Publications by authors named "Mi-Kyung Lee"

434 Publications

Estimation of Measurement Uncertainty of Factor Assays Using the Monte Carlo Simulation.

Am J Clin Pathol 2021 May 12. Epub 2021 May 12.

Department of Laboratory Medicine, Chung-Ang University College of Medicine, Seoul, Republic of Korea.

Objectives: We aimed to quantify the measurement uncertainty (MU) for factor activities using the Monte Carlo simulation (MCS), which is a computational algorithm that simulates statistical sampling to obtain numerical results through complex mathematical calculations.

Methods: The uncertainties of factor V (FV), factor VIII (FVIII), and factor X (FX) were simulated with two coagulation testing systems: ACL TOP 750 CTS (Instrumentation Laboratory) and STA Compact (Diagnostica Stago).

Results: When the factor activities were 74% (FV), 68% (FVIII), and 89% (FX), the MUs were 3.5% (FV), 9.3% (VIII), and 2.8% (FX) for ACL TOP and 8.5% (FV), 18.2% (FVII), and 6.5% (FX) for STA Compact. MCS MUs were compared with MUs obtained from running actual samples (not simulated) using a method called the top-down approach. The MCS MU results were interchangeable with MUs from the top-down approach, except for FVIII from STA Compact.

Conclusions: The MCS procedure is well suited for the quantification of MUs for factor assays over the entire measurement range.
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http://dx.doi.org/10.1093/ajcp/aqab022DOI Listing
May 2021

Negative Air Ions Alleviate Particulate Matter-Induced Inflammation and Oxidative Stress in the Human Keratinocyte Cell Line HaCaT.

Ann Dermatol 2021 Apr 8;33(2):116-121. Epub 2021 Mar 8.

Department of Dermatology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.

Background: Recent studies have revealed that particulate matter induces inflammation, oxidative stress, and several skin diseases. Experimental results have also shown that negative air ions are highly effective in removing particulate matter-induced inflammation.

Objective: The present study aimed to investigate whether negative air ions can inhibit inflammatory responses and reduce oxidative stress in HaCaT cells exposed to particulate matters.

Methods: HaCaT cells were treated with particulate matter in the presence or absence of negative air ions and the viability was evaluated by the MTT assay. Reactive oxygen species (ROS) generation was quantified by the dichlorodihydrofluorescein diacetate assay. The expression of genes and proteins was analyzed by real-time polymerase chain reaction and Western blot. Levels of inflammatory cytokines were quantified by enzyme-linked immunosorbent assay.

Results: Negative air ions were observed to downregulate the mRNA and protein levels of particulate matter-induced pro-inflammatory cytokines in HaCaT cells. In addition, negative air ion treatment suppressed particulate matter-induced intracellular ROS generation, p38 mitogen-activated protein kinase activation, and activator protein 1 (c-Fos and c-Jun) activation.

Conclusion: Our findings indicate that negative air ions exert anti-inflammatory and antioxidant effects in HaCaT cells exposed to particulate matter. Therefore, negative air ions can be used for the prevention and treatment of particulate matter-related inflammatory skin diseases.
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http://dx.doi.org/10.5021/ad.2021.33.2.116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082002PMC
April 2021

Corrigendum: Association of , , and Polymorphisms with Atopic Dermatitis in Koreans.

Ann Dermatol 2020 Dec 11;32(6):538. Epub 2020 Nov 11.

Department of Dermatology, Chung-Ang University Hospital, Seoul, Korea.

[This corrects the article on p. 197 in vol. 32.].
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http://dx.doi.org/10.5021/ad.2020.32.6.538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875246PMC
December 2020

Association of , , and Polymorphisms with Atopic Dermatitis in Koreans.

Ann Dermatol 2020 Jun 24;32(3):197-205. Epub 2020 Apr 24.

Department of Dermatology, Chung-Ang University Hospital, Seoul, Korea.

Background: Early-onset and severe atopic dermatitis (AD) in patients increase the probability of the development of allergic rhinitis or asthma. Treatment and prevention strategies in infants and young children with AD are targeted toward treating the symptoms, restoring skin barrier functions, and reducing the absorption of environmental allergens in an attempt to attenuate or block the onset of asthma and food allergy.

Objective: Given that the initiating events in AD remain poorly understood, identifying those at risk and implementing strategies to prevent AD is necessary.

Methods: Whole-exome sequencing (WES) was performed in a 43 control group and a disease group with 20 AD patients without atopic march (AM) and 20 with AM. Sanger sequencing was carried out to validate found variants in cohorts.

Results: , , and single-nucleotide polymorphisms were identified by WES as missense mutations: c.1289C>A, p.P97T (rs529208); c.1685C>A, p.P562G (rs12484684); and c.457+27>C, rs3745540, respectively. A case-control study show that total immunoglobulin E (IgE) level was significantly increased in the AA genotype of compared to the CA genotype in allergic patients. The rs12484684 of increased risk of adult-onset AD (odds ratio: 1.63) compared to the control for (A) allele frequency. AD and AM Patients with the CA genotype also had elevated IgE levels. rs3745540 of was associated with AD in dominant model (odds ratio: 2.86).

Conclusion: DOCK8 (rs529208), (rs12484684), and (rs3745540), were identified using a new WES filtering method. the result suggests that polymorphism of and might be related to increase the total IgE level.
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http://dx.doi.org/10.5021/ad.2020.32.3.197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992614PMC
June 2020

sp. nov., isolated from blood of an immunocompromised patient.

