• Journal of Yeungnam Medical Science
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• 제38권2호
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• pp.83-94
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• 2021

The global obesity epidemic and the growing elderly population largely contribute to the increasing incidence of type 2 diabetes. Insulin resistance acts as a critical link between the present obesity pandemic and type 2 diabetes. Naturally occurring reactive oxygen species (ROS) regulate intracellular signaling and are kept in balance by the antioxidant system. However, the imbalance between ROS production and antioxidant capacity causes ROS accumulation and induces oxidative stress. Oxidative stress interrupts insulin-mediated intracellular signaling pathways, as supported by studies involving genetic modification of antioxidant enzymes in experimental rodents. In addition, a close association between oxidative stress and insulin resistance has been reported in numerous human studies. However, the controversial results with the use of antioxidants in type 2 diabetes raise the question of whether oxidative stress plays a critical role in insulin resistance. In this review article, we discuss the relevance of oxidative stress to insulin resistance based on genetically modified animal models and human trials.

• International Journal of Industrial Entomology and Biomaterials
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• 제43권2호
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• pp.94-98
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• 2021

Reactive oxygen species (ROS) induce a variety of cellular responses, such as proliferation, differentiation, senescence, and apoptosis. Intestinal epithelial cells are continuously exposed to ROS, and excessive generation of ROS severely damages cells via oxidative stress. Pro-inflammatory cytokines may lead to intestinal inflammation and damage by inducing excessive ROS generation. In this study, we showed that papiliocin, an antimicrobial peptide, significantly inhibited ROS production, without affecting cell viability. Moreover, TNF-α and IL-6 expression was decreased in the intestinal epithelial cells. The activity of papiliocin may significantly contribute to preserving the integrity of the intestinal mucosa against oxidative damage and inflammation-related disorders.

• 한국임상수의학회지
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• 제32권2호
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• pp.135-140
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• 2015

염증상태에서의 CLA의 효과와 작용기전을 알아보기 위해 LPS로 자극한 RAW 264.7 세포에 있어서 ROS와 NO생산 및 NF-${\kappa}B$ 활성에 대한 t10c12-CLA의 효과를 검토하였다. 또한 이러한 효과가 세포질 내 칼슘이온의 변화와 관련이 있는지도 알아보았다. LPS 자극으로 ROS 생산은 증가하였고 이러한 증가는 칼슘결합제인 BAPTA/AM에 의해 감소하였다. t10c12-CLA 또한 LPS 자극 RAW 264.7 세포의 ROS 생산 증가를 억제시켰으며 BAPTA/AM과 함께 처리시 더욱 억제되었다. NO의 생산과 NF-${\kappa}B$ p65 활성도 t10c12-CLA, BAPTA/AM, t10c12-CLA와 BAPTA/AM의 동시처리 모두에서 현저하게 억제되었다. 이상의 결과로부터 염증 조건에서 CLA는 과도한 ROS와 NO의 생산 및 NF-${\kappa}B$의 활성을 칼슘 의존적으로 억제하여 항염증 효과를 발휘하는 것으로 생각되었다.

• 한국생명과학회:학술대회논문집
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• 한국생명과학회 2008년도 제49회 학술심포지움 및 국제학술대회
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• pp.63.2-63.2
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• 2008

• 한국식품영양과학회지
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• 제46권4호
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• pp.523-528
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• 2017

본 연구는 국내 산림자생 식물 추출물 5종(밤나무, 진달래, 산수유, 복분자딸기, 갈참나무)에 대한 지방세포 분화 억제 및 활성산소종(ROS) 생성 억제 효능을 평가하였다. 지방세포 분화 중 세포 내 지방축적 및 ROS 생성량을 비교한 결과, 국내 산림 식물 5종 모두 지방축적량 및 ROS 생성량을 농도 유의적으로 감소키는 것으로 나타났다. 특히 복분자딸기 추출물을 처리한 지방세포에서 지방 축적 및 ROS 저감에 가장 크게 나타났으며 양성대조군으로 사용된 N-acetyl-L-cysteine과 유사한 결과를 나타내었다. 또한, 복분자딸기 추출물을 처리함으로써 지방세포의 분화를 조절하는 전사인자인 $PPAR{\gamma}$, $C/EBP{\alpha}$ 및 aP2 발현이 억제됨을 확인하였다. 국내 산림 식물 5종 추출물은 천연물에서 유래한 항비만 및 항산화 활성 기능성식품 소재로 활용 가능할 것으로 생각한다.

• IMMUNE NETWORK
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• 제5권1호
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• pp.30-35
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• 2005

Background: p38 and extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) signaling are thought to have critical role in lipopolysaccharide (LPS)-induced immune response but the molecular mechanism underlying the induction of these signaling are not clear. Methods: Specific inhibitors for p38, SB203580, and for ERK, PD98059 were used. Cells were stimulated by LPS with or without specific MAPK inhibitors. Results: LPS activated inducible nitric oxide synthase (iNOS), subsequent NO productions, and pro-inflammatory cytokine gene expressions (TNF-${\alpha}$, IL-$1{\beta}$, IL-6, and IL-12). Treatment of both SB203580 and PD98059 decreased LPS-induced NO productions. Concomitant decreases in the expression of iNOS mRNA and protein were detected. SB203580 and PD98059 decreased LPS-induced gene expression of IL-$1{\beta}$ and IL-6. SB203580 increased LPS-induced expression of TNF-${\alpha}$ and IL-12, and reactive oxygen species production, but PD98059 had no effect. Conclusion: These results indicate that both p38 and ERK pathways are involved in LPS-stimulated NO synthesis, and expression of IL-$1{\beta}$ and IL-6. p38 signaling pathways are involved in LPS-induced TNF-${\alpha}$ and IL-12, and reactive oxygen species plays an important role in these signaling in macrophage.

