• Korean Journal of Food Science and Technology
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• v.39 no.3
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• pp.348-352
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• 2007

Inflammation is a complex process resulting from a variety of mechanisms. Combined inhibition of the activities of enzymes involved in the process may therefore be considered more important in anti-inflammatory property of plant extracts than any single contribution. In this study, the inhibitory effects of the ethanol extracts of thirty plant foods on the activities of secretory phospholipase $A_{2}$ ($sPLA_{2}$), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and 12-lipoxygenase (12-LOX) were examined. Several legumes, mungbean sprout and some leaf vegetables inhibited the activity of $sPLA_2$, upstream enzyme of inflammation pathway. Only soybean sprout and mungbean sprout significantly inhibited 12-LOX activity. Although most of extracts inhibited the activities of both COX-1 and COX-2, water dropwort and amaranth showed selectivity for the inhibition of COX-2 over COX-1. Especially, mungbean showed anti-inflammatory property at both upstream and downstream of inflammation pathway with relatively low $IC_{50}$ values for $sPLA_{2}$ and COX-2 enzymes. Mungbean sprout exhibited inhibitory effects on all enzymes related to early and late inflammation and soybean sprout suppressed 12-LOX and COX-2 simultaneously, although the activities of these plants were showed at relatively high concentration. Therefore, mungbean, mungbean sprout, and soybean sprout appear to exhibit anti-inflammatory effects by combined inhibition of inflammatory enzymes.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.26 no.3
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• pp.254-261
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• 2000

The present study has attempted to look into the mechanism of ras-induced carcinogenesis in a human epithelial cell system. Human epithelial cells immortalized with Ad12-SV40 hybrid virus were used to assess carcinogenic potential of the ras-oncogene. Cells transfected with pSV2-ras showed characteristics of cellular transformation. The transformation parameters such as cell density, soft-agar colony formation, and cell aggregation were significantly increased in the cells expressing ras oncoprotein. In addition, the duration required for the appearance of foci was shortened in the ras-transfected cells. Consistent with other reports, our results demonstrated an evidence that the ras-oncogene induced the cellular transformation of human epithelial cell system. When a high concentration of glucocorticoid was added into the media, transformation process was accelerated. It is speculated that glucocorticoid may provide an advantageous environment for the proliferation of the transformed cells. The induction of the intracellular free calcium concentrations following agonist treatment was significantly lower in the transformed cells than in the control cells. These effects were more manifested in the presence of extracellular cacium, indicating that the transformation process may alter the influx pathway of extracellular calcium. The induction of $IP_3$ following agonist treatment was also lower in the transformed cells than in the control cells. Thus, it is suggested that phospholipase C-coupled pathway was down-regulated in the process of the ras-induced transformation. While the levels of $TGF-{\beta}_1$ and PAI-2 mRNAs were decreased, the level of fibronectin mRNA was increased. The results indicate that mechanism of the ras-induced transformation may be associated with the altered expressions of growth regulatory factors. The present study demonstrates an evidence that the ras-induced cellular transformation may be associated with alteration of signal transduction and growth regulatory factors. The study will contribute to improve the understanding of molecular mechanism of epithelium-derived cancers including oral cancer.

• Korean Journal of Food Science and Technology
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• v.47 no.4
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• pp.534-538
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• 2015