Int J Syst Evol Microbiol 2021 Apr;71(4)

Department of Laboratory Medicine, Chung-Ang University College of Medicine, Seoul, Republic of Korea.

A novel Gram-stain-negative, facultative aerobic and rod-shaped bacterium, designated as MKL-01 and isolated from the blood of immunocompromised patient, was genotypically and phenotypically characterized. The colonies were found to be creamy yellow and convex. Phylogenetic analysis based on 16S rRNA gene and whole-genome sequences revealed that strain MKL-01 was most closely related to LMG 5886, present within a large cluster in the genus . The genome sequence of strain MKL-01 showed the highest average nucleotide identity value of 92.1 % and digital DNA-DNA hybridization value of 44.8 % with the closely related species LMG 5886. The genome size of the isolate was 5 750 268 bp, with a G+C content of 67.87 mol%. The strain could grow at 10-45 °C (optimum, 37-40 °C), in the presence of 0-10 % (w/v) NaCl (optimum, 0.5%) and at pH 6.0-10.0 (optimum, pH 7.0). Strain MKL-01 was positive for catalase and negative for oxidase. The major fatty acids were C, summed feature 3 (C7/C6 and/or C6/C7) and summed feature 8 (C7 and/or C6). The polar lipid profile consisted of phosphatidylglycerol, phosphatidylethanolamine, two unidentified phospholipids and one unidentified polar lipid. Moreover, strain MKL-01 contained ubiquinone Q-8 as the sole respiratory quinone. Based on its molecular, phenotypic and chemotaxonomic properties, strain MKL-01 represents a novel species of the genus ; the name sp. nov. is proposed for this strain. The type strain is MKL-01.
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http://dx.doi.org/10.1099/ijsem.0.004759DOI Listing
April 2021

Evaluation of rapid SARS-CoV-2 antigen tests, AFIAS COVID-19 Ag and ichroma COVID-19 Ag, with serial nasopharyngeal specimens from COVID-19 patients.

PLoS One 2021 8;16(4):e0249972. Epub 2021 Apr 8.

Department of Laboratory Medicine, Chung-Ang University College of Medicine, Seoul, Republic of Korea.

We evaluated the diagnostic accuracy of two newly developed, point-of-care, rapid antigen tests (RATs) for detecting SARS-CoV-2, the AFIAS COVID-19 Ag and the ichromaTM COVID-19 Ag, and investigated antigen kinetics. A total of 200 serially collected nasopharyngeal (NP) specimens from 38 COVID-19 patients and 122 specimens from negative controls were analyzed. Diagnostic sensitivity and specificity were assessed in comparison to molecular test results and subdivided according to targeted genes (E, RdRP, and N) and days post-symptom onset (PSO). For the kinetics evaluation, cut-off-indices from serial NP specimens were used according to the number of days PSO. Both RATs showed sensitivity of 91.3‒100% for specimens with cycle threshold (Ct) < 25. The specificity of AFIAS was 98.7‒98.9% and that of ichromaTM was 100.0%. The kappa values of AFIAS and ichromaTM for the molecular testing of specimens with Ct < 25 (RdRP) were 0.97 and 1.00, respectively. The sensitivity of AFIAS and ichromaTM for all genes was lower for specimens collected at 8‒14 PSO than for those collected before 7-days PSO. The kinetics profiles showed that antigen levels gradually decreased from ≤ 7-days PSO to > 22-days PSO. Both RATs showed excellent specificity and acceptable sensitivity for NP specimens with higher viral loads and for specimens collected within 7-days PSO. Hence, they have the potential to become useful tools for the early detection of SARS-CoV-2. However, because of concerns about false negativity, RATs should be used in conjunction with molecular tests.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249972PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8031412PMC
April 2021

Effects of Edible Insect Larva Fermentation Extract as a Substitute Protein on Hepatosteatogenesis and Proteomic Changes in Obese Mice Induced by High-Fat Diet.

Int J Mol Sci 2021 Mar 31;22(7). Epub 2021 Mar 31.

Department of Food and Nutrition, Sunchon National University, Suncheon 57922, Korea.

Mealworms ( larva) are an edible insect and a protein-rich food; however, research on mealworms as a substitute protein is insufficient. In this study, mealworm fermentation extract (TMP) was assessed as a replacement for soy protein (SP) in a control diet (CON) or a high-fat diet (HFD) of mice for 12 weeks. TMP substitution reduced body weight, body weight gain, body fat mass (perirenal and mesenteric), fat size, glucose intolerance, and insulin resistance compared to the HFD-SP group. TMP alleviated hepatic steatosis (lipid contents and lipid droplets) in high-fat-fed mice and down-regulated the , , and gene levels. Proteomic analysis showed that a HFD for 12 weeks up-regulated 20 proteins and down-regulated 17 proteins in mice fed SP. On the other hand, TMP reversed the protein profiles. TMP significantly down-regulated KHK, GLO1, ATP5H, SOD, and DDAH1 and up-regulated DLD, Mup1, CPS1, Ces3b, PDI, and HYOU1 compared to the HFD-SP group. These proteins are involved in the glucose, lipid, and amino acid metabolism, as well as in oxidative stress and endoplasmic reticulum stress. Thus, substituting SP for TMP helped improve HFD-induced obesity, steatosis, and insulin resistance in mice. These results suggest that TMP is a potential substitute for commonly used protein sources.
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http://dx.doi.org/10.3390/ijms22073615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037111PMC
March 2021

The impact of environmental variables on the spread of COVID-19 in the Republic of Korea.

Sci Rep 2021 03 16;11(1):5977. Epub 2021 Mar 16.

