuracy were satisfactory. The (mean) concentrations of O-desmethyltramadol (ODMT) and N,O-didesmethyltramadol (NODMT) in the CYP2D6*10/*10 and CYP2D6*5/*5 groups were lower than those in the CYP2D6*wt/*wt group, while the (mean) concentrations of N-desmethyltramadol (NDMT) were higher. Moreover, the ratios of ODMT/tramadol, NDMT/tramadol and NODMT/NDMT were well correlated with the CYP2D6 genotypes. The developed method was successfully applied to the clinical study, which demonstrated that the concentrations of a drug and its metabolites in hair were dependent on the polymorphism of its metabolizing enzyme.
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http://dx.doi.org/10.1007/s12272-018-1013-7DOI Listing
May 2018

The targeted inhibition of Hsp90 by a synthetic small molecule, DPide offers an effective treatment strategy against TNBCs.

Oncol Rep 2018 Apr 7;39(4):1775-1782. Epub 2018 Feb 7.

College of Pharmacy, Keimyung University, Daegu 704‑701, Republic of Korea.

Triple-negative breast cancers (TNBCs) are the most aggressive and metastatic subtype of breast cancers and exhibit poor clinical outcome due to the lack of drug target receptors such as estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (Her2). The limited effectiveness of therapeutic options and the poor prognosis of TNBC patients emphasize the urgent need for identifying new therapeutic agents. In this regard, heat shock protein 90 (Hsp90) has emerged as a promising therapeutic target for the treatment of TNBCs. Hsp90 is a molecular chaperone that regulates the folding, stability, and function of many oncogenic proteins. Hence, the inhibition of Hsp90 chaperone function leads to a simultaneous blockage of multiple signaling pathways in the proliferation and survival of cancers. In the present study, we performed the design, synthesis, and biological evaluation of Hsp90 inhibitors and found that a synthetic small molecule, DPide exerted a potent anticancer activity against TNBC cell line, MDA‑MB‑231 and non‑small cell lung cancer (NSCLC) cell line, H1975 with GI50 values of 0.478 and 1.67 µM, respectively. Soft‑agar colony formation assay also revealed that DPide suppressed the anchorage‑independent growth of MDA‑MB‑231 cells. Western blot analysis indicated that the treatment of MDA‑MB‑231 cells with DPide induced the proteasomal degradation of EGFR, Her2, Met, Akt, c‑Raf, and Cdk4 and the consequent cleavage of PARP, leading to apoptotic cell death. DPide also inhibited the migration and MMP9 activity of MDA‑MB‑231 cells, suggesting that the metastatic potential of TNBCs could be suppressed by DPide. Collectively, DPide offers an effective therapeutic option for the treatment TNBCs.
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http://dx.doi.org/10.3892/or.2018.6250DOI Listing
April 2018

Asiatic acid attenuates methamphetamine-induced neuroinflammation and neurotoxicity through blocking of NF-kB/STAT3/ERK and mitochondria-mediated apoptosis pathway.

J Neuroinflammation 2017 Dec 11;14(1):240. Epub 2017 Dec 11.

College of Pharmacy, Keimyung University, 1095 Dalgubeoldaero, Dalseo-Gu, Daegu, 42601, Republic of Korea.

Background: Methamphetamine (METH) is a commonly abused drug that may result in neurotoxic effects. Recent studies have suggested that involvement of neuroinflammatory processes in brain dysfunction is induced by misuse of this drug. However, the mechanism underlying METH-induced inflammation and neurotoxicity in neurons is still unclear. In this study, we investigated whether asiatic acid (AA) effected METH-mediated neuroinflammation and neurotoxicity in dopaminergic neuronal cells. And we further determined whether the effect involved in the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator of transcription (STAT)3 and extracellular signal-regulated kinase (ERK) pathway.

