• BMB Reports
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• 제55권2호
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• pp.81-86
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• 2022

Macrophages are a major cellular component of innate immunity and are mainly known to have phagocytic activity. In the tumor microenvironment (TME), they can be differentiated into tumor-associated macrophages (TAMs). As the most abundant immune cells in the TME, TAMs promote tumor progression by enhancing angiogenesis, suppressing T cells and increasing immunosuppressive cytokine production. N-myc downstream-regulated gene 2 (NDRG2) is a tumor suppressor gene, whose expression is down-regulated in various cancers. However, the effect of NDRG2 on the differentiation of macrophages into TAMs in breast cancer remains elusive. In this study, we investigated the effect of NDRG2 expression in breast cancer cells on the differentiation of macrophages into TAMs. Compared to tumor cell-conditioned medium (TCCM) from 4T1-mock cells, TCCM from NDRG2-over-expressing 4T1 mouse breast cancer cells did not significantly change the morphology of RAW 264.7 cells. However, TCCM from 4T1-NDRG2 cells reduced the mRNA levels of TAM-related genes, including MR1, IL-10, ARG1 and iNOS, in RAW 264.7 cells. In addition, TCCM from 4T1-NDRG2 cells reduced the expression of TAM-related surface markers, such as CD206, in peritoneal macrophages (PEM). The mRNA expression of TAM-related genes, including IL-10, YM1, FIZZ1, MR1, ARG1 and iNOS, was also downregulated by TCCM from 4T1-NDRG2 cells. Remarkably, TCCM from 4T1-NDRG2 cells reduced the expression of PD-L1 and Fra-1 as well as the production of GM-CSF, IL-10 and ROS, leading to the attenuation of T cell-inhibitory activity of PEM. These data showed that compared with TCCM from 4T1-mock cells, TCCM from 4T1-NDRG2 cells suppressed the TAM differentiation and activation. Collectively, these results suggest that NDRG2 expression in breast cancer may reduce the differentiation of macrophages into TAMs in the TME.

• Nutrition Research and Practice
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• 제17권2호
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• pp.371-385
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• 2023

BACKGROUND/OBJECTIVES: Soy isoflavone (SIF) and soy lecithin (SL) have beneficial effects on many chronic diseases, including neurodegenerative diseases. Regretfully, there is little evidence to show the combined effects of these soy extractives on the impairment of cognition and abnormal cerebral blood flow (CBF). This study examined the optimal combination dose of SIF + SL to provide evidence for improving CBF and protecting cerebrovascular endothelial cells. MATERIALS/METHODS: In vivo study, SIF50 + SL40, SIF50 + SL80 and SIF50 + SL160 groups were obtained. Morris water maze, laser speckle contrast imaging (LSCI), and hematoxylin-eosin staining were used to detect learning and memory impairment, CBF, and damage to the cerebrovascular tissue in rat. The 8-hydroxy-2'-deoxyguanosine (8-OHdG) and the oxidized glutathione (GSSG) were detected. The anti-oxidative damage index of superoxide dismutase (SOD) and glutathione (GSH) in the serum of an animal model was also tested. In vitro study, an immortalized mouse brain endothelial cell line (bEND.3 cells) was used to confirm the cerebrovascular endothelial cell protection of SIF + SL. In this study, 50 µM of Gen were used, while the 25, 50, or 100 µM of SL for different incubation times were selected first. The intracellular levels of 8-OHdG, SOD, GSH, and GSSG were also detected in the cells. RESULTS: In vivo study, SIF + SL could increase the target crossing times significantly and shorten the total swimming distance of rats. The CBF in the rats of the SIF50 + SL40 group and SIF50 + SL160 group was enhanced. Pathological changes, such as attenuation of the endothelium in cerebral vessels were much less in the SIF50 + SL40 group and SIF50 + SL160 group. The 8-OHdG was reduced in the SIF50 + SL40 group. The GSSG showed a significant decrease in all SIF + SL pretreatment groups, but the GSH showed an opposite result. SOD was upregulated by SIF + SL pretreatment. Different combinations of Genistein (Gen)+SL, the secondary proof of health benefits found in vivo study, showed they have effective anti-oxidation and less side reaction on protecting cerebrovascular endothelial cell. SIF50 + SL40 in rats experiment and Gen50 + SL25 in cell test were the optimum joint doses on alleviating cognitive impairment and regulating CBF through protecting cerebrovascular tissue by its antioxidant activity. CONCLUSIONS: SIF+SL could significantly prevent cognitive defect induced by β-Amyloid through regulating CBF. This kind of effect might be attributed to its antioxidant activity on protecting cerebral vessels.

