• The Korean Journal of Physiology and Pharmacology
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• v.26 no.6
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• pp.457-468
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• 2022

It has been demonstrated that APPL1 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1) is involved in the regulation of several growth-related signaling pathways and thus closely associated with the development and progression of some cancers. Diallyl trisulfide (DAT), a garlic-derived bioactive compound, exerts selective cytotoxicity to various human cancer cells through interfering with pro-survival signaling pathways. However, whether and how DAT affects survival of human hepatocellular carcinoma (HCC) cells remain unclear. Herein, we tested the hypothesis of the involvement of APPL1 in DAT-induced cytotoxicity in HCC HepG2 cells. We found that Lys 63 (K63)-linked polyubiquitination of APPL1 was significantly decreased whereas phosphorylation of APPL1 at serine residues remained unchanged in DAT-treated HepG2 cells. Compared with wild-type APPL1, overexpression of APPL1 K63R mutant dramatically increased cell apoptosis and mitigated cell survival, along with a reduction of phosphorylation of STAT3, Akt, and Erk1/2. In addition, DAT administration markedly reduced protein levels of intracellular TNF receptor-associated factor 6 (TRAF6). Genetic inhibition of TRAF6 decreased K63-linked polyubiquitination of APPL1. Moreover, the cytotoxicity impacts of DAT on HepG2 cells were greatly attenuated by overexpression of wild-type APPL1. Taken together, these results suggest that APPL1 polyubiquitination probably mediates the inhibitory effects of DAT on survival of HepG2 cells by modulating STAT3, Akt, and Erk1/2 pathways.

• Journal of Korean Society of Transportation
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• v.10 no.2
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• pp.25-42
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• 1992

The purpose of this paper is to construct a model to compute a progression adjustment factor on a signalized network. In a way to construct the model, a simulation method is introduced and the TRAF-NETSIM is used as a tool of simulation. The structure of the network chooses an urban arterial network so as to measure the effect of progression and compute average stopped delay on each link. A regression model is constructed by using the results of the simulation. The stepwise variable selection in the regression model in used. The findings of this paper are as follows: i)The secondary queue and platoon ratio are sensitive to the values of the progression adjustment factor ii) The continuous model can practically reflect on various situations in the real world. The platoon adjustment factor can be computed by this model and the data required for this model can be easily obtained in the field.

• Journal of Korean Society of Transportation
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• v.12 no.2
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• pp.5-30
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• 1994

다이아몬드형 인터체인지는 고속도로와 노면가로가 교차할 경우 방향별 교통류를 처리하는데 보편적으로 사용하는 인터체인지이다. 인터체인지에 교통량의 부하가 과도해지 면 인터체인지내부의 교차로에서 발생한 대기차량이 종종 고속도로본선으로 역류하여 본선 의 교통소통에 문제를 야기하며 특히 고속도로의 안전에도 큰 위험요소가 된다. 본 논문은 과포화상태의 다이아몬드형 인터체인지의 교통신호제어를 다루며, 신호시간계획을 산출하는 동적 최적화모형(dynamic optimization model)을 제시한다. 최적화 모형은 지체도최소화를 목적함수로 하며, 함수계측법의 형태가 된다. 본 모형의 핵심은 신호제어에 따라 발생하는 대기차량길이를 모형화하여 대기차량길이가 정해진 상한치를 초과하지 않도록 하는 신호시 간계획을 산출하는데 있다. 제시된 동적모형은 다이아몬드형 인터체인지의 신호시간을 위하 여 널리 사용되는 PASSER III와 최적해를 상호 비교한다. TRAF-NETSIM을 통한 시뮬레이 션의 결과에 따르면 동적 모형이 우수한 결과를 보이며, 대기차량의 길이를 효과적으로 제 어하는 것으로 판명된다.

• Journal of the Korean Society of Marine Environment & Safety
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• v.26 no.1
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• pp.31-38
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• 2020

