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Establishment of the large-scale longitudinal multi-omics dataset in COVID-19 patients: data profile and biospecimen

  • Jo, Hye-Yeong;Kim, Sang Cheol;Ahn, Do-hwan;Lee, Siyoung;Chang, Se-Hyun;Jung, So-Young;Kim, Young-Jin;Kim, Eugene;Kim, Jung-Eun;Kim, Yeon-Sook;Park, Woong-Yang;Cho, Nam-Hyuk;Park, Donghyun;Lee, Ju-Hee;Park, Hyun-Young
    • BMB Reports
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    • v.55 no.9
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    • pp.465-471
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    • 2022
  • Understanding and monitoring virus-mediated infections has gained importance since the global outbreak of the coronavirus disease 2019 (COVID-19) pandemic. Studies of high-throughput omics-based immune profiling of COVID-19 patients can help manage the current pandemic and future virus-mediated pandemics. Although COVID-19 is being studied since past 2 years, detailed mechanisms of the initial induction of dynamic immune responses or the molecular mechanisms that characterize disease progression remains unclear. This study involved comprehensively collected biospecimens and longitudinal multi-omics data of 300 COVID-19 patients and 120 healthy controls, including whole genome sequencing (WGS), single-cell RNA sequencing combined with T cell receptor (TCR) and B cell receptor (BCR) sequencing (scRNA(+scTCR/BCR)-seq), bulk BCR and TCR sequencing (bulk TCR/BCR-seq), and cytokine profiling. Clinical data were also collected from hospitalized COVID-19 patients, and HLA typing, laboratory characteristics, and COVID-19 viral genome sequencing were performed during the initial diagnosis. The entire set of biospecimens and multi-omics data generated in this project can be accessed by researchers from the National Biobank of Korea with prior approval. This distribution of large-scale multi-omics data of COVID-19 patients can facilitate the understanding of biological crosstalk involved in COVID-19 infection and contribute to the development of potential methodologies for its diagnosis and treatment.

Anti-inflammatory and Anti-oxidant Activities of Aster Scaber Ethanol Extract

  • Saba, Evelyn;Je, Nayeong;Song, Ji Eun;Shi, Sangwoo;Lee, Juho;Jung, Oneyoung;Han, Beom Jun;Lee, Soo Young;Park, Jongwon;Lee, Yuan Yee;Rhee, Man Hee
    • Biomedical Science Letters
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    • v.28 no.3
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    • pp.170-177
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    • 2022
  • In mountainous regions, wild herbs which can also be edible in nature for humans and animals possess a wide array of biologically diversified properties. It is because of the fact that due to the cold weather of mountains; they are enriched in certain kinds of phytochemicals such as anti-oxidants, anti-inflammatory and many more. One such kind of an herb is Aster scaber (AS) in Korean. It is a widely cultivated culinary herb in Korean peninsula and used as a side dish in Korean culinary cuisine. In view of its extensive use in cuisine, we geared to unravel the anti-oxidant and anti-inflammatory effects of AS in murine alveolar macrophage cell line (MH-S). 2,2'-Azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) assays revealed a dose dependent (7.8~1,000 ㎍/mL) inhibition of oxidation by AS 70% ethanol (ASE) extract as compared to Trolox and Ascorbic acid respectively. Nitric oxide assay (NO) showed a dose dependent decrease (5~40 ㎍/mL) in MH-S cells with ASE when stimulated with Coal Fly Ash (CFA). Moreover, this dose for NO reduction was also found to be least cytotoxic for cells as determined by cellular viability (MTT) assay. The gene expression of pro-inflammatory mediators (iNOS and COX-2) and cytokines (IL-6 and IL-1β) and were also dose dependently inhibited by ASE in MH-S cells through RT-PCR. Therefore, in light of these findings, AS exhibited a strong anti-oxidant and anti-inflammatory agent. These results also justify the extensive use of this mountainous herb in culinary practices for beneficial effects on human health.

Effects of long-term tubular HIF-2α overexpression on progressive renal fibrosis in a chronic kidney disease model

