• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.2
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• pp.146-153
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• 2014

Gami-Sopungsan (GS) is one of the traditional korean remedy. We investigated the anti-inflammation and anti-atopic dermatitis (AD) effect of GS. No cytotoxicity of GS was observed in the range of $1{\sim}100{\mu}g/m{\ell}$ on Raw 264.7 cells. The Inflammatory response of Raw 264.7 cells were induced by lipopolysaccharide (LPS), followed by GS treatment at indicated concentrations (0, 1, 10 and $100{\mu}g/m{\ell}$). At $100{\mu}g/m{\ell}$ concentration, GS showed inhibitory effect on LPS-induced nitric oxide production by 20%. Production of IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ was decreased by approximately 56%, 36% and 79%, respectively upon GS treatment at $100{\mu}g/m{\ell}$. 200 mg/kg of GS was orally administered to NC/Nga mice, where AD was induced by 1-chloro 2,4-dinitrobenzene. There were no significant difference between GS treated group and the control group on body weight and food intake changes during growth. The back skin of GS group showed decrease in erythema, pruritus, dry skin, edema, excoriation, erosion and lichenification level through naked eye observations. In addition, leukocyte infiltration and the thickness of epidermis were significantly decreased in the skin tissues (back and ear). The serum IgE levels were decreased by 28.8% in the GS treated group. The GS treated group showed remarkable inhibition of IL-4 (83%), IL-5 (95%), IL-6 (62%) and TNF-${\alpha}$ (84%) in serum, indicating that GS has similar or higher efficacy than those of the dexamethasone treated group. From the results above, we conclude that GS has significant anti-inflammation and anti-AD effects on Raw 264.7 cells and NC/Nga mice. The results should provide fundamental and valuable data for the research on natural products being developed against atopic dermatitis.

• Biomolecules & Therapeutics
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• v.22 no.4
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• pp.347-354
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• 2014

Larrea nitida is a plant that belongs to the Zygophyllaceae family and is widely used in South America to treat inflammatory diseases, tumors and menstrual pain. However, its pharmacological activity remains unclear. In this study we evaluated the property of selective estrogen receptor modulator (SERM) of Larrea nitida extracts (LNE) as a phytoestrogen that can mimic, modulate or disrupt the actions of endogenous estrogens, depending on the tissue and relative amount of other SERMs. To investigate the property of SERM of LNE, we performed MCF-7 cell proliferation assays, estrogen response element (ERE)-luciferase reporter gene assay, human estrogen receptor (hER) binding assays and in vivo uterotrophic assay. To gain insight into the active principles, we performed a bioassay-guided analysis of LNE employing solvents of various polarities and using classical column chromatography, which yielded 16 fractions (LNs). LNE showed high binding affinities for $hER{\alpha}$ and $hER{\beta}$ with $IC_{50}$ values of $1.20{\times}10^{-7}$ g/ml and $1.00{\times}10^{-7}$ g/ml, respectively. LNE induced $17{\beta}$-estradiol (E2)-induced MCF-7 cell proliferation, however, it reduced the proliferation in the presence of E2. Furthermore, LNE had an atrophic effect in the uterus of immature rats through reducing the expression level of progesterone receptor (PR) proteins. LN08 and LN10 had more potent affinities for binding on $hER{\alpha}$ and ${\beta}$ than other fractions. Our results indicate that LNE had higher binding affinities for $hER{\beta}$ than $hER{\alpha}$, and showed SERM properties in MCF-7 breast cancer cells and the rat uterus. LNE may be useful for the treatment of estrogen-related conditions, such as female cancers and menopause.

