• IMMUNE NETWORK
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• v.16 no.4
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• pp.242-248
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• 2016

Thymic atrophy is a complication that results from exposure to many environmental stressors, disease treatments, and microbial challenges. Such acute stress-associated thymic loss can have a dramatic impact on the host's ability to replenish the necessary naïve T cell output to reconstitute the peripheral T cell numbers and repertoire to respond to new antigenic challenges. We have previously reported that treatment with the orexigenic hormone ghrelin results in an increase in the number and proliferation of thymocytes after dexamethasone challenge, suggesting a role for ghrelin in restraint stress-induced thymic involution and cell apoptosis and its potential use as a thymostimulatory agent. In an effort to understand how ghrelin suppresses thymic T cell apoptosis, we have examined the various signaling pathways induced by receptor-specific ghrelin stimulation using a restraint stress mouse model. In this model, stress-induced apoptosis in thymocytes was effectively blocked by ghrelin. Western blot analysis demonstrated that ghrelin prevents the cleavage of pro-apoptotic proteins such as Bim, Caspase-3, and PARP. In addition, ghrelin stimulation activates the Akt and Mitogen-activated protein kinases (MAPK) signaling pathways in a time/dose-dependent manner. Moreover, we also revealed the involvement of the FoxO3a pathway in the phosphorylation of Akt and ERK1/2. Together, these findings suggest that ghrelin inhibits apoptosis by modulating the stress-induced apoptotic signal pathway in the restraint-induced thymic apoptosis.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.1
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• pp.21-30
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• 2024

The challenging clinical outcomes associated with advanced cervical cancer underscore the need for a novel therapeutic approach. Monensin, a polyether antibiotic, has recently emerged as a promising candidate with anti-cancer properties. In line with these ongoing efforts, our study presents compelling evidence of monensin's potent efficacy in cervical cancer. Monensin exerts a pronounced inhibitory impact on proliferation and anchorage-independent growth. Additionally, monensin significantly inhibited cervical cancer growth in vivo without causing any discernible toxicity in mice. Mechanism studies show that monensin's anti-cervical cancer activity can be attributed to its capacity to inhibit the Wnt/β-catenin pathway, rather than inducing oxidative stress. Monensin effectively reduces both the levels and activity of β-catenin, and we identify Akt, rather than CK1, as the key player involved in monensin-mediated Wnt/β-catenin inhibition. Rescue studies using Wnt activator and β-catenin-overexpressing cells confirmed that β-catenin inhibition is the mechanism of monensin's action. As expected, cervical cancer cells exhibiting heightened Wnt/β-catenin activity display increased sensitivity to monensin treatment. In conclusion, our findings provide pre-clinical evidence that supports further exploration of monensin's potential for repurposing in cervical cancer therapy, particularly for patients exhibiting aberrant Wnt/β-catenin activation.

• Clinical and Experimental Reproductive Medicine
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• v.51 no.3
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• pp.236-246
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• 2024

Objective: Nicotinamide mononucleotide (NMN) is extensively utilized as an anti-aging agent and possesses anti-inflammatory properties. Lipopolysaccharide (LPS) activates Toll-like receptor 4, a process modulated by intracellular signaling pathways such as the Wnt/β-catenin pathway. This study investigated the impact of NMN on osteogenesis in the presence of LPS. Methods: To elucidate the role of NMN in osteogenesis in the context of Gram-negative bacterial infection after LPS treatment, we cultured a mouse pre-osteoblast cell line (MC3T3-E1) and subsequently incubated it with NMN and/or LPS. We then evaluated osteogenic activity by measuring alkaline phosphatase activity, assessing gene expression and protein levels, and performing Alizarin Red S staining and immunocytochemistry. Results: MC3T3-E1 cells underwent successful differentiation into osteoblasts following treatment with osteogenic induction medium. LPS diminished features related to osteogenic differentiation, which were subsequently partially reversed by treatment with NMN. The restorative effects of NMN on LPS-exposed MC3T3-E1 cells were further substantiated by elucidating the role of Wnt/β-catenin signaling, as confirmed through immunocytochemistry. Conclusion: This study showed that infection with Gram-negative bacteria disrupted the osteogenic differentiation of MC3T3-E1 cells. This adverse effect was partially reversed by administering a high-dose of NMN. Drawing on these results, we propose that NMN could serve as a viable therapeutic strategy to preserve bone homeostasis in elderly and immunocompromised patients.

