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| WoS | SCOPUS | Document Type | Document Title | Abstract | Authors | Affiliation | ResearcherID (WoS) | AuthorsID (SCOPUS) | Author Email(s) | Journal Name | JCR Abbreviation | ISSN | eISSN | Volume | Issue | WoS Edition | WoS Category | JCR Year | IF | JCR (%) | FWCI | FWCI Update Date | WoS Citation | SCOPUS Citation | Keywords (WoS) | KeywordsPlus (WoS) | Keywords (SCOPUS) | KeywordsPlus (SCOPUS) | Language | Publication Stage | Publication Year | Publication Date | DOI | JCR Link | DOI Link | WOS Link | SCOPUS Link |
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| ○ | ○ | Article | Multiple Functions of Fubp1 in Cell Cycle Progression and Cell Survival | The discovery of novel and critical genes implicated in malignant development is a topic of high interest in cancer research. Intriguingly, a group of genes named "double-agent" genes were reported to have both oncogenic and tumor-suppressive functions. To date, less than 100 "double-agent" genes have been documented. Fubp1 is a master transcriptional regulator of a subset of genes by interacting with a far upstream element (FUSE). Mounting evidence has collectively demonstrated both the oncogenic and tumor suppressive roles of Fubp1 and the debate regarding its roles in tumorigenesis has been around for several years. Therefore, the detailed molecular mechanisms of Fubp1 need to be determined in each context. In the present study, we showed that the Fubp1 protein level was enriched in the S phase and we identified that Fubp1 deficiency altered cell cycle progression, especially in the S phase, by downregulating the mRNA expression levels ofCcnagenes encoding cyclin A. Although this Fubp1-cyclin A axis appears to exist in several types of tumors, Fubp1 showed heterogeneous expression patterns among various cancer tissues, suggesting it exhibits multiple and complicated functions in cancer development. In addition, we showed that Fubp1 deficiency confers survival advantages to cells against metabolic stress and anti-cancer drugs, suggesting that Fubp1 may play both positive and negative roles in malignant development. | Kang, Mingyu; Kim, Hyeon Ji; Kim, Tae-Jun; Byun, Jin-Seok; Lee, Jae-Ho; Lee, Deok Heon; Kim, Wanil; Kim, Do-Yeon | Kyungpook Natl Univ, Sch Dent, Dept Pharmacol, Daegu 700412, South Korea; Kyungpook Natl Univ, Sch Dent, Dept Oral Med, Daegu 700412, South Korea; Keimyung Univ, Dept Anat, Sch Med, Daegu 42601, South Korea; Kyungpook Natl Univ, Kyungpook Natl Univ Hosp, Dept Thorac & Cardiovasc Surg, Sch Med, Daegu 42601, South Korea; Daegu Haany Univ, Coll Bioind, Dept Cosmet Sci & Technol, Gyongsan 712715, South Korea; Kyungpook Natl Univ, Sch Dent, Brain Sci & Engn Inst, Dept Pharmacol, Daegu 700412, South Korea | Kim, Hee/AAU-6368-2021; Lee, Jae-Ho/I-1935-2019; Kim, Yong-Tae/HQZ-0240-2023; Kim, Do-Yeon/AET-3021-2022 | 57204540968; 57216816929; 57200911346; 55430621800; 55224798300; 39561353900; 7405813437; 57203012542 | alsrb5788@naver.com;gusw11634@naver.com;toy5988@naver.com;jsbyun@knu.ac.kr;anato82@dsmc.or.kr;ldhms@naver.com;wkim@dhu.ac.kr;dykim82@knu.ac.kr; | CELLS | CELLS-BASEL | 2073-4409 | 9 | 6 | SCIE | CELL BIOLOGY | 2020 | 6.6 | 26.9 | 0.25 | 2025-06-25 | 10 | 9 | Fubp1; cell cycle; cyclin A; cell death; lung cancer; double-agent | BINDING-PROTEIN; DNA-REPLICATION; SQUAMOUS-CELL; C-MYC; BREAST; CANCER; EXPRESSION; OVEREXPRESSION; AMPLIFICATION; TRANSCRIPTION | Cell cycle; Cell death; Cyclin A; Double-agent; Fubp1; Lung cancer | Animals; Cell Cycle; Cell Survival; Cyclin A; DNA-Binding Proteins; Gene Expression Regulation, Neoplastic; Mice; Neoplasms; NIH 3T3 Cells; RNA, Messenger; RNA-Binding Proteins; Transcription, Genetic; cyclin A; messenger RNA; nucleic acid binding protein; protein fubp1; unclassified drug; cyclin A; DNA binding protein; FUBP1 protein, human; messenger RNA; RNA binding protein; Article; cancer tissue; carcinogenesis; cell cycle progression; cell cycle S phase; cell heterogeneity; cell survival; controlled study; down regulation; genetic transcription; human; human tissue; metabolic stress; mRNA expression level; protein function; animal; cell cycle; cell survival; gene expression regulation; genetics; metabolism; mouse; neoplasm; NIH 3T3 cell line; pathology | English | 2020 | 2020-06 | 10.3390/cells9061347 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | ||
| ○ | ○ | Article | Regorafenib Regulates AD Pathology, Neuroinflammation, and Dendritic Spinogenesis in Cells and a Mouse Model of AD | The oral multi-target kinase inhibitor regorafenib, which targets the oncogenic receptor tyrosine kinase (RTK), is an effective therapeutic for patients with advanced gastrointestinal stromal tumors or metastatic colorectal cancer. However, whether regorafenib treatment has beneficial effects on neuroinflammation and Alzheimer's disease (AD) pathology has not been carefully addressed. Here, we report the regulatory function of regorafenib in neuroinflammatory responses and AD-related pathology in vitro and in vivo. Regorafenib affected AKT signaling to attenuate lipopolysaccharide (LPS)-mediated expression of proinflammatory cytokines in BV2 microglial cells and primary cultured microglia and astrocytes. In addition, regorafenib suppressed LPS-induced neuroinflammatory responses in LPS-injected wild-type mice. In 5x FAD mice (a mouse model of AD), regorafenib ameliorated AD pathology, as evidenced by increased dendritic spine density and decreased A beta plaque levels, by modulating APP processing and APP processing-associated proteins. Furthermore, regorafenib-injected 5x FAD mice displayed significantly reduced tau phosphorylation at T212 and S214 (AT100) due to the downregulation of glycogen synthase kinase-3 beta (GSK3 beta) activity. Taken together, our results indicate that regorafenib has beneficial effects on neuroinflammation, AD pathology, and dendritic spine formation in vitro and in vivo. | Han, Kyung-Min; Kang, Ri Jin; Jeon, Hyongjun; Lee, Hyun-ju; Lee, Ji-Soo; Park, HyunHee; Jeon, Seong Gak; Suk, Kyoungho; Seo, Jinsoo; Hoe, Hyang-Sook | Korea Brain Res Inst KBRI, Dept Neural Dev & Dis, 61 Cheomdan Ro, Daegu 41068, South Korea; Daegu Gyeongbuk Inst Sci & Technol, Dept Brain & Cognit Sci, Daegu 42988, South Korea; Kyungpook Natl Univ, Sch Med, Brain Sci & Engn Inst, Dept Pharmacol, Daegu 41944, South Korea | Seo, Jinsoo/AAD-4950-2019 | 57211004682; 57211491762; 59886233900; 57210856291; 57218142904; 58833770300; 57191415116; 7005114595; 7401783716; 8948946800 | hkm5344@kbri.re.kr;flwls2001@kbri.re.kr;Newace@kbri.re.kr;hjlee@kbri.re.kr;su943c@kbri.re.kr;hyunhee16hh@gmail.com;jsg7394@kbri.re.kr;ksuk@knu.ac.kr;jsseo@dgist.ac.kr;sookhoe72@kbri.re.kr; | CELLS | CELLS-BASEL | 2073-4409 | 9 | 7 | SCIE | CELL BIOLOGY | 2020 | 6.6 | 26.9 | 0.82 | 2025-06-25 | 20 | 27 | regorafenib; neuroinflammation; dendritic spine; amyloid beta; tau; aging | AMYLOID-BETA PEPTIDE; ALZHEIMERS; MICROGLIA; PROTEIN; TAU; NEUROBIOLOGY; INVOLVEMENT; PATHWAYS; KINASE; ROLES | Aging; Amyloid beta; Dendritic spine; Neuroinflammation; Regorafenib; Tau | Alzheimer Disease; Amyloid beta-Peptides; Animals; Anti-Inflammatory Agents; Cell Line; Cells, Cultured; Dendritic Spines; Glycogen Synthase Kinase 3 beta; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Microglia; Neuronal Outgrowth; Neuroprotective Agents; Phenylurea Compounds; Proto-Oncogene Proteins c-akt; Pyridines; Signal Transduction; tau Proteins; amyloid beta protein; beta secretase; complementary DNA; cyclooxygenase 2; cytokine; flavine adenine nucleotide; glial