• Parasites, Hosts and Diseases
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• v.36 no.4
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• pp.261-268
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• 1998

The present study was undertaken to investigate the role of cysteine proteinase of Trichomonas vaginalis in escaping from host defense mechanism. A cysteine proteinase of T. vaginalis was purified by affinity chromatography and gel filtration. Optimum pH for the purified proteinase activity was 6.0. The proteinase was inhibited by cysteine and serine proteinase inhibitors such as E-64, NEM, IAA, leupeptin. TPCK and TLCK, and also by $Hg^{2+}$, but not affected by serine-, metallo-, and aspartic proteinase inhibitors such as PMSF, EDTA and pepstatin A. However, it was activated by the cysteine proteinase activator, DTT. The molecular weight of a purified proteinase was 62 kDa on gel filtration and 60 kDa on SDS-PAGE. Interestingly, the purified proteinase was able to degrade serum IgA, secretory IgA, and serum IgG in time- and dose-dependent manners. In addition, the enzyme also degraded hemoglobin in a dose-dependent manner. These results suggest that the acidic cysteine proteinase of T. vaginalis may play a dual role for parasite survival in conferring escape from host humoral defense by degradation of immunoglobulins, and in supplying nutrients to parasites by degradation of hemoglobin.

• Molecular & Cellular Toxicology
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• v.5 no.3
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• pp.193-197
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• 2009

Suppressors of cytokine signaling (SOCS) proteins were originally identified as negative feedback regulators of cytokine signaling and include the Janus kinase/Signal transducer and activator of transcription (JAK/STAT) pathways. Recent studies have shown that SOCS proteins negatively regulate the receptor tyrosine kinase (RTK) pathway including the insulin receptor (IR), EGFR, and KIT signaling pathways. In addition, SOCS1 and SOCS3 have been reported to have anti-tumor effects in human hepatocellular carcinoma (HCC). However, it is uncertain whether other members of the SOCS family are associated with tumor development and progression. In this study, to investigate whether SOCS6 is aberrantly regulated in HCC, we examined the expression level of SOCS6 in HCC by Western blot analysis and immunohistochemical staining. The results showed that SOCS6 was down-regulated in all examined HCCs compared to the corresponding normal tissues. In addition, expression of SOCS6 was observed in the cytoplasm of most normal and precancerous tissue, but not in the HCCs by immunohistochemical staining. This is first report to demonstrate that SOCS6 is aberrantly regulated in HCC. These findings suggest that underexpression of SOCS6 is involved in hepatocarcinogenesis, and SOCS6 may play a role, as a tumor suppressor, in HCC development and progression.

• Korean Journal of Veterinary Research
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• v.35 no.2
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• pp.229-236
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• 1995

The effect of ${\alpha}_1$-adrenoceptor(${\alpha}_1$-AR) stimulation on intracellular pH($pH_i$), $Na^+$ activity($a_{Na}{^i}$) and contractility were investigated in isolated papillary muscles of euthyroid or hyperthyroid guinea pig with conventional microelectrode, $Na^+$ or $H^+$-selective microelectrodes, and tension transducer. Stimulation of the ${\alpha}_1$-AR by phenylephrine produced a decrease in $a_{Na}{^i}$ in euthyroid preparations. This decrease in $a_{Na}{^i}$ was abolished in presence of PKC activator, phorbol dibutyrate, and increased contrary to decrease. Phenylephrine also increased $a_{Na}{^i}$ in hyperthyroid ones. However, phenylrephtine produced an increase in $pH_i$ in both euthyroid and hyperthyroid ones. These changes were blocked by prazosin, an antagonist of ${\alpha}_1$-AR. These findings suggest that the changes in $a_{Na}{^i}$ and $pH_i$ are mediated by a stimulation of $Na^+-H^+$ exchange via ${\alpha}_1$-AR stimulation. This study focused on the increase in $a_{Na}{^i}$, $pH_i$ and contractility. The increase in $pH_i$ was blocked by amiloride or EIPA, $Na^+-H^+$ exchange inhibitors. Therefore, the increase in $a_{Na}{^i}$ and $pH_i$ mediated by ${\alpha}_1$-AR appeared to be due to an influx of $Na^+$ and a reduction of $H^+$ through $Na^+-H^+$ exchange. This study also revealed that the increase in $pH_i$ and $a_{Na}{^i}$ might be related to the sustained positive inotropic response. The $a_{Na}{^i}$ increase may contribute to the intracellular $Ca^{2+}$ through the $Na^+-Ca^{2+}$ exchange, and the $pH_i$ increase could cause an increase in the $Ca^{2+}$ sensitivity of myofilaments and may augment the ${\alpha}_1$-AR-mediated positive inotropic response.