• Journal of Nutrition and Health
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• 제47권6호
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• pp.394-402
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• 2014

본 연구는 황칠나무의 부위별 추출물의 항당뇨효능을 평가하기 위해, 황칠나무의 잎과 줄기의 열수추출물과 에탄올추출물을 분리하여 항산화능과 당뇨질환 개선효능을 측정하였다. 그 결과, total polyphenol과 total flavonoid의 농도는 DLW에서 가장 높게 나타났으며, 다음으로 DLE, DSW, DSE 순서로 나타났다. 또한, DPPH 소거능은 DLW가 대부분의 농도에서 가장 높게 나타났으며, DLE는 $500{\mu}g/mL$의 농도에서 가장 높은 DPPH 소거능을 나타내었다. 항산화능이 우수한 DLW와 DLE를 선정하여 STZ로 유도된 당뇨모델동물에 2주간 투여하여 항당뇨 효능을 분석하였다. 그 결과, 체중은 STZ/vehicle 처리군이 급격히 감소하였으나 STZ/DLW와 STZ/DLE 처리군에서 서서히 감소하였다. 혈당량은 STZ/vehicle 처리군에서 급격히 증가하였으며, STZ/DLW 처리군과 STZ/DLE 처리군에서만 유의적인 감소를 나타내었다. 그러나, 혈청 내 인슐린의 농도는 STZ/vehicle 처리군에 비하여 STZ/DLW와 STZ/DLE 처리군에서 증가하였으며, 특히 STZ/DEL-200 처리군에서 가장 높은 농도를 나타내었다. 이러한 변화는 췌장의 조직학적 변화와 면역염색의 결과에서도 동일하게 관찰되었다. 더불어, 뇨당 농도는 STZ/vehicle 처리군에서 급격히 증가하였으며, 오직 STZ/DLW-200 처리군과 STZ/DLE-200 처리군에서만 유의적으로 감소하였다. 이러한 결과는 황칠나무의 잎의 열수추출물과 에탄올추출물은 우수한 항산화효능과 베타세포의 사멸을 억제함으로서 당뇨질환을 개선하는 효능이 있음을 제시하고 있으며, 특히, 200 mg/kg의 농도가 우수한 효능을 나타내는 농도임을 제시하고 있다.

• 생명과학회지
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• 제33권12호
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• pp.1002-1014
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• 2023

다양한 질병의 발병 및 진행을 예방하기 위해 오랫동안 사용되어 온 대계는 항산화 활성을 포함하여 광범위한 생리 활성을 갖는 것으로 보고되었으나, 간세포에서의 효능에 대한 연구는 여전히 미비한 실정이다. 본 연구에서는 간세포에서 대계 에탄올 추출물(EECJ)의 항산화 활성 및 관련 기전을 조사하기 위해 인간 간세포암종 HepG2 세포주를 선택하였고, 산화적 스트레스를 모방하기 위해 H₂O₂를 처리하였다. 본 연구 결과에 따르면 EECJ는 H₂O₂가 처리된 HepG2 세포에서 세포 생존율의 감소와 LDH의 방출을 유의적으로 억제하였다. EECJ는 또한 세포 형태학적 변화의 관찰, 유세포 분석 및 LC3의 발현 결과에서 입증된 바와 같이 H₂O₂에 의해 유도된 자가포식을 유의하게 감소시켰으며, H₂O₂에 의해 유도된 세포사멸과 세포주기의 교란을 약화시켰다. 이는 H₂O₂에 노출된 HepG2 세포가 EECJ에 의하여 지속적인 세포 분열과 증식이 유지되고 있음을 의미한다. 또한, EECJ가 강력한 항산화 활성을 가지고 있음을 세포 내 ROS 및 미토콘드리아 슈퍼옥사이드 생산의 차단으로 확인하였으며, 이는 H₂O₂에 의해 감소된 세포 내 GSH 함량의 회복과 MnSOD 및 GPx의 발현 및 활성을 보존과 연관성이 있었다. 비록 EECJ에 함유된 활성 성분의 분석과 in vivo 동물 모델에서의 검증이 요구되지만, 본 연구의 결과는 EECJ가 산화적 스트레스로 인한 간세포의 손상을 예방하고 치료하기 위한 잠재적인 후보로 사용될 수 있음을 의미한다.

