• Journal of Life Science
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• v.19 no.2
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• pp.157-162
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• 2009

Nitric oxide (NO) is a diffusible, multifunctional and transcellular messenger that has been implicated in numerous physiological and pathological conditions. It has been reported that NO induced apoptosis in tumor cells, macrophage cells and inhibited apoptosis in normal cells, endothelial cells. To examine whether NO could induce apoptosis in MCF-7 cells, cells were treated with SIN-1 (3-morpholinosydnonimine), NO donor. Cell viability did not change in SIN-1 treated cells for 48 h and there was no significantly changes in cell cycle progression or growth pattern by FACS analysis. But p53 protein, an apoptosis-related factor, increased SIN-1 treatment time dependently. Bcl-2, MDM2 and p21 were also accumulated. Bax level did not change. A major role of inhibiting apoptosis by NO in MCF-7 cells, cobalt chloride ($CoCl_2$) was added to cells preincubated with SIN-1. Whereas $CoCl_2$ treated cells underwent apoptosis, for 24 h SIN-1 preincubated cells were not induced apoptosis. Inactivated proteins, MDM2 and bcl-2, by $CoCl_2$ levels also increased in SIN-1 pre-treated cells. These results suggested that SIN-1 blocked p53 by MDM2 activation and inhibited apoptosis by inducing p21 and bcl-2 expression.

• Journal of Life Science
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• v.28 no.6
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• pp.733-737
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• 2018

Cucurbitacin-I, a natural triterpenoid derived from Cucurbitaceae family plants, exhibits a number of potentially useful pharmacological and biological activities. Indeed, the previous study demonstrated that cucurbitacin-I reduced the proliferation of colon cancer cells by enhancing apoptosis and causing cell cycle arrest at the G2/M phase. CD44, a type I transmembrane protein with the function of adhering to cells, mediates between the extracellular matrix and other cells through hyaluronic acid. Recent studies have demonstrated that an overexpression of the CD44 membrane receptor results in tumor initiation and growth, specific behaviors of cancer stem cells, the development of drug resistance, and metastasis. The aim was to examine the effect of cucurbitacin-I on CD44 expression human ovarian cancer cells because the effect of cucurbitacin-I on CD44 expression has not been reported. The expressions of CD44 mRNA and protein were detected using a quantitative real-time reverse-transcription polymerase chain reaction and a Western blot analysis, respectively. Treatment with cucurbitacin-I inhibited the expression of CD44 mRNA and protein. A subsequent analysis revealed that cucurbitacin-I blocked the phosphorylation of activator protein-1 (AP-1) and nuclear factor kappa-B ($NF-{\kappa}B$), which are key regulators of CD44 expression. Taken together, the data demonstrate that cucurbitacin-I regulates the AP-1 and $NF-{\kappa}B$ signaling pathways, leading to decreased CD44 expression.

• Biomedical Science Letters
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• v.18 no.2
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• pp.104-111
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• 2012

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases which degrade extracellular matrix (ECM) during embryogenesis, wound healing, and tissue remodeling. Dysregulation of MMP activity is also associated with various pathological inflammatory conditions. In this study, we examined the expression pattern of MMPs during PMA-induced differentiation of THP-1 monocytic cells into macrophages. We found that MMP1, MMP8, MMP3, MMP10, MMP12, MMP19, MMP9, and MMP7 were upregulated during differentiation whereas MMP2 remained unchanged. Expression of MMPs increased in a time-dependent manner; MMP1, MMP8, MMP3, MMP10, and MMP12 increased beginning at 60 hr post PMA treatment whereas MMP19, MMP9, and MMP7 increased beginning at 24 hr post PMA treatment. To identify signal transduction pathways involved in PMA-induced upregulation of MMPs, we treated PMA-differentiated THP-1 cells with specific inhibitors for PKC, MEK1, NF-${\kappa}B$, PI3K, p38 MAPK and PLC. We found that inhibition of the MEK1 pathway blocked PMA-induced upregulation of all MMPs to varying degrees except for MMP-2. In addition, expression of select MMPs was inhibited by PI3K, p38 MAPK and PLC inhibitors. In conclusion, we show that of the MMPs examined, most MMPs were up-regulated during differentiation of monocyte into macrophage via the MEK1 pathway. These results provide basic information for studying MMPs expression during macrophage differentiation.