Methods: We used the human dopaminergic neuroblastoma SH-SY5Y cell line, murine microglial BV2 cell line, and primary culture of rat embryo mesencephalic neurons. Pro-inflammatory cytokine production was monitored by ELISA and RT/real-time PCR. The cell cycle distribution and mitochondrial membrane integrity was analyzed by flow cytometry. We used immunoblotting, DNA-binding activity, and immunofluorescence staining to analyze the effect of AA on activation of the NF-κB, STAT3, MAPK-ERK, and apoptosis signaling pathways.

Results: METH induced TNF receptor (TNFR) expression and led to morphological changes of cells. Additionally, this drug increased pro-inflammatory cytokine (TNFα and IL-6) expression. AA significantly suppressed METH-induced TNFR expression in concentration dependent. Increased secretion of TNFα and IL-6 was inhibited in METH-stimulated neuronal cells by AA administration. AA showed significant protection against METH-induced translocation of NF-κB/STAT3 and ERK phosphorylation. AA inhibited METH-induced proteolytic fragmentation of caspase-3 and PARP. The pro-apoptotic protein Bax was significantly decreased, while the anti-apoptotic protein Bcl-xL was increased by AA treatment in METH-stimulated cells. A similar protective effect of AA on mitochondrial membrane integrity was also confirmed by flow cytometry and immunofluorescence staining.

Conclusions: Based on the literatures and our findings, AA is a promising candidate for an anti-neurotoxic agent, and it can potentially be used for the prevention and treatment of various neurological disorders.
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http://dx.doi.org/10.1186/s12974-017-1009-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725763PMC
December 2017

Design, synthesis, and biological evaluation of a series of resorcinol-based N-benzyl benzamide derivatives as potent Hsp90 inhibitors.

Eur J Med Chem 2018 Jan 21;143:390-401. Epub 2017 Nov 21.

College of Pharmacy, Keimyung University, Daegu 704-701, South Korea. Electronic address:

Heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone that is responsible for the stabilization and maturation of many oncogenic proteins. Therefore, Hsp90 has emerged as an attractive target in the field of cancer chemotherapy. In this study, we report the design, synthesis, and biological evaluation of a series of Hsp90 inhibitors. In particular, compound 30f shows a significant Hsp90α inhibitory activity with IC value of 5.3 nM and an excellent growth inhibition with GI value of 0.42 μM against non-small cell lung cancer cells, H1975. Compound 30f effectively reduces the expression levels of Hsp90 client proteins including Her2, EGFR, Met, Akt, and c-Raf. Consequently, compound 30f promotes substantial cleavages of PARP, Caspase 3, and Caspase 8, indicating that 30f induces cancer cell death via apoptotic pathway. Moreover, cytochrome P450 assay indicates that compound 30f has weak inhibitory effect on the activities of five major P450 isoforms (IC > 5 μM for 1A2, 2C9, 2C19, 2D6, and 3A), suggesting that clinical interactions between 30f and the substrate drugs of the five major P450 isoforms are not expected. Compound 30f also inhibits the tumor growth in a mouse xenograft model bearing subcutaneous H1975 without noticeable abnormal behavior and body weight changes. The immunostaining and western immunoblot analysis of EGFR, Met, Akt in xenograft tissue sections of tumor further demonstrate a good agreement with the in vitro results.
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http://dx.doi.org/10.1016/j.ejmech.2017.11.054DOI Listing
January 2018

Role of hair pigmentation in drug incorporation into hair.

Forensic Sci Int 2017 Dec 11;281:171-175. Epub 2017 Nov 11.

College of Pharmacy, Keimyung University, 1095 Dalgubeoldaero, Dalseo-gu, Daegu 42601, Republic of Korea. Electronic address:

Hair analysis has notably expanded its application as a bio-monitor for drug or toxicant exposure. Hair pigmentation is proposed as a major factor affecting drug incorporation into hair; however, the mechanisms underlying the incorporation of drugs into hair are still unclear. In the present study, the effect of hair pigmentation on drug incorporation into hair was examined using rats carrying hair with different melanin status and human cells (SK-Mel-28 cells, HaCaT cells and the co-cultured HaCaT cells with SK-Mel-28 cells) representing the main pigmentary unit in hair. Tramadol, a synthetic opioid analgesic, was selected as a model drug. The distribution of tramadol and its phase I (O-desmethyltramadol [ODMT], N-desmethyltramadol [NDMT] and N,O-didesmethyltramadol [NODMT]) and phase II metabolites (ODMT-glucuronide and NODMT-glucuronide) was investigated in non-pigmented and pigmented hair from Long-Evans rats. Moreover, the incorporation levels of ODMT and ODMT-glucuronide were compared in hair cells. The concentrations of tramadol and its phase I metabolites were significantly higher in pigmented rat hair while those of phase II metabolites did not showed any consistent significant difference depending on the status of hair pigmentation. ODMT was taken up to a greater extent than ODMT-glucuronide by SK-Mel-28 cells, HaCaT cells and the co-cultured HaCaT cells with SK-Mel-28 cells. Notably, the incorporated level of ODMT was higher in SK-Mel-28 cells than HaCaT cells and the concentration difference of ODMT was significantly larger than that of ODMT-glucuronide. This study clearly demonstrated that hair pigmentation played a role as a facilitating factor for the incorporation of basic compounds and provided insight into the drug incorporation process into hair.
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http://dx.doi.org/10.1016/j.forsciint.2017.11.004DOI Listing
December 2017

A novel chalcone-based molecule, BDP inhibits MDA‑MB‑231 triple-negative breast cancer cell growth by suppressing Hsp90 function.

Oncol Rep 2017 Oct 25;38(4):2343-2350. Epub 2017 Aug 25.

College of Pharmacy, Keimyung University, Daegu 704-701, Republic of Korea.

Triple-negative breast cancer (TNBC) is a molecularly diverse and heterogeneous disease and the molecular heterogeneity of TNBC increases the difficulty in improving survival rates. To date, therapeutic approaches for the treatment of TNBC such as hormonal chemotherapy and trastuzumab-based therapy have been limited by the lack of target receptors such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her2), emphasizing the urgent need for identifying new therapeutic options. In this regard, heat shock protein 90 (Hsp90) has emerged as an attractive therapeutic target for TNBC. Hsp90 plays a central role in regulating correct folding, stability, and function of numerous oncogenic proteins. In the present study, we evaluated the in vitro effect of a small molecule Hsp90 inhibitor, (E)-3-(2-bromo-3,4,5-trimethoxyphenyl)-1-(2,4-dihydroxyphenyl)prop-2-en-1-one (BDP) on TNBC cell line, MDA‑MB‑231. This study indicated that BDP efficiently inhibited the growth of MDA‑MB‑231 cells in a dose- and time-dependent manner. BDP induced overall degradation of multiple oncogenic proteins including EGFR, Her2, Met, Akt, c‑Raf, and Cdk4, consequently leading to apoptotic cell death. The flow cytometric analysis revealed that BDP promoted cell cycle arrest at G2/M phases. Moreover, BDP treatment attenuated the migration of MDA‑MB‑231 cells and impaired MMP9 activity, which are essential processes for tumor metastasis. Collectively, BDP represents a new class of Hsp90 inhibitor and shows therapeutic potential for TNBC treatment.
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http://dx.doi.org/10.3892/or.2017.5925DOI Listing
October 2017

The association between genetic polymorphisms of the interleukin-23 receptor gene and susceptibility to uveitis: a meta-analysis.

BMC Ophthalmol 2017 May 30;17(1):81. Epub 2017 May 30.

Korea University College of Medicine, Seoul, South Korea.

Background: Uveitis is an eye inflammatory disease, which is sometimes associated with underlying systemic disease. Interleukin-23 plays an important role in autoimmune disease. The aim of this meta-analysis was to evaluate the association between the interleukin-23 receptor (IL-23R) and susceptibility to uveitis.

