• BMB Reports
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• v.52 no.2
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• pp.119-126
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• 2019

The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) initiates the extrinsic apoptotic pathway through formation of the death-inducing signaling complex (DISC), followed by activation of effector caspases. TRAIL receptors are composed of death receptors (DR4 and DR5), decoy receptors (DcR1 and DcR2), and osteoprotegerin. Among them, only DRs activate apoptotic signaling by TRAIL. Since the levels of DR expressions are higher in cancer cells than in normal cells, TRAIL selectively activates apoptotic signaling pathway in cancer cells. However, multiple mechanisms, including down-regulation of DR expression and pro-apoptotic proteins, and up-regulation of anti-apoptotic proteins, make cancer cells TRAIL-resistant. Therefore, many researchers have investigated strategies to overcome TRAIL resistance. In this review, we focus on protein regulation in relation to extrinsic apoptotic signaling pathways via ubiquitination. The ubiquitin proteasome system (UPS) is an important process in control of protein degradation and stabilization, and regulates proliferation and apoptosis in cancer cells. The level of ubiquitination of proteins is determined by the balance of E3 ubiquitin ligases and deubiquitinases (DUBs), which determine protein stability. Regulation of the UPS may be an attractive target for enhancement of TRAIL-induced apoptosis. Our review provides insight to increasing sensitivity to TRAIL-mediated apoptosis through control of post-translational protein expression.

• Journal of Acupuncture Research
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• v.31 no.2
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• pp.87-98
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• 2014

Objectives : We investigated whether snake venom toxin(SVT) from Vipera lebetina turanica sensitizes HT29 human epithelial colorectal cancer cells to tumor necrosis factor(TNF)-related apoptosis-inducing ligand(TRAIL) induced apoptosis in cancer cells. Methods : Cell viability assay was used to assess the inhibitory effect of TRAIL on cell growth of HT29 human colorectal cancer cells. And 6-diamidino-2-phenylindole(DAPI), terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay(TUNEL) staining assay were used to evaluate cell-apoptosis. Western blot analysis were conducted to observe apoptosis related proteins and death receptor. To assess whether the synergized inhibitory effect of SVT and TRAIL on reactive oxygen species(ROS) generation was reversed by strong anti-oxidative agent. Results : SVT with TRAIL inhibited HT29 cell growth different from TRAIL alone. Consistent with cell growth inhibition, the expression of TRAIL receptors; Expression of death receptor(DR)4 and DR5 was significantly increased and intrinsic pro-apoptotic cleaved caspase-3, -9 was subsequently increased together with increase of Bax/Bcl-2 ratio and extrinsic pro-apototic caspase-8 was also activated. In addition, the expression of anti-apoptotic survival proteins, a marker of TRAIL resistance(eg, cFLIP, survivin, X-linked inhibitor of apoptosis protein(XIAP) and Bcl-2) was suppressed by the combination treatment of SVT and TRAIL. Pretreatment with the ROS scavenger N-acetylcysteine abolished the SVT and TRAIL-induced upregulation of DR4 and DR5 expression and expression of the intrinsic pro-apoptotic caspase-3 and-9. Conclusion : The collective results suggest that SVT facilitates TRAIL-induced apoptosis in $HT_{29}$ human epithelial colorectal cancer cells through up-regulation of the TRAIL receptors; DR4 and DR5 and consecutive induction of bilateral apoptosis via regulating apoptosis related proteins.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2751-2756
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• 2015

Background: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can specifically induce apoptosis limited to various cancer cells, so this reagent is considered a promising medicine for cancer therapy. TRAIL also exerts effects on non-apoptotic signals, relevant to processes such as metastasis, autophagy and proliferation in cancer cells. However, the mechanisms of TRAIL-regulated non-apoptotic signals are unclear. The purpose of this study was to investigate MADD/CXCR7 effects in TRAIL-mediated breast cancer cell migration. Materials and Methods: The ability of MADD/CXCR7 to regulate MVP signaling in TRAIL-mediated breast cancer cells migration was evaluated by transwell migration assay, quantitative RT-PCR, Western blotting and knock down experiments. Results: In this study, we found that treatment with TRAIL resulted in induced expression levels of MADD and CXCR7 in breast cancer cells. Knock down of MADD followed by treatment with TRAIL resulted in increased cell migration compared to either treatment alone. Similarly, through overexpression and knockdown experiments, we demonstrated that CXCR7 also positively regulated TRAIL-inhibited migration. Surprisingly, knock down of MADD lead to inhibition of TRAIL-induced CXCR7 mRNA and protein expression and overexpression of CXCR7 lead to the reduction of MADD expression, indicating that MADD is an upstream regulatory factor of TRAIL-triggered CXCR7 production and a negative feedback mechanism between MADD and CXCR7. Furthermore, we showed that CXCR7 is involved in MADD-inhibited migration in breast cancer cells. Conclusions: Our work defined a novel signaling pathway implicated in the control of breast cancer migration.