• The Journal of Internal Korean Medicine
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• v.32 no.2
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• pp.153-169
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• 2011

Objectives : This study was performed to investigate the anti-fibrogenic effect and the effect on cell growth and apoptosis in YJCGT, YJCGT YSO and YJCGT YSCO on thioacetamide-induced rat liver tissue and the immortalized human hepatic cell line LX2. Materials and Methods : LX2 cells were treated with various concentrations (0, 50, 150, 300 ug/ml) of YJCGT, Y+YSO, and Y+YSCO extract for 24, 48 and 72 hours. After the treatment, cell viability was measured by using MTT assay. Caspase inhibitor assay, and cell viability were determined by a colorimetric assay with PMS/MTS solution. Rat liver fibrosis was induced by intraperitoneal thioacetamide injection 150 mg/kg 3 times a week for 5 weeks. After the treatment, body weight, liver & spleen weights, liver function test, the complete blood cell count and the change of portal pressure were studied. After YJCGT, Y+YSO, and Y+YSCO treatment, percentages of collagen in thioacetamide-induced rat liver tissue were measured. Results : The viability of the LX2 cell decreased in a dose- and time-dependent manner. Exposure of LX2 cells to YJCGT, YJCGT+YSO and YJCGT+YSCO induced caspase-3 activation, but co-treatment of YJCGT, YJCGT+YSO and YJCGT+YSCO with the pan-caspase inhibitor Z-VAD-FMK, and the caspase-3 inhibitor Z-DEVE-FMK, blocked apoptosis. There was no difference in rat body weight between the thioacetamide only group and the YJCGT, YJCGT+YSO and YJCGT+YSCO groups. In the YJCGT, YJCGT YSO and YJCGT YSCO groups, the serum level of GPT significantly went down compared with the thioacetamide only group. In the YJCGT, Y+YSO, Y+YSCO groups, white blood cell elevated by thioacetamide injection decreased but RBC, Hgb, and Hct increased. In the Y+YSO group, the portal pressure elevated by thioacetamide injection significantly decreased. In the histological finding, thioacetamide injections caused severe fibrosis, but YJCGT, Y+YSO, and Y+YSCO treatment significantly reduced the amounts of hepatic collagens. Conclusions : YJCGT, Y+YSO, and Y+YSCO inhibit the growth of LX2 cells by inducing apoptosis through caspase activity. YJCGT, Y+YSO, and Y+YSCO have beneficial effects on the treatment of cirrhotic patients as well as patients with chronic hepatitis.

• Journal of Korean Neurosurgical Society
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• v.30 no.8
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• pp.992-997
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• 2001

Objectives : Essential hyperhidrosis is a common condition characterized by excessive body sweating. Excessive sweating beyond what is necessary to maintain normal body temperature need not be considered pathological unless it interferes with one's occupation and/or life-style. The existing non-operative therapeutic options seldom give sufficient relief or show a transient effect. In this regard, the thoracic sympathectomy may provide a definitive cure. In the past, surgical procedures were highly invasive and caused significant morbidity, but the minimally invasive thoracoscopic procedure provided detailed visualization of sympathetic ganglia and is associated with minimally postoperative morbidity. Nowadays, thoracoscopic transthoracic sympathectomy is accepted as the treatment of choice for essential hyperhidrosis. In palmar hyperhidrosis, however, the level of sympathetic chain to be blocked has been somewhat obscure. It is assumed that the incidence of compensatory hyperhidrosis may closely related to the extent of thoracic sympathectomy. Material & Methods : To compare the results of posterior midline approach with endoscopic sympathectomy, and the results of T2 with T2, 3 sympathectomy or sympathicotomy, we retrospectively studied 62 patients treated for palmar hyperhidrosis between September 1993 and May 2000. We reviewed medical records and recently interviewed the patients by telephone calls. Results : The treatment effect of T2 sympathectomy is no different from T2, 3 sympathectomy. But, the incidence of compensatory hyperhidrosis is less in the T2 sympathectomy group than the T2, 3 sympathectomy group. Conclusion : Thoracoscopic sympathectomy is considered a simple, safe, and effective method for treating palmar hyperhidrosis, with a shorter operation time, fewer hospital days, and a better cosmetic result, as compared with the open approaches. However, sympathicotomy seems to provide the advantages of a limited extent of denervation and the resultant decrease of compensatory hyperhidrosis compared to sympathectomy.

