816 results on '"Kyung, Min"'
Search Results
2. Radiosynthesis and characterization of [18F]BS224: a next-generation TSPO PET ligand insensitive to the rs6971 polymorphism
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Hyun Soo Park, Valentino Laquintana, Sanghee Lee, Nunzio Denora, Su Bin Kim, Byung Chul Lee, Pietro Delre, Kyung-Min Kim, Seok Yong Lee, Sang Eun Kim, Antonio Lopalco, Annalisa Cutrignelli, Hye Won Kim, Massimo Franco, Giuseppe Felice Mangiatordi, Angela Lopedota, In Ho Song, and Hyewon Youn
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PK-11195 ,biology ,Radiosynthesis ,General Medicine ,Ligand (biochemistry) ,Molecular biology ,chemistry.chemical_compound ,Non-competitive inhibition ,chemistry ,In vivo ,Docking (molecular) ,Translocator protein ,biology.protein ,Radiology, Nuclear Medicine and imaging ,Binding site - Abstract
Purpose Translocator protein 18-kDa (TSPO) positron emission tomography (PET) is a valuable tool to detect neuroinflammed areas in a broad spectrum of neurodegenerative diseases. However, the clinical application of second-generation TSPO ligands as biomarkers is limited because of the presence of human rs6971 polymorphism that affects their binding. Here, we describe the ability of a new TSPO ligand, [18F]BS224, to identify abnormal TSPO expression in neuroinflammation independent of the rs6971 polymorphism. Methods An in vitro competitive inhibition assay of BS224 was conducted with [3H]PK 11195 using membrane proteins isolated from 293FT cells expressing TSPO-wild type (WT) or TSPO-mutant A147T (Mut), corresponding to a high-affinity binder (HAB) and low-affinity binder (LAB), respectively. Molecular docking was performed to investigate the interaction of BS224 with the binding sites of rat TSPO-WT and TSPO-Mut. We synthesized a new 18F-labeled imidazopyridine acetamide ([18F]BS224) using boronic acid pinacol ester 6 or iodotoluene tosylate precursor 7, respectively, via aromatic 18F-fluorination. Dynamic PET scanning was performed up to 90 min after the injection of [18F]BS224 to healthy mice, and PET imaging data were obtained to estimate its absorbed doses in organs. To evaluate in vivo TSPO-specific uptake of [18F]BS224, lipopolysaccharide (LPS)-induced inflammatory and ischemic stroke rat models were used. Results BS224 exhibited a high affinity (Ki = 0.51 nM) and selectivity for TSPO. The ratio of IC50 values of BS224 for LAB to that for HAB indicated that the TSPO binding affinity of BS224 has low binding sensitivity to the rs6971 polymorphism and it was comparable to that of PK 11195, which is not sensitive to the polymorphism. Docking simulations showed that the binding mode of BS224 is not affected by the A147T mutation and consequently supported the observed in vitro selectivity of [18F]BS224 regardless of polymorphisms. With optimal radiochemical yield (39 ± 6.8%, decay-corrected) and purity (> 99%), [18F]BS224 provided a clear visible image of the inflammatory lesion with a high signal-to-background ratio in both animal models (BPND = 1.43 ± 0.17 and 1.57 ± 0.37 in the LPS-induced inflammatory and ischemic stroke rat models, respectively) without skull uptake. Conclusion Our results suggest that [18F]BS224 may be a promising TSPO ligand to gauge neuroinflammatory disease-related areas in a broad range of patients irrespective of the common rs6971 polymorphism.
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- 2021
3. Uptake of KRAS Testing and Anti-EGFR Antibody Use for Colorectal Cancer in the VA
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Julie Lynch, Kristine E. Lynch, Christy Morrissey, Danil V. Makarov, Daniel J. Becker, Michael J. Kelley, Scott E. Sherman, Steve Y. Lee, and Kyung Min Lee
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Adult ,Male ,0301 basic medicine ,Cancer Research ,medicine.drug_class ,Colorectal cancer ,medicine.disease_cause ,Monoclonal antibody ,Cohort Studies ,Proto-Oncogene Proteins p21(ras) ,03 medical and health sciences ,0302 clinical medicine ,Anti-EGFR Antibody ,medicine ,Humans ,Genetic Testing ,Epidermal growth factor receptor ,neoplasms ,Aged ,Retrospective Studies ,Aged, 80 and over ,biology ,business.industry ,Antibodies, Monoclonal ,ORIGINAL REPORTS ,Middle Aged ,medicine.disease ,digestive system diseases ,ErbB Receptors ,030104 developmental biology ,Oncology ,Precision oncology ,030220 oncology & carcinogenesis ,Veterans Health Services ,Cancer research ,biology.protein ,Female ,KRAS ,Colorectal Neoplasms ,business - Abstract
PURPOSEAdvances in precision oncology, including RAS testing to predict response to epidermal growth factor receptor monoclonal antibodies (EGFR mAbs) in colorectal cancer (CRC), can extend patients’ lives. We evaluated uptake and clinical use of KRAS molecular testing, guideline recommended since 2010, in the Veterans Affairs Healthcare System (VA).MATERIALS AND METHODSWe conducted a retrospective cohort study of patients with stage IV CRC diagnosed in the VA 2006-2015. We gathered clinical, demographic, molecular, and treatment data from the VA Corporate Data Warehouse and 29 commercial laboratories. We performed multivariable analyses of associations between patient characteristics, KRAS testing, and EGFR mAb treatment.RESULTSAmong 5,943 patients diagnosed with stage IV CRC, only 1,053 (17.7%) had KRAS testing. Testing rates increased from 2.3% in 2006 to 28.4% in 2013. In multivariable regression, older patients (odds ratio, 0.17; 95% CI, 0.09 to 0.32 for ≥ age 85 v < 45 years) and those treated in the Northeast and South regions were less likely, and those treated at high-volume CRC centers were more likely to have KRAS testing (odds ratio, 2.32; 95% CI, 1.48 to 3.63). Rates of potentially guideline discordant care were high: 64.3% (321/499) of KRAS wild-type (WT) went untreated with EGFR mAb and 8.8% (401/4,570) with no KRAS testing received EGFR mAb. Among KRAS-WT patients, survival was better for patients who received EGFR mAb treatment (29.6 v 18.8 months; P < .001).CONCLUSIONWe found underuse of KRAS testing in advanced CRC, especially among older patients and those treated at lower-volume CRC centers. We found high rates of potentially guideline discordant underuse of EGFR mAb in patients with KRAS-WT tumors. Efforts to understand barriers to precision oncology are needed to maximize patient benefit.
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- 2021
4. Relaxing Effect of Novel Cosmetic Ingredient using Lactobacillus gasseri HDB1102 on Skin Problems Caused by Particulate Matter
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Seo-Jin Yang, Kyung-Min Kim, Ji-Won Song, and Seung-Hun Lee
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Cosmetic ingredient ,biology ,Chemistry ,Food science ,Particulates ,Lactobacillus gasseri ,biology.organism_classification - Abstract
In this study, we developed Dermabiotics HDB1102 using Lactobacillus gasseri HDB1102 to relieve skin irritation caused by particulate matter (PM). L. gasseri HDB1102 was provided from cell bank and identified by 16S ribosomal RNA gene sequencing. Dermabiotics HDB1102 was manufactured by heating, centrifuging, and filtering culture medium of L. gasseri HDB1102. When 0-2.5%(v/v) Dermabiotics HDB1102 was treated, cytotoxicity on normal human epidermal keratinocytes (NHEKs) and human fibroblast was not observed by using MTT assay. The mRNA expression levels of cytochrome P450 1A1 (CYP1A1), interleukin (IL)-1β, and IL-8 on Dermabiotics HDB1102 treated cells decreased compared to PM-treated cells. Conversely, the mRNA expressions of aquaporin-3 (AQP-3), CD-44, and collagen type 1 (COL-1) on Dermabiotics HDB1102 treated cells were dose-dependent higher than those of non-treated cells. These results indicated that Dermabiotics HDB1102 have anti-inflammatory, moisturizing, and anti-wrinkle effects and could be used as a potential cosmetic ingredient to alleviate skin symptoms caused by PM.
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- 2021
5. Cyclosporin A Enhances Cardiac Differentiation by Inhibiting Wnt/β-Catenin Signaling in Human Embryonic Stem Cells
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Mu Seog Choe, Han Cheol Yeo, Joong Sun Kim, Jae Boum Youm, Seung Hak Choi, Ho Jae Han, Kyung Min Baek, Kyung Seob Lim, Woochul Chang, Seung Tack Oh, So Jin Kim, Won-Young Choi, and Min Young Lee
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Cardiac differentiation ,Biomedical Engineering ,Wnt signaling pathway ,Wnt β catenin signaling ,Bioengineering ,Biology ,Applied Microbiology and Biotechnology ,Embryonic stem cell ,Cell biology ,Cyclosporin a ,embryonic structures ,Inducer ,Induced pluripotent stem cell ,Mesodermal Differentiation ,Biotechnology - Abstract
Efficient cardiac differentiation of human pluripotent stem cells (hPSCs) is essential for their use in the field of basic research as well as in cell-based therapy. Regulation of the Wnt/β-catenin pathway is a key step in the process of cardiac differentiation of hPSCs. In this study, we reported cyclosporin A (CsA), a strong immunosuppressor, as an inducer of cardiac differentiation in human embryonic stem cells (hESCs). Our results showed that CsA promoted cardiac differentiation in the mesodermal differentiation stage of hESCs and that this effect was mediated by the inhibition of Wnt/β-catenin signaling. Therefore, our results provide novel information about CsA as a Wnt/β-catenin inhibitor as well as a strategy for the cardiac differentiation of hESCs.
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- 2021
6. Molecular Characterization of Carbapenem-resistant, Colistin-resistant Klebsiella pneumoniae Isolates from a Tertiary Hospital in Jeonbuk, Korea
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Jaehyeon Lee, Tae Hee Lee, Chang-Seop Lee, Hwang Jm, Minhyeon Cho, and Kyung Min Chung
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biology ,Carbapenem resistant ,business.industry ,Klebsiella pneumoniae ,Virology ,Immunology ,Colistin ,Medicine ,business ,biology.organism_classification ,Microbiology ,medicine.drug - Published
- 2021
7. The role of NUMB/NUMB isoforms in cancer stem cells
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Jaekwon Seok, Ssang-Goo Cho, Hye Yeon Choi, Kyung Min Lim, and Geun-Ho Kang
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animal structures ,Cell division ,Carcinogenesis ,Notch signaling pathway ,Nerve Tissue Proteins ,Biology ,medicine.disease_cause ,Biochemistry ,NUMB ,Cancer stem cell ,NUMB isoforms ,Cell Line, Tumor ,Asymmetric cell division ,medicine ,Humans ,Protein Isoforms ,Cell Lineage ,Molecular Biology ,Cell Proliferation ,Receptors, Notch ,Cell growth ,Asymmetric Cell Division ,fungi ,Membrane Proteins ,General Medicine ,Invited Mini Review ,Cell biology ,Alternative Splicing ,NOTCH signaling pathway ,embryonic structures ,Cancer stem cell (CSC) ,Neoplastic Stem Cells ,Tumor Suppressor Protein p53 ,Stem cell ,Cell Division ,hormones, hormone substitutes, and hormone antagonists - Abstract
Cancer stem cells (CSCs) are a subpopulation of cancer that can self-renew and differentiate into large tumor masses. Evidence accumulated to date shows that CSCs affect tumor proliferation, recurrence, and resistance to chemotherapy. Recent studies have shown that, like stem cells, CSCs maintain cells with self-renewal capacity by means of asymmetric division and promote cell proliferation by means of symmetric division. This cell division is regulated by fate determinants, such as the NUMB protein, which recently has also been confirmed as a tumor suppressor. Loss of NUMB expression leads to uncontrolled proliferation and amplification of the CSC pool, which promotes the Notch signaling pathway and reduces the expression of the p53 protein. NUMB genes are alternatively spliced to produce six functionally distinct isoforms. An interesting recent discovery is that the protein NUMB isoform produced by alternative splicing of NUMB plays an important role in promoting carcinogenesis. In this review, we summarize the known functions of NUMB and NUMB isoforms related to the proliferation and generation of CSCs. [BMB Reports 2021; 54(7): 335-343].
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- 2021
8. Quantitative Proteomics Reveals Knockdown of CD44 Promotes Proliferation and Migration in Claudin-Low MDA-MB-231 and Hs 578T Breast Cancer Cell Lines
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Hyeyoon Kim, Min Sun Jin, In Ae Park, Han Suk Ryu, Jongmin Woo, Kyung Min Lee, Dohyun Han, and Kisoon Dan
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Proteomics ,0301 basic medicine ,Cell ,Breast Neoplasms ,Biochemistry ,03 medical and health sciences ,Cell Movement ,Cancer stem cell ,Cell Line, Tumor ,medicine ,Humans ,Cell Proliferation ,030102 biochemistry & molecular biology ,biology ,Cell growth ,CD44 ,General Chemistry ,Cell cycle ,Claudin-Low ,Cell biology ,Gene Expression Regulation, Neoplastic ,Hyaluronan Receptors ,030104 developmental biology ,medicine.anatomical_structure ,Claudins ,Proteome ,MCF-7 Cells ,biology.protein ,Female - Abstract
CD44 is a transmembrane glycoprotein that can regulate the oncogenic process. This is known to be a marker of the claudin-low subtype of breast cancer, as well as a cancer stem cell marker. However, its functional regulatory roles are poorly understood in claudin-low breast cancer. To gain comprehensive insight into the function of CD44, we performed an in-depth tandem mass tag-based proteomic analysis of two claudin-low breast cancer cell lines (MDA-MB-231 and Hs 578T) transfected with CD44 siRNA. As a result, we observed that 2736 proteins were upregulated and 2172 proteins were downregulated in CD44-knockdown MDA-MB-231 cells. For Hs 578T CD44-knockdown cells, 412 proteins were upregulated and 443 were downregulated. Gene ontology and network analyses demonstrated that the suppression of this marker mediates significant functional alterations related to oncogenic cellular processes, including proliferation, metabolism, adhesion, and gene expression regulation. A functional study confirmed that CD44 knockdown inhibited proliferation by regulating the expression of genes related to cell cycle, translation, and transcription. Moreover, this promoted the expression of multiple cell adhesion-associated proteins and attenuated cancer cell migration. Finally, our proteomic study defines the landscape of the CD44-regulated proteome of claudin-low breast cancer cells, revealing changes that mediate cell proliferation and migration. Our proteomics data set has been deposited to the ProteomeXchange Consortium via the PRIDE repository with the data set identifier PXD015171.