The purpose of this study was to investigate the biological benefits of apple peel. The antioxidant and anti-inflammatory activities of a 70% ethanol extract of apple peel were examined. The total phenolic compound and flavonoid contents of apple peel were $6.8{\pm}0.5mg$ gallic acid equivalent/g of fresh weight and $3.3{\pm}0.3mg$ catechin equivalent/g of fresh weight, respectively. Antioxidant activity was evaluated by measuring 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity. The DPPH radical scavenging activity of apple peel was $18.9{\pm}1.6$, $46.3{\pm}2.3$ and $58.1{\pm}3.9%$ at concentrations of 0.1, 0.5 and 1.0 mg/mL, respectively (p<0.05). The anti-inflammatory effect was investigated by measuring the inhibition of inflammatory enzymes. Apple peel significantly inhibited secretory phospholipase, cyclooxygenase-1, cyclooxygenase-2, and lipoxygenase activity by up to $53.5{\pm}2.3$, $13.4{\pm}1.8$, $64.8{\pm}5.4$ and $44.4{\pm}4.5%$, respectively (p<0.05). Taken together, these findings suggest that apple peel may act as an antioxidant by radical scavenging and may possess potential anti-inflammatory properties for suppressing the activity of inflammatory enzymes. These results also suggest that apple peel can be utilized as a health functional food ingredient possessing antioxidant and anti-inflammatory activities.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.925-935
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• 1996

Background : In order to elucidate one of the pathogenic mechanisms of ARDS associated with pulmonary surfactant and oxidant injury, acute lung injury was induced by N-nitroso N-methylurethane (NNNMU). In this model, the role of phospholipase $A_2$ ($PLA_2$), surfactant, gamma glutamyl transferase (GGT) and morphology were investigated to delineate one of the pathogenic mechanisms of ARDS by inhibition of $PLA_2$ with high dose of dexamethasone. Method: Acute lung injury was induced in Sprague-Dawley rats by NNNMU which is known to induce acute lung injury in experimental animals. To know the function of the alveolar type II cells, GGT activity in the lung and bronchoalveolar lavage was measured. Surfactant phospholipid was measured also. $PLA_2$ activity was measured to know the role of $PLA_2$ in ARDS. Morphological study was performed to know the effect of $PLA_2$ inhibition on the ultrastructure of the lung by high dose of dexamethasone. Results : Six days after NNNMU treatment (4 mg/kg), conspicuous pulmonary edema was induced and the secretion of pulmonary surfactant was decreased significantly. In the acutely injured rats' lung massive infiltration of leukocytes was observed. At the same time rats given NNNMU had increased $PLA_2$ and GGT activity tremendously. Morphological study revealed bizarre shaped alveolar type II cells and hypertrophied lamellar bodies in the cytoplasm of the alveolar type II cells. But after dexamethasone treatment (20 mg/kg, for six days) in NNNMU-treated rats, these changes were diminished i.e. there were decrease of pulmonary edema and increase of surfactant secretion from alveolar type D cells. Rats given dexamethasone and NNNMU had decreased $PLA_2$ and GGT activity in comparison to NNNMU induced ARDS rats. Conclusion : Inhibition of $PLA_2$ by high dose of dexamethasone decreased pathological findings caused by infiltration of leukocytes and respiratory burst. Based on these experimental results, it is suggested that an activation of $PLA_2$ is the one of the major factors to evoke the acute lung injury in NNNMU-induced ARDS rats.

• Journal of Life Science
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• v.31 no.9
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• pp.787-795
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• 2021

Eupatorium chinensis var. simplicifolium (EUC) has anti-inflammatory and antioxidant effects. Young sprouts of EUC have been used as food for a long time, and the whole EUC plant has been used as an herbal remedy in oriental medicine. Arteriosclerosis, or chronic inflammation in arterial vessels, is a cardiovascular disease and is involved in various disorders. Cardiovascular diseases such as restenosis and neuropathic hyperplasia are mainly caused by abnormal growth and movement due to multiple growth factors in vascular smooth muscle cells (VSMCs). Platelet-derived growth factor (PDGF) is a mitogen released from damaged vessel walls and is involved in the proliferation and migration of VSMCs. To determine the effects of EUC on the abnormal proliferation and migration of VSMCs, the present study investigated intracellular signaling pathways in PDGF-BB-induced VSMCs treated with and without EUC. Pretreating PDGF-BB-induced VSMCs with EUC tended to effectively decrease cell proliferation and migration. Subsequently, the intracellular growth-related signaling pathways of AKT, phospholipase C gamma (PLC-γ), and mitogen-activated protein kinase (MAPK) were investigated using western blotting to confirm inhibited phosphorylation. Furthermore, flow cytometry data showed that EUC blocked the cell cycle of VSMCs. These results suggest that EUC can inhibit the proliferation and migration of VSMCs by controlling the cell cycle and growth factor receptors. Furthermore, this indicates that EUC can be used as a preventative against cardiovascular disease resulting from abnormal proliferation and migration of VSMCs.