Department of Laboratory Medicine, Chung-Ang University College of Medicine, 102 Heukseok-ro, Dongjak-gu, Seoul, 06973, Republic of Korea.

Corona virus disease 2019 (COVID-19) has been declared a global pandemic and is a major public health concern worldwide. In this study, we aimed to determine the role of environmental factors, such as climate and air pollutants, in the transmission of COVID-19 in the Republic of Korea. We collected epidemiological and environmental data from two regions of the Republic of Korea, namely Seoul metropolitan region (SMR) and Daegu-Gyeongbuk region (DGR) from February 2020 to July 2020. The data was then analyzed to identify correlations between each environmental factor with confirmed daily COVID-19 cases. Among the various environmental parameters, the duration of sunshine and ozone level were found to positively correlate with COVID-19 cases in both regions. However, the association of temperature variables with COVID-19 transmission revealed contradictory results when comparing the data from SMR and DGR. Moreover, statistical bias may have arisen due to an extensive epidemiological investigation and altered socio-behaviors that occurred in response to a COVID-19 outbreak. Nevertheless, our results suggest that various environmental factors may play a role in COVID-19 transmission.
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http://dx.doi.org/10.1038/s41598-021-85493-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966806PMC
March 2021

Enhanced Stability of Indocyanine Green by Encapsulation in Zein-Phosphatidylcholine Hybrid Nanoparticles for Use in the Phototherapy of Cancer.

Pharmaceutics 2021 Feb 26;13(3). Epub 2021 Feb 26.

Department of Integrated Bioscience and Biotechnology, Sejong University, Seoul 05006, Korea.

Indocyanine green (ICG) is a clinically approved near-infrared dye that has shown promise as a photosensitizer for the phototherapy of cancer. However, its chemical instability in an aqueous solution has limited its clinical application. Encapsulating ICG in liposomes, phosphatidylcholine nanoparticles (PC-NP), has shown partial effectiveness in stabilizing it. Prompted by our recent finding that the zein-phosphatidylcholine hybrid nanoparticles (Z/PC-NP) provide an advanced drug carrier compared to PC-NP, we herein investigated the potential of Z/PC-NP as an improved ICG formulation. Dynamic light scattering analysis, transmission electron microscopy, and Fourier-transform infrared spectroscopy studies showed that ICG was encapsulated in Z/PC-NP without hampering the high colloidal stability of the Z/PC-NP. During storage, the Z/PC-NP almost completely inhibited the ICG aggregation, whereas the PC-NP did so partially. The Z/PC-NP also more effectively blocked the ICG degradation compared to the PC-NP. The phototoxicity of ICG encapsulated in Z/PC-NP on cancer cells was twofold higher than that in the PC-NP. The ICG encapsulated in Z/PC-NP, but not in PC-NP, maintained its photocytotoxicity after four-day storage. These findings highlight the promising potential of Z/PC-NP as an ICG formulation that provides a higher stabilization effect than PC-NP.
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http://dx.doi.org/10.3390/pharmaceutics13030305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996753PMC
February 2021

sp. nov., a moderately halophilic bacterium isolated from the faeces of a cow.

Int J Syst Evol Microbiol 2019 Jun 2;71(3). Epub 2021 Mar 2.

Korean Collection for Type Cultures (KCTC), Biological Resource Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Republic of Korea.

A Gram-stain-positive, facultatively anaerobic, endospore-forming, rod-shaped strain, AGMB 02131, which grew at 20-40 °C (optimum 30 °C), pH 3.0-11.0 (optimum pH 4.0) and in the presence of 0-18 % (w/v) NaCl (optimum 10 %), was isolated from a cow faecal sample and identified as a novel strain using a polyphasic taxonomic approach. The phylogenetic analysis based on 16S rRNA gene sequences along with the whole genome (92 core gene sets) revealed that AGMB 02131 formed a group within the genus , and showed the highest sequence similarity with DSM 28131 (96.9 %), following by DSM 18926 (96.6 %). The genome of AGMB 02131 comprised 70 contigs, the chromosome length was 4 038 965 bp and it had a 38.5 % DNA G+C content. Digital DNA-DNA hybridization revealed that AGMB 02131 displayed 21.4 % genomic DNA relatedness with the most closely related strain, DSM 18926. AGMB 02131 contains all of the conserved signature indels that are specific for members of the genus . The major cellular fatty acids (>10 %) of AGMB 02131 were Cω9, C and C. The major polar lipids present were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. On the basis of the phenotypic, phylogenetic, genomic and chemotaxonomic features, AGMB 02131 represents a novel species of the genus , for which the name sp. nov. is proposed. The type strain is AGMB 02131 (=KCTC 43221=CCTCC AB 2020077).
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http://dx.doi.org/10.1099/ijsem.0.004721DOI Listing
June 2019

Pharmacokinetic Estimation Models-based Approach to Predict Clinical Implications for CYP Induction by Calcitriol in Human Cryopreserved Hepatocytes and HepaRG Cells.

Pharmaceutics 2021 Jan 29;13(2). Epub 2021 Jan 29.

College of Pharmacy, Gachon University, Incheon 21936, Korea.

