• Molecules and Cells
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• v.42 no.3
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• pp.237-244
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• 2019

Understanding the mechanisms of cancer drug resistance is a critical challenge in cancer therapy. For many cancer drugs, various resistance mechanisms have been identified such as target alteration, alternative signaling pathways, epithelial-mesenchymal transition, and epigenetic modulation. Resistance may arise via multiple mechanisms even for a single drug, making it necessary to investigate multiple independent models for comprehensive understanding and therapeutic application. In particular, we hypothesize that different resistance processes result in distinct gene expression changes. Here, we present a web-based database, CDRgator (Cancer Drug Resistance navigator) for comparative analysis of gene expression signatures of cancer drug resistance. Resistance signatures were extracted from two different types of datasets. First, resistance signatures were extracted from transcriptomic profiles of cancer cells or patient samples and their resistance-induced counterparts for >30 cancer drugs. Second, drug resistance group signatures were also extracted from two large-scale drug sensitivity datasets representing ~1,000 cancer cell lines. All the datasets are available for download, and are conveniently accessible based on drug class and cancer type, along with analytic features such as clustering analysis, multidimensional scaling, and pathway analysis. CDRgator allows meta-analysis of independent resistance models for more comprehensive understanding of drug-resistance mechanisms that is difficult to accomplish with individual datasets alone (database URL: http://cdrgator.ewha.ac.kr).

• Korean Journal of Acupuncture
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• v.35 no.4
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• pp.187-202
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• 2018

Objectives : Non-invasive transcranial electrical stimulation is one of therapeutic interventions to change in neural excitability of the cortex. Transcranial electro-acupuncture (TEA) can modulate brain functions through changes in cortical excitability as a model of non-invasive transcranial electrical stimulation. Some composites of fermented Scutellaria baicalenis (FSB) can activate intercellular signaling pathways for activation of brain-derived neurotrophic factor that is critical for formation of neural plasticity in stroke patients. This study was aimed at evaluation of combinatory treatment of TEA and FSB on behavior recovery and cortical neural excitability in rodent focal stroke model. Methods : Focal ischemic stroke was induced by photothrombotic injury to the motor cortex of adult rats. Application of TEA with 20 Hz and $200{\mu}A$ in combination with daily oral treatment of FBS was given to stroke animals for 3 weeks. Motor recovery was evaluated by rotating bean test and ladder working test. Electrical activity of cortical pyramidal neurons of stroke model was evaluated by using multi-channel extracellular recording technique and thallium autometallography. Results : Compared with control stroke group who did not receive any treatment, Combination of TEA and FSB treatment resulted in more rapid recovery of forelimb movement following focal stroke. This combination treatment also elicited increase in spontaneous firing rate of putative pyramidal neurons. Furthermore expression of metabolic marker for neural excitability was upregulated in peri-infract area under thallium autometallography. Conclusions : These results suggest that combination treatment of TEA and FSB can be a possible remedy for motor recovery in focal stroke.

• Korean Journal of Veterinary Research
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• v.58 no.4
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• pp.201-209
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• 2018

Canine mammary tumors are among the most frequently observed cutaneous tumors in female dogs. Cancer stem cells (CSCs), referred to as tumor-initiating cells, are thought to have properties similar to normal stem cells such as the ability to self-renewal and to differentiate into various cell types. Biological understanding of CSCs and the critical pathways involved in their maintenance are important in research and therapy for mammary tumors. We conducted the present study on sphere formation from REM134 cells by using methylcellulose to produce tumorspheres on a large scale and compared the specific markers of the spheres-formed and plating-cultured REM134 cells. The results revealed that the tumorspheres cultured in methylcellulose had higher seeding density and improved morphology compared to those produced in normal sphere formation medium. Expression levels of stemness markers and CSC-related markers were higher in tumorsphere-forming cells than in plating-cultured cells. Subsequently, we transplanted the tumorsphere-forming and plating-cultured cells into female nude mice to examine their tumorigenic potential. Tumor volume increased rapidly in mice transplanted with tumorsphere-derived cells compared to plating-cultured cells. We observed a novel sphere-forming condition for REM134 cells and showed that REM134 cell tumorspheres can exhibit improved CSC properties.

