• Experimental and Molecular Medicine
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• v.50 no.11
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• pp.10.1-10.11
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• 2018

Although early studies suggested that bladder cancer (BCa) is more prevalent in men than in women, muscle-invasive rates are higher in women than in men, suggesting that sex hormones might play important roles in different stages of BCa progression. In this work, we found that estrogen receptor beta ($ER{\beta}$) could increase BCa cell proliferation and invasion via alteration of miR-92a-mediated DAB2IP (DOC-2/DAB2 interacting protein) signals and that blocking miR-92a expression with an inhibitor could partially reverse $ER{\beta}$-enhanced BCa cell growth and invasion. Further mechanism dissection found that $ER{\beta}$ could increase miR-92a expression at the transcriptional level via binding to the estrogen-response-element (ERE) on the 5' promoter region of its host gene C13orf25. The $ER{\beta}$ up-regulated miR-92a could decrease DAB2IP tumor suppressor expression via binding to the miR-92a binding site located on the DAB2IP 3' UTR. Preclinical studies using an in vivo mouse model also confirmed that targeting this newly identified $ER{\beta}$/miR-92a/DAB2IP signal pathway with small molecules could suppress BCa progression. Together, these results might aid in the development of new therapies via targeting of this $ER{\beta}$-mediated signal pathway to better suppress BCa progression.

• BMB Reports
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• v.48 no.11
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• pp.597-598
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• 2015

Mitochondrial respiratory defect is a key bioenergetics feature of hepatocellular carcinoma (HCC) cells. However, their involvement and roles in HCC development and progression remain unclear. Recently, we identified 10 common mitochondrial defect (CMD) signature genes that may be induced by retrograde signaling-mediated transcriptional reprogramming in response to HCC mitochondrial defects. HCC patients with enriched expression of these genes had poor prognostic outcomes, such as shorter periods of overall survival and recurrence-free survival. Nuclear protein 1 (NUPR1), a key transcription regulator, was up-regulated by Ca⁺⁺-mediated retrograde signaling. NUPR1-centric network analysis and a biochemical promoter-binding assay demonstrated that granulin (GRN) is a key downstream effector of NUPR1 for the regulation of HCC cell invasiveness; association analysis of the NUPR1-GRN pathway supported this conclusion. Mitochondrial respiratory defects and retrograde signaling thus play pivotal roles in HCC progression, highlighting the potential of the NUPR1-GRN axis as a novel diagnostic marker and therapeutic target for HCC.

• Molecules and Cells
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• v.45 no.5
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• pp.343-352
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• 2022

The advent of the assay for transposase-accessible chromatin using sequencing (ATAC-seq) has shown great potential as a leading method for analyzing the genome-wide profiling of chromatin accessibility. A comprehensive reference to the ATAC-seq dataset for disease progression is important for understanding the regulatory specificity caused by genetic or epigenetic changes. In this study, we present a genome-wide chromatin accessibility profile of 44 liver samples spanning the full histological spectrum of nonalcoholic fatty liver disease (NAFLD). We analyzed the ATAC-seq signal enrichment, fragment size distribution, and correlation coefficients according to the histological severity of NAFLD (healthy control vs steatosis vs fibrotic nonalcoholic steatohepatitis), demonstrating the high quality of the dataset. Consequently, 112,303 merged regions (genomic regions containing one or multiple overlapping peak regions) were identified. Additionally, we found differentially accessible regions (DARs) and performed transcription factor binding motif enrichment analysis and de novo motif analysis to determine new biomarker candidates. These data revealed the gene-regulatory interactions and noncoding factors that can affect NAFLD progression. In summary, our study provides a valuable resource for the human epigenome by applying an advanced approach to facilitate diagnosis and treatment by understanding the non-coding genome of NAFLD.

