• Journal of Ginseng Research
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• 제44권1호
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• pp.96-104
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• 2020

Objectives: Oleanolic acid, a minor element of ginsenosides, and its derivatives have been shown to have cytotoxicity against some tumor cells. The impact of cytotoxic effect of oleanolic acid 3-acetate on ovarian cancer SKOV3 cells and endometrial cancer HEC-1A cells were examined both in vivo and in vitro to explore the underlying mechanisms. Methods: Cytotoxic effects of oleanolic acid 3-acetate were assessed by cell viability, phosphatidylserine exposure on the cell surface, mitochondrial release of cytochrome C, nuclear translocation of apoptosis-inducing factor, depolarization of mitochondrial transmembrane potential (∆Ψ_m), and generation of reactive oxygen species (ROS). In vivo inhibition of tumor growth was also assessed with xenografts in immunocompromised mice. Results: Oleanolic acid 3-acetate exhibited potent cytotoxicity toward SKOV3 and HEC-1A cells by decreasing cell viability in a concentration-dependent manner. Importantly, oleanolic acid 3-acetate effectively suppressed the growth of SKOV3 cell tumor xenografts in immunocompromised mice. Furthermore, oleanolic acid 3-acetate induced apoptotic cell death as revealed by loss of ∆Ψ_m, release of cytochrome c, and nuclear translocation of apoptosis-inducing factor with a concomitant activation of many proapoptotic cellular components including poly(ADP-ribose) polymerase, Bcl-2, and caspases-8, caspase-3, and caspase-7. Oleanolic acid 3-acetate, however, caused a decrease in ROS production, suggesting the involvement of an ROS-independent pathway in oleanolic acid 3-acetate-induced apoptosis in SKOV3 and HEC-1A cells. Conclusion: These findings support the notion that oleanolic acid 3-acetate could be used as a potent anticancer supplementary agent against ovarian and endometrial cancer. Oleanolic acid 3-acetate exerts its proapoptotic effects through a rather unique molecular mechanism that involves an unconventional ROS-independent but mitochondria-mediated pathway.

• Archives of Pharmacal Research
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• 제21권4호
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• pp.423-428
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• 1998

The ligand binding signals to a wide variety of seven transmembrane cell surface receptors are transduced into intracellular signals through heterotrimeric G-proteins. Recently, there have been reports which show diverse coupling patterns of ligand-activated receptors to the members of Gq family $\alpha$ subunits. In order to shed some light on these complex signal processing networks, interactions between G$\alpha$q family of G protein and neurokinin-2 receptor as well as muscarinic M$_{1}$ receptor, which are considered to be new thearpeutic targets in asthma, were studied. Using washed membranes from Cos-7 cells co-transfected with different G.alpha.q and receptor cDNAs, the receptors were stimulated with various concentrations of carbachol and neurokinin A and the agonist-dependent release of [$^3H$]inositol phosphates through phospholipase C beta-1 activation was measured. Differential coupling of Gaq family of G-protein to muscarinic M$_{1}$ receptor and neurokinin-2 receptor was observed. The neurokinin-2 receptor shows a ligand-mediated response in membranes co-transfected with G$\alpha$q, G$\alpha$11 and G$\alpha$14 but not G$\alpha$16 and the ability of the muscarinic $M_1$ receptor to activate phospholipase C through G$\alpha$/11 but not G$\alpha$14 and G$\alpha$16 was demonstrated. Clearly G$\alpha$/11 can couple $\M_1$ and neurokinin-2 receptor to activate phospholipase C. But, there are differences in the relative coupling of the G$\alpha$14 and G$\alpha$16 subunits to these receptors.

