• Journal of Life Science
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• v.26 no.1
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• pp.50-58
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• 2016

The root bark of Ulmus macrocarpa has been used in traditional medicine for the treatment of various diseases such as edema, infection and inflammation. Nevertheless, the biological activities and underlying mechanisms of the immunomodulatory effects remain unclear. In this study, as part of our ongoing screening program to evaluate the immunomodulatory potential of new compounds from traditional medicinal resources, we investigated the effects of U. macrocarpa water extract (UME) on immune modulation in a murine RAW 264.7 macrophage model. As immune response parameters, the productions of as nitric oxide (NO) and cytokines such tumor necrotic factor (TNF)-α, interleukin (IL)-1β and IL-10 were evaluated. Although the release of IL-1β remained unchanged in UME-treated RAW 264.7 macrophages, the productions of NO, TNF-α and IL-10 were significantly increased, along with the increased expression of inducible NO synthase, TNF-α and IL-10 expression at concentrations with no cytotoxicity. UME treatment also induced the nuclear translocation of nuclear factor κB (NF-κB), and phosphorylation of Akt and mitogen-activated protein kinases (MAPKs) indicating that UME activated macrophages through the activation of NF-κB, phosphoinositide-3-kinase (PI3K)/Akt and MAPKs signaling pathways in RAW 264.7 macrophages. Furthermore, pre-treatment with UME significantly attenuated the production of NO, but not TNF-α, IL-1β and IL-10, in lipopolysaccharide-stimulated RAW 264.7 cells suggesting that UME may be useful in preventing inflammatory diseases mediated by excessive production of NO. These findings suggest that the beneficial therapeutic effects of UME may be attributed partly to its ability to modulate immune functions in macrophages.

• Journal of Life Science
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• v.21 no.11
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• pp.1518-1525
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• 2011

Sorafenib is the only approved systemic, therapeutic agent for hepatocellular carcinoma (HCC). The use of Ginseng Extract (GE) in cancer patients is growing worldwide; however, drug interaction between sorafenib and GE has not been illuminated. Four different human cancer cell lines including HepG2 were used and immunocompetent mice were implanted subcutaneously with a mouse HCC cell line. Treatment with low dose GE stimulated cell growth, while a high dose inhibited growth. pERK (phosphorylation of extracellular signal-regulated kinase) was concomitantly increased and decreased respective of different doses of GE. Antitumoral effect of sorafenib decreased in non-proliferating phase cells but was sensitized after low dose GE (LDG) treatment. PD98059 (ERK phosphorylation inhibitor) efficiently blocked ERK phosphorylation, resulting in loss of sorafenib sensitization even after LDG treatment. In the HCC mouse model, LDG alone slightly increased tumor size while sorafenib alone significantly decreased it. However, a combination of LDG and sorafenib significantly decreased tumor size compared with sorafenib alone. Increase of pERK was observed in some normal mice organs and mild inflammatory change was observed in some of these organs, suggesting pERK activation by LDG may cause unexpected toxicity in normal cells. GE, dose-dependently, induced stimulation or inhibition in some human cancer cell lines. Combinational use of GE and sorafenib possibly potentiated an antitumoral response to sorafenib. pERK level has been provided as a potential predictive marker for sorafenib. Our result may suggest GE's dual effects in relation to pERK level in HCC cancer cell lines, and that certain doses of GE can sensitize sorafenib.

• Korean Journal of Food Science and Technology
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• v.32 no.3
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• pp.590-597
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• 2000