• Journal of Radiation Protection and Research
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• 제33권1호
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• pp.13-20
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• 2008

석유 및 정유관련 산업에서 다중상(multi-phase flow) 유체의 배관 내 흐름은 일반적인 현상의 하나이다. 그러나 각각의 상에 대한 정확한 유량측정은 항상 정확한 결과획득을 얻는데 장애의 근원으로 작용하였다. 일반 상업용 유량계는 일정 이상의 기포가 포함된 유체 흐름의 경우 유량계측에 상당한 오차를 유발한다. 본 연구에서는 ${\gamma}$-ray attenuation 기법을 이용하여 clamp-on 타입으로 배관 외부에서 다중상 유체흐름의 유량 측정을 수행하였다. 사용된 밀봉 감마선원으로는 $^{137}Cs$ 20 mCi와 17 mCi 두 개의 동위원소를 사용하였으며, 감마선 검출기로는 $2"{\times}2"$ NaI(Tl) 섬광계수관을 이용하였다. 방사선 검출기로부터 데이터를 수집하고 각각의 데이터에 대해 푸리에 변환과 필터링을 통해 노이즈를 최소화하였다. 복원된 신호에 대해 상호상관함수(cross correlation function)를 적용하여 두 검출기 사이의 통과시간(transit time)을 측정함으로써 유량을 산정하였다. 배관 내 기포함량 측정을 통해 유량을 보정해줌으로써 측정유량의 정확도를 높였다. 두 선원간의 거리가 4D(D; inner diameter) 그리고 본 실험의 측정조건(N/S: $0.12{\sim}0.15$, sampling time ${\Delta}\;t$: 4msec) 하에서 기포량(단면적 대비 $6.1\;%{\sim}9.2\;%$) 보정을 통해 산정된 유량은 계측오차가 실제 평균유량 대비 1.7 % 이하인 정확도를 보였다. 또한 두 밀봉 감마선원 간의 거리가 가까울수록 통과시간 측정에 정확도가 향상되므로 보다 정확한 유량측정이 가능하였다. 본 연구를 통해 다중상 혼합유체의 유량을 밀봉감마선원과 상호상관 기법으로 이용하여 계측할 수 있음을 확인하였다. 방사성동위원소의 선택 및 계측시스템의 최적화 조건 등에 대한 추가연구가 수행된다면 석유화학 산업과 같은 장치산업의 유지관리 측면에 경제적으로 크게 기여할 수 있을 것으로 판단된다.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2007년도 Proceedings of The Convention
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• pp.79-92
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• 2007