Calcitriol, a vitamin D metabolite, is approved for various indications because it is the bioactive form of vitamin D in the body. The purpose of this study was to predict the clinical significance of cytochrome P450 (CYP) induction by calcitriol using in vitro human cryopreserved hepatocytes, HepaRG experimental systems, and various pharmacokinetic estimation models. CYP2B6, 3A4, 2C8, and 2C9 mRNA levels increased in a concentration-dependent manner in the presence of calcitriol in human cryopreserved hepatocytes and HepaRG cells. Using the half maximal effective concentration (EC) and maximum induction effect (E) obtained from the in vitro study, a basic kinetic model was applied, suggesting clinical relevance. In addition, a static mechanistic model showed the improbability of a clinically significant effect; however, the calculated area under the plasma concentration-time curve ratio (AUCR) was marginal for CYP3A4 in HepaRG cells. To clarify the effect of CYP3A4 in vivo, physiologically based pharmacokinetic (PBPK) modeling was applied as a dynamic mechanistic model, revealing a low clinically significant effect of CYP3A4 induction by calcitriol. Therefore, we conclude that CYP induction by calcitriol treatment would not be clinically significant under typical clinical conditions.
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http://dx.doi.org/10.3390/pharmaceutics13020181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911399PMC
January 2021

Transcriptomic, Protein-DNA Interaction, and Metabolomic Studies of VosA, VelB, and WetA in Aspergillus nidulans Asexual Spores.

mBio 2021 02 9;12(1). Epub 2021 Feb 9.

School of Food Science and Biotechnology, Kyungpook National University, Daegu, Republic of Korea

In filamentous fungi, asexual development involves cellular differentiation and metabolic remodeling leading to the formation of intact asexual spores. The development of asexual spores (conidia) in is precisely coordinated by multiple transcription factors (TFs), including VosA, VelB, and WetA. Notably, these three TFs are essential for the structural and metabolic integrity, i.e., proper maturation, of conidia in the model fungus To gain mechanistic insight into the complex regulatory and interdependent roles of these TFs in asexual sporogenesis, we carried out multi-omics studies on the transcriptome, protein-DNA interactions, and primary and secondary metabolism employing conidia. RNA sequencing and chromatin immunoprecipitation sequencing analyses have revealed that the three TFs directly or indirectly regulate the expression of genes associated with heterotrimeric G-protein signal transduction, mitogen-activated protein (MAP) kinases, spore wall formation and structural integrity, asexual development, and primary/secondary metabolism. In addition, metabolomics analyses of wild-type and individual mutant conidia indicate that these three TFs regulate a diverse array of primary metabolites, including those in the tricarboxylic acid (TCA) cycle, certain amino acids, and trehalose, and secondary metabolites such as sterigmatocystin, emericellamide, austinol, and dehydroaustinol. In summary, WetA, VosA, and VelB play interdependent, overlapping, and distinct roles in governing morphological development and primary/secondary metabolic remodeling in conidia, leading to the production of vital conidia suitable for fungal proliferation and dissemination. Filamentous fungi produce a vast number of asexual spores that act as efficient propagules. Due to their infectious and/or allergenic nature, fungal spores affect our daily life. species produce asexual spores called conidia; their formation involves morphological development and metabolic changes, and the associated regulatory systems are coordinated by multiple transcription factors (TFs). To understand the underlying global regulatory programs and cellular outcomes associated with conidium formation, genomic and metabolomic analyses were performed in the model fungus Our results show that the fungus-specific WetA/VosA/VelB TFs govern the coordination of morphological and chemical developments during sporogenesis. The results of this study provide insights into the interdependent, overlapping, or distinct genetic regulatory networks necessary to produce intact asexual spores. The findings are relevant for other species such as the major human pathogen and the aflatoxin producer .
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http://dx.doi.org/10.1128/mBio.03128-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885118PMC
February 2021

Ten-Year Prevalence Trends of Phenotypically Identified Community-Associated Methicillin-Resistant Strains in Clinical Specimens.

Ann Lab Med 2021 Jul;41(4):386-393

Chung-Ang University College of Medicine, Seoul, Korea.

Background: Community-associated methicillin-resistant (CA-MRSA) strains were first detected in hospitals in Korea between the late 2000s and early 2010s. However, there is limited information regarding the prevalence of CA-MRSA strains among hospital isolates and their phenotypic changes over the last decade. We investigated the prevalence trend of CA-MRSA strains isolated from different clinical specimens and their phenotypic changes between September 2009 and September 2019.

Methods: CA-MRSA strains were phenotypically identified by confirming their resistance to penicillin (PCN) and oxacillin (OXA) and evaluating their susceptibility to trimethoprim-sulfamethoxazole, rifampin, fusidic acid, tetracycline, and at least one of the following four antimicrobials: clindamycin (CLI), erythromycin (ERY), ciprofloxacin (CIP), and gentamicin (GEN). A CA-MRSA strain that exhibited resistance to ERY, CLI, CIP, or GEN was classified as having resistance pattern I, II, III, or IV, respectively, regardless of its resistance to other antimicrobial agents.

Results: Of the 8,278 MRSA isolates identified in specimens obtained two days after admission, 1,385 (16.73%) were CA-MRSA strains. The prevalence of CA-MRSA strains increased from 12.2% to 26.6% (3.21% per period, =0.05). Resistance type analysis revealed an increasing trend in the prevalence of PCN/OXA-resistant (1.84%; =0.049) and PCN/OXA/ERY/CLI/CIP-resistant (0.98%; =0.04) CA-MRSA strains and in resistance pattern III strains (2.08%; =0.004).

Conclusions: The prevalence of CA-MRSA strains in Korea has increased significantly over the last decade, and CA-MRSA strains have gained phenotypic diversity beyond PCN/OXA-resistance, including antimicrobial resistance to non-β-lactams, especially CIP.
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http://dx.doi.org/10.3343/alm.2021.41.4.386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884191PMC
July 2021

Climate Change, Food Supply, and Dietary Guidelines.

