Publications by authors named "Mi-Sun Kim"

291 Publications

Sleep time and duration is associated with periodontitis in a representative sample of Koreans.

J Periodontol 2021 May 26. Epub 2021 May 26.

Department of Health Care Administration and Policy, School of Public Health, University of Nevada, Las Vegas, NV.

Background: So far, studies on the association between sleep and periodontitis have shown conflicting results. This study assessed the association among sleep duration, sleep time, and periodontitis among a nationally representative Korean population and the mediation effect of WBC.

Methods: We analyzed data from the Seventh Korean National Health and Nutrition Examination Survey (KNHANES VII) collected from 2016 to 2018. With the screenings by age (45 to 64), edentate, and the adequacy of information provided, the analysis was confined to a selected group of respondents of 4407 with measurements for the sleep survey and periodontal health status out of total 24,269. Periodontitis was defined according to the World Health Organization's community periodontal index (CPI) code greater than or equal to three, and severe periodontitis was defined as CPI code 4. Multivariable logistic regression analysis was used to test the association between sleep and periodontitis controlling the confounding factors.

Results: Those who went to bed during the daytime were associated with periodontitis (OR = 1.49, 95% confidence interval [CI]: 1.07 to 2.07). In a combined sleep time and duration model, those who went to bed at night with a sleep duration of 9 hours or more were associated with periodontitis (OR = 1.69, 95% CI: 1.04 to 2.77) and severe periodontitis (OR = 1.88, 95% CI: 1.02-3.45). WBC count had the highest impact on the association between sleep time and periodontitis.

Conclusions: Our findings suggest that an extra-long sleep duration and going to bed during the daytime are associated with periodontitis.
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http://dx.doi.org/10.1002/JPER.20-0252DOI Listing
May 2021

A Study of 3CLpros as Promising Targets against SARS-CoV and SARS-CoV-2.

Microorganisms 2021 Apr 3;9(4). Epub 2021 Apr 3.

Graduate School of Pharmaceutical Sciences, Ewha Womans University, 52, Ewhayeodae-gil, Seoul 03760, Korea.

The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), results in serious chaos all over the world. In addition to the available vaccines, the development of treatments to cure COVID-19 should be done quickly. One of the fastest strategies is to use a drug-repurposing approach. To provide COVID-19 patients with useful information about medicines currently being used in clinical trials, twenty-four compounds, including antiviral agents, were selected and assayed. These compounds were applied to verify the inhibitory activity for the protein function of 3CLpros (main proteases) of SARS-CoV and SARS-CoV-2. Among them, viral reverse-transcriptase inhibitors abacavir and tenofovir revealed a good inhibitory effect on both 3CLpros. Intriguingly, sildenafil, a cGMP-specific phosphodiesterase type 5 inhibitor also showed significant inhibitory function against them. The in silico docking study suggests that the active-site residues located in the S1 and S2 sites play key roles in the interactions with the inhibitors. The result indicates that 3CLpros are promising targets to cope with SAR-CoV-2 and its variants. The information can be helpful to design treatments to cure patients with COVID-19.
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http://dx.doi.org/10.3390/microorganisms9040756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065850PMC
April 2021

Effect of adenomyosis on adverse obstetrical outcomes in twin pregnancies achieved with assisted reproductive technology.

J Obstet Gynaecol 2021 Apr 23:1-10. Epub 2021 Apr 23.

Department of Obstetrics and Gynecology, CHA Bundang Medical Center, Seongnam-si, Republic of Korea.

The incidence of twin pregnancy with adenomyosis (AD) is increasing due to advanced maternal age and infertility treatment. We retrospectively analysed the data of 45 dichorionic twin pregnancies complicated with AD in contrast to a control group of dichorionic twin pregnancies without AD ( = 130). Compared with those in the control group, the AD group had a higher overall foetal loss rate (8.9% vs. 0.8%; adjusted  = .031; odds ratio (OR), 13.6; 95% confidence interval (CI), 1.27-146.3), higher early preterm delivery rate (20% vs. 6.9%; adjusted  = .007; OR, 4.22; 95% CI, 1.47-12.13) and higher rate of hypertensive disorders of pregnancy (26.7% vs. 7.7%; adjusted  = .005; OR, 3.94; 95% CI, 1.5-10.2). Patients in the AD group were significantly more likely to require transfusion during or after delivery (17.8% vs. 5.4%;  = .026) and have smaller babies (2168 g vs. 2399 g;  = .004) compared with those in the control group. This is the first study to report that twin pregnancies with AD may be treated as high-risk for placental dysfunction and may need closer monitoring during pregnancy.Impact Statement The incidence of twin pregnancy with adenomyosis (AD) is increasing due to advanced maternal age and infertility treatment. However, there are very few studies on the effect of AD on pregnancy outcomes. This is the first study to report that twin pregnancies with AD have higher rates of early preterm delivery, hypertensive disorders of pregnancy, and transfusion compared to controls. The results of this study can be used in counselling twin pregnancies with AD. Further research is needed to confirm the current findings.
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http://dx.doi.org/10.1080/01443615.2020.1867969DOI Listing
April 2021

Are occupational and environmental noises associated with periodontitis? Evidence from a Korean representative cross-sectional study.

BMC Public Health 2021 03 29;21(1):616. Epub 2021 Mar 29.

Department of Dental Hygiene, Kyungdong University, Wonju, South Korea.

Background: Evidences have shown that noise could be a risk factor for cardiovascular and metabolic diseases. Since periodontitis and CVD are characterized by inflammation, it is reasonable to doubt that occupational/environmental noise is a risk factor for periodontitis. The aim of this study was to examine the relationship between occupational/environmental noise and periodontitis in a nationally representative sample of Korean adults.