• Journal of the Korean Crystal Growth and Crystal Technology
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• v.29 no.6
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• pp.257-263
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• 2019

Lightweight geopolymers were fabricated with non-milled IGCC slag and Si sludge as a bloating material. The relationship between addition amount of Si sludge and physical/chemical properties of lightweight geopolymers was investigated. When the geopolymers were made by mixing IGCC slag, alkali activator, and more than 10 wt.% Si sludge, the temperature of the geopolymer pastes reached higher than 130℃ in a few minutes. This exothermic reaction accelerated the geopolymer reaction; however, it was difficult to make geopolymer specimens because of a rapid bloating reaction. Both compressive strength and density of the specimens tend to decrease with an addition of Si sludge; however, there was little difference in both compressive strength and density with addition of Si sludge more than 10 wt.%. Because there was a limit to get low density geopolymers by simply increasing the addition of Si sludge, the control of pore size and distribution of geopolymer is more important by controlling flow rate of the paste through the control of W/S ratio. Therefore, it is important to control process conditions, appropriate W/S ratio for the bloating than the control of Si sludge. The optimum W/S ratio was 0.20 for the addition of Si sludge less than 30 wt.% and W/S ratio should be more than 0.28 for the addition of Si sludge more than 30 wt.%, although there was no practical application in fact.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5835-5842
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• 2015

Background: Melatonin, which is mainly produced by the pineal gland, has a good inhibitory effect on cell growth of multiple cancer types. However, the underlying molecular mechanisms of anti-tumor activity for colon cancer have not been fully elucidated. In this study, we investigated the effects of melatonin on migration in human colon cancer RKO cells and the potential molecular mechanisms. Materials and Methods: The viability of RKO cells was investigated by MTT assay after treatment with melatonin, SB203580 (p38 inhibitor) and phorbol 12-myristate 13-acetate (PMA, MAPK activator) alone or in combination for 48h. The effects of melatonin, and ML-7, a selective inhibitor of myosin light chain kinase (MLCK), and SB203580, and PMA on the migration of RKO cells were analyzed by in vitro scratch-wound assay. The relative mRNA levels of MLCK was assessed by real-time quantitative RT-PCR. Western blotting analysis was performed to examine the expression of MLCK, phosphorylation of myosin light chain (pMLC) and p38 (pp38). Results: The proliferation and migration of human colon cancer RKO cells were inhibited significantly after treatment with melatonin. The expression levels of MLCK and phosphorylation of MLC of RKO cells were reduced, and real-time quantitative RT-PCR showed that melatonin had significant effects on suppressing the expression of MLCK. Furthermore, the phosphorylation level of p38, which showed the same trend, was also reduced when cells were treated by melatonin. In addition, ML-7 (25umol/l) could down-regulate the phosphorylation of p38. Conclusions: Melatonin could inhibit the proliferation and migration of RKO cells, and further experiments confirmed that p38 MAPK plays an important role in regulating melatonin-induced migration inhibition through down-regulating the expression and activity of MLCK.

