• Journal of Life Science
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• v.29 no.11
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• pp.1179-1191
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• 2019

Cancer cells undergo the epithelial-mesenchymal transition (EMT) and show unique oncogenic metabolic phenotypes such as the glycolytic switch (Warburg effect) which are important for tumor development and progression. The EMT is a critical process for tumor invasion and metastasis. High-mobility group box 1 (HMGB1) is a chromatin-associated nuclear protein, but it acts as a damage-associated molecular pattern molecule when released from dying cells and immune cells. HMGB1 induces the EMT, as well as invasion and metastasis, thereby contributing to tumor progression. Here, we show that HMGB1 induced the EMT by activating Snail. In addition, the HMGB1/Snail cascade was found induce a glycolytic switch. HMGB1 also suppressed mitochondrial respiration and cytochrome c oxidase (COX) activity by a Snail-dependent reduction in the expression of the COX subunits COXVIIa and COXVIIc. HMGB1 also upregulated the expression of several key glycolytic enzymes, including hexokinase 2 (HK2), phosphofructokinase-2/fructose-2,6-bisphosphatase 2 (PFKFB2), and phosphoglycerate mutase 1 (PGAM1), in a Snail-dependent manner. However, HMGB1 was found to regulate some other glycolytic enzymes including lactate dehydrogenases A and B (LDHA and LDHB), glucose transporter 1 (GLUT1), and monocarboxylate transporters 1 and 4 (MCT1 and 4) in a Snail-independent manner. Transfection with short hairpin RNAs against HK2, PFKFB2, and PGAM1 prevented the HMGB1-induced EMT, indicating that glycolysis is associated with HMGB1-induced EMT. These findings demonstrate that HMGB1 signaling induces the EMT, glycolytic switch, and mitochondrial repression via Snail activation.

• Journal of Life Science
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• v.31 no.2
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• pp.209-218
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• 2021

This study aimed to evaluate the anti-obesity effects of Cudrania tricuspidata leaf extract in the order of leaf development on the shoot (L0, L1, L2, L3, L4, and L5). The leaves at the apex of a Cudrania tricuspidata shoot were classified as L0; the next leaves of the apex were classified as L1, L2, L3, and L4 from highest to lowest; and the lowest leaf was classified as L5. A series of 70% ethyl alcohol leaf extracts were screened for the inhibitory effects of adipogenesis in 3T3-L1 preadipocytes. We found that the apical leaf extract of Cudrania tricuspidata (CTL0) was the most effective. Next, a study was conducted on the inhibitory action mechanism of CTL0. Treatment with CTL0 significantly suppressed the differentiation of 3T3-L1 preadipocytes in a dose-dependent manner, as confirmed by the decrease in lipid droplet content observed with Oil Red O staining. Treatment with 12.5 ㎍/ml, 25 ㎍/ml, and 50 ㎍/ml of CTL0 significantly reduced the lipid droplet content. Glucose and cellular triglyceride concentrations were reduced in the 3T3-L1 cells on the CTL0-treated medium compared to the differentiation medium (DM control, DMEM + insulin + dexamethasone + rosiglitazone). Compared with DM, CTL0 significantly inhibited the expression of key pro-adipogenic transcription factors, including peroxisome proliferator-activated receptor γ (PPARγ), LPL, A-FABP, and Glut4. These findings show that CTL0 extract has potent anti-obesity effects.

• Economic and Environmental Geology
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• v.54 no.3
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• pp.399-408
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• 2021

Natural soil was artificially contaminated with heavy metals (Cd, Pb, and Zn), and the movement of earthworm was characterized in real time using the ViSSET system composed of vibration sensor and the other components. The manifestation mechanism of ecological toxicity of heavy metals was interpreted based on the accumulative frequency of earthworm movement obtained from the real-time monitoring as well as the conventional indices of earthworm behavior, such as the change in body weight before and after tests and biocumulative concentrations of each contaminant. The results showed the difference in the earthworm movement according to the species of heavy metal contaminants. In the case of Cd, the earthworm movement was decreased with increasing its concentration and then tended to be increased. The activity of earthworm was severely increased with increasing Pb concentration, but the movement of earthworm was gradually decreased with increasing Zn concentration. The body weight of earthworm was proved to be greatly decreased in the Zn-contaminated soil, but it was similarly decreased in Cd- and Pb-contaminated soils. The bioaccumulation factor (BAF) was higher in the sequence of Cd > Zn > Pb, and particularly the biocumulative concentration of Pb did not show a clear tendency according to the Pb concentrations in soil. It was speculated that Cd is accumulated as a metallothionein-bound form in the interior of earthworm for a long time. In particular, Cd has a bad influence on the earthworm through the critical effect at its higher concentrations. Pb was likely to reveal its ecotoxicity via skin irritation or injury of sensory organs rather than ingestion pathway. The ecotoxicity of Zn seemed to be manifested by damaging the cell membranes of digestive organs or inordinately activating metabolism. Based on the results of real-time monitoring of earthworm movement, the half maximal effective concentration (EC50) of Pb was estimated to be 751.2 mg/kg, and it was similar to previously-reported ones. The study confirmed that if the conventional indices of earthworm behavior are combined with the results of newly-proposed method, the mechanism of toxicity manifestation of heavy metal contaminants in soils is more clearly interpreted.