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- 2021
9. Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes
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Stephen R. Atkinson, Philip S. Tsao, Evangelos Evangelou, VA Million Veteran Program, Karl-Heinz Herzig, David E. Kaplan, Marina Serper, Behrooz Z. Alizadeh, Benjamin F. Voight, Xiyun Jiang, Julie A. Lynch, Dipender Gill, Danish Saleheen, Marjo-Riitta Järvelin, André G. Uitterlinden, Rui Pinto, Raha Pazoki, Peter J. van der Most, Paul Elliott, Verena Zuber, Matthias Farlik, Ioanna Tzoulaki, Mark Thursz, Harold Snieder, Marijana Vujkovic, Christopher J. O'Donnell, Mohsen Ghanbari, Kyung Min Lee, Saredo Said, Matthias Wielscher, Kyong-Mi Chang, M. Arfan Ikram, Joshua Elliott, Rotonya M. Carr, Robert J. de Knegt, Abbas Dehghan, Life Course Epidemiology (LCE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Medical Research Council (MRC), Epidemiology, Gastroenterology & Hepatology, and Internal Medicine
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Enzymologic ,Male ,0301 basic medicine ,LD SCORE REGRESSION ,General Physics and Astronomy ,Physiology ,Genome-wide association study ,Cardiovascular ,Oral and gastrointestinal ,DISEASE ,Cohort Studies ,Rotterdam Study ,0302 clinical medicine ,Risk Factors ,Databases, Genetic ,2.1 Biological and endogenous factors ,Aetiology ,POPULATION ,RISK ,education.field_of_study ,Multidisciplinary ,biology ,medicine.diagnostic_test ,HERITABILITY ,Liver Disease ,Alanine Transaminase ,gamma-Glutamyltransferase ,Single Nucleotide ,Middle Aged ,Heart Disease ,Liver ,Cardiovascular Diseases ,VA Million Veteran Program ,MENDELIAN RANDOMIZATION ,Female ,030211 gastroenterology & hepatology ,HEALTH ,Science ,Population ,Single-nucleotide polymorphism ,BIOBANK ,Polymorphism, Single Nucleotide ,Gene Expression Regulation, Enzymologic ,White People ,General Biochemistry, Genetics and Molecular Biology ,Databases ,03 medical and health sciences ,Insulin resistance ,Metabolic Diseases ,Genetic ,Lifelines Cohort Study ,SDG 3 - Good Health and Well-being ,Mendelian randomization ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Genetic Testing ,Polymorphism ,GENOME-WIDE ASSOCIATION ,education ,Metabolic and endocrine ,METAANALYSIS ,Aged ,Genetic testing ,business.industry ,General Chemistry ,Mendelian Randomization Analysis ,Alkaline Phosphatase ,Lipid Metabolism ,medicine.disease ,Good Health and Well Being ,030104 developmental biology ,Gene Expression Regulation ,Alanine transaminase ,biology.protein ,Insulin Resistance ,Digestive Diseases ,business ,Genome-Wide Association Study - Abstract
Plasma levels of liver enzymes provide insights into hepatic function and related diseases. Here, the authors perform a genome-wide association study on three liver enzymes, identifying genetic variants associated with their plasma concentration as well as links to metabolic and cardiovascular diseases.Serum concentration of hepatic enzymes are linked to liver dysfunction, metabolic and cardiovascular diseases. We perform genetic analysis on serum levels of alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) using data on 437,438 UK Biobank participants. Replication in 315,572 individuals from European descent from the Million Veteran Program, Rotterdam Study and Lifeline study confirms 517 liver enzyme SNPs. Genetic risk score analysis using the identified SNPs is strongly associated with serum activity of liver enzymes in two independent European descent studies (The Airwave Health Monitoring study and the Northern Finland Birth Cohort 1966). Gene-set enrichment analysis using the identified SNPs highlights involvement in liver development and function, lipid metabolism, insulin resistance, and vascular formation. Mendelian randomization analysis shows association of liver enzyme variants with coronary heart disease and ischemic stroke. Genetic risk score for elevated serum activity of liver enzymes is associated with higher fat percentage of body, trunk, and liver and body mass index. Our study highlights the role of molecular pathways regulated by the liver in metabolic disorders and cardiovascular disease.
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- 2021
10. Role of Alicyclic Conformation-Isomerization in the Photomechanical Performance of Azobenzene-Functionalized Cross-Linked Polyimides Containing Tetra-Substituted Cyclohexane Moieties
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Kyung Min Lee, David H. Wang, Deborah H. Lee, Matthew L. Baczkowski, Loon-Seng Tan, Michael E. McConney, and Hajin Park
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chemistry.chemical_classification ,Polymers and Plastics ,biology ,Cyclohexane ,Chemistry ,Organic Chemistry ,02 engineering and technology ,010402 general chemistry ,021001 nanoscience & nanotechnology ,biology.organism_classification ,01 natural sciences ,0104 chemical sciences ,Inorganic Chemistry ,Alicyclic compound ,chemistry.chemical_compound ,Azobenzene ,Polymer chemistry ,Materials Chemistry ,Tetra ,0210 nano-technology ,Isomerization - Abstract
The classical "chair-twist boat-boat" conformational dynamics (CD) of cyclohexane is thermally activated. Here we report on the photoinduced/azobenzene-assisted CD of bilaterally fused cyclohexane moieties contributing to large photomechanical response of cross-linked azobenzene-functionalized polyimides (X-azoPI), based on 1,2,4,5-cyclohexane-tetracarboxylic-dianhydride (CHDA), exhibiting a photobending angle and photogenerated stress, up to ∼90° and 370 kPa, respectively. In contrast, X-azoPI containing planar pyromellitimide (PMDI) or cage-like bicyclo[2.2.2]oct-7-ene-2,3,5,6-tetracarboxylic-diimide (BCDI) show smaller photomechanical responses. The superior photomechanical performance of X-azoPI with constrained cyclohexane-diimide (CHDI) units is attributed to an increased mobility of segments comprising "hinged" p-phenylene rings, azobenzene, and CHDI units in the cross-link sites. Blue light irradiation initiates the motions driven by photoisomerization/reorientation of azobenzenes connected to CHDI units, whose CD is then amplified, leading to longer-range segmental mobility, more local free volume, and culminating in large photoinduced bending. The trapping of redistributed CHDI's stereoisomers in X-azoPI backbone at
- Published
- 2022
11. Multi-omic profiling of histone variant H3.3 lysine 27 methylation reveals a distinct role from canonical H3 in stem cell differentiation
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Matteo Trovato, Simone Sidoli, Benjamin A. Garcia, Yekaterina Kori, Zuo-Fei Yuan, Kyung-Min Noh, and Peder J. Lund
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biology ,Cellular differentiation ,Lysine ,Promoter ,Cell Differentiation ,Methylation ,Biochemistry ,Article ,Cell biology ,Chromatin ,Histones ,Mice ,Histone ,Gene expression ,Genetics ,biology.protein ,Nucleosome ,Animals ,Molecular Biology ,Transcription factor ,Protein Processing, Post-Translational ,Transcription Factors - Abstract
Histone variants, such as histone H3.3, replace canonical histones within the nucleosome to alter chromatin accessibility and gene expression. Although the biological roles of selected histone post-translational modifications (PTMs) have been extensively characterized, the potential differences in the function of a given PTM on different histone variants is almost always elusive. By applying proteomics and genomics techniques, we investigate the role of lysine 27 tri-methylation specifically on the histone variant H3.3 (H3.3K27me3) in the context of mouse embryonic stem cell pluripotency and differentiation as a model system for development. We demonstrate that while the steady state overall levels of methylation on both H3K27 and H3.3K27 decrease during differentiation, methylation dynamics studies indicate that methylation on H3.3K27 is maintained more than on H3K27. Using a custom-made antibody, we identify a unique enrichment of H3.3K27me3 at lineage-specific genes, such as olfactory receptor genes, and at binding motifs for the transcription factors FOXJ2/3. REST, a predicted FOXJ2/3 target that acts as a transcriptional repressor of terminal neuronal genes, was identified with H3.3K27me3 at its promoter region. H3.3K27A mutant cells confirmed an upregulation of FOXJ2/3 targets upon the loss of methylation at H3.3K27. Thus, while canonical H3K27me3 has been characterized to regulate the expression of transcription factors that play a general role in differentiation, our work suggests H3.3K27me3 is essential for regulating distinct terminal differentiation genes. This work highlights the importance of understanding the effects of PTMs not only on canonical histones but also on specific histone variants, as they may exhibit distinct roles.
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- 2022
12. In vivo enrichment of busulfan-resistant germ cells for efficient production of transgenic avian models
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Jae Yong Han, Kyung Je Park, Young-Min Kim, Kyung Min Jung, and Jin Se Park
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Alkylating Agents ,Heterozygote ,Transgene ,Science ,Drug Resistance ,Biology ,Germline ,Article ,Animals, Genetically Modified ,Chimera (genetics) ,In vivo ,Microsomes ,medicine ,Animals ,Busulfan ,Glutathione Transferase ,Animal biotechnology ,Multidisciplinary ,Embryo ,Embryonic stem cell ,Cell biology ,medicine.anatomical_structure ,Germ Cells ,Genetic engineering ,Models, Animal ,Medicine ,Stem cell ,Chickens ,Germ cell ,Biotechnology ,Cloning - Abstract
Most transgenic animals are generated using a genome-modified stem cell system and genome modification directly in embryos. Although this system is well-established in the development of transgenic animals, donor cell-derived transgenic animal production is inefficient in some cases. Especially in avian models such as chickens, the efficiency of transgenic animal production through primordial germ cells (PGCs) is highly variable compared with embryonic manipulation of mammalian species. Because germ cell and germline-competent stem cell-mediated systems that contain the transgene are enriched only at the upstream level during cell cultivation, the efficiency of transgenic animal production is unreliable. Therefore, we developed an in vivo selection model to enhance the efficiency of transgenic chicken production using microsomal glutathione-S-transferase II (MGSTII)-overexpressing PGCs that are resistant to the alkylating agent busulfan, which induces germ cell-specific cytotoxicity. Under in vitro conditions, MGSTII-tg PGCs were resistant to 1 μM busulfan, which was highly toxic to wild-type PGCs. In germline chimeric roosters, transgene-expressing germ cells were dominantly colonized in the recipient testes after busulfan exposure compared with non-treated germline chimera. In validation of germline transmission, donor PGC-derived progeny production efficiency was 94.68%, and the transgene production rate of heterozygous transgenic chickens was significantly increased in chickens that received 40 mg/kg busulfan (80.33–95.23%) compared with that of non-treated germline chimeras (51.18%). This system is expected to significantly improve the efficiency of generating transgenic chickens and other animal species by increasing the distribution of donor cells in adult testes.
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- 2021
13. Halotolerant bacteria mitigate the effects of salinity stress on soybean growth by regulating secondary metabolites and molecular responses
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Muhammad Aaqil Khan, Sajjad Asaf, Kyung-Min Kim, Sang-Mo Kang, Atlaw Anbelu Sahile, Arjun Adhikari, Muhammad Hamayun, Rahmatullah Jan, Muhammad Imran, and In-Jung Lee
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0106 biological sciences ,0301 basic medicine ,Siderophore ,Plant Science ,Biology ,Rhizobacteria ,Bacterial Physiological Phenomena ,01 natural sciences ,Polyphenol oxidase ,Salt Stress ,Antioxidants ,03 medical and health sciences ,Salinity stress ,Dry weight ,Plant Growth Regulators ,Gene Expression Regulation, Plant ,Carotenoid ,chemistry.chemical_classification ,Bacteria ,Indoleacetic Acids ,Inoculation ,Sodium ,Botany ,food and beverages ,Salt Tolerance ,Halotolerant PGPR ,Salinity ,Phytohormones ,Horticulture ,030104 developmental biology ,chemistry ,QK1-989 ,Shoot ,Rhizosphere ,Potassium ,Soybeans ,Gene expression ,Soybean ,010606 plant biology & botany ,Research Article - Abstract
Background Salinity is a major threat to the agriculture industry due to the negative impact of salinity stress on crop productivity. In the present study, we isolated rhizobacteria and evaluated their capacities to promote crop growth under salt stress conditions. Results We isolated rhizospheric bacteria from sand dune flora of Pohang beach, Korea, and screened them for plant growth-promoting (PGP) traits. Among 55 bacterial isolates, 14 produced indole-3-acetic acid (IAA), 10 produced siderophores, and 12 produced extracellular polymeric and phosphate solubilization. Based on these PGP traits, we selected 11 isolates to assess for salinity tolerance. Among them, ALT29 and ALT43 showed the highest tolerance to salinity stress. Next, we tested the culture filtrate of isolates ALT29 and ALT43 for IAA and organic acids to confirm the presence of these PGP products. To investigate the effects of ALT29 and ALT43 on salt tolerance in soybean, we grew seedlings in 0 mM, 80 mM, 160 mM, and 240 mM NaCl treatments, inoculating half with the bacterial isolates. Inoculation with ALT29 and ALT43 significantly increased shoot length (13%), root length (21%), shoot fresh and dry weight (44 and 35%), root fresh and dry weight (9%), chlorophyll content (16–24%), Chl a (8–43%), Chl b (13–46%), and carotenoid (14–39%) content of soybean grown under salt stress. Inoculation with ALT29 and ALT43 also significantly decreased endogenous ABA levels (0.77-fold) and increased endogenous SA contents (6–16%), increased total protein (10–20%) and glutathione contents, and reduced lipid peroxidation (0.8–5-fold), superoxide anion (21–68%), peroxidase (12.14–17.97%), and polyphenol oxidase (11.76–27.06%) contents in soybean under salinity stress. In addition, soybean treated with ALT29 and ALT43 exhibited higher K+ uptake (9.34–67.03%) and reduced Na+ content (2–4.5-fold). Genes involved in salt tolerance, GmFLD19 and GmNARK, were upregulated under NaCl stress; however, significant decreases in GmFLD19 (3–12-fold) and GmNARK (1.8–3.7-fold) expression were observed in bacterial inoculated plants. Conclusion In conclusion, bacterial isolates ALT29 and ALT43 can mitigate salinity stress and increase plant growth, providing an eco-friendly approach for addressing saline conditions in agricultural production systems.