• BMB Reports
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• v.52 no.7
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• pp.415-423
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• 2019

Signal transducer and activator of transcription 3 (STAT3) is a cytoplasmic transcription factor that regulates cell proliferation, differentiation, apoptosis, angiogenesis, inflammation and immune responses. Aberrant STAT3 activation triggers tumor progression through oncogenic gene expression in numerous human cancers, leading to promote tumor malignancy. On the contrary, STAT3 activation in immune cells cause elevation of immunosuppressive factors. Accumulating evidence suggests that the tumor microenvironment closely interacts with the STAT3 signaling pathway. So, targeting STAT3 may improve tumor progression, and anti-cancer immune response. In this review, we summarized the role of STAT3 in cancer and the tumor microenvironment, and present inhibitors of STAT3 signaling cascades.

• Journal of Korean Society of Transportation
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• v.25 no.6
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• pp.33-42
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• 2007

This research proposes strategies about providing detour route information and traffic management for flood disasters. Suggested strategies are based on prevention and preparation concepts including prediction, optimization, and simulation in order to minimize damage. Specifically, this study shows the possibility that average travel speed is increased by proper signal progression during downpours or heavy snowfalls. In addition, in order to protect the drivers and vehicles from dangerous situations, this study proposes a route guidance strategy based on variational inequalities such as flooding. However, other roads can have traffic congestion by the suggested strategies. Thus, this study also shows the possibility to solve traffic congestion of other roads in networks with emergency signal modes.

• Journal of Korean Society of Transportation
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• v.20 no.6
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• pp.31-43
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• 2002

Traffic signal control methods are suggested to improve the operational effectiveness of COSMOS system in Seoul. First. a method that improves progression of the corridor traffic flow within a common sub-area was explored. Applying this method, both frequency and magnitude of offset transition were reduced as compared to the existing method. In addition, the level of connection among neighboring corridors increased by applying the method, thus the qualify of progression was also improved. Second, a practical guideline on signal phase design was proposed to improve the efficiency of actuated operations for the left-turn movement. Last, a method for estimating optimal queue length parameters was surveyed and evaluated. An evaluation study was performed for the suggested methods through both field and simulation studies. Results showed that the proposed methods gave better performance than the existing methods. It is expected that the use of proposed methods can improve operational performance of COSMOS.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.31 no.5
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• pp.399-408
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• 2005

In the progression of the Temporomandibular Joint Disorder(TMD), not only deformation and perforation of disc occur. But also fibrotic adhesion and inflammatory changes to the retrodiscal tissue can be seen in addition to the condylar degenerative change (e.g. osteoarthritis). However, the correct diagnosis,?planning for appropriate treatment, and prediction of prognosis are limited, because there are no means to stage the progression of the disorder. In this study relative signal intensity of retrodiscal tissue in MRI and the synovial fluid concentration of matrix metalloproteinase-2 (MMP-2), MMP-9, and Interleukin-6(IL-6) in the 23 temporomandibular joints(TMJ), from 17 patients with TMD were evaluated as a possible diagnostic marker. The relative signal intensity of retrodiscal tissue was referenced to brain gray matter with same region of interest(ROI) size. The concentrations of MMP-2, MMP-9, and IL-6 were evaluated by Enzyme Linked Immunosorbent Assay (ELISA). The collected data were compared with condylar degenerative change, joint effusion and disc position observed in MRI. The relative signal intensity of the retrodiscal tissue was increased significantly when degenerative changes were present. In addition, there was significantly high signal intensity in the presence of a disc displaced without reduction. The concentration of IL-6 was significantly increased when condylar degenerative change was no observed. And there were no changes in the levels of IL-6 according to disc position and joint effusion measurement. Moreover, there were no significant relevance between the concentration of total MMP-2 and active MMP-9 in synovial fluid, relative to degenerative changes in the mandibular condyle, to joint effusion, and to disc position observed on MRI images. In conclusion, the relative signal intensity of the retrodiscal tissue can be regarded as a mean of diagnosing the procession of TMD in a non-invasive manner. But more additional studies are required for the levels of MMP-2. MMP-9, and IL-6 to determine their potentials as a diagnostic marker for TMD.