Oxidative stress have known to be a risk factor for the degenerative processes and closely related to a lot of diseases. It is well established that antioxidants are good in protection and therapeutic means against oxidative damage. There is increasing interest in natural antioxidants and many natural antioxidants have been found and utilized as the possible protection for various diseases and skin aging. We have screened natural antioxidant agents for cosmeceuticals, nutraceuticals, and drugs as therapeutic and preventive means against oxidative stress, and have developed a number of novel antioxidants from various natural sources. A novel melanin synthesis inhibitor, Melanocin A, isolated from the metabolite of a fungal strain Eupenicillium shearii F80695 inhibited mushroom tyrosinase and melanin biosynthesis of B16 melanoma cells with $IC_{50}$ value of 9.0 nM and MIC value of $0.9\;{\mu}M$, respectively. Melanocin A also exhibited potent antioxidant activity by scavenging of DPPH and superoxide anion radicals. UV was found to increase the level of hydrogen peroxides and other reactive oxygen species (ROS) in skin tissues. This increase in ROS may not only alter the structure and function of many genes and proteins directly but may also modulate their expressions through signal transduction pathways and, ultimately, lead to skin damage. We investigated the effect of Melanocin A on UV-induced premature skin aging. Firstly, the effect of Melanocin A on UV-induced matrix metalloproteinase (MMP)-9 expression in an immortalized human keratinocyte cell line, HaCaT in vitro was investigated. Acute UV irradiation induced MMP-9 expression at both the mRNA and protein levels and Melanocin A suppressed this expression in a dose-dependent manner. We then investigated UV-induced skin changes in hairless mice in vivo by Melanocin A. Chronic exposure of hairless mouse dorsal skin to UV increased skin thickness and induced wrinkle formation and the gelatinase activities of MMP-2 and MMP-9. Moreover, Melanocin A significantly suppressed UV-induced morphologic skin changes and MMP-2 and MMP-9 expression. These results show that Melanocin A can prevent the harmful effects of UV that lead to skin aging. Therefore, we suggest that Melanocin A should be viewed as a potential therapeutic agent for preventing and/or treating premature skin aging. Terrein is a bioactive fungal metabolite isolated from Penicillium species. Terrein has a relatively simple structure and can be easily synthesized. However, the biologic effects of terrein are comparatively unknown. We found for the first time that terrein potently inhibit melanin production in melanocytes and has a strong hypopigmentary effect in a spontaneously immortalized mouse melanocyte cell line, Mel-Ab. Treatment of Mel-Ab cells with terrein (10-100 mM) for 4 days significantly reduced melanin levels in a dose-dependent manner. In addition, terrein at the same concentration also reduced tyrosinase activity. We then investigated whether terrein influences the extracellular signal-regulated protein kinase (ERK) pathway and the expression of microphthalmia-associated transcription factor (MITF), which is required for tyrosinase expression. Terrein was found to induce sustained ERK activation and MITF down-regulation, and luciferase assays showed that terrein inhibits MITF promoter activity in a dose-dependent manner. To elucidate the correlation between ERK pathway activation and a decreased MITF transcriptional level, PD98059, a specific inhibitor of the ERK pathway, was applied before terrain treatment and found to abrogate the terrein-induced MITF attenuation. Terrein also reduced the tyrosinase protein level for at least 72 h. These results suggest that terrain reduces melanin synthesis by reducing tyrosinase production via ERK activation, and that this is followed by MITF down-regulation.

• 대한본초학회지
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• 제23권2호
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• pp.179-192
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• 2008

Objectives : Draconis Resina (DR) has been used as a traditional Korean herbal medicine since ancient times, and today it is used as a medication for wounds, tumors, diarrhea, rheumatism, in the itching of insect bites and with other conditions in the folk medicine. The aim of this study was to determine whether fractionated extracts of DR inhibit free radical generation, intracellular oxidation, production of nitrite, an index of NO, PGE2, iNOS, COX-2 and proinflammatory cytokines in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages, Methods : DR extract prepared with methanol, and then fractionated with hexane, dichloromethane, ethylacetate, n-butanol and water. Inhibitory effect of DR onto free radical generation was determined by measuring DPPH, superoxide anions and nitric oxide scavenging activities in vitro. Cytotoxic activity of extracts on RAW 264.7 cells was measured using 5-(3-caroboxymeth-oxyphenyl)-2H-tetra-zolium inner salt (MTS) assay. Intracelluar oxidation was analysed by DCF-DA assay. The nitric oxide (NO) production was measured by Griess reagent system. The levels of iNOS and COX-2 expression were confirmed by western blot. And proinflammatory cytokines were measured by ELISA kit. Results : Our results indicated that fractionated extracts, especially dichloromethane and ethyl acetate extracts, significantly inhibited free radical generation, the LPS-induced H202, NO, PGE2 production and iNOS, COX-2 expression accompanied by an attenuation of TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 formation in macrophages. Conclusions : Our results indicate that dichloromethane and ethyl acetate extracts of DR have potential as an agent of chronic inflammatory diseases.

• Nutrition Research and Practice
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• 제8권6호
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• pp.618-624
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• 2014