Methods: This cross-sectional study used data from the 7th Korean National Health and Nutrition Examination Survey. The study sample included 8327 adults aged 40 to 80 years old. Noise exposure and the duration of the exposure were assessed with self-report questionnaires. The dependent variable was periodontitis. Age, gender, place of residence, income, marital status, smoking, frequency of daily tooth brushing, recent dental checkup, and diabetes were included as covariates. Logistic regression analyses estimated the association between noise exposure and periodontitis.

Results: Those who were exposed to environmental noise during their lifetime had an increased prevalence of severe periodontitis (odds ratio [OR] 1.88; 95% confidence interval [CI] 1.05 to 3.40), and this association was strengthened as the duration of the environmental noise exposure was longer (OR of > 120 months 2.35 and OR of ≤120 months 1.49). There was a combined relationship for severe periodontitis between occupational and environmental noise exposure (OR of both exposures 2.62, OR of occupational exposure only 1.12, and OR of environmental exposure only 1.57).

Conclusion: Our study shows that noise exposure is associated with periodontitis, and the association was higher in the synergism between occupational and environmental interaction.
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http://dx.doi.org/10.1186/s12889-021-10672-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008658PMC
March 2021

A study of inhibitors of d--β-d--heptose-1-phosphate adenylyltransferase from as a potential antibiotic target.

J Enzyme Inhib Med Chem 2021 Dec;36(1):776-784

College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha W. University, Seoul, Republic of Korea.

d--β-d--heptose-1-phosphate adenylyltransferase from (HldC) is the fourth enzyme in the ADP-l--β-d--heptose biosynthesis pathway producing a lipopolysaccharide core. Therefore, HldC is an anti-melioidosis target. Three ChemBridge compounds purchased from ChemBridge Corporation (San Diego, CA) were found to have an effective inhibitory activity on HldC. Interestingly, ChemBridge 7929959 was the most effective compound due to the presence of the terminal benzyl group. The enzyme kinetic study revealed that most of them show mixed type inhibitory modes against ATP and βG1P. The induced-fit docking indicated that the medium affinity of ChemBridge 7929959 is originated from its benzyl group occupying the substrate-binding pocket of HldC. The inhibitory role of terminal aromatic groups was proven with ChemBridge 7570508. Combined with the previous study, ChemBridge 7929959 is found to work as a dual inhibitor against both HldC and HddC. Therefore, three ChemBridge compounds can be developed as a potent anti-melioidosis agent with a novel inhibitory concept.
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http://dx.doi.org/10.1080/14756366.2021.1900166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993394PMC
December 2021

Factors Affecting Physical and Mental Fatigue among Female Hospital Nurses: The Korea Nurses' Health Study.

Healthcare (Basel) 2021 Feb 13;9(2). Epub 2021 Feb 13.

College of Nursing, Konyang University, 158 Gwanjeodong-ro, Seo-gu, Daejeon 35365, Korea.

Nurses often experience work-related physical and mental fatigue. This study sought to identify the levels of physical and mental fatigue present among Korean female nurses and discern factors influencing their onset. This cross-sectional study analyzed data from the Korea Nurses' Health Study (KNHS). A total of 14,839 hospital nurses were assessed by hierarchical regression analysis. The mean scores of physical and mental fatigue were 12.57 and 5.79 points, respectively. After adjusting for confounding variables, the work department had a significant influence on both physical and mental fatigue, that is, nurses working in special care units experienced greater degrees of both physical and mental fatigue than those working in general units. Nurse fatigue is an important consideration to monitor to ensure nurses' continued wellbeing as well as good patient safety levels. Therefore, it is necessary to establish a strategy to mitigate nursing fatigue while considering the characteristics of specific departments. In nursing practice, the introduction of a counseling program and guarantee of rest time that can alleviate the mental and physical fatigue of nurses working in special care units should be considered.
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http://dx.doi.org/10.3390/healthcare9020201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918797PMC
February 2021

Genomic Association Study for Cognitive Impairment in Parkinson's Disease.

Front Neurol 2020 4;11:579268. Epub 2021 Feb 4.

Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Cognitive impairment is very common in Parkinson's disease (PD) and constitutes the most debilitating complication of this disease. However, to date, few studies have investigated a genome-wide association in the development of cognitive impairment of PD. We aimed to identify the genetic loci associated with cognitive impairment in patients with sporadic PD by ethnicity-specific genotyping. We recruited 1,070 patients with PD and performed a genome-wide association study using the Korean Chip, a microarray chip containing 827,400 single-nucleotide polymorphisms (SNPs) optimized for the Korean population. Multiple logistic regression models adjusting for age, sex, years of education, and disease duration were used to compare between patients with and without cognitive impairment, which was defined using the Mini-Mental Status Examination (MMSE) score (MMSE score ≥ 26 vs. < 26) or the Montreal Cognitive Assessment (MoCA) score (MoCA score ≥24 vs. < 24). SNP rs10495397 was most significantly associated with cognitive impairment based on the MMSE scores (OR = 3.21; 95% CI = 1.96-5.25, = 3.36 × 10) and showed the strongest association with cognitive impairment based on the MoCA scores. However, none of the SNPs were statistically significant after Bonferroni correction. may play a role in cognitive impairment in PD by the pathogenic mechanism of neuroinflammation. However, more studies are needed to replicate and validate the results of our functional study.
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http://dx.doi.org/10.3389/fneur.2020.579268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890115PMC
February 2021

A triple-targeting inhibitory activity of Rose Bengal on polysaccharide biosynthesis of Burkholderia pseudomallei.

Arch Pharm (Weinheim) 2021 Jun 8;354(6):e2000360. Epub 2021 Feb 8.

Department of Pharmacy, College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea.

