• 동의생리병리학회지
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• 제28권3호
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• pp.317-321
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• 2014

Amyloid-${\beta}$ protein ($A{\beta}$) is a pathological component of Alzheimer's disease (AD) by participating in the senile plaque formation in the patient's brain. Although the exact mechanism of $A{\beta}$ toxicity is not fully elucidated, it is considered to be closely related to its fibrillation process. For prevention of AD, recent studies have suggested various small molecules which inhibit $A{\beta}$ fibrillation. In this report, ${\beta}$-asarone found in acorus plant has been investigated as an anti-amyloid molecule. ${\beta}$-Asarone was demonstrated to prevent in vitro fibrillation of $A{\beta}$ by inducing the oligomer formation that obviously decreased cytotoxicity. Therefore, ${\beta}$-asarone could be suggested as an inhibitory agent of $A{\beta}$ fibrillation and toxicity, which would help us not only to understand underlying principle of amyloidogenesis mechanism but also to develop a controlling strategy toward AD.

• Journal of Microbiology and Biotechnology
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• 제24권5호
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• pp.605-613
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• 2014

We have previously shown that paraquat (PQ)-induced oxidative stress causes dramatic damage in various human cell lines. Naringenin (NG) is an active flavanone, which has been reported to have beneficial bioactivities, including antioxidative, anti-inflammatory, and antitumorigenic activities, with a relatively low toxicity to normal cells. In this study, we intended to assess the cytoprotective effect of NG against PQ-induced toxicity in the human bronchial epithelial BEAS-2B cell line. Co-treatment with NG in PQ-treated BEAS-2B cells can reduce PQ-induced cellular toxicity. NG can also decrease the generation of intracellular ROS caused by PQ treatment. We also observed that treatment with NG in PQ-exposed BEAS-2B cells can significantly induce the expression of antioxidant-related genes, including GPX2, GPX3, GPX5, and GPX7. NG co-treatment can also activate the NRF2 transcription factor and promote its nuclear translocation. In addition, NG co-treatment can induce the expression of NRF2-downstream target genes such as that of heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1). A small interfering RNA study revealed that the knockdown of NRF2 can abrogate NG-mediated protection of the cells from PQ-induced cellular toxicity. We propose that NG effectively alleviates PQ-induced cytotoxicity in human bronchial epithelial BEAS-2B cells through the NRF2-regulated antioxidant defense pathway, and NG might be a good therapeutic candidate molecule in oxidative stress-related diseases.

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2813-2818
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• 2012

Background: Considerable evidence suggests that metadherin (MTDH) is a potentially crucial mediator of tumor malignancy and an important therapeutic target for simultaneously enhancing chemotherapy efficacy and reducing metastasis risk. Inhibition of MTDH expression by RNA interference has been shown in several previous research, but silencing MTDH expression by microRNA (miRNA) interference in breast cancer has not been established. In the present study, we investigated the role of MTDH-miRNA in down-regulation of proliferation, motility and migration of breast carcinoma cells. Methods: Expression vectors of recombinant plasmids expressing artificial MTDH miRNA were constructed and transfected to knockdown MTDH expression in MDA-MB-231 breast cancer cells. Expression of MTDH mRNA and protein was detected by RT-PCR and Western blot, respectively. MTT assays were conducted to determine proliferation, and wound healing assays and transwell migration experiments for cell motility and migration. Results: Transfection of recombinant a plasmid of pcDNA-MTDH-miR-4 significantly suppressed the MTDH mRNA and protein levels more than 69% in MDA-MB-231 breast cancer cells. This knockdown significantly inhibited proliferation, motility and migration as compared with controls. Conclusions: MTDH-miRNA may play an important role in down-regulating proliferation, motility and migration in breast cancer cells, and should be considered as a potential small molecule inhibitor therapeutic targeting strategy for the future.