• BMB Reports
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• v.53 no.7
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• pp.379-384
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• 2020

Exposure to Ultraviolet (UV) light induces photoaging of skin, leading to wrinkles and sunburn. The perennial herb Humulus japonicus, widely distributed in Asia, is known to have anti-inflammatory, antimicrobial, and antioxidant effects. However, the physiological activities of isolated compounds from H. japonicus have rarely been investigated. This study focused on the isolation of active compounds from H. japonicus and the evaluation of their effects on photoaging in UVB-irradiated human fibroblast (Hs68) cells. When the extract and four fractions of H. japonicus were treated respectively in UVB-irradiated Hs68 cells to investigate anti-photoaging effects, the ethyl acetate (EtOAc) fraction showed the strongest inhibitory effect on MMP1 secretion. From EtOAc fraction, we isolated luteolin-8-C-glucoside (1), apigenin-8-C-glucoside (2), and luteolin-7-O-glucoside (3). These compounds suppressed UVB-induced MMP-1 production by inhibiting the phosphorylation of the mitogen-activated protein kinases (MAPKs) and activator protein-1 (AP-1). When the antioxidant activity of the compounds were estimated by conducting western blot, calculating the bond dissociation energies of the O-H bond (BDE) at different grade, and measuring radical scavenging activity, we found luteolin-8-C-glucoside (1) showed the strongest activity on the suppression of UVB-induced photoaging. These results demonstrate the inhibitory effect of three flavone glycosides derived from H. japonicus on MMP-1 production, MAPK and AP-1 signaling, and oxidative stress; this could prove useful in suppressing UVB induced photoaging.

• Journal of Acupuncture Research
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• v.32 no.3
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• pp.69-81
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• 2015

Purpose : The first purpose of this study is to find out whether the water extract of Rehmanniae Radix Preparat(RRP), Cuscutae Semen(CS) and their combination(Ssangbohwan, SBH) have the effect of suppressing Receptor activator of nuclear factor kappa-B ligand(RANKL)-induced osteoclast differentiation. The second purpose of this study is to find out whether the water extract of RRP, CS and SBH have the effect of inhibiting osteoporosis in an osteoporosis model induced by lipopolysaccharide(LPS). Methods : After promoting differentiation of osteoclasts by treating the RANKL, we observed the effect by the administration of RRP, CS and SBH. In addition, by means of Reverse transcription polymerase chain reaction(RT-PCR), we assayed mRNA expression levels of NFATc1, c-Fos, TRAP and GAPDHS(Glyceraldehyde-3-phosphate dehydrogenase, spermatogeni) from bone marrow macrophages(BMMs). Similarly, the protein expression levels of NFATc1 (Nuclear factor of activated T-cells, cytoplasmic1), C-Fos, MAPKs(Mitogen-activated protein kinases) and ${\beta}$-actin in cell lysates were analyzed by means of Western Blotting. Finally, we determined the anti-osteoporotic effects of RRP, CS and SBH, through the use of Lipopolysaccharide-induced bone-loss mouse. Results : RRP, CS and SBH showed remarkable inhibitive effect on RANKL-treated osteoclast differentiation without cytotoxicity. SBH inhibited the phosphorylation of p38, Jun N-terminal kinases(JNK), and I-${\kappa}B$ and down-regulated the induction of c-Fos and NFATc1 by RANKL. RRP, CS suppressed degradation of I-${\kappa}B$, but it did not affect c-Fos and NFATc1 by RANKL. Lastly, in vivo data showed that RRP and SBH prevented bone erosion by LPS treatment. Conclusions : These results demonstrate SBH can be effective remedy for bone-loss diseases such as osteoporosis.

• Journal of Acupuncture Research
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• v.33 no.3
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• pp.29-43
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• 2016