• Journal of Society of Preventive Korean Medicine
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• v.26 no.1
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• pp.11-23
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• 2022

Objectives : The aim of this study was to develop a clinical pathway (CP) model for the integrative treatment of non-invasive breast cancer, with western medicine and Korean traditional medicine. Methods : The checklist model was composed in four types according to the target patients: DCIS inpatients, DCIS outpatients, LCIS inpatients, LCIS outpatients. The vertical axis of the pathway consists of 11 categories of actions applied to the patient. The horizontal axis was in accordance with the flow of time, comprising three periods during inpatient care and seven periods during outpatient care. In addition, CP was also composed in flow chart form. The pathway model was developed through a literature review of clinical practice guidelines, conference publications, papers, books, and websites. Results : The integrative CP model for non-invasive breast cancer was developed. Conclusions : The goal of the CP suggested in this study was to improve non-invasive breast cancer patients' quality of life and to supplement conventional treatment, by alleviating the side effects. The model developed through this study could serve as the basis when developing CPs in a real-world integrative medical environment. This could lead to a reduction in cost and time for CP development, thus bringing about efficiency in the clinical setting.

• Journal of Ginseng Research
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• v.46 no.4
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• pp.572-584
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• 2022

Background: Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion of trinucleotide CAG repeat in the Huntingtin (Htt) gene. The major pathogenic pathways underlying HD involve the impairment of cellular energy homeostasis and DNA damage in the brain. The protein kinase ataxia-telangiectasia mutated (ATM) is an important regulator of the DNA damage response. ATM is involved in the phosphorylation of AMP-activated protein kinase (AMPK), suggesting that AMPK plays a critical role in response to DNA damage. Herein, we demonstrated that expression of polyQ-expanded mutant Htt (mHtt) enhanced the phosphorylation of ATM. Ginsenoside is the main and most effective component of Panax ginseng. However, the protective effect of a ginsenoside (compound K, CK) in HD remains unclear and warrants further investigation. Methods: This study used the R6/2 transgenic mouse model of HD and performed behavioral tests, survival rate, histological analyses, and immunoblot assays. Results: The systematic administration of CK into R6/2 mice suppressed the activation of ATM/AMPK and reduced neuronal toxicity and mHTT aggregation. Most importantly, CK increased neuronal density and lifespan and improved motor dysfunction in R6/2 mice. Conversely, CK enhanced the expression of Bcl2 protected striatal cells from the toxicity induced by the overactivation of mHtt and AMPK. Conclusions: Thus, the oral administration of CK reduced the disease progression and markedly enhanced lifespan in the transgenic mouse model (R6/2) of HD.

• Molecules and Cells
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• v.45 no.8
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• pp.537-549
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• 2022

Preproenkephalin (PPE) is a precursor molecule for multiple endogenous opioid peptides Leu-enkephalin (ENK) and Met-ENK, which are involved in a wide variety of modulatory functions in the nervous system. Despite the functional importance of ENK in the brain, the effect of brain-derived factor(s) on PPE expression is unknown. We report the dual effect of neural epidermal growth factor (EGF)-like-like 2 (NELL2) on PPE gene expression. In cultured NIH3T3 cells, transfection of NELL2 expression vectors induced an inhibition of PPE transcription intracellularly, in parallel with downregulation of protein kinase C signaling pathways and extracellular signal-regulated kinase. Interestingly, these phenomena were reversed when synthetic NELL2 was administered extracellularly. The in vivo disruption of NELL2 synthesis resulted in an increase in PPE mRNA level in the rat brain, suggesting that the inhibitory action of intracellular NELL2 predominates the activation effect of extracellular NELL2 on PPE gene expression in the brain. Biochemical and molecular studies with mutant NELL2 structures further demonstrated the critical role of EGF-like repeat domains in NELL2 for regulation of PPE transcription. These are the first results to reveal the spatio-specific role of NELL2 in the homeostatic regulation of PPE gene expression.

• Journal of Microbiology and Biotechnology
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• v.32 no.10
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• pp.1245-1252
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• 2022