  • Dal-Ah Kim;Mi-Ran Lee;Hyung Jung Oh;Myong Kim;Kyoung Hye Kong
    • BMB Reports
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    • v.56 no.3
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    • pp.196-201
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    • 2023
  • Renal fibrosis is the final manifestation of chronic kidney disease (CKD) regardless of etiology. Hypoxia-inducible factor-2 alpha (HIF-2α) is an important regulator of chronic hypoxia, and the late-stage renal tubular HIF-2α activation exerts protective effects against renal fibrosis. However, its specific role in progressive renal fibrosis remains unclear. Here, we investigated the effects of the long-term tubular activation of HIF-2α on renal function and fibrosis, using in vivo and in vitro models of renal fibrosis. Progressive renal fibrosis was induced in renal tubular epithelial cells (TECs) of tetracycline-controlled HIF-2α transgenic (Tg) mice and wild-type (WT) controls through a 6-week adenine diet. Tg mice were maintained on doxycycline (DOX) for the diet period to induce Tg HIF-2α expression. Primary TECs isolated from Tg mice were treated with DOX (5 ㎍/ml), transforming growth factor-β1 (TGF-β1) (10 ng/ml), and a combination of both for 24, 48, and 72 hr. Blood was collected to analyze creatinine (Cr) and blood urea nitrogen (BUN) levels. Pathological changes in the kidney tissues were observed using hematoxylin and eosin, Masson's trichrome, and Sirius Red staining. Meanwhile, the expression of fibronectin, E-cadherin and α-smooth muscle actin (α-SMA) and the phosphorylation of p38 mitogen-activated protein kinase (MAPK) was observed using western blotting. Our data showed that serum Cr and BUN levels were significantly lower in Tg mice than in WT mice following the adenine diet. Moreover, the protein levels of fibronectin and E-cadherin and the phosphorylation of p38 MAPK were markedly reduced in the kidneys of adenine-fed Tg mice. These results were accompanied by attenuated fibrosis in Tg mice following adenine administration. Consistent with these findings, HIF-2α overexpression significantly decreased the expression of fibronectin in TECs, whereas an increase in α-SMA protein levels was observed after TGF-β1 stimulation for 72 hr. Taken together, these results indicate that long-term HIF-2α activation in CKD may inhibit the progression of renal fibrosis and improve renal function, suggesting that long-term renal HIF-2α activation may be used as a novel therapeutic strategy for the treatment of CKD.

Evaluating the activity of N-89 as an oral antimalarial drug

  • Nagwa S. M. Aly;Hiroaki Matsumori;Thi Quyen Dinh;Akira Sato;Shin-ichi Miyoshi;Kyung-Soo Chang;Hak Sun Yu;Takaaki Kubota;Yuji Kurosaki;Duc Tuan Cao;Gehan A. Rashed;Hye-Sook Kim
    • Parasites, Hosts and Diseases
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    • v.61 no.3
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    • pp.282-291
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    • 2023
  • Despite the recent progress in public health measures, malaria remains a troublesome disease that needs to be eradicated. It is essential to develop new antimalarial medications that are reliable and secure. This report evaluated the pharmacokinetics and antimalarial activity of 1,2,6,7-tetraoxaspiro[7.11]nonadecane (N-89) using the rodent malaria parasite Plasmodium berghei in vivo. After a single oral dose (75 mg /kg) of N-89, its pharmacokinetic parameters were measured, and t1/2 was 0.97 h, Tmax was 0.75 h, and bioavailability was 7.01%. A plasma concentration of 8.1 ng/ml of N-89 was maintained for 8 h but could not be detected at 10 h. The dose inhibiting 50% of parasite growth (ED50) and ED90 values of oral N-89 obtained following a 4-day suppressive test were 20 and 40 mg/kg, respectively. Based on the plasma concentration of N-89, we evaluated the antimalarial activity and cure effects of oral N-89 at a dose of 75 mg/kg 3 times daily for 3 consecutive days in mice harboring more than 0.5% parasitemia. In all the N-89-treated groups, the parasites were eliminated on day 5 post-treatment, and all mice recovered without a parasite recurrence for 30 days. Additionally, administering oral N-89 at a low dose of 50 mg/kg was sufficient to cure mice from day 6 without parasite recurrence. This work was the first to investigate the pharmacokinetic characteristics and antimalarial activity of N-89 as an oral drug. In the future, the following steps should be focused on developing N-89 for malaria treatments; its administration schedule and metabolic pathways should be investigated.

