• Genomics & Informatics
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• 제21권2호
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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.

• 대한한의학회지
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• 제45권1호
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• pp.114-125
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• 2024

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

• BMB Reports
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• 제48권1호
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• pp.54-59
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• 2015

IL-10-producing B (Breg) cells regulate various immune responses. However, their phenotype remains unclear. CD40 expression was significantly increased in B cells by LPS, and the Breg cells were also enriched in $CD40^{hi}CD5^+$ B cells. Furthermore, CD40 expression on Breg cells was increased by IL-10, CD40 ligand, and B cell-activating factor, suggesting that $CD40^{hi}$ is a common phenotype of Breg cells. LPS-induced CD40 expression was largely suppressed by an anti-IL-10 receptor antibody and in IL-$10^{-/-}CD5^+CD19^+$ B cells. The autocrine effect of IL-10 on the CD40 expression was largely suppressed by an inhibitor of JAK/STAT3. In vivo, the LPS treatment increased the population of $CD40^{hi}CD5^+$ Breg cells in mice. However, the population of $CD40^{hi}CD5^+$ B cells was minimal in IL-$10^{-/-}$ mice by LPS. Altogether, our findings show that Breg cells are largely enriched in $CD40^{hi}CD5^+$ B cells and the autocrine effect of IL-10 is critical to the formation of $CD40^{hi}CD5^+$ Breg cells.

• Molecular & Cellular Toxicology
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• 제5권3호
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• pp.193-197
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• 2009

Suppressors of cytokine signaling (SOCS) proteins were originally identified as negative feedback regulators of cytokine signaling and include the Janus kinase/Signal transducer and activator of transcription (JAK/STAT) pathways. Recent studies have shown that SOCS proteins negatively regulate the receptor tyrosine kinase (RTK) pathway including the insulin receptor (IR), EGFR, and KIT signaling pathways. In addition, SOCS1 and SOCS3 have been reported to have anti-tumor effects in human hepatocellular carcinoma (HCC). However, it is uncertain whether other members of the SOCS family are associated with tumor development and progression. In this study, to investigate whether SOCS6 is aberrantly regulated in HCC, we examined the expression level of SOCS6 in HCC by Western blot analysis and immunohistochemical staining. The results showed that SOCS6 was down-regulated in all examined HCCs compared to the corresponding normal tissues. In addition, expression of SOCS6 was observed in the cytoplasm of most normal and precancerous tissue, but not in the HCCs by immunohistochemical staining. This is first report to demonstrate that SOCS6 is aberrantly regulated in HCC. These findings suggest that underexpression of SOCS6 is involved in hepatocarcinogenesis, and SOCS6 may play a role, as a tumor suppressor, in HCC development and progression.

• 대한한의학회지
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• 제31권2호
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• pp.91-108
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• 2010

Background & Objective: The aim of this study was to investigate the effect of P. radix on the inflammatory related gene expression in IL-$1{\beta}$-stimulated primary human gingival fibroblast using Whole Transcript Sense Target (WT-ST). Method: Human gingival fibroblast was incubated with P. radix [100 or $200\;{\mu}g/ml$], and IL-$1{\beta}$ [$1ng/m{\ell}$] added an hour later. After 24h, total RNA was extracted using RNeasy Mini Kit and the whole gene expression patterns were performed using WT-ST Labeling $Assay^{(R)}$. Result: In the DEG results, 782 genes were up-regulated in the IL-$1{\beta}$-treated group as compared to control and among those, 43 genes were associated with inflammation. 981 genes were down-regulated after treatment with IL-$1{\beta}$ and of those 7 genes were associated with inflammation. 1439 genes were up-regulated after treatment with P. radix plus IL-$1{\beta}$-treated when compared to IL-$1{\beta}$-treated alone group and 1225 genes were down-regulated in the same condition. Among the down-regulated genes, 5 were associated with inflammation- and inhibitor genes such as GDF15 and LIF. In the analysis of the P. radix plus IL-$1{\beta}$-treated group, the most significant pathways were the cytokine-cytokine receptor interaction, toll-like receptor signaling, JAK-STAT signaling and tyrosine metabolism. The gene expression patterns in the P. radix $200{\mu}g/m{\ell}$ plus IL-$1{\beta}$-treated group appear to be more involved in the metabolism-related pathways than in the $100{\mu}g/m{\ell}$ plus IL-$1{\beta}$-treated group. Conclusion & Discussion: By microarray analysis of gene expression data, we are able to identify gene expression patterns associated with not only anti-inflammation effect but also transcription function of P. radix.