BACKGROUND/OBJECTIVES: Isoflavones are widely believed to be beneficial to human health, in relation to their antioxidant potentials. Exercise can cause an imbalance between reactive oxygen species (ROS) and antioxidants. This study was conducted in order to investigate the ability of isoflavones in amelioration of oxidative stress induced by exercise. MATERIALS/METHODS: Male Sprague-Dawley rats were assigned to one of four groups: isoflavone-free with no exercise (CON-sd), isoflavone-free with exercise (CON-ex), isoflavone-supplemented with no exercise (ISF-sd), and isoflavone-supplemented with exercise (ISF-ex). Animals exercised on the treadmill for 30 minutes per day, five days per week. TBARS as a marker of oxidative stress and antioxidant enzyme activity, including SOD, GSH-px, and catalase were determined in liver tissue. Serum lipid profile was also examined. RESULTS: A significant effect of isoflavone alone was observed on abdominal fat pad mass. ISF-ex had significantly less abdominal fat pad than CON-ex. Both exercise and isoflavone treatment had significant effects on lowering plasma triglyceride (TG), thus, the ISF-ex group had a significantly lower TG level than the CON-sd group, by 30.9%. However, no differences were observed in plasma cholesterol, HDL-C, and cholesterol/HDL-C ratio. Exercise, isoflavone, and exercise-isoflavone interaction effects were significant on thiobarbituric acid reactive substances (TBARS) (P = 0.001, 0.002, and 0.005, respectively). The CON-ex group showed a higher TBARS level than the other three groups. By contrast, in the ISF-ex group, TBARS was restored to the level of the ISF-sd or CON-sd group. Isoflavone had a significant effect on superoxide dismutase (SOD) (P = 0.022) and catalase activities (P = 0.049). Significantly higher SOD and catalase activities were observed in ISF-ex than CON-ex. SOD and catalase activities showed an inverse pattern of TBARS. Taken together, isoflavones increased the activities of SOD and catalase with concomitant decreases in TBARS, indicative of decreased oxidative stress. CONCLUSIONS: Isoflavone supplementation enhances antioxidant action with attenuation of exercise-induced oxidative stress, as measured by decreases in TBARS, and inhibits body fat accumulation and plasma TG increase. Antioxidative effects ascribed to isoflavones may be partially exerted via enhancement of antioxidant enzyme activities.

• Journal of Microbiology and Biotechnology
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• 제22권8호
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• pp.1170-1176
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• 2012

In this study, we aimed to evaluate the effect of ${\alpha}$-cyperone on S. aureus. We used a hemolysin test to examine the hemolytic activity in supernatants of S. aureus cultured with increasing concentrations of ${\alpha}$-cyperone. In addition, we evaluated the production of ${\alpha}$-hemolysin (Hla) by Western blotting. Real-time RT-PCR was performed to test the expression of hla (the gene encoding Hla) and agr (accessory gene regulator). Furthermore, we investigated the protective effect of ${\alpha}$-cyperone on Hla-induced injury of A549 lung cells by live/dead and cytotoxicity assays. We showed that in the presence of subinhibitory concentrations of ${\alpha}$-cyperone, Hla production was markedly inhibited. Moreover, ${\alpha}$-cyperone protected lung cells from Hla-induced injury. These findings indicate that ${\alpha}$-cyperone is a promising inhibitor of Hla production by S. aureus and protects lung cells from this bacterium. Thus, ${\alpha}$-cyperone may provide the basis for a new strategy to combat S. aureus pneumonia.

• 대한임상검사과학회지
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• 제48권4호
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• pp.280-286
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• 2016

폴리페놀 성분은 심혈관질환에서 좋은 효과를 나타낸다고 보고되고 있다. 폴리페놀성 화합물인 3,4-다이하이드록시 하이드로시나믹산은 항산화 활성과 항암 활성을 나타낸다고 보고되었다. 이 연구의 목적은 3,4-다이하이드록시 하이드로시나믹산이 항동맥 경화 효과를 나타내는지를 뉴질랜드 흰 토끼에서 평가하는 것이다. 8주동안 고콜레스테롤 식이를 급여한 대조그룹 토끼의 광범위한 동맥 부위에서 동맥경화 초기병변이 형성되었다. 반면에 고콜레스테롤 식이를 급여하면서 3,4-다이하이드록시 하이드로시나믹산을 투여한 토끼에서는 대조 그룹의 토끼에 비해 동맥경화 병변 형성이 감소하였고, 병변 내로 침윤한 대식세포의 양도 감소하였다. 이러한 3,4-다이하이드록시 하이드로시나믹산의 효과에서 전신적으로나 국부적으로 독성이 관찰되지 않았다. 간의 아실-코엔자임 A: 콜레스테롤 아실트렌스페라제 활성이 고콜레스테롤 식이를 급여하면서 3,4-다이하이드록시 하이드로시나믹산을 투여한 토끼에서 대조 그룹의 토끼에 비해 22% 감소하였다. 이러한 연구 결과는 3,4-다이하이드록시 하이드로시나믹산이 토끼에서 아실-코엔자임 A: 콜레스테롤 아실트렌스페라제를 억제함으로써 항동맥경화 효과를 나타낸다는 것을 증명해 준다.