• IMMUNE NETWORK
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• v.21 no.6
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• pp.42.1-42.20
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• 2021

Eosinophils play critical roles in the maintenance of homeostasis in innate and adaptive immunity. Although primarily known for their roles in parasitic infections and the development of Th2 cell responses, eosinophils also play complex roles in other immune responses ranging from anti-inflammation to defense against viral and bacterial infections. However, the contributions of pattern recognition receptors in general, and NOD-like receptors (NLRs) in particular, to eosinophil involvement in these immune responses remain relatively underappreciated. Our in vivo studies demonstrated that NLRC4 deficient mice had a decreased number of eosinophils and impaired Th2 responses after induction of an allergic airway disease model. Our in vitro data, utilizing human eosinophilic EoL-1 cells, suggested that TLR2 induction markedly induced pro-inflammatory responses and inflammasome forming NLRC4 and NLRP3. Moreover, activation by their specific ligands resulted in caspase-1 cleavage and mature IL-1β secretion. Interestingly, Th2 responses such as secretion of IL-5 and IL-13 decreased after transfection of EoL-1 cells with short interfering RNAs targeting human NLRC4. Specific induction of NLRC4 with PAM3CSK4 and flagellin upregulated the expression of IL-5 receptor and expression of Fc epsilon receptors (FcεR1α, FcεR2). Strikingly, activation of the NLRC4 inflammasome also promoted expression of the costimulatory receptor CD80 as well as expression of immunoregulatory receptors PD-L1 and Siglec-8. Concomitant with NLRC4 upregulation, we found an increase in expression and activation of matrix metalloproteinase (MMP)-9, but not MMP-2. Collectively, our results present new potential roles of NLRC4 in mediating a variety of eosinopilic functions.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.8
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• pp.1167-1174
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• 2013

Cancer cells exhibit increased demand for glutamine-derived carbons to support anabolic processes. Indeed, the spectrum of glutamine-dependent tumors and the mechanisms through which glutamine supports cancer metabolism remain areas of active investigation. In the present study, we investigated the effects of glutamine deprivation on the correlation between tightening of tight junctions (TJs) and anti-invasive activity in human prostate carcinoma LnCap cells. Glutamine deprivation markedly inhibited cell motility and invasiveness in a time-dependent manner. The anti-invasive activity of glutamine deprivation was associated with an increased tightness of the TJ, which was demonstrated by an increase in transepithelial electrical resistance (TER). The activities of matrix metalloproteinase (MMP)-2 and MMP-9 were inhibited in a time-dependent fashion by glutamine deprivation, which was correlated with a decrease in expression of their mRNA and proteins and up-regulation of tissue inhibitors of metalloproteinases (TIMPs) expression. Furthermore, glutamine deprivation repressed the levels of the claudin family members, which are major components of TJs that play a key role in the control and selectivity of paracellular transport. Moreover, the levels of E-cadherin, a type I transmembrane glycoprotein, and snail, an epithelial to mesenchymal transition regulator and zinc finger transcription factor, were markedly modulated by glutamine deprivation. Taken together, these findings suggest that TJs and MMPs are critical targets of glutamine deprivation-induced anti-invasion in human prostate carcinoma LnCap cells.

• Journal of Korean Medicine Rehabilitation
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• v.25 no.2
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• pp.15-35
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• 2015

