• BMB Reports
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• 제57권4호
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• pp.188-193
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• 2024

Gastric cancer (GC), a leading cause of cancer-related mortality, remains a significant challenge despite recent therapeutic advancements. In this study, we explore the potential of targeting cell surface glucose-regulated protein 94 (GRP94) with antibodies as a novel therapeutic approach for GC. Our comprehensive analysis of GRP94 expression across various cancer types, with a specific focus on GC, revealed a substantial overexpression of GRP94, highlighting its potential as a promising target. Through in vitro and in vivo efficacy assessments, as well as toxicological analyses, we found that K101.1, a fully human monoclonal antibody designed to specifically target cell surface GRP94, effectively inhibits GC growth and angiogenesis without causing in vivo toxicity. Furthermore, our findings indicate that K101.1 promotes the internalization and concurrent downregulation of cell surface GRP94 on GC cells. In conclusion, our study suggests that cell surface GRP94 may be a potential therapeutic target in GC, and that antibody-based targeting of cell surface GRP94 may be an effective strategy for inhibiting GRP94-mediated GC growth and angiogenesis.

• Journal of Ginseng Research
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• 제27권2호
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• pp.56-61
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• 2003

복강 내당능 시험과 MLD STZ 당뇨를 유발시킨 rat에서 백삼, 홍삼, 화기삼의 항당뇨 활성을 비교한 결과를 요약하면 다음과 같다. 1. 복강 내당능 시험에서 백삼은 효과를 나타내지 못한 반면 홍삼과 화기삼은 대조군에 대하여 유의적인 변차를 나타내었다. MLD STZ로 당뇨를 유발시킨 SD계 흰쥐에 백삼, 홍삼, 화기삼을 2주간 투여 후 혈당강하 활성을 비교한 결과 홍삼 투여군의 혈당이 가장 낮았으며 백삼과 화기삼은 비슷한 크기의 활성을 나타내었다. 2. 백삼과 홍삼, 화기삼은 모두 고혈당에 의한 체중 감소 현상을 개선시켰으며 각 투여군 간에는 유의적인 차이는 없었다. 3. 당뇨의 대표적인 증상인 다식 (多食)과 다음 (多飮)현상이 백삼, 홍삼, 화기삼 투여에 의하여 개선되었으며 그 중 홍삼에 의한 효과가 가장 컸다. 4. 혈당강하 활성과 ginsenoside profile간의 상관관계를 살펴본 결과 PPT/PPD ratio가 가장 큰 홍삼의 혈당강하 활성이 백삼과 화기삼에 비해 높은 것으로 보아 PPT/PPD ratio가 혈당강하 활성의 key ratio가 아닌가 추측된다.

• EDISON SW 활용 경진대회 논문집
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• 제6회(2017년)
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• pp.635-642
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• 2017

Cobelli와 그의 동료들이 제안한 포도당 농도에 따른 췌장의 인슐린 분비 모델(Cobelli model)은 비교적 단순한 모델이지만 Grodsky의 실험 뿐만 아니라 일련의 관련 실험을 재현하였다. 하지만 이 모델은 췌장 베타세포 내 인슐린 분포를 미분형식으로 표현하였고, 적분을 통해 인슐린 양을 계산하였다. 그로 인해 각 시간 스텝에서 포도당의 양에 따라 적분 구간만큼 반복적인 계산을 수행해야만 했다. 이에 본 연구에서는 Cobelli model을 재현하면서 좀 더 효과적으로 결과를 얻을 수 있는 새로운 Multi-RRP model을 제시하였다. Multi-RRP model은 RRP를 과립의 자극 여부에 따라 RRPhigh와 RRPlow로 나누어 각각의 인슐린 분비를 계산하는 방법으로, 포도당의 변화에 따라 RRP의 수를 증가시켜 인슐린의 분비량을 산출한다. 이 Multi-RRP model의 시뮬레이션 결과는 Cobelli model과 동일한 경향을 보이며, Grodsky의 계단 실험과의 비교에서는 Cobelli model보다 실험 결과에 더 접근한다. 또한, 시뮬레이션 시간 비교를 통해 효율성을 확인하였고, Multi-RRP model이 Cobelli model보다 16배 이상 효율이 더 높은 것으로 확인되었다.