The rheological properties of ${\beta}-glucans$ isolated from non-waxy and waxy barley were investigated. ${\beta}-Glucan$ solutions showed pseudoplastic properties and their behaviors were explained by applying Power law model in the range of concentrations$(1{\sim}4%)$ and temperatures$(20{\sim}65^{\circ}C)$. The effects of temperature and concentration on the apparent viscosity at $700\;s^{-1}$ shear rate were examined by applying Arrhenius equation and power law equation, and their effect was more pronounced in waxy ${\beta}-glucan$ solutions. The activation energy for flow of ${\beta}-glucan$ solutions decreased with the increase of concentration, and the concentration-dependent constant A increased with the increase of temperature. The intrinsic viscosity of waxy ${\beta}-glucan$ was higher than that of non-waxy ${\beta}-glucan$. The transition from dilute to concentrate region occurred at a critical coil overlap parameter $C^*[{\eta}]=0.02.$ The slopes of non-waxy and waxy ${\beta}-glucan$ at $C[{\eta}] were similar, but the slope of waxy ${\beta}-glucan$ at $C[{\eta}]>C^*[{\eta}]$ was higher than that of non-waxy ${\beta}-glucan$. Dynamic viscoelasticity measurement showed that cross-over happened, and storage modulus was higher than loss modulus at frequency range above cross-over. ${\beta}-Glucan$ solutions formed weak gels after stored for 24 hr.

• Tuberculosis and Respiratory Diseases
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• v.51 no.5
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• pp.437-447
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• 2001

Background: TNF-alpha is related to the generation of lung fibrosis in patients with UIP. The precise mechanism leading to lung fibrosis by TNF-alpha is unknown. However, the activation of a transcription factor like AP-1(down stream of c-jun N-terminal kinase, JNK) by TNF-alpha may be related to the induction of fibrogenic cytokines like PDGF or IGF-I. Furthermore, JNK was reported to be activated in the radiation-induced lung fibrosis model. This study examined JNK activity in patients with UIP. Methods : The expression of phosphorous JNK(p-JNK), macrophage/monocyte specific markers, CD68, and cytokeratin was evaluated by immunohistochemical(IHC) staining of lung tissues from patients with UIP and lung cancer. An in vitro kinase assay was performed with alveolar macrophages obtained by a bronchol-avleolar lavage from patients with UIP and healthy persons as the control. Results : The IHC stain showed that p-JNK is expressed in the almost all of the alveolar macrophages and smooth muscle cells in patients with UIP. In case of the normal areas of the lung from patients with lung cancer, the alveolar macrophages showed little p-JNK expression. Interestingly, increased JNK activity was not found in the in vitro kinase assay of the alveolar macrophages obtained from both patients with UIP and healthy persons as the control. Furthermore, 10 ng/mL of TNF-alpha failed to increase the JNK activity of the alveolar macrophages in both patients with UIP and healthy people. Conclusion : The JNK was activated constitutionally in patients with UIP. However, the role of JNK in the pathogenesis of lung fibrosis needs to be clarified.

• Journal of Acupuncture Research
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• v.22 no.3
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• pp.37-51
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• 2005

Mast cell is a cell that functions mainly in our body with a respect to inflammation and allergic response. Bee venom has been progressed in a study as a model related to mechanism in alleviation of pain until now, but it is being progressed in a study relevant to immunocyte in anti-inflammation or anti-allergic response. The present study is aimed to present the basis related to a future study of gene, by researching the influence of melittin and MCD Peptide, which are major ingredients in Bee venom, upon the expression of gene in the mast cell strain. In this study, it dealt with melittin and MCD Peptide respectively, in the effective concentration after passing though the experiment of cytotoxicity by using human mast cell strain. Also, with the respect in the aspect of expression in gene that changes at this time, information was obtained through the technique of analyzing microarray. Through experimental statistics, when regarding a case that global M is significant in more than 1 or -1, in melittin, all 7 genes were accelerated, and 8 inhibited. In MCDP, 7 genes were accelerated and 17 genes inhibited. The function in the body to which these genes are related, was associated with the protein binding within a cell, the activation in the function of lymphocyte, the acceptor related to macrophage antigen. In cell nucleus, substance related to GABA A receptor, protein associated with cAMP reactive element, substance related to complement system No.8 and to B-cell, protein substance related to polycystic kidney disease, substance related to inflammation, and the protein substance of influencing coagulation of blood. Through these results of analysis, it could obtain more useful materials in clarifying the mechanism of action in melittin and MCD peptide, which are in charge of mainly medical action in the abdomen. Also, it is thought that an in-depth study on the influence of main ingredients in Bee venom, the wholly honey bee venom aqua upon anti-allergic response or anti-inflammation are further required.

