• BMB Reports
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• v.54 no.3
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• pp.176-181
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• 2021

Bcl-x, a member of the Bcl-2 family, plays a key role in apoptosis. Alternative splicing of Bcl-x pre-mRNA through alternative 5' splice-site selection produces an anti-apoptotic mRNA isoform that includes exon 2b and a pro-apoptotic Bcl-x mRNA isoform that excludes exon 2b. Here we used Bcl-x minigene and identified SRSF2 and SRSF6 as two regulatory factors of 5' splice-site selection of Bcl-x pre-mRNA. We selected binding clusters closer to 5' splice-sites from multiple potential binding sites of SRSF2 and SRSF6 to perform loss of functions analysis through site-directed mutagenesis. Our results demonstrated that these mutations did not abolish regulatory functions of SRSF2 or SRSF6, indicating that a single binding motif or a cluster was not a functional target of these proteins in Bcl-x pre-mRNA splicing. Random deletion mutagenesis did not disrupt the role of SRSF2 and SRSF6. Importantly, mutagenesis of 5' splice-site to a conserved or a weaker score demonstrated that the weaker strength of the target 5' splice-site or higher strength of the other 5' splice-site strength limited the role of SRSF2 and SRSF6 in 5' splice-site activation.

• Journal of Oral Medicine and Pain
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• v.24 no.2
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• pp.145-161
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• 1999

The proto-oncogene bcl-2 confers a survival advantage to cells by blocking programmed cell death (apoptosis). Overexpression of bcl-2 probably plays a role in tumorigenesis, and the expression of the bcl-2 protein has been investigated in many kinds of tumors. An increased expression of nitric oxide synthetase(NOS) has been observed in human colon cancer cell lines as well as in human gynecological, breast, and CNS tumors. However there have been only a few reports on the expression of bcl-2 and $NOS_2$ in oral white lesions and cancer. The aim of this study was to investigate the relationship between the expression of Bcl-2 and $NOS_2$ and several pathological parameters such as histological types and layers. We reported desregulation of bcl-2 and $NOS_2$ expression during progression from oral white lesion, lichen planus and leukoplakia to squamous cell carcinoma. The obtained results were as follows: 1. Immunohistochemical analysis with monoclonal antibodies to bcl-2 oncoprotein and $NOS_2$ in formalin-fixed paraffin-embedded tissue sections revealed that bcl-2 expression is restricted to the basal cell layer and $NOS_2$ was mild expressed only in subepithelial inflammatory cells in normal human mucosa. There wasn't specific finding of those in lichen planus and leukoplakia. 2. Bcl-2 immunoreactivity in severe epithelial dysplasia or CIS occurs throughout the epithelium, $NOS_2$ reactivity in most superficial layer were noted. 3. In well-differentiated squamous cell carcinomas, mostly bcl-2 was overexpressed. In moderated and poor squamous cell carcinomas, the expression of $NOS_2$ was increased and that of bcl-2 was decreased. 4. The immunoreactivity of bcl-2 was 12.5% of normal mucosa, 30% of leukoplakia, 44% of lichen planus and 67% of carcinoma in situ. In carcinoma, those were 43%, 50% and 67% according to differentiation, respectively. 5. The immunoreactivity of $NOS_2$ was 25% of normal mucosa, 70% of leukoplakia, 78% of lichen planus and 100% of carcinoma in situ and epithelial dysplasia. In carcinoma, those were higher in moderated(100%) and poor(83%) squamous cell carcinomas than in well differentiated type(71%). 6. The expression of bcl-2 and $NOS_2$ by Western blot was increased highly in lichen planus and leukoplakia. Therefore, the expression of bcl-2 was increased in the white and precancerous lesions and that was decreased by differentiation of carcinoma. However, $NOS_2$ immunoreactivity in carcinoma in situ was lower than those in moderated and poor squamous cell. These findings suggest that the interaction of bcl-2 and $NOS_2$ may be roled importantly in growth and development of carcinoma.

