• 생명과학회지
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• 제21권8호
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• pp.1109-1119
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• 2011

예로부터 한국, 일본 및 중국에서 민간처방 약재 및 건강식품으로 사용되어온 매실은 다양한 효능을 가지는 것으로 알려져 있으나 인체 암세포에서 유발하는 항암작용 및 그에 따른 분자생물학적 기작에 대해서는 명확히 밝혀져 있지 않다. 본 연구에서는 인체 혈구암 U937 세포에서 매실의 메탄올 추출물(MEPM)이 유발하는 항암효과 및 항암기전을 조사한 결과, MEPM 처리 농도 의존적으로 암세포의 성장억제 및 apoptosis를 유발하는 것으로 나타났다. MEPM에 의해서 유발되는 apoptosis에는 XIAP 및 survivin 등과 같은 IAP family의 발현 감소와 더불어 FasL의 발현 증가, Bcl-2의 발현 감소 및 Bid의 단편화 현상이 관여하는 것으로 나타났으며, 두 가지 apoptosis 유발 개시 및 최종 apoptosis 단계에서 중요한 역할을 하는 caspase-8과 -9 및 -3의 활성화와 그에 따른 다양한 기질단백질의 발현 감소 및 단편화가 동반되었음을 알 수 있었다. 또한 인위적인 caspase-3의 활성 차단으로 MEPM에 의하여 유발되는 apoptosis가 현저하게 억제되는 것으로 나타났다. 이상의 결과에서 MEPM은 암세포의 chemotherapeutic agent로서의 가능성을 확인하였지만 향후 지속적인 연구를 통하여 활성물질의 동정 및 관련 기전의 비교 등이 지속적으로 이루어져야 할 것으로 생각된다.

• Journal of Ginseng Research
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• 제41권3호
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• pp.247-256
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• 2017

Background: KG-135, a standardized formulation enriched with Rk1, Rg3, and Rg5 ginsenosides, has been shown to inhibit various types of cancer cells; however, the underlying mechanisms are not fully understood. In this study, we explored its effects in A549 human lung cancer cells to investigate the induction of Forkhead Class box O3a (FOXO3a) and autophagy. Methods: Cell viability was determined by sulforhodamine B staining. Apoptosis and cell cycle distribution were analyzed using flow cytometry. The changes of protein levels were determined using Western blot analysis. Autophagy induction was monitored by the formation of acidic vesicular organelles stained with acridine orange. Results: KG-135 effectively arrested the cells in G1 phase with limited apoptosis. Accordingly, a decrease of cyclin-dependent kinase-4, cyclin-dependent kinase-6, cyclin D1, and phospho-retinoblastoma protein, and an increase of p27 and p18 proteins were observed. Intriguingly, KG-135 increased the tumor suppressor FOXO3a and induced the accumulation of autophagy hallmark LC3-II and acidic vesicular organelles without an increase of the upstream marker Beclin-1. Unconventionally, the autophagy adaptor protein p62 (sequestosome 1) was increased rather than decreased. Blockade of autophagy by hydroxychloroquine dramatically potentiated KG-135-induced FOXO3a and its downstream (FasL) ligand accompanied by the cleavage of caspase-8. Meanwhile, the decrease of Bcl-2 and survivin, as well as the cleavage of caspase-9, were also drastically enhanced, resulting in massive apoptosis. Conclusion: Besides arresting the cells in G1 phase, KG-135 increased FOXO3a and induced an unconventional autophagy in A549 cells. Both the KG-135-activated extrinsic FOXO3a/FasL/caspase-8 and intrinsic caspase-9 apoptotic pathways were potentiated by blockade of autophagy. Combination of KG-135 and autophagy inhibitor may be a novel strategy as an integrative treatment for cancers.

• 생명과학회지
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• 제30권6호
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• pp.532-541
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• 2020