• Korean Journal of Animal Reproduction
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• v.25 no.1
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• pp.71-77
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• 2001

This experiment was designed to improve the production efficiency of germ-line chimeric mice from phospholipase C (PLC)-$\beta$3 or peroxiredoxin (Prx) E -targeted ($\Delta$) ES cells by the investigating the manipulation conditions and characteristics of Jl ES cells. Four targeting clones were isolated to investigate the karyotypical and morphological stability prior to injection. All clones ($\Delta$PLC$\beta$-3 C3, $\Delta$Prx II C3, C10 and I5) showed more than 80% euploidism, however, most of $\Delta$PLC$\beta$-3 C3 clones were extensively differentiated compared to the other clones. Nine of 13 $\Delta$Prx II chimeras appeared to have at least 80% chimerism, whereas $\Delta$PLC$\beta$-3 C3 chimeras had 20% chimerism at most. Therefore, the morphological stability of ES cells under stable euploidism might mainly affect the production rate of high-coat chimeric mice. To increase the collection rate of injectable blastocysts (IBs), 5 to 10 week -aged C57BL/6J female mice were sacrificed at 3.5 days post-coitum. Ten week-aged mice were the most optimal IB donors by showing the highest collection rate (2.94/mouse) of injectable blastocysts without increase of non-injectable embryos (0.29/mouse). Foster mothers might be another factor because ICR x C57BL/6J F1 foster mother showed more increased productivity in litter size (2.8 vs. 5.6) and chimera (0 vs. 35.3%) than those of ICR foster mothers. In conclusion, the efficient production of germ-line chimeras mainly depends on the maintenance of ES cell morphology during targeting procedure, and the establishment of manipulation conditions might be a key point to maximize it.

• Radiation Oncology Journal
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• v.15 no.2
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• pp.79-95
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• 1997

Purpose : Phospholipase C(PLC) isozymes play significant roles in signal transduction mechanism. $PLC-\gamma$ 1 is one of the key regulatory enzymes in signal transduction for cellular proliferation and differentiation. Ras oncoprotein, EGFR, and PKC are also known to be involved in cell growth. The exact mechanisms of these signal transduction following irradiation, however, were not clearly documented Thus, this study was Planned to determine the biological significance of PLC, ras oncoprotein, EGFR, and PKC in damage and regeneration of rat intestinal mucosa following irradiation. Material and Method : Sixty Sprague-Dawley rats were irradiated to entire body with a single dose of 8Gy. The rats were divided into S groups according to the sacrifice days after irradiation. The expression of PLC, ras oncoprotein, EGFR and PKC in each group were examined by the immunoblotting and immunohistochemistry. The histopathologic findings were observed using H&I stain, and the mitoses for the evidence of regeneration were counted using the light microscopy & PCNA kit. The Phosphoinositide(PI) hydrolyzing activity assay was also done for the indirect evaluation of $PLC-\gamma$ 1 activity. Results: In the immunohistochemistry , the expression of $PLC-{\beta}$ was negative for all grøups. The expression of $PLC-{\gamma}1$ was highest in the group III followed by group II in the proliferative zone of mucosa. The expression of $PKC-{\delta}1$ was strongly positive in group 1 followed by group II in the damaged surface epithelium. The above findings were also confirttled in the immunoblotting study. In the immunoblotting study, the expressions of $PLC-{\beta}$, $PLC-{\gamma}1$, and $PKC-{\delta}1$ were the same as the results of immunohis-tochemistry. The expression of ras oncoprctein was weakly positive in groups II, III and IV. The of EGFR was the highest in the group II, III, follwed by group IV and the expression of PKC was weakly positive in the group II and III. Conclusion: $PLC-{\gamma}1$ mediated signal transduction including ras oncoprotein, EGFR, and PKC play a significant role in mucosal regeneration after irradiation. $PLC-{\delta}1$ mediated signal transduction might have an important role in mucosal damage after irradiation. Further studies will be necessary to confirm the signal transduction mediating the $PKC-{\delta}1$.