• Journal of Life Science
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• v.28 no.1
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• pp.37-42
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• 2018

Non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1) is a transforming growth factor beta (TGF-${\beta}$) superfamily gene associated with pro-apoptotic and anti-tumorigenic activities. In the present study, we investigated if caffeic acid phenethyl ester (CAPE) derived from propolis could induce the expression of anti-tumorigenic gene NAG-1. Our results indicate that CAPE significantly induced NAG-1 expression in a time- and concentration-dependent manner in HCT116 cells. We also found that CAPE induced NAG-1 expression in a concentration-dependent manner in another human colorectal cancer cell line, LOVO. In addition, CAPE triggered apoptosis, which was detected with Western blot analysis using poly-(ADP-ribose) polymerase antibody. NAG-1 induction by CAPE was not dependent on transcription factor p53, which was confirmed with Western blot analysis using p53 null HCT116 cells. The luciferase assay results indicated that the new cis-elements candidates were located between -474 and -1,086 of the NAG-1 gene promoter. CAPE dramatically induced activating transcription factor 3 (ATF3) expression, but not cAMP response element-binding protein (CREB), which shares the same binding sites with ATF3. The co-transfection experiment with pCG-ATF3 and pCREB showed that only ATF3 was associated with NAG-1 up-regulation by CAPE, whereas CREB had no effect. In conclusion, the results suggest that CAPE could induce the expression of anti-tumorigenic gene NAG-1 mainly through ATF3.

• Journal of Preventive Medicine and Public Health
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• v.24 no.3 s.35
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• pp.287-304
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• 1991

Tolerance to several toxic effects of cadmium, including lethality has been shown following pretreatment with cadmium and zinc. This study was designed to determine if tolerance also develops to Cd-induced hepatotoxicityandrenaltoxicity. Three groups of rats (A, B, C), each consisting of 16 rats, were studied and each group was divided into four subgroups (1, 2, 3, 4), 4 rats for each subgroup. Rats were subcutaneously pretreated with saline (A), $CdCl_2$ (0.5 mg/kg, B), and $ZnCl_2$ (13.0 mg/kg, C) during time periods of $1{\sim}6$ weeks. At the end of the period, rats were challenged with $CdCl_2$ (3.0, 6.0 and 9.0 mg/kg, ip). After giving the challenge dose, cadmium and metallothionein (MT) concentrations were determined and also observed the histologic change in liver and kidney. The concentration of cadmium in liver and kidney increased dose-dependently to the challenge dosage. These da indicate the kidney is a major target organ of chronic cadmium poisoning, and suggest that cadmium induced hepatic injury, via release of Cd-MT, may play an important role in the nephrotoxicity observed in response to long-term exposure to cadmium. In addition, histologic examination of group $A_2,\;A_3\;and\;A_4$ revealed moderate to severe cadmium toxicity, evidenced by infiltration of inflammatory cells, cell swelling, pyknosis, enlarged sinusoids and necrosis in liver, and tubule cell necrosis and degeneration in kidney. However, MT concentrations in liver and kidney were increased by the pretreatment of $CdCl_2$ and $ZnCl_2$, and their morphological findings were not significantly changed, comparing with control group. Higher MT concentration in liver and kidney observed in the pretreated groups constitutes a plausible explanation of the protective effects of pretreatment against the cadmium toxicity after challenge dosing.

• Journal of Preventive Medicine and Public Health
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• v.34 no.2
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• pp.109-118
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• 2001

The purpose of this review is to discuss the debate concerning the interpretation of epidemiologic studies on particles and health effects. Study of the 1952 air pollution disaster in London established that very high levels of particulate-based smog can cause dramatic increases in daily mortality. However, recent epidemiologic studies have reported statistically significant health effects and mortality due to low levels of air pollution. The statistical significance does not prove causation in observational studies; therefore it is necessary to evaluate these associations. There are arguments for and against each of the numerous studies using Hill's criteria, however the body of accepted evidence supports the causal association. In particular, a high level of consistency in the estimated effect of PM10 has been observed across studies worldwide. The mechanism of the relationship between air pollution and health effects is not obvious. The mechanism of particle-induced injury may involve the production of an inflammatory response by the particulate. The harvesting and the threshold effect are also major concerns regarding the health effects of air pollution. However, current epidemiologic findings indicate that linear models lacking a threshold are appropriate for assessing the effect of particulate air pollution on daily mortality even at current levels.

