• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.4
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• pp.888-894
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• 2009

It has been reported that silibinin, a natural polyphenolic flavonoid, induces cell death in various cancer cell types. However, the underlying mechanisms by which silibinin induces apoptosis in human glioma cells are poorly understood. The present study was therefore undertaken to examine the effect of silibinin on glioma cell apoptosis and to determine its underlying mechanism in human glioma cells. Apoptosis was estimated by FACS analysis. Reactive oxygen species (ROS) generation and mitochondrial membrane potential (${\Psi}m$) were measured using fluorescence dyes DCFH-DA and $DiOC_6$(3), respectively. Cytochrome c release from mitochondria and caspase-3 activation were estimated by Western blot analysis using specific antibodies. Exposure of cells to 30 mM silibinin induced apoptosis starting at 6 h, with increasing effects after 12-48h in a time-dependent manner. Silibinin caused ROS generation and disruption of ym, which were associated with the silibinin-induced apoptosis. The silibinin-induced ROS generation and disruption in ym were prevented by inhibitors of mitochondrial electron transport chain. The hydrogen peroxide scavenger catalase blocked ROS generation and apoptosis induced by silibinin. Silibinin induced cytochrome c release into cytosolic fraction and its effect was prevented by catalase and cyclosporine A. Silibinin treatment caused caspase-3 activation, which was inhibited by DVED-CHO and cyclosporine A. Pretreatment of caspase inhibitors also protected against the silibinin-induced apoptosis. These findings indicate that ROS generation plays a critical role in the initiation of the silibinin-induced apoptotic cascade by mediation of the mitochondrial apoptotic pathway including the disruption of ${\Psi}m$, cytochrome c release, and caspase-3 activation.

• The KIPS Transactions:PartD
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• v.10D no.1
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• pp.161-166
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• 2003

Information lead time is defined as the time spent by processing orders from some buyers, whereas order lead time is defined as producing and supplying the products. The information lead time significantly serve to magnify the increase in variability due to demand forecasting. This paper models a decentralized supply chain composed of cascade type which has four type phases (or divisions) such as retailer, wholesaler, distributor, and factory. Each phases is managed by different centers individually with their own local inventory information. We investigate whether each phase's Information lead time affects companies networked a value chain. In particular, on several experiments performed with a programmed simulation (like a MIT beer game), we study the following question ; Can information lead times do better than material lead times in cost-benefit perspective\ulcorner Can more much Information lead times in downstream reasonably do worser than in upstream when playing the simulation\ulcorner In the conclusion, we show the importance of information lead time on a SC and, besides, guarantee that improvement of information lead time in upstream do more effective than one in downstream in cost-benefit perspective.

• Archives of Plastic Surgery
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• v.39 no.4
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• pp.317-321
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• 2012

Background Many topical hemostatics are widely applied for bleeding control. They can be classified into two categories according to their mechanism of action on the clotting cascade in a biologically active or passive manner. Passive hemostatics include cellulose and gelatin. We performed an experimental study to compare the effect of passive hemostatics in wound healing by applying them to a rectus abdominis muscle defect of white mice. Methods Surgicel is a sterile absorbable knitted fabric prepared by the controlled oxidation of regenerated cellulose. Spongostan is an absorbable hemostatic gelatin sponge. In 30 mice, a $1{\times}1$ cm defect was created on the rectus abdominis muscle and the materials were applied in three ways: control group, cellulose (Surgicel) group, gelatin (Spongostan) group. For the histologic analysis, biopsies were performed at 3 and 28 days. Results After 3 days, the cellulose group showed limited granulation formation with acute inflammatory reactions similar to the control group. At the 28th day, moderate amounts of granulation tissue formation was observed with milder inflammatory reactions than the control group. In the gelatin group, after 3 days, gelatin remnants were observed surrounded by severe inflammatory changes. After 28 days, the same quantity of gelatin remnants could be still observed. Conclusions This study suggests that cellulose is associated with minimal morbidity in wound healing, while the use of gelatin shows severe adverse tissue reactions with delayed wound healing. Consequently, cellulose is better than gelatin when considering wound healing.