fibrillary acidic protein; glycogen synthase kinase 3beta; immunoglobulin enhancer binding protein; inducible nitric oxide synthase; interleukin 18; interleukin 1beta; interleukin 6; lipopolysaccharide; messenger RNA; mitogen activated protein kinase 1; mitogen activated protein kinase 3; regorafenib; STAT3 protein; tau protein; toll like receptor 4; tumor necrosis factor; tumor necrosis factor alpha converting enzyme; amyloid beta protein; antiinflammatory agent; carbanilamide derivative; glycogen synthase kinase 3beta; lipopolysaccharide; neuroprotective agent; protein kinase B; pyridine derivative; regorafenib; tau protein; agar gel electrophoresis; Akt signaling; Alzheimer disease; animal cell; animal experiment; animal model; animal tissue; Article; astrocyte; BV-2 cell line; controlled study; dendritic spine; down regulation; enzyme activity; enzyme linked immunosorbent assay; Golgi stain; immunocytochemistry; immunohistochemistry; JAK-STAT signaling; male; microglia; mouse; MTT assay; nervous system inflammation; nonhuman; protein expression; protein phosphorylation; real time polymerase chain reaction; software; Western blotting; Alzheimer disease; animal; C57BL mouse; cell culture; cell line; dendritic spine; drug effect; metabolism; neurite outgrowth; signal transduction | English | 2020 | 2020-07 | 10.3390/cells9071655 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | ||
| ○ | ○ | Article | Safety and Tolerability of Stromal Vascular Fraction Combined with β-Tricalcium Phosphate in Posterior Lumbar Interbody Fusion: Phase I Clinical Trial | The rates of pseudarthrosis remain high despite recent advances in bone graft substitutes for spinal fusion surgery. The aim of this single center, non-randomized, open-label clinical trial was to determine the feasibility of combined use of stromal vascular fraction (SVF) and beta-tricalcium phosphate (beta-TCP) for patients who require posterior lumbar interbody fusion (PLIF) and pedicle screw fixation. Two polyetheretherketone (PEEK) cages were inserted into the intervertebral space following complete removal of the intervertebral disc. The PEEK cage (SVF group) on the right side of the patient was filled with beta-TCP in combination with SVF, and the cage on the left side (control group) was filled with beta-TCP alone. Fusion rate and cage subsidence were assessed by lumbar spine X-ray and CT at 6 and 12 months postoperatively. At the 6-month follow-up, 54.5% of the SVF group (right-sided cages) and 18.2% of the control group (left-sided cages) had radiologic evidence of bone fusion (p = 0.151). The 12-month fusion rate of the right-sided cages was 100%, while that of the left-sided cages was 91.6% (p = 0.755). Cage subsidence was not observed. Perioperative combined use of SVF with beta-TCP is feasible and safe in patients who require spinal fusion surgery, and it has the potential to increase the early bone fusion rate following spinal fusion surgery. | Kim, Kyoung-Tae; Kim, Kwang Gi; Choi, Un Yong; Lim, Sang Heon; Kim, Young Jae; Sohn, Seil; Sheen, Seung Hun; Heo, Chan Yeong; Han, Inbo | Kyungpook Natl Univ, Sch Med, Dept Neurosurg, Daegu 41944, South Korea; Kyungpook Natl Univ Hosp, Dept Neurosurg, Daegu 41566, South Korea; Gachon Univ, Coll Med, Dept Biomed Engn, Seongnam Si 13120, South Korea; Gachon Univ, Dept Hlth Sci & Technol, Gachon Adv Inst Hlth Sci & Technol GAIHST, Seongnam Si 13120, South Korea; CHA Univ, CHA Bundang Med Ctr, Dept Neurosurg, Seongnam Si 13496, South Korea; Seoul Natl Univ, Bundang Hosp, Dept Plast & Reconstruct Surg, Seongnam Si 13620, South Korea | ; Heo, Chan/J-5719-2012; kim, kwanggi/D-6890-2012 | 57209540640; 57201369790; 57874739200; 57219463612; 57211074065; 55047974500; 57523864600; 26027502900; 9338449900 | nskimkt7@gmail.com;kimkg@gachon.ac.kr;nschoiuy@gmail.com;smion123@naver.com;youngjae@gachon.ac.kr;sisohn@hanmail.net;nssheen@gmail.com;lionheo@gmail.com;hanib@cha.ac.kr; | CELLS | CELLS-BASEL | 2073-4409 | 9 | 10 | SCIE | CELL BIOLOGY | 2020 | 6.6 | 26.9 | 0.37 | 2025-06-25 | 9 | 11 | spinal stenosis; posterior lumbar interbody fusion; stromal vascular fraction; bone graft substitute | ANTERIOR CERVICAL DISKECTOMY; DEMINERALIZED BONE-MATRIX; STEM-CELLS; OSTEOGENIC DIFFERENTIATION; ADIPOSE-TISSUE; ILIAC CREST; GRAFT; SCAFFOLDS; COMPLICATIONS; BIOMATERIALS | Bone graft substitute; Posterior lumbar interbody fusion; Spinal stenosis; Stromal vascular fraction | Adipose Tissue; Aged; Calcium Phosphates; Female; Humans; Ketones; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Middle Aged; Polyethylene Glycols; Pseudarthrosis; Spinal Fusion; Treatment Outcome; calcium phosphate; cell extract; stromal vascular fraction; unclassified drug; beta-tricalcium phosphate; calcium phosphate; ketone; macrogol; polyetheretherketone; abdominal fat; adipose derived stem cell; adipose tissue; adult; aged; Article; backache; bone density; bone graft; Brantigan Steffee classification system; cell differentiation; cell isolation; cell suspension; clinical article; computer assisted tomography; controlled study; density gradient centrifugation; drug safety; drug tolerability; evaluation and follow up; feasibility study; female; fusion rate; gastrointestinal endoscopy; human; human cell; human tissue; inflammation; intermittent claudication; intervertebral disk; intra-abdominal fat; laminectomy; leg pain; liposuction; low back pain; lumbar disk hernia; lumbar spinal stenosis; lumbar spine; lung nodule; male; middle aged; nerve root compression; nuclear magnetic resonance imaging; parameters; phase 1 clinical trial; posterior lumbar interbody fusion; prospective study; pseudarthrosis; radiodiagnosis; randomized controlled trial; regenerative medicine; smoking; spinal fusion rate; spondylolisthesis; Staphylococcus epidermidis; surgical infection; surgical technique; visual analog scale; X ray analysis; clinical trial; mesenchymal stem cell; mesenchymal stem cell transplantation; metabolism; procedures; pseudarthrosis; spine fusion; treatment outcome | English | 2020 | 2020-10 | 10.3390/cells9102250 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | ||
| ○ | ○ | Article | Sorting Nexin 27 Regulates the Lysosomal Degradation of Aquaporin-2 Protein in the Kidney Collecting Duct | Sorting nexin 27 (SNX27), a PDZ (Postsynaptic density-95/Discs large/Zonula occludens 1) domain-containing protein, cooperates with a retromer complex, which regulates intracellular trafficking and the abundance of membrane proteins. Since the carboxyl terminus of aquaporin-2 (AQP2c) has a class I PDZ-interacting motif (X-T/S-X-Phi), the role of SNX27 in the regulation of AQP2 was studied. Co-immunoprecipitation assay of the rat kidney demonstrated an interaction of SNX27 with AQP2. Glutathione S-transferase (GST) pull-down assays revealed an interaction of the PDZ domain of SNX27 with AQP2c. Immunocytochemistry of HeLa cells co-transfected with FLAG-SNX27 and hemagglutinin (HA)-AQP2 also revealed co-localization throughout the cytoplasm. When the PDZ domain was deleted, punctate HA-AQP2 labeling was localized in the perinuclear region. The labeling was intensively overlaid by Lysotracker staining but not by GM130 labeling, a cis-Golgi marker. In rat kidneys and primary cultured inner medullary collecting duct cells, the subcellular redistribution of SNX27 was similar to AQP2 under 1-deamino-8-D-arginine vasopressin (dDAVP) stimulation/withdrawal. Cell surface biotinylation assay showed that dDAVP-induced AQP2 translocation to the apical plasma membrane was unaffected after SNX27 knockdown in mpkCCD