Annu Rev Public Health 2021 Apr 26;42:233-255. Epub 2021 Jan 26.

Faculty of Social Sciences, Behavior and Health Education, Hanoi University of Public Health, Bac Tu Liem District, Hanoi 100000, Vietnam; email:

Food production is affected by climate change, and, in turn, food production is responsible for 20-30% of greenhouse gases. The food system must increase output as the population increases and must meet nutrition and health needs while simultaneously assisting in achieving the Sustainable Development Goals. Good nutrition is important for combatting infection, reducing child mortality, and controlling obesity and chronic disease throughout the life course. Dietary guidelines provide advice for a healthy diet, and the main principles are now well established and compatible with sustainable development. Climate change will have a significant effect on food supply; however, with political commitment and substantial investment, projected improvements will be sufficient to provide food for the healthy diets needed to achieve the Sustainable Development Goals. Some changes will need to be made to food production, nutrient content will need monitoring, and more equitable distribution is required to meet the dietary guidelines. Increased breastfeeding rates will improve infant and adult health while helping to reduce greenhouse gases.
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http://dx.doi.org/10.1146/annurev-publhealth-012420-105044DOI Listing
April 2021

Tertiary RNA Folding-Targeted Drug Screening Strategy Using a Protein Nanopore.

Anal Chem 2021 02 21;93(5):2811-2819. Epub 2021 Jan 21.

Disease Target Structure Research Center, KRIBB, Daejeon 34141, Republic of Korea.

Bacterial riboswitch RNAs are attractive targets for novel antibiotics against antibiotic-resistant superbacteria. Their binding to cognate metabolites is essential for the regulation of bacterial gene expression. Despite the importance of RNAs as therapeutic targets, the development of RNA-targeted, small-molecule drugs is limited by current biophysical methods. Here, we monitored the specific interaction between the adenine-sensing riboswitch aptamer domain (ARS) and adenine at the single-molecule level using α-hemolysin (αHL) nanopores. During adenine-induced tertiary folding, adenine-bound ARS intermediates exhibited characteristic nanopore events, including a two-level ionic current blockade and a ∼ 5.6-fold longer dwell time than that of free RNA. In a proof-of-concept experiment, tertiary RNA folding-targeted drug screening was performed using a protein nanopore, which resulted in the discovery of three new ARS-targeting hit compounds from a natural compound library. Taken together, these results reveal that αHL nanopores are a valuable platform for ultrasensitive, label-free, and single-molecule-based drug screening against therapeutic RNA targets.
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http://dx.doi.org/10.1021/acs.analchem.0c03941DOI Listing
February 2021

HbxB Is a Key Regulator for Stress Response and β-Glucan Biogenesis in .

Microorganisms 2021 Jan 11;9(1). Epub 2021 Jan 11.

School of Food Science and Biotechnology Kyungpook National University, Daegu 41566, Korea.

Homeobox transcription factors are conserved in eukaryotes and act as multi-functional transcription factors in filamentous fungi. Previously, it was demonstrated that HbxB governs fungal development and spore viability in . Here, the role of HbxB in was further characterized. RNA-sequencing revealed that HbxB affects the transcriptomic levels of genes associated with trehalose biosynthesis and response to thermal, oxidative, and radiation stresses in asexual spores called conidia. A phenotypic analysis found that deletion mutant conidia were more sensitive to ultraviolet stress. The loss of increased the mRNA expression of genes associated with β-glucan degradation and decreased the amount of β-glucan in conidia. In addition, deletion affected the expression of the sterigmatocystin gene cluster and the amount of sterigmatocystin. Overall, these results indicated that HbxB is a key transcription factor regulating trehalose biosynthesis, stress tolerance, β-glucan degradation, and sterigmatocystin production in conidia.
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http://dx.doi.org/10.3390/microorganisms9010144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827800PMC
January 2021

Effect of spin-orbit coupling on strong field ionization simulated with time-dependent configuration interaction.

J Chem Phys 2020 Dec;153(24):244109

Department of Chemistry, Wayne State University, Detroit, Michigan 48202, USA.

Time-dependent configuration interaction with a complex absorbing potential has been used to simulate strong field ionization by intense laser fields. Because spin-orbit coupling changes the energies of the ground and excited states, it can affect the strong field ionization rate for molecules containing heavy atoms. Configuration interaction with single excitations (CIS) has been employed for strong field ionization of closed shell systems. Single and double excitation configuration interaction with ionization (CISD-IP) has been used to treat ionization of degenerate states of cations on an equal footing. The CISD-IP wavefunction consists of ionizing single (one hole) and double (two hole/one particle) excitations from the neutral atom. Spin-orbit coupling has been implemented using an effective one electron spin-orbit coupling operator. The effective nuclear charge in the spin-orbit coupling operator has been optimized for Ar, Kr, Xe, HX (X = Cl, Br, and I). Spin-orbit effects on angular dependence of the strong field ionization have been studied for HX and HX. The effects of spin-orbit coupling are largest for ionization from the π orbitals of HX. In a static field, oscillations are seen between the Π and Π states of HX. For ionization of HX by a two cycle circularly polarized pulse, a single peak is seen when the maximum in the carrier envelope is perpendicular to the molecular axis and two peaks are seen when it is parallel to the axis. This is the result of the greater ionization rate for the π orbitals than for the σ orbitals.
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http://dx.doi.org/10.1063/5.0034807DOI Listing
December 2020

Complete mitochondrial genome sequence of Afla-Guard, commercially available non-toxigenic .