Objectives This study was performed to investigate the effects of Bujasasim-tang ethanol extract (BST) on oxidative stress, inflammation and osteoarthritic rat model. Methods To ensure safety of BST, heavy metal levels were measured and cytotoxicity test was done. In vitro, To evaluate antioxidative effects of BST, total phenolic contents, 1,1-diphenyl-2-picryl-hydrazyl (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) scavenging activity, reactive oxygen species (ROS) levels were measured. Also, to evaluate anti-inflammatory effects of BST treated group, total nitric oxide (NO) and pro-inflammatory cytokines (IL-$1{\beta}$, IL-6, TNF-${\alpha}$) levels were measured in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. In vivo, We injected MIA $50{\mu}l$ (60 mg/ml) into knee joints of rats to induce osteoarthritis. Rats were divided into total 3 groups (normal, control, BST treated group, each n=7). Normal group was not treated at all without inducing osteoarthritis and taken normal diet. Control group was induced osteoarthritis by MIA and taken with 2 ml of distilled water once a day for 4 weeks. BST treated group was induced osteoarthritis by MIA and taken BST 2 ml (200 mg/kg/mouse) once a day for 4 weeks. We evaluated dynamic weight bearing with the Incapacitance Test Meter. At the end of experiment, the rats were sacrificed to observe the functions of liver and kidney, changes of WBC, neutrophil, lymphocyte, monocyte levels in blood, to evaluate the levels of pro-inflammatory cytokines, tissue inhibitor of metallopreteinases-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), prostaglandin $E_2$ ($PGE_2$), leukotriene $B_4$ ($LTB_4$) within serum. We observed change of articular structures by Hematoxylin & Eosin (H&E), safranin-O staining method and measured amount of cartilage by micro CT-arthrography. Statistical analysis was done by unpaired student's t-test with significance level at p<0.05 in SPSS 11.0 for windows. Results 1. Safety of the BST was identified. 2. AST, ALT, BUN, creatinine levels of BST treated group were within normal limit. In vitro, 1. DPPH and ABTS free radical scavenging activities of BST showed dose-dependent increase. 2. ROS production were significantly decreased. 3. Total nitric oxide (NO) and IL-$1{\beta}$ production were decreased. 4. IL-6 and TNF-${\alpha}$ production were significantly decreased. In vivo, 1. Weight bearing ability was significantly increased. 2. WBC, neutrophil, lymphocyte, monocyte levels in blood were decreased. 3. IL-$1{\beta}$ and TNF-${\alpha}$ levels in serum were significantly decreased. and the IL-6 level was decreased. 4. TIMP-1, MMP-9, $LTB_4$, $PGE_2$ levels in serum were significantly decreased. 5. Cartilage volume of BST treated group was significantly increased. Also changes of cartilage, synovial membrane, fibrous tissue were suppressed. Conclusions The results obtained in this study Bujasasim-tang have effects of antioxidative, anti-inflammatory, relieve pain and protection of cartilage. Therefore we expect that Bujasasim-tang is effective treatment for osteoarthritis.

• Korean Journal of Pharmacognosy
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• v.35 no.2 s.137
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• pp.110-115
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• 2004

For the evaluation of anti-tumor activity of Korean Oldenlandia Herb (KOH) and Radix (KOR), our experiment was performed with methanol extracts of KOH and KOR. They did not shown any cytotoxicity against HT1080 cell lines. However, they effectively showed anti-metastatic activity through inhibition of the adhesion of HT1080 cells to gelatin, downregulated the expression of MMP2 and uPA and upregulated the expression of TIMP2. They also inhibited tube formation of HUVECs induced by bFGF. However, they did not affect DNA topoisomerase I activity. Simiarly, the T/Cs % in KOH and KOR treated mice were increased 134.9% and 171 %, respectively at 2500 mg/kg. These results suggest that KOH and KOR exert anti-tumor activity via anti-metastatic and anti-angiogenic activities. The further study for isolation of effective compounds and its exact mechanism and comparative study with Chinese Oldenlandia Herba will be required.

• Journal of Acupuncture Research
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• v.20 no.5
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• pp.159-171
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• 2003

Objective: To study on the anti-cancer, anti-metastasis and immune response improvement effects of Herbal-acupuncture with Asparagus cochinchinensis infusion solution. Methods: we put into Chung-wan(CV12) and Kwanwon(CV4) of C57bl/6 which are corresponding to human body with Asparagus coc hinchinensis infusion solution. We observed the effect on the expres sion of MMP-9. the expression of cytokine gene, number of pulmon ary colony, histological analysis on tissue metastasis of lung and liver. the expression of cytokine gene on PBMC. the number of $CD3e^+/CD4^+$. $CD3e^+/CD8^+$, $NK^+$ cell. Results: The results were obtained as follows I) The effect on expression of MMP-9. the expression of cytokine gen e was inhibited significantly in all the sample groups. compared with control group. 2) In pulmonary colony, sample groups were decreased significantly, compared with control group. especially, the group put into Chung-wan(CV12) was decreased significantly. 3) Histological analysis of sample groups inhibited significantly in all th e sample groups compared with that control groups in both of lung and liver. especially, the group put into Chung-wan(CV12) was inhibited significantly. 4) The effect on cytokine gene expression on PBMC of all the sample groups were increased significantly, compared with control group. 5) In flow cytometry, $CD3e^+/CD4^+$ $CD3e^+/CD8^+$, $NK^+$ cell in sample groups were increased compared with control group.

