Publications by authors named "Seung Eun Choi"

13 Publications

  • Page 1 of 1

Digital Therapeutics: Exploring the Possibilities of Digital Intervention for Myopia.

Front Digit Health 2021 27;3:710644. Epub 2021 Aug 27.

Department of Ophthalmology, Seoul National University College of Medicine, Seoul University Bundang Hospital, Seongnam, South Korea.

Pediatric myopia is increasing globally and has become a major public health issue. However, the mechanism of pediatric myopia is still poorly understood, and there is no effective treatment to prevent its progression. Based on results from animal and clinical studies, certain neuronal-humoral factors (NHFs), such as IGF-1, dopamine, and cortisol may be involved in the progression of pediatric myopia. Digital therapeutics uses evidence-based software as therapeutic interventions and it has the potential to offer innovative treatment strategies for pediatric myopia beyond conventional treatment methods. In this perspective article, we introduce digital therapeutics SAT-001, a software algorithm that modulates the level of NHFs to reduce the progression of pediatric myopia. The proposed mechanism is based on a theoretical hypothesis derived from scientific research and clinical studies and will be further confirmed by evidence generated from clinical studies involving pediatric myopia.
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http://dx.doi.org/10.3389/fdgth.2021.710644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521975PMC
August 2021

Ultrafast H-selective nanoporous multilayer graphene membrane prepared by confined thermal annealing.

Chem Commun (Camb) 2021 Sep 9;57(70):8730-8733. Epub 2021 Aug 9.

Department of Chemical and Biomolecular Engineering, Yonsei University, Yonsei-ro 50, Seodaemun-gu, Seoul 120-749, Republic of Korea.

H selective dense pores are generated in a graphene oxide (GO) layer by thermal-decomposition of oxygen-functional groups under high pressure. The nanoporous GO membrane shows H/CO selectivity of 12.1 and H permeability of 10360 Barrer.
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http://dx.doi.org/10.1039/d1cc02946kDOI Listing
September 2021

Diamine vapor treatment of viscoelastic graphene oxide liquid crystal for gas barrier coating.

Sci Rep 2021 May 4;11(1):9518. Epub 2021 May 4.

Department of Chemical and Biomolecular Engineering, Yonsei University, Yonsei-ro 50, Seodaemun-gu, Seoul, 03722, Republic of Korea.

A layered graphene oxide/ethylenediamine (GO/EDA) composite film was developed by exposing aqueous GO liquid crystal (GOLC) coating to EDA vapor and its effects on the gas barrier performance of GO film were systematically investigated. When a GO/EDA coating with a thickness of approximately 1 μm was applied to a neat polyethylene terephthalate (PET) film, the resultant film was highly impermeable to gas molecules, particularly reducing the gas permeance up to 99.6% for He and 98.5% for H in comparison to the neat PET film. The gas barrier properties can be attributed to the long diffusion length through stacked GO nanosheets. The EDA can crosslink oxygen-containing groups of GO, enhancing the mechanical properties of the GO/EDA coating with hardness and elastic modulus values up to 1.14 and 28.7 GPa, respectively. By the synergistic effect of the viscoelastic properties of GOLC and the volatility of EDA, this coating method can be applied to complex geometries and EDA intercalation can be spontaneously achieved through the scaffold of the GOLC.
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http://dx.doi.org/10.1038/s41598-021-88955-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096969PMC
May 2021

Graphene Oxide Nanoribbon Hydrogel: Viscoelastic Behavior and Use as a Molecular Separation Membrane.

ACS Nano 2020 09 9;14(9):12195-12202. Epub 2020 Sep 9.

Department of Chemical and Biomolecular Engineering, YONSEI University, Yonsei-ro 50, Seodaemun-gu, Seoul, (03722), Republic of Korea.