• 한국해양생명과학회지
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• 제7권2호
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• pp.187-195
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• 2022

붕어(무게 28.1±3.7 g, 길이 10.0±1.0 cm)에 0, 2.0×10⁴, 2.0×10⁵, 2.0×10⁶, 2.0×10⁷ CFU/ml의 Aeromonas hydrophila를 주사 후 2주간 실험을 실시하였다. A. hydrophila로 인위감염한 Carassius carassius의 2주 뒤 반수치사농도는 19.776×10⁵ CFU/ml이었다. 혈액학적 지표에서는 A. hydrophila에 의해 혈색소와 적혈구 수가 유의하게 감소한 반면, 적혈구 용적은 유의적 변화가 없었다. 마그네슘, 칼슘과 같은 혈장 무기 성분은 유의적으로 감소하였다. 유기 혈장 성분에서 A. hydrophila 인위감염에 의해 혈장 포도당과 콜레스테롤이 유의하게 증가한 반면, 총 단백질은 유의하게 감소하였다. 혈장 효소 성분인 ALP는 A. hydrophila 인위감염에 의해 유의하게 증가하였다. 본 연구의 결과는 C. carassius에 대한 A. hydrophila의 인위감염이 치명적인 병원성 세균으로 혈액학적 성상 및 혈장 성분에 유의한 생리학적 변화를 유도하였음을 의미한다.

• BMB Reports
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• 제39권1호
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• pp.26-36
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• 2006

Differential Display PCR technique (DD-PCR) was used for the analysis of altered gene expression in hemocytes of Vibrio harveyi-infected Penaeus monodon. Forty-four combinations of arbitrary and oligo(dT) primers were used to screen for differentially expressed genes. A total of 79 differentially expressed bands could be identified from 33 primer combinations. These included 48 bands (61%) whose expression level increased and 31 bands (39%) decreased after V. harveyi challenge. Subsequently, forty-eight differential display fragments were successfully reamplified and cloned. A total of 267 clones were randomly selected and sequenced. The sequence analysis showed that 85 (31%) out of 267 clones were matched with sequences in the GenBank database which represented 24 different genes with known functions. Among the known genes, glucose transporter 1, interferon-related developmental regulator 1, lysozyme, profilin, SERPINB3, were selected for further confirmation of their differentially expression patterns by real-time PCR. The results showed increasing in expression level of the selected genes in shrimp hemocytes after microbial challenge suggesting the involvement of such genes in bacterial response in shrimp. The anti-lipopolysaccharide factor type 3 (ALFPm3) gene, previously reported in P. monodon (Supungul et al., 2002) was found among the up-regulated genes but diversity due to amino acid changes was observed. Increase in ALFPm3 transcripts upon V. harveyi injection is in accordance with that found in the previous study.

• 한국발생생물학회지:발생과생식
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• 제20권3호
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• pp.187-196
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• 2016

The objective of the current study was to determine acute plasma stress responses in two size groups of juvenile Epinephelus akaara (average body weight: $8.4{\pm}2.1$ and $3.3{\pm}0.6g$; 150 and 120 days after hatch, respectively) exposed to abrupt salinity drops (from 34 practical salinity unit, PSU seawater to 18, 10 PSU (experiment 1) or 26, 18, 10 PSU (experiment 2), respectively). Plasma glucose, glutamic oxalate transaminase, glutamic pyruvate transaminase, red blood cell counts, and gill histology were determined during 72 h exposure. Significantly increased plasma glucose, glutamic oxalate transaminase levels, and red blood cell counts were observed in fish exposed to 18 or 10 PSU. Histological changes, such as hyperplasia and lifting of epithelium in the gill secondary lamellae, were also observed in fish exposed to 18 or 10 PSU at 72 h post-drop. E. akaara exposed to sudden salinity drops to 18 or 10 PSU still seems to undergo the primary adjustment phase before fish reaches a new homeostasis, whereas fish exposed to 26 PSU seems to mount osmotic changes. Therefore, the no observed adverse effect levels for 72 h acute salinity challenge was 26 PSU in our study, and salinity drop to 18 PSU and below can possibly cause acute adverse effect, in which fish could be vulnerable to additional stresses such as a temperature changes or handling stress.