• Journal of Microbiology and Biotechnology
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• v.9 no.1
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• pp.106-112
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• 1999

The therapeutic potential of phosphodiesterase 4(PDE4) inhibitors in inflammatory diseases including some autoimmune diseases has been explored recently with some hopeful results. These PDE4 inhibitors are thought to show their anti-inflammatory effect by down-regulating tumor necrosis factor-a (TNF-$\alpha$) production in lymphocytes and macrophages. A high concentration of TNF-$\alpha$has been found in rheumatoid arthritis (RA) synovium and reducing TNF-$\alpha$using biological agents was proven to be an effective RA treatment. To test the possibility of using PDE4 inhibitors for RA treatment, the effects of a newly synthesized PDE4 inhibitor, DWP205505, on TNF-$\alpha$ and IL-10 production was tested in cells isolated from normal peripheral blood and rheumatoid arthritis synovial fluid. Cytokine production was assayed at the protein level by sandwich enzyme-linked immunosorbent assay (ELISA) and at the mRNA expression level by semi-quantitative RT-PCR. Another PDE4 inhibitor, RP73401, was used for comparison. DWP205505 and RP73401 had no harmful effect on cell viability up to 10 $\mu$M concentration during the 24 h culture period. DWP205505 as well as RP73401 significantly reduced TNF-$\alpha$ secretion from lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (pBMC) and synovial fluid mononuclear cells (SFMC). The effect of DWP205505 or RP73401 treatment on the mRNA expression of TNF-$\alpha$ was also studied in LPS-stimulated PBMC and SFMC. TNF-$\alpha$ mRNA expression was increased by LPS stimulation and both of the PDE4 inhibitors suppressed TNF-$\alpha$ mRNA expression. For interleukin-l0 (IL-l0), a little different results were obtained from PBMC and SFMC; IL-l0 secretion was unaffected by LPS stimulation and only minimally affected by both of the PDE4 inhibitors in PBMC. In unstimulated SFMC, DWP205505 and RP73401 slightly enhanced IL-10 secretion, while they reduced IL-l0 secretion from LPS-stimulated SFMC where IL-l0 secretion was a lot higher than unstimulated SFMC. These results suggest that the newly synthesized PDE4 inhibitor DWP205505 may have anti-rheumatoid arthritis activity.

• Journal of Life Science
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• v.33 no.1
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• pp.15-24
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• 2023

To examine the antitumor effect of proso millet grains, whether proso millet grains exert apoptotic activity against human cancer cells was investigated. When the cytotoxicity of 80% ethanol (EtOH) extract of proso millet grains was tested against various cancer cells using MTT assay, more potent cytotoxicity was observed against human breast cancer MDA-MB-231 cells than against other cancer cells. When the EtOH extract was evaporated to dryness, dissolved in water, and then further fractionated by sequential extraction using four organic solvents (n-hexane, methylene chloride, ethyl acetate, and n-butanol), the BuOH fraction exhibited the highest cytotoxicity against MDA-MB-231 cells. Along with the cytotoxicity, TUNEL-positive apoptotic nucleosomal DNA fragmentation and several apoptotic responses including BAK/BAX activation, mitochondria membrane potential (Δψm) loss, mitochondrial cytochrome c release into the cytosol, activation of caspase-8/-9/-3, and degradation of poly (ADP-ribose) polymerase (PARP) were detected. However, human normal mammary epithelial MCF-10A cells exhibited a significantly lesser extent of sensitivity compared to malignant MDA-MB-231 cells. Irrespective of Fas-associated death domain (FADD)-deficiency or caspase-8-deficiency, human T acute lymphoblastic leukemia Jurkat cells displayed similar sensitivities to the cytotoxicity of BuOH fraction, excluding an involvement of extrinsic apoptotic mechanism in the apoptosis induction. These results demonstrate that the cytotoxicity of BuOH fraction from proso millet grains against human breast cancer MDA-MB-231 cells is attributable to intrinsic apoptotic cell death resulting from BAK/BAX activation, and subsequent mediation of mitochondrial damage-dependent activation of caspase cascade.

