• Journal of Life Science
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• v.31 no.10
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• pp.873-884
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• 2021

The purpose of present study is to investigate the role of artesunate (ART) in enhancing anticancer effect of nonsteroidal anti-inflammatory drug (NSAID) on human cancer cells, and we elucidate a possible molecular mechanism of this combination effect. We showed that the combined effect of ART with NSAID such as celecoxib (CCB) or dimethyl-CCB (DMC) in various type of human cancer cells. After ART treatment, the expression of p62, nuclear factor erythroid 2-like 2 (NRF2) and cancer stemness (CS)-related proteins including CD44, CD133, aldehyde dehydrogenase 1 (ALDH1), octamer-binding transcription factor 4 (Oct4), mutated p53 (mutp53) and c-Myc was down-regulated. ART induced autophagy as reduction of the autophagy receptor p62, which was associated with up-regulation of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP), and simultaneous down-regulation of NRF2 and CS-related proteins was occurred in the human cancer cells. These results indicate a possibility that ART activates autophagy through ATF4-CHOP cascade leading to down-regulation of CS-related proteins and subsequently eradicated cancer stem cells. In addition, co-treatment with ART and imatinib was more effective than either drug alone on growth inhibition and apoptosis induction of cancer cells. In conclusion, induction of autophagy-dependent cell death by ART might play a critical role in mediating the synergistic effect of drug combination (ART/NSAID and ART/imatinib). Therefore, ART could be a promising candidate as a chemosensitizer to enhance the anticancer effects of NSAID and imatinib.

• Journal of Life Science
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• v.31 no.9
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• pp.796-805
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• 2021

Hepatic endoplasmic reticulum (ER) stress contributes to the development of steatosis and insulin resistance. The components of unfolded protein response (UPR) regulate lipid metabolism. Recent studies have reported an association between ER stress and aberrant cellular lipid control; moreover, research has confirmed the involvement of sterol regulatory element-binding proteins (SREBPs)-the central regulators of lipid metabolism-in the process. However, the exact role of SREBPs in controlling lipid metabolism during ER stress and its contribution to fatty liver disease remain unknown. Here, we show that SREBP-1c deficiency protects against ER stress-induced hepatic steatosis in mice by regulating UPR, inflammation, and fatty acid oxidation. SREBP-1c directly regulated inositol-requiring kinase 1α (IRE1α) expression and mediated ER stress-induced tumor necrosis factor-α activation, leading to a reduction in expression of peroxisome proliferator-activated receptor γ coactivator 1-α and subsequent impairment of fatty acid oxidation. However, the genetic ablation of SREBP-1c prevented these events, alleviating hepatic inflammation and steatosis. Although the mechanism by which SREBP-1c deficiency prevents ER stress-induced inflammatory signaling remains to be elucidated, alteration of the IRE1α signal in SREBP-1c-depleted Kupffer cells might be involved in the signaling. Overall, the results suggest that SREBP-1c plays a crucial role in the regulation of UPR and inflammation in ER stress-induced hepatic steatosis.

• Korean Journal of Family Social Work
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• no.55
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• pp.91-128
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• 2017

The purpose of this study is to develop an effective intervention strategy for marriage migrant woman in family therapy. For this purpose, we collected counseling cases of professional counselors who successfully completed counseling and attempted the qualitative analysis of treatment intervention strategies and effects. The results of the study were obtained by dividing the meaning units in the immigrant woman's statements made during the counseling process composed of a total of 6 sessions. The counselors were analyzed to have tried the following intervention strategies. They attempted the following six strategies: Helping emotional differentiation by searching for unresolved emotional problems, dealing with undifferentiation due to family projection process and love triangle, dealing with multi-generational transfer process of the original family relationship patterns and coping mechanism, shedding lihgt on ineffectiveness of inconsistent communication due to emotional oppression applying a communication model of MRI, switching client's awareness through reorganization, suggesting a way of communication that leads to real self. Such counselors' attempts resulted in positive changes and treatment effects were found to include first, cognitive insights and motivation for change, second, improved communication skills and third, anxiety reduction and self-differentiation. Due to their husbands' refusal to participate in counseling, marriage migrant women often get involved in counseling alone, so they tend to worry that the effectiveness of family therapy may be low but it was found that the proper intervention of the counselor could improve the ability of the wife to resolve conflicts, which would be a great help in solving problems such as family violence and this study is meaningful in that it provided the appropriate therapeutic intervention strategies needed.