• Physical Therapy Rehabilitation Science
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• 제6권1호
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• pp.14-19
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• 2017

Objective: To investigate the effect of performing three different bridge exercise conditions on the activities of four different muscles using surface electromyography (sEMG) in healthy young adults. Design: Cross-sectional study. Methods: A total of 20 healthy young adults (10 males, 10 females) voluntarily participated in this study. All subjects randomly performed three different bridge conditions as follows: general bridge exercise, isometric hip abduction (IHAB) with a blue Theraband (Hygenic Corp., USA), and isometric hip adduction (IHAD) with a Swiss ball (Hygenic Corp.). The muscle activities of bilateral erector spinae (ES), gluteus maximus (GM), biceps femoris (BF), and external oblique (EO) muscles during the bridge exercises were measured using sEMG. Subjects performed each of the three bridge conditions three times in random order and mean values were obtained. Results: For bilateral ES and BF, there was a significant increase in muscle activity in the IHAD condition compared to the general bridge and IHAB condition (p<0.05). For bilateral GM, there was a significant increase in muscle activity in the IHAB condition compared to the general bridge condition (p<0.05) and there was a significant increase in muscle activity in the IHAB condition compared to IHAD condition (p<0.05). For left EO, a significant increase was observed in the IHAD condition compared to the general bridge condition (p<0.05). Conclusions: ES and BF muscle activity increases were observed with hip adduction and increased GM activity was observed with hip abduction. These findings may be applicable within the clinical field for selective trunk and lower extremity muscle activation and advanced rehabilitation purposes.

• Molecules and Cells
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• 제38권2호
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• pp.122-129
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• 2015

DBM-2198, a six-membered azasugar nucleotide (6-AZN)-containing phosphorothioate (P = S) oligonucleotide (AZPSON), was described in our previous publication [Lee et al. (2005)] with regard to its antiviral activity against a broad spectrum of HIV-1 variants. This report describes the mechanisms underlying the anti-HIV-1 properties of DBM-2198. The LTR-mediated reporter assay indicated that the anti-HIV-1 activity of DBM-2198 is attributed to an extracellular mode of action rather than intracellular sequence-specific antisense activity. Nevertheless, the antiviral properties of DBM-2198 and other AZPSONs were highly restricted to HIV-1. Unlike other P = S oligonucleotides, DBM-2198 caused no host cell activation upon administration to cultures. HIV-1 that was pre-incubated with DBM-2198 did not show any infectivity towards host cells whereas host cells pre-incubated with DBM-2198 remained susceptible to HIV-1 infection, suggesting that DBM-2198 acts on the virus particle rather than cell surface molecules in the inhibition of HIV-1 infection. Competition assays for binding to HIV-1 envelope protein with anti-gp120 and anti-V3 antibodies revealed that DBM-2198 acts on the viral attachment site of HIV-1 gp120, but not on the V3 region. This report provides a better understanding of the antiviral mechanism of DBM-2198 and may contribute to the development of a potential therapeutic drug against a broad spectrum of HIV-1 variants.

• 한국전문물리치료학회지
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• 제20권4호
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• pp.32-39
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• 2013

Abdominal curl-up exercise may excessively increased superficial neck flexor such as sternocleidomastoid (SCM) muscle. Also, the muscle activity of the abdominal muscles haven't investigated during abdominal curl-up with craniocervical flexion (CCF). Therefore, the purpose of our study was to determine the effect of CCF on the muscle activity of the abdominal and SCM muscles during abdominal curl-up. Twelve healthy subjects (six men and six women) with no history of abdominal or lower back pain within 6 weeks were recruited. Surface electromyographic signals were collected on SCM, rectus abdominis (RA), internal oblique (IO), and external oblique (EO) muscles bilaterally during performing the traditional abdominal curl-up and the abdominal curl-up with CCF. Paired t-tests were used to compare the differences in the muscle activity of the bilateral SCM, RA, EO, and IO muscles between the traditional abdominal curl-up and the abdominal curl-up with CCF (p<.05). There was significantly lower electromyogram (EMG) activity of the both SCMs during the abdominal curl-up with CCF (Right SCM, $39.50{\pm}15.29%MVIC$; Left SCM, $38.24{\pm}17.31%MVIC$) than with the traditional abdominal curl-up (Right SCM, $54.85{\pm}20.05%MVIC$; Left SCM, $53.18{\pm}26.72%MVIC$) (p<.05). The activity of abdominal muscles were not significantly different between the traditional abdominal curl-up and the abdominal curl-up with CCF. The abdominal curl-up with CCF requires significantly less muscle activity of SCM. Consequently, the abdominal curl-up with CCF is recommended to prevent excessive activation of superficial cervical flexors during abdominal curl-up exercise.

