• Genomics & Informatics
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• v.21 no.3
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• pp.42.1-42.23
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• 2023

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, one of the most deadly infections in humans. The emergence of multidrug-resistant and extensively drug-resistant Mtb strains presents a global challenge. Mtb has shown resistance to many frontline antibiotics, including rifampicin, kanamycin, isoniazid, and capreomycin. The only licensed vaccine, Bacille Calmette-Guerin, does not efficiently protect against adult pulmonary tuberculosis. Therefore, it is urgently necessary to develop new vaccines to prevent infections caused by these strains. We used a subtractive proteomics approach on 23 virulent Mtb strains and identified a conserved membrane protein (MmpL4, NP_214964.1) as both a potential drug target and vaccine candidate. MmpL4 is a non-homologous essential protein in the host and is involved in the pathogen-specific pathway. Furthermore, MmpL4 shows no homology with anti-targets and has limited homology to human gut microflora, potentially reducing the likelihood of adverse effects and cross-reactivity if therapeutics specific to this protein are developed. Subsequently, we constructed a highly soluble, safe, antigenic, and stable multi-subunit vaccine from the MmpL4 protein using immunoinformatics. Molecular dynamics simulations revealed the stability of the vaccine-bound Tolllike receptor-4 complex on a nanosecond scale, and immune simulations indicated strong primary and secondary immune responses in the host. Therefore, our study identifies a new target that could expedite the design of effective therapeutics, and the designed vaccine should be validated. Future directions include an extensive molecular interaction analysis, in silico cloning, wet-lab experiments, and evaluation and comparison of the designed candidate as both a DNA vaccine and protein vaccine.

• Genomics & Informatics
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• v.21 no.3
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• pp.29.1-29.9
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• 2023

Preterm birth (PTB), a pregnancy-related disease, is defined as a birth before 37 weeks of gestation. It is a major cause of maternal mortality and morbidity worldwide, and its incidence rate is steadily increasing. Various genetic factors can contribute to the etiology of PTB. Vascular endothelial growth factor A (VEGFA) gene is an important angiogenic gene and its polymorphisms have been reported to be associated with PTB development. Therefore, we conducted a case-control study to evaluate the association between VEGFA rs699947, rs2010963, and rs3025039 polymorphisms and PTB in Korean women. A total of 271 subjects (116 patients with PTB and 155 women at ≥38 weeks of gestation) were analyzed in this study. The genotyping of VEGFA gene polymorphisms was performed using polymerase chain reaction- restriction fragment length polymorphism. No significant association between the patients with PTB and the control groups was confirmed. In the combination analysis, we found a significant association between PTB and VEGFA rs699947 CC-rs2010963 GG-rs3025039 CC combination (odds ratio, 3.77; 95% confidence interval, 1.091 to 13.032; p = 0.031). The VEGFA rs699947, rs2010963, and rs3025039 polymorphisms might have no genetic association with the pathogenesis of PTB in Korean women. However, the combination analysis indicates the possibility that VEGFA acts in PTB pathophysiology. Therefore, larger sample sets and replication studies are required to further elucidate our findings.

• Genomics & Informatics
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• v.21 no.3
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• pp.40.1-40.11
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• 2023

Microbial community profiling using 16S rRNA amplicon sequencing allows for taxonomic characterization of diverse microorganisms. While amplicon sequence variant (ASV) methods are increasingly favored for their fine-grained resolution of sequence variants, they often discard substantial portions of sequencing reads during quality control, particularly in datasets with large number samples. We present a streamlined pipeline that integrates FastP for read trimming, HmmUFOtu for operational taxonomic units (OTU) clustering, Vsearch for chimera checking, and Kraken2 for taxonomic assignment. To assess the pipeline's performance, we reprocessed two published stool datasets of normal Korean populations: one with 890 and the other with 1,462 independent samples. In the first dataset, HmmUFOtu retained 93.2% of over 104 million read pairs after quality trimming, discarding chimeric or unclassifiable reads, while DADA2, a commonly used ASV method, retained only 44.6% of the reads. Nonetheless, both methods yielded qualitatively similar β-diversity plots. For the second dataset, HmmUFOtu retained 89.2% of read pairs, while DADA2 retained a mere 18.4% of the reads. HmmUFOtu, being a closed-reference clustering method, facilitates merging separately processed datasets, with shared OTUs between the two datasets exhibiting a correlation coefficient of 0.92 in total abundance (log scale). While the first two dimensions of the β-diversity plot exhibited a cohesive mixture of the two datasets, the third dimension revealed the presence of a batch effect. Our comparative evaluation of ASV and OTU methods within this streamlined pipeline provides valuable insights into their performance when processing large-scale microbial 16S rRNA amplicon sequencing data. The strengths of HmmUFOtu and its potential for dataset merging are highlighted.