• The Journal of Korean Obstetrics and Gynecology
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• v.21 no.4
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• pp.90-103
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• 2008

목적 : 본 연구는 현호색의 메탄올 추출물(Corydalis Tuber Extract:CTE)이 인간 유방암 세포인 MCF-7 세포의 자멸사에 미치는 영향을 알아보고자 하였다. 방법 : 현호색 메탄올 추출물로 인간유방암에서 유래된 MCF-7 세포를 처리하였다. CTE의 세포자멸사 유도 효과는 MTT, FACS, TUNEL, DNA laddering and immunoblot assay를 통하여 측정하였다. 결과: 본 연구에서 현호색 메탄올 추출물은 MCF-7 세포의 활성을 감소시켰다. CTE로 처리한 MCF-7 세포는 용량에 따라 세포 자멸사 과정이 증가했다. CTE에 노출하였을 때 Bcl-2와 $Bcl-_{XL}$의 발현을 억제하고, 미토콘드리아로부터 세포질로 cytochrome-c를 방출하며, caspase와 PARP의 절단을 유발하여 세포자멸사가 증가했다. 현호색 메탄올 추출물에 존재하는 성분중에서 coptisine이 세포 활성도를 효과적으로 감소시킨 것으로 사료된다. 결론: 실험결과 현호색 메탄올 추출물이 유방암의 임상 치료에 있어 가능성 있는 치료 방법이 될 수 있을 것으로 사료된다.

• Journal of Life Science
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• v.19 no.10
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• pp.1489-1494
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• 2009

This study was designed to investigate the effects of swimming and minocycline on motor function recovery and Bcl-2 expression after spinal cord injury (SCI) in rats. After operation, neurological motor behavior test (BBB scale) on days 1, 4, 7, 10, and 14 were tested. Western blot and immunohistochemical assessment (Bcl-2) were performed on day 14. BBB scale started to show a statistically significant difference on day 7 (p<0.05). On day 14, it showed the most significant (p<0.05) difference. Expression of Bcl-2 increased in all the experimental groups. In particular, the highest expression of Bcl-2 appeared in the swimming and minocycline groups. Based on these results, minocycline and swimming were the most effective factors in the motor behavior function and immunohistochemical assessment of SCI rats.

• YAKHAK HOEJI
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• v.43 no.3
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• pp.385-390
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• 1999

Camptothecin (CPT) has been known to induce apoptosis in various cancer cell lines. To examine the intracellular apoptotic death signal initiated by CPT, we investigated the possible connection between caspase-3 activation and GSH depletion during CPT-induced apoptosis in HL-60 cells. Treatment of cells with $1{\;}{\mu}M$ CPT induced PARP cleavage accompanied by DNA fragmentation. z-VAD-fmk, a caspase-3 inhibitor, blocked the CPT-induced DNA fragmentation. Pretreatment of cells with N-acetylcysteine, a precursor of GSH biosynthesis, failed to inhibit CPT-induced PARP celavage and DNA gragmenatation. No significant changes in GSH depletion is not essential for caspase activation during CPT-induced apoptosis. We also investigated whether CPT-induced apoptosis is associated with changes of the levels of Bax and Bcl-2, two proteins involved in the control of apoptosis. Bcl-2 levels exhibited a late decrease compared with the kinetics of DNA fragmentation, whereas Bax levels increased more rapidly after CPT treatment. These results suggest that Bax plays more important role than Bcl-2 in inducing DNA fragmentation and may function upsteam of proteolytic activation of caspase-3 pathway in CPT-induced apoptosis.

• Biomedical Science Letters
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• v.25 no.3
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• pp.237-246
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• 2019

Left ventricular hypertrophy (LVH) refers to the expansion and the enlarged myocardium due to the increased resistance to ejection from the left ventricle to the aorta and/or the periphery, or the long-term burden imposed by the blood increase. Hypertension is a major risk factor that accounts for more than 50% of the causes of cardiovascular disease. If hypertension endure in the long term, the myocardium responds to abnormal heartbeat in the heart. Therefore, the prevalence of left ventricular hypertrophy also increases. As a result of genome-wide association study (GWAS) analysis for European people, PDGFC, MARK3, and BCL2 were related to blood pressures. In this study, the genetic polymorphisms of PDGFC, MARK3, and BCL2 were extracted and selected based on Korean genomic and epidemiologic data, and then logistic regression analysis was performed on LVH. As a result, one SNP (rs9307953) in PDGFC gene, four SNPs (rs6575983, rs17679475, rs2273703 and rs10141388) in MARK3 gene and two SNPs (rs17756073 and rs17070739) in BCL2 gene were statistically significant. The rs6575983 of the MARK3 gene showed the highest significance level ($P=7.2{\times}10^{-3}$) among the SNPs and the relative risk of 1.08 (95% confidence interval: 1.06 to 1.45). These results suggest that the polymorphisms of PDGFC, MARK3, and BCL2 not only affect European blood pressures but also correlate with LVH in Korean. These results suggest that increased understanding of the genetic correlations of the pathogenesis of LVH.