Sugar nucleotidyltransferases (SNTs) participate in various biosynthesis pathways constructing polysaccharides in Gram-negative bacteria. In this study, a triple-targeting inhibitory activity of Rose Bengal against SNTs such as d-glycero-α-d-manno-heptose-1-phosphate guanylyltransferase (HddC), d-glycero-β-d-manno-heptose-1-phosphate adenylyltransferase (HldC), and 3-deoxy-d-manno-oct-2-ulosonic acid cytidylyltransferase (KdsB) from Burkholderia pseudomallei is provided. Rose Bengal effectively suppresses the nucleotidyltransferase activity of the three SNTs, and its IC values are 10.42, 0.76, and 5.31 µM, respectively. Interestingly, Rose Bengal inhibits the three enzymes regardless of their primary, secondary, tertiary, and quaternary structural differences. The experimental results indicate that Rose Bengal possesses the plasticity to shape its conformation suitable to interact with the three SNTs. As HddC functions in the formation of capsular polysaccharides and HldC and KdsB produce building blocks to constitute the inner core of lipopolysaccharide, Rose Bengal is a potential candidate to design antibiotics in a new category. In particular, it can be developed as a specific antimelioidosis agent. As the mortality rate of the infected people caused by B. pseudomallei is quite high, there is an urgent need for specific antimelioidosis agents. Therefore, a further study is being carried out with derivatives of Rose Bengal.
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http://dx.doi.org/10.1002/ardp.202000360DOI Listing
June 2021

Inhibition of d-glycero-β-d-manno-heptose 1-phosphate adenylyltransferase from Burkholderia pseudomallei by epigallocatechin gallate and myricetin.

Biochem J 2021 01;478(1):235-245

Graduate School of Pharmaceutical Sciences, Ewha Womans University, 52, Ewhayeodae-gil, Seoul 03760, Korea.

Flavonoids play beneficial roles in various human diseases. In this study, a flavonoid library was employed to probe inhibitors of d-glycero-β-d-manno-heptose-1-phosphate adenylyltransferase from Burkholderia pseudomallei (BpHldC) and two flavonoids, epigallocatechin gallate (EGCG) and myricetin, have been discovered. BpHldC is one of the essential enzymes in the ADP-l-glycero-β-d-manno-heptose biosynthesis pathway constructing lipopolysaccharide of B. pseudomallei. Enzyme kinetics study showed that two flavonoids work through different mechanisms to block the catalytic activity of BpHldC. Among them, a docking study of EGCG was performed and the binding mode could explain its competitive inhibitory mode for both ATP and βG1P. Analyses with EGCG homologs could reveal the important functional moieties, too. This study is the first example of uncovering the inhibitory activity of flavonoids against the ADP-l-glycero-β-d-manno-heptose biosynthesis pathway and especially targeting HldC. Since there are no therapeutic agents and vaccines available against melioidosis, EGCG and myricetin can be used as templates to develop antibiotics over B. pseudomallei.
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http://dx.doi.org/10.1042/BCJ20200677DOI Listing
January 2021

Crystal structure of pharmaceutical-grade human serum albumin.

Int J Biol Macromol 2021 Jan 23;166:221-228. Epub 2020 Oct 23.

College of Pharmacy, Ewha W. University, Seoul 03760, Republic of Korea. Electronic address:

Human serum albumin (HSA) is the most abundant protein in human plasma and plays versatile biological role. HSA has been widely used to treat several diseases and develop biocompatible biomaterials for biomedical applications. However, pharmaceutical-grade HSA (p-HSA) showed the altered oxidative and ligand-binding properties compare to native HSA. To investigate the influences of the manufacturing process on the molecular state of HSA, we determined the first crystal structure of p-HSA using the commercial HSA solution without any defatting step and further purification and carried out mass spectrometry to identify bound ligands. The crystal structure of p-HSA revealed that medium- and long-chain fatty acids and tryptophan are bound to p-HSA and one free cysteine is oxidized to cysteine-sulfenic acid. The mass spectra of p-HSA also confirmed the existence of fatty acids and tryptophan in p-HSA. Our results enhance understanding of the molecular state of p-HSA and can be utilized to produce p-HSA solutions and HSA-based biomaterials that has a higher biorelevance.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.10.152DOI Listing
January 2021

Epigenome-wide DNA methylation profiling of preeclamptic placenta according to severe features.

Clin Epigenetics 2020 08 24;12(1):128. Epub 2020 Aug 24.

Center for Prenatal Biomarker Research, CHA Advanced Research Institute, CHA Bundang Medical Center, Seongnam-si, Gyeonggi-do, Republic of Korea.

Background: Preeclampsia (PE) is an obstetric disorder with significant morbidities for both the mother and fetus possibly caused by a failure of the placental trophoblast invasion. However, its pathophysiology largely remains unclear. Here, we performed DNA methylation profiling to determine whether differential patterns of DNA methylation correlate with PE and severe features of PE.

Materials And Methods: We extracted DNA from placental tissues of 13 normal, five PE, and eight PE pregnant women with severe features. Genome-wide DNA methylation analysis was performed using the Illumina HumanMethylation 850K BeadChip. New functional annotations of differentially methylated CpGs (DMCs) in PE were predicted using bioinformatics tools.

Results: Significant differences were evident for 398 DMCs, including 243 DMCs in PE and 155 DMCs in PE with severe features, compared with normal placental tissues. Of these, 12 hypermethylated DMCs and three hypomethylated DMCs were observed in both PE groups, thus were independent from severe features. Three hundred seventy-nine DMCs were identified by the presence or absence of severe features. Two hundred genes containing these DMCs were associated with developmental processes and cell morphogenesis. These genes were significantly associated with various PE complications such as disease susceptibility, viral infections, immune system diseases, endocrine disturbance, seizures, hematologic diseases, and thyroid diseases.

Conclusions: This is the first study to investigate the genome-scale DNA methylation profiles of PE placentas according to severe features. The epigenetic variation in the placentas probably resulted in altered developmental processes and immune dysregulation, contributing to PE. This study provides basic information to refine the clinical and pathological mechanisms of the severe features in placenta-mediated PE.
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http://dx.doi.org/10.1186/s13148-020-00918-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444072PMC
August 2020

Feasibility of 3-Dimensional Visual Guides for Preparing Pediatric Zirconia Crowns: An In Vitro Study.

