• 생명과학회지
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• 제17권8호통권88호
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• pp.1129-1134
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• 2007

bPDI가 ER내 misfolding 단백질의 생성을 제한함으로써 곤충변역과 관계하는지를 해석하기 위하여 bPDI가 과발현(overexpression)되는 곤충세포주와 이와 반대로 bPDI가 억제발현(knock-down)되는 곤충세포주를 제작하여 bPDI가 곤충면역에 관련하는지를 해석하였다. bPDI가 과발현되는 세포주 (Sf9-bPDI)는 정상세포주(Sf9)나 pIZT/V5-His 벡터만 도입된 세포주(Sf9-pIZT)에 비하여 생존율이 30% 이상 높았지만, bPDI의 전사체 발현이 억제된 세포주(Sf9-bPDI-dsRNA)는 오히려 정상세포주나 pIZT/V5-His 벡터만 도입된 세포주에 비하여 생존율이 약 15%낮았다. 이와 같은 결과로써, bPDI는 ER내 misfolding 단백질의 생성을 제한함으로써 곤충의 ERSE과 밀접하게 관련할 것이라 추정할 수 있었다.

• 대한두경부종양학회지
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• 제35권2호
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• pp.19-25
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• 2019

Background/Objectives: Although anaplastic thyroid carcinoma (ATC) is rare, it is one of the deadliest forms of thyroid cancer. The fatality rate for ATC is high, and the survival rate at one year after diagnosis is <20%. The present study aimed to investigate the anti-tumor activities of paclitaxel, radiation, and tyrosine kinase inhibitor (TKI) combined therapy in anaplastic thyroid cancer cells both in vitro and in vivo and explore its effects on apoptotic cell death pathways. Materials & Methods: ATC cell line was exposed to TKI, lenvatinib in the presence or absence of paclitaxel with radiation, and cell viability was determined by MTT assay. Effects of the combined treatment on cell cycle and intracellular signaling pathways were assessed by flow cytometry and western blot analysis. The ATC cell line xenograft model was used to examine the anti-tumor activity in vivo. Results: Our data revealed that the combined administration of paclitaxel, TKI, and radiation decreased cell viability in ATC cells, and also significantly increased apoptotic cell death in these cells, as demonstrated by the cleavage of caspase-3 and DNA fragmentation. This combination therapy reduced anti-apoptotic factor levels in ATC cells, while significantly decreasing tumor volume and increasing survival in ATC xenografts. Conclusion: These results indicate that administering the combination of paclitaxel, TKI, and radiation therapy may exert significant anticancer effects in preclinical models, potentially suggesting a new clinical approach for treating patients with ATC.

• Journal of Microbiology and Biotechnology
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• 제15권3호
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• pp.609-615
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• 2005

The safety and immunogenicity of an attenuated recombinant Salmonella vaccine strain, Salmonella enterica serovar Typhimurium llaB, was assessed. This vaccine strain could survive in low pH condition, and its ability of intracellular survival did not differ from that of S. enterica serovar Typhimurium UK1, which is the wild-type of the vaccine strain. The mortality of the mice orally administered with the vaccine strain was $50\%$ at the dose of $10^7$ CFU. All mice administered with $10^5\;or\;10^3$ CFU of the vaccine strain survived for 3 days postinoculation (pi). However, all mice administered with more than $10^3$ CFU of the vaccine strain died within 3 days pi. To examine the protective effect of the vaccine strain, mice were orally immunized with $10^4\;and\;10^6$ CFU of the bacteria. Control mice were given with 0.5 ml of phosphate buffered saline (PBS). After 8 days, the mice were challenged with $10^9$ CFU of S. enterica serovar Typhimurium UK1, and mortality was examined for 5 days. The survival rates of the mice immunized with $10^4\;and\;10^6$ CFU of the vaccine strain were $60\%\;and\;80\%$, respectively, whereas all control mice died within 2 days after challenging. To investigate the immunogenicity of S. enterica serovar Typhimurium llaB, mice were orally immunized with $10^5\;or\;10^6$ CFU ml of the vaccine strain. Five mice of each group were sacrificed at 5 and 12 days after immunization, and results showed that immunization of the vaccine strain led to increases of IgG1, IgG2, and IgM titers against S. enterica serovar Typhimurium UK1 in mouse sera, cytokine expressions such as IL-2, IL-4, IL-6, and IL-10 in spleen, and the lymphocyte proliferation response to mitogens (concanavalin A or LPS) stimulation.

