• BMB Reports
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• v.45 no.3
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• pp.153-158
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• 2012

Geft is a guanine nucleotide exchange factor, which can specifically activate Rho family of small GTPase by catalyzing the exchange of bound GDP for GTP. Geft is highly expressed in the excitable tissue as heart and skeletal muscle and plays important roles in many cellular processes, such as cell proliferation, migration, and cell fate decision. However, the in vivo role of Geft remains unknown. Here, we generated a Geft conditional knockout mouse by flanking exons 5-17 of Geft with loxP sites. Cre-mediated deletion of the Geft gene in heart using Mef2c-Cre transgenic mice resulted in a dramatic decrease of Geft expression. Geft knockout mice develop normally and exhibit no discernable phenotype, suggesting Geft is dispensable for the development of the second heart field in mouse. The Geft conditional knockout mouse will be a valuable genetic tool for uncovering the in vivo roles of Geft during development and in adult homeostasis.

• Journal of Microbiology and Biotechnology
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• v.26 no.4
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• pp.700-709
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• 2016

The mitogen-activated protein kinase HOG1 (high-osmolarity glycerol response pathway) plays a crucial role in the response of yeast to hyperosmotic shock. Trichosporonoides oedocephalis produces large amounts of polyols (e.g., erythritol and glycerol) in a culture medium. However, the effects of HOG1 gene knockout and environmental stress on the production of these polyols have not yet been studied. In this study, a To-HOG1 null mutation was constructed in T. oedocephalis using the loxP-Kan-loxP/Cre system as replacement of the targeted genes, and the resultant mutants showed much smaller colonies than the wild-type controls. Interestingly, compared with the wild-type strains, the results of shake-flask culture showed that To-HOG1 null mutation increased erythritol production by 1.44-fold while decreasing glycerol production by 71.23%. In addition, this study investigated the effects of citric acid stress on the T. oedocephalis HOG1 null mutants and the wild-type strain. When the supplementation of citric acid in the fermentation medium was controlled at 0.3% (w/v), the concentration of erythritol produced from the wild-type and To-HOG1 knockout mutant strains improved by 18.21% and 21.65%, respectively.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.36 no.1
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• pp.1-20
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• 2023

Objectives : The purpose of this study was to evaluate the anti-inflammatory effect of Tanghwajitongsan(THJTS) through inhibition of NF-κB and MAPK. Methods : We evaluated cell survival rate by MTT assay, NO production by nitrite content in the culture medium. We quantified TNF-α, IL-1β, IL-6 and PGE₂ of the cultured supernatant by ELISA. And we evaluated the effect of THJTS on protein expression of NF-κB, MAPK, iNOS and COX-2 by Western blot analysis. THJTS ameliorates LPS-activated alterations in protein expression of NF-κB, p-38, iNOS and COX-2 and production of NO, pro-inflammatory cytokines and PGE₂. Also, THJTS ameliorates LOX, PGN and FLA-activated alterations in protein expression of NO, iNOS. THJTS ameliorates only PGN-activated alterations in protein expression of COX-2. Results : THJTS ameliorates LPS-activated alterations in protein expression of NF-κB, p-38, iNOS and COX-2 and production of NO, pro-inflammatory cytokines and PGE₂. Also, THJTS ameliorates LOX, PGN and FLA-activated alterations in protein expression of NO, iNOS. THJTS ameliorates only PGN-activated alterations in protein expression of COX-2. Conclusions : This study can provide scientific evidence for the anti-inflammatory effects and underlying mechanisms of THJTS.

• Biomolecules & Therapeutics
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• v.26 no.2
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• pp.121-129
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• 2018

Oxidized low-density lipoprotein (ox-LDL)-induced macrophage foam cell formation and apoptosis play critical roles in the pathogenesis of atherosclerosis. Thioredoxin-1 (Trx) is an antioxidant that potently protects various cells from oxidative stress-induced cell death. However, the protective effect of Trx on ox-LDL-induced macrophage foam cell formation and apoptosis has not been studied. This study aims to investigate the effect of recombinant human Trx (rhTrx) on ox-LDL-stimulated RAW264.7 macrophages and elucidate the possible mechanisms. RhTrx significantly inhibited ox-LDL-induced cholesterol accumulation and apoptosis in RAW264.7 macrophages. RhTrx also suppressed the ox-LDL-induced overproduction of lectin-like oxidized LDL receptor (LOX-1), Bax and activated caspase-3, but it increased the expression of Bcl-2. In addition, rhTrx markedly inhibited the ox-LDL-induced production of intracellular reactive oxygen species (ROS) and phosphorylation of p38 mitogen-activated protein kinases (MAPK). Furthermore, anisomycin (a p38 MAPK activator) abolished the protective effect of rhTrx on ox-LDL-stimulated RAW264.7 cells, and SB203580 (a p38 MAPK inhibitor) exerted a similar effect as rhTrx. Collectively, these findings indicate that rhTrx suppresses ox-LDL-stimulated foam cell formation and macrophage apoptosis by inhibiting ROS generation, p38 MAPK activation and LOX-1 expression. Therefore, we propose that rhTrx has therapeutic potential in the prevention and treatment of atherosclerosis.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.12
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• pp.1675-1679
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• 2011