본 연구는 지방감소를 위한 소재개발로 감국 유산균 발효물이 갖는 지방구세포 분화 억제효과를 관찰하였다. 감국 추출물의 세포독성을 극복하는 유산균의 발효물을 제작하였다. 3T3-L1 세포주에서 감국 추출물 및 발효물이 갖는 세포독성은 모두 없었다(1day culture). 감국 추출물 처리 대조군과 비교하여 3T3-L1 세포주에 처리시 증식 유도된 발효물을 선별하였다. 감국 추출물 및 발효물의 분화억제 및 세포생존률 FACS분석은 분화 유도된 세포가 모든 실험군에서 줄어들었다. 3T3-L1 세포주에서 감국 추출물과 발효물 처리가 protein kinase B (Akt) pathway활성이 증가하였고, 단백질 발현은 지방구세포로 분화되면서 Gli2의 수준은 감소하였다. Hedgehog를 조절하는 유산균은 KCTC 3115인 것을 알 수 있었다. 분화와 관련된 KCTC 3115 및 KCTC 3109 발효군에서 단백질 수준에서 C/EBPα 및 FAS를 감소, pACC는 증가시키는 것을 확인하였다. 감국 추출물과 4개의 감국 유산균 발효물 중 Lactococcus lactis subsp. lactis KCTC 3115 발효물이 지방구세포 분화 신호를 더 효과적으로 조절하고, hedgehog을 같이 조절하여 지방전구세포의 분화를 억제하는 것을 알 수 있었다. Hedgehog 신호를 조절하면서 분화를 억제하는 물질에 대한 연구가 더 필요할 것으로 판단된다. 따라서 감국 발효물의 생리활성 물질 중 향후 매커니즘 분석을 위한 활성물질의 자료가 더 필요할 것으로 여겨지며, 감국 추출물 및 감국 발효물의 hedgehog 신호조절이 새로운 비만치료제로 개발될 수 있음을 위한 가능성을 제시하고자 한다.

• Fisheries and Aquatic Sciences
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• 제27권3호
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• pp.180-194
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• 2024

Mass mortalities of mud crab Scylla spp. larvae due to pathogenic Vibrio spp. outbreaks have frequently occurred in hatcheries. To overcome this problem, probiotics containing Bacillus subtilis bacteria are applied to inhibit pathogenic ones. We tested different doses of probiotic-containing B. subtilis (10⁸ CFU/g) on the Scylla tranquebarica larvae and investigated the microbiota population, including Vibrio. Water quality, larvae development, and crablet production were also monitored. The recently hatched larvae were grown in twelve conical fiber tanks filled with 200 L sterile seawater, with a salinity of 30 ppt at a stocking density of 80 ind/L. Four different doses of probiotics were applied in the larvae rearing, namely, A = 2.5 mg/L, B = 5 mg/L, C = 7.5 mg/L, and D = 0 mg/L, with three replicates. Next-generation sequencing analysis was used to obtain the abundance of microbes in the whole body of megalopa and the water media for larvae rearing after applying probiotics. Sixteen Raw Deoxyribonucleic Acid samples (eight from a whole body of megalopa extraction from four treatments of probiotics defined as A, B, C, D, and eight from water media extraction from four treatments of probiotic defined as E, F, G, H) were prepared. Then, they were sent to the Genetics Science Laboratory for NGS analysis. Ammonia, nitrite, total organic matter (TOM), larvae, and crablet production were monitored. Based on the Next-generation sequencing analysis data, the Vibrio spp. decreased significantly (p < 0.05) than control test (D) in megalopa-applied probiotics at the doses of 2.5 mg/L (A) and 7.5 mg/L (C) and in the water media for megalopa rearing treated with probiotics at the dosage of 5.0 mg/L (F). Ammonia in the zoea stage in B treatment and TOM in the zoea and megalopa stage in B and C treatments were decreased significantly (p < 0.05). It impacts the higher number of zoea survival in treatments B and C. Finally, it results in a significantly high crablet production in treatments B and C. Therefore, the dosage of 5 mg/L to 7.5 mg/L improves crablet S. tranquebarica production significantly.

• Journal of Nutrition and Health
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• 제47권1호
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• pp.1-11
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• 2014