• Journal of Veterinary Clinics
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• v.30 no.5
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• pp.339-345
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• 2013

Mitogen-activated protein kinases (MAPKs) are a family of central signaling molecules that respond to numerous stimuli and are known to participate in processes of cell survival and death. However, it is not clear on data for cell-type specific activation of MAPKs in the progression of gastric ulcer. In the present study, we assessed how MAPKs localized at various cell types during the progression of gastric ulcer induced by ibuprofen. Gastric ulcer was induced by the repeated treatment of 200 mg/kg ibuprofen with 8 hrs interval in a day. Animals were sacrificed at 24 hrs, 48 hrs, and 72 hrs after oral treatment of ibuprofen and gastric tissues were subjected to immunohistochemical and immunoblotting evaluation. Immunoreactivity of phospho-extracellular signal-regulated kinase (p-ERK) was mainly expressed at the proliferating zone of gastric mucosa in control rats. But, these signals for p-ERK were highly shifted from cells of proliferating zone to parietal cells of the basal regions 24 hrs after treatment of ibuprofen. p-ERK signal was strongly expressed in epithelial cells adjacent to ulcer margin and new capillary and infiltrated inflammatory cells within granulation tissue of the ulcer base above 48 hrs after treatment of ibuprofen. While, phospho-c-Jun $NH_2$ terminal kinase (p-JNK) was mainly localized to the nuclei of the surface epithelial cells and the glandular epithelial cells in early gastric injury. Also, p-JNK was often observed as a scattered pattern in different regions of gastric mucosa with early gastric injury. Gradually, signal of p-JNK was strongly stained in infiltrated inflammatory cells and fibroblasts within severe ulcer base. Phospho-p38 (p-p38) MAPK was observed as scattered pattern within connective tissues of gastric mucosa. Especially, p-p38 MAPK showed strong signal in infiltrated macrophages within ulcer base. These results show that each MAPK has a specific role in various cell types during the progression of gastric ulcer.

• Korean Journal of Pharmacognosy
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• v.50 no.1
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• pp.18-24
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• 2019

Andrographolide, the main compound of Andrographis paniculata (A. paniculata), shows various biological properties including anti-viral, anti-inflammatory, anti-diabetic, and hepatoprotective effects. Our previous study has shown that A. paniculata extract exerts antiaging effects by activation of stemness in epidermal stem cells (EpSCs). In this study, we investigated the effect of andrographolide as a main compound of A. paniculata on EpSCs and its mechnism of action using several in vitro assays. Andrographolide increased the proliferation of EpSCs and induced cell cycle progression. Additionally, andrographolide increased VEGF production and the expression of stem cell markers integrin ${\beta}1$ and p63. Furthermore, phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), S6 ribosomal protein (S6RP) and Akt were increased by andrographolide. Taken together, these results indicate that andrographolide-induced proliferation of EpSCs is mediated by the ERK1/2, Akt-dependent pathway with increased production of VEGF and upregulated stemness through integrin ${\beta}1$ and p63.

• Transactions of the Korean Society of Automotive Engineers
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• v.14 no.5
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• pp.84-92
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• 2006

Freeway Corridors consist of urban freeways and parallel arterials that drivers can use alternatively. Ramp metering in freeways and signal control in arterials are contemporary traffic control methods that have been developed and applied in order to improve traffic conditions of freeway corridors. However, most of the existing studies have focused on either optimal ramp metering in freeways, or progression signal strategies between arterial intersections. There have been no traffic control systems in Korea that integrates the freeway ramp metering and arterial signal control. The effective control strategies for freeway operations may cause negative effects on arterial traffic. On the other hand, traffic congestion and bottleneck phenomenon of arterials due to the increasing peak-hour travel demand and ineffective signal operation may generate an accessibility problem to freeway ramps. Thus, the main function of the freeway which is the through-traffic process has not been successful. The purpose of this study is to develop an integrated control model that connects freeway ramp metering systems and signal control systems in arterial intersections. And Optimization of integrated control model which consists of ramp metering and signal control is another purpose. Optimization results are verified by comparison with the results from MATDYMO.