• YAKHAK HOEJI
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• v.45 no.1
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• pp.116-124
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• 2001

Nitric oxide is a labile, gaseous, broad spectrum second messenger that used in various tissues and cells. If it is induced by endogenously and exogenously in the neuronal cells, it is able to mediate analgesia or hyperalgesia at the periphery and in the spinal level respectively. This dual role of nitric oxide in the sensory system is very intriguing but has not been fully understood yet. In this experiment, acetylcholine (300 $\mu$g/paw), sodium nitroprusside (600 $\mu$g/paw), and L-arginine (300 $\mu$g/paw) represented antinociceptive effect to noxious topical stimulus, but pronociceptive responses followed by spinally application (20$\mu$g/5$\mu$l, 10$\mu$g/3$\mu$l, 500$\mu$g/5$\mu$l respectively). Calcium ion is critical element which activates nitric oxide synthase, therefore verapamil (300 $\mu$g/paw) and NOS inhibitor (20 mg/kg, L-NAME or L-NOArg) are injected into right hind paw (i.pl.). When verapamil is combined with NOS inhibitors analgesic effects through NO-cGMP pathway are inhibited as compared with ACh alone. Diluted formalin (2.5%), when injected into rats'hind paw (0.05 ml), elicited a biphasic algesic responses and nitric oxide had an analgesic effect on both $A\delta$ and C sensory nerve fibers which manipulate the phases respective1y. Nitric oxides, which produced from constitutive nitric oxide synthase, activated cyclooxygenase-type I and then prostaglandins are produced from them. So, indomethacin and ibuprofen, inhibitors of COX$_1$enzyme, when pretreated intraperitoneally (100 mg/kg) could reduce the hyperalgesic state. From these results, it is possible to imagine that the intrathecally administered NO donors expressed hyperalgesia through both long-term potentiation mechanism and arachidonic acid-prostaglandin cascade.

• The Journal of Korean Medicine
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• v.26 no.1 s.61
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• pp.37-45
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• 2005

In the present study, we examined the effect of crude methanolic extract (CME) from Euonymus alatus (Thunb.) Sieb on arachidonic acid (AA) cascade in SKBR3 human breast cancer cell line. CME had a potent inhibitory activity of prostaglandin E2 (PGE2) release induced by A23187, a $Ca^{2+}$ ionophore. The inhibition was concentration-dependent, with the 50 value of about 5 M. CME had no inhibitory effect on A23187-induced phosphorylation of p42/p44 extracellular signal regulated kinase/mitogen-activated protein kinase or on the liberation of [14C]-AA from the cells labeled with [14C]-AA. However, CME concentration-dependently inhibited the conversion of AA to $PGE_2$ in microsomal preparations, showing its possible inhibition of cyclooxygenase (COX). In enzyme assay in vitro, CME inhibited the activities of both constitutive COX (COX­I) and inducible COX (COX-2) in a concentration-dependent manner, with the 50 values of about 0.8 and 2M, respectively. Lineweaver-Burk plot analysis indicated that CME competitively inhibited the activities of both COX-l and -2. This study is a first demonstration that CME directly inhibits COX activity.