• Journal of Preventive Medicine and Public Health
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• v.24 no.4 s.36
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• pp.485-495
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• 1991

This study examined the effects of referral requirements for insurance patients which have been enforced since July 1, 1989 when medical insurance coverage was extended to the whole population except beneficiaries of medical assistance program. The requirements are mainly aimed at discouraging the use of tertiary care hospitals by imposing restrictions on the patient's choice of a medical service facility. The expectation is that such change in the pattern of medical care utilization would produce several desirable effects including increased efficiency in patient care and balanced development of various types of medical service facilities. In this study, these effects were assessed by the change in the number of out-patient visits and bed-days per illness episode and the share of each type of facility in the volume of services and the amount of expenditures after the implementation of the new referral system. The data for analysis were obtained from the claims to the insurance for government and school employees. The sample was drawn from the claims for the patients treated during the first six months of 1989, prior to the enforcement of referral requirements, and those of the patients treated during the first six months of 1990, after the enforcement. The 1989 sample included 299,824 claims (3.6% of total) and the 1990 sample included 332,131 (3.7% of total). The data were processed to make the unit of analysis an illness episode instead of an insurance claim. The facilities and types of care utilized for a given illness episode are defined to make up the pathway of medical care utilization. This pathway was conceived of as a Markov Chain process for further analysis. The conclusion emerged from the analysis is that the enforcement of referral requirements resulted in less use of tertiary care hospitals, and thereby decreased the volume of services and the amount of insurance expenses per illness episode. However, there are a few points that have to be taken into account in relation to the conclusion. The new referral system is likely to increase the use of medical services not covered by insurance, so that its impact on national health expenditures would be different from that on insurance expenditures. The extension of insurance coverage must have inereased patient load for all types of medical service organizations, and this increase may be partly responsible for producing the effects attributed to the new referral system. For example, excessive patient load for tertiary care hospitals may lead to the transfer of their patients to other types of facilities. Another point is that the data for this study correspond to very early phase of the new system. But both patients and medical care providers would adapt themselves to the new system to avoid or overcome its disadvantages for them, so as that its effects could change over time. Therefore, it is still necessary to closely monitor the impact of the referral requirements.

• Journal of Korea Water Resources Association
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• v.55 no.2
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• pp.159-170
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• 2022

As the severity of water-related disasters increases in urban watersheds due to climate change, reducing flood damage in urban watersheds is one of the important issues. This study focuses on prioritizing the optimal site for permeable pavement to maximize the efficiency of reducing flood damage in urban watersheds in the future climate environment using multi-criteria decision making techniques. The Mokgamcheon watershed which is considerably urbanized than in the past was selected for the study area and its 27 sub-watersheds were considered as candidate sites. Six General Circulation Model (GCM) of Coupled Model Intercomparison Project 6(CMIP6) according to two Shared Socioeconomic Pathway (SSP) scenarios were used to estimate future monthly precipitation for the study area. The Driving force-Pressure-State-Impact-Response (DPSIR) framework was used to select the water quantity evaluation criteria for prioritizing permeable pavement, and the study area was modeled using ArcGIS and Storm Water Management Model (SWMM). For the values corresponding to the evaluation criteria based on the DPSIR framework, data from national statistics and long-term runoff simulation value of SWMM according to future monthly precipitation were used. Finally, the priority for permeable pavement was determined using the Fuzzy TOPSIS and Minimax regret method. The high priorities were concentrated in the downstream sub-watersheds where urbanization was more progressed and densely populated than the upstream watersheds.