Mitochondrial DNA B Resour 2020 Oct 21;5(3):3590-3592. Epub 2020 Oct 21.

Department of Pharmaceutical Engineering, Woosuk University, Wanju, Republic of Korea.

Afla-Guard is a commercial non-toxigenic strain used to decrease aflatoxin contamination level in field. Its mitochondrial genome was sequenced, showing that its length is 29,208 bp with typical configuration of mitochondrial genome. 17 SNPs and 27 INDELs were identified by comparing with previous mitochondrial genome. Phylogenetic trees present that of Afla-Guard was clustered with the previous mitochondrial genome.
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http://dx.doi.org/10.1080/23802359.2020.1825129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594763PMC
October 2020

Complete mitochondrial genome sequence of SRRC1009: insight of intraspecific variations on mitochondrial genomes.

Mitochondrial DNA B Resour 2020 Oct 21;5(3):3585-3587. Epub 2020 Oct 21.

Department of Pharmaceutical Engineering, Woosuk University, Wanju, Republic of Korea.

The mitogenome of SRRC1009 was sequenced to investigate intraspecific variations on mitochondrial genomes of . It shows 29,202 bp with a typical configuration of mitogenome. Sixteen SNPs and 22 INDELs and 17 SNPs and 27 INDELs were identified against AflaGuard and JQ355000, respectively. Phylogenetic trees present in the three mitochondrial genomes were clustered with mitochondrial genome in one clade.
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http://dx.doi.org/10.1080/23802359.2020.1771226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594760PMC
October 2020

A Novel Species of the Genus Isolated From Human Blood Using Whole-Genome Sequencing.

Ann Lab Med 2021 05;41(3):323-327

Department of Laboratory Medicine, Chung-Ang University College of Medicine, Seoul, Korea.

Whole-genome sequencing (WGS) is an easily accessible and valuable tool in clinical microbiology, which can be used for identifying novel and rare species. We isolated gram-positive cocci from the blood of a pediatric patient, which could not be phenotypically identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) (BioMérieux, Marcy-l'Étoile, France). We could not identify the isolate to the species level using 16S ribosomal RNA (rRNA) sequencing. WGS was performed using the Illumina MiSeq platform (Illumina, San Diego, CA, USA); however, the subsequent genomic sequence database search using the TrueBac ID-Genome system (ChunLab, Inc., Seoul, Korea) did not yield any hits with an average nucleotide identity value >95.0%, which is the cut-off for species-level identification. Phylogenetic analysis suggested that the isolate belonged to a new species, forming a subcluster with . Our data demonstrate that WGS allows a more accurate annotation of microbial genomes than other clinical microbiology tools, such as MALDI-TOF MS and 16S rRNA sequencing. This is the first report of the isolation of a novel species from a clinical sample.
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http://dx.doi.org/10.3343/alm.2021.41.3.323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748104PMC
May 2021

Bioavailability of the Common Cold Medicines in Jellies for Oral Administration.

Pharmaceutics 2020 Nov 10;12(11). Epub 2020 Nov 10.

Department of Pharmaceutical Sciences, Woosuk University, Jeonbuk 55338, Korea.

Jellies for oral administration have been suggested as alternative dosage forms to conventional tablets for improved palatability and compliances for pediatric and geriatric patients. To evaluate the effect of jelly formulation on the bioavailability of cold medicines, two types of jellies were prepared for a fixed-dose combination of acetaminophen (AAP), chlorpheniramine maleate (CPM), dextromethorphan hydrobromide (DMH), and dl-methylephedrine hydrochloride (MEH). Jelly-S and Jelly-H were fabricated using carrageenan and locust bean gum in the absence and presence of xanthan gum, respectively. In vitro dissolution and in vivo absorption of the four drugs in the jellies were compared with other conventional formulations, a syrup and two types of immediate-release (IR) tablets with different hardness, Tablet-S (15 kPa) and Tablet-H (20 kPa). All the formulations exhibited more than 80% dissolution rate within 2 h even though the syrup, Jelly-S, and Tablet-S showed higher 30-min dissolution compared to Jelly-H and Tablet-H. The dissolution rates from the jellies decreased with increasing pH, which resulted in the slowest dissolution in pH 6.8 compared to the syrup and IR tablets. When administered orally to beagle dogs, all five formulations were determined not to be bioequivalent. However, Jelly-S and Jelly-H showed 0.82-1.05 of the geometric mean ratios (GMRs) of AUC for all four drugs compared to the syrup suggesting comparable absorption. In two IR tablets, GMRs of AUC were in a range of 0.55-0.95 indicating a tendency of lower absorption than the syrup and jellies. In conclusion, jelly can be a patient-centered formulation with comparable bioavailability to syrup.
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http://dx.doi.org/10.3390/pharmaceutics12111073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697653PMC
November 2020

Probing the Neuraminidase Activity of Influenza Virus Using a Cytolysin A Protein Nanopore.

Anal Chem 2020 11 14;92(21):14303-14308. Epub 2020 Oct 14.

Disease Target Structure Research Center, Division of Biomedical Research, KRIBB, Daejeon 34141, Republic of Korea.