• Journal of Acupuncture Research
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• v.17 no.4
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• pp.149-159
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• 2000

Bee-venom Acupucture has good effect on pain control but We may be anxious about the problem of side-effect. Bee-venom components are composed of phospholipase $A_2$, hyaluronidase, melitin, apamin, MCD peptide, citrate and so on. Especially Apamin, MCD peptide and histamine cause severe reacting that is named Anaphylaxis. Anaphylaxis is a clinical syndrome characterized by the acute system reaction of multiple organ systems to an IgE-mediated immunologic mediator release in previously sensitized individuals. Respiratory and dermatologic manifestations are the most commonly expressed clinical features of anaphylaxis, and a majority of anaphylactic reactions initially appear to be localized to these two systems. Anaphylatic reaction of bee-venom are expressed clinically ulticaria, itching sensation, erythema, dizziness, nausea, hypotension and so on. Especially ulticaria and erythema are end points of increased vascular permeability and vasodilatation at the other extreme of the clinical spectrum, Gastrointestinal mucosal edema and smooth muscle contraction can result in cramping abdominal pain, nausea, and vomiting. Therefore, we have observed anaphylatic reaction of bee-venom in 11 patients, who visited WonKwang University Kunpo Oriental Medical Center, treated bee venom. The results were summarized as follows : 1. The patient distribution ratio, in regard to sex, was shown to be 1 : 2.67 for male to females. In regard to age, it was shown that people in their 30's was the most predominant case, followed by people in their 20's, 30's, 50's and 60's, respectively. 2. When Anaphylaxis was occured, it was observed to abnormality of CBC, LFT, IgE, IgG. 3. In regard to patient condition, it was observed that fatigue was most frequent. 4. In regard to the number of times and quantity of bee venom inj., it was observed that anaphylaxis is most frequent at 7-10 times(1.6-2.0cc) 5. In regard to duration of reaction, it was observed that people in their l0min' was most frequent. In disappearing duration of anaphylaxic reaction, The results showed under 60min lcases(9%), 60-120min 7cases(64%) and 180-240min 3cases(27%). 6. In symptoms of anaphylaxis, The results showed hypotension 8cases(19%), itching sensation 7cases(16%), nausea 4cases(9%), erythema 4cases(9%) and dizziness 4cases(9%). In mentality, The results showed drowsy 8case(73%) and alert 3cases(27%). 7. Generally, patients were treated with Avil, Dexa IM and PDS, peniramine, cimetidine, Q-zyme per os after H/S, N/S inj. $O_2$ was supplied according to patient's symptom. In 1 severe case, Dopamine was iv injected.

• Genomics & Informatics
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• v.6 no.4
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• pp.181-191
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• 2008