널리 음용되고 있는 녹차의 EGCG과 우리나라 국민의 상당수가 복용하고 있는 건강기능성 식품 성분인 글루코사민은 이전의 연구들을 통해서 지방세포의 분화를 억제하는데 효과가 있다고 보고되어왔다. 이 두 물질의 병합처리로 기대되어지는 지방세포에서의 adipogenesis 및 지방축적감소에 대한 상승효과는 검증된 바 없으며, 효과에 대한 cell cycle 차원에서의 접근은 없었다. 본 연구 결과에서 EGCG와 Glucosamine 6-phosphate는 adipogenesis 전사인자인 $PPAR{\gamma}$, $C/EBP{\alpha}$, SREBP1에 대한 직접적인 발현 억제 뿐아니라, $PPAR{\gamma}$, $C/EBP{\alpha}$, SREBP1와 매개된 FAS, ACSL1, LPL과 같은 adipogenic target 유전자의 발현 감소를 통하여 지방세포의 분화와 지방세포 내 지방축적을 감소시키는 효과를 나타냈다. 그리고 HSL과 perilipin의 발현조절을 통해 부분적인 lipolytic effet도 나타냈다. 또한 지방세포의 분화가 개시되는데 있어 중요한 DNA의 remodeling 과정인 mitotic clonal expansion (MCE) 과정 중 G0/G1 phase 단계에서 cell cycle 정지 유도와 그로인한 S phase 및 G2/M phase로 세포주기이행의 방해를 통해 지방세포가 분화되는 것은 억제하였다. 이러한 효과들은 EGCG 농도가 높아질수록, 그리고 EGCG를 단독으로 처리한경우보다 Glucosamine 6-phosphate와 병합하였을 때 효과적이었다. 따라서 EGCG 단독처리 및 glucosamine 6-phosphate와의 병합처리는 지방세포에서 adipogenesis와 adipogenic관련 유전자들의 발현 억제 및 MCE 단계의 cell cycle arrest를 통해 지방세포의 분화를 억제하고 지방축적을 감소시켜 항비만 효과를 나타냈으며, 이러한 효과는 두 성분의 병합처리에서 조금 더 효과적이었다고 할 수 있다. 비록 두 성분의 병합처리가 기대했던 만큼은 아니었으나 항비만 효과에 대한 상승효과가 있다고 볼 수 있다.

• Fisheries and Aquatic Sciences
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• 제5권2호
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• pp.108-113
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• 2002

Apical and subapical fragments of Gracilaria verrucosa (Hudson) Papenfuss (Rhodophyta) were cultured on a temperature-light gradient table with four temperature $(15,\;20,\;25\;and\;30^{\circ}C)$ and five light intensity $(20,\;40,\;60,\;80\; and\;100{\mu}mol\;photons\;m^{-2}s^{-l})$ regimes to examine growth responses. Their growth was measured weekly. Plant weight and lateral branch formation were affected by temperature and light intensity. As compared with other reports, relative growth rate (RGR) in both fragments was more or less high with 6.27 to $11.95\%$ $day^{-1}$. It was lowest at $15^{\circ}C$ with $20\mu mol$ photons $m^{-2}s^{-l}$, whereas, the highest value was recorded at $25^{\circ}C$ with $100\mu mol$ photons $m^{-2}s^{-l}$ During the experimental period, the growth pattern in G. verrucosa was significantly different between apical and subapical fragments, even though RGR based on weight was similar. Growth in apical fragments depended on elongation by apical growth. By contrast, subapical fragments mainly increased their weights by proliferation of lateral branch. This suggests that intercalary activity (e.g. lateral branch formation) is also an important means for growth of the thallus in Korean G. verrucosa. In conclusion, the relatively high growth potential with the intercalary activity in G. verrucosa will be helpful for mariculture in Korea.

• Biomolecules & Therapeutics
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• 제23권1호
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• pp.31-38
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• 2015

Histone acetylation plays a critical role in the regulation of transcription by altering the structure of chromatin, and it may influence the resistance of some tumor cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) by regulating the gene expression of components of the TRAIL signaling pathway. In this study, we investigated the effects and molecular mechanisms of trichostatin A (TSA), a histone deacetylase inhibitor, in sensitizing TRAIL-induced apoptosis in Caki human renal carcinoma cells. Our results indicate that nontoxic concentrations of TSA substantially enhance TRAIL-induced apoptosis compared with treatment with either agent alone. Cotreatment with TSA and TRAIL effectively induced cleavage of Bid and loss of mitochondrial membrane potential (MMP), which was associated with the activation of caspases (-3, -8, and -9) and degradation of poly (ADP-ribose) polymerase (PARP), contributing toward the sensitization to TRAIL. Combined treatment with TSA and TRAIL significantly reduced the levels of the cellular Fas-associated death domain (FADD)-like interleukin-$1{\beta}$-converting enzyme (FLICE) inhibitory protein (c-FLIP), whereas those of death receptor (DR) 4, DR5, and FADD remained unchanged. The synergistic effect of TAS and TRAIL was perfectly attenuated in c-$FLIP_L$-overexpressing Caki cells. Taken together, the present study demonstrates that down-regulation of c-FLIP contributes to TSA-facilitated TRAIL-induced apoptosis, amplifying the death receptor, as well as mitochondria-mediated apoptotic signaling pathways.