cells. In contrast, the dDAVP-induced AQP2 protein abundance was significantly attenuated without changes in AQP2 mRNA expression. Moreover, the AQP2 protein abundance was markedly declined during the dDAVP withdrawal period after stimulation under SNX27 knockdown, which was inhibited by lysosome inhibitors. Autophagy was induced after SNX27 knockdown in mpkCCD cells. Lithium-induced nephrogenic diabetes insipidus in rats revealed a significant downregulation of SNX27 in the kidney inner medulla. Taken together, the PDZ domain-containing SNX27 interacts with AQP2 and depletion of SNX27 contributes to the autophagy-lysosomal degradation of AQP2. | Choi, Hyo-Jung; Jang, Hyo-Ju; Park, Euijung; Tingskov, Stine Julie; Norregaard, Rikke; Jung, Hyun Jun; Kwon, Tae-Hwan | Kyungpook Natl Univ, Sch Med, Dept Biochem & Cell Biol, Taegu 41944, South Korea; Daegu Gyeongbuk Med Innovat Fdn, New Drug Dev Ctr, Taegu 41061, South Korea; Kyungpook Natl Univ, BK21 Plus KNU Biomed Convergence Program, Dept Biomed Sci, Sch Med, Taegu 41944, South Korea; Aarhus Univ, Dept Clin Med, DK-8200 Aarhus, Denmark; Johns Hopkins Univ, Sch Med, Dept Med, Div Nephrol, Baltimore, MD 21205 USA | Tingskov, Stine/X-3155-2019; Jung, Hyun Jun/LKM-4480-2024; Kwon, Tae-Hwan/ABA-1981-2020; PARK, EUIJUNG/LMO-3130-2024 | 56296381300; 57214330719; 50961544700; 57195718966; 8642489000; 36985354100; 7202206089 | sky1339@nate.com;gywn0001@naver.com;euijung.park.84@gmail.com;sjt@clin.au.dk;rn@clin.au.dk;hjung24@jhmi.edu;thkwon@knu.ac.kr; | CELLS | CELLS-BASEL | 2073-4409 | 9 | 5 | SCIE | CELL BIOLOGY | 2020 | 6.6 | 26.9 | 0.66 | 2025-06-25 | 19 | 20 | aquaporin-2; lysosomal degradation; retromer complex; sorting nexin 27 | NEPHROGENIC DIABETES-INSIPIDUS; PLASMA-MEMBRANE; AQP2 EXPRESSION; PDZ-DOMAIN; LITHIUM; TRAFFICKING; PHOSPHORYLATION; RETROMER; CHANNEL; PROLIFERATION | aquaporin-2; lysosomal degradation; retromer complex; sorting nexin 27 | Animals; Aquaporin 2; Autophagy; Diabetes Insipidus; HEK293 Cells; HeLa Cells; Humans; Kidney Tubules, Collecting; Lithium; Lysosomes; Male; Protein Binding; Proteolysis; Rats, Sprague-Dawley; RNA, Small Interfering; Sorting Nexins; aquaporin 2; lithium; protein binding; small interfering RNA; sorting nexin; animal; autophagy; diabetes insipidus; genetics; HEK293 cell line; HeLa cell line; human; kidney collecting tubule; lysosome; male; metabolism; pathology; protein degradation; Sprague Dawley rat | English | 2020 | 2020-05 | 10.3390/cells9051208 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | ||
| ○ | Article | SPON1 Can Reduce Amyloid Beta and Reverse Cognitive Impairment and Memory Dysfunction in Alzheimer's Disease Mouse Model | Alzheimer's disease (AD) is a complex, age-related neurodegenerative disease that is the most common form of dementia. However, the cure for AD has not yet been founded. The accumulation of amyloid beta (Aβ) is considered to be a hallmark of AD. Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), also known as beta secretase is the initiating enzyme in the amyloidogenic pathway. Blocking BACE1 could reduce the amount of Aβ, but this would also prohibit the other functions of BACE1 in brain physiological activity. SPONDIN1 (SPON1) is known to bind to the BACE1 binding site of the amyloid precursor protein (APP) and blocks the initiating amyloidogenesis. Here, we show the effect of SPON1 in Aβ reduction in vitro in neural cells and in an in vivo AD mouse model. We engineered mouse induced neural stem cells (iNSCs) to express Spon1. iNSCs harboring mouse Spon1 secreted SPON1 protein and reduced the quantity of Aβ when co-cultured with Aβ-secreting Neuro 2a cells. The human SPON1 gene itself also reduced Aβ in HEK 293T cells expressing the human APP transgene with AD-linked mutations through lentiviral-mediated delivery. We also demonstrated that injecting SPON1 reduced the amount of Aβ and ameliorated cognitive dysfunction and memory impairment in 5xFAD mice expressing human APP and PSEN1 transgenes with five AD-linked mutations. | Park, Soo Yong; Kang, Joo Yeong; Lee, Taehee; Nam, Donggyu; Jeon, Chang-Jin; Kim, Jeong Beom | Stem Cell Research Center, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), 44919, Ulsan, South Korea; Stem Cell Research Center, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), 44919, Ulsan, South Korea; Stem Cell Research Center, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), 44919, Ulsan, South Korea; Stem Cell Research Center, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), 44919, Ulsan, South Korea; Neuroscience Laboratory, Department of Biology, College of Natural Sciences, Kyungpook National University, 41566, Daegu, South Korea; Stem Cell Research Center, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), 44919, Ulsan, South Korea | 57210437081; 57216961795; 58338625800; 57061865600; 7006894339; 24166866700 | Cells | CELLS-BASEL | N/A | 2073-4409 | 9 | 5 | SCIE | CELL BIOLOGY | 2020 | 6.6 | 26.9 | 0.33 | 2025-06-25 | 13 | Alzheimer’s disease; amyloid beta; beta-secretase; gene therapy; HEK 293T cells; induced neural stem cells; SPON1; stem cell-based gene therapy | Alzheimer Disease; Amyloid beta-Peptides; Animals; Bystander Effect; Cognitive Dysfunction; Disease Models, Animal; Extracellular Matrix Proteins; Female; Humans; Memory Disorders; Mice, Inbred C57BL; Neural Stem Cells; amyloid beta protein; scleroprotein; SPON1 protein, human; Alzheimer disease; animal; bystander effect; C57BL mouse; cognitive defect; complication; disease model; female; human; memory disorder; metabolism; neural stem cell | English | Final | 2020 | 10.3390/cells9051275 | 바로가기 | 바로가기 | 바로가기 | ||||||||
| ○ | ○ | Article | Src Inhibition Attenuates Liver Fibrosis by Preventing Hepatic Stellate Cell Activation and Decreasing Connective Tissue Growth Factor | The SRC kinase family comprises non-receptor tyrosine kinases that are ubiquitously expressed in all cell types. Although Src is reportedly activated in pulmonary and renal fibrosis, little is known regarding its role in liver fibrosis. This study investigated whether the inhibition of Src protects against liver fibrosis. The expression of Src was upregulated in thioacetamide (TAA)-induced fibrotic mouse liver and cirrhosis of patients, and phospho-Src was upregulated during activation of hepatic stellate cells (HSC). In addition, Src inhibition reduced the expression of alpha-smooth muscle actin (alpha SMA) in primary HSCs and suppressed transforming growth factor beta (TGF-beta)-induced expression of connective tissue growth factor (CTGF) in hepatocytes. Src inhibitor Saracatinib also attenuated TAA-induced expression of type I collagen, alpha SMA, and CTGF in mouse liver tissues. The antifibrotic effect of Src inhibitors was associated with the downregulation of Smad3, but not of signal transducer and activator of transcription 3 (STAT3). In addition, Src inhibition increased autophagy flux and protected against liver fibrosis. These results suggest that Src plays an important role in liver fibrosis and that Src inhibitors could be treat liver fibrosis. | Seo, Hye-Young; Lee, So-Hee; Lee, Ji-Ha; Kang, Yu Na; Hwang, Jae Seok; Park, Keun-Gyu; Kim, Mi Kyung; Jang, Byoung Kuk | Keimyung Univ, Dept Internal Med, Sch Med, Daegu 42601, South Korea; Keimyung Univ, Inst Med Sci, Sch Med, Daegu 42601, South Korea; Keimyung Univ, Dept Pathol, Sch Med, Daegu 42601, South Korea; Kyungpook Natl Univ, Sch Med, Dept Internal Med, Daegu 41944, South Korea | 7202015536; 57196076317; 57218287685; 7402784356; 57205851488; 57202558343; 59124316400; 