• Journal of the Korean Institute of Electrical and Electronic Material Engineers
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• v.21 no.12
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• pp.1051-1056
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• 2008

In this study, the investigations of the TiN etching characteristics were carried out with addition of $Cl_2$ gas in an inductively coupled $BCl_3$-base plasma system. Dry etching of the TiN was studied by varying the etching parameters including $Cl_2$ gas addition ratio, RF power, DC-bias voltage and pressure. The etch rate of TiN thin film was maximum when the $Cl_2$ gas addition flow was 2 sccm with fixed other conditions. As the RF power DC-bias voltage were increased, the etch rate of TiN thin film showed increasing tendency. $BCl_3/Cl_2$/Ar plasmas were characterized by optical emission spectroscopy (OES) analysis. The chemical reaction on the surface of the etched TiN films was investigated with X-ray photoelectron spectroscopy (XPS).

• Proceedings of the Korean Vacuum Society Conference
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• 2011.08a
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• pp.137-137
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• 2011

펄스 직류 $BCl_3$ 플라즈마의 전기적 특성과 GaAs의 건식식각을 연구하였다. 공정변수는 펄스 직류 전압 (350~550 V), 펄스 직류 주파수 (100~250 kHz), 리버스 시간 (0.4~1.2 ${\mu}s$)이었다. 전기적 특성은 오실로스코프를 이용하여 분석하였다. 펄스 직류 전원의 경우 평균 전압이 일정하더라도 주파수가 커지거나 리버스 시간이 커지면 peak-to-peak 전압이 증가한다는 사실을 이해하였다. GaAs 식각 실험 후 샘플의 식각률, 식각 선택비, 표면 형상을 비교, 분석하였다. GaAs의 식각 결과는 식각 속도, 식각 선택비, 표면 형상, 잔류 물질 분석을 실시하엿다. 본 실험에서는 1대의 기계적 펌프만을 상ㅇ하여 진공 압력을 유지하였다. GaAs의 식각 속도는 10 sccm $BCl_3$를 사용한 경우 최대 0.4 ${\mu}m$까지 얻을 수 있었다. 감광제에 대한 최대 식각 선택비는 약 2.5 : 1이었다. BCl₃ 플라즈마의 경우 75 mTorr의 저진공 조건에서는 500 V, 250 kHz, 0.7 ${\mu}s$의 실험에서 가장 좋은 식각 특성을 얻을 수 있엇다. X-레이 광전 분석기 데이터에 의하면, 식각된 GaAs의 표면을 깨끗하였으며, 염소와 관련된 잔류 물질은 거의 발견되지 않았다.

• Journal of the Korean Institute of Electrical and Electronic Material Engineers
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• v.13 no.3
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• pp.188-192
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• 2000

In this study PZT etching was performed using planar inductively coupled Ar/Cl$_2$/BCI$_3$ plasma. The etch rate of PZT film was 2450 $\AA$/min at Ar(20)/BCl$_3$(80) gas mixing ratio and substrate temperature of 8$0^{\circ}C$. X-ray photoelectron spectroscopy(XPS) analysis for films composition of etched PZT surface was utilized. The chemical bond of PbO is broken by ion bombardment and Cl radical, and the peak of metal Pb in a Pb 4f narrow scan begins to appear upon etching. As increasing additive BCl$_3$content the relative content of oxygen decreases rapidly in contrast with etch rate of PZT thin film. So we though that the etch rate of PZT thin film increased because abundant B and BCl radicals made volatile oxy-compound such as B$_{x}$/O$_{y}$ and/or BClO$_{x}$ bond. We achieved etch profile of about 80$^{\circ}$ at Ar(20)/BCl$_3$(80) gas mixing condition and substrate temperature of 8$0^{\circ}C$TEX>X>.

• Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
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• 2004.11a
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• pp.183-186
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• 2004

The dry etch behavior of PZT thin films was investigated in $BCl_3/N_2$ plasma. The experiments were carried out with measuring etch rates and selectivities of PZT to $SiO_2$ as a function of gas concentration and input rf power, chamber pressure. The maximum etch rate was 126 nm/min when 30% $N_2$ was added to $BCl_3$ chemistry. Also, as input rf power increases, the etch rate of PZT thin films was increased. Langmuir probe measurement showed the noticeable influence of $BCl_3/N_2$ mixing ratio on electron temperature and electron density as input rf power increased. The variation of Cl radical density as plasma parameters changed was examined by Optical Emission Spectroscopy (OES) analysis. According to X-ray diffraction (XRD) analysis, PZT thin films were damaged in plasma and an increase in (100), (200) and (111) phases showed the improvement in structure of the PZT thin films after the $O_2$ annealing process.