• The KSFM Journal of Fluid Machinery
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• v.16 no.6
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• pp.19-25
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• 2013

The effect of tip gap height on heat/mass transfer characteristics on the floor of cavity squealer tip has been investigated in a turbine cascade for power generation by employing the naphthalene sublimation technique. The squealer rim height is chosen to be an optimal one of $h_{st}/c$ = 5.51% for the tip gap height-to-chord ratios of h/c = 1.0, 2.0, 3.0 and 4.0%. The results show that heat transfer on the cavity floor is strongly dependent upon the behavior of the cavity flow falling down onto the floor. For lower h/c, the floor heat transfer is influenced by the tip leakage flow falling down along the inner face of the suction-side squealer, whereas the floor heat transfer for higher h/c is augmented mainly due to the impingement of leakage flow on the floor near the leading edge. Compared to the plane tip surface heat transfer, the cavity floor heat transfer is less influenced by h/c. For h/c = 1.0%, the average thermal load is as low as a half of the plane tip surface one, and the difference in the thermal load between the two cases tends to decrease with increasing h/c.

• Molecules and Cells
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• v.38 no.2
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• pp.145-150
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• 2015

Continuous intra- and extracellular stresses induce disorder of $Ca^{2+}$ homeostasis and accumulation of unfolded protein in the endoplasmic reticulum (ER), which results in ER stress. Severe long-term ER stress triggers apoptosis signaling pathways, resulting in cell death. Neural epidermal growth factor-like like protein 2 (NELL2) has been reported to be important in protection of cells from cell death-inducing environments. In this study, we investigated the cytoprotective effect of NELL2 in the context of ER stress induced by thapsigargin, a strong ER stress inducer, in Cos7 cells. Overexpression of NELL2 prevented ER stress-mediated apoptosis by decreasing expression of ER stress-induced C/EBP homologous protein (CHOP) and increasing ER chaperones. In this context, expression of anti-apoptotic Bcl-xL was increased by NELL2, whereas NELL2 decreased expression of pro-apoptotic proteins, such as cleaved caspases 3 and 7. This anti-apoptotic effect of NELL2 is likely mediated by extracellular signal-regulated kinase (ERK) signaling, because its inhibitor, U0126, inhibited effects of NELL2 on the expression of anti- and pro-apoptotic proteins and on the protection from ER stress-induced cell death.

• Journal of Environmental Health Sciences
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• v.31 no.4 s.85
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• pp.316-321
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• 2005

4개 업종(축전지제조업, 광명단 제조업, 2차 제련업, 라디에타 제조업)에서 근무하는 총 100명의 근로자를 대상으로 8단계다단충돌기(eight stages personal cascade imparter)에 의한 입자 크기 별 납농도를 측정하였다 크기 별 납 농도는 총납(PbA), 흡입성납(IPM-PbA), 흉곽성납(TPM-PbA), 호흡성납(RPM-PbA), $1{\mu}m$ 미만의 납$(Pb_{1\mu})$ 그리고 $1{\mu}m$ 이상의 소화성납$(Pb_{ing})$이었다. 동일한 근로자(100명)를 대상으로 혈액에서 납농도를 측정하였다. 혈액 중 납은 원자흡광광도계(atomic absorption spectrometry)의 Zeeman effect graphite furnace를 이용하여 분석하였다. 총 납의 노출농도는 노출기준$(50\;ug/m^3)$을 크게 초과하였다. 평균 호흡성 납 노출농도$(115.7\;ug/m^3)$ 총 납의 노출기준을 훨씬 초과하였다. $1{\mu}m$미만의 납$(Pb_{1\mu})$ 노출농도의 범위는 0.7에서 $(492.2\;ug/m^3)$이나 되었다. 근로자의 $46\%$가 혈액 중 납 농도 40 ug/dL을 초과하였다. 60 ug/dL을 초과한 경우도 $13\%$나 되었다. 입자 크기가 큰 납인 총납, 흡입성 납 그리고 호흡성 납 농도는 혈액 중 납 농도와 유의한 상관을 보였다(p<0.0001). 그러나 가장 높은 상관은 $1{\mu}m$미만의 납$(Pb_{1\mu})$ 혈액 중 납과의 관계였다. T-test에서 $50ug/m^3$이상의 호흡성 납을 나타낸 근로자 그룹과 $50ug/m^3$ 이하의 근로자 그룹간에의 혈액 중 납 농도는 유의한 차이가 있는 것으로 나타났다(p=0.000). 이러한 연구결과는 입자크기 구분이 없는 현재의 총납에 의한 노출기준과 측정방법은 미세 납 먼지에 노출되는 근로자의 납흡수를 보호하는데 한계점이 있다는 것을 의미한다. 향후 납 입자크기는 물론 근로자의 개인적인 위생과 작업내용 등을 변수로 납 흡수에 영향을 미치는 종합적인 요인을 찾아내는 연구를 진행할 필요가 있다.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.5
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• pp.367-375
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• 2022