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- 2021
14. STK3/STK4 signalling in adipocytes regulates mitophagy and energy expenditure
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Juhyeong Han, Young Suk Jung, Ji Hyun Park, Abhirup Saha, James G. Granneman, Minsu Kim, Jeanho Yun, Sangkyu Lee, Cheoljun Choi, Kyung-Min Kim, Yeonho Son, Eun Ju Bae, Yoon Keun Cho, Yun Hee Lee, Doeun Kim, Hyeonyeong Im, Mi-Ock Lee, and Je Kyung Seong
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Adipose Tissue, White ,Endocrinology, Diabetes and Metabolism ,Adipose tissue ,Protein Serine-Threonine Kinases ,Mitochondrion ,Biology ,Serine-Threonine Kinase 3 ,Cell Line ,Mice ,chemistry.chemical_compound ,Adipose Tissue, Brown ,Physiology (medical) ,Adipocyte ,Mitophagy ,Brown adipose tissue ,Adipocytes ,Internal Medicine ,medicine ,Animals ,Humans ,Obesity ,Mice, Knockout ,Hippo signaling pathway ,Kinase ,Intracellular Signaling Peptides and Proteins ,Cell Biology ,Thermogenin ,Cell biology ,medicine.anatomical_structure ,chemistry ,Energy Metabolism ,Signal Transduction - Abstract
Obesity reduces adipocyte mitochondrial function, and expanding adipocyte oxidative capacity is an emerging strategy to improve systemic metabolism. Here, we report that serine/threonine-protein kinase 3 (STK3) and STK4 are key physiological suppressors of mitochondrial capacity in brown, beige and white adipose tissues. Levels of STK3 and STK4, kinases in the Hippo signalling pathway, are greater in white than brown adipose tissues, and levels in brown adipose tissue are suppressed by cold exposure and greatly elevated by surgical denervation. Genetic inactivation of Stk3 and Stk4 increases mitochondrial mass and function, stabilizes uncoupling protein 1 in beige adipose tissue and confers resistance to metabolic dysfunction induced by high-fat diet feeding. Mechanistically, STK3 and STK4 increase adipocyte mitophagy in part by regulating the phosphorylation and dimerization status of the mitophagy receptor BNIP3. STK3 and STK4 expression levels are elevated in human obesity, and pharmacological inhibition improves metabolic profiles in a mouse model of obesity, suggesting STK3 and STK4 as potential targets for treating obesity-related diseases. Cho et al. show regulation of mitophagy, and thereby energy expenditure, in adipocytes by the Hippo pathway kinases STK3 and STK4, independently of classical Hippo signalling. Genetic inactivation of Stk3 and Stk4 is shown to protect mice from the adverse metabolic effects of diet-induced obesity.
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- 2021
15. Construction of risk assessment manual for genetically modified rice (Oryza sativa L.)
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So Young Lee, Eun-Gyeong Kim, Jae-Ryoung Park, Yoon-Hee Jang, Rahmatullah Jan, Taehun Ryu, and Kyung-Min Kim
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0106 biological sciences ,Oryza sativa ,business.industry ,fungi ,food and beverages ,04 agricultural and veterinary sciences ,Plant Science ,Genetically modified crops ,Biology ,01 natural sciences ,Genetically modified rice ,Genetically modified organism ,Biotechnology ,Environmental risk ,Germination ,Agriculture ,040103 agronomy & agriculture ,0401 agriculture, forestry, and fisheries ,Risk assessment ,business ,Agronomy and Crop Science ,010606 plant biology & botany - Abstract
Worldwide, grain consumption is increased and grain prices are rising. This has led to a steady increase in the production of highly productive and more affordable genetically modified (GM) crops. However, GM crops are highly concerned about potential environmental risks due to the introduction of external genes and genetic modification. Therefore, it is essential to evaluate the environmental risk of genetically modified organisms that can prove the safety of these GM crops. In this research, we analyzed the potential for weediness, unintended gene transfer, and viability in the natural environment for risk assessment of GM rice. To analyze the potential for weediness of GM rice, viviparous germination, shattering, and germination rate were measured. To analyze the potential release of the introduced gene into the environment by unintended gene transfer, the expression of the introduced gene through protein immune response and PCR was analyzed. The seed germination rate of GM rice was measured from low temperature and frozen soil to analyze their survival ability in the natural environment. There was no significant difference between GM rice and parent in all test items. Therefore, the weediness of GM rice did not occur. The items of the GMO risk assessment constructed in this research can be used as important basic material not only for rice but also for GM crops of various varieties.
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- 2021
16. Regulatory roles of G-protein coupled receptors in adipose tissue metabolism and their therapeutic potential
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Kyung-Min Kim, Ji Hyun Park, Yun Hee Lee, Hyeonyeong Im, Seowoo Im, and Juhyeong Han
- Subjects
0301 basic medicine ,Sphingosine 1 Phosphate Receptor Modulators ,Adrenergic receptor ,Pyridines ,Druggability ,Adipose tissue ,Adrenoceptor ,Review ,Biology ,Energy homeostasis ,Receptors, G-Protein-Coupled ,03 medical and health sciences ,Phosphoserine ,0302 clinical medicine ,GPCR ,Adipose Tissue, Brown ,Metabolic Diseases ,Drug Discovery ,Brown adipose tissue ,medicine ,Animals ,Humans ,Obesity ,Receptor ,G protein-coupled receptor ,Organic Chemistry ,Adenosine receptor ,Thermogenesis ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Lysophospholipid receptor ,Frizzled receptor ,Molecular Medicine ,Pyrazoles ,Energy Metabolism ,030217 neurology & neurosurgery - Abstract
The high incidence of obesity has increased the need to discover new therapeutic targets to combat obesity and obesity-related metabolic diseases. Obesity is defined as an abnormal accumulation of adipose tissue, which is one of the major metabolic organs that regulate energy homeostasis. However, there are currently no approved anti-obesity therapeutics that directly target adipose tissue metabolism. With recent advances in the understanding of adipose tissue biology, molecular mechanisms involved in brown adipose tissue expansion and metabolic activation have been investigated as potential therapeutic targets to increase energy expenditure. This review focuses on G-protein coupled receptors (GPCRs) as they are the most successful class of druggable targets in human diseases and have an important role in regulating adipose tissue metabolism. We summarize recent findings on the major GPCR classes that regulate thermogenesis and mitochondrial metabolism in adipose tissue. Improved understanding of GPCR signaling pathways that regulate these processes could facilitate the development of novel pharmacological approaches to treat obesity and related metabolic disorders.
- Published
- 2021
17. Absolute quantification of tumor-infiltrating immune cells in high-grade glioma identifies prognostic and radiomics values
- Author
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Eui-Cheol Shin, Ho Kang, Kyu Sung Choi, Tae Min Kim, A. Reum Kim, Jin Wook Kim, Seung Hong Choi, Sojin Kim, Joo Ho Lee, Chae Eun Lee, Hyeon Jong Yu, Sung Hye Park, Yong Hwy Kim, Tamrin Chowdhury, Min Sung Kim, Kyung Min Kim, Soon-Tae Lee, Jae Kyung Won, and Chul-Kee Park
- Subjects
Cancer Research ,medicine.diagnostic_test ,Tumor-infiltrating lymphocytes ,Absolute quantification ,Immunology ,Tumor-associated macrophage ,biochemical phenomena, metabolism, and nutrition ,Biology ,Phenotype ,Flow cytometry ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Isocitrate dehydrogenase ,Oncology ,medicine ,Cancer research ,Immunology and Allergy ,Effective diffusion coefficient ,030215 immunology - Abstract
To understand the tumor immune microenvironment precisely, it is important to secure the quantified data of tumor-infiltrating immune cells, since the immune cells are true working unit. We analyzed unit immune cell number per unit volume of core tumor tissue of high-grade gliomas (HGG) to correlate their immune microenvironment characteristics with clinical prognosis and radiomic signatures. The number of tumor-infiltrating immune cells from 64 HGG core tissue were analyzed using flow cytometry and standardized. After sorting out patient groups according to diverse immune characteristics, the groups were tested if they have any clinical prognostic relevance and specific radiomic signature relationships. Sparse partial least square with discriminant analysis using multimodal magnetic resonance images was employed for all radiomic classifications. The median number of CD45 + cells per one gram of HGG core tissue counted 865,770 cells which was equivalent to 8.0% of total cells including tumor cells. There was heterogeneity in the distribution of immune cell subpopulations among patients. Overall survival was significantly better in T cell-deficient group than T cell-enriched group (p = 0.019), and T8 dominant group than T4 dominant group (p = 0.023). The number of tumor-associated macrophages (TAM) and M2-TAM was significantly decreased in isocitrate dehydrogenase mutated HGG. Radiomic signature classification showed good performance in predicting immune phenotypes especially with features extracted from apparent diffusion coefficient maps. Absolute quantification of tumor-infiltrating immune cells confirmed the heterogeneity of immune microenvironment in HGG which harbors prognostic impact. This immune microenvironment could be predicted by radiomic signatures non-invasively.
- Published
- 2021
18. Skin barrier dysfunction and filaggrin
- Author
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Yeonjoon Kim and Kyung Min Lim
- Subjects
Keratinocytes ,0301 basic medicine ,Filaggrin Proteins ,Bleomycin ,Permeability ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Intermediate Filament Proteins ,Drug Discovery ,Keratin ,Stratum corneum ,medicine ,Animals ,Humans ,skin and connective tissue diseases ,chemistry.chemical_classification ,Corneocyte ,integumentary system ,biology ,Organic Chemistry ,Skin Diseases, Genetic ,Calpain ,Atopic dermatitis ,medicine.disease ,Water Loss, Insensible ,Amino acid ,Cell biology ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Gene Expression Regulation ,chemistry ,030220 oncology & carcinogenesis ,Proteolysis ,biology.protein ,Molecular Medicine ,Dermatologic Agents ,Epidermis ,Signal Transduction ,Filaggrin - Abstract
Skin barrier dysfunction caused by endogenous or exogenous factors can lead to various disorders such as xerosis cutis, ichthyoses, and atopic dermatitis. Filaggrin is a pivotal structural protein of the stratum corneum (SC) and provides natural moisturizing factors that play a role in skin barrier functions. Filaggrin aggregates keratin filaments, resulting in the formation of a keratin network, which binds cornified envelopes and collapse keratinocytes to flattened corneocytes. This complex network contributes to the physical strength of the skin. Filaggrin is degraded by caspase-14, calpain 1, and bleomycin hydrolases into amino acids and amino acid metabolites such as trans-urocanic acid and pyrrolidone carboxylic acid, which are pivotal natural moisturizing factors in the SC. Accordingly, filaggrin is important for the pathophysiology of skin barrier disorders, and its deficiency or dysfunction leads to a variety of skin disorders. Here, the roles and biology of filaggrin, related skin diseases, and a therapeutic strategy targeting filaggrin are reviewed. In addition, several drug candidates of different mode of actions targeting filaggrin, along with their clinical efficacy, are discussed.
- Published
- 2021
19. Genetic Polymorphisms in Activating Transcription Factor 3 Binding Site and the Prognosis of Early-Stage Non-Small Cell Lung Cancer
- Author
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Mi Jeong Hong, Sook Kyung Do, Chang Ho Kim, Eung Bae Lee, Seung Soo Yoo, Young Woo Do, Yong Hoon Lee, Won Ki Lee, Hye Won Seo, Sun Ha Choi, Seung Ick Cha, Jaehee Lee, Ji Yun Jeong, Shin Yup Lee, Jang Hyuck Lee, Sukki Cho, Jae Yong Park, Hyo Gyoung Kang, Jin Eun Choi, Jieun Park, Kyung Min Shin, and Sanghoon Jheon
- Subjects
Male ,Cancer Research ,Lung Neoplasms ,Genotype ,Activating transcription factor ,Adenocarcinoma of Lung ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases ,Polymorphism (computer science) ,Carcinoma, Non-Small-Cell Lung ,Biomarkers, Tumor ,medicine ,Humans ,Allele ,Promoter Regions, Genetic ,Lung cancer ,Adaptor Proteins, Signal Transducing ,Activating Transcription Factor 3 ,Binding Sites ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,Survival Rate ,Oncology ,Expression quantitative trait loci ,Carcinoma, Squamous Cell ,Cancer research ,Carcinoma, Large Cell ,Adenocarcinoma ,Female ,Follow-Up Studies - Abstract
Background: Activating transcription factor 3 (ATF3) plays a significant role in cancer development and progression. We investigated the association between variants in expression quantitative trait loci (eQTLs) within ATF3 binding regions and the prognosis of non-small cell lung cancer (NSCLC) after surgery. Methods: A total of 772 patients with NSCLC who underwent curative surgery were enrolled. Using a public database (http://galaxyproject.org), we selected 104 single nucleotide polymorphisms (SNPs) in eQTLs in the ATF3 binding regions. The association of those SNPs with disease-free survival (DFS) was evaluated. Results: Among those SNPs, HAX1 rs11265425T>G was associated with significantly worse DFS (aHR = 1.30, 95% CI = 1.00–1.69, p = 0.05), and ME3 rs10400291C>A was associated with significantly better DFS (aHR = 0.66, 95% CI = 0.46–0.95, p = 0.03). Regarding HAX1 rs11265425T>G, the significant association remained only in adenocarcinoma, and the association was significant only in squamous cell carcinoma regarding ME3 rs10400291C>A. ChIP-qPCR assays showed that the two variants reside in active enhancers where H3K27Ac and ATF3 binding occurs. Promoter assays showed that rs11265425 G allele had significantly higher HAX1 promoter activity than T allele. HAX1 RNA expression was significantly higher in tumor than in normal lung, and higher in rs11265425 TG+GG genotypes than in TT genotype. Conversely, ME3 expression was significantly lower in tumor than in normal lung, and higher in rs10400291 AA genotype than in CC+CA genotypes. Conclusions: In conclusion, this study shows that the functional polymorphisms in ATF3 binding sites, HAX1 rs11265425T>G and ME3 rs10400291C>A are associated with the clinical outcomes of patients in surgically resected NSCLC.