The preparation of carbon materials based hydrogels and their viscoelastic properties are essential for their broad application and scale-up. However, existing studies are mainly focused on graphene derivatives and carbon nanotubes, and the behavior of graphene nanoribbon (GNR), a narrow strip of graphene, remains elusive. Herein, we demonstrate the concentration-driven gelation of oxidized GNR (graphene oxide nanoribbon, GONR) in aqueous solvents. Exfoliated individual GONRs sequentially assemble into strings (∼1 mg/mL), nanoplates (∼20 mg/mL), and a macroporous scaffold (50 mg/mL) with increasing concentration. The GONR hydrogels exhibit viscoelastic shear-thinning behavior and can be shear-coated to form large-area GONR films on substrates. The entangled and stacked structure of the GONR film contributed to outstanding nanofiltration performance under high pressure, cross-flow, and long-term filtration, while the precise molecular separation with 100% rejection rate was maintained for sub-nanometer molecules.
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http://dx.doi.org/10.1021/acsnano.0c05902DOI Listing
September 2020

Quantitative Modeling Analysis Demonstrates the Impact of CYP2C19 and CYP2D6 Genetic Polymorphisms on the Pharmacokinetics of Amitriptyline and Its Metabolite, Nortriptyline.

J Clin Pharmacol 2019 04 19;59(4):532-540. Epub 2018 Nov 19.

Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, Seoul, Korea.

Amitriptyline is a tricyclic antidepressant that is metabolized mainly by CYP2C19 and CYP2D6 enzymes. Higher plasma levels of amitriptyline and its active metabolite, nortriptyline, are associated with an increased risk of adverse events including anticholinergic effects. The aim of this study was to evaluate the effects of CYP2C19 and CYP2D6 genetic polymorphisms on amitriptyline and nortriptyline pharmacokinetics. Twenty-four Korean healthy adult male volunteers were enrolled in the study after stratification by their CYP2C19 and CYP2D6 genotypes. Serial blood draws for pharmacokinetic analysis were made after a single oral 25-mg dose of amitriptyline was administered. Plasma amitriptyline and nortriptyline concentrations were measured by a validated liquid chromatography with tandem mass spectrometry. Population pharmacokinetic modeling analysis was conducted using NONMEM, which evaluated the effects of CYP2C19 and CYP2D6 genotypes on amitriptyline and nortriptyline pharmacokinetics. The biotransformation of amitriptyline into nortriptyline was significantly different between subjects with the CYP2C19*2/*2, *2/*3, and *3/*3 genotypes and those with the other genotypes, with an estimated metabolic clearance of 17 and 61.5 L/h, respectively. Clearance of amitriptyline through pathways other than biotransformation into nortriptyline was estimated as 18.8 and 30.6 L/h for subjects with the CYP2D6*10/*10 and *10/*5 genotypes and those with the other genotypes, respectively. This study demonstrated a quantitative effect of the CYP2C19 and CYP2D6 genotypes on amitriptyline and nortriptyline pharmacokinetics. Production of nortriptyline from amitriptyline was associated with CYP2C19 genotypes, and clearance of amitriptyline through pathways other than biotransformation into nortriptyline was associated with CYP2D6 genotypes. These observations may be useful in developing individualized, optimal therapy with amitriptyline.
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http://dx.doi.org/10.1002/jcph.1344DOI Listing
April 2019

Effects of CYP2C19 Genetic Polymorphisms on PK/PD Responses of Omeprazole in Korean Healthy Volunteers.

J Korean Med Sci 2017 05;32(5):729-736

Clinical Research Division, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju, Korea.

The aim of this study was to examine the effects of CYP2C19*2 and *3 genetic polymorphisms on omeprazole pharmacokinetic (PK) and pharmacodynamic (PD) responses. Twenty-four healthy Korean volunteers were enrolled and given 20 mg omeprazole orally once daily for 8 days. The genotypes of CYP2C19 single nucleotide polymorphisms (SNPs) (*2, *3, and *17) were screened. The plasma concentrations of omeprazole, omeprazole sulfone, and 5-hydroxy (5-OH) omeprazole were determined by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The noncompartmental method was used for the determination of PK parameters. Change of mean pH and proportion (%) of time of gastric pH above 4.0 were estimated. The poor metabolizer (PM) group had the lowest metabolic ratio and exhibited the highest area under the curve (AUC) for omeprazole among the CYP2C19 phenotype groups. The PM group showed the greatest change of mean pH and the highest % time of gastric pH above 4.0. The relationship between AUC of omeprazole and % time of gastric pH above 4.0 was confirmed. The study demonstrates that CYP2C19*2 and *3 influence the PKs and PDs of omeprazole in Korean healthy volunteers.
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http://dx.doi.org/10.3346/jkms.2017.32.5.729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383603PMC
May 2017

