• Title/Summary/Keyword: agent model

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Anti-inflammatory Activity on LPS-stimulated in vitro RAW 264.7 Cells and in vivo Zebrafish of Heterosigma akshiwo

  • Kim, Junseong;Choi, Youn Kyung;Lee, Ji-Hyeok;Kim, Seo-Young;Kim, Hyun-Soo;Jeon, You-Jin;Heo, Soo-Jin
    • Journal of Chitin and Chitosan
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    • v.22 no.3
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    • pp.185-193
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    • 2017
  • Red tide Heterosigma akashiwo (H. akashiwo), a microscopic alga of the class Raphidophyceae, causes extensive damage to all marine ecosystems. It is essential to reduce the damage to marine ecosystems for them to be used as a resource. In this study, we used organic solvent fractionation to obtain an ethyl acetate-methanol extract from H. akashiwo (HAEM80) and then evaluated its anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and a zebrafish model. HAME80 markedly inhibited the production of nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$). It also down-regulated the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and decreased the secretion of interleukin-$1{\beta}$ ($IL-1{\beta}$) in LPS-stimulated RAW 264.7 cells. HAME80 reduced yolk edema and improved the survival rate of LPS-stimulated zebrafish embryos; in addition, the extract significantly reduced the production of ROS and NO and attenuated cell death in this model. Gas chromatography-mass spectrometry (GC-MS) of the extract was used to confirm the identity of peaks 1-20. Taken together, our data suggest that H. akashiwo is a beneficial anti-inflammatory agent.

3D-culture models as drug-testing platforms in canine lymphoma and their cross talk with lymph node-derived stromal cells

  • An, Ju-Hyun;Song, Woo-Jin;Li, Qiang;Bhang, Dong-Ha;Youn, Hwa-Young
    • Journal of Veterinary Science
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    • v.22 no.3
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    • pp.25.1-25.16
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    • 2021
  • Background: Malignant lymphoma is the most common hematopoietic malignancy in dogs, and relapse is frequently seen despite aggressive initial treatment. In order for the treatment of these recurrent lymphomas in dogs to be effective, it is important to choose a personalized and sensitive anticancer agent. To provide a reliable tool for drug development and for personalized cancer therapy, it is critical to maintain key characteristics of the original tumor. Objectives: In this study, we established a model of hybrid tumor/stromal spheroids and investigated the association between canine lymphoma cell line (GL-1) and canine lymph node (LN)-derived stromal cells (SCs). Methods: A hybrid spheroid model consisting of GL-1 cells and LN-derived SC was created using ultra low attachment plate. The relationship between SCs and tumor cells (TCs) was investigated using a coculture system. Results: TCs cocultured with SCs were found to have significantly upregulated multidrug resistance genes, such as P-qp, MRP1, and BCRP, compared with TC monocultures. Additionally, it was revealed that coculture with SCs reduced doxorubicin-induced apoptosis and G2/M cell cycle arrest of GL-1 cells. Conclusions: SCs upregulated multidrug resistance genes in TCs and influenced apoptosis and the cell cycle of TCs in the presence of anticancer drugs. This study revealed that understanding the interaction between the tumor microenvironment and TCs is essential in designing experimental approaches to personalized medicine and to predict the effect of drugs.

Effect of hydrogen-rich water on the lactic acid level in metformin-treated diabetic rats under hypoxia