Alternative Immunossays

  • Barnard, G.J.R.;Kim, J.B.;Collins, W.P.
    • Korean Journal of Animal Reproduction
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    • v.9 no.2
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    • pp.133-139
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    • 1985
  • An immunoassay may be defined as an analytical procedure involving the competitive reaction between a limiting concentration of specific antibody and two populations of antigen, one of which is labelled or immobillized. The advent of immunoassay has revolutionised our knowledge of reproductive physiology and the practice of veterinary and clinical medicine. Radioimmunoassay (RIA) was the first of these methods to be developed, which meausred the analyte with good sensitivity, accuracy and precision (1,2). The essential components of RIA are:-(i) a limited concentration of antibodies, (ii) a reference preparation, and (iii) an antigen labelled with a radioisotope (usually tritium or iodine-125). Most procedures invelove isolating the antibody-bound fraction and measuring the amount of labelled antigen. Good facilities are available for scintilltion counting, data reduction nd statistical analysis. RIA is undergoing refinement through:-(i) the introduction of new techniques to separate the antibody-bound and free fractions which minimize the misclassification of labelled antigen into these compartments, and the amount of non-specfic binding. (3), (ii) the development of non-extration for the measurement of haptens (4), (iii) the determination of a, pp.rent free (i.e. non-protein bound) analytes (5), and (iv) the use of monoclonal antibodies(6). In 1968, Miles and Hales introduced in important new type of immunoassay which they termed immunora-diometric assay (IRMA) based on t도 use of isotopically labelled specific antibodies(7) in a move from limited to excess reagent systems. The concept of two-site IRMAs (with a capture antibody on a solid-phase, and a second labelled antibody to a different antigenic determinant of the analyte) has enabled the development of more sensitive and less-time consuming methods for the measurement of protein hormones ovar wide concentration of analyte (8). The increasing use of isotopic methos for diverse a, pp.ications has exposed several problems. For example, the radioactive half-life and radiolysis of the labelled reagent limits assay sensitivity and imposes a time limit on the usefulness of a kit. In addition, the potential health hazards associated with the use and disposal of radioactive cmpounds and the solvents and photofluors necessary for liquid scientillation counting are incompatable with the development of extra-laboratory tests. To date, the most practical alternative labels to radioisotopes, for the measurement of analytes in a concentration > 1 ng/ml, are erythrocytes, polystyrene particiles, gold sols, dyes and enzymes or cofactors with a visual or colorimetric end-point(9). Increased sensitivity to<1 pg/ml may be obtained with fluorescent and chemiluminescent labels, or enzymes with a fluorometric, chemiluminometric or bioluminometric end-point. The sensitivity of any immunoassay or immunometric assay depends on the affinity of the antibody-antigen reaction, the specific activity of the label, the precision with which the reagents are manipulated and the nonspecific background signal (10). The sensitivity of a limited reagent system for the measurement of haptens or proteins is mainly dependent upon the affinity of the antibodies and the smalleest amount of reagent that may be manipulated. Consequently, it is difficult in practice to improve on the sensitivity obtained with iodine-125 as the label. Conversely, with excess reagent systems for the measurement of proteins it is theoretically possible to increase assay sensitivity at least 1000 fold with alternative luminescent labels. To date, a 10-fold improvement has been achieved, and attempts are being made to reduce the influence of other variables on the specific signal from the immunoreaction.

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Establishment of Dyeing Data for Silk Fabrics and Cells Using Diospyros kaki Thunb (감나무 열매를 이용한 실크 및 세포에 대한 염색 데이터 확립)

  • Suk-Yul Jung
    • Journal of Internet of Things and Convergence
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    • v.9 no.3
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    • pp.27-33
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    • 2023
  • In this study, it was analyzed with the dyeing pattern of Diospyros kaki Thunb (persimmon) and was tried to numerically evaluate how the dyeing pattern in silk fabrics and cells was changed by different mordants. When the dyed silk fabrics were sufficiently dried, the silk fabrics were found to have a pale yellow color. Interestingly, iron II sulfate mordant changed the color change the most, silk fabrics were dyed with a color close to brown or dark purple. For numerical analysis, 19% and 62.5% color changes could be induced by sodium tartrate plus citric acid and copper acetate, respectively. Iron II sulfate induced the greatest difference than that of untreated mordants at 88%. About 5% and 10% of Chinese hamster ovary (CHO) cells were stained by sodium tartrate plus citric acid and copper acetate, respectively. The staining effect induced by iron II sulfate was about 2.4 times higher than the staining effect by sodium tartrate plus citric acid. In previous studies, staining results have been visually confirmed. However, this results not only visually confirmed the dyeing, but also quantified the color change. In particular, if numerical results are continuously integrated into big data, any researcher will be able to easily obtain similar results even if the method, time, volume, etc. are changed. In addition, the numerical data of this study is considered to be an important basis for building a database for IoT construction and computer analysis.

Artesunate inhibits collagen-induced human platelets aggregation through regulation of PI3K/Akt and MAPK pathway (PI3K/Akt 및 MAPK 기전 조절을 통한 Artesunate의 콜라겐 유도의 사람 혈소판 응집 억제효과)

  • Lee, Dong-Ha
    • Journal of Applied Biological Chemistry
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    • v.65 no.1
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    • pp.57-62
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    • 2022
  • Excessive activation and aggregation of platelets is a major cause of cardiovascular disease. Therefore, inhibition of platelet activation and aggregation is considered an attractive therapeutic target in preventing and treating cardiovascular diseases. In particular, strong platelet activation and aggregation by collagen secreted from the vascular endothelium are characteristic of vascular diseases. Artesunate is a compound extracted from the plant roots of Artemisia or Scopolia species, and has been reported to be effective in anticancer and Alzheimer's disease fields. However, the effect and mechanism of artesunate on collagen-induced platelet activation and aggregation have not been elucidated. In this study, the effect of artesunate on collagen-induced human platelet aggregation was confirmed and the mechanism of action of artesunate was clarified. Artesunate inhibited the phosphorylation of PI3K/Akt and Mitogen-activated protein kinases, which are phosphoproteins that are known to act in the signal transduction process when platelets are activated. In addition, artesunate decreased TXA2 production and decreased granule secretion in platelets such as ATP and serotonin release. As a result, artesunate strongly inhibited platelet aggregation induced by collagen, a strong aggregation inducer secreted from vascular endothelial cells, with an IC50 of 106.41 µM. These results suggest that artesunate has value as an effective antithrombotic agent for inhibiting the activation and aggregation of human platelets through vascular injury.