- Published
- 2021
20. Acremonidin E produced by Penicillium sp. SNF123, a fungal endophyte of Panax ginseng, has antimelanogenic activities
- Author
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K.O. Kim, Hae In Jeong, Kyung Min Lim, Sang Jip Nam, and Inho Yang
- Subjects
0301 basic medicine ,Melanogenesis ,Tyrosinase ,Melanocyte ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Plant use of endophytic fungi in defense ,03 medical and health sciences ,Ginseng ,0302 clinical medicine ,Penicillium sp. SNF12 ,lcsh:Botany ,medicine ,Cytotoxicity ,chemistry.chemical_classification ,biology ,Chemistry ,Panax ginseng ,food and beverages ,Acremonidin E ,biology.organism_classification ,lcsh:QK1-989 ,030104 developmental biology ,medicine.anatomical_structure ,Enzyme ,Complementary and alternative medicine ,Biochemistry ,Cell culture ,030220 oncology & carcinogenesis ,Penicillium ,Endophytic fungus ,Biotechnology - Abstract
Background Ginseng extracts and ginseng-fermented products are widely used as functional cosmetic ingredients for their whitening and antiwrinkle effects. Recently, increasing attention has been given to bioactive metabolites isolated from endophytic fungi. However, little is known about the bioactive metabolites of the fungi associated with Panax ginseng Meyer. Methods An endophytic fungus, Penicillium sp. SNF123 was isolated from the root of P. ginseng, from which acremonidin E was purified. Acremonidin E was tested on melanin synthesis in the murine melanoma cell line B16F10, in the human melanoma cell line MNT-1, and in a pigmented 3D-human skin model, Melanoderm. Results Acremonidin E reduced melanogenesis in α-melanocyte-stimulating hormone (α-MSH)-stimulated B16F10 cells with minimal cytotoxicity. qRT–PCR analysis demonstrated that acremonidin E downregulated melanogenic genes, including tyrosinase and tyrosinase-related protein 1 (TRP-1), while their enzymatic activities were unaffected. The antimelanogenic effects of acremonidin E were further confirmed in MNT-1 and a pigmented 3D human epidermal skin model, Melanoderm. Immunohistological examination of the Melanoderm further confirmed the regression of both melanin synthesis and melanocyte activation in the treated tissue. Conclusion This study demonstrates that acremonidin E, a bioactive metabolite derived from a fungal endophyte of P. ginseng, can inhibit melanin synthesis by downregulating tyrosinase, illuminating the potential utility of microorganisms associated with P. ginseng for cosmetic ingredients.
- Published
- 2021
21. A simple metastatic brain cancer model using human embryonic stem cell‐derived cerebral organoids
- Author
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Seung Pil Yun, Kyung Seob Lim, Mu Seog Choe, Han Cheol Yeo, Woochul Chang, Chang Min Bae, Ho Jae Han, Kyung-min Baek, In-Sik Shin, Min Young Lee, and Joong Sun Kim
- Subjects
0301 basic medicine ,Human Embryonic Stem Cells ,Antineoplastic Agents ,Cell Communication ,Biology ,Biochemistry ,Cell Line ,03 medical and health sciences ,0302 clinical medicine ,Gefitinib ,Cell Movement ,Cell Line, Tumor ,Cell Adhesion ,Genetics ,medicine ,Organoid ,Humans ,Cell adhesion ,Molecular Biology ,Cell Proliferation ,Neurons ,Brain Neoplasms ,Brain ,Cancer ,medicine.disease ,Embryonic stem cell ,Organoids ,HEK293 Cells ,030104 developmental biology ,A549 Cells ,Cancer cell ,Cancer research ,030217 neurology & neurosurgery ,Biotechnology ,Brain metastasis ,medicine.drug ,Cerebral organoid - Abstract
Every year, hundreds of thousands of people die because of metastatic brain cancer. Most metastatic cancer research uses 2D cell culture or animal models, but they have a few limitations, such as difficulty reproducing human tissue structures. This study developed a simple 3D in vitro model to better replicate brain metastasis using human cancer cells and human embryonic stem cell-derived cerebral organoids (metastatic brain cancer cerebral organoid [MBCCO]). The MBCCO model successfully reproduced metastatic cancer processes, including cell adhesion, proliferation, and migration, in addition to cell-cell interactions. Using the MBCCO model, we demonstrated that lung-specific X protein (LUNX) plays an important role in cell proliferation and migration or invasion. We also observed astrocyte accumulation around and their interaction with cancer cells through connexin 43 in the MBCCO model. We analyzed whether the MBCCO model can be used to screen drugs by measuring the effects of gefitinib, a well-known anticancer agent. We also examined the toxicity of gefitinib using normal cerebral organoids (COs). Therefore, the MBCCO model is a powerful tool for modeling human metastatic brain cancer in vitro and can also be used to screen drugs.
- Published
- 2020
22. Effects of Radiofrequency Electromagnetic Fields and Ionizing Radiation on Amyloid Precursor Protein Processing and Cell Death
- Author
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Sang Bong Jeon, Kyung Min Lim, Yun Sil Lee, Hae June Lee, Sojung Choi, Hyung-Do Choi, Nam Kim, and Kyeonghee Yoon
- Subjects
0301 basic medicine ,Electromagnetic field ,Programmed cell death ,QC501-766 ,Computer Networks and Communications ,amyloid protein precursor processing ,Ionizing radiation ,03 medical and health sciences ,0302 clinical medicine ,Amyloid precursor protein ,Medicine ,Electrical and Electronic Engineering ,Instrumentation ,Radiation ,biology ,business.industry ,TK1-9971 ,Electricity and magnetism ,030104 developmental biology ,cell death ,biology.protein ,Biophysics ,Electrical engineering. Electronics. Nuclear engineering ,business ,ionizing radiation ,rf-emf ,030217 neurology & neurosurgery - Abstract
The growing concerns regarding the adverse biological effects of radiofrequency electromagnetic fields (RF-EMFs), which are generated by common electronic devices, on the human brain led us to investigate their impact on Alzheimer’s disease (AD). We aimed to establish the effects of RF-EMF on the expression of molecular markers associated with amyloid precursor protein (APP), cell death, and clonogenic survival in HT22 and APP-overexpressing 7w-PSML cells. We compared the effects of RF-EMF at a high specific absorption rate (SAR) level with the neuronal-cell-death-inducing effects of ionizing radiation (IR). RF-EMF exposure (8 W/kg SAR) promoted the protein expression of ADAM10 (α-secretase) in the HT22 cells (p < 0.05) and downregulated the APP mRNA level in the 7w-PSML cells (p < 0.01). In contrast, IR (10 Gy) significantly reduced the APP and a disintegrin and metalloproteinase 10 (ADAM10) levels without altering their respective mRNA levels in these cells. Interestingly, IR exposure significantly upregulated BACE1 (α-secretase) at both the protein and mRNA levels, suggesting adverse effects in AD. IR induced cell death and reduced clonogenic survival in both cell lines. Although RF-EMF (high SAR level) influenced APP processing, it did not induce any deleterious change in either cell line. Thus, further studies are necessary to clarify the influence of RF-EMF on AD.
- Published
- 2020
23. Inhibition of MUC1 exerts cell-cycle arrest and telomerase suppression in glioblastoma cells
- Author
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Kyung Min Kim, Chul-Kee Park, Soo Ji Park, Chae Eun Lee, Tamrin Chowdhury, Kyoungmi Kim, Sojin Kim, Ho Kang, Hyeon Jong Yu, Youngbeom Seo, and Hak Jae Kim
- Subjects
Telomerase ,Cell cycle checkpoint ,Molecular biology ,lcsh:Medicine ,digestive system ,Article ,Medical research ,Cell Movement ,Cell Line, Tumor ,Humans ,skin and connective tissue diseases ,lcsh:Science ,neoplasms ,Cancer ,Cell Proliferation ,Gene knockdown ,Multidisciplinary ,biology ,Cell growth ,Brain Neoplasms ,Mucin-1 ,lcsh:R ,Telomere Homeostasis ,Transforming growth factor beta ,Cell Cycle Checkpoints ,Cell cycle ,biological factors ,digestive system diseases ,Telomere ,Survival Rate ,biology.protein ,Cancer research ,lcsh:Q ,CDKN1B ,Glioblastoma ,Signal Transduction - Abstract
Mucin 1 (MUC1) is a transmembrane glycoprotein involved in tumorigenesis of diverse cancers. However, the role of MUC1 in glioblastoma (GBM) has not yet been fully explored. In this study, the anticancer mechanism of MUC1 suppression in GBM was investigated. The expression level of MUC1 was analyzed in human glioma and paired normal brain tissues. MUC1 was overexpressed in GBM and was negatively associated with overall survival. Moreover, we silenced MUC1 to investigate its effect in GBM cell lines and found that knockdown of MUC1 inhibited cell proliferation and resulted in cell cycle arrest at G1 phase. MUC1 silencing decreased the phosphorylation of RB1 and increased the expression of CDKN1B. Gene set enrichment analysis showed that a series of genes related to cell cycle, telomere maintenance and transforming growth factor Beta (TGF-β) signaling in epithelial mesenchymal transition (EMT) were influenced by MUC1 knockdown. Notably, the reduced TERT expression levels combined with impaired telomerase activity and the switching of telomere maintenance mechanism to alternative lengthening of telomeres (ALT) were observed after MUC1 knockdown. Our results support the role of MUC1 in oncological process in GBM which can be developed as a therapeutic target for cell cycle control and telomere maintenance mechanism.
- Published
- 2020
24. Modulation of sugar and nitrogen in callus induction media alter PAL pathway, SA and biomass accumulation in rice callus
- Author
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Muhammad Aaqil Khan, Sajjad Asaf, Kyung-Min Kim, Rahmatullah Jan, and In-Jung Lee
- Subjects
0106 biological sciences ,chemistry.chemical_classification ,Sucrose ,fungi ,Flavonoid ,food and beverages ,Horticulture ,Biology ,musculoskeletal system ,01 natural sciences ,body regions ,chemistry.chemical_compound ,surgical procedures, operative ,Flavonoid biosynthesis ,chemistry ,Callus ,Anthocyanin ,Browning ,Food science ,Sugar ,Salicylic acid ,010606 plant biology & botany - Abstract
In this study, the effect of varying nitrogen and sucrose concentrations in culture media was evaluated with respect to biomass production, accumulation of flavonoids, anthocyanin, and associated gene expression in rice callus. The callus was induced on control MS (M1), sugar-deficient (M2), sugar-excessive (M3), nitrogen-deficient (M4), and nitrogen-excessive (M5) media. The results indicated that the callus induction percentage (CIP) as well as the size and fresh weight of the callus were inhibited by all types of media compared with control media. Varying the sucrose and nitrogen concentration significantly affected callus morphology and caused a browning effect. Genes related to flavonoid biosynthesis (CHS, CHI, F3H, FLS and DFR) were upregulated in the callus cultured in all four media types compared with control media. Likewise, flavonoid and anthocyanin accumulation were higher in callus grown in excessive sugar- and nitrogen-containing media compared with control media. Unlike flavonoids, salicylic acid (SA) regulation was significantly higher in callus grown in sugar- and nitrogen-deficient media compared with control media. Sugar content was significantly higher in callus cultured in sugar-excessive media, whereas it was reduced in the callus cultured in the other media types compared with control media. Finally, chlorophyll was reduced in all callus media compared with the control media. The current study concluded that, varying concentration of sugar and nitrogen inhibit callus development and morphology via alteration of secondary metabolites and their related genes.
- Published
- 2020
25. The VEGF inhibitor vatalanib regulates AD pathology in 5xFAD mice
- Author
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Hyunju Lee, Kyung-Min Han, Hyunhee Park, Hyang-Sook Hoe, and Seong Gak Jeon
- Subjects
0301 basic medicine ,Male ,Vascular Endothelial Growth Factor A ,Pathology ,medicine.medical_specialty ,Vatalanib ,medicine.drug_class ,Angiogenesis ,Amyloid beta ,Pyridines ,Tyrosine kinase inhibitor ,Mice, Transgenic ,tau Proteins ,5xFAD mice ,Tyrosine-kinase inhibitor ,lcsh:RC346-429 ,Micro Report ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,0302 clinical medicine ,Alzheimer Disease ,Medicine ,Animals ,Humans ,Phosphorylation ,Molecular Biology ,lcsh:Neurology. Diseases of the nervous system ,biology ,business.industry ,Masitinib ,Dasatinib ,Vascular endothelial growth factor ,030104 developmental biology ,chemistry ,biology.protein ,Phthalazines ,Tau ,business ,Tyrosine kinase ,Alzheimer’s disease ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Alzheimer’s disease (AD) is a highly prevalent neurodegenerative disease characterized by Aβ accumulation and tau hyperphosphorylation. Epidemiological evidence for a negative correlation between cancer and AD has led to the proposed use of tyrosine kinase inhibitors (TKIs) such as dasatinib and masitinib for AD, with reported beneficial effects in the AD brain. The TKI vatalanib inhibits angiogenesis by inhibiting vascular endothelial growth factor receptor (VEGFR). Although changes in VEGF and VEGFR have been documented in AD, the effect of vatalanib on AD pathology has not been investigated. In this study, the effects of vatalanib on tau phosphorylation and Aβ accumulation in 5xFAD mice, a model of AD, were evaluated by immunohistochemistry. Vatalanib administration significantly reduced tau phosphorylation at AT8 and AT100 by increasing p-GSK-3β (Ser9) in 5xFAD mice. In addition, vatalanib reduced the number and area of Aβ plaques in the cortex in 5xFAD mice. Our results suggest that vatalanib has potential as a regulator of AD pathology.