• Journal of Acupuncture Research
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• v.18 no.3
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• pp.79-93
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• 2001

Objective : This study was purposed to investigate the anti-cancer and anti-metastasis and immune response of Aqua-acupuncture with Amomum amarum Lourerio infusion solution. Methods : The Amomum amarum Lourerio infusion solution put into Chung-wan(CV12) of BALB/c or C57BL6 mice were rised to cancer by B15-F10 and HT1080, S-180 cancer cell line. Results : The following result have been obtained 1. The effect on expression of MMP-9 gene about the HT1080 cancer cell line was increased in 100, $50{\mu}g/m{\ell}$ diluent groups, compared with control group. 2. The effect on expression of MMP-9 gene about the B15-F10 cancer cell line was increased in all the sample groups, compared with control group. 3. S-180 cancer cell line transplants in BALB/c mice were inhibited significantly in weight inctease in all the sample groups, compared with control group. 4. The effect on spleen cell proliferation was decreased in all the sample groups, compared with control group. 5. The $IFN-{\gamma}$ in all the sample groups and the $TNF-{\alpha}$ in 25 and $12.5{\mu}g/m{\ell}$ diluent groups was increased. 6. In flow cytometry, the number of CD4+, CD19+ cell in all the sample group was increased and the number of CD8+ cell in $100{\mu}g/m{\ell}$ diluent group, compared with control group. Conclusion : According to the result, Aqua-acupuncture with Amomum amarum Lourerio infusion solution has significant anti-cancer, anti-metastasis and Immune response improvement.

• Nutrition Research and Practice
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• v.6 no.6
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• pp.499-504
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• 2012

This study attempted to investigate the effects of resveratrol on the differentiation of adipocytes. After cells were treated with various concentrations of resveratrol (0, 10, 20, and 40 ${\mu}mol/L$), adipocyte proliferation, the protein expression of transcription factors, and MMPs' activities were determined. Cell proliferation was inhibited more within 4 days of incubation (P<0.05), and lipid accumulation in adipocyte was significantly inhibited by 93.8%, 92.4% and 91.5%, respectively, after two days of 10, 20, and 40 ${\mu}mol/L$ resveratrol treatment (P<0.05). Six days of incubation with the three resveratrol concentrations caused a significantly decreases of 63%, 59.9%, and 25.1% GPDH activity as a dose-dependent response. The triglyceride concentration also decreased significantly with the increase of resveratrol concentration (P<0.05). The protein expression of CCAAT/enhancer-binding protein (C/$EBP{\beta}$) was decreased significantly by 56% and 30% while $PPAR{\gamma}$ was significantly reduced by 57% and 15% with resveratrol treatments of 20 and 40 ${\mu}mol/L$, respectively (P<0.05). The protein expression of C/$EBP{\alpha}$ was decreased by 83%, 74%, and 38% to increased dosage levels, with significance determined for this decrease from 20 ${\mu}mol/L$ of resveratrol. The protein expression of fatty acid binding protein (FABP4) was decreased significantly by 88%, 72%, and 46% with the increase of resveratrol concentration. The activity of MMP-2 was decreased significantly by 84%, 70%, and 63% while MMP-9 activity was decreased significantly by 74%, 62%, and 39% with the increased resveratrol concentrations of 10, 20, and 40 ${\mu}mol/L$, respectively (P<0.05).