58849853600 | seo568@hanmail.net;jy16162727@naver.com;jihain10@gmail.com;Yunakang@dsmc.or.kr;gastro@dsmc.or.kr;kpark@knu.ac.kr;mdkmk@dsmc.or.kr;jangha106@dsmc.or.kr; | CELLS | CELLS-BASEL | 2073-4409 | 9 | 3 | SCIE | CELL BIOLOGY | 2020 | 6.6 | 26.9 | 1.36 | 2025-06-25 | 48 | 49 | Src; saracatinib; PP2; liver fibrosis; HSC; TGF-beta; hepatocyte; CTGF; Smad3; autophagy | KINASE; AUTOPHAGY; FAMILY | autophagy; CTGF; hepatocyte; HSC; liver fibrosis; PP2; saracatinib; Smad3; Src; TGF-β | Animals; Autophagy; Benzodioxoles; Cells, Cultured; Connective Tissue Growth Factor; Hepatic Stellate Cells; Humans; Liver Cirrhosis; Male; Mice, Inbred C57BL; Phosphorylation; Quinazolines; src-Family Kinases; STAT3 Transcription Factor; Thioacetamide; Transforming Growth Factor beta; Up-Regulation; 1,3 benzodioxole derivative; connective tissue growth factor; protein tyrosine kinase; quinazoline derivative; saracatinib; STAT3 protein; thioacetamide; transforming growth factor beta; animal; autophagy; C57BL mouse; cell culture; drug effect; enzymology; hepatic stellate cell; human; liver cirrhosis; male; metabolism; pathology; phosphorylation; upregulation | English | 2020 | 2020-03 | 10.3390/cells9030558 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | |||
| ○ | ○ | Article | The MAO Inhibitor Tranylcypromine Alters LPS- and Aβ-Mediated Neuroinflammatory Responses in Wild-type Mice and a Mouse Model of AD | Monoamine oxidase (MAO) has been implicated in neuroinflammation, and therapies targeting MAO are of interest for neurodegenerative diseases. The small-molecule drug tranylcypromine, an inhibitor of MAO, is currently used as an antidepressant and in the treatment of cancer. However, whether tranylcypromine can regulate LPS- and/or A beta-induced neuroinflammation in the brain has not been well-studied. In the present study, we found that tranylcypromine selectively altered LPS-induced proinflammatory cytokine levels in BV2 microglial cells but not primary astrocytes. In addition, tranylcypromine modulated LPS-mediated TLR4/ERK/STAT3 signaling to alter neuroinflammatory responses in BV2 microglial cells. Importantly, tranylcypromine significantly reduced microglial activation as well as proinflammatory cytokine levels in LPS-injected wild-type mice. Moreover, injection of tranylcypromine in 5xFAD mice (a mouse model of AD) significantly decreased microglial activation but had smaller effects on astrocyte activation. Taken together, our results suggest that tranylcypromine can suppress LPS- and A beta-induced neuroinflammatory responses in vitro and in vivo. | Park, HyunHee; Han, Kyung-Min; Jeon, Hyongjun; Lee, Ji-Soo; Lee, Hyunju; Jeon, Seong Gak; Park, Jin-Hee; Kim, Yu Gyung; Lin, Yuxi; Lee, Young-Ho; Jeong, Yun Ha; Hoe, Hyang-Sook | Korea Brain Res Inst KBRI, Dept Neural Dev & Dis, 61 Cheomdan Ro, Daegu 41062, South Korea; Daegu Gyeongbuk Inst Sci & Technol, Dept Brain & Cognit Sci, Daegu 42988, South Korea; Kyungpook Natl Univ, Sch Dent, Dept Pharmacol, Daegu 41940, South Korea; Korea Basic Sci Inst KBSI, Res Ctr Bioconvergence Anal, Cheongju 28119, Chungbuk, South Korea; Korea Brain Res Inst KBRI, Neurovasc Res Grp, 61 Cheomdan Ro, Daegu 41062, South Korea; Univ Sci & Technol UST, Bioanalyt Sci, Daejeon 34113, South Korea | Park, Jin/C-5307-2016; Kim, Young-Bo/AAR-8052-2021; lin, yuxi/HKF-6212-2023 | 58833770300; 57211004682; 59886233900; 57218142904; 57210856291; 57191415116; 57218759715; 57221687604; 57195379449; 56151243400; 57198837019; 8948946800 | hyunhee16hh@gmail.com;hkm5344@kbri.re.kr;newace16@kbri.re.kr;su943c@kbri.re.kr;hjlee@kbri.re.kr;jsg7394@kbri.re.kr;Mingmeng1005@gmail.com;cosmos0468@gmail.com;linyuxi@kbsi.re.kr;mr0505@kbsi.re.kr;yunha.jeong@kbri.re.kr;sookhoe72@kbri.re.kr; | CELLS | CELLS-BASEL | 2073-4409 | 9 | 9 | SCIE | CELL BIOLOGY | 2020 | 6.6 | 26.9 | 0.33 | 2025-06-25 | 14 | 16 | neuroinflammation; MAO inhibitor; microglia; amyloid beta; LPS | MONOAMINE-OXIDASE INHIBITORS; NITRIC-OXIDE; DISEASE; CELLS; ACETYLCHOLINESTERASE; ANTIDEPRESSANTS; ANTIOXIDANT; DERIVATIVES; ACTIVATION; PHENELZINE | amyloid beta; LPS; MAO inhibitor; microglia; neuroinflammation | Alzheimer Disease; Animals; Disease Models, Animal; Humans; Inflammation; Lipopolysaccharides; Mice; Monoamine Oxidase Inhibitors; Tranylcypromine; lipopolysaccharide; monoamine oxidase inhibitor; tranylcypromine; Alzheimer disease; animal; disease model; human; inflammation; metabolism; mouse; pathology | English | 2020 | 2020-09 | 10.3390/cells9091982 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | ||
| ○ | ○ | Article | Yeast-Based Genetic Interaction Analysis of Human Kinome | Kinases are critical intracellular signaling proteins. To better understand kinase-mediated signal transduction, a large-scale human-yeast genetic interaction screen was performed. Among 597 human kinase genes tested, 28 displayed strong toxicity in yeast when overexpressed. En masse transformation of these toxic kinase genes into 4653 homozygous diploid yeast deletion mutants followed by barcode sequencing identified yeast toxicity modifiers and thus their human orthologs. Subsequent network analyses and functional grouping revealed that the 28 kinases and their 676 interaction partners (corresponding to a total of 969 genetic interactions) are enriched in cell death and survival (34%), small-molecule biochemistry (18%) and molecular transport (11%), among others. In the subnetwork analyses, a few kinases were commonly associated with glioma, cell migration and cell death/survival. Our analysis enabled the creation of a first draft of the kinase genetic interactome network and identified multiple drug targets for inflammatory diseases and cancer, in which deregulated kinase signaling plays a pathogenic role. | Kim, Jae-Hong; Seo, Yeojin; Jo, Myungjin; Jeon, Hyejin; Lee, Won-Ha; Yachie, Nozomu; Zhong, Quan; Vidal, Marc; Roth, Frederick P.; Suk, Kyoungho | Kyungpook Natl Univ, Brain Sci & Engn Inst, Dept Pharmacol, Daegu 41944, South Korea; Kyungpook Natl Univ, Dept Biomed Sci, BK21 Plus KNU Biomed Convergence Program, Sch Med, Daegu 41944, South Korea; Kyungpook Natl Univ, Sch Life Sci, Brain Korea 21 Plus KNU Creat BioRes Grp, Daegu 41566, South Korea; Univ Toronto, Donnelly Ctr, Toronto, ON M5G 1X5, Canada; Univ Toronto, Dept Mol Genet, Toronto, ON M5G 1X5, Canada; Univ Toronto, Dept Comp Sci, Toronto, ON M5G 1X5, Canada; Sinai Hlth Syst, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5S 2S1, Canada; Wright State Univ, Dept Biol Sci, Dayton, OH 45435 USA; Dana Farber Canc Inst, Ctr Canc Syst Biol CCSB, Boston, MA 02215 USA; Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA; Korea Brain Res Inst, Daegu, South Korea; Univ Tokyo, Synthet Biol Div, Res Ctr Adv Sci & Technol, Tokyo, Japan; Keio Univ, Inst Adv Biosci, Tsuruoka, Yamagata, Japan; Japan Sci & Technol Agcy JST, PRESTO, Tokyo 1538904, Japan | Vidal, Marc/Y-2466-2019; zhong, quan/AAE-8893-2021; Roth, Frederick/H-6308-2011 | 55926599800; 57195556965; 57189727853; 56822943800; 57205609794; 12141160200; 7102024394; 7202764997; 7103020414; 7005114595 | kim86217@nate.com;seoyodini@naver.com;jinyhoi11@naver.com;hyejin7432@hanmail.net;whl@knu.ac.kr;nzmyachie@gmail.com;zhongquan99@gmail.com;Marc_Vidal@dfci.harvard.edu;fritz.roth@gmail.com;ksuk@knu.ac.kr; | CELLS | CELLS-BASEL | 2073-4409 | 9 | 5 | SCIE | CELL BIOLOGY | 2020 | 6.6 | 26.9 | 0.16 | 2025-06-25 | 4 | 4 | yeast; kinase; genetic interaction; network; bar-seq | INTERACTION NETWORKS; KINASE; OVEREXPRESSION; DATABASE; SCREEN | Bar-seq; Genetic interaction; Kinase; Network; Yeast | Epistasis, Genetic; Gene Ontology; Gene Regulatory Networks; Humans; Protein-Serine-Threonine Kinases; Proteome; Saccharomyces cerevisiae; activin receptor 1; ephrin type a receptor 4; inhibitor of nuclear factor kappa b kinase epsilon; mitogen activated protein kinase 9; protein kinase; protein kinase C theta; proto oncogene tyrosine protein kinase src; serine threonine protein kinase pak 1 protein; serine threonine protein kinase pak 2 protein; tyrosine protein kinase abl 1; unclassified drug; protein serine threonine kinase; proteome; Article; cell death; cell migration; cell survival; controlled study; DNA barcoding; DNA sequence; enzyme activity; fungal strain; gene interaction; gene mutation; gene ontology; gene overexpression; genetic transformation; glioma; heredity; high throughput analysis; human; kinome; nonhuman; phenotype; promoter region; signal transduction; toxicity; transport at the cellular level; yeast; epistasis; gene regulatory network; genetics; metabolism; Saccharomyces cerevisiae | English | 2020 | 2020-05 | 10.3390/cells9051156 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | ||
