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김리라,맹필재 충남대학교 생물공학연구소 2007 생물공학연구지 Vol.13 No.-
Cell growth is an important phenomenon for self-renewal, organogenesis, and tumor expansion. This cell growth is tightly regulated on cell cycle by very complex and huge amount factors. Cell cycle is consisted by G (Gap) phase, M (mitosis) phase, and S (Synthesis), which contain specific regulation factors, cyclin and cyclin-dependent kinase (cdk). In other mechanism to regulate cell cycle, cell cycle-checkpoints indicate steps to regulate cell cycle on DNA damage checkpoint and spindle checkpoint. Fission yeast has been used as good model system for investigation of eukaryotic cell cycle. We have known the complete fission yeast genomic sequence and haven plentiful biochemical and proteomic information. On the basis of the information, we can make several mutants to analysis the roles of cell cycle regulatory factors and identify new factors. Here, we introduce how to use yeast model to discover the relation between mutants and cell cycle phenotypes and briefly explain the results from our functional study.
( Ju Hyun Oh ),( Grace Hyun J. Kim ),( David W Dai ),( S Sam Weigt ),( Jonathan G Goldin ),( Lila Pourzand ),( Jooae Choe ),( Fereidoun Abtin ),( Matthew S. Brown ),( Pangyu Teng ),( Jin Woo Song ) 대한결핵 및 호흡기학회 2021 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.129 No.-
Background Interstitial lung disease (ILD) includes a heterogeneous group of disease entities. Idiopathic pulmonary fibrosis (IPF) is ultimately fatal, and accurate diagnosis of IPF is critical to clinical decision making. Visual interpretation of chest high resolution CT (HRCT) is subjective and has limited reproducibility, especially with early disease. So we have previously developed attention-gated deep learning algorithm to diagnosis IPF and machine learning to predict IPF progression. The overall aim of IS-IPF is to collect the data from two centers of excellence and evaluate the robustness of the algorithm. We present the preliminary data of the patients studied following disease classification by the multidisciplinary review committees (MDCs) at UCLA and Asan Medical Center (AMC). Methods The IS-IPF study plans to include 234 IPF and 266 non-IPF cases from two large ILD centers (UCLA and AMC). Eligible patients were evaluated in ILD MDC, were >18 years old, had a HRCT, pulmonary function testing, and a committee diagnosis of IPF or non-IPF. Relevant demographic information was collected from the medical record. Results Total 185 IPF and 266 non-IPF patients’ HRCT images have been collected in the IS-IPF study. By center, 51 IPF and 133 non- IPF patients’ HRCT were collected from UCLA, and 134 IPF and 133 non-IPF patients’ HRCT were collected from AMC. On MDC diagnosis, non-IPF cohorts consisted of 33% hypersensitivity pneumonitis, and 67% other connective tissue disease-ILD. Mean age was 61 years (63 IPF and 58 non-IPF), and 63% were male (82% IPF and 57 % non-IPF). Up to date, the predicted FVC was 74.7% and the predicted DLco was 61.6 % in the IPF cohort. Data collection is on-going. Conclusions These well-characterized cohorts will be used to evaluate HRCT image signatures for distinguishing IPF from other ILD, and predicting patient-specific IPF progression within 2 years of diagnosis.
Kyung-Sun Heo,Sung-Woo Ryoo,Lila Kim,Miyoung Nam,Seung-Tae Baek,Hyemi Lee,Ah-Reum Lee,Song-Kyu Park,Youngwoo Park,Chang-Seon Myung,Dong-Uk Kim,허광래 한국분자세포생물학회 2008 Molecules and cells Vol.26 No.5
Low-density lipoprotein (LDL) induces cell proliferation in human aortic smooth muscle cells (hAoSMCs), which may be involved in atherogenesis and intimal hyperplasia. Recent studies have demonstrated that Cl- channels are related to vessel cell proliferation induced by a variety of stimuli. In this study, we investigated a potential role of Cl- channels in the signaling pathway of LDL effects on hAoSMC proliferation with a focus on the activation of Erk1/2-PI3K/Akt and the subsequent upregulation of Egr-1. Cl- channel blockers, DIDS, but neither NPPB nor Furosemide, completely abolished the LDL-induced DNA synthesis and cell proliferation. Moreover, DIDS, but not NPPB, significantly decreased LDL-stimulated Cl- concentration, as judged by flow cytometry analysis using MQAE as a Cl--detection dye. DIDS pretreatment completely abolished the activation of Erk1/2 and PI3K/Akt in a dose-dependent manner that is the hallmark of LDL activation, as judged by Western blot and proliferation assays. Moreover, pretreatment with DIDS (Cl- channel blockers) but not LY294002 (PI3K inhibitors) completely abolished the LDL-induced upregulation of Egr-1 to the same extent as PD98059 (MEK inhibitors to inhibit Erk), as judged by Western blot and luciferase reporter assays. This is the first report, to our knowledge, that DIDS-sensitive Cl--channels play a key role in the LDL-induced cell proliferation of hAoSMCs via the activation of Erk1/2 and PI3K/Akt and the upregulation of Egr-1.