The influences of SLCO1B1 and ABCB1 genotypes on the pharmacokinetics of simvastatin, in relation to CYP3A4 inhibition.

Pharmacogenomics 2017 Apr 28;18(5):459-469. Epub 2017 Mar 28.

Clinical Research Division, National Institute of Food & Drug Safety Evaluation, Ministry of Food & Drug Safety, Cheongju, Republic of Korea.

Aim: To investigate the combined effects of SLCO1B1 and ABCB1 genotypes on the pharmacokinetics of simvastatin and its active metabolite simvastatin acid, in relation to CYP3A4 inhibition.

Methods: We conducted a single-dose pharmacokinetic study of simvastatin in 26 healthy volunteers screened for their SLCO1B1 c.521T>C and ABCB1 c.1236C>T-2677G>T-3435C>T genotypes, with and without amlodipine pretreatment. The genetic effects and drug-interaction effect on simvastatin pharmacokinetic parameters were analyzed using a linear-mixed model.

Results: The SLCO1B1 c.521T>C variant significantly increased exposure to simvastatin acid by around 40% (p < 0.05), similar to that caused by the amlodipine pretreatment. The ABCB1 gene showed no influence on exposure to simvastatin or simvastatin acid.

Conclusion: Only SLCO1B1, not ABCB1 genotype, is likely to be associated with simvastatin-induced myopathy. SLCO1B1 genotyping may be particularly beneficial in simvastatin users who are co-administered CYP3A4 inhibitors.
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http://dx.doi.org/10.2217/pgs-2016-0199DOI Listing
April 2017

Embryotoxicity assessment of developmental neurotoxicants using a neuronal endpoint in the embryonic stem cell test.

J Appl Toxicol 2012 Aug 1;32(8):617-26. Epub 2011 Dec 1.

Center for Drug Development Assistance, National Institute of Food and Drug Safety Evaluation, Korea Food and Drug Administration, Cheongwon-gun, Chungcheongbuk-do 363-951, South Korea.

The embryonic stem cell test (EST) is a validated in vitro embryotoxicity test; however, as the inhibition of cardiac differentiation alone is used as a differentiation endpoint in the EST, it may not be a useful test to screen embryotoxic chemicals that affect the differentiation of noncardiac tissues. Previously, methylmercury (MeHg), cadmium and arsenic compounds, which are heavy metals that induce developmental neurotoxicity in vivo, were misclassified as nonembryotoxic with the EST. The aim of this study was to improve the EST to correctly screen such developmental neurotoxicants. We developed a neuronal endpoint (Tuj-1 ID₅₀) using flow cytometry analysis of Tuj-1-positive cells to screen developmental neurotoxicants (MeHg, valproic acid, sodium arsenate and sodium arsenite) correctly using an adherent monoculture differentiation method. Using Tuj-1 ID₅₀ in the EST instead of cardiac ID₅₀, all of the tested chemicals were classified as embryotoxic, while the negative controls were correctly classified as nonembryotoxic. To support the validity of Tuj-1 ID₅₀) , we compared the results from two experimenters who independently tested MeHg using our modified EST. An additional neuronal endpoint (MAP2 ID₅₀), obtained by analyzing the relative quantity of MAP2 mRNA, was used to classify the same chemicals. There were no significant differences in the three endpoint values of the two experimenters or in the classification results, except for isoniazid. In conclusion, our results indicate that Tuj-1 ID₅₀ can be used as a surrogate endpoint of the traditional EST to screen developmental neurotoxicants correctly and it can also be applied to other chemicals.
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http://dx.doi.org/10.1002/jat.1747DOI Listing
August 2012

Effects of compression/stretching of the spermatic cord and blunt dissection on testicular growth and fertility.