Int J Environ Res Public Health 2020 08 8;17(16). Epub 2020 Aug 8.

Department of Pediatric Dentistry, School of Dentistry, Kyung Hee University, Seoul 02447, Korea.

This study evaluated the feasibility of a tooth preparation guide for prefabricated zirconia crowns (PZCs). Three-dimensional surface data for PZCs of the left maxillary primary first molar and left mandibular primary second molar were obtained using a model scanner. The tooth preparation data were digitally designed to harmonize with the adjacent teeth on the mixed dentition model and visualized using a color-coded map, which presents the required amount of tooth reduction. Twenty participants were recruited for preparing teeth with and without using the tooth preparation guide. The following three parameters were evaluated: tooth preparation time, harmony score, and amount of tooth reduction. The preparation time when using the guide was significantly reduced ( < 0.05), and a significant difference was observed in the harmony scores for the maxillary primary first molar preparation. Furthermore, the amount of tooth reduction was significantly different for both maxillary and mandibular primary molars ( < 0.05) in terms of the occlusal distal surface and buccal line angle in the maxillary primary first molars, and the smooth surfaces, proximal surfaces, and mesial line angles in the mandibular primary second molars. Thus, the results suggest that a tooth preparation guide could facilitate better tooth preparation for PZCs.
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http://dx.doi.org/10.3390/ijerph17165732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459926PMC
August 2020

Cognitive profile as a predictor of the long-term outcome after deep brain stimulation in Parkinson's disease.

J Neurol Sci 2020 Oct 28;417:117063. Epub 2020 Jul 28.

Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address:

Background: Although dementia is a contraindication for deep brain stimulation (DBS) in patients with Parkinson's disease (PD), the concept is supported by little scientific evidence. Moreover, it is unclear whether PD with mild cognitive impairment (PD-MCI) or domain-specific cognitive impairments affect the outcome of DBS in non-demented PD patients.

Objective: To investigate the influence of baseline cognitive profiles of PD on the outcome of DBS.

Methods: Baseline cognitive levels of patients with PD who underwent DBS were classified into PD with dementia (PDD) (n = 15), PD-MCI (n = 210), and normal cognition (PD-NC) (n = 79). The impact of the cognitive level on key DBS outcome measures [mortality, nursing home admission, progression to Hoehn&Yahr (HY) stage 5 and progression to PDD] were analyzed using Cox regression models. We also investigated whether impairment of a specific cognitive domain could predict these outcomes in non-demented patients.

Results: Patients with PDD showed a substantially higher risk of nursing home admission and progression to HY stage 5 compared with patients with PD-MCI [hazard ratio (HR) 4.20, P = .002; HR = 5.29, P < .001] and PD-NC (HR 7.50, P < .001; HR = 7.93, P < .001). MCI did not alter the prognosis in patients without dementia, but those with visuospatial impairment showed poorer outcomes for nursing home admission (P = .015), progression to HY stage 5 (P = .027) and PDD (P = .006).

Conclusions: Cognitive profiles may stratify the pre-operative risk and predict long-term outcomes of DBS in PD.
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http://dx.doi.org/10.1016/j.jns.2020.117063DOI Listing
October 2020

Application of magnetic resonance computer-aided diagnosis for preoperatively determining invasive disease in ultrasonography-guided core needle biopsy-proven ductal carcinoma in situ.

Medicine (Baltimore) 2020 Jul;99(31):e21257

Division of Biomedical Engineering, Hankuk University of Foreign Studies, Gyeonggi-do, Republic of Korea.

The aim of this study was to analyze kinetic and morphologic features using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with computer-aided diagnosis (CAD) to predict occult invasive components in cases of biopsy-proven ductal carcinoma in situ (DCIS).We enrolled 138 patients with 141 breasts who underwent preoperative breast MRI and were diagnosed with DCIS via ultrasonography (US)-guided core needle biopsy performed at our institution during January 2009 to December 2012. Their clinical, mammographic, ultrasonographic, MRI, and final histologic findings were retrospectively reviewed. Their mammographic, ultrasonographic, and MRI findings were analyzed according to the American College of Radiology Breast Imaging Reporting and Data System. CAD findings of detectability, initial (fast, medium, and slow) and delay (persistent, plateau, and washout) phase enhancement kinetic descriptor, peak enhancement percentage, and lesion size were evaluated. Continuous and categorical variables were analyzed using independent t test and χ or Fisher exact test, respectively. Independent factors for predicting the presence of invasive component were evaluated by multivariate logistic regression analysis.Final histologic findings revealed that 55 breasts (39%) had DCIS with an invasive component. MRI-detected, CAD-detected, or pathologic lesion size (P = .002, P = .001, P < .001, respectively), delay washout kinetics and detectability on CAD (P < .001 and P = .004, respectively), presence of symptoms (P = .01), presence of comedonecrosis (P < .001), nuclear grade (P = .001), abnormality on mammography (P = .02), or US (P = .03) were significantly different between pure DCIS and the DCIS with an invasive component group on univariate analysis. Of those findings, multivariate analysis revealed that delay washout on CAD (odds ratio [OR], 4.36; 95% confidence interval [CI], 1.96-9.69; P = .0003) and pathologic size (OR, 1.29; 95% CI 1.05-1.57; P = .014) were independent predictive factors for the presence of an invasive component.Delay washout kinetic features measured by CAD and pathologic tumor size are potentially useful for predicting occult invasion in cases of biopsy-proven DCIS.Breast MRI including a CAD system would be helpful for predicting invasive components in cases of biopsy-proven DCIS and for selecting patients for sentinel lymph node biopsy.
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http://dx.doi.org/10.1097/MD.0000000000021257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402737PMC
July 2020

Flavonoids with inhibitory activity against SARS-CoV-2 3CLpro.