| ○ | ○ | Article | DRIM: A Web-Based System for Investigating Drug Response at the Molecular Level by Condition-Specific Multi-Omics Data Integration | Pharmacogenomics is the study of how genes affect a person's response to drugs. Thus, understanding the effect of drug at the molecular level can be helpful in both drug discovery and personalized medicine. Over the years, transcriptome data upon drug treatment has been collected and several databases compiled before drug treatment cancer cell multi-omics data with drug sensitivity (IC50, AUC) or time-series transcriptomic data after drug treatment. However, analyzing transcriptome data upon drug treatment is challenging since more than 20,000 genes interact in complex ways. In addition, due to the difficulty of both time-series analysis and multi-omics integration, current methods can hardly perform analysis of databases with different data characteristics. One effective way is to interpret transcriptome data in terms of well-characterized biological pathways. Another way is to leverage state-of-the-art methods for multi-omics data integration. In this paper, we developed Drug Response analysis Integrating Multi-omics and time-series data (DRIM), an integrative multi-omics and time-series data analysis framework that identifies perturbed sub-pathways and regulation mechanisms upon drug treatment. The system takes drug name and cell line identification numbers or user's drug control/treat time-series gene expression data as input. Then, analysis of multi-omics data upon drug treatment is performed in two perspectives. For the multi-omics perspective analysis, IC50-related multi-omics potential mediator genes are determined by embedding multi-omics data to gene-centric vector space using a tensor decomposition method and an autoencoder deep learning model. Then, perturbed pathway analysis of potential mediator genes is performed. For the time-series perspective analysis, time-varying perturbed sub-pathways upon drug treatment are constructed. Additionally, a network involving transcription factors (TFs), multi-omics potential mediator genes, and perturbed sub-pathways is constructed, and paths to perturbed pathways from TFs are determined by an influence maximization method. To demonstrate the utility of our system, we provide analysis results of sub-pathway regulatory mechanisms in breast cancer cell lines of different drug sensitivity. DRIM is available at: http://biohealth.snu.ac.kr/software/DRIM/. | Oh, Minsik; Park, Sungjoon; Lee, Sangseon; Lee, Dohoon; Lim, Sangsoo; Jeong, Dabin; Jo, Kyuri; Jung, Inuk; Kim, Sun | Seoul Natl Univ, Dept Comp Sci & Engn, Seoul, South Korea; Seoul Natl Univ, Bioinformat Inst, Seoul, South Korea; Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul, South Korea; Chungbuk Natl Univ, Dept Comp Engn, Cheongju, South Korea; Kyungpook Natl Univ, Dept Comp Sci & Engn, Daegu, South Korea; Seoul Natl Univ, Inst Engn Res, Dept Comp Sci & Engn, Seoul, South Korea | Lee, Sangseon/KBQ-8699-2024; Lim, Sangsoo/GXM-6835-2022; Lee, Dohoon/HLQ-0307-2023 | 57193770393; 58161443100; 57190819617; 57209851895; 57191446217; 57200327738; 56037547500; 56067575500; 36063436900 | sunkim.bioinfo@snu.ac.kr; | FRONTIERS IN GENETICS | FRONT GENET | 1664-8021 | 11 | SCIE | GENETICS & HEREDITY | 2020 | 4.599 | 27.0 | 0.59 | 2025-06-25 | 10 | 13 | multi-omics; drug-response; time-series; perturbed pathway; web-system; pharmacogenomics | BREAST-CANCER; RESISTANCE; LAPATINIB; NETWORKS; PHARMACOGENOMICS; SENSITIVITY; INHIBITOR; LANDSCAPE; PROGNOSIS; PREDICT | drug-response; multi-omics; perturbed pathway; pharmacogenomics; time-series; web-system | ATP binding cassette subfamily G member 2; breast cancer resistance protein; caspase 8; codanin 1; dynactin subunit 6; E2F transcription factor 1; epidermal growth factor receptor 2; Erb B2 receptor tyrosine kinase 3; estrogen receptor; heat shock transcription factor 1; lapatinib; microRNA; mitogen activated protein kinase kinase 7; progesterone receptor; programmed death 1 ligand 1; transcription factor; tumor protein p53; tumor suppressor protein; unclassified drug; apoptosis; area under the curve; Article; artificial neural network; bioinformatics; breast cancer; breast cancer cell line; controlled study; copy number variation; deep learning; DNA methylation; down regulation; drug response; drug sensitivity; gene expression; gene expression profiling; gene interaction; gene overexpression; gene regulatory network; genetic algorithm; human; IC50; immunosuppressive treatment; machine learning; mathematical analysis; MDA-MB cell line; MDA-MB-231 cell line; measurement accuracy; molecular diagnosis; nerve cell network; omics; pharmacogenomics; Pi3K/Akt signaling; signal transduction; social network; threshold limit value; time series analysis | English | 2020 | 2020-11-12 | 10.3389/fgene.2020.564792 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | |||
| ○ | ○ | Article | Targeting X chromosome-linked inhibitor of apoptosis protein in mucoepidermoid carcinoma of the head and neck: A novel therapeutic strategy using nitidine chloride | Nitidine chloride (NC) was recently reported to exhibit a wide range of pharmacological properties for several diseases, including cancer. Here we report for the first time that NC is a potential therapeutic agent for mucoepidermoid carcinoma (MEC) occurring in the head and neck because it suppresses X chromosome-linked inhibitor of apoptosis protein (XIAP) in human MEC in vitro and in vivo. The antitumor effects of NC were evaluated by trypan blue exclusion assay, western blotting, live/dead assay, 4',6-diamidino-2-phenylindole (DAPI) staining, human apoptosis antibody array, immunofluorescence staining, immunohistochemistry, small interfering RNA assay, transient transfection of XIAP overexpression vector, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and histopathological examination of organs. NC inhibited cell viability and induced caspase-dependent apoptosis in vitro. A human apoptosis antibody array assay showed that XIAP is suppressed by NC treatment. XIAP was overexpressed in oral squamous cell carcinoma (OSCC) tissues that arose from the head and neck, and high XIAP expression was correlated with poor prognosis in OSCC patients. XIAP depletion significantly increased apoptosis, and ectopic XIAP overexpression attenuated the apoptosis induced by NC treatment. NC suppressed tumor growth in vivo at a dosage of 5 mg/kg/day. The