• BMB Reports
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• v.34 no.3
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• pp.237-243
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• 2001

Taxol, a natural product extracted from the Taxus brevifolia, is known to have significant anti-tumor activities against many common cancers, including ovarian and breast cancers. Despite the pronounced anti-tumor activity of this compound, its poor solubility in aqueous solutions hampers its clinical applications. We studied the anticancer mechanisms of the water-soluble taxol diethylenetriamine pentaacetate (DTPA) used for radiolabeling, and compared it to that of taxol. In vitro cytotoxicities of taxol and taxol-DTPA conjugate were tested in HT29 human colorectal cancer cells by the MTT method. As the result, the $IC_{50}$ value of the taxol-DTPA conjugate was about three fold higher than that of taxol. When analyzed by an agarose gel electrophoresis, the DNA ladders became evident after the incubation of cells with the taxol-DTPA conjugate for 24 h. We also found morphological changes of the cells undergoing apoptosis with electron microscopy Next, we examined the signal pathway of taxol-DTPA conjugate-induced apoptosis in HT29 cells. The activation of extracellular signal-regulated protein kinase (ERK1/2) occurred at 10, 30, 60 and 120 min after 200 nM taxol-DTPA conjugate treatment. The pretreatment of the MEK inhibitor (PD98059) completely blocked the taxol-DTPA conjugate-induced ERK1/2 activation. The activated ERK1/2 translocated into the nucleus at the same time and phosphorylated its transcriptional factor, c-Jun. These results suggest that the taxol-DTPA conjugate has an apoptotic activity in HT29 cells, and that its proapoptic activity might be related with the signal transduction via ERK1/2 and c-Jun similar to that of taxol.

• The Korean Journal of Physiology
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• v.26 no.2
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• pp.99-111
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• 1992

Permissive action of thyroid hormone at the level of Ca channel and responsible mechanisms underlying thyroid hormone-induced change in myocardial contractile state and $T_3-induced$ arrhythmias were investigated in rabbit ventricular or atrial myocytes using whole cell patch clamp technique. Single cells were isolated by Langendorff perfusion with collagenase. Cardiac myocytes were incubated in $low-Cl^-,$, $high-K^+$ medium containing $1_{\mu}M\;L-triiodothyronine\;(T_3)$ at $4^{\circ}C$ for 2.10 hours. The calcium currrent $(I_{Ca})$ was increased in $T_3$ loaded cells, however, the shape of current voltage curve and reverse potential did not altered. Cyclic AMP, cyclic GMP, isoprenaline and 3-isobutyl-1-methyl-xanthine increased $I_{Ca}$ in euthyroid and hyperthyroid conditions, and acetylcholine blocked the increase of $I_{Ca}\;in\;T_3$ loaded cells. The amplitude of $I_{Ca}$ was much larger after perfusing cGMP than cGMP in both conditions, whereas the degree of increase of $I_{Ca}$ was greater after perfusing cAMP than cGMP in $T_3$ loaded cells. The degree of increase of $I_{Ca}$ after perfusing isoprenaline or IBMX also was greater in $T_3$ loaded cells than in control cells. Background current induced by isoprenaline also increased in $T_3$ loaded cells. The Ca release dependent inward current was increased in amplitude but its activation and inactivation time course was not changed in $T_3$ loaded cells. Activation of Na pump current was not changed in $T_3$ loaded cells. From the above results it is suggested that thyroid hormone induced increase in the contractile state of cardiac myocytes are accompanied by augmented $I_{Ca}$ and the increase of Ca release from sarcoplasmic reticulum and the permissive action of thyroid hormone to catecholamines could induce arrhythmias through the increase of $I_{Ca}$ and background current.