J Enzyme Inhib Med Chem 2020 Dec;35(1):1539-1544

College of Pharmacy, Graduates School of Pharmaceutical Sciences, Ewha W. University, Seoul, Republic of Korea.

Coronavirus disease 2019 (COVID-19) has been a pandemic disease of which the termination is not yet predictable. Currently, researches to develop vaccines and treatments is going on globally to cope with this disastrous disease. Main protease (3CLpro) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the good targets to find antiviral agents before vaccines are available. Some flavonoids are known to inhibit 3CLpro from SARS-CoV which causes SARS. Since their sequence identity is 96%, a similar approach was performed with a flavonoid library. Baicalin, herbacetin, and pectolinarin have been discovered to block the proteolytic activity of SARS-CoV-2 3CLpro. An docking study showed that the binding modes of herbacetin and pectolinarin are similar to those obtained from the catalytic domain of SARS-CoV 3CLpro. However, their binding affinities are different due to the usage of whole SARS-CoV-2 3CLpro in this study. Baicalin showed an effective inhibitory activity against SARS-CoV-2 3CLpro and its docking mode is different from those of herbacetin and pectolinarin. This study suggests important scaffolds to design 3CLpro inhibitors to develop antiviral agents or health-foods and dietary supplements to cope with SARS-CoV-2.
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http://dx.doi.org/10.1080/14756366.2020.1801672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470085PMC
December 2020

Transabdominal fetal reduction: a report of 124 cases.

J Obstet Gynaecol 2021 Jan 24;41(1):32-37. Epub 2020 Jul 24.

Department of Obstetrics and Gynecology, CHA Bundang Medical Center, Seongnam-si, Republic of Korea.

To prevent fetal loss, preterm delivery, and perinatal morbidity of multifetal pregnancies (MPs), fetal reduction (FR) is offered to some patients. We retrospectively analysed the data of 124 MPs that underwent transabdominal FR to twin ( = 63) and singleton ( = 61) pregnancies at a mean gestational age of 12 + 6 weeks between December 2006 and January 2018. FR was performed transabdominally with the injection of potassium chloride into the intracardiac or intrathoracic space of the fetus or fetuses after ultrasound screening for nuchal translucency and anatomical defects. The initial number of embryos were 48 twins, 63 triplets, 11 quadruplets, and 2 quintuplets. The procedure-related pregnancy loss rate was 0.8% (1/124), the overall pregnancy loss rate was 2.4% (3/124), the fetal loss rate was 1.6% (2/124), and the neonatal death rate was 0.8% (1/124). The baby take-home rates were 96% for twin pregnancies and 96.7% for singletons. This study shows that transabdominal FR is an effective and safe procedure with a pregnancy loss rate of 2.4%.Impact statement The incidence of multifetal pregnancies has increased over the years. Because multifetal pregnancies increase perinatal morbidity and mortality due to prematurity, fetal reduction is offed to some patients. The results of this study add to the growing body of research on fetal reduction. The study showed that transabdominal fetal reduction is a safe procedure with a pregnancy loss rate of 2.4%. The results of this study can be used in counselling couples with multifetal pregnancies who are considering fetal reduction. Further research is needed to confirm the current findings.
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http://dx.doi.org/10.1080/01443615.2019.1677577DOI Listing
January 2021

Age-dependent efficacy of subthalamic nucleus deep brain stimulation in young- and late-onset Parkinson's disease based on a 10 year follow-up.

J Neurol Sci 2020 09 25;416:117004. Epub 2020 Jun 25.

Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, South Korea. Electronic address:

Introduction: Long-term efficacy and safety of subthalamic nucleus deep brain stimulation (STN DBS) in patients with young-onset Parkinson's disease (YOPD) and late-onset PD (LOPD) (i.e. motor symptom initial appearance at ages ≤40 and > 40 years, respectively) was compared to identify relationships between PD onset age and the efficacy of DBS.

Methods: Statistical analyses compared specific motor and non-motor features among 13 patients with YOPD and 11 with LOPD. Medication reduction patterns and dyskinesia severity scores at baseline and after 1, 3, 5, and 10 years of follow-up were also analyzed using a repeated measures ANOVA tests. Lastly, a correlation analysis identified relationships between the impact of DBS settings (volume of activated tissue) and levodopa equivalent daily dose (LED), dyskinesia severity scores, Unified Parkinson's Disease Rating Scale (UPDRS) part III, and UPDRS part II (disability) scores.

Results: Ten years after DBS surgery, the reduction of LED from baseline (85.9 ± 592.6 mg versus 623.2 ± 464.9 mg; p = .023) and levodopa-induced dyskinesia (LID) scores (Unified Dyskinesia Rating Scale [UDysRS] parts III items 16-22; 1.6 ± 2.8 versus 5.5 ± 4.1; p = .013) were significantly lower in YOPD patients than LOPD patients. There were no significant differences between the two groups regarding UPDRS part III score improvement in response to levodopa, psychosis occurrence, or adverse effects.

Conclusion: Ten years after STN DBS surgery, LOPD patients showed greater LED reduction, and YOPD patients showed greater LID improvement, although the general long-term outcomes were similar between YOPD and LOPD patients.
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http://dx.doi.org/10.1016/j.jns.2020.117004DOI Listing
September 2020

A study of Rose Bengal against a 2-keto-3-deoxy-d--octulosonate cytidylyltransferase as an antibiotic candidate.

J Enzyme Inhib Med Chem 2020 Dec;35(1):1414-1421

Graduate School of Pharmaceutical Sciences, Ewha Woman's University, Seoul, Republic of Korea.