• Genomics & Informatics
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• v.21 no.4
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• pp.50.1-50.9
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• 2023

Vaccine development is one of the key efforts to control the spread of coronavirus disease 2019 (COVID-19). However, it has become apparent that the immunity acquired through vaccination is not permanent, known as the waning effect. Therefore, monitoring the proportion of the population with immunity is essential to improve the forecasting of future waves of the pandemic. Despite this, the impact of the waning effect on forecasting accuracies has not been extensively studied. We proposed a method for the estimation of the effective immunity (EI) rate which represents the waning effect by integrating the second and booster doses of COVID-19 vaccines. The EI rate, with different periods to the onset of the waning effect, was incorporated into three statistical models and two machine learning models. Stringency Index, omicron variant BA.5 rate (BA.5 rate), booster shot rate (BSR), and the EI rate were used as covariates and the best covariate combination was selected using prediction error. Among the prediction results, Generalized Additive Model showed the best improvement (decreasing 86% test error) with the EI rate. Furthermore, we confirmed that South Korea's decision to recommend booster shots after 90 days is reasonable since the waning effect onsets 90 days after the last dose of vaccine which improves the prediction of confirmed cases and deaths. Substituting BSR with EI rate in statistical models not only results in better predictions but also makes it possible to forecast a potential wave and help the local community react proactively to a rapid increase in confirmed cases.

• Korean Journal of Radiology
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• v.23 no.10
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• pp.998-1008
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• 2022

Objective: The present study aimed to assess the relationship between incidental abnormalities on thoracic computed tomography (CT) and mortality in a general screening population using a long-term follow-up analysis. Materials and Methods: We retrospectively collected the medical records and CT images of 840 participants (mean age ± standard deviation [SD], 58.5 ± 6.7 years; 564 male) who underwent thoracic CT at a single health promotion center between 2007 and 2010. Two thoracic radiologists independently reviewed all CT images and evaluated any incidental abnormalities (interstitial lung abnormality [ILA], emphysema, coronary artery calcification [CAC], aortic valve [AV] calcification, and pulmonary nodules). Kaplan-Meier analysis with log-rank and z-tests was performed to assess the relationship between incidental CT abnormalities and all-cause mortality in the subsequent follow-up. Cox proportional hazards regression was performed to further identify risk factors of all-cause mortality among the incidental CT abnormalities and clinical factors. Results: Among the 840 participants, 55 (6%), 171 (20%), 288 (34%), 396 (47%), and 97 (11%) had findings of ILA, emphysema, CAC, pulmonary nodule, and AV calcification, respectively, on initial CT. The participants were followed up for a mean period ± SD of 10.9 ± 1.4 years. All incidental CT abnormalities were associated with all-cause mortality in univariable analysis (p < 0.05). However, multivariable analysis further revealed fibrotic ILA as an independent risk factor for all-cause mortality (hazard ratio, 2.52 [95% confidence interval, 1.02-6.22], p = 0.046). ILA were also identified as an independent risk factor for lung cancer or respiratory disease-related deaths. Conclusion: Incidental abnormalities on screening thoracic CT were associated with increased mortality during the long-term follow-up. Among incidental CT abnormalities, fibrotic ILA were independently associated with increased mortality. Appropriate management and surveillance may be required for patients with fibrotic ILA on thoracic CT obtained for general screening purposes.

• The Journal of Korean Medicine
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• v.45 no.1
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• pp.114-125
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• 2024

Objectives: Network pharmacology is an analysis method that explores drug-centered efficacy and mechanism by constructing a compound-target-disease network based on system biology, and is attracting attention as a methodology for studying herbal medicine that has the characteristics for multi-compound therapeutics. Thus, we investigated the potential functions and pathways of Myrrha on Allergic Rhinitis (AR) via network pharmacology analysis and molecular docking. Methods: Using public databases and PubChem database, compounds of Myrrha and their target genes were collected. The putative target genes of Myrrha and known target genes of AR were compared and found the correlation. Then, the network was constructed using STRING database, and functional enrichment analysis was conducted based on the Gene Ontology (GO) Biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathways. Binding-Docking stimulation was performed using CB-Dock. Results: The result showed that total 3 compounds and 55 related genes were gathered from Myrrha. 33 genes were interacted with AR gene set, suggesting that the effects of Myrrha are closely related to AR. Target genes of Myrrha are considerably associated with various pathways including 'Fc epsilon RI signaling pathway' and 'JAK-STAT signaling pathway'. As a result of blinding docking, AKT1, which is involved in both mechanisms, had high binding energies for abietic acid and dehydroabietic acid, which are components of Myrrha. Conclusion: Through a network pharmacological method, Myrrha was predicted to have high relevance with AR by regulating AKT1. This study could be used as a basis for studying therapeutic effects of Myrrha on AR.