Objectives : The purpose of this study was to investigate the effect of LR3 and SP6 acupuncture on liver damage of streptozotocin-induced diabetic mice. Methods : Male ICR mice were divided into four groups, consisting of the normal mice group(N), acupuncture-free diabetic mice group(Con), LR3-acupuncture diabetic mice group(LR3) and SP6-acupuncture diabetic mice group(SP6). The following measurements were taken: Body weight, food intake and water intake for 2 weeks; liver weight, and glucose levels in the serum and liver; ALT and AST in the serum; reactive oxygen species(ROS), reduced glutathione(GSH) and oxidized glutathione(GSSG) in the liver; and lastly, receptor for advanced glycation endproducts( RAGE), $N{\varepsilon}-carboxymethyl$ lysine(CML), $N{\varepsilon}-carboxyethyl$ lysine(CEL), phosphorylation of inhibitory kappa B alpha($p-I{\kappa}B{\alpha}$), nuclear factor-kappa B($NF-{\kappa}B$), activator protein-1(AP-1), cyclooxygenase-2(COX-2), inducible nitric oxide synthase(iNOS), tumor necrosis factor-alpha($TNF-{\alpha}$), ${\beta}-actin$, cytochrome c and caspase in the liver. Results : The liver weight and GSH/GSSG ratio were significantly increased in SP6 compared to Con. The glucose levels in the liver were significantly decreased in LR3 compared to Con. The generation of ROS and GSSG were significantly decreased in SP6 compared to Con. The expressions of RAGE, CML, AP-1, $TNF-{\alpha}$, cytochrome c and caspase 3 were significantly decreased in LR3 compared to Con. The expressions of $p-I{\kappa}B{\alpha}$, $NF-{\kappa}B$, AP-1, COX-2, iNOS and caspase 3 were significantly decreased in SP6 compared to Con. Conclusion : It is predicted that LR3 acupuncture is related to reduced glucose levels in the liver and expressions of AGE, and that, SP6 acupuncture is related to reduced oxidative stress-related transcription factors and inflammation-related proteins. Therefore, we suggest that LR3 and SP6 acupuncture have protective effects on the liver of streptozotocin-induced diabetic mice by preventing apoptosis.

• Journal of Acupuncture Research
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• v.34 no.2
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• pp.1-18
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• 2017

Objectives : The purpose of this study was to evaluate the effects of water extracts of Eucommiae cortex (EC), Psoraleae semen (PS), and their combination on receptor activator of nuclear factor-kappa-B ligand (RANKL)-induced osteoclast differentiation. Methods : We assayed the protein expression levels of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), c-Fos, mitogen-activated protein kinases (MAPKs), and ${\beta}-actin$ in cell lysates using western blotting. Similarly, mRNA expression levels of NFATc1, c-Fos, tartrateresistant acid phosphate (TRAP), and glyceraldehyde-3-phosphate dehydrogenase, spermatogeni (GAPDHS) from bone marrow macrophages (BMMs) were analyzed using reverse transcription-polymerase chain reaction (RT-PCR). Furthermore, we determined the anti-osteoporotic effects of the water extracts of EC, PS, and their combination in a lipopolysaccharide (LPS)-induced bone-loss mouse model. Results : The in vitro data revealed showed that the combination of EC and PS extract showed a more remarkable inhibition of osteoclast differentiation than each herb did alone. The combination downregulated the induction of c-Fos, NFATc1, and TRAP by suppressing the phosphorylation of p38 and c-Jun N-terminal kinases (JNKs) and inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$). Lastly, the in vivo data showed that PS reduced the LPS-induced bone erosion. Conclusion : The result of this study suggests that EC and PS could be potential therapeutic agents for bone loss diseases such as osteoporosis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.37 no.5
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• pp.386-395
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• 2011

Introduction: Osteoporosis is a major health problem in the elderly that involves changes in the properties of bone as well as impaired bone healing around a titanium implant in both humans and animals. This study examined effect of low intensity pulsed ultrasound (LIPUS) on the bone healing process around a titanium implant in osteoporosis-induced rats. Materials and Methods: Sixteen rats were divided into two groups. A control group with osteoporosis induced by removing both ovaries and an experimental group of rats that were applied with LIPUS after osteoporosis had been induced. A screw type titanium implant (diameter, 2.0 mm: length, 3.5 mm, Cowell-Medi, KOREA) was placed into the tibias of 16 rats. The control and experimental group contained 8 rats each. The rats were sacrificed at 1, 2, 4, and 8 weeks after implantation to examine the histopathology and immunochemistry. Results: The histopathology examination revealed earlier new bone formation in the experimental group than the control group. In particular, at 1 week after implantation, more new bone matrix and collagen were observed around the implant of the experimental group compared to the control group. Immunochemistry analysis showed that the level of OPG expression of the experimental group was higher in the early stages than in the control group. After 8 weeks, the levels of OPG expression were similar in both groups. The expression level of receptor activator of nuclear factor kB ligand (RANKL) was stronger in the experimental group than the control group. After 4 weeks, the level of RANKL expression was similar in both groups. Conclusion: These results suggest that the application of LIPUS to implantation can promote bone healing around titanium in osteoporosis animals.