• 한국양식학회지
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• 제21권2호
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• pp.82-88
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• 2008

본 연구는 치어기 조피볼락 Sebastes schlegeli 사료내 생균제 첨가가 넙치의 성장 및 면역반응에 미치는 영향을 평가하였다. 실험사료는 주 단백질원으로 북양어분(white fish meal), 콘글루텐밀(corn gluten meal), 탈피대두박(dehulled soybean meal)을 사용하였으며, 탄수화물원으로는 밀가루(wheat flour)를, 지질원으로는 고도불포화지방산(n-3 HUFA)이 다량 함유된 오징어간유(squid liver oil)를 사용하였다. 생균제의 첨가효과를 확인하기 위하여 B. polyfermenticus(BP), Bacillus licheniformis(BL) 및 복합종균(B. polyfermenticus+Saccharomyces cerevisiae; BP+SC)을 실험사료 내에 각각 $1.0{\times}10^7$ CFU/kg diet 수준으로 첨가하였다. 2주간의 예비사육 후, 평균무게 $12.0{\pm}0.1g(mean{\pm}SD)$인 조피볼락을 500 L 원형수조에 각 실험구 당 각각 20마리씩 3반복으로 무작위로 배치하였고, 실험사료는 1일 2회 어체중의 $1.7{\pm}0.6%$(오전 10시, 오후 4시)씩 12주간 공급 하였다. 증체율, 사료효율, 일간성장율 및 단백질 전환효율에 있어서 BP+SC를 공급한 실험구가 대조구(control)에 비하여 유의하게 높게 나타났지만(P<0.05), BP, BL 및 BP+SC를 공급한 실험구간에는 유의한 차이가 나타나지 않았다. 생존율에 있어서는 모든 실험구간에 있어 유의한 차이가 나타나지 않았다. 전어체 지방함량에 있어서 대조구가 다른 모든 실험구에 비해 높게 나타났으며, 전어체 단백질, 회분 및 수분함량에 있어서는 모든실험구간에 유의한 차이가 없었다. 혈액분석에 있어서 혈장내 glucose의 함량은 BP+SC를 공급한 실험구가 대조구에 비해 유의적으로 낮게 나타났으나, BP, BL 및 BP+SC를 공급한 실험구간에는 유의적인 차이가 나타나지 않았다. Respiratory burst activity(NBT assay)에 있어서 BP+SC와 BL을 공급한 실험구가 대조구에 비해 유의적으로 낮게 나타났으며, BP, BL 및 BP+SC를 공급한 실험구간에는 유의적인 차이가 나타나지 않았다. 혈청의 lysozyme 활성에 있어서는 BP와 BL을 공급한 실험구가 대조구에 비해 높게 나타났으며, BP, BL 및 BP+SC를 공급한 실험구간에는 유의적인 차이가 나타나지 않았다. 공격실험 결과, 폐사는 Edwardsiella tarda를 접종한지 1일 후부터 시작하여 11일째 종료 하였다. 생균제를 투여한 모든 실험구가 대조구에 비해 초기폐사율이 낮게 나타났다. 공격실험 후 8일째부터 종료시 까지는 BP+SC를 공급한 실험구가 대조구에 비해 유의적으로 낮게 나타났으며, BP, BL및 BP+SC를 공급한 실험구간에는 유의한 차이가 나타나지 않았다. 상기 결과를 토대로, 조피볼락 사료내 B. polyfermenticus, B. licheniformis 및 B. polyfermenticus 와 S. cerevisiae의 혼합첨가는 조피볼락의 성장 및 사료효율 증진과 항산화능 및 특정질병저항성에 좋은 효과를 나타낼 수 있을 것으로 사료된다.