Neuraminidase (NA), one of the major surface glycoproteins of influenza A virus (IAV), is an important diagnostic biomarker and antiviral therapeutic target. Cytolysin A (ClyA) is a nanopore sensor with an internal constriction of 3.3 nm, enabling the detection of protein conformations at the single-molecule level. In this study, a nanopore-based approach is developed for analysis of the enzymatic activity of NA, which facilitates rapid and highly sensitive diagnosis of IAV. Current blockade analysis of the d-glucose/d-galactose-binding protein (GBP) trapped within a type I ClyA-AS (ClyA mutant) nanopore reveals that galactose cleaved from sialyl-galactose by NA of the influenza virus can be detected in real time and at the single-molecule level. Our results show that this nanopore sensor can quantitatively measure the activity of NA with 40-80-fold higher sensitivity than those previously reported. Furthermore, the inhibition of NA is monitored using small-molecule antiviral drugs, such as zanamivir. Taken together, our results reveal that the ClyA protein nanopore can be a valuable platform for the rapid and sensitive point-of-care diagnosis of influenza and for drug screening against the NA target.
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http://dx.doi.org/10.1021/acs.analchem.0c03399DOI Listing
November 2020

Metabolomics Study of Serum from a Chronic Alcohol-Fed Rat Model Following Administration of Defatted Larva Fermentation Extract.

Metabolites 2020 Oct 29;10(11). Epub 2020 Oct 29.

College of Pharmacy, Sunchon National University, Suncheon 57922, Korea.

We have previously showed that defatted mealworm fermentation extract (MWF) attenuates alcoholic liver injury by regulating lipid, inflammatory, and antioxidant metabolism in chronic alcohol-fed rats. The current metabolomics study was performed to monitor biochemical events following the administration of MWF (daily for eight weeks) to a rat model of alcoholic liver injury by gas chromatography-tandem mass spectrometry (GC-MS/MS). The levels of 15 amino acids (AAs), 17 organic acids (OAs), and 19 free fatty acids (FFAs) were measured in serum. Analysis of variance (ANOVA), principal component analysis (PCA), and partial least squares discriminant analysis (PLS-DA) were used to compare the levels of 51 metabolites in serum. In particular, 3-hydroxybutyric acid (3-HB), pyroglutamic acid (PG), octadecanoic acid, and docosahexaenoic acid (DHA) were evaluated as high variable importance point (VIP) scores and PCA loading scores as determined by PLS-DA and PCA, and these were significantly higher in the MWF and silymarin groups than in the EtOH group. MWF showed a protective effect from alcohol-induced liver damage by elevating hepatic β-oxidation activity, and serum 3-HB levels were significantly higher in the MWF group than in the EtOH control group. Glycine levels were higher in the MWF group than in the EtOH group, and PG levels (related to glutathione production) were also elevated, indicating a reduction in alcohol-related oxidative stress. In addition, MWF is protected from alcohol-induced inflammation and steatosis by increasing serum DHA, palmitic, and octadecanoic acid levels as compared with the EtOH group. These results suggest that MWF might attenuate alcoholic liver disease, due to its anti-inflammatory and antioxidant effects by up-regulating hepatic β-oxidation activity and down-regulating liver FFA uptake.
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http://dx.doi.org/10.3390/metabo10110436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693418PMC
October 2020

Antibody kinetics and serologic profiles of SARS-CoV-2 infection using two serologic assays.

PLoS One 2020 22;15(10):e0240395. Epub 2020 Oct 22.

Department of Laboratory Medicine, Chung-Ang University College of Medicine, Seoul, Republic of Korea.

Background: Coronavirus disease 2019 (COVID-19) is an emerging threat worldwide. This study aims to assess the serologic profiles and time kinetics of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with COVID-19 using two immunoassays.

Methods: A total of 97 samples serially collected from 17 patients with COVID-19 and 137 negative control samples were analyzed for IgM and IgG against SARS-CoV-2 using the AFIAS COVID-19 Ab (Boditech Med Inc., Chuncheon, Republic of Korea) and the EDI™ Novel Coronavirus COVID-19 ELISA Kit (Epitope Diagnostics, Inc., San Diego, CA).

Results: With both assays, IgM and IgG rapidly increased after 7 days post symptom onset (PSO). IgM antibody levels reached a peak at 15-35 d PSO and gradually decreased. IgG levels gradually increased and remained at similar levels after 22-35 d. The diagnostic sensitivities of IgM/IgG for ≤14d PSO were 21.4%/35.7~57.1% and increased to 41.2~52.9%/88.2~94.1% at >14 d PSO with specificities of 98.5%/94.2% for AFIAS COVID-19 Ab and 100.0%/96.4% for EDI™ Novel Coronavirus COVID-19 ELISA Kit. Among 137 negative controls, 12 samples (8.8%) showed positive or indeterminate results.

Conclusions: The antibody kinetics against SARS-CoV-2 are similar to common findings of acute viral infectious diseases. Antibody testing is useful for ruling out SARS-CoV-2 infection after 14 d PSO, detecting past infection, and epidemiologic surveys.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240395PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580996PMC
November 2020

Changes in DNA methylation after 6-week exercise training in colorectal cancer survivors: A preliminary study.

Asia Pac J Clin Oncol 2020 Oct 13. Epub 2020 Oct 13.

Exercise Medicine Center for Diabetes and Cancer Patients, Institute of Convergence of Science (ICONS), Yonsei University, Seoul, South Korea.

Aim: Behavioral interventions such as exercise may induce epigenetic changes. Only few studies investigated the effects of exercise on epigenetic alterations in colorectal cancer survivors. The aim of this study was to explore the changes of genome-wide DNA methylation after 6-week exercise training in colorectal cancer survivors.

Methods: This preliminary study used a subset of data from a randomized controlled trial in 15 colorectal cancer survivors. Participants were randomized either to the 6-week exercise group or control group. The exercise intervention consisted of a weekly, group-based, supervised resistance exercise program and a home-based same resistance exercise plus walking six times per week. Blood samples were collected at baseline and after the intervention and data from eight subjects were analyzed for genome-wide DNA methylation on 865,918 CpG sites.