Gastric cancer stem cells (GCSCs) are a major cause of radioresistance and chemoresistance in gastric cancer (GC). Therefore, targeting GCSCs is regarded as a powerful strategy for the effective treatment of GC. Atorvastatin is a widely prescribed cholesterol-lowering drug that inhibits 3-hydroxy-3-methylglutaryl-coenzyme A reductase, a rate-limiting enzyme in the mevalonate pathway. The anticancer activity of atorvastatin, a repurposed drug, is being investigated; however, its therapeutic effect and molecular mechanism of action against GCSCs remain unknown. In this study, we evaluated the anticancer effects of atorvastatin on MKN45-derived GCSCs. Atorvastatin significantly inhibited the proliferative and tumorsphere-forming abilities of MKN45 GCSCs in a mevalonate pathway-independent manner. Atorvastatin induced cell cycle arrest at the G0/G1 phase and promoted apoptosis by activating the caspase cascade. Furthermore, atorvastatin exerted an antiproliferative effect against MKN45 GCSCs by inhibiting the expression of cancer stemness markers, such as CD133, CD44, integrin α6, aldehyde dehydrogenase 1A1, Oct4, Sox2, and Nanog, through the downregulation of β-catenin, signal transducer and activator of transcription 3, and protein kinase B activities. Additionally, the combined treatment of atorvastatin and sorafenib, a multi-kinase targeted anticancer drug, synergistically suppressed not only the proliferation and tumorsphere formation of MKN45 GCSCs but also the in vivo tumor growth in a chick chorioallantoic membrane model implanted with MKN45 GCSCs. These findings suggest that atorvastatin can therapeutically eliminate GCSCs.

• Journal of Life Science
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• v.27 no.11
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• pp.1245-1255
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• 2017

Most cancer cells produce ATP predominantly through glycolysis instead of through mitochondrial oxidative phosphorylation, even in the presence of oxygen. The phenomenon is termed the Warburg effect, or the glycolytic switch, and it is thought to increase the availability of biosynthetic precursors for cell proliferation. EMTs have critical roles in the initiation of the invasion and metastasis of cancer cells. The glycolytic switch and EMT are important for tumor development and progression; however, their correlation with tumor progression is largely unknown. The Snail transcription factor is a major factor involved in EMT. The Snail expression is regulated by distal-less homeobox 2 (Dlx-2), a homeodomain transcription factor that is involved in embryonic and tumor development. The Dlx-2/Snail cascade is involved in Wnt-induced EMTs and the glycolytic switch. This study showed that in response to Wnt signaling, the Dlx-2/Snail cascade induces the expression of PFKFB2, which is a glycolytic enzyme that synthesizes and degrades fructose 2, 6-bisphosphate (F2,6BP). It also showed that PFKFB2 shRNA prevents Wnt-induced EMTs in the breast-tumor cell line MCF-7. The prevention indicated that glycolysis is linked to Wnt-induced EMT. Additionally, this study showed PFKFB2 shRNA suppresses in vivo tumor metastasis and growth. Finally, it showed the PFKFB2 expression is higher in breast, colon and ovarian cancer tissues than in matched normal tissues regardless of the cancers' stages. The results demonstrated that PFKFB2 is an important regulator of EMTs and metastases induced by the Wnt, Dlx-2 and Snail factors.