  • Zhao, Chuan;Guo, Yushu;Wang, Ruoxi;Cheng, Cheng;Chen, Xiangmei
    • The Korean Journal of Physiology and Pharmacology
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    • v.25 no.6
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    • pp.517-523
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    • 2021
  • The present study aims to investigate the impact of hydrogen-rich water on the lactic acid level in metformin-treated diabetic rats under hypoxia. Thirty Sprague-Dawley rats were randomly divided into five groups, including normal diet group, and diabetes model (DM) group, DM + metformin treatment (DMM) group, DMM + hypoxia treatment (DMMH) group and DMMH + hydrogen-rich water (DMMHR) group. We found that the levels of lactic acid, pyruvate and lactate dehydrogenase were significantly lower in the blood of DMMHR group than DMMH group. Superoxide dismutase and glutathione levels in liver and heart were significantly higher in DMMH group after hydrogen-rich water treatment, while malondialdehyde and oxidized glutathione levels were decreased in DMMHR group when compared with DMMH group, which indicates that hydrogen-rich water could reduce oxidative stress. qPCR analysis demonstrated that that pro-apoptotic genes Bax/Caspase-3 were upregulated in DM group and metformin treatment suppressed their upregulation (DMM group). However, hypoxic condition reversed the effect of metformin on apoptotic gene expression, and hydrogen-rich water showed little effect on these genes under hypoxia. HE staining showed that hydrogen-rich water prevented myocardial fiber damages under hypoxia. In summary, we conclude that hydrogen-rich water could prevent lactate accumulation and reduce oxidant stress in diabetic rat model to prevent hypoxia-induced damages. It could be served as a potential agent for diabetes patients with metformin treatment to prevent lactic acidosis and reduce myocardial damages under hypoxic conditions.

Immunostimulatory Effects of Blueberry Yeast Fermented Powder Against Cyclophosphamide-induced Immunosuppressed Model (Cyclophosphamide에 의한 면역저하 동물모델에서 블루베리 효모 발효 분말의 면역증강 효과)

  • Jeong, Do Youn;Yang, Hee Jong;Jeong, Su Ji;Kim, Min Guk;Yun, Chi Young;Lee, Hak Yong;Lee, Yang Hee;Shin, Dong Yeop;Yang, Yea gin;Lee, Hae Seong;Park, Young Mi
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.33 no.1
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    • pp.48-55
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    • 2019
  • Current studies have been reported that fruits such as berries may contain both antioxidant and antitumor polyphenols that may be important in this regard. We investigated the immunostimulatory effect of fermented blueberry (Vaccinium corymbosum L.) on cyclophosphamide-induced immunosuppression in animal model. Rats were administered blueberry yeast fermented powder (BYFP) at doses 30, 100, and 300 mg/kg for 4 weeks after cyclophosphamide (Cy) treatment, respectively. The immunomodulatory effect of BYFP were measured both in vitro and in vivo, and the changes of blood components were also analyzed. We found that BYFP recovered immunosuppression-mediated decreased liver, spleen, and thymus weights as well as up regulation of white blood cell, lymphocyte, and neutrophil in blood. Moreover, BYFP up-regulated IL-2, TNF-${\alpha}$, and IFN-${\gamma}$ pro-inflammatory cytokine production compared to immune suppressed control group, respectively. According to histological studies, BYFP regenerated significantly on Cy-mediated injured spleen at the high doses (BYFP 300) comparison with Cy-treated groups (immunosuppression). Collectively, these findings suggest that BYFP may have the potential as a dietary immunostimulatory agent.

Effect of Lactobacillus casei fermented Senna tora L. seeds and its active compound via muscarinic M3 signaling on the improvement of intestinal function in rats

  • Jang, Ji-Hun;Lee, Ki-Ho;Nho, Jong-Hyun;Lee, Hyun-Joo;Yang, Beo-Dul;Park, Ho;Cho, Hyun-Woo;An, Byeong-Kwan;Kim, Sun-Ra;Yong, Ju-Hyun;Park, Ro-Dong;Jung, Ho-Kyung
    • Journal of Applied Biological Chemistry
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    • v.63 no.4
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    • pp.365-373
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    • 2020
  • We previously reported the potential of Senna tora L. seeds fermented by Lactobacillus casei (FSL) as a laxative agent in a loperamide-induced constipation rat model. Here, we examine the mechanism of action of FSL and its bioactive compound, revealed herein, on loperamide-induced constipation Sprague Dawley rat model. We identified the compound aurantio-obtusin (AO) using HPLC quantitative analysis. Rats were randomly assigned to six experimental groups (eight rats each)-normal and constipated groups (loperamide, FSL [100, 300, 500 mg/kg], and AO [1 mg/kg]). The FSL and AO-treated group showed an increase in the frequency, amount, and water content of feces in the constipated rat. Moreover, FSL and AO increased the intestinal transit speed in the constipated rat. Histological analysis revealed that FSL and AO recovered the intestinal mucus, the number of goblet cells, as well as thickness of the mucosa layer and muscle. Furthermore, the protein levels of the muscarinic acetylcholine receptor M3, which is involved in intestine contraction, were recovered in the FSL and AO-treated group. Its downstream signaling pathway (p-protein kinase C) was recovered by FSL and AO treatment. In conclusion, fermentation of S. tora L. seeds increases AO, which improves intestinal function, indicating that FSL is effective for treating constipation.