• Proceedings of the Korean Society of Crop Science Conference
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• 2017.06a
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• pp.35-35
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• 2017

How do plants take up water from soils especially when water is scarce in soils? Plants have a strategy to respond to water deficit to manage water necessary for their survival and growth. Plants regulate water transport inside them. Water flows inside the plant via (i) apoplastic pathway including xylem vessel and cell wall and (ii) cell-to-cell pathway including water channels sitting in cell membrane (aquaporins). Water transport across the root and leaf is explained by a composite transport model including those pathways. Modification of the components in those pathways to change their hydraulic conductivity can regulate water uptake and management. Apoplastic barrier is modified by producing Casparian band and suberin lamellae. These structures contain suberin known to be hydrophobic. Barley roots with more suberin content from the apoplast showed lower root hydraulic conductivity. Root hydraulic conductivity was measured by a root pressure probe. Plant root builds apoplastic barrier to prevent water loss into dry soil. Water transport in plant is also regulated in the cell-to-cell pathway via aquaporin, which has received a great attention after its discovery in early 1990s. Aquaporins in plants are known to open or close to regulate water transport in response to biotic and/or abiotic stresses including water deficit. Aquaporins in a corn leaf were opened by illumination in the beginning, however, closed in response to the following leaf water potential decrease. The evidence was provided by cell hydraulic conductivity measurement using a cell pressure probe. Changing the hydraulic conductivity of plant organ such as root and leaf has an impact not only on the speed of water transport across the plant but also on the water potential inside the plant, which means plant water uptake pattern from soil could be differentiated. This was demonstrated by a computer simulation with 3-D root structure having root hydraulic conductivity information and soil. The model study indicated that the root hydraulic conductivity plays an important role to determine the water uptake from soil with suboptimal water, although soil hydraulic conductivity also interplayed.

• Journal of Ginseng Research
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• v.47 no.6
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• pp.714-725
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• 2023

Background: Our previous investigation indicated that the preparation of Panax ginseng Meyer (P. ginseng) inhibited melanogenesis. It comprised salicylic acid (SA), protocatechuic acid (PA), p-coumaric acid (p-CA), vanillic acid (VA), and caffeic acid (CA). In this investigation, the regulatory effects of P. ginseng phenolic acid monomers on melanin production were assessed. Methods: In vitro and in vivo impact of phenolic acid monomers were assessed. Results: SA, PA, p-CA and VA inhibited tyrosinase (TYR) to reduce melanin production, whereas CA had the opposite effects. SA, PA, p-CA and VA significantly downregulated the melanocortin 1 receptor (MC1R), cycle AMP (cAMP), protein kinase A (PKA), cycle AMP-response element-binding protein (CREB), microphthalmia-associated transcription factor (MITF) pathway, reducing mRNA and protein levels of TYR, tyrosinase-related protein 1 (TYRP1), and TYRP2. Moreover, CA treatment enhanced the cAMP, PKA, and CREB pathways to promote MITF mRNA level and phosphorylation. It also alleviated MITF protein level in α-MSH-stimulated B16F10 cells, comparable to untreated B16F10, increasing the expression of phosphorylation glycogen synthase kinase 3β (p-GSK3β), β-catenin, p-ERK/ERK, and p-p38/p38. Furthermore, the GSK3β inhibitor promoted p-GSK3β and p-MITF expression, as observed in CA-treated cells. Moreover, p38 and ERK inhibitors inhibited CA-stimulated p-p38/p38, p-ERK/ERK, and p-MITF increase, which had negative binding energies with MC1R, as depicted by molecular docking. Conclusion: P. ginseng roots' phenolic acid monomers can safely inhibit melanin production by bidirectionally regulating melanin synthase transcription. Furthermore, they reduced MITF expression via MC1R/cAMP/PKA signaling pathway and enhanced MITF post-translational modification via Wnt/mitogen-activated protein kinase signaling pathway.