• Journal of Life Science
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• v.29 no.9
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• pp.1016-1022
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• 2019

Owing to increased interest in preventing obesity in an aging society, both men and women spend considerable amount of cost on obesity managements. In this study, we investigated the natural substances on anti-obesity activities in 3T3-L1 pre-adipocytes. Also, to improve anti-obesityeffects, research using 3T3-L1 pre-adipocytes cells is crucial. The anti-obesity effect of 70% ethanol extract from Torilis Japonica Decandolle on the differentiation of 3T3-L1 pre-adipocytes to adipocytes was investigated by suppressing adipocyte differentiation and lipid accumulation with Oil Red O assay, and western blot analysis. Compared to the control, 70% ethanol extract of Torilis Japonica Decandolle was significantly inhibited adipocyte differentiation and intracellular triglyceride (TG) level at a concentration of $100{\mu}g/ml$. To determine the mechanism of reduction in TG content, we determined the level of protein expression of obesity-related proteins, such as peroxisome-proliferatorsactivated-receptor-${\gamma}$ ($PPAR{\gamma}$) and CCAAT enhancer-binding-proteins-${\alpha}$ ($C/EBP{\alpha}$), and Acetyl-CoA carboxylase (ACC) phosphorylation. As a results, 70% ethanol extract of Torilis Japonica Decandolle significantly decreased protein expression of $PPAR{\gamma}$, $C/EBP{\alpha}$ and ACC phosphorylation. These results indicate that 70% ethanol extract of Torilis Japonica Decandolle is the most effective candidate for preventing obesity. However further studies will be needed to identify the active compounds that confer the anti-obesity activity of Torilis Japonica Decandolle.

• Korean Journal of Clinical Laboratory Science
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• v.51 no.3
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• pp.370-378
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• 2019

The hepatic ischemic model has recently been widely used for the epidemiological study of ischemic reperfusion injury. This study was carried out to investigate the protective effect of vanillin, which is known to have antioxidant and anti-inflammatory effects, against hepatic and renal injury using an ischemia-reperfusion rat model, and we also investigated the mechanism related to vanillins' protective effect. The test material was administered at a concentration of 100 mg/kg for 3 days, followed by ligation of the liver for 60 minutes to induce ischemia reperfusion. As control groups, there was a negative control, sham control and ischemia-reperfusion-only ischemia reperfusion control, and the controls groups were compared with the drug administration group. In the vanillin group, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were significantly inhibited compared with the AST and ALT activities of the ischemia-reperfusion group, and histopathological examination showed significant reduction of both inflammation and necrosis. The malondialdehyde (MDA) and superoxide dismutase (SOD) levels were significantly different from the ischemia-reperfusion group. In conclusion, vanillin showed a hepatocyte protective action by alleviating the cellular inflammation and cell necrosis caused by hepatic ischemia-reperfusion, and vanillin mitigated inflammatory changes in the kidney glomeruli and distal tubules. The protective effect is considered to be caused by vanillin's antioxidant function. Further studies such as on cell death and possibly vanillin's same effect on damaged tissue will be necessary for clinical applications such as organ transplantation.

• Korean Journal of Plant Resources
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• v.32 no.2
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• pp.109-115
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• 2019

In this study, we evaluated the anti-cancer activity and potential molecular mechanism of 70% ethanol extracts of branches from Taxillus yadoriki parasitic to Neolitsea sericea (TN-NS-B) against human lung cancer cells, A549. TY-NS-B dose-dependently suppressed the growth of A549 cells. TY-NS-B decreased ${\beta}$-catenin protein level, but not mRNA level in A549 cells. The downregulation of ${\beta}$-catenin protein level by TY-NS-B was attenuated in the presence of MG132. Although TY-NS-B phosphorylated ${\beta}$-catenin protein, the inhibition of $GSK3{\beta}$ by LiCl did not blocked the reduction of ${\beta}$-catenin by TY-NS-B. In addition, TY-NS-B decreased ${\beta}$-catenin protein in A549 cells transfected with Flag-tagged wild type ${\beta}$-catenin or Flag-tagged S33/S37/T41 mutant ${\beta}$-catenin construct. Our results suggested that TN-NS-B may downregulate ${\beta}$-catenin protein level independent on $GSK3{\beta}$-induced ${\beta}$-catenin phosphorylation. Based on these findings, TY-NS-B may be a potential candidate for the development of chemopreventive or therapeutic agents for human lung cancer.

• Molecules and Cells
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• v.44 no.1
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• pp.38-49
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• 2021

Airway mucus secretion is an essential innate immune response for host protection. However, overproduction and hypersecretion of mucus, mainly composed of the gel-forming MUC5AC protein, are significant risk factors for patients with asthma and chronic obstructive pulmonary disease (COPD). The transforming growth factor β (TGFβ) signaling pathway negatively regulates MUC5AC expression; however, the underlying molecular mechanism is not fully understood. Here, we showed that TGFβ significantly reduces the expression of MUC5AC mRNA and its protein in NCI-H292 cells, a human mucoepidermoid carcinoma cell line. This reduced MUC5AC expression was restored by a TGFβ receptor inhibitor (SB431542), but not by the inhibition of NF-κB (BAY11-7082 or Triptolide) or PI3K (LY294002) activities. TGFβ-activated Smad3 dose-dependently bound to MUC5AC promoter. Notably, TGFβ-activated Smad3 recruited HDAC2 and facilitated nuclear translocation of HDAC2, thereby inducing the deacetylation of NF-κB at K310, which is essential for a reduction in NF-κB transcriptional activity. Both TGFβ-induced nuclear translocation of Smad3/HDAC2 and deacetylation of NF-κB at K310 were suppressed by a Smad3 inhibitor (SIS3). These results suggest that the TGFβ-activated Smad3/HDAC2 complex is an essential negative regulator for MUC5AC expression and an epigenetic regulator for NF-κB acetylation. Therefore, these results collectively suggest that modulation of the TGFβ1/Smad3/HDAC2/NF-κB pathway axis can be a promising way to improve lung function as a treatment strategy for asthma and COPD.