Frequent occurrences of multi-drug resistance of pathogenic Gram-negative bacteria threaten human beings. The CMP-2-keto-3-deoxy-d--octulosonic acid biosynthesis pathway is one of the new targets for antibiotic design. 2-Keto-3-deoxy-d--octulosonate cytidylyltransferase (KdsB) is the key enzyme in this pathway. KdsB proteins from (), (), (), and () have been assayed to find inhibitors. Interestingly, Rose Bengal (4,5,6,7-tetrachloro-2',4',5',7'-tetraiodofluorescein) was turned out to be an inhibitor of three KdsBs (KdsB, KdsB, and KdsB) with promising IC values and increased thermostability. The inhibitory enzyme kinetics of Rose Bengal revealed that it is competitive with 2-keto-3-deoxy--octulosonic acid (KDO) but non-competitive against cytidine 5'-triphosphate (CTP). Induced-fit docking analysis of KdsB revealed that Arg160 and Arg185 together with other interactions in the substrate binding site seemed to play an important role in binding with Rose Bengal. We suggest that Rose Bengal can be used as the scaffold to develop potential antibiotics.
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http://dx.doi.org/10.1080/14756366.2020.1751150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717453PMC
December 2020

The association between mastication and mild cognitive impairment in Korean adults.

Medicine (Baltimore) 2020 Jun;99(23):e20653

Department of Preventive and Social Dentistry, Seoul National University, Seoul, South Korea.

Currently, a few of studies revealed that there is an association between mastication and cognitive impairment. There is no study of Korean adult representative samples in relation to mastication and cognitive decline. This study was to investigate the relationship between mastication and mild cognitive impairment in Korean adults.A population-based cross-sectional study was conducted in which a total of 7029 subjects (2987 men and 4042 women) over 45 years old were surveyed from the Korea Longitudinal Study on Aging (KLoSA), Round 5th survey. Logistic regression analysis was performed for the study data controlling for confounding factors such as age, gender, education, income, smoking, drinking, exercise, wearing denture, and the number of chronic diseases.Decreased chewing function is associated with mild cognitive impairment (odds ratio [OR] = 3.24, 95% confidence interval [CI] = 2.67-3.93) after controlling for confounding variables. In the participants who did not wear dentures, the reduction of chewing function was strongly correlated with mild cognitive impairment (OR = 3.97, 95% CI = 3.11-5.08).Mastication was associated with mild cognitive impairment. To prevent cognitive decline, health specialists should pay more attention to the decline of the mastication in people without dentures.
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http://dx.doi.org/10.1097/MD.0000000000020653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306381PMC
June 2020

Long-term Effects of Bilateral Subthalamic Deep Brain Stimulation on Postural Instability and Gait Difficulty in Patients with Parkinson's Disease.

J Mov Disord 2020 May 29;13(2):127-132. Epub 2020 May 29.

Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Objective: The long-term effects of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) on postural instability and gait difficulty (PIGD) in patients with Parkinson's disease (PD) remain unclear. In this study, we aimed to evaluate the longterm effects of STN-DBS surgery on PIGD symptoms in patients with advanced-stage PD.

Methods: This study included 49 consecutively included patients with PD who underwent bilateral STN-DBS. The Unified Parkinson's Disease Rating Scale (UPDRS) scores and subscores for PIGD were assessed at baseline and at 1, 3, and 5 years postoperatively. The PIGD subscore was divided into PIGD-motor and PIGD-activities of daily living (ADL) scores according to parts III and II of the UPDRS, respectively.

Results: The PIGD-motor and PIGD-ADL scores at the "medication-off" state improved at 3 and 5 years, respectively. Overall, the UPDRS III and II scores at "medication-off" improved at 5 years. The UPDRS IV score also significantly improved and the levodopa equivalent daily dosage decreased at all follow-ups. Finally, the PIGD-motor score at baseline was able to predict long-term improvement in the PIGD-motor score at the 5-year follow-up.

Conclusion: The STN-DBS has both short- and long-term effects on PIGD, as well as overall motor function, in patients with advanced PD. The degree of PIGD at the preoperative evaluation can be used to predict long-term outcomes after STN-DBS surgery.
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http://dx.doi.org/10.14802/jmd.19081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280933PMC
May 2020

Treatment of superimposed preeclampsia on chronic hypertension in a twin pregnancy with automatic continuous positive airway pressure: a case report.

BMC Pulm Med 2020 Jun 3;20(1):157. Epub 2020 Jun 3.

Department of Obstetrics and Gynecology, CHA Bundang Medical Center, 59 Yatap-ro, Seongnam, 13496, Republic of Korea.

Background: Obstructive sleep apnoea (OSA) is related with adverse pregnancy outcomes, including preeclampsia. However, there are small studies about treatment of OSA with automatic continuous positive airway pressure (CPAP) in adverse obstetric outcomes.

Case Presentation: We introduce a case of 34 year old twin pregnant woman diagnosed with superimposed preeclampsia on chronic hypertension at 28 + 1/7 weeks of gestation. A level III polysomnography showed obstructive sleep apnoea, and automatic CPAP was applied. After the CPAP treatment concomitant with an antihypertensive drugs, both blood pressure and urinary protein concentration were reduced. The pregnancy safely continued for 49 days (to 35 + 1/7 weeks), with stable blood pressure, allowing prolongation of gestation of the foetuses.

Conclusion: This is the first case to report OSA with preeclampsia in a twin pregnancy. Our results suggest that automatic CPAP as an adjunct treatment to antihypertensive drugs may be beneficial in controlling blood pressure in early-onset preeclampsia associated with OSA.
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http://dx.doi.org/10.1186/s12890-020-01196-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268687PMC
June 2020

Production of Flavonoids in Callus Cultures of Aiton.

Plants (Basel) 2020 May 28;9(6). Epub 2020 May 28.

Plant Systems Engineering Research Center, KRIBB, 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Korea.