• Journal of Life Science
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• v.11 no.2
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• pp.181-189
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• 2001

Cytokines are hormone-like proteins which mediate and regulast inflammatory and immune responses. Transforming growth factor -$\beta$1(TGF-$\beta$) plays an important role in the control of the immune response and wound healing, and in the development o various tissues and organs, Nitric oxide(NO) is major messenger molecule regulating immune function and blood vessel dilation and serving as a neurotransmitter in the brain and peripheral nervous system. Also, NO is to be a potent mutagen that cause mutation in the p53 tumor suppressor gene in early phases of human gastric carcinogenesis. The purpose of this study was to investigate the effect of Helicobacter phlori lystes, lipopolysaccharide (LPS), and Staphylococcus enterotoxin B(SEB) on production of TGF-$\beta$1 and NO by human fibroblasts. Primary cultured human fibroblasts were incubated with H. pylori lysates(Hp), LPs, SEB, Hp+LPS, Hp+SEB, Hp+LPS+SEB. Cultured supernatants that were collected at 24, 48 and 72 hr were assessed for TGF-$\beta$1 by enzyme-linked immunosorbent assay and NO production by quantification of nitrite ion. TGF-$\beta$1 production in fibroblasts exposed with Hp, LPS or SEB for 48 hrs was enhanced, but for 72 hrs inhibited. Its production by doble exposure such as Hp+LPS, Hp+SEB, Hp+LPS+SEB was lowered in comparison with single exposure of Hp in cases of 24 and 48 hrs incubation, but for 72 hrs decreased in Hp vaculoating toxin(+), increased in Hp vacuolating toxin(-). No production in fibroblasts increaed at all doses of LPS. But its production by exposure of SEB increased or decreased according to dose and incubation time. Also, NO production by Hp vacuolating toxin(+) increased at all doses, but its production by Hp vacuolating toxin(-) decreased. Its production by doble exposure such as Hp+LPS, Hp+SEB, Hp+LPS+SEB decreased in comparison with single exposure Hp Therefore, quantities pf TGB-$\beta$1 and NO released by human fibroblasts shows differences according to kinds of stimulants. Also, in care stimulated with same kinds of stimulants, its productions exhibit quantitative differences according to exposure times. These results suggest that the decreased of TGF-$\beta$1 in fibroblasts by mixed exposure with Hp producing vacuolating toxin and bacterial toxins such as LPS and SEB may effect negatively in healing of host tissue and increased of NO by infection oh H. pylori may related to the increased susceptibility for human gastric carcinogenesis.

• Journal of Life Science
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• v.25 no.11
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• pp.1255-1264
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• 2015

Cnidium officinale, a traditional herb, has diverse beneficial pharmacological activities, such as anti-inflammatory, antioxidant, anticancer, and antiangiogenesis effects. However, the cellular and molecular mechanisms of apoptosis by C. officinale are poorly defined. The present study investigated the proapoptotic effects of water, ethanol, and methanol extract of C. officinale (WECO, EECO, and MECO, respectively) in human leukemia U937 cells. The antiproliferative activity of EECO was higher than that of WECO and MECO. The antiproliferative effect of EECO treatment in U937 cells was associated with the induction of apoptotic cell death, including increased populations of annexin-V positive cells, the formation of apoptotic bodies, DNA fragmentation, and increased numbers of cells with a loss of mitochondrial membrane potential (MMP, Δψm). EECO-induced apoptotic cell death was associated with upregulation of death receptor 4 (DR4) and down-regulation of cellular inhibitor of apoptosis protein-1 (cIAP-1), Bcl-2, and total Bid. The EECO treatment also induced the proteolytic activation of caspases (-3, -8, and -9), and degradation of caspase-3 substrate proteins, such as poly(ADP-ribose) polymerase (PARP), β-catenin, and phospholipase C-γ1 (PLCγ1). In addition, the EECO treatment effectively activated the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. However, compound C, a specific inhibitor of AMPK, significantly reduced EECO-induced apoptosis. These results indicate that AMPK is a key regulator of apoptosis in response to EECO in human leukemia U937 cells.

