• Title/Summary/Keyword: Reduced mechanism

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Justicidin A Reduces β-Amyloid via Inhibiting Endocytosis of β-Amyloid Precursor Protein

  • Chun, Yoon Sun;Kwon, Oh-Hoon;Oh, Hyun Geun;Cho, Yoon Young;Yang, Hyun Ok;Chung, Sungkwon
    • Biomolecules & Therapeutics
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    • v.27 no.3
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    • pp.276-282
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    • 2019
  • ${\beta}$-amyloid precursor protein (APP) can be cleaved by ${\alpha}$-, and ${\gamma}$-secretase at plasma membrane producing soluble ectodomain fragment ($sAPP{\alpha}$). Alternatively, following endocytosis, APP is cleaved by ${\beta}$-, and ${\gamma}$-secretase at early endosomes generating ${\beta}$-amyloid ($A{\beta}$), the main culprit in Alzheimer's disease (AD). Thus, APP endocytosis is critical for $A{\beta}$ production. Recently, we reported that Monsonia angustifolia, the indigenous vegetables consumed in Tanzania, improved cognitive function and decreased $A{\beta}$ production. In this study, we examined the underlying mechanism of justicidin A, the active compound of M. angustifolia, on $A{\beta}$ production. We found that justicidin A reduced endocytosis of APP, increasing $sAPP{\alpha}$ level, while decreasing $A{\beta}$ level in HeLa cells overexpressing human APP with the Swedish mutation. The effect of justicidin A on $A{\beta}$ production was blocked by endocytosis inhibitors, indicating that the decreased APP endocytosis by justicidin A is the underlying mechanism. Thus, justicidin A, the active compound of M. angustifolia, may be a novel agent for AD treatment.

Alleviation of Senescence via ATM Inhibition in Accelerated Aging Models

  • Kuk, Myeong Uk;Kim, Jae Won;Lee, Young-Sam;Cho, Kyung A;Park, Joon Tae;Park, Sang Chul
    • Molecules and Cells
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    • v.42 no.3
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    • pp.210-217
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    • 2019
  • The maintenance of mitochondrial function is closely linked to the control of senescence. In our previous study, we uncovered a novel mechanism in which senescence amelioration in normal aging cells is mediated by the recovered mitochondrial function upon Ataxia telangiectasia mutated (ATM) inhibition. However, it remains elusive whether this mechanism is also applicable to senescence amelioration in accelerated aging cells. In this study, we examined the role of ATM inhibition on mitochondrial function in Hutchinson-Gilford progeria syndrome (HGPS) and Werner syndrome (WS) cells. We found that ATM inhibition induced mitochondrial functional recovery accompanied by metabolic reprogramming, which has been known to be a prerequisite for senescence alleviation in normal aging cells. Indeed, the induced mitochondrial metabolic reprogramming was coupled with senescence amelioration in accelerated aging cells. Furthermore, the therapeutic effect via ATM inhibition was observed in HGPS as evidenced by reduced progerin accumulation with concomitant decrease of abnormal nuclear morphology. Taken together, our data indicate that the mitochondrial functional recovery by ATM inhibition might represent a promising strategy to ameliorate the accelerated aging phenotypes and to treat age-related disease.

Studies on vibration control effects of a semi-active impact damper for seismically excited nonlinear building

  • Lu, Zheng;Zhang, Hengrui;Masri, Sami F.
    • Smart Structures and Systems
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    • v.24 no.1
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    • pp.95-110
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    • 2019
  • The semi-active impact damper (SAID) is proposed to improve the damping efficiency of traditional passive impact dampers. In order to investigate its damping mechanism and vibration control effects on realistic engineering structures, a 20-story nonlinear benchmark building is used as the main structure. The studies on system parameters, including the mass ratio, damping ratio, rigid coefficient, and the intensity of excitation are carried out, and their effects both on linear and nonlinear indexes are evaluated. The damping mechanism is herein further investigated and some suggestions for the design in high-rise buildings are also proposed. To validate the superiority of SAID, an optimal passive particle impact damper ($PID_{opt}$) is also investigated as a control group, in which the parameters of the SAID remain the same, and the optimal parameters of the $PID_{opt}$ are designed by differential evolution algorithm based on a reduced-order model. The numerical simulation shows that the SAID has better control effects than that of the optimized passive particle impact damper, not only for linear indexes (e.g., root mean square response), but also for nonlinear indexes (e.g., component energy consumption and hinge joint curvature).