Results: Compared to the control group, the exercise group shows notable methylation changes in 756 CpG sites (22.7-25.2%). Gene ontology and disease annotation analysis showed that the genes targeting 81 CpG sites in promoter region with significant group-difference were linked in biological process such as immune response and transcription and related to metabolic and immune diseases. Also, hypermethylation on genes related to disease prevention seemed to be inhibited in the exercise group compared to the control group, indicating a likelihood of transcriptional activity of these genes.

Conclusion: We found a preliminary evidence of the positive effects of exercise intervention on epigenetic markers in colorectal cancer survivors. Larger scale randomized controlled trials are warranted to further investigate our findings.
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http://dx.doi.org/10.1111/ajco.13482DOI Listing
October 2020

Velvet activated McrA plays a key role in cellular and metabolic development in Aspergillus nidulans.

Sci Rep 2020 09 15;10(1):15075. Epub 2020 Sep 15.

Department of Bacteriology, University of Wisconsin, 1550 Linden Drive, Madison, 53706, USA.

McrA is a key transcription factor that functions as a global repressor of fungal secondary metabolism in Aspergillus species. Here, we report that mcrA is one of the VosA-VelB target genes and McrA governs the cellular and metabolic development in Aspergillus nidulans. The deletion of mcrA resulted in a reduced number of conidia and decreased mRNA levels of brlA, the key asexual developmental activator. In addition, the absence of mcrA led to a loss of long-term viability of asexual spores (conidia), which is likely associated with the lack of conidial trehalose and increased β-(1,3)-glucan levels in conidia. In supporting its repressive role, the mcrA deletion mutant conidia contain more amounts of sterigmatocystin and an unknown metabolite than the wild type conidia. While overexpression of mcrA caused the fluffy-autolytic phenotype coupled with accelerated cell death, deletion of mcrA did not fully suppress the developmental defects caused by the lack of the regulator of G-protein signaling protein FlbA. On the contrary to the cellular development, sterigmatocystin production was restored in the ΔflbA ΔmcrA double mutant, and overexpression of mcrA completely blocked the production of sterigmatocystin. Overall, McrA plays a multiple role in governing growth, development, spore viability, and secondary metabolism in A. nidulans.
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http://dx.doi.org/10.1038/s41598-020-72224-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493923PMC
September 2020

Robot-Assisted Partial Nephrectomy for Treatment of Juxtaglomerular Cell Tumor of the Kidney: A Case Report.

J Endourol Case Rep 2020 4;6(2):77-79. Epub 2020 Jun 4.

Department of Urology, Chung-Ang University College of Medicine, Seoul, Korea.

A juxtaglomerular cell tumor (JGCT), or a reninoma, is a rare renal tumor that can cause secondary hypertension. This is the first reported JGCT that was resected through robotic surgery. We present a case of a 27-year-old female patient with 1.35-cm-sized JGCT in the lower pole of the right kidney. We effectively removed a JGCT through robot-assisted partial nephrectomy without any complications. The robot-assisted partial nephrectomy procedure could be a suitable choice for JGCT resection.
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http://dx.doi.org/10.1089/cren.2019.0066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383434PMC
June 2020

In vivo quantitative analysis of advanced glycation end products in atopic dermatitis-Possible culprit for the comorbidities?

Exp Dermatol 2020 10 25;29(10):1012-1016. Epub 2020 Sep 25.

Department of Dermatology, Chung-Ang University College of Medicine, Seoul, Korea.

Advanced glycation end products (AGEs) interact with the membrane-bound receptor for AGEs (RAGE), consequently amplifying the inflammatory response. Soluble receptor for AGE (sRAGE) and endogenous secretory RAGE (esRAGE) act as decoys for AGE and competitively sequester RAGE ligands, thereby serving a cytoprotective role. Our objective was to investigate AGE expression and their receptors in the serum and skin of patients with atopic dermatitis (AD). In this case-control study, the levels of AGE, sRAGE and esRAGE were measured in the blood samples and corneocytes of 29 adult patients with AD and 12 healthy controls by ELISA. Corneocyte AGE levels increased in the AD group (P = .002). Higher corneocyte AGE levels were observed in the severe AD than in the milder form of AD. No significant difference in serum AGE level was observed in patients with AD and healthy controls. Serum sRAGE markedly decreased in patients with AD (P = .007) and serum esRAGE followed a similar trend. In conclusion, dermal accumulation of AGE in AD may have a role in fuelling skin inflammation. The potential after-effects of reduced neutralizer on systemic risk need further evaluation.
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http://dx.doi.org/10.1111/exd.14167DOI Listing
October 2020

Performance evaluation of EuDx™ ufPCR Flu & RSV detection kit for detection of influenza A/B and respiratory syncytial virus.

J Microbiol Immunol Infect 2020 Jun 27. Epub 2020 Jun 27.

Department of Laboratory Medicine, Chung-Ang University College of Medicine, Seoul, Republic of Korea. Electronic address:

EuDx™ ufPCR Flu & RSV Detection Kit (EUDIPIA, Chungcheongbuk-do, Republic of Korea) is a recently developed molecular assay for simultaneously detecting influenza A/B and respiratory syncytial virus (RSV). We evaluated this assay in a clinical setting and demonstrated its excellent performance for diagnosing influenza A/B and RSV infections.
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http://dx.doi.org/10.1016/j.jmii.2020.06.012DOI Listing
June 2020