• Applied Biological Chemistry
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• 제29권2호
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• pp.198-206
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• 1986

정제인삼(精製人蔘)사포닌의 수용액을 분자투석막(分子透析膜)(분자량(分子量) 12000)을 통(通)하여 투석(透析)하거나 Bio-Gel P-2(분자량(分子量) $200{\sim}2000$)gel을 통과시켜 분취(分取)하고 HPLC로 ginsenoside를 분석(分析)하였다. Ginsenoside는 분자결합양상(分子結合樣相)과 분자내(分子內) 친수성기(親水性基)의 공간배열(空間配列)에 따라 3군(群)으로 분류(分類)되었다. 제(第) I 군(群)은 거대(巨大)미셀 형성자(形成者)로 결합분자수(結合分子數)가 10이상이며 I면친수기형(面親水基形)이고 panaxadiol인 $Ginsenoside\;Rb_1$, $Rb_2$, Rc 및 Rd가 포함된다. 제(第)II군(群)은 소(小)미셀형성자(形成者)로 결합분자수(結合分子數)가 10이상(以上)에서 1까지이고 불완전(不完全) 양면친수기형(兩面親水基形)이며 triol인 $Rg_2$와 Rf 및 diol인 $Rg_3$가 포함된다. 제(第)III군(群)은 단분자(單分子)로 존재(存在)하며 양면친수기형(兩面親水基形)이고 triol인 Re와 $Rg_1$을 포함한다.

• 천문학논총
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• 제14권1호
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• pp.33-37
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• 1999

We have constructed a synthetic spectrum of the 2.5 micron $C_2H$ bands and compared them with diminutive structures in the near-infrared spectra of Comets P/Halley and West (1976 VI). We found that the Q branches of the $C_2H$ bands coincide with two small emission peaks in the spectra of the comets. We undertook Monte Carlo simulations using observed emission intensities of $C_2$ and possibly $C_2H$ in Comet P/Halley in order to derive a lifetime range of $C_2H$ and a production rate at the time of observations of P/Halley. We obtained a $C_2H$ production rate of $1\times10^{27}\;sec^{-1}$ for P/Halley on December 20, 1985, assuming the 2.5 micron features are due to $C_2H$. We derived a very short lifetime (<100 seconds) of $C_2H$ at 1AU heliocentric distance, assuming that the only parent molecule for $C_2H$ and $C_2$ is $C_2H$. Using this short lifetime we were unable to fit our $C_2$ distribution model to $C_2$ distribution curves observed by O'Dell et al.(1988), because our curve shows a steep slope compared with the observed one. We conclude that there must be significant additional source(s) for $C_2H$ and $C_2$ other than $C_2H_2$.

• BMB Reports
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• 제35권1호
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• pp.116-126
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• 2002

Nitric oxide (NO), synthesized from L-arginine by NO synthases, is a small, lipophilic, diffusible, highly reactive molecule with dichotomous regulatory roles in many biological events under physiological and pathological conditions. NO can promote apoptosis (pro-apoptosis) in some cells, whereas it inhibits apoptosis (anti-apoptosis) in other cells. This complexity is a consequence of the rate of NO production and the interaction with biological molecules such as metal ion, thiol, protein tyrosine, and reactive oxygen species. Long-lasting overproduction of NO acts as a pro-apoptotic modulator, activating caspase family proteases through the release of mitochondrial cytochrome c into cytosol, up-regulation of the p53 expression, and alterations in the expression of apoptosis-associated proteins, including the Bcl-2 family. However, low or physiological concentrations of NO prevent cells from apoptosis that is induced by the trophic factor withdrawal, Fas, $TNF{\alpha}$/ActD, and LPS. The anti-apoptotic mechanism is understood on the basis of gene transcription of protective proteins. These include: heat shock protein, hemeoxygenase, or cyclooxygenase-2 and direct inhibition of the apoptotic executive effectors caspase family protease by S-nitrosylation of the cysteine thiol group in their catalytic site in a cell specific way. Our current understanding of the mechanisms by which NO exerts both pro- and anti-apototic action is discussed in this review article.

• BMB Reports
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• 제51권6호
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• pp.308-313
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• 2018

Small-molecule inhibitors are widely used to treat a variety of inflammatory diseases. In this study, we found a novel anti-inflammatory compound, 1-[(2R,4S)-2-methyl-4-(phenylamino)-1,2,3,4-tetrahydroquinolin-1-yl]prop-2-en-1-one (MPQP). It showed strong anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. These effects were exerted through the inhibition of the production of NO and pro-inflammatory cytokines, such as interleukin (IL)-6, $IL-1{\beta}$, and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$). Furthermore, MPQP decreased the expression levels of inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2). Additionally, it mediated the inhibition of the phosphorylation of p38, c-Jun N-terminal kinase (JNK), the inhibitor of ${\kappa}B{\alpha}$ ($I{\kappa}B{\alpha}$), and their upstream kinases, $I{\kappa}B$ kinase (IKK) ${\alpha}/{\beta}$, mitogen-activated protein kinase kinase (MKK) 3/6, and MKK4. Furthermore, the expression of IL-1 receptor-associated kinase 1 (IRAK1) that regulates $NF-{\kappa}B$, p38, and the JNK signaling pathways, was also increased by MPQP. These results indicate that MPQP regulates the IRAK1-mediated inflammatory signaling pathways by targeting IRAK1 or its upstream factors.