Thuy Le Lam Nguyen,Yujin Jin,Lila Kim,Kyung-Sun Heo 대한약학회 2022 Archives of Pharmacal Research Vol.45 No.9
Excessive production and migration of vascularsmooth muscle cells (VSMCs) are associated with vascularremodeling that causes vascular diseases, such as restenosisand hypertension. Angiotensin II (Ang II) stimulation is akey factor in inducing abnormal VSMC function. This studyaimed to investigate the eff ects of 6′-sialyllactose (6′SL), ahuman milk oligosaccharide, on Ang II-stimulated cell proliferation,migration and osteogenic switching in rat aorticsmooth muscle cells (RASMCs) and human aortic smoothmuscle cells (HASMCs). Compared with the control group,Ang II increased cell proliferation by activating MAPKs,including ERK1/2/p90RSK/Akt/mTOR and JNK pathways. However, 6′SL reversed Ang II-stimulated cell proliferationand the ERK1/2/p90RSK/Akt/mTOR pathways in RASMCsand HASMCs. Moreover, 6′SL suppressed Ang II-stimulatedcell cycle progression from G0/G1 to S and G2/M phasesin RASMCs. Furthermore, 6′SL eff ectively inhibited cellmigration by downregulating NF-κB-mediated MMP2/9 andVCAM-1 expression levels. Interestingly, in RASMCs, 6′SLattenuated Ang II-induced osteogenic switching by reducingthe production of p90RSK-mediated c-fos and JNK-mediatedc-jun, leading to the downregulation of AP-1-mediatedosteopontin production. Taken together, our data suggestthat 6′SL inhibits Ang II-induced VSMC proliferation and migration by abolishing the ERK1/2/p90RSK-mediated Aktand NF-κB signaling pathways, respectively, and osteogenicswitching by suppressing p90RSK- and JNK-mediated AP-1activity.
Heo, Kyung-Sun,Ryoo, Sung-Woo,Kim, Lila,Nam, Miyoung,Baek, Seung-Tae,Lee, Hyemi,Lee, Ah-Reum,Park, Song-Kyu,Park, Youngwoo,Myung, Chang-Seon,Kim, Dong-Uk,Hoe, Kwang-Lae Korean Society for Molecular Biology 2008 Molecules and cells Vol.26 No.5
<P>Low-density lipoprotein (LDL) induces cell proliferation in human aortic smooth muscle cells (hAoSMCs), which may be involved in atherogenesis and intimal hyperplasia. Recent studies have demonstrated that Cl- channels are related to vessel cell proliferation induced by a variety of stimuli. In this study, we investigated a potential role of Cl- channels in the signaling pathway of LDL effects on hAoSMC proliferation with a focus on the activation of Erk1/2-PI3K/Akt and the subsequent upregulation of Egr-1. Cl- channel blockers, DIDS, but neither NPPB nor Furosemide, completely abolished the LDL-induced DNA synthesis and cell proliferation. Moreover, DIDS, but not NPPB, significantly decreased LDL-stimulated Cl- concentration, as judged by flow cytometry analysis using MQAE as a Cl--detection dye. DIDS pretreatment completely abolished the activation of Erk1/2 and PI3K/Akt in a dose-dependent manner that is the hallmark of LDL activation, as judged by Western blot and proliferation assays. Moreover, pretreatment with DIDS (Cl- channel blockers) but not LY294002 (PI3K inhibitors) completely abolished the LDL-induced upregulation of Egr-1 to the same extent as PD98059 (MEK inhibitors to inhibit Erk), as judged by Western blot and luciferase reporter assays. This is the first report, to our knowledge, that DIDS-sensitive Cl--channels play a key role in the LDL-induced cell proliferation of hAoSMCs via the activation of Erk1/2 and PI3K/Akt and the upregulation of Egr-1.</P>
Elsa M. Janle,Mary Ann Lila,Michael Grannan,Lauren Wood,Aine Higgins,Gad G. Yousef,Randy B. Rogers,Helen Kim,George S. Jackson,Lap Ho,Connie M. Weaver 한국식품영양과학회 2010 Journal of medicinal food Vol.13 No.4
Grape polyphenols confer potential health benefits, including prevention of neurodegenerative diseases. To determine the absorption and tissue distribution of the complex grape polyphenol mixture, 14C-labeled polyphenols were biosynthesized by grape cell suspension cultures, during co-incubation with radioisotopically labeled sucrose, and fractionated into polyphenolic subfractions. The pharmacokinetics and distribution of grape polyphenols into blood, brain, and peripheral interstitial fluid were determined by tracking the 14C label. The blood peak 14C concentration of the fractions ranged from 15 minutes to 4 hours. Absorption and tissue distribution varied greatly between fractions. Concentrations in interstitial fluid were lower than in blood. The amount of residual label in the brain at 24 hours ranged from 0.1% to 1.7% of the dose, depending on the fraction. 14C label found in the brain tissue and brain microdialysate indicated that grape polyphenols or their metabolites are able to cross the blood–brain barrier. Using 14C-labeled plant polyphenols it is possible to track the compounds or their metabolic products into any tissue and determine distribution patterns in spite of low concentrations. A central question regarding the potential role of dietary polyphenolics in neurodegenerative research is whether they are bioavailable in the brain. Our observations indicate that some grape-derived polyphenolics do reach the brain, which suggests their potential value for applications in neurodegenerative disorders.