• 생명과학회지
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• 제12권6호
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• pp.812-820
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• 2002

이 연구는 주변의 김치들을 수거하여 젖산에 내성을 가진 Leuconostoc mesenteroides을 선택배지를 이용하여 분리하고, 지방산 조성을 분석하여 동정한 결과, Leuconostoc mesenteroides LM3균주로 동정했다. 이어서 그의 성장패턴을 관찰하고, 유도기와 지수성장기에서 젖산을 첨가한 결과 성장저해가 일어났음을 확인했으며, 젖산의 최종농도가 0.4%이상인 배지에서는 성장속도가 느려짐을 알았다. 그리고 정지기시작단계에서 고농도의 젖산을 단시간 처리하였을 때, 대조균주가 생존하지 못하는 4%농도에서도 Leuconostoc mesenteroides LM3군주가 생존하는 것을 확인하여 산에 대한 내성이 뛰어남을 알 수 있었다. 이에 trehalose 농도의 변화, 그리고 trehalase와 ATPase 활성을 측정하였고, 이를 통해 젖산에 의한 세포내의 변화를 관찰하였다. 그 결과, 각 성장시기별로 0.6% 젖산을 첨가했을 때 Leuconostoc mesenteroides LM3균주가 trehalose 축적률이 높아졌으나 trehalase활성엔 큰 변화가 없었다. ATPase 활성은 감소하는 경향을 보였으나 시기별 활성은 일정하였고, 세포내 pH를 측정한 결과 Leuconostoc mesenteroides LM3균주는 pH 6으로 일정하게 유지되었다.

• 대한의생명과학회지
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• 제13권2호
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• pp.119-125
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• 2007

It is widely known that protein tyrosine kinases (PTKs) are involved in controlling many biological processes such as cell growth, differentiation, proliferation, survival and apoptosis. An $\alpha3\beta4$ subunit combination acts as a major functional acetylcholine receptor (nAChRs) in male rat major pelvic ganglion (MPG) neurons, and their activation induces fast inward currents and intracellular calcium increases. Recently it has been reported that the activity of acetylcholine receptors (AChRs) in some neurons can be negatively regulated by PTKs. However, the exact mechanism of regulation of nAChRs by PTKs is poorly understood. Therefore, we examined the potential role particular in nAChR by PTK using electrophysiology and calcium imaging in male rat MPG neurons. ACh induced inward currents and $(Ca^{2+})_i$ increases in MPG neurons, concomitantly. These responses were inhibited by more than 90% in $Na^+$- or $Ca^{2+}$- free solution. $\alpha$-conotoxin AuIB, a selective $\alpha3\beta4$ nAChR blocket, inhibited ACh-induced inward currents. Genistein (10 $\mu$M), a broad-spectrum tyrosine kinase inhibitor, markedly decreased ACh-induced currents and $Ca^{2+}$ transients, whereas 10 $\mu$M genistin, an inactive analogue, had little effect. Overall these data suggest that the activities of $\alpha3\beta4$ AChRs in MPG neurons are positively regulated by PTK. In conclusion, trosine kinase may be one of the key factors in the regulation of $\alpha3\beta4$ nAChRs in rat MPG neurons, which may play an important roles in the autonomic neuronal function such as synaptic transmission, autonomic reflex, and neuronal plasticity.

• Biomolecules & Therapeutics
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• 제26권6호
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• pp.568-575
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• 2018

In order to discover lifespan-extending compounds made from natural resources, activity-guided fractionation of Zingiber officinale Roscoe (Zingiberaceae) ethanol extract was performed using the Caenorhabditis elegans (C. elegans) model system. The compound 6-gingerol was isolated from the most active ethyl acetate soluble fraction, and showed potent longevity-promoting activity. It also elevated the survival rate of worms against stressful environment including thermal, osmotic, and oxidative conditions. Additionally, 6-gingerol elevated the antioxidant enzyme activities of C. elegans, and showed a dose-depend reduction of intracellular reactive oxygen species (ROS) accumulation in worms. Further studies demonstrated that the increased stress tolerance of 6-gingerol-mediated worms could result from the promotion of stress resistance proteins such as heat shock protein (HSP-16.2) and superoxide dismutase (SOD-3). The lipofuscin levels in 6-gingerol treated intestinal worms were decreased in comparison to the control group. No significant 6-gingerol-related changes, including growth, food intake, reproduction, and movement were noted. These results suggest that 6-gingerol exerted longevity-promoting activities independently of these factors and could extend the human lifespan.