• Journal of Korean Academy of Oral and Maxillofacial Radiology
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• v.23 no.2
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• pp.229-250
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• 1993

This study was performed to investigate the morphological and structural changes of bone tissues and the effects of irradiation on the mandibular bodies of rats which were fed low calcium diets. In order to carry out this experiment, 160 seven-week old Sprague-Dawley strain rats weighing about 150 gm were selected and equally divided into one normal diet group of 80 rats and one low calcium diet group with the remainder. These groups were then subdivided into two groups, 40 were assigned rats for each subdivided group, exposed to radiation. The Group 1 was composed of forty non-irradiated rats with normal diet, Group 2 of forty irradiated rats with normal diet, Group 3 forty non-irradiated rats with low calcium diet, and Group 4 forty irradiated rats with low calcium diet. The two irradiation groups received a single dose of 20 Gy on the jaw area only and irradiated with a cobalt-50 teletherapy unit. The rats with normal and low calcium diet groups were serially terminated by ten on the 3rd, the 7th, the 14th, and the 21st day after irradiation. After termination, both sides of the dead rats mandible were removed and fixed with 10% neutral formalin. The bone density of mandibular body was measured by use of bone mineral densitometer(Model DPX -alpha, Lunar Corp., U.SA). Triga Mark ill nuclear reactor in Korea Atomic Research Institute was used for neutron activation and then calcium contents of mandibular body were measured by using a 4096 multichannel analyzer (EG and G ORTEC 919 MCA, U.SA). Also the mandibular body was radiographed with a soft X-ray apparatus(Hitex Co., Ltd., Japan). Thereafter, the obtained microradiograms were observed by a light microscope and were used for the morphometric analysis using a image analyzer(Leco 2001 System, Leco Co., Canada). The morphometric analysis was performed for parameters such as the total area, the bone area, the inner and outer perimeters of the bone. The obtained results were as follows: 1. In the morphometric analysis, total area and outer perimeter of the mandibular bodies of Group 3 were a little smaller than that of Group 1. The mean bone width and bone area were much smaller than that of Group 1 and the inner perimeter of Group 3 was much longer than that of Group 1. The total area and outer perimeter of Group 2 and Group 4 showed little difference. The mean bone width and bone area of Group 4 were smaller than that of Group 2 and the inner perimeter of Group 4 was longer than that of Group 2. 2. The remarkable decreases of the number and thickness of trabeculae and also the resorption of endosteal surface of cortical bone could be seen in the microradiogram of Group 3, Group 4 since the 3rd day of experiment. On the 21st day of experiment, the above findings could be more clearly seen in Group 4 than in Group 3. 3. The bone mineral density of Group 3 was lesser than that of Group 1 and the bone mineral density of Group 4 was lesser than that of Group 2 on the 7th, 14th, 21st days. The irradiation caused the bone mineral density to be decreased regardless of diet. In the case of Groups with low calcium diet, the bone mineral density was much decreased on the 21st day than on the 3rd day of experiment. 4. The calcium content in mandible of Group 3 was smaller than that of Group 1 throughout the experiment. roup 4 showed the least amount of calcium content. The irradiation caused the calcium content to be decreased regardless of diet. In the case of Groups with low calcium diet, the calcium content was much decreased on the 21st day than on the 3rd day of experiment. In conclusion, the present study demonstrated that morphological changs and decrease of bone mass due to resorption of bone by low calcium diet, and that the resorption of bone could be found in the spongeous bone and endosteal surface of cortical bone. So the problem of resorption of bone must be considered when the old and the postmenopausal women are taken radiotherapy because the irradiation seems to be accelerated the resorption of osteoporotic bone.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.5
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• pp.537-544
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• 2017