The characteristics of ship traffic routes and the long term fluctuation in marine traf ic volume of the incoming and outgoing routes of the Yeosu Gwangyang Port were analyzed using vessel traffic data from the past 22 years and a real-time vessel traffic volume survey performed for 72 hours per year, for three years, between 2015 and 2017. As of 2017, the number of vessels passing through Yeosu Gwangyang Port was about 66,000 and the total tonnage of these ships was about 804,564 thousand tons, which is a 400 % increase from the 189,906 thousand tons shipped in 1996. Specifically, the dangerous cargo volume was 140,000 thousand tons, which is a 250 % increase compared to 1996. According to the real-time vessel traffic volume survey, the average daily number of vessels was 357, and traf ic route utilization rates were 28.1 % in the Nakpo sea area, 43.8 % in the specified sea area, and the coastal area traf ic route, Dolsan coastal area, and Kumhodo sea area showed the same rate of 6.8 %. Many routes meet in the Nakpo sea area and, parallel and cross passing were frequent. Many small work vessels entered the specific sea area from the neighboring coastal area traffic route and frequently intersected the path of larger vessels. The anchorage waiting rate for cargo ships was about 24 %, and the nightly passing rate for dangerous cargo ships such as chemical vessels and tankers was about 20 %. Although the vessel traffic volume of Yeosu Gwangyang Port increases every year, the vessel traffic routes remain the same. Therefore, the risk of accidents is constantly increasing. The route conditions must be improved by dredging and expanding the available routes to reduce the high risk of ship accidents due to overlapping routes, by removing reefs, and by reinforcing navigational aids. In addition, the entry and exit time for dangerous cargo ships at high-risk ports must be strictly regulated. Advancements in the VTS system can help to actively manage the traffic of small vessels using the coastal area traffic route.

• The Journal of Internal Korean Medicine
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• v.29 no.3
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• pp.543-553
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• 2008

Objective: The goal of this study was to determine the anti-asthma mechanism of SF on TNF-${\alpha}$ induced activation on A549 (human type II-like epithelial) cells. Using oligonucleotide microarray, we sought to establish the molecular mechanism of the protective effects of SF on A549 cells. Material & Methods : Cells were cultured in three different conditions: 1) negative control group was cultured in normal condition of DMEM, 2) positive control group was activated with TNF-${\alpha}$, IL-4. and IL-1${\beta}$, and 3) SF treated group was previously treated with 0.1${\mu}g/ml$ SF after TNF-${\alpha}$, IL-4. and IL-1 activation. Cells of positive control and SF treated groups were cultured for 30 min, 1hr, 3hr and 6hr. Results : The comparative analysis of the gene expression profile revealed that proinflammatory cytokines such as IL1F8, IL1F9, IL1R1. IL1RN, IL1RAPL1, IL8, TNFRSF4, TNFSF10c, TNFSF13, TRAF5, and TRAF7 and inflammation-related genes including MMP2, MMP11, MMP14, MMP15, MMP16, MMP19, MMP25, and MMP27 were down regulated with SF treatment. Cell adhesion molecule genes such as ITGB1, ITGBL1, selectin P ligand, selectin E, ICAM2, ICAM3, VCAM1, PECAM, FCER1G and MMP28 genes were also down-regulated in SF treated A549 cells. Conclusion : These results suggest that the anti-asthmatic effects of SF could be mediated by regulating specific genes related with cell adhesion, proinflammatory cytokine and inflammation-related genes in A549 cells.

• Journal of Life Science
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• v.31 no.4
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• pp.389-399
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• 2021

This study determined the effects of Centella asiatica leaf on H₂O₂ induced cell cycle arrest, mitochondrial activity, and proinflammatory cytokine production in human dermal fibroblast (HDF) cells. We used an 80% methanol extract of C. asiatica, its ethyl acetate fraction, and asiaticoside, the major constituent of C. asiatica. The C. asiatica extract, its ethyl acetate fraction, and asiaticoside attenuated G1 cell cycle-arrest and the apoptotic effect caused by H₂O₂-induced oxidative stress. The cells treated with C. asiatica extract, its ethyl acetate fraction, and asiaticoside secreted lower levels of TNF-α and IL-6. The antioxidant effect of asiaticoside was higher than that of C. asiatica extract and its ethyl acetate fraction. Treatment with C. asiatica extract, its ethyl acetate fraction, and asiaticoside also increased the mitochondrial membrane potential and restored normal mitochondrial morphology. Following H₂O₂ stress induction, cells treated with C. asiatica extract, its ethyl acetate fraction, and asiaticoside showed increased mitochondrial oxygen consumption rates and decreases in the TLR4-MyD88-TRAF6-p65 pathway activity. These findings suggest that C. asiatica extract, its ethyl acetate fraction, and asiaticoside have antioxidant and anti-inflammatory effects, as well as the ability to control the mitochondrial activities of HDF cells.