• Food Science of Animal Resources
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• v.36 no.4
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• pp.494-498
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• 2016

Cold plasma has been developed to reduce microbial contamination and to improve safety of food and medical products. In addition, the technology can be used in the manufacture of sausages without addition of nitrite. To be applied in food industry commercially, the new technology should be safe and efficient. However, toxicological test of plasma-treated food is limited. Therefore, the purpose of this study was to determine the mutagenicity and immune toxicity of the meat products cured with plasma-treated water (PTW) as a nitrite source. Emulsion sausages were prepared with no nitrite (control), sodium nitrite (SCS), and PTW (SCP). For a mutagenicity test, the Ames test was performed with the sausage samples. For immune toxicity test, 8-wk-old female Balb/c mice were given free access to the sausages in order to evaluate the tumor necrosis factor (TNF)-α level. As a result, no mutagenicity was detected in the sausages by the Ames test. The serum TNF-α values were less than 10 pg/mL in mice after feeding control and treated samples for 32 d, indicating that no inflammatory response was occurred by feeding the sausages made by PTW. Therefore, the present study opens the possibility of using plasma-treated water as a nitrite source without any toxicity.

• The Korean Journal of Malacology
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• v.28 no.4
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• pp.377-384
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• 2012

The importance of biological resources has been gradually increasing, and mollusks have been utilized as main fishery resources in terrestrial ecosystems. But little is known about genomic and transcriptional analysis in mollusks. This is the first report on the transcriptomic profile of Meretrix lusoria. In this study, we constructed cDNA library and determined 542 of distinct EST sequences composed of 284 singletons and 95 contigs. At first, we identified 180 of EST sequences that have significant hits on protein sequences of the exclusive Mollusks database through BLASTX program and 343 of EST sequences that have significant hits on NCBI NR database. We also found that 211 of putative sequences through local BLAST (blastx, E < e-10) search against KOG database were classified into 16 functional categories. Some kinds of immune response related genes encoding allograft inflammatory factor 1 (AIF-1), B-cell translocation gene 1 (BTG1), C-type lectin A, thioester-containing protein and 26S proteasome regulatory complex were identified. To determine phylogenetic relationship, we identified partial sequences of four genes (COX1, COX2, 12S rRNA and NADH dehydrogenase) that significantly matched with the mitochondrial genomes of 3 species-Ml (Meretrix lusoria), Mp (Meretrix petechialis) and Mm (Meretrix meretrix). As a result, we found that there was a little bit of a difference between sequences of Korean isolates and other known isolates. This study will be useful to develop breeding technology and might also be helpful to establish a classification system.

• Journal of Trauma and Injury
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• v.19 no.1
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• pp.67-73
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• 2006

Purpose: The arterial base deficit (BD) has proven to be useful in the evaluation and management of trauma patients. Indicators such as the Triage-Revised Trauma Score (t-RTS) and the systemic inflammatory response syndrome (SIRS) score have been used as triage tools for emergency trauma patients in Korea. The purpose of this study was to assess the usefulness of the initial BD in predicting injury severity and outcome in the trauma population. Methods: The medical records of 308 consecutive trauma patients admitted to the Emergency Center of Masan Samsung Hospital from January 2004 to December 2004 were carefully examined prospectively and retrospectively, and 291 patients were selected as subjects for this research. The SIRS score and the t-RTS were calculated based on the records from the emergency department, and the BD was calculated based on the arterial blood gas analysis obtained within 30 minutes of admission. The efficiency of the three indicators as triage tools was evaluated by using cross tabulations in two - by - two matrices and by using a receiver operating characteristic (ROC) curve analysis. Results: When the mortality was used as the outcome parameter, the sensitivity and the accuracy of the initial BD were higher than those of the SIRS score (p<0.05) and were same as those of the t-RTS. The areas under the ROC curves of the initial BD, the SIRS score, and the t-RTS were $0.740{\pm}0.087$, $0.696{\pm}0.082$, and $0.871{\pm}0.072$, respectively (95% confidence interval). When emergency operation and blood transfusion requirements were used as outcome parameters, the comparisons of the sensitivities and the accuracies of the initial BD and the other two indicators showed the same pattern as mentioned above. The areas under the ROC curves of the initial BD were 0.7~0.8 and were larger than those of the SIRS score (p<0.05). Conclusion: The ability of the initial BD to predict injury severity and outcome was similar to those of the t-RTS and the SIRS score. Therefore, the authors suggest that the initial BD may be used as an alternative to previous triage tools for trauma patients.