• Journal of Ginseng Research
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• v.48 no.4
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• pp.384-394
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• 2024

Background: Herpes simplex virus type 1 (HSV-1), known to latently infect the host's trigeminal ganglion, can lead to severe herpes encephalitis or asymptomatic infection, potentially contributing to neurodegenerative diseases like Alzheimer's. The virus generates reactive oxygen species (ROS) that significantly impact viral replication and induce chronic inflammation through NF-κB activation. Nuclear factor E2-related factor 2 (Nrf2), an oxidative stress regulator, can prevent and treat HSV-1 infection by activating the passive defense response in the early stages of infection. Methods and results: Our study investigated the antiviral effects of ginsenoside Rg5, an Nrf2 activator, on HSV-1 replication and several host cell signaling pathways. We found that HSV-1 infection inhibited Nrf2 activity in host cells, induced ROS/NF-κB signaling, and triggered inflammatory cytokines. However, treatment with ginsenoside Rg5 inhibited ROS/NF-κB signaling and reduced inflammatory cytokines through NRF2 induction. Interestingly, the Nrf2 inhibitor ML385 suppressed the expression of NAD(P)H quinone oxidoreductase 1(NQO1) and enhanced the expression of KEAP1 in HSV-1 infected cells. This led to the reversal of VP16 expression inhibition, a protein factor associated with HSV-1 infection, thereby promoting HSV-1 replication. Conclusion: These findings suggest for the first time that ginsenoside Rg5 may serve as an antiviral against HSV-1 infection and could be a novel therapeutic agent for HSV-1-induced neuroinflammation.

• Korean Journal of Radiology
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• v.1 no.2
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• pp.79-83
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• 2000

Objective: To describe the thin-section CT findings of arc-welders' pneumoconiosis. Materials and Methods: Eighty-five arc-welders with a three to 30 (mean, 15)-year history of exposure underwent thin-section CT scanning. The extent of abnormalities detected was correlated with the severity of dyspnea and pulmonary function tests. For comparison, images of 43 smoking males (mean 25 pack-year) who underwent thin-section CT for other reasons (smokers' group) were also analyzed. Results: Fifty-four welders (63.5%) and six smokers (14.0%) showed positive findings. Predominant thin-section CT findings were poorly-defined centrilobular micronodules (30/54, 55.6%), branching linear structure (18/54, 33.3%), and ground-glass attenuation (6/54, 11.1%). In the smokers' group, poorly-defined micronodules were found in four patients, branching linear structures in one, and ground-glass attenuation in one. In welders, the extent of abnormalities seen on thin-section CT showed no significant correlation with the severity of dyspnea or the results of pulmonary funotion test. Conclusion: Poorly-defined centrilobular micronodules and branching linear structures were the thin-section CT findings most frequently seen in patients with arc-welders' pneumoconiosis. Less commonly, extensive ground-glass attenuation was also seen.

• Korean Journal of Radiology
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• v.1 no.3
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• pp.135-141
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• 2000

Objective: To compare the clinical utility of the different imaging techniques used for the evaluation of tracheobronchial diseases. Materials and Methods: Forty-one patients with tracheobronchial diseases [tuberculosis (n = 18), bronchogenic carcinoma (n = 10), congenital abnormality (n = 3), post-operative stenosis (n = 2), and others (n = 8)] underwent chest radiography and spiral CT. Two sets of scan data were obtained: one from routine thick-section axial images and the other from thin-section axial images. Multiplanar reconstruction (MPR) and shaded surface display (SSD) images were obtained from thin-section data. Applying a 5-point scale, two observers compared chest radiography, routine CT, thin-section spiral CT, MPR and SSD imaging with regard to the detection, localization, extent, and characterization of a lesion, information on its relationship with adjacent structures, and overall information. Results: SSD images were the most informative with regard to the detection (3.95±0.31), localization (3.95±0.22) and extent of a lesion (3.85±0.42), and overall information (3.83±0.44), while thin-section spiral CT scans provided most information regarding its relationship with adjacent structures (3.56±0.50) and characterization of the lesion (3.51±0.61). Conclusion: SSD images and thin-section spiral CT scans can provide valuable information for the evaluation of tracheobronchial disease.

• Journal of Animal Science and Technology
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• v.66 no.5
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• pp.876-890
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• 2024

A balanced intestinal microbiome controls intestinal bacterial diseases, helps regulate immunity, and digests and utilizes nutrients, ultimately having a positive effect on the productivity of industrial animals. Yeasts help in the digestion process by breaking down indigestible fibers and producing organic acids, vitamins, and minerals. In particular, polysaccharides such as beta-glucan and mannan-oligosaccharides, which are present in the cell wall of yeast, inhibit the adhesion of pathogens to the surface of the gastrointestinal tract and increase resistance to disease to help maintain and improve intestinal health. Among the yeast additives used in animal feed, Saccharomyces cerevisiae is one of the most commonly used probiotics. However, it does not naturally reside in the intestine, so if it is supplied in combination with other species of probiotics that can compensate for it, many benefits and synergies can be expected for pigs in terms of maintaining intestinal health such as supplementing the immune system and improving digestion. A number of previous studies have demonstrated that dietary complex probiotic supplementation has growth-promoting effects in pigs, suggesting that multiple strains of probiotics may be more effective than single strain probiotics due to their additive and synergistic effects. In practice, however, the effects of complex probiotics are not always consistent, and can be influenced by a variety of factors. Therefore, this review comprehensively examines and discusses the literature related to the effects of complex probiotics using Saccharomyces cerevisiae in pig production.