J Pediatr Surg 2009 Nov;44(11):2163-7

Department of Surgery, Seoul National University College of Medicine, Jongno-gu, Seoul 110-799, South Korea.

Purpose: This study was performed to investigate whether compression/stretching of the spermatic cord or blunt dissection influences testicular development and fertility. In addition, the authors evaluated whether the extents of testicular damage differ between these 2 surgical manipulations.

Methods: Forty-four prepubertal male Sprague-Dawley (SD) rats (Harlan Sprague-Dawley Inc, Indianapolis, Ind) were divided into 3 groups: (1) the control group (CG) animals underwent a sham operation in the right groin, (2) the experimental group 1 (EG1) underwent compression/stretching of the right spermatic cord, and (3) the experimental group 2 (EG2) underwent dissection around the right spermatic cord structures. Testicular volumes, weights, mean seminiferous tubular diameters (MSTDs), mean testicular biopsy scores, and numbers of offspring and of pregnant females were evaluated.

Results: Right (operative) and left (nonoperative) testicular volumes were smaller in the EG2 group than in the CG or EG1 groups. Left MSTDs in the EG1 and EG2 groups increased more than in the CG group. Numbers of Sertoli cells in left testes differed in the 3 groups, in the order EG1 < CG < EG2. Mean testicular biopsy scores, offspring numbers, and pregnant female numbers were no different in the 3 groups.

Conclusions: Both surgical manipulations influenced testicular growth, but they did not compromise spermatogenesis or fertility in SD rats.
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http://dx.doi.org/10.1016/j.jpedsurg.2009.03.025DOI Listing
November 2009

Pancreatic islets induce CD4(+) [corrected] CD25(-)Foxp3(+) [corrected] T-cell regulated tolerance to HY-mismatched skin grafts.

Transplantation 2008 Nov;86(10):1352-60

Department of Microbiology and Immunology, Seoul National University Hospital, Seoul, South Korea.

Background: The ability to induce and maintain antigen-specific immunologic tolerance is the ultimate goal in allo-transplantation. Here, we report that the transplantation of unmanipulated murine pancreatic islets across the HY disparity induced transplantation tolerance that prevented HY-mismatched skin grafts being rejected.

Methods: Three hundred islet equivalent of freshly isolated islets from male C57BL/6 donor mice was transplanted underneath the kidney capsule of syngeneic female recipients rendered diabetic by streptozotocin. Nephrectomy was carried out to remove the islet graft and retransplantation was performed using the contralateral kidney. For skin transplantation, donor tail skin was transplanted onto the lateral thorax.

Results: Islets from male C57BL/6 donors transplanted to syngeneic female recipients cured diabetes and the mice survived indefinitely. The acceptance of second grafts and rejection of third party islet grafts indicated antigen-specific transplantation tolerance. However, flow cytometry and ELISPOT analysis demonstrated that the HY-specific T cells were not deleted or anergized. A 2-fold increase of CD4+Foxp3+ regulatory T cells (Tregs) was observed in spleen and lymph nodes. Notably, CD25- Tregs increased threefold over levels in naïve mice. Adoptive transfer of CD4+ T cells to neonatal mice could transfer tolerance. At the graft site in long-term tolerant mice, CD4+ T cells, 40% of which were CD4+Foxp3+ Tregs (43% CD25-, 57% CD25+) infiltrated the peri-islet spaces.

Conclusions: Unmanipulated pancreatic islets can induce immunologic tolerance associated with peripherally induced CD4+Foxp3+ Tregs, a significant proportion of which notably are CD25-.
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http://dx.doi.org/10.1097/TP.0b013e31818aa43cDOI Listing
November 2008

Assessment of the quantitative real-time polymerase chain reaction using a cDNA standard for human group A rotavirus.