• Korean Journal of Environment and Ecology
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• v.10 no.2
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• pp.191-204
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• 1997

Eight major trails of Soraksan National Park were selected to investigate the use impacts on environmental edterioration of trail according to the different amount of use. The entire width, bare width, maximum depth and slope of trail as the trail condition surveyed at the total of 188 points were significantly greater on the more heavily-used trail. Major deterioration types of trail were root-exposure, widening, rock-exposure, divergence in order of frequency. And trail conditions of edteriorated points were significantly different from those of non-deteriorated points. The damaged area more severe than Class 4 on trail reached about 10,864m$^{2}$ in total, and especially about 4,560m$^{2}$ in the section between Huiunkak Shelter-Munomigogae trail. The dominant trees of trail edge vegetation were be Quercus mongolica in upper layer, but in lower lauer Carpinus laxiflora, Lespedeza maximowiczii for valley and Carpinus laxiflora, Ghododendron mucronulatum var. cilatum, Tripterygium regelii for ridge.. Especially coverage and number of individuals was highest on Munomighgae-Taech'ongbong trail of the largest use of amount, and each trail was dissimilar in species composition of lower layer of edge vegetation.

• Journal of Korean Society of Forest Science
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• v.101 no.2
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• pp.309-316
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• 2012

The purpose of this study is to conduct a visitor survey which provides demographical characteristics, a profile of the characteristic, travel behavior in different forest trails; Bukhansan trail, Uljin trail, Jirisan trail. Bukhansan trail (second course) is about 3 km and many visitors are nearby residents for the walking. Uljin trail is 80 km, especially conducting visitor reservation guide system and most visitors are 30s and 50s. Jirisan trail is total 209.3 km (a total of 17 courses), networking regional trail routes and was most popular between the ages of 20 and 39. The results showed that Bukhansan trail was used for light walking course, and visitors preferred health related activities. In Uljin trail, visitors expected trekking with nature-based activities and visitors of Jirisan trail seemed to prefer trekking and request more trail's walkability than other trail users.

• Korean Journal of Environment and Ecology
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• v.5 no.1
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• pp.91-103
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• 1991

Use impacts on environmental deteriorations of trail and campsite were studied in Chirisan National Park in 1991. The entire width, bare width and maximum depth of trail as the trail condition were significantly greater on the more heavily used trail. Trail conditions, especially altitude, entire width and maximum depth of deteriorated points which were surveyed at the total of 82 were significantly different from those of non-deteriorated points. On the ridge trail, the damaged are more severe than Class 4 reaches about 34,000$m^2$ and use impacts on campsite and deterioration were also accelerated. The dominant trees of the upper layer in trail edge vegetation are changed from Carpinus tschonoskii to Quercus serrata, Carpinus laxiflora and to Quercus mongolica, Carpins laxiflora at Hwaeomsa trail, and from Quercus serrata to Quercus mongolica at Piagol trail. Also Lespedoza maximowiczii, Symplocos chinensis, Deutzia prunifolia, Weigela Subsessilis appear as the dominant lower species at Hwaeomsa trail, L. maximowiczii, S. chinensis, Stephanandra incisa, Rhododendron schlippenbachii for Piagol trail.

• Journal of Wetlands Research
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• v.17 no.2
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• pp.176-183
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• 2015

This study is aimed at deducting the evaluation standard of the walking tour trail and evaluating the real condition of trail facilities and operation & management. On the basis of the research on the walking tour, this study deducted the evaluation index of the trail facilities and administrative control, and divided it into visit resources, visit facilities and trail operation-management. This study selected the course of high use satisfaction among the Ganghwa Nadeul-gil section, and evaluated the real condition of Ganghwa Nadeul-gil trail by classifying the route as nature-oriented trail and culture-oriented trail. In case of nature-oriented trail, it's necessary to discover living culture resources of the village linked with the trail, and to develop amenities using bus stations and supermarket. In case of culture-oriented trail, it's required that economic regeneration plan should be arranged using the declining facilities.