• 한국세라믹학회지
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• 제39권4호
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• pp.367-376
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• 2002

$SrZr_{1-x}Y_xO_{3-\delta}$(x=0.05, 0.10)-금속전극 계에서 임피던스법과 d.c.법으로 전기전도도를 측정함으로써 고체전해질 및 전극전도도를 고찰하였다. 고체전해질과 anode를 통한 전기전도도는 $P_W^{1/2}$(PW는 수증기분압)에 의존하여 증가함을 보였다. Cathode 전도도는 $P_{O2}^{1/4}$에 비례함을 보였으며, 수증기분압 증가와 함께 감소하여 고체전해질내의 전자 결함의 농도와 함께 증가하는 것을 알 수 있었다. 수소분위기에서는 수증기의 첨가가 anode와 cathode 두 방향의 전극반응 속도 모두를 촉진하였다. 도펀트 첨가량이 5%에서 10%로 증가될 때 anode와 고체전해질의 전기전도도가 3배 이상 크게 증가하여 유효 산소이온공공의 농도가 급격히 증가함을 알 수 있었다. Pt와 Ag전극을 통한 cathode 전도도의 활성화에너지가 거의 같은 값을 나타냈으며 이는 cathode반응의 속도가 금속전극이 아니라 고체전해질표면에서 일어나는 반응에 의하여 결정되는 것으로 해석되었다.

• IMMUNE NETWORK
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• 제11권6호
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• pp.390-398
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• 2011

Background: Epstein Barr virus (EBV) infected B cells are transformed into lymphoblastoid cell lines. Some researchers suggested some a few similarities between this process and carcinogenesis. We observed the expression of CD80 and CD86, co-stimulatory molecules on EBV-transformed B cells and changes of CD54 expression after stimulation of CD80 and CD86. Methods: CD80 and CD86 were stimulated using anti-CD80 and anti-CD86 monoclonal antibodies. To assess apoptosis and surface protein expression, flow cytometric analysis was performed. Intracellular signal molecules were evaluated by RT-PCR and immunoblot. Morphology and localization of proteins were examined using inverted or confocal microscope. Results: Cross-linking of CD80 and CD86 induced apoptosis and interfered with proliferation of EBV-transformed B cells, and dispersion of clumped cells. We also examined that their stimulation induced ROS accumulation and reduced CD54 expression. Interestingly, we observed that CD80 and CD86 diminished the expression of CD54 in different methods. Both CD80 and CD86 downregulated activation of focal adhesion kinase. CD80 stimulus inhibited CD54 expression through mainly RhoA inactivation, while CD86 down-regulated Ras and JNK phosphorylation. Conclusion: These results suggest that co-stimulatory CD80 and CD86 molecules, expressed EBV-transformed B cells, may play a role in apoptosis and cell adhesion.

• IMMUNE NETWORK
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• 제9권3호
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• pp.90-97
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• 2009

Background: CD147, as a cellular receptor for cyclophilin A (CypA), is a multifunctional protein involved in tumor invasion, inflammation, tissue remodeling, neural function, and reproduction. Recent observations showing the expression of CD147 in leukocytes indicate that this molecule may have roles in inflammation. Methods: In order to investigate the role of CD147 and its ligand in the pathogenesis of atherosclerosis, human atherosclerotic plaques were analyzed for the expression pattern of CD147 and CypA. The cellular responses and signaling molecules activated by the stimulation of CD147 were then investigated in the human macrophage cell line, THP-1, which expresses high basal level of CD147 on the cell surface. Results: Staining of both CD147 and CypA was detected in endothelial cell layers facing the lumen and macrophage-rich areas. Stimulation of CD147 with its specific monoclonal antibody induced the expression of matrix metalloproteinase (MMP)-9 in THP-1 cells and it was suppressed by inhibitors of both ERK and NF-${\kappa}B$. Accordingly, the stimulation of CD147 was observed to induce phosphorylation of ERK, phosphorylation-associated degradation of $I{\kappa}B$, and nuclear translocation of NF-${\kappa}B$ p65 and p50 subunits. Conclusion: These results suggest that CD147 mediates the inflammatory activation of macrophages that leads to the induction of MMP-9 expression, which could play a role in the pathogenesis of inflammatory diseases such as atherosclerosis.