Induced pluripotent stem cells (iPSCs) can be generated from somatic cells using Oct4, Sox2, Klf4, and c-Myc (OSKM). Small molecules can enhance reprogramming. Licochalcone D (LCD), a flavonoid compound present mainly in the roots of Glycyrrhiza inflata, acts on known signaling pathways involved in transcriptional activity and signal transduction, including the PGC1-α and MAPK families. In this study, we demonstrated that LCD improved reprogramming efficiency. LCD-treated iPSCs (LCD-iPSCs) expressed pluripotency-related genes Oct4, Sox2, Nanog, and Prdm14. Moreover, LCD-iPSCs differentiated into all three germ layers in vitro and formed chimeras. The mesenchymal-to-epithelial transition (MET) is critical for somatic cell reprogramming. We found that the expression levels of mesenchymal genes (Snail2 and Twist) decreased and those of epithelial genes (DSP, Cldn3, Crb3, and Ocln) dramatically increased in OR-MEF (OG2^+/+/ROSA26^+/+) cells treated with LCD for 3 days, indicating that MET effectively occurred in LCD-treated OR-MEF cells. Thus, LCD enhanced the generation of iPSCs from somatic cells by promoting MET at the early stages of reprogramming.

• Journal of Korean Medicine Rehabilitation
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• v.32 no.4
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• pp.73-82
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• 2022

Objectives The purpose of this study is to develop a case study protocol to complete final version of Korean medicine clinical pathway (CP) by applying Korean medicine CP based on carpal tunnel syndrome Korean medicine clinical practice guidelines developed by clinical experts to clinical field. Methods After applying previously developed CP, 10-point Likert scale questionnaires on satisfaction of CP, appropriateness and improvement on out patient department (OPD) treatments are carried out in the 2^nd week of OPD treatment. An open-ended questionnaire is also carried out to ask if there is any requirement to be added or improved among CP interventions. Results Final version of CP is going to be completed based on the questionnaire, excluding articles of which average or median value is less than 5 from 10-point Likert scale. Conclusions This evidence-based case study protocol is expected to contribute development of carpal tunnel syndrome clinical pathway.

• Genomics & Informatics
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• v.21 no.2
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• pp.16.1-16.14
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• 2023

Coronavirus disease 2019 (COVID-19) is a viral infection produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus epidemic, which was declared a global pandemic in March 2020. The World Health Organization has recorded around 43.3 billion cases and 59.4 million casualties to date, posing a severe threat to global health. Severe COVID-19 indicates viral pneumonia caused by the SARS-CoV-2 infections, which can induce fatal consequences, including acute respiratory distress syndrome (ARDS). The purpose of this research is to better understand the COVID-19 and ARDS pathways, as well as to find targeted single nucleotide polymorphism. To accomplish this, we retrieved over 100 patients' samples from the Sequence Read Archive, National Center for Biotechnology Information. These sequences were processed through the Galaxy server next generation sequencing pipeline for variant analysis and then visualized in the Integrative Genomics Viewer, and performed statistical analysis using t-tests and Bonferroni correction, where six major genes were identified as DNAH7, CLUAP1, PPA2, PAPSS1, TLR4, and IFITM3. Furthermore, a complete understanding of the genomes of COVID-19-related ARDS will aid in the early identification and treatment of target proteins. Finally, the discovery of novel therapeutics based on discovered proteins can assist to slow the progression of ARDS and lower fatality rates.

• Genomics & Informatics
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• v.21 no.1
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• pp.3.1-3.10
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• 2023

Characterization as well as prediction of the secondary and tertiary structure of hypothetical proteins from their amino acid sequences uploaded in databases by in silico approach are the critical issues in computational biology. Severe acute respiratory syndrome-associated coronavirus (SARS-CoV), which is responsible for pneumonia alike diseases, possesses a wide range of proteins of which many are still uncharacterized. The current study was conducted to reveal the physicochemical characteristics and structures of an uncharacterized protein Q6S8D9_SARS of SARS-CoV. Following the common flowchart of characterizing a hypothetical protein, several sophisticated computerized tools e.g., ExPASy Protparam, CD Search, SOPMA, PSIPRED, HHpred, etc. were employed to discover the functions and structures of Q6S8D9_SARS. After delineating the secondary and tertiary structures of the protein, some quality evaluating tools e.g., PROCHECK, ProSA-web etc. were performed to assess the structures and later the active site was identified also by CASTp v.3.0. The protein contains more negatively charged residues than positively charged residues and a high aliphatic index value which make the protein more stable. The 2D and 3D structures modeled by several bioinformatics tools ensured that the proteins had domain in it which indicated it was functional protein having the ability to trouble host antiviral inflammatory cytokine and interferon production pathways. Moreover, active site was found in the protein where ligand could bind. The study was aimed to unveil the features and structures of an uncharacterized protein of SARS-CoV which can be a therapeutic target for development of vaccines against the virus. Further research are needed to accomplish the task.