- Published
- 2020
26. Overexpression of OsF 3 H modulates WBPH stress by alteration of phenylpropanoid pathway at a transcriptomic and metabolomic level in Oryza sativa
- Author
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Sajjad Asaf, Kyung-Min Kim, Muhammad Aqil Khan, Rahmatullah Jan, and In-Jung Lee
- Subjects
0106 biological sciences ,0301 basic medicine ,Agricultural genetics ,Molecular biology ,Transgene ,lcsh:Medicine ,Biology ,01 natural sciences ,Article ,Plant breeding ,03 medical and health sciences ,chemistry.chemical_compound ,lcsh:Science ,Gene ,Regulation of gene expression ,Genetics ,Multidisciplinary ,Oryza sativa ,Phenylpropanoid ,fungi ,lcsh:R ,Wild type ,food and beverages ,Gene regulation ,030104 developmental biology ,chemistry ,Anthocyanin ,lcsh:Q ,Gene expression ,Delphinidin ,010606 plant biology & botany - Abstract
The whitebacked planthopper (WBPH), has become a devastating pest for rice crops, causes serious yield losses each year, and urgently needs biological control. Here, we developed a WBPH-resistant rice cultivar by overexpressing the OsF3H gene. A genetic functional analysis of the OsF3H gene confirmed its role in facilitating flavonoid contents and have indicated that the expression of the OsF3H gene is involved in regulation of the downstream genes (OsDFR and OsFLS) of the flavonoid pathway and genes (OsSLR1 and OsWRKY13) involved in other physiological pathways. OxF3H (OsF3H transgenic) plants accumulated significant amounts of the flavonols kaempferol (Kr) and quercetin (Qu) and the anthocyanins delphinidin and cyanidin, compared to the wild type, in response to the stress induced by WBPH. Similarly, OsF3H-related proteins were significantly expressed in OxF3H lines after WBPH infestation. The present study, indicated that the regulation of JA in OxF3H plants was suppressed due the overexpression of the OsF3H gene, which induced the expression of downstream genes related to anthocyanin. Similarly, the OsWRKY13 transcriptional factor was significantly suppressed in OxF3H plants during WBPH infestation. Exogenous application of Kr and Qu increased the survival rates of susceptible TN1 lines in response to WBPH, while decreased the survival rate of first instar WBPHs, indicating that both flavonols exhibit pesticide activity. Phenotypic demonstration also affirms that OxF3H plants show strong resistance to WBPH compared with wild type. Collectively, our result suggested that OsF3H overexpression led to the up-regulation of defense related genes and enhanced rice resistance to WBPH infestation.
- Published
- 2020
27. Production of quail (Coturnix japonica) germline chimeras by transfer of Ficoll-enriched spermatogonial stem cells
- Author
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Young-Min Kim, Kyung Je Park, Kyung Min Jung, Jae Yong Han, Jin Se Park, and Ho Yeon Cho
- Subjects
Male ,Differential centrifugation ,Homeobox protein NANOG ,Adult Germline Stem Cells ,biology ,Chimera ,Equine ,Ficoll ,Coturnix ,Quail ,Spermatogonia ,Germline ,Cell biology ,Transplantation ,Food Animals ,biology.animal ,Animals ,Animal Science and Zoology ,Stem cell ,Small Animals ,Percoll ,Cells, Cultured - Abstract
Due to the absence of long-term in vitro germline competent stem cell maintenance systems and efficient methods for germline transmission, efforts to develop an effective transgenic system in quail has remained limited. To overcome this limitation, here we produced germline chimeric quails through transplantation of spermatogonial stem cells (SSCs) enriched by density gradient methods utilizing Ficoll-Paque PLUS (Ficoll), Percoll and sucrose solution as a practical strategy for germline transmission in quail. For all gradient methods, testicular cells were separated as two fractions, and the expression levels of SSC-specific genes (GFRA1, ITGA6, ITGB1) and pluripotency genes (NANOG, POUV) were examined. As a result, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and RNA probe hybridization analysis revealed that the upper fraction that was separated by Ficoll showed the highest expression of SSC-specific and pluripotency genes among all fractions. Cells in the upper Ficoll gradient fraction also displayed reduced heterochromatin distribution, as observed in differentiated spermatogonia using transmission electron microscopy (TEM). These results indicate that SSCs were enriched in the upper fraction by Ficoll density gradient centrifugation. Subsequent transplantation experiments revealed that the efficiency of germline transmission to donor-derived gametes in the germline chimeras with transplanted SSCs and whole testicular cells was 0–13.2% and 0–4.4%, respectively. Collectively, these results demonstrate that quail SSCs were easily enriched with a density gradient method and that this method is a feasible and practical way to preserve the germplasm of quail. Furthermore, we can expect to apply this method in research examining the production of transgenic quail and preservation of avian species.
- Published
- 2020
28. The thin red line between species – genomic differentiation ofGymnosomaMeigen, a taxonomically challenging genus of parasitoid flies (Diptera: Tachinidae)
- Author
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Theo Zeegers, Marko Mutanen, Jaakko L. O. Pohjoismäki, and Kyung Min Lee
- Subjects
0106 biological sciences ,0303 health sciences ,biology ,Tachinidae ,Morphology (biology) ,biology.organism_classification ,Gymnosoma ,010603 evolutionary biology ,01 natural sciences ,Parasitoid ,03 medical and health sciences ,Evolutionary biology ,Dna barcodes ,Genus ,Insect Science ,Line (text file) ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology - Published
- 2020
29. Genetic determinants of increased body mass index mediate the effect of smoking on increased risk for type 2 diabetes but not coronary artery disease
- Author
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Peter W.F. Wilson, Scott M. Damrauer, Philip S. Tsao, Yan V. Sun, Kelly Cho, Zhuoran Ding, Christopher J. O'Donnell, Marijana Vujkovic, Kyung Min Lee, VA Million Veteran Program, Julie A. Lynch, Themistocles L. Assimes, Kyong-Mi Chang, Benjamin F. Voight, Christopher S. Thom, and Michael G. Levin
- Subjects
AcademicSubjects/SCI01140 ,medicine.medical_specialty ,Diabetes risk ,Coronary Artery Disease ,Type 2 diabetes ,Biology ,Polymorphism, Single Nucleotide ,Body Mass Index ,Coronary artery disease ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Mendelian randomization ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Obesity ,030212 general & internal medicine ,Risk factor ,Association Studies Article ,Molecular Biology ,Genetics (clinical) ,030304 developmental biology ,0303 health sciences ,Smoking ,Mendelian Randomization Analysis ,General Medicine ,medicine.disease ,Diabetes Mellitus, Type 2 ,Body mass index ,Genome-Wide Association Study - Abstract
Clinical observations have linked tobacco smoking with increased type 2 diabetes risk. Mendelian randomization analysis has recently suggested smoking may be a causal risk factor for type 2 diabetes. However, this association could be mediated by additional risk factors correlated with smoking behavior, which have not been investigated. We hypothesized that body mass index (BMI) could help to explain the association between smoking and diabetes risk. First, we confirmed that genetic determinants of smoking initiation increased risk for type 2 diabetes (OR 1.21, 95% CI: 1.15–1.27, P = 1 × 10−12) and coronary artery disease (CAD; OR 1.21, 95% CI: 1.16–1.26, P = 2 × 10−20). Additionally, 2-fold increased smoking risk was positively associated with increased BMI (~0.8 kg/m2, 95% CI: 0.54–0.98 kg/m2, P = 1.8 × 10−11). Multivariable Mendelian randomization analyses showed that BMI accounted for nearly all the risk smoking exerted on type 2 diabetes (OR 1.06, 95% CI: 1.01–1.11, P = 0.03). In contrast, the independent effect of smoking on increased CAD risk persisted (OR 1.12, 95% CI: 1.08–1.17, P = 3 × 10−8). Causal mediation analyses agreed with these estimates. Furthermore, analysis using individual-level data from the Million Veteran Program independently replicated the association of smoking behavior with CAD (OR 1.24, 95% CI: 1.12–1.37, P = 2 × 10−5), but not type 2 diabetes (OR 0.98, 95% CI: 0.89–1.08, P = 0.69), after controlling for BMI. Our findings support a model whereby genetic determinants of smoking increase type 2 diabetes risk indirectly through their relationship with obesity. Smokers should be advised to stop smoking to limit type 2 diabetes and CAD risk. Therapeutic efforts should consider pathophysiology relating smoking and obesity.
- Published
- 2020
30. Genetic diversity of rice germplasm (Oryza sativa L.) of java island, Indonesia
- Author
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Addieni Zulfa Karimah, Tri Agus Siswoyo, Kyung Min Kim, and Mohammad Ubaidillah
- Subjects
0106 biological sciences ,Germplasm ,Genetic diversity ,Oryza sativa ,Java ,business.industry ,Locus (genetics) ,04 agricultural and veterinary sciences ,Plant Science ,Biology ,01 natural sciences ,Biotechnology ,Agriculture ,040103 agronomy & agriculture ,0401 agriculture, forestry, and fisheries ,Microsatellite ,Allele ,business ,Agronomy and Crop Science ,computer ,010606 plant biology & botany ,computer.programming_language - Abstract
The role of genetic diversity in crop germplasm is an important concept within genetic conservation. In this research, 43 accessions were analyzed at the agro-morphological and genetic levels. Clustering based on the agro-morphological resulted in four sub-groups. Analysis at the genetic level was conducted using 22 microsatellites, which revealed a total number of alleles to be 203, with a range per allele between 2 and 17 and an average of 9.2 alleles per locus. The highest and lowest Polymorphic Information Content (PIC) values were found in RM431 and RM11, which were 0.95 and 0.67, respectively. The genetic diversity value ranged from 0.71 to 0.95. The genetic similarity among accessions ranged from 0.00 to 0.90. Clustering based on the genetic relatedness divided the Java rice samples into two major groups. The classification created through this research many inform future breeding programs aimed at improving the quality and quantity of yield production.
- Published
- 2020
31. Impact of transgenic sugarcane overexpressing SoSPS1 gene on bacterial diversity, enzyme activity and minerals content in soil rhizosphere
- Author
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Tri Handoyo, Kyung-Min Kim, Bambang Sugiharto, Fitria Ekawati Wulandari, and Suherman
- Subjects
0106 biological sciences ,Rhizosphere ,education.field_of_study ,Microorganism ,Population ,04 agricultural and veterinary sciences ,Plant Science ,Biology ,biology.organism_classification ,01 natural sciences ,Horticulture ,Transformation (genetics) ,Nutrient ,040103 agronomy & agriculture ,biology.protein ,0401 agriculture, forestry, and fisheries ,Sucrose-phosphate synthase ,Soil fertility ,education ,Agronomy and Crop Science ,Bacteria ,010606 plant biology & botany ,Biotechnology - Abstract
The transgenic sugarcane overexpressing SoSPS1 gene increased sugar content which may alter the root exudation that interact with soil rhizosphere microorganism. The microbial plays an important role in biochemical cycling and nutrient transformation in the soil. Therefore, it is important to investigate the potential risk of the transgenic sugarcane on soil ecosystem. This study is designed to evaluate the impact of overexpressing gene for sucrose-phosphate synthesis (SoSPS1) on the bacterial diversity, enzyme activity and nutrient contents. The transgenic sugarcane showed no significant difference in the population of culturable bacteria in the soil rhizosphere compared to non-transgenic counterpart. The populations of total, nitrogen-fixing and phosphate-solubilizing bacteria were similar in transgenic and non-transgenic sugarcane, although the bacterial population tends to increase at later sugarcane growth stage may due to the rise in nutrition from the root exudation. The PCR analysis showed no detection of horizontal gene flow in the bacteria. However, urease activity was significantly decreased in the transgenic sugarcane concomitant with lower nitrogen content in the soil rhizosphere at a later growth stage might due to the transgenic sugarcane lines increased nitrogen absorption for higher growth rate. Furthermore, the nutrient contents, such as organic carbon, phosphorus, potassium, magnesium and calcium, slightly varied in the soil rhizosphere but did not affected by the transgenic sugarcane. The results suggested that the transgenic sugarcane overexpressing SoSPS1 gene may not affect the bacterial diversity, nutrient contents and soil ecosystem.
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- 2020
32. NH4+ Suppresses NO3–-Dependent Lateral Root Growth and Alters Gene Expression and Gravity Response in OsAMT1 RNAi Mutants of Rice (Oryza sativa)
- Author
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Vikranth Kumar, Sung Hoon Kim, Ryza A. Priatama, Jin Hee Jeong, Moch Rosyadi Adnan, Bernet Agung Saputra, Chul Min Kim, Byoung Il Je, Soon Ju Park, Ki Hong Jung, Kyung Min Kim, Yuan Hu Xuan, and Chang-deok Han
- Subjects
inorganic chemicals ,0106 biological sciences ,0301 basic medicine ,chemistry.chemical_classification ,Oryza sativa ,Mutant ,Lateral root ,food and beverages ,Plant Science ,Biology ,01 natural sciences ,Cell biology ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,chemistry ,Auxin ,RNA interference ,Gene expression ,Ammonium ,Gene ,010606 plant biology & botany - Abstract
The AMT1 family comprises major ammonium transporters in rice roots. In this study, we utilized AMT1 RNAi mutants (amt1) to explore how AMT1 affects NH4+- and NO3–-mediated morphological development and NH4+-responsive gene expression in roots. In the presence of NH4+, amt1 showed inhibition of NO3–- dependent lateral root development. The inhibitory action of NH4+ on lateral root growth was independent of the NO3– concentrations supplied to amt1 roots. The results of split root assays indicated that NH4+ exerts systemic action in inhibiting NO3–-dependent lateral root development in amt1. Further study with NAA and NOA, a potent auxin flux inhibitor, suggested that perturbation of membrane dynamics might not be the primary cause of the inhibitory action of NH4+ on NO3–-mediated lateral root growth in amt1 mutants. RNA-seq analysis of NH4+-responsive genes showed that approximately half of DEGs observed in wild-type roots were not detected in the DEGs of amt1 roots. Gene ontology enrichment analysis suggested that the expression of specific functional gene groups were affected by amt1 during the early response to NH4+. Auxin-responsive gene expression and root gravity responses were altered in amt1. This study demonstrated that AMT1 affects the interactions not only between ammonium and nitrate in lateral root growth but also between auxin and NH4+ in rice roots.