• Korean Journal of Food Science and Technology
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• v.23 no.1
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• pp.88-92
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• 1991

To analyze the effects of the system parameters on the target parameters, which include the amount of water evaporation, water solubility index(WSI) and water absorption index(WAI), test trials of fractional factorial design of the three process variables at three levels were carried out for corn grit with a laboratory twin-screw extruder with three different screw configurations. The system parameters collected from the trials, such as extrusion temperature, specific mechanical energy input(SME) and mean residence time(RT), were showed the ranges of $129{\sim}182^{\circ}C$, $67{\sim}163\;kwh/ton$ and $12{\sim}34\;sec$, respectively. Within these ranges of the system parameters, the target parameters were able to be quantified by using multiple regression equations. The correlation of results with the system parameters blocked by the screw configuration as dependent variables, yield correlation coefficients above 0.90, and the correlation using the system parameters obtained from whole experiment system as the dependent variables yield correlation coefficients around 0.80. The functional relationship, which can be quantified by second order polynomial regression equation with only two system parameters within necessary degree of accuracy, can he graped in three dimensional surface response and contour diagrams.

• Journal of Biomedical Engineering Research
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• v.19 no.5
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• pp.503-511
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• 1998

In this study, the stress distribution for different tibial components was observed In order to Investigate the load transfer and potential failure mechanism of the tibial components subjected to dynamic impact loading and also to evacuate the effect of bone-implant bonding conditions on the implant system. The 3-dimensional finite element models included an intact tibia, cemented metal-backed tibial component, uncemented metal-blocked tibial component, cemented all-polyethylene tibial component, and metal-backed component with a debonded bone/stem interface. The results showed that the cemented metal-hocked component Induced slightly higher peak stress at stem tip than the uncemented component. The peak stress of the all-polyethylene tibia1 component at stem trip showed about half thats of metal-backed tibial components. The all-polyethylene component showed a similar dynamic response to intact tibia. In case of debonded bone/stem interface, the peak stress below the metal tray was three times Higher than that of the fully bonded interface and unstable stress distribution at the stem tip was observed with time, which causes another adverse bone apposition and implant loosening. Thus, the all-polyethylene tibial component bonded fully to the surrounding bone might be most desirable system under an impact loading.

• The Korean Journal of Pain
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• v.3 no.1
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• pp.27-33
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• 1990

In the past decades there has been a growth of interest in the use of stellate ganglion block (SGB) as part of the diagnosis and therapy for the disease of the head, neck and upper extremities. For the evaluation of changes in hemodynamics and temperature of the affected extremity after the SGB, unilateral SGB (either right or left) was performed by local injection of 10 ml of 1% lidocaine without epinephrine in 45 patients (right side SGB: 25, left side SGB: 20) with various diseases. Systolic and diastolic blood pressure, pulse rate and skin temperature of the ipsilateral hand were studied before and 1, 2, 3, 4, 5, 10, 15, 30 and 60 minutes after the block. The results were as follows: 1) Changes of blood pressure: Systolic and distolic blood pressure after either right or left side SGB showed no statistically significant change. 2) Changes of pulse rate: While the left side SGB showed a mild decrease without statistical significance, the right side SGB showed a statistically significant decrease at 30 and 60 minutes after the block (p<0.05). 3) Changes of skin temperature of the blocked hand: Either side SGB produced a gradual increase in temperature with time and showed statistical significance from 10 minutes in the left side block (p<0.01), and a from 10 minutes after the block in the right side (p<0.01). Both sides SGB showed a maximal increase at 30 minutes after the block and a small decrease at 60 minutes after the block compared to the 30 minutes value. 4) Despite the successful SGB. 4 of 45 patients failed to produce a significant increase in skin temperature on the affected upper extremity. In conclusion, unilateral SGB with 1% lidocaine at the 6th cervical vertebral level is a safe method for use on an outpatient basis, and an increase in skin temperature in the affected upper extremity is necessary to confirm the successful therapeutic effect on disease of the upper extremity.