number of TUNEL-positive cells increased and the protein expression of XIAP was consistently downregulated in NC-treated tumor tissues. In addition, NC caused no histopathological changes in the liver or kidney. These findings provide new insights into the mechanism of action underlying the anticancer effects of NC and demonstrate that NC is a promising therapeutic agent for the treatment of human MEC of the head and neck. Key messages center dot Nitidine chloride induces caspase-dependent apoptosis in MEC of the head and neck. center dot High XIAP expression correlates with poor prognosis of OSCC patients. center dot Nitidine chloride suppresses tumor growth in vivo without any systemic toxicities. center dot Targeting XIAP is a novel chemotherapeutic strategy for MEC of the head and neck. | Kwon, Hye-Jeong; Yoon, Kyungsil; Jung, Ji-Youn; Ryu, Mi Heon; Kim, Sung-Hyun; Yoo, Eun-Seon; Choi, So-Young; Yang, In-Hyoung; Hong, Seong Doo; Shin, Ji-Ae; Cho, Sung-Dae | Seoul Natl Univ, Sch Dent, Dept Oral Pathol, Seoul 03080, South Korea; Seoul Natl Univ, Dent Res Inst, Seoul 03080, South Korea; Natl Canc Ctr, Div Translat Sci, Comparat Biomed Res Branch, Goyang 10408, South Korea; Kongju Natl Univ, Dept Compan & Lab Anim Sci, Yesan 32439, South Korea; Pusan Natl Univ, Dept Oral Pathol, Sch Dent, Yangsan Campus, Yangsan 50612, South Korea; Kyungpook Natl Univ, Sch Dent, Dept Oral & Maxillofacial Surg, Daegu 41940, South Korea | 57193906014; 59911001500; 7402895089; 35771492000; 57205720454; 57205714045; 57202918688; 56720844900; 35248278600; 35330719900; 7404884194 | sky21sm@snu.ac.kr;efiwdsc@snu.ac.kr; | JOURNAL OF MOLECULAR MEDICINE-JMM | J MOL MED | 0946-2716 | 1432-1440 | 98 | 11 | SCIE | GENETICS & HEREDITY;MEDICINE, RESEARCH & EXPERIMENTAL | 2020 | 4.599 | 27.0 | 0.16 | 2025-06-25 | 2 | 2 | Mucoepidermoid carcinoma of salivary gland; Nitidine chloride; X chromosome-linked inhibitor of apoptosis protein; Apoptosis | NATURAL-PRODUCTS; SIGNALING PATHWAY; SALIVARY-GLAND; CELL-DEATH; XIAP; EXPRESSION; OVEREXPRESSION; RESISTANCE; MARKER; GROWTH | Apoptosis; Mucoepidermoid carcinoma of salivary gland; Nitidine chloride; X chromosome-linked inhibitor of apoptosis protein | Antineoplastic Agents; Apoptosis; Benzophenanthridines; Biomarkers, Tumor; Carcinoma, Mucoepidermoid; Cell Line, Tumor; Cells, Cultured; Fluorescent Antibody Technique; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms; Humans; Immunohistochemistry; Molecular Targeted Therapy; X-Linked Inhibitor of Apoptosis Protein; 4',6 diamidino 2 phenylindole; antineoplastic agent; caspase; nitidine; small interfering RNA; trypan blue; X linked inhibitor of apoptosis; antineoplastic agent; benzophenanthridine derivative; nitidine; tumor marker; X linked inhibitor of apoptosis; XIAP protein, human; adult; animal experiment; animal model; animal tissue; antineoplastic activity; apoptosis; Article; cancer inhibition; cancer prognosis; cancer tissue; cell count; cell viability; controlled study; data analysis software; down regulation; drug mechanism; female; gene overexpression; head and neck cancer; head and neck squamous cell carcinoma; histopathology; human; human cell; immunofluorescence test; immunohistochemistry; in vitro study; in vivo study; male; mouth squamous cell carcinoma; mucoepidermoid tumor; nonhuman; protein targeting; transient transfection; TUNEL assay; Western blotting; cell culture; drug effect; fluorescent antibody technique; gene expression regulation; genetics; head and neck tumor; metabolism; molecularly targeted therapy; mucoepidermoid tumor; pathology; tumor cell line | English | 2020 | 2020-11 | 10.1007/s00109-020-01977-w | 바로가기 | 바로가기 | 바로가기 | 바로가기 | ||
| ○ | ○ | Article | 7,3′,4′-Trihydroxyisoflavone, a Metabolite of the Soy Isoflavone Daidzein, Suppresses α-Melanocyte-Stimulating Hormone-Induced Melanogenesis by Targeting Melanocortin 1 Receptor | 7,3 ',4 '-Trihydroxyisoflavone (7,3 ',4 '-THIF) is a metabolite of daidzein which is a representative isoflavone found in soybean. Recent studies suggested that 7,3 ',4 '-THIF exerts a hypopigmentary effect in B16F10 cells, however, its underlying molecular mechanisms and specific target protein remain unknown. Here, we found that 7,3 ',4 '-THIF, but not daidzein, inhibited alpha-melanocyte-stimulating hormone (MSH)-induced intracellular and extracellular melanin production in B16F10 cells by directly targeting melanocortin 1 receptor (MC1R). Western blot data showed that 7,3 ',4 '-THIF inhibited alpha-MSH-induced tyrosinase, tyrosinase-related protein-1 (TYRP-1), and tyrosinase-related protein-2 (TYRP-2) expressions through the inhibition of Microphthalmia-associated transcription factor (MITF) expression and cAMP response element-binding (CREB) phosphorylation. 7,3 ',4 '-THIF also inhibited alpha-MSH-induced dephosphorylation of AKT and phosphorylation of p38 and cAMP-dependent protein kinase (PKA). cAMP and Pull-down assays indicated that 7,3 ',4 '-THIF strongly inhibited forskolin-induced intracellular cAMP production and bound MC1R directly by competing with alpha-MSH. Moreover, 7,3 ',4 '-THIF inhibited alpha-MSH-induced intracellular melanin production in human epidermal melanocytes (HEMs). Collectively, these results demonstrate that 7,3 ',4 '-THIF targets MC1R, resulting in the suppression of melanin production, suggesting a protective role for 7,3 ',4 '-THIF against melanogenesis. | Kim, Ji Hye; Lee, Jae-Eun; Kim, Taewon; Yeom, Myung Hun; Park, Jun Seong; di Luccio, Eric; Chen, Hanyong; Dong, Zigang; Lee, Ki Won; Kang, Nam Joo | Kyungpook Natl Univ, Sch Food Sci & Biotechnol, Daegu, South Korea; Korea Inst Oriental Med, Korean Med Applicat Ctr, Daegu, South Korea; Amorepacific Corp R&D Ctr, Skin Res Inst, Yongin, South Korea; Kyungpook Natl Univ, Coll Nat Sci, Sch Life Sci, Dept Genet Engn, Daegu, South Korea; Univ Minnesota, Hormel Inst, Austin, MN USA; Seoul Natl Univ, World Class Univ Biomodulat Major, Dept Agr Biotechnol, Seoul, South Korea; Seoul Natl Univ, Adv Inst Convergence Technol, Suwon, South Korea; Seoul Natl Univ, Res Inst Bio Food Ind, Inst Green Bio Sci & Technol, Pyeongchang, South Korea | ; di Luccio, Eric/Z-5388-2019 | 58446623800; 57203144423; 57658010600; 36602012600; 57188967765; 6602656101; 56146715600; 57225955964; 55802370813; 8315288500 | njkang@knu.ac.kr; | FRONTIERS IN MOLECULAR BIOSCIENCES | FRONT MOL BIOSCI | 2296-889X | 7 | SCIE | BIOCHEMISTRY & MOLECULAR BIOLOGY | 2020 | 5.246 | 27.3 | 0.85 | 2025-06-25 | 18 | 20 | 7; 3′ 4′ -Trihydroxyisoflavone; α -MSH; melanogenesis; depigmentation; melanocortin 1 receptor | ORTHO-DIHYDROXYISOFLAVONE DERIVATIVES; FERMENTED SOYBEAN PASTE; IN-VITRO; TYROSINASE; GENISTEIN; CELLS; DIFFERENTIATION; PROLIFERATION; TRANSCRIPTION; CONSTITUENTS | 3′; 4′-Trihydroxyisoflavone; 7; depigmentation; melanocortin 1 receptor; melanogenesis; α-MSH | English | 2020 | 2020-12-03 | 10.3389/fmolb.2020.577284 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | ||||