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- 2020
33. Glucose oxidase-copper hybrid nanoflowers embedded with magnetic nanoparticles as an effective antibacterial agent
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Moon Il Kim, Kyung Min Yeon, Manab Deb Adhikari, Hong Jae Cheon, Jungbae Kim, Inseon Lee, and Tai Duc Tran
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Staphylococcus aureus ,Bioconversion ,02 engineering and technology ,medicine.disease_cause ,Biochemistry ,Glucose Oxidase ,03 medical and health sciences ,Structural Biology ,Escherichia coli ,medicine ,Glucose oxidase ,Amines ,Molecular Biology ,030304 developmental biology ,Antibacterial agent ,0303 health sciences ,biology ,Chemistry ,General Medicine ,Hydrogen-Ion Concentration ,021001 nanoscience & nanotechnology ,Combinatorial chemistry ,Anti-Bacterial Agents ,Membrane ,Biocatalysis ,biology.protein ,Magnetic nanoparticles ,Magnetic Iron Oxide Nanoparticles ,0210 nano-technology ,Antibacterial activity ,Oxidation-Reduction ,Biosensor ,Copper - Abstract
Bacterial contamination causes various problems ranging from bacterial infection to biofouling. As an effective and non-toxic agent for bacterial de-contamination, glucose oxidase (GOx)-copper hybrid nanoflowers embedded with amine-functionalized magnetic nanoparticles (NH2-MNPs), called ‘MNP-GOx NFs’, are developed. Positively-charged NH2-MNPs and negatively-charged GOx molecules are first interacted via electrostatic attraction which can be controlled by changing the buffer pH, and the follow-up addition of copper(II) sulfate leads to blooming of nanoflowers (MNP-GOx NFs) after incubation at room temperature for 3 days. MNP-GOx NFs show effective antibacterial activity by generating H2O2 from GOx-catalyzed glucose oxidation. For example, 99.9% killings of Staphylococcus aureus and Escherichia coli are achieved after 3 h treatment of 106/mL cells with 0.2 and 3.0 mg/mL MNP-GOx NFs, respectively, revealing that Gram-positive S. aureus with mono-layer membrane system is more vulnerable to the treatment of MNP-GOx NFs than Gram-negative E. coli with two-layer membrane system. MNP-GOx NFs can maintain 97% of bactericidal activity even after recycled uses by magnetic separation for eight times iterative bacterial killings. Finally, MNP-GOx NFs are employed for the fabrication of antibacterial gauzes. MNP-GOx NFs have also opened up a great potential for their applications in biosensors, biofuel cells and bioconversion as well as bacterial de-contamination.
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- 2020
34. A case report of fulminant endophthalmitis caused by Streptococcus dysgalactiae in a patient with traumatic corneal laceration
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Yong Woo Lee, Kyu Yeon Hwang, Sang Wroul Song, Kyung Min Koh, Byoung Yeop Kim, Young A Kwon, Dongwon Lee, and Kook Young Kim
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0301 basic medicine ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,030106 microbiology ,Enucleation ,Visual Acuity ,Vitrectomy ,Case Report ,Hypopyon ,Lacerations ,Eye Infections, Bacterial ,03 medical and health sciences ,0302 clinical medicine ,Endophthalmitis ,lcsh:Ophthalmology ,Intensive care ,Streptococcal Infections ,medicine ,Humans ,Aged ,Ultrasonography ,Corneal laceration ,biology ,business.industry ,Retinal detachment ,Streptococcus ,General Medicine ,medicine.disease ,biology.organism_classification ,eye diseases ,Surgery ,Anti-Bacterial Agents ,Ophthalmology ,lcsh:RE1-994 ,Acute Disease ,030221 ophthalmology & optometry ,sense organs ,Streptococcus dysgalactiae ,business ,Scleritis ,Corneal Injuries - Abstract
Background To report a case of enucleation caused by Streptococcus dysgalactiae endophthalmitis after traumatic corneal laceration. Case presentation A 69-year-old man with history of retinal detachment treated with vitrectomy and subsequent cataract surgery presented with traumatic corneal laceration while cutting grass. Appropriate repair of corneal laceration and intravitreal antibiotics (vancomycin, ceftazidime) injection was performed. S. dysgalactiae which was sensitive to the conventional antibiotics (Ampicillin, Ceftriaxone, Levofloxacin, etc.) detected by aqueous culture. One day following primary closure, the patient developed a complete hypopyon and vitreous membranes. Despite vigorous systemic and intravitreal antibiotics administration with vitrectomy, endophthalmitis was not controlled and patient’s ocular pain was increased. The vitreous culture was also positive for S. dysgalactiae. Finally, total enucleation was performed 9 days after trauma due to fulminant endophthalmitis with severe scleritis. Conclusion Progression of traumatic endophthalmitis associated with S. dysgalactiae can be fulminant. Sufficient warning to patient about enucleation and intensive care is needed in the case of this infection.
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- 2020
35. Thermotolerance effect of plant growth-promoting Bacillus cereus SA1 on soybean during heat stress
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Sajjad Asaf, Kyung-Min Kim, Muhammad Aaqil Khan, In-Jung Lee, Sang-Mo Kang, Abdul Latif Khan, and Rahmatullah Jan
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Crops, Agricultural ,Thermotolerance ,0106 biological sciences ,0301 basic medicine ,Microbiology (medical) ,Antioxidant ,medicine.medical_treatment ,lcsh:QR1-502 ,Biology ,01 natural sciences ,Microbiology ,Heat stress ,lcsh:Microbiology ,Superoxide dismutase ,03 medical and health sciences ,chemistry.chemical_compound ,Bacillus cereus ,Gene Expression Regulation, Plant ,B. cereus SA1 ,Phytohormone ,Heat shock protein ,Endophytes ,medicine ,Food science ,Abscisic acid ,Chlorophyll fluorescence ,Heat-Shock Proteins ,Soil Microbiology ,Plant Proteins ,fungi ,food and beverages ,Ascorbic acid ,Amino acid ,030104 developmental biology ,chemistry ,biology.protein ,Gibberellin ,Soybeans ,Salicylic Acid ,Soybean ,Heat-Shock Response ,Salicylic acid ,Abscisic Acid ,Research Article ,010606 plant biology & botany ,HSP expression - Abstract
Background Incidences of heat stress due to the changing global climate can negatively affect the growth and yield of temperature-sensitive crops such as soybean variety, Pungsannamul. Increased temperatures decrease crop productivity by affecting biochemical, physiological, molecular, and morphological factors either individually or in combination with other abiotic stresses. The application of plant growth-promoting endophytic bacteria (PGPEB) offers an ecofriendly approach for improving agriculture crop production and counteracting the negative effects of heat stress. Results We isolated, screened and identified thermotolerant B. cereus SA1 as a bacterium that could produce biologically active metabolites, such as gibberellin, indole-3-acetic acid, and organic acids. SA1 inoculation improved the biomass, chlorophyll content, and chlorophyll fluorescence of soybean plants under normal and heat stress conditions for 5 and 10 days. Heat stress increased abscisic acid (ABA) and reduced salicylic acid (SA); however, SA1 inoculation markedly reduced ABA and increased SA. Antioxidant analysis results showed that SA1 increased the ascorbic acid peroxidase, superoxide dismutase, and glutathione contents in soybean plants. In addition, heat stress markedly decreased amino acid contents; however, they were increased with SA1 inoculation. Heat stress for 5 days increased heat shock protein (HSP) expression, and a decrease in GmHSP expression was observed after 10 days; however, SA1 inoculation augmented the heat stress response and increased HSP expression. The stress-responsive GmLAX3 and GmAKT2 were overexpressed in SA1-inoculated plants and may be associated with decreased reactive oxygen species generation, altered auxin and ABA stimuli, and enhanced potassium gradients, which are critical in plants under heat stress. Conclusion The current findings suggest that B. cereus SA1 could be used as a thermotolerant bacterium for the mitigation of heat stress damage in soybean plants and could be commercialized as a biofertilizer only in case found non-pathogenic.
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- 2020
36. Brn3a/Pou4f1 Functions as a Tumor Suppressor by Targeting c-MET/STAT3 Signaling in Thyroid Cancer
- Author
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Mi Ae Lim, Yan Li Jin, Seung-Nam Jung, Yea Eun Kang, Chan Oh, Gun Ho Lee, Ho-Ryun Won, Jae Won Chang, Lihua Liu, Bon Seok Koo, Taejeong Oh, and Kyung Min Lee
- Subjects
STAT3 Transcription Factor ,medicine.medical_specialty ,Epithelial-Mesenchymal Transition ,C-Met ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Biochemistry ,Metastasis ,chemistry.chemical_compound ,Endocrinology ,Cell Movement ,Cell Line, Tumor ,Internal medicine ,medicine ,Humans ,Genes, Tumor Suppressor ,Thyroid Neoplasms ,STAT3 ,Thyroid cancer ,Transcription factor ,Transcription Factor Brn-3A ,biology ,business.industry ,Kinase ,Gene Expression Profiling ,Biochemistry (medical) ,Receptor Protein-Tyrosine Kinases ,Cell migration ,Microarray Analysis ,medicine.disease ,Gene Expression Regulation, Neoplastic ,chemistry ,STAT protein ,biology.protein ,Cancer research ,business ,Signal Transduction - Abstract
Background Brn3a/Pou4f1 is a class IV POU domain-containing transcription factor and has been found to be expressed in a variety of cancers. However, the mechanism and action of Brn3a in thyroid cancer has not been investigated. Purpose To investigate the role of Brn3a in thyroid cancer progression and its clinical implication. Methods We examined Brn3a expression status in patients with thyroid cancer and analyzed relationships between Brn3a expression and clinicopathological findings using The Cancer Genome Atlas (TCGA) database. For functional in vitro analysis, proliferation, migration, invasion assay, and Western blotting were performed after overexpression or suppression of Brn3a. Results The promoter hypermethylation of Brn3a was found in patients with aggressive thyroid cancer and Brn3a was downregulated in tissues of patients with thyroid cancer. In TCGA database, the low-Brn3a-expression group revealed a more aggressive phenotype, including T stage and extrathyroid extension when compared with the high-Brn3a-expression group. Overexpression of Brn3a suppressed cell migration and invasion via regulation of epithelial-mesenchymal transition (EMT)-associated proteins in thyroid cancer cell lines. Brn3a overexpression also downregulated signal transducer and activator of transcription 3 (STAT3) signaling through suppression of tyrosine-protein kinase Met (c-MET). In contrast, knockdown of Brn3a by small interfering ribonucleic acid (siRNA) significantly increased cell migration and invasion through upregulation of c-MET/STAT3. These results imply that Brn3a suppresses tumor metastasis via c-MET/STAT3 inhibition and EMT suppression in thyroid cancer. Conclusions Our findings show that Brn3a is a potential tumor suppressor that leads to reduced cancer cell migration and invasion in thyroid cancer. Elucidation of the Brn3a-regulated cancer pathways may therefore provide novel therapeutic strategies to control thyroid cancer metastasis.
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- 2020
37. Revision of the genus Hoplodrina Boursin, 1937 (Lepidoptera, Noctuidae, Xyleninae). I. Hoplodrina octogenaria (Goeze, 1781) and its sister species H. alsinides (Costantini, 1922) sp. rev. in Europe
- Author
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Marko Mutanen, Stefano Scalercio, Peter Huemer, Kyung Min Lee, Oleg Pekarsky, László Ronkay, and Jean Haxaire
- Subjects
cryptic species ddRAD sequencing DNA barcoding morphology owlet moths ,0106 biological sciences ,0301 basic medicine ,Insecta ,Morphology (biology) ,Carbotriplurida ,01 natural sciences ,DNA barcoding ,Genus ,lcsh:Zoology ,morphology ,Bilateria ,lcsh:QL1-991 ,Molecular genetics ,owlet moths ,Invertebrata ,Molecular systematics ,ddRAD sequencing ,Pterygota ,cryptic species ,biology ,Nomenclature ,Cenozoic ,Cephalornis ,Dichagyris zaghroica azerica ,Circumscriptional names ,Heteroneura ,Caradrinina ,Europe ,Lepidoptera ,Boltonocostidae ,Sympatric speciation ,Circumscriptional name ,Noctuidae ,Caradrinini ,Porina ,Coelenterata ,Research Article ,Cossina ,Species complex ,Arthropoda ,Ortopla ,Nephrozoa ,Protostomia ,Basal ,Circumscriptional names of the taxon under ,010603 evolutionary biology ,DNA sequencing ,Noctuoidea ,Lepidoptera genitalia ,Faunistics & Distribution ,03 medical and health sciences ,Systematics ,Panorpida ,Genetics ,Animalia ,Eumetabola ,Galacticoidea ,Ecology, Evolution, Behavior and Systematics ,Taxonomy ,Strashila incredibilis ,biology.organism_classification ,030104 developmental biology ,Bombycina ,Notchia ,Evolutionary biology ,Ecdysozoa ,Amphiesmenoptera ,Animal Science and Zoology ,Ditrysia ,Hoplodrina - Abstract
The taxonomic status of the European Hoplodrina octogenaria (Goeze, 1781) is discussed and its partly sympatric sister species, Hoplodrina alsinides (Costantini, 1922) sp. rev., is separated and re-described based on morphological and molecular taxonomic evidence. The adults and their genitalia are illustrated and DNA barcodes, as well as genome-wide single nucleotide polymorphism data collected by fractional genome sequencing (ddRAD), of the two species are provided.
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- 2020
38. Using genomic information for management planning of an endangered perennial, Viola uliginosa
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Branko Vreš, Jarmo Saarikivi, Kyung Min Lee, Lado Kutnar, Maxim A. Dzhus, Laura Kvist, Pertti Ranta, Marko Mutanen, Zoology, Helsinki Institute of Urban and Regional Studies (Urbaria), Helsinki Institute of Sustainability Science (HELSUS), Environmental Sciences, and Ecosystems and Environment Research Programme
- Subjects
0106 biological sciences ,demography ,EFFECTIVE POPULATION-SIZE ,Endangered species ,nature conservation ,SOFTWARE ,RAD sekvenciranje ,01 natural sciences ,genomic diversity ,Population genomics ,Monophyly ,Effective population size ,RARE ,Viola ,vijoličevke ,0303 health sciences ,education.field_of_study ,Ecology ,conservation ,Habitat ,EDGE ,1181 Ecology, evolutionary biology ,LOW GENETIC DIVERSITY ,Inbreeding ,population genomics ,udc:58 ,Population ,RANGE EXPANSION ,Biology ,RAD sequencing ,010603 evolutionary biology ,genska raznolikost ,03 medical and health sciences ,DNA-SEQUENCE ,lcsh:QH540-549.5 ,demografija ,education ,varstvo narave ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,Nature and Landscape Conservation ,botanika ,15. Life on land ,VIABILITY ,barska vijolica ,Biological dispersal ,N-E ,lcsh:Ecology ,populacijska genetika - Abstract
Species occupying habitats subjected to frequent natural and/or anthropogenic changes are a challenge for conservation management. We studied one such species, Viola uliginosa, an endangered perennial wetland species typically inhabiting sporadically flooded meadows alongside rivers/lakes. In order to estimate genomic diversity, population structure, and history, we sampled five sites in Finland, three in Estonia, and one each in Slovenia, Belarus, and Poland using genomic SNP data with double-digest restriction site-associated DNA sequencing (ddRAD-seq). We found monophyletic populations, high levels of inbreeding (mean population F-SNP = 0.407-0.945), low effective population sizes (N-e = 0.8-50.9), indications of past demographic expansion, and rare long-distance dispersal. Our results are important in implementing conservation strategies for V. uliginosa, which should include founding of seed banks, ex situ cultivations, and reintroductions with individuals of proper origin, combined with continuous population monitoring and habitat management.