Inhibitory activity of gintonin on inflammation in human IL-1β-stimulated fibroblast-like synoviocytes and collagen-induced arthritis in mice

  • Kim, Mijin;Sur, Bongjun;Villa, Thea;Nah, Seung Yeol;Oh, Seikwan
    • Journal of Ginseng Research
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    • v.45 no.4
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    • pp.510-518
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    • 2021
  • Background: Gintonin is a newly derived glycolipoprotein from the roots of ginseng. The purpose of this study is to investigate the anti-arthritic efficacy of Gintonin on various proteases and inflammatory mediators that have an important role in arthritis. Methods: Fibroblast-like synoviocytes (FLS) were treated with Gintonin and stimulated with interleukin (IL)-1β 1 hour later. The antioxidant effect of Gintonin was measured using MitoSOX and H2DCFDA experiments. The anti-arthritic efficacy of Gintonin was examined by analyzing the expression levels of inflammatory mediators using RT-PCR, western blot, and ELISA. The phosphorylation of mitogen-activated protein kinase (MAPK) pathways and translocation of nuclear factor kappa B (NF-κB)/p65 into the nucleus were also analyzed using western blot, ELISA, and immunocytochemistry. Collagen-induced arthritis (CIA) mice model was used. Mice were orally administered with Gintonin (25, 50, and 100 mg/kg) every 2 days for 45 days. The body weight, arthritis score, squeaking score, and paw volume were measured as the behavioral parameters. After sacrifice, H&E and safranin-O staining were performed for histological analysis. Results: Gintonin significantly inhibited the expression of inflammatory intermediates. Gintonin prevented NF-κB/p65 from moving into the nucleus through the JNK and ERK MAPK phosphorylation in FLS cells. Moreover, Gintonin suppressed the symptoms of arthritis in the CIA mice model. Conclusion: As a result, the antioxidant and anti-inflammatory effects of Gintonin were demonstrated, and ultimately the anti-arthritic effect was proved. Collectively, Gintonin has a great potential as a therapeutic agent for arthritis treatment.

Protective effects of Populus tomentiglandulosa against cognitive impairment by regulating oxidative stress in an amyloid beta25-35-induced Alzheimer's disease mouse model

  • Kwon, Yu Ri;Kim, Ji-Hyun;Lee, Sanghyun;Kim, Hyun Young;Cho, Eun Ju
    • Nutrition Research and Practice
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    • v.16 no.2
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    • pp.173-193
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    • 2022
  • BACKGROUND/OBJECTIVES: Alzheimer's disease (AD) is one of the most representative neurodegenerative disease mainly caused by the excessive production of amyloid beta (Aβ). Several studies on the antioxidant activity and protective effects of Populus tomentiglandulosa (PT) against cerebral ischemia-induced neuronal damage have been reported. Based on this background, the present study investigated the protective effects of PT against cognitive impairment in AD. MATERIALS/METHODS: We orally administered PT (50 and 100 mg/kg/day) for 14 days in an Aβ25-35-induced mouse model and conducted behavioral experiments to test cognitive ability. In addition, we evaluated the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum and measured the production of lipid peroxide, nitric oxide (NO), and reactive oxygen species (ROS) in tissues. RESULTS: PT treatment improved the space perceptive ability in the T-maze test, object cognitive ability in the novel object recognition test, and spatial learning/long-term memory in the Morris water-maze test. Moreover, the levels of AST and ALT were not significantly different among the groups, indicating that PT did not show liver toxicity. Furthermore, administration of PT significantly inhibited the production of lipid peroxide, NO, and ROS in the brain, liver, and kidney, suggesting that PT protected against oxidative stress. CONCLUSIONS: Our study demonstrated that administration of PT improved Aβ25-35-induced cognitive impairment by regulating oxidative stress. Therefore, we propose that PT could be used as a natural agent for AD improvement.