• Korean Journal of Environment and Ecology
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• v.6 no.2
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• pp.168-179
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• 1993

Use impacts on environmental deteriorations of trail were studied on the three major trails of Sobaeksan National Park in 1992. The entire width and bare width of trail as the trail condition were significantly greater on the more heavily used trail. Maximum depth of trail was not so great in spite of steeper grade of trail in comparison with the other National Parks. Percentages of deepening. rock-exposed. diverged points as the deterioration types of trail which were surveyed at the total of 105 points were high and trail conditions were significantly different from those of non-deteriorated points. On the Ridge trail. the damaged area more severe than Class 4 reaches about 10,335$m^2$ and the deterioration is accelerated. The dominant trees of the the upper layer in trail edge vegetation are changed from Q. mongolica. Aar mono to Q. mongolica for Huibang trail. and from Pinus densiflora. Q. mongolica to P. densiflora and to Q. mongolica for Biro trail as altitude increases. Rhododendron schlippenbachii. Weigelu subsessilis. Salix hulteni. Rubus crataeglfolius were classified for tolerant species and R. coreanus. Vaccinium koreanum for intolerant species to use impacts. Highly competetive species on the Ridge trail were grouped R. schlippenbachii. W. subsessilis. Rubus crataegifolius and Symplocos chinensis for. pilosa.

• Korean Journal of Environment and Ecology
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• v.1 no.1
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• pp.35-45
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• 1987

To survey trail damage and vegetational change around trail at Bukhan Mountain National Park in Korea, field survey was executed over Bukhan mountain district during August, 1987. Trail damage was surveyed for he section of 7.18km from Ui valley to Jeongnung valley in which user's density was high. Ground vegetation was surveyed with a belt-transect method from trail edge to forest and edge species were surveyed with a belt method along trail edge. Interrelation between trail damage and user's density was not dear. Damage class II of trail showed 23.9% of the surveyed section and class III showed 8.0% and class II and III of natural trail showed 19.7% and those of facilitated trail showed 12.3%. The length of damage class II and III requiring readjustment were estimated as 3.65 km and 1.22km from the main trail course of 15.3km at Bukhan mountain district. In case of no intervention to forest by users, vegetational change around trails was appeared up to 6-8 m from trailside. But in case of intervention to forest by users, vegetational change was not coincident with the change of soil hardness and was diverse locally. Quercus mongolica, Lespedeza cyrtobotrya and Rbo-dodendron mucronulatum were appeared as Raunkiaer frequency class E, and Weigela subsessilis. Lespedeza maximowiczii, Rhododendron schlippenbachii and Sorbus alnifolid were appeared as class D at trail edge of ridge-Quercus mongolica was appeared as class E and Rhododenderon mucrounulatium. Stephanandra incisa were appeared as class D at trail edge of midslope. Rhododenron mucronulatum. Lespedeza maximowiczii and Stepanandra incisa were appeared as class D at trail edge of valley. Lespedeza cyrtobotrya. Lespedeza maximowiczii and Stephanandra incisa were appeared as class D at trail edge of valley beside motorway.

• Korean Journal of Environment and Ecology
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• v.18 no.2
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• pp.175-183
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• 2004

They are raising the necessity to prepare the conservational management strategy for the trail on the ridge of the Baekdudaegan where deterioration of natural environment along the trail as the rapid increase of visitors to the Baekdudaegan. The purpose of this study, followed after the Kwon and Lee(2003), is to research the deterioration condition of the trail between Namdeogyusan and Sosagogae on the Baekdudaegan. To accomplish the purpose, not only trail condition such as altitude, entire width, bare width, maximum depth and slope of trail, but also deterioration types of trail were surveyed at the total 182 points for 32.3km in length. Furthermore, impact rating class, which could be effective means to check the step and extent of deterioration process, was judged on each points of trail. Results informs us that the deterioration condition of the trail between Namdeogyusan and Sosagogae is not reached the level of grave concern yet, but some points and sections of trail are in urgent need of the integrated and organized maintenance. And some managerial strategies of trail were proposed in connection with the maintenance for trail on the Baekdudaegan ridge.