• Title/Summary/Keyword: Modulation

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Treatment with Rutin - A Therapeutic Strategy for Neutrophil-Mediated Inflammatory and Autoimmune Diseases - Anti-inflammatory Effects of Rutin on Neutrophils -

  • Nikfarjam, Bahareh Abd;Adineh, Mohtaram;Hajiali, Farid;Nassiri-Asl, Marjan
    • Journal of Pharmacopuncture
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    • v.20 no.1
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    • pp.52-56
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    • 2017
  • Objectives: Neutrophils represent the front line of human defense against infections. Immediately after stimulation, neutrophilic enzymes are activated and produce toxic mediators such as pro-inflammatory cytokines, nitric oxide (NO) and myeloperoxidase (MPO). These mediators can be toxic not only to infectious agents but also to host tissues. Because flavonoids exhibit antioxidant and anti-inflammatory effects, they are subjects of interest for pharmacological modulation of inflammation. In the present study, the effects of rutin on stimulus-induced NO and tumor necrosis factor $(TNF)-{\alpha}$ productions and MPO activity in human neutrophils were investigated. Methods: Human peripheral blood neutrophils were isolated using Ficoll-Hypaque density gradient centrifugation coupled with dextran T500 sedimentation. The cell preparations containing > 98% granulocytes were determined by morphological examination through Giemsa staining. Neutrophils were cultured in complete Roswell Park Memorial Institute (RPMI) medium, pre-incubated with or without rutin ($25{\mu}M$) for 45 minutes, and stimulated with phorbol 12-myristate 13-acetate (PMA). Then, the $TNF-{\alpha}$, NO and MPO productions were analyzed using enzyme-linked immunosorbent assay (ELISA), Griess Reagent, and MPO assay kits, respectively. Also, the viability of human neutrophils was assessed using tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), and neutrophils were treated with various concentrations of rutin ($1-100{\mu}M$), after which MTT was appended and incubated at $37^{\circ}C$ for 4 hour. Results: Rutin at concentrations up to $100{\mu}M$ did not affect neutrophil viability during the 4-hour incubation period. Rutin significantly decreased the NO and $TNF-{\alpha}$ productions in human peripheral blood neutrophils compared to PMA-control cells (P < 0.001). Also, MPO activity was significantly reduced by rutin (P < 0.001). Conclusion: In this in vitro study, rutin had an anti-inflammatory effect due to its inhibiting NO and $TNF-{\alpha}$ productions, as well as MPO activity, in activated human neutrophils. Treatment with rutin may be considered as a therapeutic strategy for neutrophil-mediated inflammatory/autoimmune diseases.

Changes of Regional Homogeneity and Amplitude of Low Frequency Fluctuation on Resting-State Induced by Acupuncture (침자극에 의한 안정성 네트워크 변화를 관찰하기 위한 Regional Homogeneity와 Amplitude of Low Frequency Fluctuation의 변화 비교: fMRI연구)

  • Yeo, Sujung
    • Korean Journal of Acupuncture
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    • v.30 no.3
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    • pp.161-170
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    • 2013
  • Objectives : Our study aimed to investigate the sustained effects of sham (SHAM) and verum acupuncture (ACUP) into the post-stimulus resting state. Methods : In contrast to previous studies, in order to define the changes in resting state induced by acupuncture, changes were evaluated with a multi-method approach by using regional homogeneity (ReHo) and amplitude of low frequency fluctuation (ALFF). Twelve healthy participants received SHAM and ACUP stimulation right GB34 (Yanglingquan) and the neural changes between post- and pre-stimulation were detected. Results : The following results were found; in both ReHo and ALFF, the significant foci of; left and right middle frontal gyrus, left medial frontal gyrus, left superior frontal gyrus, and right posterior cingulate cortex, areas that are known as a default mode network, showed increased connectivity. In addition, in ReHo, but not in ALFF, brain activation changes in the insula, anterior cingulate cortex, and the thalamus, which are associated with acupuncture pain modulation, were found. Conclusions : In this study, results obtained by using ReHo and ALFF, showed that acupuncture can modulate the post-stimulus resting state and that ReHo, but not ALFF, can also detect the neural changes that were induced by the acupuncture stimulations. Although more future studies with ReHo and ALFF will be needed before any firm conclusions can be drawn, our study shows that particularly ReHo could be an interesting method for future clinical neuroimaging studies on acupuncture.