Flavonoids, including maackiain (Maac) from Aiton roots, have many pharmacological properties, such as antitumor, antimicrobial, and antifungal activities. This research aimed to develop an in vitro plant and callus culture system for for the purpose of generating an alternative production system for enhancing Maac production, as Maac is usually present in very small amounts in roots. We arranged the optimal conditions of different tissues of and supplemented the medium with various plant growth regulators (PGRs). The highest induction and proliferation rates of callus was shown in combination treatments of all concentrations of thidiazuron (TDZ) and picloram. In addition, calli induced with leaf explants cultured on 2.0 mg/L picloram and 0.5 mg/L 6-benzyladenine (BA) in Murashige and Skoog (MS) medium had the highest accumulation of the active metabolite Maac. In vitro shoots were regenerated on medium containing combinations of TDZ and α-Naphthalene acetic acid (NAA). A reliable protocol for the mass production of secondary metabolites using a callus culture of was successfully established.
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http://dx.doi.org/10.3390/plants9060688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356026PMC
May 2020

Re-Irradiation and Its Contribution to Good Prognosis in Recurrent Glioblastoma Patients.

Brain Tumor Res Treat 2020 Apr;8(1):29-35

Department of Neurosurgery, Bundang CHA Medical Center, CHA University College of Medicine, Seongnam, Korea.

Background: Radiation therapy, one of the strongest anti-cancer treatments, is already performed to treat primary glioblastoma; however, the effect of repeated radiation therapy for recurrent tumors has not been fully explored. The aim of this study was to determine the efficacy of re-irradiation in treating recurrent glioblastoma.

Methods: The study included 36 patients with recurrent glioblastoma treated with repeated radiation therapy between 2002 and 2016. Stereotactic radiosurgery (SRS) and hypo-fractionated stereotactic radiotherapy (HSRT) were performed in these patients.

Results: Fourteen patients received SRS with a median dose of 25 Gy (range, 20-32 Gy) in 1-5 fractions. Twenty-two patients received HSRT with a median dose of 40 Gy (range, 31.5-52 Gy) in 6-20 fractions. There were six treatment-related grade 3 adverse events. Survival analysis showed that re-irradiation significantly prolonged overall survival (OS) and progression-free survival (PFS). The median OS and one-year OS rate after re-irradiation were 17.2 months and 60.4%, respectively. The median PFS and 6-month PFS rate after re-irradiation were 4.4 months and 41.9%, respectively. Of the 36 patients, three survived without any progression in their condition.

Conclusion: Re-irradiation for recurrent glioblastoma showed favorable outcomes. Radiation dose and fractionation should be carefully considered to minimize radiation necrosis.
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http://dx.doi.org/10.14791/btrt.2020.8.e10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221471PMC
April 2020

Inhibition of African swine fever virus protease by myricetin and myricitrin.

J Enzyme Inhib Med Chem 2020 Dec;35(1):1045-1049

College of Pharmacy and Graduates School of Pharmaceutical Sciences, Ewha W. University, Seoul, Republic of Korea.

African swine fever (ASF) caused by the ASF virus (ASFV) is the most hazardous swine disease. Since a huge number of pigs have been slaughtered to avoid a pandemic spread, intense studies on the disease should be followed quickly. Recent studies reported that flavonoids have various antiviral activity including ASFV. In this report, ASFV protease was selected as an antiviral target protein to cope with ASF. With a FRET (Fluorescence resonance energy transfer) method, ASFV protease was assayed with a flavonoid library which was composed of sixty-five derivatives classified based on ten different scaffolds. Of these, the flavonols scaffold contains a potential anti-ASFV protease activity. The most prominent flavonol was myricetin with IC of 8.4 M. Its derivative, myricitrin, with the rhamnoside moiety was also showed the profound inhibitory effect on ASFV protease. These two flavonols apparently provide a way to develop anti-ASFV agents based on their scaffold.
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http://dx.doi.org/10.1080/14756366.2020.1754813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178854PMC
December 2020

Age-dependent facial subcutaneous fat thickness by high-frequency medical diagnostic ultrasound system.

Skin Res Technol 2020 09 20;26(5):769-771. Epub 2020 Mar 20.

R&D Center, LG Household & Health Care (LG H&H), Seoul, Korea.

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http://dx.doi.org/10.1111/srt.12858DOI Listing
September 2020

Assessing the Presence of Post-Traumatic Stress and Turnover Intention Among Nurses Post-Middle East Respiratory Syndrome Outbreak: The Importance of Supervisor Support.

Workplace Health Saf 2020 Jul 9;68(7):337-345. Epub 2020 Mar 9.

Seoul Health Foundation.

South Korea faced the Middle East Respiratory Syndrome (MERS) outbreak for the first time in 2015, which resulted in 186 infected patients and 39 deaths. This study investigated the level of post-traumatic stress disorder (PTSD) and turnover intention, the relationship between PTSD and turnover intention, and the buffering effect of supervisor support among nurses post-MERS outbreak. : In total, 300 nurses from three of 15 isolation hospitals in South Korea were invited to participate. We collected data pertaining to PTSD, turnover intention, supervisor support, work-related factors, and socio-demographic factors through a structured survey distributed to the nurses at the hospitals after the outbreak. For the statistical analyses, descriptive statistics and multiple regression were employed. : Of the 147 participants, 33.3% were involved in the direct care of the infected patients, whereas 66.7% were involved in the direct care of the suspected patients. More than half (57.1%) of the nurses experienced PTSD, with 25.1% experienced full PTSD and 32.0% with moderate or some level of PTSD. The mean score of turnover intention was 16.3, with the score range of 4 to 20. The multiple regression analysis revealed that PTSD was positively associated with turnover intention, and supervisor support had a strong buffering effect. : These findings confirmed that after a fatal infectious disease outbreak like MERS, nurses experience high level of PTSD and show high intention to leave. Organizational strategies to help nurses to cope with stress and to prevent turnover intention, especially using supervisor support, would be beneficial.
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http://dx.doi.org/10.1177/2165079919897693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201205PMC
July 2020

Flexible loop and helix 2 domains of TCTP are the functional domains of dimerized TCTP.