| ○ | ○ | Article | Current status of antimicrobial stewardship programmes in Korean hospitals: results of a 2018 nationwide survey | Background: Antimicrobial stewardship programmes (ASPs) are suggested as a vital strategy to address antimicrobial resistance. Aim: To examine the current status of ASPs in Korean hospitals, to identify problems and challenges for the implementation of proper ASPs, and to provide a reference for developing more effective ASP policies. Methods: A questionnaire based on the 'Seven Core Elements of Hospital Antibiotic Stewardship Programs' from the US Centers for Disease Control and Prevention was developed, modified from the previous questionnaire on ASPs in Korea, 2015. ASP-participating physicians such as infectious disease specialists (IDSs), paediatric IDSs, and directors of infection control departments were targeted. Only one ASP-associated physician per hospital participated in the survey. Findings: The survey response rate was 88.4% (84/95). The median number of medical personnel participating in ASPs was 3 (interquartile range (IQR): 1-5), most of whom were IDS (median: 2; IQR: 1-2). Only 6.0% (5/84) of hospitals had full-time workers for ASPs. Whereas restrictive measures for designated antimicrobials were widely implemented among Korean hospitals (88.1%, 74/84), the proportion of hospitals with interventions for inappropriate long-term antimicrobial use and a conversion strategy from parenteral to oral antimicrobial administration was only 9.5% (8/84) and 1.2% (1/84), respectively. Lack of time, personnel, and appropriate compensation was perceived as the major barrier to establishing an ASP in Korean hospitals. Conclusion: ASPs in Korean hospitals were primarily carried out by one or two IDSs, and programmes mostly comprised restrictive measures for designated antimicrobials. National-level support to implement appropriate ASPs in Korean hospitals is necessary. (C) 2019 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved. | Kim, B.; Lee, M. J.; Moon, S. M.; Park, S. Y.; Song, K-H; Lee, H.; Park, J. S.; Lee, M. S.; Choi, S-M; Yeom, J-S; Kim, J. Y.; Kim, C-J; Chang, H-H; Kim, E. S.; Kim, T. H.; Kim, H. B. | Hanyang Univ, Dept Internal Med, Coll Med, Seoul, South Korea; Inje Univ, Coll Med, Dept Internal Med, Sanggye Paik Hosp, Seoul, South Korea; Seoul Natl Univ, Coll Med, Dept Internal Med, Div Infect Dis,Bundang Hosp, Seoul, South Korea; Hallym Univ, Dept Internal Med, Div Infect Dis, Sacred Heart Hosp, Anyang, South Korea; Soonchunhyang Univ, Coll Med, Dept Internal Med, Div Infect Dis,Seoul Hosp, Seoul, South Korea; Seoul Natl Univ, Coll Med, Dept Pediat, Bundang Hosp, Seoul, South Korea; Seoul Natl Univ, Coll Med, Dept Lab Med, Bundang Hosp, Seoul, South Korea; Kyung Hee Univ, Dept Internal Med, Div Infect Dis, Sch Med, Seoul, South Korea; Catholic Univ Korea, Coll Med, Dept Internal Med, Div Infect Dis, Seoul, South Korea; Yonsei Univ, Dept Internal Med, Coll Med, Seoul, South Korea; Incheon Med Ctr, Dept Internal Med, Div Infect Dis, Incheon, South Korea; Ewha Womans Univ, Dept Internal Med, Div Infect Dis, Coll Med, Seoul, South Korea; Kyungpook Natl Univ, Sch Med, Dept Internal Med, Div Infect Dis, Daegu, South Korea | Hen Hong, Chang/ITT-2813-2023; Kim, Hong Bin/J-5452-2012; Kim, Tae Hyong/L-7336-2015; Yeom, Joon/Q-5559-2019; Kim, Hee/AAU-6368-2021; Kim, Jaeheon/KLC-8792-2024; Kim, Sooyeon/AAA-8521-2022; Kim, Jung/L-9791-2019; Kim, Jin/AAS-5810-2021; Kim, Eu/J-5424-2012 | 55622077200; 55520467500; 36554757200; 55259986400; 23398486700; 57281223200; 35082469500; 55759244100; 7408120168; 7004196941; 57211142178; 45361165100; 7407521688; 22938086900; 55927274000; 35307429400 | eskim@snubh.org; | JOURNAL OF HOSPITAL INFECTION | J HOSP INFECT | 0195-6701 | 1532-2939 | 104 | 2 | SCIE | INFECTIOUS DISEASES;PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH | 2020 | 3.926 | 27.3 | 1.49 | 2025-06-25 | 35 | 33 | Antimicrobial; Stewardship; Resistance; Hospital; Korea | INFECTIOUS-DISEASES-SOCIETY; ANTIBIOTIC STEWARDSHIP; IMPACT; TEAMS | Antimicrobial; Hospital; Korea; Resistance; Stewardship | Anti-Infective Agents; Antimicrobial Stewardship; Hospitals; Humans; Practice Guidelines as Topic; Republic of Korea; Surveys and Questionnaires; amikacin; doripenem; ertapenem; gentamicin; imipenem; linezolid; meropenem; teicoplanin; tigecycline; vancomycin; voriconazole; antiinfective agent; antibiotic resistance; antimicrobial stewardship; Article; compensation; controlled study; drug monitoring; education program; hospital; human; infectious disease specialist; medical director; personnel shortage; prescription; public reporting (health care); questionnaire; reward; South Korea; time; antimicrobial stewardship; comparative study; organization and management; practice guideline; procedures | English | 2020 | 2020-02 | 10.1016/j.jhin.2019.09.003 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | |
| ○ | ○ | Article | Delivery of Periodontopathogenic Extracellular Vesicles to Brain Monocytes and Microglial IL-6 Promotion by RNA Cargo | Gram-negative bacterial extracellular vesicles (EVs), also known as outer membrane vesicles (OMVs), are secreted from bacterial cells and have attracted research attention due to their role in cell-to-cell communication. During OMV secretion, a variety of cargo such as extracellular RNA (exRNA) is loaded into the OMV. The involvement of exRNAs from a range of bacteria has been identified in several diseases, however, their mechanism of action has not been elucidated. We have recently demonstrated that OMVs secreted by the periodontopathogen Aggregatibacter actinomycetemcomitans can cross the blood-brain barrier (BBB) and that its exRNA cargo could promote the secretion of proinflammatory cytokines in the brain. However, it was unclear whether the brain immune cells could actually take up bacterial OMVs, which originate outside of the brain, in an appropriate immune response. In the present study, using monocyte-specific live CX3CR1-GFP mice, we visualized OMV-colocalized meningeal macrophages and microglial cells into which bacterial OMVs had been loaded and intravenously injected through tail veins. Our results suggested that meningeal macrophages uptake BBB-crossed OMVs earlier than do cortex microglia. BV2 cells (a murine microglia cell line) and exRNAs were also visualized after OMV treatment and their proinflammatory cytokine levels were observed. Interleukin (IL)-6 and NF-kappa B of BV2 cells were activated by A. actinomycetemcomitans exRNAs but not by OMV DNA cargo. Altogether, these findings indicate that OMVs can successfully deliver exRNAs into brain monocyte/microglial cells and cause neuroinflammation, implicating a novel pathogenic mechanism in neuroinflammatory diseases. | Ha, Jae Yeong; Choi, Song-Yi; Lee, Ji Hye; Hong, Su-Hyung; Lee, Heon-Jin | Kyungpook Natl Univ, Sch Dent, Dept Microbiol & Immunol, Daegu, South Korea; Pusan Natl Univ, Sch Dent, Dent & Life Sci Inst, Dept Oral Pathol, Yangsan, South Korea; Kyungpook Natl Univ, Brain Sci & Engn Inst, Daegu, South Korea | 57220581488; 57210356632; 55689992200; 8691449100; 36462383000 | heonlee@knu.ac.kr; | FRONTIERS IN MOLECULAR BIOSCIENCES | FRONT MOL BIOSCI | 2296-889X | 7 | SCIE | BIOCHEMISTRY & MOLECULAR BIOLOGY | 2020 | 5.246 | 27.3 | 2.9 | 2025-06-25 | 73 | 69 | periodontitis; small RNA; extracellular vesicle; Aggregatibacter actinomycetemcomitans; outer membrane vesicle | OUTER-MEMBRANE VESICLES; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; MICRORNA-SIZE; MACROPHAGES; LOCALIZATION; BARRIER; ALPHA | Aggregatibacter actinomycetemcomitans; extracellular vesicle; outer membrane vesicle; periodontitis; small RNA | English | 2020 | 2020-11-24 | 10.3389/fmolb.2020.596366 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | |||||