In this study, the anti-inflammatory effect of Polyopes affinis ethanol extract (PAEE) was investigated using LPS-stimulated RAW 264.7 cells and a croton oil-induced ICR mice model. Treatment with PAEE significantly reduced production of nitric oxide (NO) and pro-inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor $(TNF)-{\alpha}$, and $IL-1{\beta}$] in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. PAEE treatment also reduced expression of inducible NO synthase, cyclooxygenase-2, nuclear $factor-{\kappa}B$, and mitogen-activated protein kinases in LPS-stimulated RAW 264.7 cells. In the croton oil-induced ear edema test, application of PAEE (10~250 mg/kg body weight) reduced ear edema in a dose-dependent manner, and PAEE treatment at 50 mg/kg body weight showed similar inhibitory effects compared with prednisolone (10 mg/kg body weight). Histological analysis revealed reduced dermal thickness and lower number of infiltrated mast cells. These results suggest that PAEE might be used as a promising anti-inflammatory agent for inhibition of LPS-induced inflammation and ear edema formation.

• 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.24 no.6
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• pp.664-670
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• 2014

In the present study, we investigate the role of V. vulnificus in promoting the inflammation of mouse ileal ephitelium and its related signaling pathways. ICR mice were infected orally with V. vulnificus ($1{\times}10^9CFU$) for 16 h as a representative model of food-borne infection. To find the major portal of entry of V. vulnificus in mouse intestine, we have measured the levels of bacterial colonization in small intestine, colon, spleen, and liver. V. vulnificus appeared to colonize in intestine and colon in the order of ileum >> jejunum> colon, but lack in the duodenum, spleen, and liver. V. vulnificus in ileum caused severe necrotizing enteritis and showed shortened villi heights accompanied by an expanded width and inflammation, compared with the control mice. V. vulnificus induced ileal epithelium inflammation by activating phosphorylation of PKC and membrane translocation of $PKC{\alpha}$. V. vulnificus induced the phosphorylation of ERK and JNK, but did not affect p38 MAPK phosphorylation. Notably, V. vulnificus stimulated the I-${\kappa}B$-dependent phosphorylation of NF-${\kappa}B$ in mouse ileal epithelium. Finally, the ileal infection of V. vulnificus resulted in a significant increase in expression of proinflammatory cytokines and Toll-like receptors, respectively, compared to the control. Collectively, our results indicate that V. vulnificus induces ileal epithelium inflammation by increasing NF-${\kappa}B$ phosphorylation via activation of PKC, ERK, and JNK, which is critical for host defense mechanism in food-borne infection by V. vulnificus.

• Korean Chemical Engineering Research
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• v.48 no.2
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• pp.259-267
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• 2010

The catalytic wet oxidations of the wastewater containing azo dye Reactive Black 5(RB5) with heterogeneous catalyst of CuO have been carried out to investigate the effects of temperature($190{\sim}230^{\circ}C$) and catalyst concentration(0.00~0.20 g/l) on the removals of colour and total organic carbon TOC. The wastewater colour was measured with spectrophotometer, and the oxidation rate was estimated with TOC. About 90% of colour was removed during 120 min in thermal degradation of the RB5 wastewater at $230^{\circ}C$, while TOC was not removed at all. As increasing reaction temperature and catalyst concentration, the removal rates of colour and TOC increased in the catalytic wet oxidations of RB5 wastewater. The effects of catalyst were already considerable even at 0.01 g CuO/l, while the removal rates of colour and TOC increased negligibly with increasing the catalyst concentration above 0.05 g CuO/l. The initial destruction rates of the wastewater colour have shown the first-order kinetics with respect to the wastewater colour. TOC changes during catalytic wet oxidations have been well described with the global model, in which the easily degradable TOC was distinguished from non-degradable TOC of the wastewater. The impacts of reaction temperature on the destruction rate of the wastewater colour and TOC could be described with Arrhenius relationship. Activation energies of the colour removal reaction in thermal degradation, wet oxidation, and catalytic wet oxidation(0.20 g CuO/l) of the RB5 wastewater were 108.4, 78.3 and 74.1 kJ/mol, respectively. The selectivity of wastewater TOC into the non-degradable intermediates relative to the end products in the catalytic wet oxidations of RB5 wastewater was higher compared to that in phenol wet oxidations.