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- 2020
39. Lysine 4 of histone H3.3 is required for embryonic stem cell differentiation, histone enrichment at regulatory regions and transcription accuracy
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Matteo Trovato, Nichole Diaz, Daria Bunina, Judith B. Zaugg, Maja Gehre, Marlena J. Lübke, Benjamin A. Garcia, Kyung-Min Noh, and Simone Sidoli
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Transcription, Genetic ,RNA polymerase II ,Regulatory Sequences, Nucleic Acid ,Histones ,Mice ,03 medical and health sciences ,Histone H3 ,0302 clinical medicine ,Gene expression ,Genetics ,Animals ,Humans ,Nucleosome ,Promoter Regions, Genetic ,Enhancer ,030304 developmental biology ,0303 health sciences ,Alanine ,biology ,Lysine ,Cell Differentiation ,Mouse Embryonic Stem Cells ,Chromatin Assembly and Disassembly ,Nucleosomes ,Cell biology ,Chromatin ,Histone Code ,Enhancer Elements, Genetic ,HEK293 Cells ,Histone ,Regulatory sequence ,Mutation ,biology.protein ,RNA Polymerase II ,030217 neurology & neurosurgery - Abstract
Mutations in enzymes that modify histone H3 at lysine 4 (H3K4) or lysine 36 (H3K36) have been linked to human disease, yet the role of these residues in mammals is unclear. We mutated K4 or K36 to alanine in the histone variant H3.3 and showed that the K4A mutation in mouse embryonic stem cells (ESCs) impaired differentiation and induced widespread gene expression changes. K4A resulted in substantial H3.3 depletion, especially at ESC promoters; it was accompanied by reduced remodeler binding and increased RNA polymerase II (Pol II) activity. Regulatory regions depleted of H3.3K4A showed histone modification alterations and changes in enhancer activity that correlated with gene expression. In contrast, the K36A mutation did not alter H3.3 deposition and affected gene expression at the later stages of differentiation. Thus, H3K4 is required for nucleosome deposition, histone turnover and chromatin remodeler binding at regulatory regions, where tight regulation of Pol II activity is necessary for proper ESC differentiation.
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- 2020
40. Diversity, Physicochemical, and Structural Properties of Indonesian Aromatic Rice Cultivars
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Innani Mukarromatus Sholehah, Didik Pudji Restanto, Kyung-Min Kim, and Tri Handoyo
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0106 biological sciences ,Genetic diversity ,Granule (cell biology) ,food and beverages ,04 agricultural and veterinary sciences ,Plant Science ,Proximate ,Biology ,01 natural sciences ,Horticulture ,chemistry.chemical_compound ,chemistry ,Amylose ,Principal component analysis ,040103 agronomy & agriculture ,0401 agriculture, forestry, and fisheries ,Cultivar ,Agronomy and Crop Science ,Pandan wangi ,Aromatic rice ,010606 plant biology & botany ,Biotechnology - Abstract
The most important component of rice qualities are its appearance, cooking quality, eating quality, and nutritional quality. Indonesian had been developed a large germplasms of rice, but still poor information about its physical, genetic and structural properties, especially aromatic rice. This research was performed to investigate the genetic diversity, proximate and structural properties of local aromatic rice cultivars in Indonesia by cluster analysis and principal component analysis. Twenty-one cultivars were analyzed with Bradburry markers showed that the 9 cultivars were expressed bands of 257 bp, and other cultivars amplified with 355 bp bands, the result indicated that the BADH2.7 gene was expressed on the different exon or the presence of a controlling another gene. The clustering of aromatic rice cultivars by PCA explained that the first PC with Eigenvalue of 1.513 showed the total variance about 91.75%. The largest positive loadings of variables were amylose and trough viscosity. The second PC with Eigenvalue of 2.305 confirmed an additional 50.67% of the total variance. Indonesian aromatic rice was clustered into 3 groups based on proximate analysis and physicochemical properties. PCA analysis and 2D scatter diagram distributed the Indonesian aromatic rice became the four major groups. Starch granule images of four cluster showed the different granule forms, that cluster I (Radah Putih) is completely spherical with approximately equal sizes; cluster II (Pandan Wangi) has spherical granules unequal sizes; Cluster III (Gilirang) has polyhedral sharp-edged granules; Cluster IV (Sintanur) has polyhedral edged granules. The aromatic rice in Indonesia has a possibility of genetic proximity based on the physicochemical properties and proximate analysis with the highest variations in amylose, thermal properties and pasting properties. This information was useful for the selection of parentals in plant breeders and the processing of cultivation plant.
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- 2020
41. Enzymatically Crosslinkable Hyaluronic Acid-Gelatin Hybrid Hydrogels as Potential Bioinks for Tissue Regeneration
- Author
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Seung Bae Ryu, Kyung Min Park, Joo Young Son, Yunki Lee, Ki Dong Park, and Phuong Le Thi
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food.ingredient ,Materials science ,Polymers and Plastics ,General Chemical Engineering ,macromolecular substances ,02 engineering and technology ,010402 general chemistry ,complex mixtures ,01 natural sciences ,Horseradish peroxidase ,Gelatin ,chemistry.chemical_compound ,food ,Tissue engineering ,Hyaluronic acid ,Materials Chemistry ,Hydrogen peroxide ,chemistry.chemical_classification ,biology ,Organic Chemistry ,technology, industry, and agriculture ,Polymer ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,chemistry ,Chemical engineering ,Self-healing hydrogels ,biology.protein ,0210 nano-technology ,Biofabrication - Abstract
Hydrogels that mimic the composition and properties of the extracellular matrix have attracted great attention as potential polymeric scaffolds for tissue engineering applications. In this study, an injectable hydrogel composed of hyaluronic acid and gelatin was developed via the oxidative coupling reaction using horseradish peroxidase (HRP). The hydrogel was prepared by mixing two phenol-conjugated polymer solutions, hyaluronic acid-tyramine (HA-TA) and gelatin-hydroxyphenyl propionic acid (GH), in the presence of HRP and hydrogen peroxide (H202). The gelation rate and mechanical properties of composite hydrogel were controlled by adjusting the HRP and H202 concentrations, respectively Compared to the pure HA-TA hydrogels, the stability and cellular behaviors of composite hydrogel improved significantly In addition, the injectable hydrogel system showed good performance in 3D printing with high cell viability after one day of printing. The results suggest that enzymatically crosslinked HA-TA and GH hybrid (HA-TA/GH) composite of HA-TA and GH hydrogel has the potential as a material for tissue engineering and 3D printing biofabrication.
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- 2020
42. [18F]CB251 PET/MR imaging probe targeting translocator protein (TSPO) independent of its Polymorphism in a Neuroinflammation Model
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Kyung Min Kim, Byung-Chul Lee, Kyeong Yun Kim, Gi Jeong Cheon, Seok Yong Lee, Ha Kim, Young Hwa Kim, Sang Hee Lee, In Ho Song, Chul Hee Lee, Jae Sung Lee, Min Sun Lee, Juri Na, June-Key Chung, Sun Ha Paek, Sung Hwan Bae, Euishin Edmund Kim, Hyewon Youn, Sang Eun Kim, Keon Wook Kang, and Guen Bae Ko
- Subjects
Male ,0301 basic medicine ,Fluorine Radioisotopes ,medicine.medical_treatment ,Medicine (miscellaneous) ,multimodal imaging ,Gadolinium ,neuroinflammation ,polymorphism ,Mice ,0302 clinical medicine ,Acetamides ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,Neurons ,biology ,Chemistry ,Brain ,Ligand (biochemistry) ,Magnetic Resonance Imaging ,Cytokine ,Blood-Brain Barrier ,Cytokines ,medicine.symptom ,TSPO ,Research Paper ,Genetically modified mouse ,Mice, Transgenic ,Inflammation ,Heterocyclic Compounds, 2-Ring ,Cell Line ,03 medical and health sciences ,Immune system ,Receptors, GABA ,medicine ,Translocator protein ,Animals ,Humans ,Bioluminescence imaging ,Neuroinflammation ,Polymorphism, Genetic ,Molecular biology ,Mice, Inbred C57BL ,Disease Models, Animal ,PET/MRI ,HEK293 Cells ,RAW 264.7 Cells ,030104 developmental biology ,Positron-Emission Tomography ,Luminescent Measurements ,biology.protein ,Radiopharmaceuticals ,Tomography, X-Ray Computed ,030217 neurology & neurosurgery - Abstract
The 18 kDa translocator protein (TSPO) has been proposed as a biomarker for the detection of neuroinflammation. Although various PET probes targeting TSPO have been developed, a highly selective probe for detecting TSPO is still needed because single nucleotide polymorphisms in the human TSPO gene greatly affect the binding affinity of TSPO ligands. Here, we describe the visualization of neuroinflammation with a multimodality imaging system using our recently developed TSPO-targeting radionuclide PET probe [18F]CB251, which is less affected by TSPO polymorphisms. Methods: To test the selectivity of [18F]CB251 for TSPO polymorphisms, 293FT cells expressing polymorphic TSPO were generated by introducing the coding sequences of wild-type (WT) and mutant (Alanine → Threonine at 147th Amino Acid; A147T) forms. Competitive inhibition assay was conducted with [3H]PK11195 and various TSPO ligands using membrane proteins isolated from 293FT cells expressing TSPO WT or mutant-A147T, representing high-affinity binder (HAB) or low-affinity binder (LAB), respectively. IC50 values of each ligand to [3H]PK11195 in HAB or LAB were measured and the ratio of IC50 values of each ligand to [3H]PK11195 in HAB to LAB was calculated, indicating the sensitivity of TSPO polymorphism. Cellular uptake of [18F]CB251 was measured with different TSPO polymorphisms, and phantom studies of [18F]CB251-PET using 293FT cells were performed. To test TSPO-specific cellular uptake of [18F]CB251, TSPO expression was regulated with pCMV-TSPO (or shTSPO)/eGFP vector. Intracranial lipopolysaccharide (LPS) treatment was used to induce regional inflammation in the mouse brain. Gadolinium (Gd)-DOTA MRI was used to monitor the disruption of the blood-brain barrier (BBB) and infiltration by immune cells. Infiltration of peripheral immune cells across the BBB, which exacerbates neuroinflammation to produce higher levels of neurotoxicity, was also monitored with bioluminescence imaging (BLI). Peripheral immune cells isolated from luciferase-expressing transgenic mice were transferred to syngeneic inflamed mice. Neuroinflammation was monitored with [18F]CB251-PET/MR and BLI. To evaluate the effects of anti-inflammatory agents on intracranial inflammation, an inflammatory cytokine inhibitor, 2-cyano-3, 12-dioxooleana-1, 9-dien-28-oic acid methyl ester (CDDO-Me) was administered in intracranial LPS challenged mice. Results: The ratio of IC50 values of [18F]CB251 in HAB to LAB indicated similar binding affinity to WT and mutant TSPO and was less affected by TSPO polymorphisms. [18F]CB251 was specific for TSPO, and its cellular uptake reflected the amount of TSPO. Higher [18F]CB251 uptake was also observed in activated immune cells. Simultaneous [18F]CB251-PET/MRI showed that [18F]CB251 radioactivity was co-registered with the MR signals in the same region of the brain of LPS-injected mice. Luciferase-expressing peripheral immune cells were located at the site of LPS-injected right striatum. Quantitative evaluation of the anti-inflammatory effect of CDDO-Me on neuroinflammation was successfully monitored with TSPO-targeting [18F]CB251-PET/MR and BLI. Conclusion: Our results indicate that [18F]CB251-PET has great potential for detecting neuroinflammation with higher TSPO selectivity regardless of polymorphisms. Our multimodal imaging system, [18F]CB251-PET/MRI, tested for evaluating the efficacy of anti-inflammatory agents in preclinical studies, might be an effective method to assess the severity and therapeutic response of neuroinflammation.
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- 2020
43. Calcium peroxide-mediated in situ formation of multifunctional hydrogels with enhanced mesenchymal stem cell behaviors and antibacterial properties
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Kyung Min Park, Dieu Linh Tran, Thai Thanh Hoang Thi, Yunki Lee, Phuong Le Thi, and Ki Dong Park
- Subjects
biology ,Regeneration (biology) ,Mesenchymal stem cell ,technology, industry, and agriculture ,Biomedical Engineering ,food and beverages ,macromolecular substances ,General Chemistry ,General Medicine ,complex mixtures ,Horseradish peroxidase ,chemistry.chemical_compound ,chemistry ,Reagent ,Calcium peroxide ,Self-healing hydrogels ,biology.protein ,Biophysics ,General Materials Science ,Bone regeneration ,Hydrogen peroxide - Abstract
Injectable hydrogels can serve as therapeutic vehicles and implants for the treatment of various diseases as well as for tissue repair/regeneration. In particular, the horseradish peroxidase (HRP) and hydrogen peroxide (H2O2)-catalyzed hydrogelation system has attracted much attention, due to its ease of handling and controllable gel properties. In this study, we introduce calcium peroxide (CaO2) as a H2O2-generating reagent to gradually supply a radical source for the HRP-catalyzed crosslinking reaction. This novel therapy can create stiff hydrogels without compromising the cytocompatibility of the hydrogels due to the use of initially high concentrations of H2O2. The physico-chemical properties of the hydrogels can be controlled by varying the concentrations of HRP and CaO2. In addition, the controlled and sustained release of bioactive molecules, including H2O2, O2, and Ca2+ ions, from the hydrogels could stimulate the cellular behaviors (attachment, migration, and differentiation) of human mesenchymal stem cells. Moreover, the hydrogels exhibited killing efficacy against both Gram-negative and Gram-positive bacteria, dependent on the H2O2 and Ca2+ release amounts. These positive results suggest that hydrogels formed by HRP/CaO2 can be used as potential matrices for a wide range of biomedical applications, such as bone regeneration and infection treatment.