• Food Science and Preservation
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• v.30 no.1
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• pp.146-154
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• 2023

To develop a multi-functional ingredient, the bioconversion of katsuobushi protein was optimized using Bacillus subtilis HA and Lactobacillus plantarum KS2020. The Dendropanax morbiferus extract (DME) culture with protease activity (102 unit/mL) was prepared by B. subtilis with 2% glucose and 1% skim milk through one day of alkaline fermentation. Katsuobushi protein was effectively hydrolyzed by the DME culture at 60℃ for 3 hours, resulting in a tyrosine content of 156.85 mg%. Subsequently, a second lactic acid fermentation was carried out with 10% monosodium glutamate (MSG) using L. plantarum KS2020 to produce higher levels of GABA. Following co-cultivation for three days, DME exhibited a pH of 8.3 (0% acidity). After seven days, the viable cell count of L. plantarum increased to 9.33 CFU/mL, but viable Bacillus cells were not detected. Taken together, a multi-functional ingredient with enriched GABA, peptides, probiotics, and umami flavor was developed through lactic acid fermentation using hydrolyzed katsuobushi protein. These results indicate that katsuobushi protein could be used as a byproduct to produce a palatable protein hydrolysate using alkaline-fermented DME culture as a proteolytic enzyme source.

• Food Science and Preservation
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• v.30 no.4
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• pp.703-715
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• 2023

This study was conducted to investigate the fermentation characteristics and anti-obesity effects of acetic acid fermentation products of coffee wine. The live cell counts, soluble solids, pH and total acidity of the acetic acid unfermented coffee wine (AUFCW; day 0, before fermentation) were 6.35 log CFU/mL, 8.10 °Brix, 3.88, and 1.29%, respectively, while the acetic acid fermented coffee wine (AFCW; day 15, after fermentation) were 4.40 log CFU/mL, 8.57 °Brix, 3.07, and 7.45%, respectively. Pancreatic lipase inhibitory activity tended to increase as the acetic acid fermentation period increased. The anti-obesity effects of AFCW on 3T3-L1 cells, which was induced by MDI, were evaluated based on the lipid accumulation rate, leptin expression, and fat production-related gene expression (PPAR-γ and SREBP-1c) at the mRNA level. In the case of AFCW, the lipid accumulation rate and leptin expression were decreased to 69.37% and 50.20% at a concentration of 200 ㎍/mL, respectively, and the expression levels of PPAR-γ and SREBP-1c at the mRNA level were decreased to 79.89% and 48.81%, respectively. These results indicate that anti-obesity effect of acetic acid fermentation products could be increased by acetic acid fermentation of coffee wine.

• Food Science and Preservation
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• v.31 no.1
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• pp.183-196
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• 2024

This study investigated the protective effect of the aqueous extract of Eucommia ulmoides leaves (AEEL) against high glucose-induced human colon epithelial HT-29 cells. The 2,2'-azino-bis (3-ethyl benzothiazoline-6-sulfonic acid) (ABTS), 1,1-diphenyl-2-picrylhydrazy (DPPH) radical scavenging activities, ferric reducing/antioxidant power (FRAP), and malondialdehyde (MDA) analyses indicated that AEEL had significant antioxidant activities. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that AEEL increased cell viability against high glucose-, H₂O₂-, and lipopolysaccharide (LPS)-induced cytotoxicity in HT-29 cells. Also, the 2'-7'-dichlorodihydrofluorescein diacetate (DCF-DA) assay indicated that AEEL decreased intracellular reactive oxygen species (ROS) against high glucose-, H₂O₂-, and lipopolysaccharide (LPS)-induced cytotoxicity in HT-29 cells. AEEL showed inhibitory activities against α-glucosidase and inhibited the formation of advanced glycation end products (AGEs). AEEL showed significant positive effects on the viability and titratable acidity of L. brevis. The high-performance liquid chromatogram (HPLC) analysis identified chlorogenic acid and rutin as the major compounds of AEEL. These results suggested that AEEL has the potential to be used as a functional food source to suppress blood glucose levels and protect the gut from high glucose-induced oxidative stress.