Educational Effects of Interdisciplinary Creativity Promotion Program Based on Movie-Assisted Flipped Learning of creativity and STEAM literacy indexes in College Students (영화를 활용한 플립러닝 기반의 학제 간 융합 창의성 증진 프로그램이 대학생의 창의성과 융합인재소양에 미치는 효과)

  • Kim, Byung-Man;Youn, Jeong-Jin;Kim, Seoung-Won
    • Asia-pacific Journal of Multimedia Services Convergent with Art, Humanities, and Sociology
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    • v.7 no.7
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    • pp.37-47
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    • 2017
  • The purpose of this study is to investigate how flip learning based interdisciplinary fusion creativity promotion program using movie is effective for university students creativity and fusion talent literacy. To do this, we conducted a total of 15 sessions for a total of 89 students from 44 college students and 45 non - attendance college students who attended the "Creative Fusion Creative Encounters with Film" course at Busan Metropolitan City. The collected data were analyzed by independent sample t-test using SPSS 23.0 program. The results of this study are as follows. First, flip learning based interdisciplinary fusion creativity enhancement program using movie was significant in the order of patience / attachment, humor, self - confidence, imagination, openness, independence, and curiosity in the creativity sub - domain of college students. Second, flip learning - based interdisciplinary convergence creativity enhancement programs using movies were found to have a significant effect in the order of convergence, care, communication, and creativity in the sub - areas of university students' literacy achievement. The findings of the study proved the educational effects of the interdisciplinary creativity promotion program that was based on movie-assisted flipped learning, and this study is expected to suggest some of the right directions for education-based interdisciplinary research and to give some suggestions on that.

Recognition of General arts classes based on movie - Focused on the movie "Untouchables: 1% friendship" (영화 기반 교양교과 수업 활동 탐색 - 영화 「언터처블: 1%의 우정」 중심으로)

  • Kim, Seong-Won;Youn, Jeong-Jin
    • Asia-pacific Journal of Multimedia Services Convergent with Art, Humanities, and Sociology
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    • v.7 no.6
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    • pp.63-72
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    • 2017
  • This study made of centrally actual application in general arts classes based on movie in university. Especially, I analyzed the activities of the class with 'Untouchable: 1% friendship' among 6 films. The objects of this study are 44 students of D university in Busan Metropolitan City who take 'creative fusion from movie' general arts class which opened first semester in 2016. In this study, students were able to watch movies through the creative class, which was out of the traditional classroom method, and after 15 hours of learning the quiz online, they conducted 15 weeks as a teaching method to perform tasks, presentations, experiments, and experiences in regular class time. The results of this study are as follows. 'It is a general arts class that makes movements live,' 'It is a general arts class that shows movies from various perspectives,' and 'It is a general arts class that makes me know.' This suggests that the educational medium, which is easily accessible in everyday life, and the general arts class, which is active in the space outside the framework, are perceived as stimulating curiosity and adding fun to college students.

The Optimal Physical Treatment Process for Production of High-grade Iron Concentrate from Waelz Kiln Slag (Waelz Kiln 슬래그로부터 고품위 철 농축산물의 생산을 위한 최적 물리적 처리공정)

  • Yosep Han;Seongmin Kim;Seongsoo Han;Youngjae Kim
    • Resources Recycling
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    • v.32 no.2
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    • pp.3-11
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    • 2023
  • The aim of this study was to develop a physical treatment method for obtaining iron concentrate with a grade higher than 60% from slag generated in the Waelz Kiln (WK) process. The size of the WK slag used in this work was several millimeters, with T-Fe and ZnO contents of 40.24% and 1.03%, respectively. The slag samples were pulverized in a laboratory rod mill for various grinding times, followed by a magnetic separation test under a low magnetic intensity of 0.05 T initially. The results showed that the highest iron grade was obtained from samples with a grinding time of 10 min. Additionally, for a grinding time of 20 min, the highest grade and recovery ratios were achieved at a magnetic intensity of 0.8 T. Based on these findings, the optimal physical treatment process proposed in this study resulted in iron concentrates with a grade of 61.34% and an enrichment ratio of 1.52.