Effect of Diallyl Disulfide on Heme Oxygenase-1 Expression in Human Hepatoma Cell Line HepG2 (인간 간암세포주 HepG2에서 heme oxygenase-1 발현에 대한 diallyl disulfide의 효과)

  • Kim, Kang-Mi;Lee, Sang-Kwon;Park, Young-Chul
    • Journal of Life Science
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    • v.21 no.7
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    • pp.1046-1051
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    • 2011
  • Diallyl disulfide (DADS), the most prevalent oil-soluble organosulfur compound in garlic, is known to have diverse biological activities, including anticarcinogenic, antiatherosclerotic, antiinflammatory, and antioxidant actions. In this study, we investigated the effect of DADS on the expression of heme oxygenase-1 (HO-1) in human liver hepatoma cell line HepG2. Treatment of HepG2 cells by DADS evoked a dose-dependent growth inhibition without significant toxicity to the cells, and also induced the expression of transcription factor Nrf2. However, DADS did not have any enhancing effect on transcription and translation of HO-1 expression in HepG2 cells. In addition, DADS efficiently blocked protein synthesis of HO-1 in HepG2 cells stimulated by CoPP or hemin. But, DADS did not decrease the content of transcripts of HO-1 gene stimulated by CoPP, with accumulation of Nrf2 and small Maf in the nucleus. Based on these results, we conclude that DADS inhibits HO-1 expression by modulation of translational level of CoPP or hemin-induced HO-1 expression in HepG2 cells.

Cordycepin Induced Apoptosis via Intracellular Ca2+ Modulation and Mitochondrial Dysfunction in Human Prostate Cancer PC-3 Cells (전립선암 세포주인 PC-3에서 cordycepin에 의해 유도된 세포 내 칼슘농도 변화와 미토콘드리아 기능 상실을 통한 세포사멸 유도)

  • Kang, Dong-Min;Kim, Kwang-Youn;Yu, Sun-Nyoung;Jin, Young-Rang;Jeon, Hyun-Joo;Kim, Sang-Hun;Chun, Sung-Sik;Ko, Hack-Ryong;Ahn, Soon-Cheol
    • Journal of Life Science
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    • v.21 no.3
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    • pp.451-458
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    • 2011
  • Cordycepin (3'-deoxyadenosine), a nucleoside derivative isolated from Cordyceps militaris, is reported to have antitumor effects. However, neither its molecular mechanism nor its molecular targets are well understood. In the present study, molecular mechanisms for the anti-tumor effects of cordycepin were investigated in human prostate cancer PC-3 cells. The MTT assay was used to detect cell viability. Annexin V/FITC assay, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), and $Ca^{2+}$ flux were used to assess for the presence of apoptosis. Western blot analysis was used to detect protein expression. Treatment of cordycepin resulted in significantly decreased cell viability of PC-3 cells in a dose- and time-dependent manner. A dose-dependent apoptotic cell death was also measured by flow cytometery analysis. Molecular mechanistic studies of apoptosis unraveled cordycepin treatment resulted in significant mitochondrial dysfunction, ROS production, and elevation of $Ca^{2+}$ concentrations. These phenomena were followed activation of caspase-3, subsequently leading to PARP cleavage and cell apoptosis. Taken together, cordycepin induces apoptosis in PC-3 cells through regulation of a mitochondrial mediated pathway.

Antioxidative and Anti-inflammatory Activities of Ardisia arborescens Ethanol Extract (Ardisia arborescens 에탄올 추출물의 항산화 및 항염증 활성)

  • Jin, Kyong-Suk;Lee, Ji Young;Kwon, Hyun Ju;Kim, Byung Woo
    • Journal of Life Science
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    • v.24 no.7
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    • pp.713-720
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    • 2014
  • In this study, the antioxidative and anti-inflammatory activities of Ardisia arborescens ethanol extract (AAEE) were evaluated using in vitro assays and a cell culture model system. AAEE exhibited potent scavenging activity against 1,1-diphenyl-2-picryl hydrazyl (DPPH), similar to ascorbic acid, which was used as a positive control. Moreover, AAEE effectively suppressed lipopolysaccharide (LPS)- and hydrogen peroxide ($H_2O_2$)-induced reactive oxygen species (ROS) in RAW 264.7 cells. Furthermore, AAEE induced the expression of antioxidative enzymes, heme oxygenase 1 (HO-1), and thioredoxin reductase 1 (TrxR1), in addition to their upstream transcription factor, nuclear factor-E2-related factor 2 (Nrf2), in a dose-dependent manner. The upstream signaling pathways of mitogen-activated protein kinases (MAPKs) might regulate the modulation of HO-1, TrxR1, and Nrf2 expression. On the other hand, AAEE inhibited LPS-induced nitric oxide (NO) formation, without cytotoxicity. Suppression of NO formation was the result of AEEE-induced down-regulation of inducible NO synthase (iNOS). The suppression of NO and iNOS by AAEE might be modulated by their upstream transcription factor, nuclear factor (NF)-${\kappa}B$, and activator protein (AP)-1 pathways. Taken together, these results provide important new insights into the antioxidative and anti-inflammatory activities of A. arborescens. AAAEE might represent a promising material in the field of nutraceuticals.