To improve the quality and palatability of Kochujang, the physicochemical properties, antioxidant capacity, and sensory evaluation of Kochujang were assessed when red ginseng and wild herbal extract were added during fermentation. This study investigated the antioxidant capacities of general Kochujang (GK) and Kochujang prepared with red ginseng and fermented wild herbal extract (RGK) by employing various in vitro antioxidant assays such as DPPH and FRAP assays. Inhibition of lioxygenase (LOX) activity was also investigated. RGK exhibited significant antioxidant effects compared to control in DPPH, FRAP, and LOX assays. The LOX inhibitory activity of RGK ($68.68{\pm}3.37%$) at 100 ${\mu}g$/mL was markedly higher than those of GK ($31.21{\pm}2.64%$) and NDGA (positive control, $30.54{\pm}1.36%$). All concentrations of RGK showed significantly higher FRAP activities than that of GK. The addition of red ginseng and fermented wild herbal extract exhibited better sensory characteristics in terms of color, flavor, taste and overall preference. We concluded that RGK improves not only functional properties but also sensory properties as well.

• Natural Product Sciences
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• v.17 no.2
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• pp.90-94
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• 2011

An in vitro bioassay-guide revealed that the methanol (MeOH) extract of the whole plant of Patrinia saniculaefolia (Valerianaceae) showed cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) dual inhibitory activity by assessing their effects on the production of prostaglandin $D_2$ ($PGD_2$) and leukotriene $C_4$ ($LTC_4$) in mouse bone marrow-derived mast cells (BMMCs). Phytochemical study of the MeOH extract of this plant led to the isolation of twelve compounds; ${\beta}$-farnesene (1), squalene (2), nardostachin (3), patridoid I (4), patridoid II (5), patridoid II-A (6), oleanolic acid (7), oleanonic acid (8), 23-hydroxyursolic acid (9), oleanolic acid 3-O-${\alpha}$-L-arabinopyranoside (10), oleanolic acid 3-O-${\beta}$-D-glucopyranoside (11), oleanolic acid 3-O-[${\beta}$-D-xylopyranosyl-(1${\rightarrow}$3)-${\beta}$-D-(6-O-butyl)glucuronopyranoside] (12). Among the compounds, 4 and 5 strongly inhibited both the COX-2-dependent $PGD_2$ generation with $IC_{50}$ values of 8.7 and 13.6 ${\mu}M$, respectively, and the generation of $LTC_4$ in the 5-LOX dependent phase with $IC_{50}$ values of 41.7 and 46.9 ${\mu}M$, respectively, which suggest that the anti-inflammatory activity of P. saniculaefolia might occur in part via the inhibition of both $PGD_2$ and $LTC_4$ generation by 4 and 5.

• Journal of Plant Biology
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• v.25 no.4
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• pp.153-160
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• 1982

The kinetics of $^{14}C$ fixation have been investigated in Anabaena flos-aquae growing on ${NH}_4+$,$NO_3-$ and $NO_2-N$ in batch cultures. Growth rate was highest with ${NH}_4+$, followed by $NO_2-$ and finally $NO_2$. The compensation intensity($I_0$) and the half-saturation irradiance($K_1$) with $K_1$ were higher than with other N sources, but the maximum C fixation rate($P_{max}$) was lower. The ($P_{max}$)/$K_1$ ratio, which is analogous to quantum efficiency at low irradiance ranges, was also lower with $N_2$. All these parameters except $K_1$ decrease with culture age, or decreasing growth rate. Since $^{14}C$ uptake measures net photosynthesis, the higher values of $I_0$ and $K_1$, and the low values of $P_{max}$/$K_1$ ratio with $N_2$ appear to be related to the high energy demand of $N_2$fixation. They may also be related to the lox maximum growth rate with $NO_2-N$.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1827-1831
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• 2015