• Molecules and Cells
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• 제27권3호
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• pp.279-282
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• 2009

"Two-cysteine" peroxiredoxins are antioxidant enzymes that exert a cytoprotective effect in many models of oxidative stress. However, under highly oxidizing conditions they can be inactivated through hyperoxidation of their peroxidatic active site cysteine residue. Sulfiredoxin can reverse this hyperoxidation, thus reactivating peroxiredoxins. Here we review recent investigations that have shed further light on sulfiredoxin's role and regulation. Studies have revealed sulfiredoxin to be a dynamically regulated gene whose transcription is induced by a variety of signals and stimuli. Sulfiredoxin expression is regulated by the transcription factor AP-1, which mediates its up-regulation by synaptic activity in neurons, resulting in protection against oxidative stress. Furthermore, sulfiredoxin has been identified as a new member of the family of genes regulated by Nuclear factor erythroid 2-related factor (Nrf2) via a conserved cis-acting antioxidant response element (ARE). As such, sulfiredoxin is likely to contribute to the net antioxidative effect of small molecule activators of Nrf2. As discussed here, the proximal AP-1 site of the sulfiredoxin promoter is embedded within the ARE, as is common with Nrf2 target genes. Other recent studies have shown that sulfiredoxin induction via Nrf2 may form an important part of the protective response to oxidative stress in the lung, preventing peroxiredoxin hyperoxidation and, in certain cases, subsequent degradation. We illustrate here that sulfiredoxin can be rapidly induced in vivo by administration of CDDO-TFEA, a synthetic triterpenoid inducer of endogenous Nrf2, which may offer a way of reversing peroxiredoxin hyperoxidation in vivo following chronic or acute oxidative stress.

• Nuclear Engineering and Technology
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• 제9권4호
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• pp.203-210
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• 1977

디메틸썰폭사이드를 표지보조제로 사용하여 방사면역측정용 $^{125}$/I 표지인슈린을 효과적으로 만들 수 있었다. 디메틸썰폭사이드 조금을 통상의 표지반응 혼합물에 첨가하여 반응시간을 조절하여 보았더니 표지반응속도는 약간 느렸으나 이렇게 하여 얻은 표지인슈린은 항체와의 결합능이 좋았으며 표준곡선을 점시했을 때 큰 구배를 보였다. 표지반응수율도 반응시간을 1분으로 늘림에 따라 약 30%로 늘어났다. 평균 항체결합능(B/F)의 증가는 일정항체 희석비율하에서 표지보조제없이 표지한 인슈린을 쓴 때가 1.5인데 반해 표지보조제를 쓴 경우는 2.5로서 약 70%의 향상을 보였다. 핵자기공명분광법으로 표지혼합물에 첨가한 디메틸썰폭사이드는 클로라민티에 의해 디메틸썰폰으로 산화된다는 것을 확인하였다. Stagg등의 결과와 대략 같은 이 실험결과를 디메틸썰폭사이드와 인슈린분자 중의 유황결합이 클로라민티에 의해 경쟁적 산화를 받는 것으로 보고 이를 토의하였다.

• Biomolecules & Therapeutics
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• 제22권5호
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• pp.400-405
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• 2014

G-protein coupled receptor 119 (GPR119) has emerged as a novel target for the treatment of type 2 diabetes mellitus. GPR119 is involved in glucose-stimulated insulin secretion (GSIS) from the pancreatic b-cells and intestinal cells. In this study, we identified a novel small-molecule GPR119 agonist, HD047703, which raises intracellular cAMP concentrations in pancreatic ${\beta}$-cells and can be expected to potentiate glucose-stimulated insulin secretion from human GPR119 receptor stably expressing cells (CHO cells). We evaluated the acute efficacy of HD047703 by the oral glucose tolerance test (OGTT) in normal C57BL/6J mice. Then, chronic administrations of HD047703 were performed to determine its efficacy in various diabetic rodent models. Single administration of HD047703 caused improved glycemic control during OGTT in a dose-dependent manner in normal mice, and the plasma GLP-1 level was also increased. With respect to chronic efficacy, we observed a decline in blood glucose levels in db/db, ob/ob and DIO mice. These results suggest that HD047703 may be a potentially promising anti-diabetic agent.