• IMMUNE NETWORK
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• v.8 no.1
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• pp.1-6
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• 2008

Apoptosis signal-regulating kinase 1 (ASK1), a mitogen- activated protein kinase kinase kinase, plays pivotal roles in stress responses. In addition, ASK1 has emerged as a key regulator of immune responses elicited by pathogen-associated molecular patterns (PAMPs) and endogenous danger signals. Recent studies have demonstrated that reactive oxygen species (ROS)-dependent activation of ASK1 is required for LPS-stimulated cytokine production as well as extracellular ATP-induced apoptosis in immune cells. The mechanism of ROS-dependent regulation of ASK1 activity by thioredoxin and TRAFs has been well characterized. In this review, we focus on the molecular details of the activation of ASK1 and its involvement in innate immunity.

• Journal of the Korean Society of Food Culture
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• v.33 no.4
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• pp.337-344
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• 2018

Germinated brown rice (GBR, Orysa sartiva L.) has been reported to have anti-obesity and anti-inflammatory effects. However, the mechanisms underlying these effects in adipocytes are not fully understood. Therefore, this study was conducted to explore the anti-inflammatory mechanisms of GBR on lipopolysaccharide (LPS)-stimulated 3T3-L1 adipocytes. 3T3-L1 adipocytes were pretreated with GBR extracts (0-20 mg/mL) 1 h before LPS stimulation. The mRNA expression of adipokines and Toll-like receptor 4 (TLR4) were measured by RT-PCR. The protein expressions of TLR4-related molecules were detected by western blotting and nuclear factor-${\kappa}B$ ($NF-{\kappa}B$) activation was measured. Our results showed that GBR extract dose-dependently inhibited mRNA expression of LPS-induced tumor necrosis factor-${\alpha}$ ($TNF-{\alpha}$), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). GBR extract was found to inhibit LPS-induced mRNA expression of TLR4 and protein expression of both myeloid differentiation factor 88 (MyD88) and TNF receptor-associated factor 6 (TRAF6). Furthermore, GBR extract significantly inhibited extracellular receptor-activated kinase (ERK) phosphorylation and $NF-{\kappa}B$ activation. These results suggest that GBR extract has the anti-inflammatory effects on LPS-induced inflammation via inhibition of TLR4 signaling, includingthe ERK and $NF-{\kappa}B$ signaling pathways, in adipocytes.

• Bulletin of the Korean Chemical Society
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• v.34 no.4
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• pp.1089-1095
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• 2013

The tumor necrosis factor-receptor 1 (TNFR1)-associated death domain protein (TRADD) contains an N-terminal TRAF binding domain and a C-terminal death domain. TRADD is known to interact directly with TNF receptor 2 (TNFR2) and the Fas-associated death domain protein (FADD), which are signal transducers that activate NF-${\kappa}B$ and induce apoptosis, respectively. To date, there has been no structural information on the TRADD and FADD death domain (DDs) complex. In this study, the death domains of TRADD and FADD were co-expressed and purified from Escherichia coli for structural characterization. We found that human TRADD (hTRADD) interacted strongly with mouse FADD (mFADD) via their DDs and interacted weakly with human FADD (hFADD)-DD. Moreover, the structures of the TRADD-DD:FADD-DD complexes were separately modeled from predicted structures in the protein data bank (PDB). The results of this study will have important applications in human diseases such as cancer, AIDS, degenerative and autoimmune diseases, and infectious diseases.

• International Journal of Oral Biology
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• v.44 no.3
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• pp.89-95
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• 2019

Piperlongumine (PL) is a natural product found in long pepper (Piper longum). The pharmacological effects of PL are well known, and it has been used for pain, hepatoprotection, and asthma in Oriental medicine. No studies have examined the effects of PL on bone tissue or bone-related diseases, including osteoporosis. The current study investigated for the first time the inhibitory effects of PL on osteoclast differentiation, bone resorption, and osteoclastogenesis-related factors in RAW264.7 macrophages stimulated by the receptor activator for nuclear factor-${\kappa}B$ ligand (RANKL). Cytotoxicity was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and osteoclast differentiation and bone resorption were confirmed by tartrate-resistant acid phosphatase (TRAP) staining and pit formation analysis. Osteoclast differentiation factors were confirmed by western blotting. PL exhibited toxicity in RAW264.7 macrophages, inhibiting osteoclast formation and bone resorption, in addition to inhibiting the expression of osteoclastogenesis-related factors, such as tumor necrosis factor receptor-associated factor 6 (TRAF6), c-Fos, and NFATc1, in RANKL-stimulated RAW264.7 macrophages. These findings suggest that PL is suitable for the treatment of osteoporosis, and it serves as a potential therapeutic agent for various bone diseases.