Yujin Jin,Hyesu Jeon,Thuy Le Lam Nguyen,Lila Kim,Kyung-Sun Heo 대한약학회 2023 Archives of Pharmacal Research Vol.46 No.12
Acute lung injury (ALI) is the leading cause of respiratory diseases induced by uncontrolled inflammation and cell death. Lipopolysaccharide (LPS) is a major trigger of ALI in the progression through macrophage differentiation and the accelerated release of pro-inflammatory cytokines. The present study aimed to investigate the protective effects of human milk oligosaccharides, specifically 3′-sialyllactose (3′-SL) and 6′-sialyllactose (6′-SL), on LPS-induced ALI and elucidate their underlying signaling pathways. The inhibitory effects of 3′-SL and 6′-SL on inflammation were evaluated using LPS-treated RAW 264.7 macrophages. To establish the ALI model, mice were treated with 10 mg/kg LPS for 24 h. Histological changes in the lung tissues were assessed using hematoxylin and eosin staining and immunofluorescence. LPS causes thickening of the alveolar wall infiltration of immune cells in lung tissues and increased serum levels of TNF-α, IL-1β, and GM-CSF. However, these effects were significantly alleviated by 100 mg/kg of 3′-SL and 6′-SL. Consistent with the inhibitory effects of 3′-SL and 6′-SL on LPS-induced pro-inflammatory cytokine secretion in serum, 3′-SL and 6′-SL suppressed mRNA expression of TNF-α, IL-1β, MCP-1, iNOS, and COX2 in LPS-induced RAW 264.7 cells. Mechanistically, 3′-SL and 6′-SL abolished LPS-mediated phosphorylation of NF-κB and STAT1. Interestingly, fludarabine treatment, a STAT1 inhibitor, did not affect LPS-mediated NF-κB phosphorylation. In summary, 3′-SL and 6′-SL protect LPS-induced macrophage activation and ALI through the STAT1 and NF-κB signaling pathways.
Dung Van Nguyen,Thuy Le Lam Nguyen,Yujin Jin,Lila Kim,Chang-Seon Myung,Kyung-Sun Heo 대한약학회 2022 Archives of Pharmacal Research Vol.45 No.11
Disruption of the endothelial barrier functionand reduction in cell migration leads to endothelial dysfunction. One of the most abundant human milk oligosaccharides,6′-sialylactose (6′-SL), is reported to exert variousbiological functions related to infl ammatory responses. Inthis study, we evaluated the eff ects of 6′-SL on lipopolysaccharide(LPS)-induced infl ammation caused by endothelialbarrier damage. Our results showed that LPS at 500 ng/mLstrongly not only abolished cell migration but also hyperactivatedMAPK and NF-κB pathways. 6′-SL suppressedLPS-induced endothelial infl ammation via ERK1/2, p38,and JNK MAPK pathways. 6′-SL supported endothelialjunctions by upregulating PECAM-1 expression and mRNAlevels of tight junctions, such as ZO-1 and occludin, whichwere downregulated by LPS stimulation. It signifi cantlyinhibited the nuclear translocation of NF-κB, along withthe downregulation of infl ammatory cytokines, includingTNF-α, IL-1β, MCP-1, VCAM-1, and ICAM-1. Furthermore,6′-SL abolished NF-κB-mediated STAT3 in controllingendothelial migration and hyperpermeability viadownregulating STAT3 activation and nuclear translocation. Finally, LPS induced over-expression of VCAM-1 and ZO-1disassembly in both atheroprone and atheroprotective areasof mouse aorta, which were reversed by 6′-SL treatment. Altogether, our fi ndings suggest that 6′-SL is a potent therapeuticagent for modulating infl ammatory responses andendothelial hyperpermeability.