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- 2020
44. High-throughput functional characterization of protein phosphorylation sites in yeast
- Author
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Matteo Trovato, David Ochoa, Umut Yildiz, Kyung-Min Noh, Chelsea Szu Tu, Areeb Jawed, Athanasios Typas, Alexander G. Geiger, Vikram Govind Panse, Michaela Oborská-Oplová, Danish Memon, Mohammed Shahraz, Pedro Beltrao, Frank Stein, Lars M. Steinmetz, Cristina Viéitez, Marco Galardini, Mikhail M. Savitski, Bede P. Busby, André Mateus, Sibylle C. Vonesch, Clement M. Potel, University of Zurich, Savitski, Mikhail M, Typas, Athanasios, and Beltrao, Pedro
- Subjects
Saccharomyces cerevisiae Proteins ,Saccharomyces cerevisiae ,Mutant ,ROBUST ,Biomedical Engineering ,2204 Biomedical Engineering ,Bioengineering ,610 Medicine & health ,Computational biology ,Applied Microbiology and Biotechnology ,GENETIC-ANALYSIS ,KINASE ,2402 Applied Microbiology and Biotechnology ,Protein phosphorylation ,NETWORK ,Phosphorylation ,Gene ,Science & Technology ,biology ,1502 Bioengineering ,MUTATIONS ,10179 Institute of Medical Microbiology ,DELETION ,biology.organism_classification ,Phenotype ,Yeast ,GENOME ,Biotechnology & Applied Microbiology ,1313 Molecular Medicine ,ACID ,1305 Biotechnology ,Molecular Medicine ,570 Life sciences ,Life Sciences & Biomedicine ,Protein Processing, Post-Translational ,Function (biology) ,Biotechnology - Abstract
Phosphorylation is a critical post-translational modification involved in the regulation of almost all cellular processes. However, fewer than 5% of thousands of recently discovered phosphosites have been functionally annotated. In this study, we devised a chemical genetic approach to study the functional relevance of phosphosites in Saccharomyces cerevisiae. We generated 474 yeast strains with mutations in specific phosphosites that were screened for fitness in 102 conditions, along with a gene deletion library. Of these phosphosites, 42% exhibited growth phenotypes, suggesting that these are more likely functional. We inferred their function based on the similarity of their growth profiles with that of gene deletions and validated a subset by thermal proteome profiling and lipidomics. A high fraction exhibited phenotypes not seen in the corresponding gene deletion, suggestive of a gain-of-function effect. For phosphosites conserved in humans, the severity of the yeast phenotypes is indicative of their human functional relevance. This high-throughput approach allows for functionally characterizing individual phosphosites at scale. ispartof: NATURE BIOTECHNOLOGY vol:40 issue:3 pages:382-+ ispartof: location:United States status: published
- Published
- 2022
- Full Text
- View/download PDF
45. Callus Induction and Regeneration from Anther Cultures of Indonesian Indica Black Rice Cultivar
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Faida Nur Laeli, Kyung-Min Kim, Tri Handoyo, Anisa Maharani, and Wahyu Indra Duwi Fanata
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0106 biological sciences ,Callus formation ,Black rice ,fungi ,Stamen ,food and beverages ,04 agricultural and veterinary sciences ,Plant Science ,Biology ,01 natural sciences ,Plantlet ,Horticulture ,chemistry.chemical_compound ,Murashige and Skoog medium ,chemistry ,Callus ,040103 agronomy & agriculture ,0401 agriculture, forestry, and fisheries ,Kinetin ,Cultivar ,Agronomy and Crop Science ,010606 plant biology & botany ,Biotechnology - Abstract
The assembly of superior varieties and collection of rice germplasm involves the process of selecting and storing elders that have superior genotypic properties and phenotypes. The anther culture techniques on indica black rice cultivar have a high difficulty factor to get plants, because of the low regeneration ability at the plant formation phase from the anther callus. This study aimed to investigate the influence of the cold-pretreatment time on anther, the combination of plant growth regulators (PGR’s) concentrations, and putrescine concentrations in media for the increase callus induction and plant regeneration of indica black rice. The optimization of the cold pre-treatment time was important to obtain the high-frequency callus induction, which showed that anther at the 4°C for 8 days formed the high callus induction (20%). To accelerate the callus induction, the application of 20 µM putrescine in the MS medium could produce more friable embryogenic callus for 24 days with 27% of callus formation. Generally, the optimal medium for the high frequency of callus induction contained 2 mgL−1 NAA+0.5 mgL−1 Kinetin+20 µM putrescine. Especially indica black rice cultivars, the best media to get a high plant regeneration frequency were N6 media containing the combination of 2 mgL−1 IAA and 2,5 mgL−1 Kinetin. The total callus regenerated to plantlet about 12.5%. The study of the callus induction and in-vitro plant regeneration medium for indica black rice were still important to develop to get the best result for other cultivars.
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- 2019
46. Fictions of Obligation: Contract and Romance in Margaret Cavendish and Aphra Behn
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Eun Kyung Min
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Literature ,Literature and Literary Theory ,biology ,business.industry ,Philosophy ,Subject (philosophy) ,06 humanities and the arts ,060202 literary studies ,biology.organism_classification ,Romance ,Politics ,Aphra ,0602 languages and literature ,Obligation ,business - Abstract
This essay reads the short romances of Margaret Cavendish and Aphra Behn as complex responses to contract-based theories of obligation and the model of the political subject who enters into relationships of willing submission. Cavendish and Behn take up the subject of women’s contracts and obligations within the generic constraints of romance, but their romances belie the fiction of women freely and happily contracting with their romance heroes. Far from instancing willing submission, Cavendish’s heroines actively engage with law and go to war to subdue men who prove bad contractors and to model new forms of obligation. Behn’s romances, in contrast, teem with women who are bad contractors and whose flagrant violations of propriety and conjugality pose a sardonic challenge to conventional definitions of women’s obligations. Together, their works trouble the fiction of the willingly bound woman and attest to the diminishing power of romance to model women’s obligations in a time of continuing political crisis.
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- 2019
47. Inhibitory characteristics of flavonol-3-O-glycosides from Polygonum aviculare L. (common knotgrass) against porcine pancreatic lipase
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Jun-Young Park, Pahn-Shick Chang, Chung Sun Kim, and Kyung-Min Park
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0301 basic medicine ,Flavonols ,Hydrolases ,Swine ,Chemical structure ,lcsh:Medicine ,Mass spectrometry ,01 natural sciences ,Article ,03 medical and health sciences ,Animals ,Enzyme kinetics ,Glycosides ,Enzyme Inhibitors ,Medicinal plants ,lcsh:Science ,Pancreas ,chemistry.chemical_classification ,Multidisciplinary ,Chromatography ,biology ,Chemistry ,Plant Extracts ,010401 analytical chemistry ,lcsh:R ,Glycoside ,Polygonum aviculare ,Lipase ,biology.organism_classification ,0104 chemical sciences ,030104 developmental biology ,Enzyme ,Biocatalysis ,lcsh:Q ,Polygonum ,Digestion - Abstract
Pancreatic lipase (PL) is an enzyme that plays an essential role in the digestion of dietary lipids and is a suitable target for an anti-obesity dietary supplement. The objective of this study was to find a novel source of PL inhibitors from Korean medicinal plants and investigate the PL-inhibitory properties of the active constituents. From among 34 kinds of methanolic crude extracts, Polygonum aviculare L. showed the highest PL-inhibitory activity (63.97 ± 0.05% of inhibition). Solvent fractionation and liquid chromatography/mass spectrometry (LC/MS) analysis identified flavonol-3-O-glycosides, flavonol-3-O-(2″-galloyl)-glycosides, and flavonol aglycones as active constituents. Furthermore, the inhibitory characteristics of the major compounds were investigated in terms of enzyme kinetics and fluorescence quenching. The results suggested that the inhibitory activity of the major compounds is closely related to the tertiary structural change in PL, and that differences in inhibitory activity occurred due to slight discrepancies in their chemical structure.
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- 2019
48. Anti-Osteoarthritis and Anti-Arthrodynia Effects of a Mixture of Fermented Achyranthes japonica Nakai, Angelica gigas Nakai, and Eucommia ulmoides Oliver Extracts on Monosodium Iodoacetate-Induced Arthritis in Rats
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Johann Sohn, Hyun Cheol Jeong, Seunghun Lee, Kyung-Min Kim, Dong-Hwan Choi, Sung-Jin Lee, and Min Young Kwon
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Nutrition and Dietetics ,Monosodium iodoacetate ,biology ,Traditional medicine ,ved/biology ,Chemistry ,Achyranthes japonica ,ved/biology.organism_classification_rank.species ,Arthritis ,Eucommia ulmoides ,Osteoarthritis ,biology.organism_classification ,medicine.disease ,Angelica gigas ,medicine ,Arthrodynia ,Fermentation ,Food Science - Published
- 2019
49. Genome-wide association analysis of venous thromboembolism identifies new risk loci and genetic overlap with arterial vascular disease
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Saiju Pyarajan, Nicholas L. Smith, Julie Lynch, Sara Lindström, Michael G. Levin, Marijana Vujkovic, Charles Kooperberg, Danish Saleheen, Qing Shao, William E. Boden, Themistocles L. Assimes, Yan V. Sun, Peter D. Reaven, Sekar Kathiresan, Peter W.F. Wilson, Andrea T. Obi, Daniel J. Rader, Scott L. DuVall, David-Alexandre Trégouët, Jeffery Haessler, Pradeep Natarajan, Christopher Kabrhel, Krishna G. Aragam, Emma Busenkell, Renae Judy, Yunfeng Huang, Mary E. Haas, Peter K. Henke, J. Michael Gaziano, Jie Huang, Scott M. Damrauer, Philip S. Tsao, Kyung Min Lee, Donald R. Miller, John Concato, Kyong-Mi Chang, Jennifer E. Huffman, Mark Chaffin, Christopher J. O'Donnell, Alexander P. Reiner, Derek Klarin, Kelly Cho, Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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Male ,Genome-wide association study ,Coronary Artery Disease ,Disease ,Bioinformatics ,Mice ,0302 clinical medicine ,Risk Factors ,cardiovascular disease ,0303 health sciences ,education.field_of_study ,Venous Thromboembolism ,Middle Aged ,3. Good health ,Stroke ,Prothrombin G20210A ,Female ,Population ,Biology ,Article ,Peripheral Arterial Disease ,03 medical and health sciences ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Plasminogen Activator Inhibitor 1 ,Genetics ,medicine ,Factor V Leiden ,Animals ,Humans ,Genetic Predisposition to Disease ,Vascular Diseases ,cardiovascular diseases ,education ,Aged ,030304 developmental biology ,business.industry ,Case-control study ,population genetics ,equipment and supplies ,medicine.disease ,United Kingdom ,Mice, Inbred C57BL ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Genetic epidemiology ,Genetic Loci ,Case-Control Studies ,genome-wide association studies ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Personalized medicine ,business ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Venous thromboembolism (VTE) is a significant cause of mortality1, yet its genetic determinants remain incompletely defined. We performed a discovery genome-wide association study in the Million Veteran Program and UK Biobank testing ~13 million DNA sequence variants for association with VTE (26,066 cases; 624,053 controls) and meta-analyzed both studies, followed by independent replication with up to 17,672 VTE cases and 167,295 controls. We identified 22 novel loci, bringing the total number of VTE-associated loci to 33 and subsequently fine-mapped these associations. We developed a genome-wide polygenic risk score for VTE that identifies 5% of the population at equivalent incident VTE risk to carriers of the established F5 Leiden (p.R506Q) and prothrombin G20210A mutations. Our data provide new mechanistic insights into the genetic epidemiology of VTE and suggest a greater overlap among venous and arterial cardiovascular disease than previously suggested., Editorial summary Genome-wide analysis of venous thromboembolism identifies 22 new risk loci and facilitates construction of a polygenic risk score. Comparison to arterial vascular disease highlights shared pathophysiology and potential therapeutic strategies.
- Published
- 2019
50. Hyponatremia, Inflammation at Admission, and Mortality in Hospitalized COVID-19 Patients: A Prospective Cohort Study
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Juan Carlos Ayus, Armando Luis Negri, Michael L. Moritz, Kyung Min Lee, Daniel Caputo, Maria Elena Borda, Alan S. Go, and Carlos Eghi
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Vasopressin ,medicine.medical_specialty ,Medicine (General) ,hyponatremia ,medicine.medical_treatment ,Systemic inflammation ,C-reactive protein ,R5-920 ,Internal medicine ,Medicine ,Risk factor ,Prospective cohort study ,Original Research ,Mechanical ventilation ,biology ,business.industry ,Confounding ,COVID-19 ,General Medicine ,medicine.disease ,mortality ,inflammation ,biology.protein ,medicine.symptom ,business ,Hyponatremia - Abstract
Background: Systemic inflammation has been associated with severe coronavirus disease 2019 (COVID-19) disease and mortality. Hyponatremia can result from inflammation due to non-osmotic stimuli for vasopressin production.Methods: We prospectively studied 799 patients hospitalized with COVID-19 between March 7 and November 7, 2020, at Hospital Posadas in Buenos Aires, Argentina in order to evaluate the association between hyponatremia, inflammation, and its impact on clinical outcomes. Admission biochemistries, high-sensitivity C-reactive protein (hsCRP), ferritin, patient demographics, and outcome data were recorded. Outcomes (within 30 days after symptoms) evaluated included ICU admission, mechanical ventilation, dialysis-requiring acute kidney injury (AKI), and in-hospital mortality. Length of hospital stay (in days) were evaluated using comprehensive data from the EHR.Results: Hyponatremia (median Na = 133 mmol/L) was present on admission in 366 (45.8%). Hyponatremic patients had higher hsCRP (median 10.3 [IR 4.8–18.4] mg/dl vs. 6.6 [IR 1.6–14.0] mg/dl, p < 0.01) and ferritin levels (median 649 [IQR 492–1,168] ng/dl vs. 393 [IQR 156–1,440] ng/dl, p = 0.02) than normonatremic patients. Hyponatremia was associated with higher odds of an abnormal hsCRP (unadjusted OR 5.03, 95%CI: 2.52–10.03), and remained significant after adjustment for potential confounders (adjusted OR 4.70 [95%CI: 2.33–9.49], p < 0.01). Hyponatremic patients had increased mortality on unadjusted (HR 3.05, 95%CI: 2.14–4.34) and adjusted (HR 2.76, 95%CI:1.88–4.06) in Cox proportional hazard models. Crude 30-day survival was lower for patients with hyponatremia at admission (mean [SD] survival 22.1 [0.70] days) compared with patients who were normonatremic (mean [SD] survival 27.2 [0.40] days, p < 0.01).Conclusion: Mild hyponatremia on admission is common, is associated with systemic inflammation and is an independent risk factor for hospital mortality.Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT04493268.
- Published
- 2021
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