• 한국전기전자재료학회논문지
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• 제21권11호
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• pp.968-972
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• 2008

Ni/Ti/Al multilayer system ('/'denotes the deposition sequence) was tested for low-resistance ohmic contact formation to Al-implanted p-type 4H-SiC. Ni 30 nm / Ti 50 nm / Al 300 nm layers were sequentially deposited by e-beam evaporation on the 4H-SiC samples which were implanted with Al (norminal doping concentration = $4\times10^{19}cm^{-3}$) and then annealed at $1700^{\circ}C$ for dopant activation. Rapid thermal anneal (RTA) temperature for ohmic contact formation was varied in the range of $840\sim930^{\circ}C$. Specific contact resistances were extracted from the measured current vs. voltage (I-V) data of linear- and circular transfer length method (TLM) patterns. In constrast to Ni contact, Ni/Ti/Al contact shows perfectly linear I-V characteristics, and possesses much lower contact resistance of about $2\sim3\times10^{-4}\Omega{\cdot}cm^2$ even after low-temperature RTA at $840^{\circ}C$, which is about 2 orders of magnitude smaller than that of Ni contact. Therefore, it was shown that RTA temperature for ohmic contact formation can be lowered to at least $840^{\circ}C$ without significant compromise of contact resistance. X-ray diffraction (XRD) analysis indicated the existence of intermetallic compounds of Ni and Al as well as $NiSi_{1-x}$, but characteristic peaks of $Ti_{3}SiC_2$, a probable narrow-gap interfacial alloy responsible for low-resistance Ti/Al ohmic contact formation, were not detected. Therefore, Al in-diffusion into SiC surface region is considered to be the dominant mechanism of improvement in conduction behavior of Ni/Ti/Al contact.

• KSBB Journal
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• 제15권1호
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• pp.42-48
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• 2000

본 연구에서는 고정화 UK를 이용한 융합단백질의 절단방응에 대해 UK의 고정화, 고정화 UK의 특성과 절단방응, 절단반응 후의 분리정제 그리고 고정화 UK으 재생에 대해 실험하였다. 고정화 수율은 99% 이상이였고 고정화 후의 효소활성은 80%를 유지하였다. 융합단백질 전단반응에서 액상 UK와 고정화 UK를 이용한 회분식 반응 모두 약 70%의 절단반응을 얻었고, 특히 고정화 UK의 사용시 부반응이 매우 낮은 이점이 있었다. 컬럼식 절단반응에서는 기절의 주입속도에 따라 절단수율은 크게 변화하였다. 최적의 유속은 50%의 절단수율을 얻은 1 bed volume/h로 설정하였다. 고정화 효소반응의 이점인 안정성과 반복사용 측면에서는 액상 UK 대비 고정화 UK가 높은 열안정성을 보였고 낮은 pH에서는 10% 이상 높은 활성을 유지하였다. 반복사용을 위해 6M GuHCl을 사용하여 인위적으로 풀림, 재접힘을 한 경우 98%의 활성을 얻음으로 타당성이 있음을 제시하였다. 또한 목적 단백질의 분리를 위하여 산침전 후 expanded bed adsorption 크로마토그래피를 이용함으로써 연속화된 고수율의 정제공정을 가능하게 하였다. 이러한 고정화 UK를 이용한 절단방응 및 정제시스템을 구축함으로써 융합단백지의 생산공정에 매우 유용하게 사용될 것으로 생각되어진다.