Development of Two-Step Temperature Process to Modulate the Physicochemical Properties of β-lactoglobulin Nanoparticles

  • Ha, Ho-Kyung;Nam, Gyeong-Won;Khang, Dongwoo;Park, Sung Jean;Lee, Mee-Ryung;Lee, Won-Jae
    • Food Science of Animal Resources
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    • v.37 no.1
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    • pp.123-133
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    • 2017
  • The development of a new manufacturing process, a two-step temperature treatment, to modulate the physicochemical properties of nanoparticles including the size is critical. This is because its physicochemical properties can be key factors affecting the cellular uptake and the bioavailability of bioactive compounds encapsulated in nanoparticles. The aims of this study were to produce (beta-lactoglobulin) ${\beta}-lg$ nanoparticles and to understand how two-step temperature treatment could affect the formation and physicochemical properties of ${\beta}-lg$ nanoparticles. The morphological and physicochemical properties of ${\beta}-lg$ nanoparticles were determined using atomic force microscopy and a particle size analyzer, respectively. Circular dichroism spectroscopy was used to investigate the secondary structure of ${\beta}-lg$. The surface hydrophobicity and free thiol groups of ${\beta}-lg$ were increased with a decrease in sub-ambient temperature and an increase in mild heat temperature. As sub-ambient temperature was decreased, a decrease in ${\alpha}-helical$ content and an increase in ${\beta}-sheet$ content were observed. The two-step temperature treatment firstly involved a sub-ambient temperature treatment from 5 to $20^{\circ}C$ for 30 min, followed secondly by a mild heat temperature treatment from 55 to $75^{\circ}C$ for 10 min. This resulted in the production of spherically-shaped particles with a size ranging from 61 to 214 nm. Two-way ANOVA exhibited the finding that both sub-ambient and mild heat temperature significantly (p<0.0001) affected the size of nanoparticles. Zeta-potential values of ${\beta}-lg$ nanoparticles were reduced with increasing mild heat temperature. In conclusion, two-step temperature treatment was shown to play an important role in the manufacturing process - both due to its inducement of the conformational changes of ${\beta}-lg$ during nanoparticle formation, and due to its modulation of the physicochemical properties of ${\beta}-lg$ nanoparticles.

Ethyl acetate fraction of GGEx18 modulates feeding efficiency ratio and blood leptin level in high fat diet-fed obese mice (GGEx18의 ethyl acetate 분획물에 의한 고지방식이 비만 마우스의 식이효율과 혈중 leptin 농도에 미치는 영향)

  • Park, Ki-Jeong;Lee, Hee-Young;Lee, Hye-Rim;Yoon, Mi-Chung;Park, Sun-Dong;Lee, Yong-Tae;Shen, Zhi-Bin;Cui, Hong-Hua;Shin, Soon-Shik
    • Herbal Formula Science
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    • v.19 no.1
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    • pp.219-231
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    • 2011
  • Objectives : This study was designed to determine the effects of the GGEx18 ethyl acetate fraction(EF) on body weight gain, feeding efficiency ratio, and obesity-related factors in plasma as well as histology of liver and adipose tissues using high fat diet-fed male C57BL/6N obese mice. Methods : 8 weeks old, high fat diet-fed obese male mice were divided into 5 groups: C57BL/6N normal, control, EF(1), EF(2) and EF(3). After mice were treated with EF for 9 weeks, we measured body weight gain, food intake, feeding efficiency ratio, fat weight, plasma leptin and lipid levels. We also analysed histology of liver and adipose tissues on high fat diet-fed male C57BL/6N obese mice. Results : Compared with control, EF-treated mice had significantly lower body weight gain and feeding efficiency ratio. Consistent with the effects on body weight gain, EF significantly decreased the adipose tissue weight compared with control. Consistent with the effects on feeding efficiency ratio, EF significantly decreased plasma leptin concentrations compared with control. EF reduced the size of adipocytes as well as hepatic lipid accumulation compared with control. EF seems to be safe since not only the plasma levels of ALT and AST are within the normal range, but also EF did not show any toxic effects on organs. EF(3) was most effective among EF(1), EF(2), and EF(3) at doses of 25, 50, and 100 mg/kg, respectively. Conclusions : These results demonstrate that EF effectively reduces body weight gain, feeding efficiency ratio in high fat diet-fed obese mice, leading to the modulation of obesity. In addition, EF decreases the size of adipocytes and improves plasma lipids and controls hepatic lipid accumulation, suggesting that EF may act as a therapeutic agent for obesity.