• International Journal of Stem Cells
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• v.16 no.2
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• pp.180-190
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• 2023

Background and Objectives: Regenerative endodontic procedures (REPs) are a research hotspot in the endodontic field. One of the biggest problems of REPs is that it is difficult to realize regeneration of pulp-dentin complex and functional reconstruction. The reason is still not clear. We hypothesize that the migration may be different in different dental stem cells. Periodontal ligament stem cells (PDLSCs) may migrate faster than stem cells of apical papilla (SCAPs), differentiating into cementum-like tissue, bone-like tissue and periodontal ligament-like tissue and, finally affecting the outcomes of REPs. Hence, this study aimed to explore the mechanism that regulates the migration of PDLSCs. Methods and Results: After isolating and culturing PDLSCs and SCAPs from human third molars, we compared the migration of PDLSCs and SCAPs. Then we investigated the role of SDF-1𝛼-CXCR4/CXCR7 axis in PDLSC migration. We further investigated the impact of Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS) on PDLSC migration and the potential mechanism. PDLSCs showed better migration under both noninflammatory and inflammatory conditions than SCAPs. SDF-1𝛼 can promote the migration of PDLSCs by elevating the expression of CXCR4 and CXCR7, increasing the interaction between them, promoting expression of 𝛽-arrestin1 and activating the ERK signaling pathway. P. gingivalis LPS can promote the migration of PDLSCs toward SDF-1𝛼 through increasing the expression of CXCR4 via the NF-𝜅B signaling pathway, promoting the expression of 𝛽-arrestin1, and activating the ERK signaling pathway. Conclusions: This study helped elucidate the potential reason for the difficulty in forming pulp-dentin complex.

• Journal of The Korean Society of Agricultural Engineers
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• v.56 no.3
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• pp.19-29
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• 2014

This study was to evaluate the potential climate change impact on watershed hydrological components of evapotranspiration, surface runoff, lateral flow, return flow, and streamflow using Soil and Water Assessment Tool (SWAT). For Yongdam dam watershed (930 $km^2$), the SWAT model was calibrated for five years (2002-2006) and validated for three years (2004-2006) using daily streamflow data at three locations and daily soil moisture data at five locations. The Nash-Sutcliffe model efficiency (NSE) and coefficient of determination ($R^2$) were 0.43-0.67 and 0.48-0.70 for streamflow, and 0.16-0.65 and 0.27-0.76 for soil moisture, respectively. For future evaluation, the HadGEM3-RA climate data by Representative Concentration Pathway (RCP) 4.5 and 8.5 scenarios were adopted. The biased future data were corrected using 30 years (1982-2011, baseline period) of ground weather data. The HadGEM3-RA 2080s (2060-2099) temperature and precipitation showed increase of $+4.7^{\circ}C$ and +22.5 %, respectively based on the baseline data. The impacts of future climate change on the evapotranspiration, surface runoff, baseflow, and streamflow showed changes of +11.8 %, +36.8 %, +20.5 %, and +29.2 %, respectively. Overall, the future hydrologic results by RCP emission scenarios showed increase patterns due to the overall increase of future temperature and precipitation.

• International Journal of Oral Biology
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• v.42 no.3
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• pp.91-97
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• 2017

Although anti-aging activities of melatonin, a hormone secreted by the pineal gland, have been reported in senescence-accelerated mouse models and several types of cells, its impact and mechanism on the senescence of human dental pulp cells (HDPCs) remains unknown. In this study, we examined the impact of melatonin on cellular premature senescence of HDPCs. Here, we found that melatonin markedly inhibited senescent characteristics of HDPCs after exposure to hydrogen peroxide ($H_2O_2$), including the increase in senescence-associated ${\beta}$-galactosidase (SA-${\beta}$-gal)-positive HDPCs and the upregulation of p21 protein, an indicator for senescence. In addition, as melatonin attenuated $H_2O_2$-stimulated phosphorylation of c-Jun N-terminal kinase (JNK), while selective inhibition of JNK activity with SP600125 significantly attenuated $H_2O_2$-induced increase in SA-beta-gal activity. Results reveal that melatonin antagonizes premature senescence of HDPCs via JNK pathway. Thus, melatonin may have therapeutic potential to prevent stress-induced premature senescence, possibly correlated with development of dental pulp diseases, and to maintain oral health across the life span.