Methods: Published literature from PUBMED and EMBASE were retrieved. Seven studies were included in this meta-analysis, covering a total of 1309 cases of uveitis and 2400 controls. Meta-analyses were conducted on the associations between uveitisand rs7517847, rs17375018, and rs11209032 polymorphisms in the IL-23R gene.

Results: There were no significant associations between IL-23R polymorphisms and uveitis with regard to the following alleles: for G allele vs. T allele of rs7517847, OR 1.01, 95% CI 0.92-1.12, P = 0.83; for A allele vs. G allele of rs17375018, OR 0.68, 95% CI 0.47-0.99, P = 0.05; rs11209032 OR 1.12, 95% CI 0.84-1.51, P = 0.43. In contrast, there were significant associations between the AA + AG gene versus GG gene of rs17375018 and the AA gene versus AG + GG gene of rs11209032 polymorphism with uveitis (OR 0.59, 95% CI 0.35-0.99, P = 0.04; OR 1.32, 95% CI 1.10-1.59, P = 0.003).

Conclusions: This meta-analysis suggests that each allele of IL-23R, including rs7519847, rs17375018 and rs11209032 was negatively associated with uveitis. However, homozygote models, including the rs17375018 GG genotype and rs11209032 AA genotype, were significantly associated with uveitis.
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http://dx.doi.org/10.1186/s12886-017-0477-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450396PMC
May 2017

Hsp90 inhibitor SY-016 induces G2/M arrest and apoptosis in paclitaxel-resistant human ovarian cancer cells.

Oncol Lett 2017 Apr 1;13(4):2817-2822. Epub 2017 Mar 1.

Institute for Cancer Research, Keimyung University School of Medicine, Daegu 41931, Republic of Korea.

The aim of the present study was to evaluate the effect of a heat shock protein (Hsp)90 inhibitor, SY-016, on the paclitaxel (PTX)-resistant human ovarian cancer cell line OVCAR-3PTX, and explore its mechanism of apoptosis. In the present study, SY-016 was used in combination with PTX to determine its effect on the cell proliferation and apoptosis of OVCAR-3PTX cells. The drug-resistant tumor cells were established by stepwise sequential exposure to increasing concentrations of PTX. The cell viability and cell cycle distribution were measured by MTT assay and flow cytometric analysis, respectively. The induction of apoptosis was measured by caspase-3 activity, DNA fragmentation and western blot analyses. The cell viability significantly decreased following treatment with PTX and SY-016 as compared with either drug alone. The DNA fragmentation assay revealed an induction of apoptosis. The results from the flow cytometric analysis revealed an increase in the percentage of cells in the G2/M phase. Downregulation of B-cell lymphoma (Bcl)-2, X-linked inhibitor of apoptosis protein, survivin, Akt, nuclear factor-κB and cyclin-dependent kinase 4, as well as upregulation of Bcl-2-associated X protein, were observed. SY-016 may contribute to the induction of apoptosis in OVCAR-3PTX cells. These results suggest that SY-016 in combination with PTX may be a beneficial chemotherapeutic strategy, particularly in patients with tumors refractory to PTX.
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http://dx.doi.org/10.3892/ol.2017.5794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403452PMC
April 2017

ASIC chipset design to generate block-based complex holographic video.

Appl Opt 2017 Mar;56(9):D52-D59

In this paper, we propose a new hardware architecture implemented as a very large scaled integrated circuit by using an application-specific integrated circuit technology, where block-based calculations are used to generate holograms. The proposed hardware is structured to produce a part of a hologram in the block units in parallel. A block of a hologram is calculated using an object point, and then the calculation is repeated for all object points to obtain intermediate results that are accumulated to produce the final block of a hologram. This structure can be used to produce holograms of various sizes in real time with optimized memory access. The proposed hardware was implemented using the Hynix 0.18 μm CMOS technology of Magna Chip, Inc., and it has about 448 K gate counts and a silicon size of 3.592  mm×3.592  mm. It can generate complex holograms and operate in a stable manner at a clock frequency of 200 MHz.
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http://dx.doi.org/10.1364/AO.56.000D52DOI Listing
March 2017