• Title/Summary/Keyword: Modulation

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Modulation of Chemical Stability and Cytotoxic Effects of Epigallocatechin-3-gallate by Different Types of Antioxidants (Epigallocatechin-3-gallate의 화학안정성 및 세포독성에 미치는 각종 항산화제의 영향)

  • Kim, Mi-Ri;Kang, Smee;Hong, Jung-Il
    • Korean Journal of Food Science and Technology
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    • v.43 no.4
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    • pp.483-489
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    • 2011
  • Epigallocatechin-3-gallate (EGCG) is a polyphenolic compound frequently found in green tea, and its physiological actions have been extensively investigated. In the present study, changes in chemical stability and cytotoxic properties of EGCG in the presence of different types of antioxidants were investigated. The antioxidants used modulated the chemical stability of EGCG. Superoxide dismutase (SOD) significantly increased EGCG stability; EGCG was less stable in the presence of catalase. Ascorbic acid, N-acetylcysteine (NAC), and glutathione (GSH) stabilized EGCG concentration dependently. The $H_2O_2$ level generated from EGCG was decreased by catalase, SOD, and NAC but not by GSH. The cytotoxic effects of EGCG also decreased in the presence of NAC, catalase, and SOD. GSH, however, showed a complicated modulatory pattern according to the EGCG and GSH concentrations, and ascorbic acid rather enhanced EGCG toxicity. The results suggest that certain antioxidants could modulate the cytotoxic properties of EGCG in a cell culture system not only by removing reactive oxygen species but by modulating chemical stability and other factors, which should be considered carefully when studying reactive oxygen species-dependent mechanisms of EGCG.

Cisplatin Suppresses Proliferation of Ovarian Cancer Cells through Inhibition Akt and Modulation MAPK Pathways (Cisplatin의 난소암 세포 증식 억제에 관한 신호 전달 기전)

  • Choi, Jae-Sun
    • Korean Journal of Clinical Laboratory Science
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    • v.52 no.1
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    • pp.62-68
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    • 2020
  • Cisplatin (CDDP) is a chemotherapy agent used for patients with ovarian cancers. CDDP activates multiple signaling pathways, which causes various cellular reactions according to the type of cancer cells. Therefore, it is difficult to clearly conclude its signaling pathways. The purpose of this study is to determine the role of the signal protein of Akt/ERK1/2 and MAPK by CDDP-induced apoptosis in ovarian cancer cells (SKOV3). As a result, the number of apoptosis increased according to the TUNEL assay, and flow cytometric analysis confirmed that the percentage of sub-G1 early apoptosis was 8.73% higher than the control. The PARP and caspase-3 activity that appeared in the process of apoptosis was increased and the Bcl-2 expression was decreased. It was verified that the Akt and ERK1/2 activity was decreased, and p38 and JNK activity increased in a time dependent fashion. In conclusion, these results demonstrate that cisplatin inhibits the proliferation of ovarian cancer cells by inhibiting Akt activity and induces apoptosis by modulating the MAPK signaling pathway. However, a decrease in the ERK1/2 activity by CDDP was the opposite result to the result shown from the HeLa cells. For this reason, further research on signaling pathways is necessary. These results are expected to be useful for ovarian cancer treatment strategies targeting the MAPK pathway.

Stem Cells and Cell-Cell Communication in the Understanding of the Role of Diet and Nutrients in Human Diseases

  • Trosko James E.
    • Journal of Food Hygiene and Safety
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    • v.22 no.1
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    • pp.1-14
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    • 2007
  • The term, "food safety", has traditionally been viewed as a practical science aimed at assuring the prevention acute illnesses caused by biological microorganisms, and only to a minor extent, chronic diseases cause by chronic low level exposures to natural and synthetic chemicals or pollutants. "food safety" meant to prevent microbiological agents/toxins in/on foods, due to contamination any where from "farm to Fork", from causing acute health effects, especially to the young, immune-compromised, genetically-predisposed and elderly. However, today a broader view must also include the fact that diet, perse (nutrients, vitamins/minerals, calories), as well as low level toxins and pollutant or supplemented synthetic chemicals, can alter gene expressions of stem/progenitor/terminally-differentiated cells, leading to chronic inflammation and other mal-functions that could lead to diseases such as cancer, diabetes, atherogenesis and possibly reproductive and neurological disorders. Understanding of the mechanisms by which natural or synthetic chemical toxins/toxicants, in/on food, interact with the pathogenesis of acute and chronic diseases, should lead to a "systems" approach to "food safety". Clearly, the interactions of diet/food with the genetic background, gender, and developmental state of the individual, together with (a) interactions of other endogenous/exogenous chemicals/drugs; (b) the specific biology of the cells being affected; (c) the mechanisms by which the presence or absence of toxins/toxicants and nutrients work to cause toxicities; and (d) how those mechanisms affect the pathogenesis of acute and/or chronic diseases, must be integrated into a "system" approach. Mechanisms of how toxins/toxicants cause cellular toxicities, such as mutagenesis; cytotoxicity and altered gene expression, must take into account (a) irreversible or reversal changes caused by these toxins or toxicants; (b)concepts of thresholds or no-thresholds of action; and (c) concepts of differential effects on stem cells, progenitor cells and terminally differentiated cells in different organs. This brief Commentary tries to illustrate this complex interaction between what is on/in foods with one disease, namely cancer. Since the understanding of cancer, while still incomplete, can shed light on the multiple ways that toxins/toxicants, as well as dietary modulation of nutrients/vitamins/metals/ calories, can either enhance or reduce the risk to cancer. In particular, diets that alter the embryo-fetal micro-environment might dramatically alter disease formation later in life. In effect "food safety" can not be assessed without understanding how food could be 'toxic', or how that mechanism of toxicity interacts with the pathogenesis of any disease.

Implementation and Evaluation of Electroglottograph System (전기성문전도(EGG) 시스템의 개발 및 평가)

  • 김기련;김광년;왕수건;허승덕;이승훈;전계록;최병철;정동근
    • Journal of Biomedical Engineering Research
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    • v.25 no.5
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    • pp.343-349
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    • 2004
  • Electroglottograph(EGG) is a signal recorded from the vocal cord vibration by measuring electrical impedance across the vocal folds through the neck skin. The purpose of this study was to develop EGG system and to evaluate possibility for the application on speech analysis and laryngeal disease diagnosis. EGG system was composed of two pairs of ring electrodes, tuned amplifier, phase sensitive detector, low pass filter, and auto-gain controller. It was designed to extract electric impedance after detecting by amplitude modulation method with 2.7MHz carrier signal. Extracted signals were transmitted through line-in of PC sound card, sampled and quantized. Closed Quotient(CQ), Speed Quotient(SQ), Speed Index(SI), fundamental frequency of vocal cord vibration(F0), pitch variability of vocal fold vibration (Jitter), and peak-to-peak amplitude variability of vocal fold vibration(Shimmer) were analyzed as EGG parameters. Experimental results were as follows: the faster vocal fold vibration, the higher values in CQ parameter and the lower values in SQ and SI parameters. EGG and speech signals had the same fundamental frequency. CQ, SQ, and SI were significantly different between normal subjects and patients with laryngeal cancer. These results suggest that it is possible to implement portable EGG system to monitor the function of vocal cord and to test functional changes of the glottis.

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.