• 대한지역사회영양학회지
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• 제13권2호
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• pp.276-287
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• 2008

Diabetic mellitus in an older population is associated with increased basal oxidative stress and free radical accentuated by hyperglycemic challenge. Enhanced free radical in diabetic elderly can cause the oxidative damage and such damage can be protected by antioxidant defense system. It is believed that vitamin C, A and E are the most abundant and effective antioxidants in human plasma. The purpose of this study was to determine the antioxidant status in Korean diabetic elderly using the case-control study. The antioxidant status was examined by determining plasma levels of antioxidant vitamins (vitamin C, A, E, ${\beta}$-carotene), total antioxidant status (TAS) and thiobarbituric acid reactive substance (TBARS) and intakes of vitamin C, A, ${\beta}$-carotene and retiol. Fasting glucose and HbA1c levels and serum lipid profiles (triglyceride (TG), total cholesterol, HDL-cholesterol and LDL-cholesterol) were also determined. Diabetic subjects were 122 elderly persons over 60 years old, visiting public health center, and control subjects were 96 healthy elderly persons living in Ulsan, Korea and they were matched by age, gender, smoking and drinking status. The diabetic and control subjects were divided into sub-groups according to the status of using diet therapy and vitamin supplement. The subjects were interviewed to collect data on their general characteristics, disease history, vitamin supplement, diet therapy and health-related habits by questionnaires. Their dietary intakes were obtained by means of semi-quantitative food frequency questionnaires (SQFFQ). Fasting plasma glucose and HbA1c levels were significantly higher in diabetes than in control subjects, and plasma total cholesterol level of diabetes was not significantly different from that of control subjects. However serum HDL cholesterol level of diabetes was significantly lower and serum TG level of diabetes was significantly higher than those of control group. The average vitamin A and ${\beta}$-carotene intakes of diabetes were significantly higher than those of control subjects. There was no significant difference in plasma vitamin C, ${\beta}$-carotene, and TBARS levels between two groups, but plasma vitamin A, E and TAS levels were significantly higher in diabetes than those in control group. Plasma vitamin A and TAS levels of diabetic subjects using diet therapy were higher than those of control using diet therapy, and plasma vitamin E, ${\beta}$-carotene and TAS levels of diabetic subjects using vitamin supplements were significantly higher than those of controls using vitamin supplements. These results suggested that diabetic mellitus could enhance antioxidant defences against reactive oxygen species and interest in healthy eating such as consumption of more antioxidant nutrients.

• Molecules and Cells
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• 제38권5호
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• pp.452-456
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• 2015

Obesity is the fifth leading risk for death globally, and a significant challenge to global health. It is a common, complex, non-malignant disease and develops due to interactions between the genes and the environment. DNA methylation can act as a downstream effector of environmental signals; analysis of this process therefore holds substantial promise for identifying mechanisms through which genetic and environmental factors jointly contribute to disease risk. To assess the effects of excessive weight and obesity on gene-specific methylation levels of promoter regions, we determined the methylation status of four genes involved in inflammation and oxidative stress [interleukin 6 (IL6), tumor necrosis factor ${\alpha}$ ($TNF{\alpha}$), mitochondrial transcription factor A (TFAM), and glucose transport 4 (GLUT4)] in blood cell-derived DNA from healthy women volunteers with a range of body mass indices (BMIs) by methylation-specific PCR. Interestingly, the samples from obese individuals ($BMI{\geq}30kg/m^2$) showed significantly increased hypermethylation for IL6 gene compared to normal weight ($BMI<23kg/m^2$) and overweight sample ($23kg/m^2{\leq}BMI<30kg/m^2$) (P = 0.034 and P = 0.026). However there was no statistically significant difference in promoter methylation of the other 3 genes between each group. These findings suggest that aberrant DNA methylation of IL6 gene promoter may play an important role in the etiology and pathogenesis of obesity and IL6 methylation could be used as molecular biomarker for obesity risk assessment. Further studies are required to elucidate the potential mechanisms underlying this relationship.

• 한국어병학회지
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• 제25권2호
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• pp.67-76
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• 2012

Two bacteria strains were isolated from emaciated olive flounder (Paralichthys olivaceus) in aquafarm and were identificated as Vibrio harveyi (JV1) and Edwardsiella tarda (JE1), respectively. In the challenge experiments, we found 100% cumulative mortalities in all of olive flounder injected with JV1, JE1 or JV1+JE1 within eleven days after the injection. Two bacteria strains were reisolated from dead fish and were analyzed using the PCR method. In the physilogical analysis, the hematocrit, AST, ALT and cholesterol levels in experimental groups were increased significantly compared to those in control group, but the glucose, total protein and triglyceride levels were significantly decreased. Additionally, the lysozyme activity in the blood serum was decreased. The histopathological observations of the intestine showed that all groups had detachment and destruction of epithelial tissues except for the control group.