Background: We generated a mouse model of prostate cancer based on the adult-prostate-specific inactivation of phosphatase and tensin homolog (PTEN) using the Cre-loxP system. The potential of our mice as a useful animal model was examined by evaluating the chemopreventive efficacy of the anti-androgen, chlormadinone acetate (CMA). Materials and Methods: Six-week-old mice were treated subcutaneously with $50{\mu}g/g$ of CMA three times a week for 9 or 14 weeks and sacrificed at weeks 15 and 20. Macroscopic change of the entire genitourinary tract (GUT) and histologically evident prostate gland tumor development were evaluated. Proliferation and apoptosis status in the prostate were examined by immunohistochemistry. Results: CMA triggered significant shrinkage of not only the GUT but also prostate glands at 15 weeks compared to the control (p=0.017 and p=0.010, respectively), and the trend became more marked after a further five-weeks of treatment. The onset of prostate adenocarcinoma was not prevented but the proliferation of cancer cells was inhibited by CMA, which suggested the androgen axis is critical for cancer growth in these mice. Conclusions: Conditional PTEN-deficient mice are useful as a preclinical model for chemoprevention studies and serve as a valuable tool for the future screening of potential chemopreventive agents.

• Proceedings of the Ginseng society Conference
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• 1998.06a
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• pp.300-311
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• 1998

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), one of the most notorious toxic environmental pollutants, induces various toxic effects in many organs including testes and is regarded as an endocrine disruptor. Korean ginseng, on the other hand, has been well known for its preventive effects on lox- ins, diabetes melltus and hyperlipidemia. We investigated, histopathologically, the effect of Korean Red ginseng water extract (KR-WE) on guinea pig testes damaged by TCDD. Ninety guinea pigs were divided into 6 groups: normal control (NC) group received vehicle and saline; TCDD,1191kg b.w., was administered intraperitoneally to the single dose TCDD-treated (77) group; 100 mghg b.w.16 and 200mg1kg b.w./d KR-WE were injected intraperitoneally to the preventive groups (PIOO and P2OO, respectively) for 28 days from 1 week before TCDD injection, and to the therapeutic groups (CIOO and C2OO, respectively) for 14 days since 1 week after TCDD administration. Increment of body weight was retarded to a larger extent by TCDD. Moreover, body weight of the 77 group decreased significantly 7 days after TCDD exposure, while that of preventive groups kept increasing. Decrease in body weight was not observed in KR-WE-treated groups. Weight decrease in testes caused by TCDD was remarkably protected by KR-WE. Testicles in 77 group displayed decreased tubular size and maturation arrest at the primary or secondary spermatocyte stage. On the other hand, maturation arrest in germ cells by TCDD was improved in KR-WE treated groups. Almost complete protection of the testes was observed in PIOO and P2OO groups. In addition, the therapeutic effect was noticed in C 100 and C2OO groups. These results provided strong evidence that Korean Red ginseng might be a useful agent for the prevention and treatment of testicular damage induced by environmental pollutants.

• Biomolecules & Therapeutics
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• v.17 no.4
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• pp.379-387
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• 2009

We have previously reported that N-ethylmaleimide (NEM) induces apoptosis through activation of $K^+$, $Cl^-$-cotransport (KCC) in HepG2 human hepatoblastoma cells. In this study we investigated the possible role of phospholipase $A_2$ ($PLA_2$)-arachidonic acid (AA) signals in the mechanism of the NEM-induced apoptosis. In these experiments we used arachidonyl trifluoromethylketone ($AACOCF_3$), bromoenol lactone (BEL) and p-bromophenacyl bromide (BPB) as inhibitors of the calcium-dependent cytosolic $PLA_2$ ($cPLA_2$), the calcium-independent $PLA_2$ ($iPLA_2$) and the secretory $PLA_2$ ($sPLA_2$), respectively. BEL significantly inhibited the NEM-induced apoptosis, whereas $AACOCF_3$ and BPB did not. NEM increased AA liberation in a dose-dependent manner, which was markedly prevented only by BEL. In addition AA by itself induced $K^+$ efflux, a hallmark of KCC activation, which was comparable to that of NEM. The NEM-induced apoptosis was not significantly altered by treatment with indomethacin (Indo) and nordihydroguaiaretic acid (NDGA), selective inhibitors of cyclooxygenase (COX) and lipoxygenase (LOX), respectively. Treatment with AA or 5,8,11,14-eicosatetraynoic acid (ETYA), a non-metabolizable analogue of AA, significantly induced apoptosis. Collectively, these results suggest that AA liberated through activation of $iPLA_2$ may mediate the NEMinduced apoptosis in HepG2 cells.