• The Korea Journal of Herbology
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• v.26 no.3
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• pp.7-14
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• 2011

Object : This study evaluated the effects of Daeseungkitang(DSK) on cerebral infarct of middle cerebral artery occlusion(MCAO). Method : Sprague-Dawley rats are used for observing to induce cerebral infraction closing its middle cerebral artery temporarily and take DSK by mouth the next 5 days, observe the amount of feces and urine. It is investigated the correlation between them after examining neurological score. Results : It is resulted the below. On the 2nd day of taking DSK, the total amount of feces of the cerebral infarct rats is increased significantly. After taking DSK, the urine volume of the cerebral infarct rats does not change at all. Taking DSK significantly improves neurological score of the cerebral infarct rats. There is a significant correlation between total amount of feces of the cerebral infarct rats and neurological score, otherwise there is no significant correlation between total amount of feces and neurological score which is taken DSK. By taking DSK, the volume of cerebral infarction does not decrease significantly. Taking DSK restrains the expression of iNOS in the cerebral cortex and striatum of the cerebral infarct rats. Taking DSK restrains the expression of MMP-9 in the cerebral cortex of the cerebral infarct rats. Taking DSK restrains the edema of astrocytes of the positive reaction of GFAP in the cerebral cortex of the cerebral infarct rats. Conclusion : According to above results, Daeseungkitang(DSK) is assumed that showing reaction of protecting neuron cell by restraint brain tissue edema thorough controlling water balance.

• Journal of Haehwa Medicine
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• v.8 no.1
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• pp.793-825
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• 1999

For the development of drugs for alzheimer,s disease, the study was done to review the oriental pathology, clinical data, recent trends for research and strategy for future study. The results were as follows: 1. The medical term Chi-dsi implying alzheimer,s disease was referred for the first time in a medical book, Hwatasheneubijeon written by Hwa-Ta and its differentiation and treatment were studied more in Ming or Ching dynasties. Chi-dai can be differentated as weak(虛) syndrome and Shi(實) syndrome. This can be caused by deficiencies of renal Yin, renal Yang, cardiac Yin and hepatic blood, while that by deficiencies of pathological fluid(痰飮) and clotted blood(瘀血). 2. Dementia can be roughly classified as alzheimer's disease and multi-infarct disease. Its causes were known to be cholinergic transmitter, C-peptide, amyloid-${\beta}$, apolipoprotein, APP(amyloid precursor protein), TGF, MMP-9 and free radical. 3. In Korea experimental studies were chiefly done for the elimataion of C-peptide, amyloid-${\beta}$, apolipoprotein, APP for alzheimer's disease, for the development of drug inhibiting degerative change following CVA and loss of memory and also administrative measure was done by support of government. 4. Drugs of dimentia developed so far were Chi-Dai dan, extracts from aloe, mushroom, green tea, Ganoderma and also folic acid, vitamin C, DHEA and silk amino acid were reported to be effective in dimenta. 5. Future strategic research had better be done on dementia-inducing factors such as acetylcholine, C-peptide, amyloid-${\beta}$, apolipoprotein, APP, TGF, MMP-9 and free radical, development of animal model for dimentia, clinical study, epidemiology, nursing and administrative studies and also consortium for dimentia research should be formed so that repeated investment be avoided.

• Korean Journal of Acupuncture
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• v.36 no.2
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• pp.115-126
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• 2019

Objectives : Osteoporosis is a condition characterized by low bone mass and increased bone fragility. It has become a major problem of senior citizens. The purpose of this study is to experiment the effect of water extract of Forsythiae Fructus (wFF) on osteoclast differentiation; and the other purpose is to examine the effect of wFF on osteoporosis in ovariectomized rat. Methods : To investigate the effect of wFF on osteoclast differentiation and activity, RAW 264.7 cells were used. The number of TRAP positive cell, TRAP activity, pit area, mRNA expression of makers (RANK, TRAP, CA II, CTK, MMP-9, NFATc1, c-Fos), protein expression of makers (NFATc1, c-Fos) were investigated. For in vivo study, 40 female Sprague-Dawley (SD) rats were induced osteoporosis by ovariectomy (OVX) and then tested for anti-osteoporosis effect by administration of wFF. Results : wFF suppressed osteoclatogenesis, TRAP activity and pit area formation. Moreover, wFF decreased the expression of master differentiation factors (NFATc1, c-Fos) and also reduced the osteoclastogenesis-related markers (TRAP, CA II, CTK, MMP-9). These suggest that wFF inhibit osteoclasts differentiation and bone resorption. In the OVX rat model, wFF inhibited decreasing of BMD and trabecular area. Conclusions : Forsythiae Fructus should be effective for osteoporosis prevention and treatment.