• The Sea:JOURNAL OF THE KOREAN SOCIETY OF OCEANOGRAPHY
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• v.5 no.3
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• pp.195-207
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• 2000

Organic and inorganic characteristics including bacterial cell number, enzyme activity, nutrients, and heavy metals have been monitored in twelve acrylic experimental tanks for two weeks to estimate and compare self-purification capacities in two Korean wet-land environments, tidal flat and rice field, which are possibly different with the environments in other countries because of their own climatic conditions. FW tanks, filled with rice field soils and fresh water, consist of FW1&2 (with paddy), FW3&4 (without paddy), and FW5&6 (newly reclaimed, without paddy). SW tanks, filled with tidal flat sediments and salt water, are SW1&2 (with anoxic silty mud), SW3&4 (anoxic mud), and SW5&6 (suboxic mud). Contaminated solution, which is formulated with the salts of Cu, Cd, As, Cr, Pb, Hg, and glucose+glutamic acid, was spiked into the supernatent waters in the tanks. Nitrate concentrations in supernatent waters as well as bacterial cell numbers and enzyme activities of soils in the FW tanks (except FW5&6) are clearly higher than those in the SW tanks. Phosphate concentrations in the SW1 tank increase highly with time compared to those in the other SW tanks. Removal rates of Cu, Cd, and As in supematent waters of the FW5&6 tanks are most slow in the FW tanks, while the rates in SW1&2 are most fast in the SW tanks. The rate for Pb in the SW1&2 tanks is most fast in the SW tanks, and the rate for Hg in the FW5&6 tanks is most slow in the FW tanks. Cr concentrations decrease generally with time in the FW tanks. In the SW tanks, however, the Cr concentrations decrease rapidly at first, then increase, and then remain nearly constant. These results imply that labile organic materials are depleted in the FW5&6 tanks compared to the FW1&2 and FW3&4 tanks. Removal of Cu, Cd, As from the supernatent waters as well as slow removal rates of the elements (including Hg) are likely due to the combining of the elements with organic ligands on the suspended particles and subsequent removal to the bottom sediments. Fast removal rates of the metal ions (Cu, Cd, As) and rapid increase of phosphate concentrations in the SW1&2 tanks are possibly due to the relatively porous anoxic sediments in the SW1&2 tanks compared to those in the SW3&4 tanks, efficient supply of phosphate and hydrogen sulfide ions in pore wates to the upper water body, complexing of the metal ions with the sulfide ions, and subsequent removal to the bottom sediments. Organic materials on the particles and sulfide ions from the pore waters are the major factors constraining the behaviors of organic/inorganic elements in the supernatent waters of the experimental tanks. This study needs more consideration on more diverse organic and inorganic elements and experimental conditions such as tidal action, temperature variation, activities of benthic animals, etc.

• Journal of Global Scholars of Marketing Science
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• v.19 no.3
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• pp.17-27
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• 2009