| ○ | ○ | Article | Functional Characterization of Primordial Protein Repair Enzyme M38 Metallo-Peptidase From Fervidobacterium islandicum AW-1 | The NA23RS₀₈₁₀₀ gene of Fervidobacterium islandicum AW-1 encodes a keratin-degrading beta-aspartyl peptidase (FiBAP) that is highly expressed under starvation conditions. Herein, we expressed the gene in Escherichia coli, purified the recombinant enzyme to homogeneity, and investigated its function. The 318 kDa recombinant FiBAP enzyme exhibited maximal activity at 80 degrees C and pH 7.0 in the presence of Zn2+. Size-exclusion chromatography revealed that the native enzyme is an octamer comprising a tetramer of dimers; this was further supported by determination of its crystal structure at 2.6 angstrom resolution. Consistently, the structure of FiBAP revealed three additional salt bridges in each dimer, involving 12 ionic interactions that might contribute to its high thermostability. In addition, the co-crystal structure containing the substrate analog N-carbobenzoxy-beta-Asp-Leu at 2.7 angstrom resolution revealed binuclear Zn2+-mediated substrate binding, suggesting that FiBAP is a hyperthermophilic type-I IadA, in accordance with sequence-based phylogenetic analysis. Indeed, complementation of a Leu auxotrophic E. coli mutant strain (Delta iadA and Delta leuB) with FiBAP enabled the mutant strain to grow on isoAsp-Leu peptides. Remarkably, LC-MS/MS analysis of soluble keratin hydrolysates revealed that FiBAP not only cleaves the C-terminus of isoAsp residues but also has a relatively broad substrate specificity toward alpha-peptide bonds. Moreover, heat shock-induced protein aggregates retarded bacterial growth, but expression of BAP alleviated the growth defect by degrading damaged proteins. Taken together, these results suggest that the viability of hyperthermophiles under stressful conditions may rely on the activity of BAP within cellular protein repair systems. | La, Jae Won; Dhanasingh, Immanuel; Jang, Hyeonha; Lee, Sung Haeng; Lee, Dong-Woo | Yonsei Univ, Dept Biotechnol, Seoul, South Korea; Chosun Univ, Sch Med, Dept Cellular & Mol Med, Gwangju, South Korea; Kyungpook Natl Univ, Sch Appl Biosci, Daegu, South Korea | ; Lee, Jeong-Hoon/Q-1055-2018; DHANASINGH, IMMANUEL/HLP-9335-2023 | 57211523438; 58295458100; 57218761651; 35788005800; 57195068659 | leehicam@yonsei.ac.kr; | FRONTIERS IN MOLECULAR BIOSCIENCES | FRONT MOL BIOSCI | 2296-889X | 7 | SCIE | BIOCHEMISTRY & MOLECULAR BIOLOGY | 2020 | 5.246 | 27.3 | 0.14 | 2025-06-25 | 4 | 4 | M38 β -aspartyl peptidase; protein repair; starvation; type-I BAP; hyperthermophile stress responses; keratin degradation; Fervidobacterium islandicum AW-1 | ISOASPARTYL DIPEPTIDASE; X-RAY; MOLECULAR REPLACEMENT; ABNORMAL PROTEINS; CRYSTAL-STRUCTURE; DEGRADATION; METHYLTRANSFERASE; ACCUMULATION; DEAMIDATION; REFINEMENT | Fervidobacterium islandicum AW-1; hyperthermophile stress responses; keratin degradation; M38 β-aspartyl peptidase; protein repair; starvation; type-I BAP | English | 2020 | 2020-12-17 | 10.3389/fmolb.2020.600634 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | ||||
| ○ | ○ | Article | 6,8-Diprenylorobol Induces Apoptosis in Human Hepatocellular Carcinoma Cells via Activation of FOXO3 and Inhibition of CYP2J2 | 6,8-Diprenylorobol is a phytochemical derived from the roots of Glycyrrhiza uralensis Fisch. 6,8-Diprenylorobol exhibits several biological activities, but the effects of 6,8-diprenylorobol on cancers have been hardly investigated. This study is aimed at elucidating the anticancer effect and working mechanism of 6,8-diprenylorobol in HepG2 and Huh-7, two kinds of human hepatocellular carcinoma (HCC) cell lines. WST-1, cell counting, and colony formation assays and morphological change analysis showed that 6,8-diprenylorobol treatment decreased the cell viability and proliferation rate. Cell cycle analysis indicated that 6,8-diprenylorobol treatment increased the population of the G1/0 stage. Annexin V/PI double staining and TUNEL analysis showed that 6,8-diprenylorobol treatment increased the apoptotic cell population and DNA fragmentation. Western blot analysis showed that 6,8-diprenylorobol treatment increased the expression of cleaved PARP1, cleaved caspase-3, FOXO3, Bax, Bim, p21, and p27 but decreased the expression of Bcl2 and BclXL. Interestingly, 6,8-diprenylorobol inhibited CYP2J2-mediated astemizole O-demethylation and ebastine hydroxylase activities with Ki values of 9.46 and 2.61 mu M, respectively. CYP2J2 siRNA transfection enhanced the anticancer effect of 6,8-diprenylorobol in HepG2 and Huh-7 cells through the downregulation of CYP2J2 protein expression and upregulation of FOXO3. Taken together, this study proposes that 6,8-diprenylorobol treatment may be a useful therapeutic option against HCC by targeting CYP2J2 and FOXO3. | Lee, Chang Min; Lee, Jongsung; Jang, Su-Nyeong; Shon, Jong Cheol; Wu, Zhexue; Park, Kyungmoon; Liu, Kwang-Hyeon; Park, See-Hyoung | Hongik Univ, Dept Bio & Chem Engn, Sejong 30016, South Korea; Sungkyunkwan Univ, Dept Integrat Biotechnol, Suwon 16419, South Korea; Kyungpook Natl Univ, Coll Pharm, Plus KNU Multiom Based Creat Drug Res Team BK21, Daegu 41566, South Korea; Kyungpook Natl Univ, Res Inst Pharmaceut Sci, Daegu 41566, South Korea; Korea Inst Toxicol, Environm Chem Res Ctr, Jinju 52834, South Korea | 57210940809; 12800238500; 57211630666; 56010668800; 55523767300; 57207108900; 55768214700; 7501838385 | yycc456@naver.com;bioneer@skku.edu;wts1424@naver.com;jongcheol.shon@kitox.re.kr;wuzhexue527@gmail.com;pkm2510@hongik.ac.kr;dstlkh@knu.ac.kr;imsesame@gmail.com; | OXIDATIVE MEDICINE AND CELLULAR LONGEVITY | OXID MED CELL LONGEV | 1942-0900 | 1942-0994 | 2020 | SCIE | CELL BIOLOGY | 2020 | 6.543 | 27.4 | 0.83 | 2025-06-25 | 19 | 21 | CYTOCHROME-P450 2J2; CANCER CELLS; PRENYLATED ISOFLAVONES; ANTICANCER ACTIVITY; ERK ACTIVATION; CYCLE ARREST; HL-60 CELLS; PHYTOCHEMICALS; DEATH; PROLIFERATION | Activation; Analysis; Cancers; Cells; Counting; Electrophoresis; PI; Processing; Antineoplastic Agents, Phytogenic; Apoptosis; Carcinoma, Hepatocellular; Cytochrome P-450 Enzyme System; Forkhead Box Protein O3; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Hep G2 Cells; Humans; Liver Neoplasms; Neoplasm Proteins; Cell culture; Cell death; Cell proliferation; Electrophoresis; 6,8 diprenylorobol; antineoplastic agent; astemizole; beta actin; BIM protein; caspase 3; caspase 6; caspase 7; caspase 8; caspase 9; cytochrome P450 2J2; ebastine; glucose 6 phosphate; histone H2AX; Janus kinase; lipocortin 5; mitogen activated protein kinase p38; natural product; nicotinamide adenine dinucleotide; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1; o demethylase; phytochemical; protein Bax; protein bcl 2; protein bcl xl; protein kinase B; protein p21; protein p27; small interfering RNA; transcription factor FKHRL1; unclassified drug; antineoplastic agent; arachidonate epoxygenase; cytochrome P450; FOXO3 protein, human; transcription factor FKHRL1; tumor protein; Cell cycle analysis; Glycyrrhiza uralensis Fisch; Hepatocellular carcinoma cell; Human hepatocellular carcinoma (HCC); Hydroxylase activity; Morphological changes; Protein expressions; Western-blot analysis; antineoplastic activity; apoptosis; Article; cell counting; cell cycle G0 phase; cell population; cell proliferation; cell viability; colony formation; DNA fragmentation; down regulation; drug mechanism; enzyme activity; enzyme inhibition; G1 phase cell cycle checkpoint; genetic transfection; Hep-G2 cell line; Huh-7 cell line; human; human cell; protein expression; staining; TUNEL assay; upregulation; Western blotting; WST-1 assay; apoptosis; biosynthesis; drug effect; gene expression regulation; genetics; Hep-G2 cell line; liver cell carcinoma; liver tumor; metabolism; pathology; Molecular biology | English | 2020 | 2020-11-19 | 10.1155/2020/8887251 | 바로가기 | 바로가기 | 바로가기 | 바로가기 |
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