• 생약학회지
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• 제37권4호
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• pp.307-313
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• 2006

Reactive oxygen species (ROS) and formation of advanced glycation end products (AGEs) play an important role in the pathogenesis of diabetic nephropathy by hyperglycemia. To find natural agents improving diabetic nephropathy, 63 natural resources which used to the treatment of diabetes mellitus in a folk remedy were investigated with an in vitro system employing radical scavenging activity and inhibitory activity of AGEs formation. In results, the extracts of Aspalathus linearis, Rubus coreanus, Rosa rugosa, and Epimedium koreanum significantly inhibited the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical with $IC_{50}$ values less than $10{\mu}g/ml$. The extracts of Zea mays, Cucurbita moschata, Cudrania tricuspidata, and Aspalathus linearis effectively reduced the formation of AGEs compared with the positive control $N-acetyl-_L-cystenine$ (NAC) and aminoguanidine (AG). In addition, the extracts of Aspalathus linearis, Commelina communis, Cornus officinalis, and Lespodeza cuneata showed the all inhibitory activity against DPPH radical and AGEs formation. Also, these resources definitely showed the radical scavenging activity against peroxynitrite $(ONOO^-)$ and hydroxyl radical $({\cdot}OH)$ relating to high glucose-induced ROS production. Thus, these results suggest that some natural resources may regulate the initiation and progression of diabetic nephropathy through inhibition of ROS production and AGEs formation.

• 대한수의학회지
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• 제59권4호
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• pp.195-199
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• 2019

Disulfiram (DSF) is a member of the dithiocarbamate family that can bind copper. Recent studies have shown that DSF has anti-cancer activities, but the mechanism has not been clarified. Therefore, it is important to study the action mechanism of DSF to maximize its anticancer effects. A human leukemia cell line, HL-60, was used in this study. HL-60 cells were treated with DSF and the cellular metabolic activity was measured. DSF increased the cell death of HL-60 cells in annexin V-fluorescein isothiocyanate/propidium iodide staining analysis. In addition, DSF decreased the mitochondrial membrane potential (MMP) of the HL-60 cells. The cytotoxicity of DSF on HL-60 cells was observed at 0.4 μM. Interestingly, the reduction of MMP by DSF was recovered by N-acetyl-L-cysteine, an inhibitor of reactive oxygen species (ROS) production. This suggests that the decrease in MMP by DSF is closely related to the production of ROS in HL-60 cells, which indicates the relationship between the apoptosis of HL-60 cells by DSF and the role of the mitochondria. This study provides clinicians and researchers with valuable information regarding the anti-cancer activity of DSF in terms of the action mechanism.

• Clinical and Experimental Pediatrics
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• 제56권3호
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• pp.107-111
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• 2013

Preterm infants are vulnerable to the oxidative stress due to the production of large amounts of free radicals, antioxidant system insufficiency, and immature oligodendroglial cells. Reactive oxygen species (ROS) play a pivotal role in the development of periventricular leukomalacia. The three most common ROS are superoxide ($O2^{\cdot-}$), hydroxyl radical ($OH^{\cdot}$), and hydrogen peroxide ($H_2O_2$). Under normal physiological conditions, a balance is maintained between the production of ROS and the capacity of the antioxidant enzyme system. However, if this balance breaks down, ROS can exert toxic effects. Superoxide dismutase, glutathione peroxidase, and catalase are considered the classical antioxidant enzymes. A recently discovered antioxidant enzyme family, peroxiredoxin (Prdx), is also an important scavenger of free radicals. Prdx1 expression is induced at birth, whereas Prdx2 is constitutively expressed, and Prdx6 expression is consistent with the classical antioxidant enzymes. Several antioxidant substances have been studied as potential therapeutic agents; however, further preclinical and clinical studies are required before allowing clinical application.

• Asian-Australasian Journal of Animal Sciences
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• 제22권3호
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• pp.343-349
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• 2009

This study was designed to simplify a cryopreservation program for embryonic stem cells (ESCs) by selection of cooling method and cryoprotectant. Commercially available mouse E14 embryonic stem cells (ESCs) were cryopreserved with various protocols, and morphology and viability of the frozen-thawed ESCs and their reactive oxygen species (ROS) production were subsequently monitored. Post-thaw colony-formation of ESCs was detected only after a slow freezing using dimethyl sulfoxide (DMSO) by stepwise placement of a freezing container into a $-80^{\circ}C$ deep freezer and subsequently into -$196^{\circ}C$ liquid nitrogen, while no proliferation was detected after vitrification. When the simplified protocol was employed, the replacement of DMSO with a mixture of DMSO and ethylene glycol (EG) further improved the post-thaw survival. ROS generation in ESCs frozen-thawed with the optimized protocol was not increased compared with non-frozen ESCs. The use of fresh mouse embryonic fibroblasts as feeder cells for post-thaw subculture did not further increase post-thaw cell viability. In conclusion, a simplified slow-freezing program without employing programmable freezer but using DMSO and EG was developed which maintains cell viability and colony-forming activity of ESCs during post-thaw subculture.