Regulation of cellular functions of p53 by ubiquitination (유비퀴틴화에 의한 세포 내 p53의 기능 조절)

  • Jung, Jin-Hyuk;Lee, Joon-Young;Lee, Sun-Mi;Choe, Tae-Boo;An, Sung-Kwan
    • KSBB Journal
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    • v.24 no.3
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    • pp.217-226
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    • 2009
  • p53 undergoes various post-translational modifications, including phosphorylation, ubiquitination, sumoylation, acetylation, methylation, and poly(ADP-ribosyl)ation. Modification of p53 widely affects to various functions of p53. Acetylation and phosphorylation of p53 have been studied for regulating its transcriptional activity which is observed in various stress condition. Otherwise, ubiquitination of p53 by Mdm2 has been well-studied as a canonical ubiquitin-mediated proteasomal degradation pathway. Moreover several investigators have recently reported that ubiquitination of p53 modulates not only its proteasome-dependent degradation by poly-ubiquitination but also its localization and transcriptional activity by mono-ubiquitination which usually does not serve the proteasome dependent degradation. Here we review recent studies on the cellular functions of p53 regulated by post-translational modifications, particularly focusing on mechanisms of ubiquitination.

THE EFFECT OF DIFFERENTIAL MODULATION OF N-METHYL-D-ASPARTATE RECEPTOR ON THE PROLIFERATION OF PRIMARY CULTURED NORMAL HUMAN ORAL KERATINOCYTES: DNA SYNTHESIS RATE ANALYSIS (N-methyl-D-aspartate 수용기의 다양한 조절이 일차 배양된 정상사람구강각화세포의 증식에 미치는 영향; DNA 합성율 평가)

  • Kim, In-Soo;Paik, Ki-Suk;Chang, Mi-Sook;Lee, Won;Lee, Seung-Pyo
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.33 no.2
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    • pp.124-130
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    • 2007
  • In the present study, I investigated the effects of N-methyl-D-aspartate (NMDA), arachidonic acid (AA), and Nitric Oxide Synthase Inhibitor (NOSI), alone or in combination, on the proliferation of cultured primary normal human oral keratinocytes (NHOK). The purpose of this study was therefore the preliminary study for the examination of the interaction between these agents and NHOK in order to elucidate the mechanisms by which epithelial growth and regeneration are regulated. NHOK were obtained from gingival tissue of 20 individuals aged 20 to 29, and third passage (P3) cells were used for this study. The DNA synthesis was measured by the BrdU assay. Addition of low concentration of AA ($1{\mu}M$) and high concentration of AA with NMDA group (NMDA+AA $10{\mu}M$) made DNA synthesis rate increase significantly at the early stage. Adding NNA ($10{\mu}M$) affected DNA synthesis rate to increase significantly in 4 hours. At the early stage, DNA synthesis was significantly active in the NOS-I with NMDA groups than in the control and the NMDA-only group, while it didn't become statistically meaningful in 24 hours. AA $1{\mu}M$ and NNA $10{\mu}M$ may induce the proliferation of the NHOK independently and NOS-I may induce the proliferation of the NHOK with NMDA. These reactions might be related to the NMDA receptor in the cell and the change of the intracellular calcium ion concentration.

Performance Evaluation of the Iterative Demapping and Decoding based DVB-T2 BICM module (Iterative Demapping and Decoding 기반 차세대 유럽형 디지털 지상파 방송 시스템(DVB-T2)의 BICM 성능 평가)

  • Jeon, Eun-Sung;Seo, Jeong-Wook;Yang, Jang-Hoon;Kim, Dong-Ku
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.36 no.2A
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    • pp.172-178
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    • 2011
  • In this paper, the performance of bit interleaved of coded and modulation(BICM) module of the second generation of digital terrestrial television broadcasting system(DVB-T2) is evaluated with the help of computer simulation. The frame error rate performance is studied in AWGN, Rayleigh fading and 15% erasure channels. In addition, iterative receiver is considered that exchanges extrinsic information between the rotated demapper and the LDPC decoder. Through the simulation it is observed that under the flat fading Rayleigh channel, about 1.2dB gain at FER of $10^{-4}$ is introduced when rotated constellation and iterative demapping and decoding are employed. Under the 15% earasure channel, rotated constellation gives performance gain of about 5dB at BER of $10^{-4}$ and when IDD is applied, additional performance gain of about 3dB can be achieved.