• Biomolecules & Therapeutics
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• 제27권5호
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• pp.492-501
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• 2019

Nitrogen-containing heterocycles such as quinoline, quinazolinones and indole are scaffolds of natural products and have broad biological effects. During the last years those structures have been intensively synthesized and modified to yield new synthetic molecules that can specifically inhibit the activity of dysregulated protein kinases in cancer cells. Herein, a series of newly synthesized isoquinolinamine (FX-1 to 8) and isoindoloquinazolinone (FX-9, FX-42, FX-43) compounds were evaluated in regards to their anti-leukemic potential on human B- and T- acute lymphoblastic leukemia (ALL) cells. Several biological effects were observed. B-ALL cells (SEM, RS4;11) were more sensitive against isoquinolinamine compounds than T-ALL cells (Jurkat, CEM). In SEM cells, metabolic activity decreased with $10{\mu}M$ up to 26.7% (FX-3), 25.2% (FX-7) and 14.5% (FX-8). The 3-(p-Tolyl) isoquinolin-1-amine FX-9 was the most effective agent against B- and T-ALL cells with IC50 values ranging from 0.54 to $1.94{\mu}M$. None of the tested compounds displayed hemolysis on erythrocytes or cytotoxicity against healthy leukocytes. Anti-proliferative effect of FX-9 was associated with changes in cell morphology and apoptosis induction. Further, influence of FX-9 on PI3K/AKT, MAPK and JAK/STAT signaling was detected but was heterogeneous. Functional inhibition testing of 58 kinases revealed no specific inhibitory activity among cancer-related kinases. In conclusion, FX-9 displays significant antileukemic activity in B- and T-ALL cells and should be further evaluated in regards to the mechanisms of action. Further compounds of the current series might serve as templates for the design of new compounds and as basic structures for modification approaches.

• Asian-Australasian Journal of Animal Sciences
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• 제32권5호
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• pp.614-628
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• 2019

Objective: The inhibitory leukocyte immunoglobulin-like receptors (LILRBs) play an important role in innate immunity. The present study represents the first description of the cloning and structural and functional analysis of LILRB1 and LILRB3 isolated from two genetically disparate chicken lines. Methods: Chicken LILRB1-3 genes were identified by bioinformatics approach. Expression studies were performed by transfection, quantitative polymerase chain reaction. Signal transduction was analyzed by western blots, immunoprecipitation and flow cytometric. Cytokine levels were determined by enzyme-linked immunosorbent assay. Results: Amino acid homology and phylogenetic analyses showed that the homologies of LILRB1 and LILRB3 in the chicken line 6.3 to those proteins in the chicken line 7.2 ranged between 97%-99%, while homologies between chicken and mammal proteins ranged between 13%-19%, and 13%-69%, respectively. Our findings indicate that LILRB1 and LILRB3 subdivided into two groups based on the immunoreceptor tyrosine-based inhibitory motifs (ITIM) present in the transmembrane domain. Chicken line 6.3 has two ITIM motifs of the sequence LxYxxL and SxYxxV while line 7.2 has two ITIM motifs of the sequences LxYxxL and LxYxxV. These motifs bind to SHP-2 (protein tyrosine phosphatase, non-receptor type 11) that plays a regulatory role in immune functions. Moreover, our data indicate that LILRB1 and LILRB3 associated with and activated major histocompatibility complex (MHC) class I and ${\beta}2-microglobulin$ and induced the expression of transporters associated with antigen processing, which are essential for MHC class I antigen presentation. This suggests that LILRB1 and LILRB3 are transcriptional regulators, modulating the expression of components in the MHC class I pathway and thereby regulating immune responses. Furthermore, LILRB1 and LILRB3 activated Janus kinase2/tyrosine kinase 2 (JAK2/TYK2); signal transducer and activator of transcription1/3 (STAT1/3), and suppressor of cytokine signaling 1 genes expressed in Macrophage (HD11) cells, which induced Th1, Th2, and Th17 cytokines. Conclusion: These data indicate that LILRB1 and LILRB3 are innate immune receptors associated with SHP-2, MHC class I, ${\beta}2-microglobulin$, and they activate the Janus kinase/signal transducer and activator of transcription signaling pathway. Thus, our study provides novel insights into the regulation of immunity and immunopathology.