J Virol Methods 2006 Nov 7;137(2):280-6. Epub 2006 Aug 7.

Department of Biologics Evaluation, Korea Food and Drug Administration, Republic of Korea.

Nucleic acid amplification techniques are used frequently for rapid diagnosis of viral diseases. In this study, a real-time polymerase chain reaction protocol that uses primers specific for the viral VP4 gene and the commercial SYBR Green reagent were evaluated for the quantitative measurement of human rotavirus (HRV) RNA in human stool specimens. SYBR Green I detection involved analysis of the melting temperature of the PCR product and measurement of fluorescence at the optimum temperature. The assay resulted in a sensitive and reproducible detection of targets ranging from low (<10(2)rotavirus cDNA copies/reaction) to high numbers (>10(6)rotavirus cDNA copies/reaction). No cross-reaction was found with crude cell culture stocks of coxsackievirus, echovirus, poliovirus, hepatitis A virus and adenovirus. Analysis with the HRV cDNA standard demonstrated high reproducibility with a coefficient of variation (CV) of 0.2-0.9%. Daily performance among three different laboratories showed a CV no greater than 8%, indicating an intermediate level of variation. These results demonstrate the feasibility of this method for quantitative analysis of human rotavirus in clinical samples.
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http://dx.doi.org/10.1016/j.jviromet.2006.06.028DOI Listing
November 2006

IL-6 protects pancreatic islet beta cells from pro-inflammatory cytokines-induced cell death and functional impairment in vitro and in vivo.

Transpl Immunol 2004 Jun-Jul;13(1):43-53

Department of Biochemistry, College of Medicine, Seoul National University, 28 Yongon-Dong Chongno-gu, Seoul 110-799, South Korea.

Protection of pancreatic islet beta cells from pro-inflammatory cytokines-induced cell death and functional impairment is a key issue in developing therapeutic interventions of type 1 diabetes mellitus including islet transplantation. The effects of IL-6 on the protection of beta cells in vitro and in vivo were examined. Freshly isolated islets or MIN6 beta cells, when pre-incubated with IL-6, showed significantly higher viabilities measured by MTT assay and FACS analysis of PI stained cells against pro-apoptotic signaling delivered by IL-1beta, TNF-alpha and IFN-gamma. Insulin secretory function was also significantly protected in static culture with glucose and KCl stimulation. In vivo assessment using marginal mass syngeneic islet transplantation in mouse model revealed IL-6 conferred significantly better blood glucose control and graft survival rate over 50 days. Conclusively, IL-6 protects pancreatic islets or beta-cells from inflammatory cytokines-induced cell death and functional impairment both in vitro and in vivo. This strategy could be exploited in the clinical setting to maintain functional islet mass.
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http://dx.doi.org/10.1016/j.trim.2004.04.001DOI Listing
January 2005

Human cytomegalovirus UL18 alleviated human NK-mediated swine endothelial cell lysis.

Biochem Biophys Res Commun 2004 Feb;315(1):144-50

Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.

Human cytomegalovirus UL18, a MHC class I homologue, is known to serve as a natural killer cell (NK) decoy and to ligate NK inhibitory receptors to prevent lysis of an infected target cell. To explore whether the cell surface expression of UL18 represents a potential immune suppressive approach to evade NK-mediated cytotoxicity in the prevention of xenograft rejection, we examined the effect of the UL18 expression in vitro upon human NK-mediated cytotoxicity against swine endothelial cells (SECs). UL18 expression on SECs by a retroviral vector (PLNCX2) significantly suppressed NK-mediated SEC lysis by approximately 25-100%. The protective effect of UL18 could be mediated through ILT-2 inhibitory receptor on NKs. Additionally, the interaction between UL18 and NKs resulted in the significant reduction of IFN-gamma production. This study demonstrates that UL18 can serve as an effective tool for the evasion of NK-mediated cytotoxicity and for the inhibition of IFN-gamma production during xenograft rejection.
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http://dx.doi.org/10.1016/j.bbrc.2004.01.027DOI Listing
February 2004
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