RAS guanyl-releasing protein 3 (RasGRP3), a member of the Ras subfamily of GTPases, functions as a guanosine triphosphate (GTP)/guanosine diphosphate (GDP)-regulated switch that cycles between inactive GDP- and active GTP-bound states during signal transduction. Various growth factors enhance hepatocellular carcinoma (HCC) proliferation via activation of the Ras/Raf-1/extracellular signal-regulated kinase (ERK) pathway, which depends on RasGRP3 activation. We investigated the relationship between polymorphisms in RasGRP3 and progression of hepatitis B virus (HBV)-infected HCC in a Korean population. Nineteen RasGRP3 SNPs were genotyped in 206 patients with chronic liver disease (CLD) and 86 patients with HCC. Our results revealed that the T allele of the rs7597095 SNP and the C allele of the rs7592762 SNP increased susceptibility to HCC (OR=1.55, p=0.04 and OR=1.81${\sim}$2.61, p=0.01${\sim}$0.03, respectively). Moreover, patients who possessed the haplotype (ht) 1 (A-T-C-G) or diplotype (dt) 1 (ht1/ht1) variations had increased susceptibility to HCC (OR=1.79${\sim}$2.78, p=0.01${\sim}$0.03). In addition, we identified an association between haplotype1 (ht1) and the age of HCC onset; the age of HCC onset are earlier in ht1 +/+ than ht1 +/- or ht1 -/- (HR=0.42${\sim}$0.66, p=0.006${\sim}$0.015). Thus, our data suggest that RasGRP3 SNPs are significantly associated with an increased risk of developing HCC.

• Korean Journal of Environmental Biology
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• v.26 no.4
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• pp.330-342
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• 2008

A comprehensive quality survey for PCDDs/PCDFs and coplanar PCBs as well as heavy metals (Cu, Zn, Cd and Pb) in sediments has been investigated in August 2006, Korea. Monitoring was undertaken at five streams representing different surrounding environments throughout Juwang and Gapyeong streams (reference sites), Jungrang stream (dense population site), Ansan stream (mixed small population and industrial site), and Siheung stream (heavy industrial site). The levels of heavy metal in samples were found to be significantly higher in sediment from Siheung stream compared to those of other stream sites. The heavy metal concentrations (dry weight basis) in sediment from Siheung stream were as follows; Cd (3.7 ${\mu}g$/g), Pb (1,295 ${\mu}g$/g), Cu (713.4 ${\mu}g$/g) and Zn (358.1 ${\mu}g$/g). Among 12 coplanar PCBs and 17 PCDDs/PCDFs selected as target compounds in this study, PCB (IUPAC no. 118) and OCDD were the most abundant congeners found in all sediment samples, followed by 1,2,3,4,6,7,8-HpCDD, OCDF and 1,2,3,4,6,7,8HpCDF as well as PCB (IUPAC no. 105). These results were shown to be in the same trend as the sediment samples of other countries. The levels of PCDDs/PCDFs/coplanar PCBs in sediment samples were expressed as concentrations and WHO- TEQ values. The PCDDs/PCDFs/coplanar PCBs concentrations and their WHO-TEQ values in sediment from Siheung stream were remarkably high. The levels detected were 788.16 pg/g and 36.080 pg WHO-TEQ/g dry weight for PCDDs/ PCDFs and 314 pg/g and 0.4189 pg WHO-TEQ/g dry weight for coplanar PCBs, respectively, beyond the safety level of sediment value 20 pg WHO-TEQ/g. Sediment samples of the five streams were also monitored by sensitive biomarkers using insect immune responses: hemocyte-spreading behavior and immune-associated enzyme activities of phospholipase A$_2$ (PLA$_2$) and phenoloxidase. Organic extracts of Siheung and Jungrang sediments significantly interfered with the hemocytespreading behavior, whereas those of Ansan, Gapyeong, and Juwang did not. These organic extracts did not inhibit the PLA$_2$ and phenoloxidase activities. However, phenoloxidase was highly susceptible to exposure to aqueous extracts in all site sediments. In comparison, PLA$_2$ activities of the hemocytes were significantly inhibited only by aqueous extracts of Siheung, Jungrang, and Gapyeong sediments, but not by those of Ansan and Juwang. Despite some disparity between bioand chemical monitoring results, the biomarkers can be recommended as a device warning the contamination of biohazard environmental chemicals because of a fast and inexpensive detection method.