• Food Engineering Progress
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• v.22 no.4
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• pp.337-343
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• 2018

Coffee is a commonly consumed beverage that contains anti-inflammatory compounds such as caffeine, chlorogenic acid, cafestol, trigonelline, and kahweol. Lactobacillus plantarum is a lactic acid bacterium most frequently used in the fermentation of food products of plant origin. L. plantarum is able to degrade some food phenolic compounds and provide high value-added compounds such as powerful antioxidants or food additives approved as flavouring agents. In this study, we investigated the anti-inflammatory effects of coffee extract fermented by L. plantarum on RAW264.7 macrophages. In lipopolysaccharide-stimulated RAW264.7 cells, these coffee extracts exhibited anti-inflammatory activities through the reduction of nitric oxide (NO) production and inducible NO synthase expression. Fermented coffee extracts significantly decreased the expression of inflammatory cytokines such as tumor necrosis factor ${\alpha}$, interleukin $1{\beta}$, interleukin 6, and interferon ${\gamma}$. Cyclooxygenase-2, which is one of the key biomarkers for inflammation, was significantly suppressed. These results might be helpful for understanding the anti-inflammatory mechanism of fermented coffee extract on immune cells and, moreover, suggest that fermented coffee extract may be a beneficial anti-inflammatory agent.

• Natural Product Sciences
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• v.27 no.2
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• pp.86-98
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• 2021

This study was designed to characterize the effect of ginsenoside-Rg2 (Rg2), one of panaxatriol saponins isolated from Korean ginseng root, on the release of catecholamines (CA) in the perfused model of the rat adrenal medulla, and also to establish its mechanism of action. Rg2 (3~30 µM), administered into an adrenal vein for 90 min, depressed acetylcholine (ACh)-induced CA secretion in a dose- and time-dependent manner. Rg2 also time-dependently inhibited the CA secretion induced by 3-(m-chloro-phenyl-carbamoyl-oxy)-2-butynyltrimethyl ammonium chloride (McN-A-343), 1.1-dimethyl-4-phenyl piperazinium iodide (DMPP), and angiotensin II (Ang II). Also, during perfusion of Rg2, the CA secretion induced by high K⁺, veratridine, cyclopiazonic acid, methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoro-methyl-phenyl)-pyridine-5-carboxylate (Bay-K-8644) depressed, respectively. In the simultaneous presence of Rg2 and N^ω-nitro-L-arginine methyl ester hydrochloride ʟ-NAME), the CA secretion induced by ACh, Ang II, Bay-K-8644 and veratridine was restored nearly to the extent of their corresponding control level, respectively, compared to those of inhibitory effects of Rg2-treatment alone. Virtually, NO release in adrenal medulla following perfusion of Rg2 was significantly enhanced in comparison to the corresponding spontaneous release. Also, in the coexistence of Rg2 and fimasartan, ACh-induced CA secretion was markedly diminished compared to the inhibitory effect of fimasartan-treated alone. Collectively, these results demonstrated that Rg2 suppressed the CA secretion induced by activation of cholinergic as well as angiotensinergic receptors from the perfused model of the rat adrenal gland. This Rg2-induced inhibitory effect seems to be exerted by reducing both influx of Na⁺ and Ca²⁺ through their ionic channels into the adrenomedullary cells as well as by suppressing Ca²⁺ release from the cytoplasmic calcium store, at least through the elevated NO release by activation of NO synthase, which is associated to the blockade of neuronal cholinergic and AT₁-receptors. Based on these results, the ingestion of Rg2 may be helpful to alleviate or prevent the cardiovascular diseases, via reduction of CA release in adrenal medulla and consequent decreased CA level in circulation.

• Journal of Wetlands Research
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• v.23 no.1
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• pp.94-105
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• 2021

Two vertical flow biofilters in series (BFS) employing synthetic fiber (FBF) followed by woodchip (WBF) was investigated in order to assess its potential as an alternative to the typical vertical-horizontal flow configuration in removing nonpoint source pollutants specifically nutrients and organics. These lab-scale column biofilters were operated for 176 days alongside three other columns that were added for control and sampling purposes. The biofilter columns were fed with either a semi-artificial piggery stormwater or artificial stormwater with specific ammonia and nitrate contents. Results reveal that the BFS was more effective than a single biofilter in removing pollutants especially nitrogen. FBF was found to remove up to 100% of ammonia from the stormwater with corresponding increase in nitrate in the outflow which shows evidence of active nitrification. Meanwhile, the succeeding vertical WBF was able to subsequently remove 77% of the nitrate. The effective reduction of nitrate in a vertical flow biofilter was believed to be due to the use of woodchip which can provide a carbon source that is required for denitrification. However, further investigation is needed to support this claim. Nonetheless, the study shows the potential of vertical flow BFS as a nitrogen removal mechanism especially in areas where enough land space for horizontal flow biofilters is limited.