Price promotion typically reduces the price for a given quantity or increases the quantity available at the same price, thereby enhancing value and creating an economic incentive to purchase. It often is used to encourage product or service trial among nonusers of products or services. Thus, it is important to understand the effects of price promotions on quality perception made by consumer who do not have prior experience with the promoted brand. However, if consumers associate a price promotion itself with inferior brand quality, the promotion may not achieve the sales increase the economic incentives otherwise might have produced. More specifically, low qualitative perception through price promotion will undercut the economic and psychological incentives and reduce the likelihood of purchase. Thus, it is important for marketers to understand how price promotional informations about a brand have impact on consumer's unfavorable quality perception of the brand. Previous literatures on the effects of price promotions on quality perception reveal inconsistent explanations. Some focused on the unfavorable effect of price promotion on consumer's perception. But others showed that price promotions didn't raise unfavorable perception on the brand. Prior researches found these inconsistent results related to the timing of the price promotion's exposure and quality evaluation relative to trial. And, whether the consumer has been experienced with the product promotions in the past or not may moderate the effects. A few studies considered differences among product categories as fundamental factors. The purpose of this research is to investigate the effect of price promotional informations on consumer's unfavorable quality perception under the different conditions. The author controlled the timing of the promotional exposure and varied past promotional patterns and information presenting patterns. Unlike previous researches, the author examined the effects of price promotions setting limit to pretrial situation by controlling potentially moderating effects of prior personal experience with the brand. This manipulations enable to resolve possible controversies in relation to this issue. And this manipulation is meaningful for the work sector. Price promotion is not only used to target existing consumers but also to encourage product or service trial among nonusers of products or services. Thus, it is important for marketers to understand how price promotional informations about a brand have impact on consumer's unfavorable quality perception of the brand. If consumers associate a price promotion itself with inferior quality about unused brand, the promotion may not achieve the sales increase the economic incentives otherwise might have produced. In addition, if the price promotion ends, the consumer that have purchased that certain brand will likely to display sharply decreased repurchasing behavior. Through a literature review, hypothesis 1 was set as follows to investigate the adjustive effect of past price promotion on quality perception made by consumers; The influence that price promotion of unused brand have on quality perception made by consumers will be adjusted by past price promotion activity of the brand. In other words, a price promotion of an unused brand that have not done a price promotion in the past will have a unfavorable effect on quality perception made by consumer. Hypothesis 2-1 was set as follows : When an unused brand undertakes price promotion for the first time, the information presenting pattern of price promotion will have an effect on the consumer's attribution for the cause of the price promotion. Hypothesis 2-2 was set as follows : The more consumer dispositionally attribute the cause of price promotion, the more unfavorable the quality perception made by consumer will be. Through test 1, the subjects were given a brief explanation of the product and the brand before they were provided with a $2{\times}2$ factorial design that has 4 patterns of price promotion (presence or absence of past price promotion * presence or absence of current price promotion) and the explanation describing the price promotion pattern of each cell. Then the perceived quality of imaginary brand WAVEX was evaluated in the scale of 7. The reason tennis racket was chosen is because the selected product group must have had almost no past price promotions to eliminate the influence of average frequency of promotion on the value of price promotional information as Raghubir and Corfman (1999) pointed out. Test 2 was also carried out on students of the same management faculty of test 1 with tennis racket as the product group. As with test 1, subjects with average familiarity for the product group and low familiarity for the brand was selected. Each subjects were assigned to one of the two cells representing two different information presenting patterns of price promotion of WAVEX (case where the reason behind price promotion was provided/case where the reason behind price promotion was not provided). Subjects looked at each promotional information before evaluating the perceived quality of the brand WAVEX in the scale of 7. The effect of price promotion for unfamiliar pretrial brand on consumer's perceived quality was proved to be moderated with the presence or absence of past price promotion. The consistency with past promotional behavior is important variable that makes unfavorable effect on brand evaluations get worse. If the price promotion for the brand has never been carried out before, price promotion activity may have more unfavorable effects on consumer's quality perception. Second, when the price promotion of unfamiliar pretrial brand was executed for the first time, presenting method of informations has impact on consumer's attribution for the cause of firm's promotion. And the unfavorable effect of quality perception is higher when the consumer does dispositional attribution comparing with situational attribution. Unlike the previous studies where the main focus was the absence or presence of favorable or unfavorable motivation from situational/dispositional attribution, the focus of this study was exaus ing the fact that a situational attribution can be inferred even if the consumer employs a dispositional attribution on the price promotional behavior, if the company provides a persuasive reason. Such approach, in academic perspectih sis a large significance in that it explained the anchoring and adjng ch approcedures by applying it to a non-mathematical problem unlike the previous studies where it wis ionaly explained by applying it to a mathematical problem. In other wordn, there is a highrspedency tmatispositionally attribute other's behaviors according to the fuedach aal attribution errors and when this is applied to the situation of price promotions, we can infer that consumers are likely tmatispositionally attribute the company's price promotion behaviors. Ha ever, even ueder these circumstances, the company can adjng the consumer's anchoring tmareduce the po wibiliute thdispositional attribution. Furthermore, unlike majority of previous researches on short/long-term effects of price promotion that only considered the effect of price promotions on consumer's purchasing behaviors, this research measured the effect on perceived quality, one of man elements that affects the purchasing behavior of consumers. These results carry useful implications for the work sector. A guideline of effectively providing promotional informations for a new brand can be suggested through the outcomes of this research. If the brand is to avoid false implications such as inferior quality while implementing a price promotion strategy, it must provide a clear and acceptable reasons behind the promotion. Especially it is more important for the company with no past price promotion to provide a clear reason. An inconsistent behavior can be the cause of consumer's distrust and anxiety. This is also one of the most important factor of risk of endless price wars. Price promotions without prior notice can buy doubt from consumers not market share.