• 미생물학회지
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• 제49권3호
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• pp.215-220
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• 2013

많은 세균들은 환경적 스트레스에 대항하기 위해 세균 생존에 유용한 특정 유전자들의 전사를 유도하는 대체시그마 인자 RpoS를 활용한다. 세포 내 RpoS 단백질의 농도는 주로 ClpXP 단백질 분해효소의 조절을 통해 결정된다. RpoS를 ClpXP로 전달하기 위해서는 adaptor 단백질 RssB가 반드시 필요하다. Two-component-type response regulator RssB는 RpoS와 지속적으로 상호작용을 하지만, 다양한 환경변화에 의해 RssB-RpoS 상호작용이 억제되어 세균에서 RpoS 양을 증가시킨다. 본 총설에서는 최근까지 연구 된 RssB-RpoS 상호작용에 관여하는 RssB의 anti-adaptor 단백질 IraD, IraM, IraP 등의 조절인자들과 RssB의 N-terminal 수용체 도메인의 인산화에 대해 설명하고 요약하였다. 이러한 RssB의 정교한 활성을 통한 RpoS 분해조절 과정은 외부환경 스트레스로부터 보다 효율적으로 세균을 보호할 수 있다.

• Biomolecules & Therapeutics
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• 제18권4호
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• pp.454-462
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• 2010

The present study investigated the neuroprotective effect of Carpinus tschonoskii MAX and its intracellular protective mechanism on 6-hydroxydopamine (6-OHDA)-induced oxidative damage in PC12 cells. We found that pretreatment of PC12 cells with C. tschonoskii extract significantly inhibited the cell death induced by 6-OHDA in a dose dependent manner. C. tschonoskii extract decreased 6-OHDA-induced apoptotic events such as chromatin condensation, DNA fragmentation, the decrease of Bcl-2/Bax ratio, caspase-3 activation and PARP cleavage. C. tschonoskii extract also reduced generation of 6-OHDA-induced reactive oxygen species and nitric oxide. Furthermore, C. tschonoskii extract up-regulated the myocyte enhancer factor 2 D (MEF2D), a critical transcription factor for neuronal survival, and Akt activity, whereas it inhibited the activity of ERK1/2 and JNK. The results suggest that C. tschonoskii extract decreases 6-OHDA-induced oxidative stress and could prevent PC12 cell apoptosis induced by 6-OHDA via the up-regulation of MEF2D and Akt activity, and thus may have application in developing therapeutic agents for Parkinson's disease.

• Nutrition Research and Practice
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• 제4권4호
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• pp.259-269
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• 2010

Resistance training (RT) is associated with reduced risk of low grade inflammation related diseases, such as cardiovascular disease and type 2 diabetes. The majority of the data studying cytokines and exercise comes from endurance exercise. In contrast, evidence establishing a relationship between RT and inflammation is more limited. This review focuses on the cytokine responses both following an acute bout, and after chronic RT. In addition, the effect of RT on low grade systemic inflammation such as individuals at risk for type 2 diabetes is reviewed. Cytokines are secreted proteins that influence the survival, proliferation, and differentiation of immune cells and other organ systems. Cytokines function as intracellular signals and almost all cells in the body either secrete them or have cytokine receptors. Thus, understanding cytokine role in a specific physiological situation such as a bout of RT can be exceedingly complex. The overall effect of long term RT appears to ameliorate inflammation, but the specific effects on the inflammatory cytokine, tumor necrosis factor alpha are not clear, requiring further research. Furthermore, it is critical to differentiate between chronically and acute Interleukin-6 levels and its sources. The intensity of the RT and the characteristics of the training protocol may exert singular cytokine responses and as a result different adaptations to exercise. More research is needed in the area of RT in healthy populations, specifically sorting out gender and age RT acute responses. More importantly, studies are needed in obese individuals who are at high risk of developing low grade systemic inflammatory related diseases. Assuring adherence to the RT program is essential to get the benefits after overcoming the first acute RT responses. Hence RT could be an effective way to prevent, and delay low grade systemic inflammatory related diseases.

• Biomolecules & Therapeutics
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• 제23권6호
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• pp.582-589
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• 2015

Several theories emphasize that aging is closely related to oxidative stress and disease. The formation of excess ROS can lead to DNA damage and the acceleration of aging. Vigna angularis is one of the important medicinal plants in Korea. We isolated vitexin from V. angularis and elucidated the lifespan-extending effect of vitexin using the Caenorhabditis elegans model system. Vitexin showed potent lifespan extensive activity and it elevated the survival rates of nematodes against the stressful environments including heat and oxidative conditions. In addition, our results showed that vitexin was able to elevate antioxidant enzyme activities of worms and reduce intracellular ROS accumulation in a dose-dependent manner. These studies demonstrated that the increased stress tolerance of vitexin-mediated nematode could be attributed to increased expressions of stress resistance proteins such as superoxide dismutase (SOD-3) and heat shock protein (HSP-16.2). In this work, we also studied whether vitexin-mediated longevity activity was associated with aging-related factors such as progeny, food intake, growth and movement. The data revealed that these factors were not affected by vitexin treatment except movement. Vitexin treatment improved the body movement of aged nematode, suggesting vitexin affects healthspan as well as lifespan of nematode. These results suggest that vitexin might be a probable candidate which could extend the human lifespan.