• Nutrition Research and Practice
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• 제5권3호
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• pp.185-191
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• 2011

In Korea, chestnut production is increasing each year, but consumption is far below production. We investigated the effect of chestnut extracts on antioxidant activity and anticancer effects. Ethanol extracts of raw chestnut (RCE) or chestnut powder (CPE) had dose-dependent superoxide scavenging activity. Viable numbers of MDA-MD-231 human breast cancer cells, DU145 human prostate cancer cells, and AGS human gastric cancer cells decreased by 18, 31, and 69%, respectively, following treatment with $200{\mu}g/mL$ CPE for 24 hr. CPE at various concentrations ($0-200{\mu}g/mL$) markedly decreased AGS cell viability and increased apoptotic cell death dose and time dependently. CPE increased the levels of cleaved caspase-8, -7, -3, and poly (ADP-ribose) polymerase in a dose-dependent manner but not cleaved caspase-9. CPR exerted no effects on Bcl-2 and Bax levels. The level of X-linked inhibitor of apoptosis protein decreased within a narrow range following CPE treatment. The levels of Trail, DR4, and Fas-L increased dose-dependently in CPE-treated AGS cells. These results show that CPE decreases growth and induces apoptosis in AGS gastric cancer cells and that activation of the death receptor pathway contributes to CPE-induced apoptosis in AGS cells. In conclusion, CPE had more of an effect on gastric cancer cells than breast or prostate cancer cells, suggesting that chestnuts would have a positive effect against gastric cancer.

• Fisheries and Aquatic Sciences
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• 제15권4호
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• pp.353-359
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• 2012

Age and growth of Hemibarbus labeo caught from Goe-san Lake in South Korea from March to November, 2011, were studied. A total of 201 specimens was collected, ranging from 110 to 580 mm in total length (TL). Males and females made up 47.9% and 52.1% of the sample, respectively. Marginal increment analyses showed that vertebral increments, each composed of one opaque and one hyaline zone, were deposited annually. Opaque edges were prevalent from June to July. The relationship between TL and vertebral radius was linear, with equations of R = 0.008TL - 0.208 (male) and R = 0.009TL - 0.272 (female). Regression equations between TL and total weight (TW) were $TW=9{\times}10^{-6}TL^{2.987}$ (male), $TW=8{\times}10^{-6}TL^{3.014}$ (female), and $TW=9{\times}10^{-6}TL^{2.988}$ (combined sexes), according to the von Bertalanffy growth equation. Back-calculated TL was expressed using the von Bertalanffy equation as follows: $L_t=438.25(1-e^{-0.175(t+0.164)})$ for males, $L_t=483.36(1-e^{-0.147(t+0.115)})$ for females, and $L_t=464.86(1-e^{-0.162(t+0.176)})$ for the sexes combined. The growth performances were 4.526, 4.536, and 4.544, respectively.

• Fisheries and Aquatic Sciences
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• 제5권3호
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• pp.191-199
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• 2002

Pacific oysters Crassostrea gigas (Thunberg) were collected on April, 1999 and March­September, 2000 from Goseung Bay along the southern coast of Korea. The oysters tested cp;;ected from a depth of 0.5-2 m in which they cultured by a long line hanging method. The oxygen consumption rates (OCR) of oysters held under constant temperature and darkness (CC), were determined using an automatic intermittent-flow-respirometer (AIFR). Depending on holding periods after oyster collection, the experiments were divided into two groups: Group 7-d (held to ambient temperature for ca. 7 days) and Group 2l-d (held to ambient temperature for ca. 21 days). The OCR for Group 7-d single oyster displayed two peaks every day under CC, while Group 2l-d single oyster showed one peak every day. It is likely that the rhythmic patterns 02.6-12.8 hours) of the OCR in the Group 7-d single oyster may have been influenced by tidal currents at the sampling site. The rhythmic patterns (24.3-24.7 hours) in the Group 2l-d single oyster may have been shifted from two peaks to one peak each day under CC. The present study concludes that the OCR rhythm of wild oysters in nature is governed by two lunar-day clocks (24.8 hours); one driving one peak and the other driving the second peak. When oysters are subjected to the long-term CC conditions, one of the two-clock systems is depressed or only intermittently becomes active. Jpwever. the OCR rhythms by two to three oysters occurred arrhythmic patterns during the experiments and exhibited some evidence of weak rhythmicity of compared to those of a single oyster. It could be partly due to differences group effects.