Autism-Like Behavioral Phenotypes in Mice Treated with Systemic N-Methyl-D-Aspartate

  • Adil, Keremkleroo Jym;Gonzales, Edson Luck;Remonde, Chilly Gay;Boo, Kyung-Jun;Jeon, Se Jin;Shin, Chan Young
    • Biomolecules & Therapeutics
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    • v.30 no.3
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    • pp.232-237
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    • 2022
  • Autism spectrum disorder (ASD) having core characteristics of social interaction problems and repetitive behaviors and interests affects individuals at varying degrees and comorbidities, making it difficult to determine the precise etiology underlying the symptoms. Given its heterogeneity, ASD is difficult to treat and the development of therapeutics is slow due to the scarcity of animal models that are easy to produce and screen with. Based on the theory of excitation/inhibition imbalance in the brain with ASD which involves glutamatergic and/or GABAergic neurotransmission, a pharmacologic agent to modulate these receptors might be a good starting point for modeling. N-methyl-D-aspartic acid (NMDA) is an amino acid derivative acting as a specific agonist at the NMDA receptor and therefore imitates the action of the neurotransmitter glutamate on that receptor. In contrast to glutamate, NMDA selectively binds to and regulates the NMDA receptor, but not other glutamate receptors such as AMPA and kainite receptors. Given this role, we aimed to determine whether NMDA administration could result in autistic-like behavior in adolescent mice. Both male and female mice were treated with saline or NMDA (50 and 75 mg/kg) and were tested on various behavior experiments. Interestingly, acute NMDA-treated mice showed social deficits and repetitive behavior similar to ASD phenotypes. These results support the excitation/inhibition imbalance theory of ASD and that NMDA injection can be used as a pharmacologic model of ASD-like behaviors.

A study on narrative text analysis from the perspective of information processing - focusing on four computational methodologies (정보처리 관점에서의 서사 텍스트 분석에 관한 연구 - 네 가지 전산적 방법론을 중심으로)

  • Kwon, Hochang
    • Trans-
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    • v.13
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    • pp.141-169
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    • 2022
  • Analysis of narrative texts has been regarded as academically and practically important, and has been made from various perspectives and methods. In this paper, the computational narrative analysis methodology from the perspective of information processing was examined. From the point of view of information processing, the creation and acceptance of narrative is a bidirectional coding process mediated by narrative text, and narrative text can be said to be a multi-layered structured code. In this paper, four methodologies that share this point of view - character network analysis, text mining and sentiment analysis, continuity analysis of event composition, and knowledge analysis of narrative agents - were examined together with cases. Through this, the mechanism and possibility of computational methodology in narrative analysis were confirmed. In conclusion, the significance and side effects of computational narrative analysis were examined, and the necessity of designing a human-computer collaboration model based on the consilience of the humanities and science/technology was discussed. Based on this model, it was argued that aesthetically creative, ethically good, politically progressive, and cognitively sophisticated narratives could be made more effectively.

A slide reinforcement learning for the consensus of a multi-agents system (다중 에이전트 시스템의 컨센서스를 위한 슬라이딩 기법 강화학습)

  • Yang, Janghoon
    • Journal of Advanced Navigation Technology
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    • v.26 no.4
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    • pp.226-234
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    • 2022
  • With advances in autonomous vehicles and networked control, there is a growing interest in the consensus control of a multi-agents system to control multi-agents with distributed control beyond the control of a single agent. Since consensus control is a distributed control, it is bound to have delay in a practical system. In addition, it is often difficult to have a very accurate mathematical model for a system. Even though a reinforcement learning (RL) method was developed to deal with these issues, it often experiences slow convergence in the presence of large uncertainties. Thus, we propose a slide RL which combines the sliding mode control with RL to be robust to the uncertainties. The structure of a sliding mode control is introduced to the action in RL while an auxiliary sliding variable is included in the state information. Numerical simulation results show that the slide RL provides comparable performance to the model-based consensus control in the presence of unknown time-varying delay and disturbance while outperforming existing state-of-the-art RL-based consensus algorithms.