Sci Rep 2020 01 13;10(1):197. Epub 2020 Jan 13.

Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, 03760, Korea.

Translationally controlled tumor protein (TCTP), also called histamine releasing factor, is an evolutionarily conserved multifunctional protein in eukaryotes. We previously reported that extracellular TCTP acquires its cytokine-like function following dimerization. This study aims to identify the functional domain involved in the cytokine-like function of dimerized TCTP (dTCTP). We performed X-ray crystallographic studies and a deletion mutant of dTCTP which lacks the flexible loop domain. Synthetic peptides corresponding to TCTP domains and antibodies developed against them were examined for the anti-allergic effect. In an OVA-induced airway inflammation mouse model, inhibitory effect of synthetic peptides was evaluated. dTCTP was mediated by dimers between Cys172s of TCTP monomers. Synthetic peptides corresponding to the flexible loop and helix 2 domain of TCTP, and antibodies against them inhibited dTCTP-induced IL-8 release. In particular, the TCTP mutant lacking the flexible loop domain decreased the inflammatory cytokine activity of dTCTP. We conclude that the flexible loop and helix 2 domain of TCTP are the functional domains of dTCTP. They may have the potential to be therapeutic targets in the suppression of allergic reactions induced by dTCTP.
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http://dx.doi.org/10.1038/s41598-019-57064-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957494PMC
January 2020

GTP Preference of d-Glycero-α-d--Heptose-1-Phosphate Guanylyltransferase from .

Int J Mol Sci 2019 Dec 31;21(1). Epub 2019 Dec 31.

Graduate School of Pharmaceutical Sciences, Ewha Womans University, 52, Ewhayeodae-gil, Seoul 03760, Korea.

d-glycero-α-d--heptose-1-phosphate guanylyltransferase (HddC) is the fourth enzyme synthesizing a building component of lipopolysaccharide (LPS) of Gram-negative bacteria. Since HddC is a potential new target to develop antibiotics, the analysis of the structural and functional relationship of the complex structure will lead to a better idea to design inhibitory compounds. X-ray crystallography and biochemical experiments to elucidate the guanine preference were performed based on the multiple sequence alignment. The crystal structure of HddC from () complexed with guanosine 5'-(β-amino)-diphosphate (GMPPN) has been determined at 1.55 Å resolution. Meanwhile, the mutants revealed their reduced guanine affinity, instead of acquiring noticeable pyrimidine affinity. The complex crystal structure revealed that GMPPN is docked in the catalytic site with the aid of Glu80 positioning on the conserved motif EXXPLGTGGA. In the HddC family, this motif is expected to recruit nucleotides through interacting with bases. The crystal structure shows that oxygen atoms of Glu80 forming two hydrogen bonds play a critical role in interaction with two nitrogen atoms of the guanine base of GMPPN. Interestingly, the binding of GMPPN induced the formation of an oxyanion hole-like conformation on the L(S/A/G)X(S/G) motif and consequently influenced on inducing a conformational shift of the region around Ser55.
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http://dx.doi.org/10.3390/ijms21010280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981941PMC
December 2019

The Use of Histidine-tryptophan-ketoglutarate Solution as a New Storage Medium for the Avulsed Tooth.

J Endod 2020 Jan;46(1):74-80

Department of Pediatric Dentistry, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea. Electronic address:

Introduction: Histidine-tryptophan-ketoglutarate (HTK) is a preservation solution used for organ transplantation. The physiological pH and osmolality of this solution are known to facilitate cell proliferation and cell membrane stabilization. The purpose of the present study was to investigate the efficacy of several concentrations of HTK solution as a storage medium for avulsed teeth.

Methods: Cultured human periodontal ligament cells were stored in different concentrations of HTK solutions. After 1, 3, 6, 12, 24, 48, and 72 hours, cell viability was assessed using the Cell-Counting Kit-8 (Dojindo Molecular Technologies, Kumamoto, Japan) and LIVE/DEAD (Invitrogen, Carlsbad, CA) assay. Cell response of the most effective concentrations of HTK solution were further analyzed by gene expression profiling, and their cell viability was compared with other storage media.

Results: The highest cell viability was observed in 50% HTK solution in various concentrations of HTK solution (P < .05). In periodontal ligament cells stored in 50% HTK solution for 3 hours, the expression of genes related to angiogenesis, the inflammatory response, and cell proliferation was increased compared with the control. Compared with other storage media, the highest cell viability was observed in 50% HTK solution.

Conclusions: Our study suggests that 50% HTK solution containing cell culture medium represents a suitable storage medium for avulsed teeth.
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http://dx.doi.org/10.1016/j.joen.2019.10.013DOI Listing
January 2020

Factors influencing self-management in Parkinson's disease: A cross-sectional study.

Geriatr Nurs 2020 May - Jun;41(3):254-260. Epub 2019 Nov 26.

Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address:

This study aimed to identify factors influencing self-management in patients with Parkinson's disease (PD) based on social cognitive theory. A cross-sectional design was used; data were collected at three tertiary medical centers in Korea from a convenience sample of 356 PD patients. Higher self-management scores were associated with higher education level, having a religion, and higher family income. Self-management score was positively correlated with activities of daily living, self-efficacy, and social support, and negatively correlated with non-motor symptoms. Hierarchical regression analysis revealed that demographic factors and non-motor symptoms explained 26.2% of the variance in self-management in PD. The explanatory power increased by 7.5% when self-efficacy was added, and by 6.7% when social support was added. Assessment of self-management in patients with PD should consider self-efficacy and social support, along with demographic factors and non-motor symptoms. Self-management programs that reflect these factors may be useful for improving self-management in PD patients.
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http://dx.doi.org/10.1016/j.gerinurse.2019.10.005DOI Listing
March 2021