• Journal of Animal Science and Technology
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• 제64권5호
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• pp.922-936
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• 2022

5-Hydroxytryptamine (5-HT), a monoamine, as a local regulator in the mammary gland is a chemical signal produced by the mammary epithelium cell. In cows, studies have shown that 5-HT is associated with epithelial cell apoptosis during the degenerative phase of the mammary gland. However, studies in other tissues have shown that 5-HT can effectively promote cell viability. Whether 5-HT could have an effect on mammary cell viability in dairy cows is still unknown. The purpose of this study was to determine: (1) effect of 5-HT on the viability of bovine mammary epithelial cells and its related signaling pathways, (2) interaction between prolactin (PRL) and 5-HT on the cell viability. The bovine mammary alveolar cell-T (MAC-T) were cultured with different concentrations of 5-HT for 12, 24, 48 or 72 hours, and then were assayed using cell counting kit-8, polymerase chain reaction (PCR) and immunobloting. The results suggested that 20 μM 5-HT treatment for 12 or 24 h promote cell viability, which was mainly induced by the activation of 5-HT receptor (5-HTR) 1B and 4, because the increase caused by 5-HT vanished when 5-HTR 1B and 4 was blocked by SB224289 and SB204070. And protein expression of mammalian target of rapamycin (mTOR), eukaryotic translation elongation factor 2 (eEF2), janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5) were decreased after blocking 5-HT 1B and 4 receptors. When MAC-T cells were treated with 5-HT and PRL simultaneously for 24 h, both the cell viability and the level of mTOR protein were significantly higher than that cultured with 5-HT or PRL alone. In conclusion, our study suggested that 5-HT promotes the viability of MAC-T cells by 5-HTR 1B and/or 4. Furthermore, there is a reciprocal relationship between PRL and 5-HT.

• 생명과학회지
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• 제33권5호
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• pp.397-405
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• 2023

항산화제로서 산화적 손상의 방지에 중요한 역할을 하는 것으로 알려진 glutathione (GSH)의 면역 조절에 대한 연구는 현재까지 제대로 이루어지지 않았다. 본 연구에서 우리는 환원형 GSH인 luthione^®이 RAW 264.7 세포에서 면역 강화 효과가 있는지를 조사하였다. 유세포 분석 및 면역 형광 실험의 결과에 의하면, luthione은 대조군 세포에 비해 대식세포의 대표적인 기능인 식세포 활성을 luthione 처리 농도 의적으로 증가시키는 것으로 나타났다. 또한, cytokine array의 결과에 의하면, IL-5, IL-1β와 IL-27의 발현이 luthione이 처리된 세포에서 유의하게 증가하였다. 아울러 luthione에 의한 TNF-α 및 IL-1β의 생성 증가는 그들의 단백질 발현 증가를 통해 이루어졌으며, NO 및 PGE₂와 같은 면역 매개체 유리의 증가는 iNOS 및 COX-2의 발현 증가와 관련이 있었으며, 이는 M1 대식세포 분화 마커인 CD86 발현의 증가와 연관성이 있었다. 그리고 heatmap 분석을 통하여 SOCS1/3 매개 STAT/JAK 신호 전달 경로가 luthione에 의한 면역 조절 증가에 관여함을 확인하였다. 결론적으로, 우리의 결과는 luthione이 M1 macrophage polarization의 분자 조절자로 작용하여 면역 능력을 향상시킬 수 있음을 시사한다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권8호
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• pp.3395-3402
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• 2015

Background: Preoperative 5-fluorouracil (5-FU)-based chemoradiotherapy is a standard treatment for locally advanced colorectal cancer (CRC). However, CRC cells often develop chemoradiation resistance (CRR). Recent studies have shown that long non-coding RNA (lncRNA) plays critical roles in a myriad of biological processes and human diseases, as well as chemotherapy resistance. Since the roles of lncRNAs in 5-FU-based CRR in human CRC cells remain unknown, they were investigated in this study. Materials and Methods: A 5-FU-based concurrent CRR cell model was established using human CRC cell line HCT116. Microarray expression profiling of lncRNAs and mRNAs was undertaken in parental HCT116 and 5-FU-based CRR cell lines. Results: In total, 2,662 differentially expressed lncRNAs and 2,398 mRNAs were identified in 5-FU-based CRR HCT116 cells when compared with those in parental HCT116. Moreover, 6 lncRNAs and 6 mRNAs found to be differentially expressed were validated by quantitative real time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated involvement of many, such as Jak-STAT, PI3K-Akt and NF-kappa B signaling pathways. To better understand the molecular basis of 5-FU-based CRR in CRC cells, correlated expression networks were constructed based on 8 intergenic lncRNAs and their nearby coding genes. Conclusions: Changes in lncRNA expression are involved in 5-FU-based CRR in CRC cells. These findings may provide novel insight for the prognosis and prediction of response to therapy in CRC patients.