A comparative study on the nitrogen utilization efficiency and growth rate of domestic keumgang and chokyeong wheat

  • Lee, Won Je;Jeong, Chan Young;Lee, Seokjin;Kang, Chon-Sik;Lee, Hojoung
    • Journal of Applied Biological Chemistry
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    • v.62 no.1
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    • pp.67-71
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    • 2019
  • All countries, including Korea, are currently experiencing the effect of rapid climate change. As a result, the cultivation area of many crops including wheat is changing, or productivity is falling sharply. If enough nitrogen is present in the soil, the increase in atmospheric carbon dioxide due to the greenhouse effect can lead to increased photosynthesis of plants, resulting in increased productivity. By contrast, a low proportion of nitrogen in soil does not increase production, often leading to the use of nitrogen fertilizers to increase crop productivity: this causes serious environmental pollution due to the leakage of nitrogen fertilizers used by crops. Increasing the understanding of the molecular level of the plant nitrogen use efficiency mechanism may contribute to increased productivity of crops and reduced of environmental pollution by nitrogen. In Korea, cultivars have developed 35 kinds of wheat, such as 'keumgang' and 'Chokyeong', which can be used for specific purposes such as baking or noodles. In this study we investigate 'keumgang' and 'Chokyeong' in order to elucidate the mechanism of nitrogen use ability of wheat and contribute to the reduction of environmental pollution by providing guidelines for the proper use of nitrogenous fertilizer.

Inhibitory Effects of Esculetin Through the Down-Regulation of PI3K/MAPK Pathway on Collagen-Induced Platelets Aggregation (Esculetin이 PI3K/MAPK 경로 하향 조절을 통해 collagen 유도의 혈소판 응집 억제에 미치는 효과)

  • Park, Chang-Eun;Lee, Dong-Ha
    • Korean Journal of Pharmacognosy
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    • v.52 no.3
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    • pp.127-133
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    • 2021
  • Platelet activation plays a major role in cardiovascular disorders (CVDs). Thus, disrupting platelet activation represents an attractive therapeutic target on CVDs. Esculetin, a bioactive 6,7-dihydroxy derivative of coumarin, possesses pharmacological activities against obesity, diabetes, renal failure, and CVDs. In other report, the effect of esculetin has been examined in human platelet activation and experimental mouse models, and esculetin inhibited collagen- and arachidonic acid-induced platelet aggregation in washed human platelets. However, it had no effects on other agonists such as thrombin and U46619, and its mechanism is not also clearly known. This study investigated the effect of esculetin on collagen-induced human platelet aggregation, and we clarified the mechanism. Esuletin has effects on the down regulation of PI3K/Akt and MAPK, phosphoproteins that act in the signaling process in platelet aggregation. The effects of esculetin reduced of TXA2 production and phospholipase A2 activation, and intracellular granule secretion including ATP and serotonin, leading to inhibit platelet aggregation. These results clearly clarified the effect of esculetin in inhibiting platelet activity and thrombus formation in humans.

Swertia pseudochinensis Methanol Extract Inhibits IgE-mediated Allergic Response In vitro and In vivo (자주쓴풀 메탄올추출물의 IgE-매개 알레르기 반응 억제 및 기전)

  • Jeon, Sun Ha;Kim, Young Mi
    • Korean Journal of Pharmacognosy
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    • v.51 no.4
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    • pp.317-324
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    • 2020
  • Mast cells play a key role in IgE-mediated allergic response. We investigated whether Swertia pseudochinensis Hara extract (SPE) inhibits IgE-mediated allergic response in mast cells and an allergic animal model. Additionally, we explored SPE's mechanism of action in mast cells. Our results showed that SPE inhibited both antigen-stimulated degranulation and the production of TNF-α and IL-4 in bone marrow-derived mast cells (BMMCs) and rat basophilic leukemia (RBL)-2H3 cells. SPE also suppressed allergic response in IgE-mediated passive cutaneous anaphylaxis (PCA) in mice. As for the mechanism of action of SPE in mast cells, it inhibited the activation of Syk kinase, a critical signaling protein in the FcεRI-mediated signaling pathway, and also the activation of LAT, a downstream adaptor protein of Syk. We further observed the reduced activation of mitogen-activated protein (MAP) kinases (P38, ERK1/2, and JNK) and Akt in mast cells. Our results described for the first time that SPE has an anti-allergic effect by suppressing mast cells through the inhibition of Syk kinase. Therefore, SPE may be useful for the treatment of type I allergic diseases.

Humic Substances Suppresses the Proliferation of TC-1 Cells, the Lung Cancer Cell

  • Eun Ju Yang;Jeong Hyun Chang
    • Biomedical Science Letters
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    • v.29 no.4
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    • pp.280-286
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    • 2023
  • In humic substances, fulvic acid (FA) is a subclass of diverse compounds known as humic substances, which are by-products of organic degradation from microorganisms. FA can suppress the proliferation of tumor cells. Despite numerous studies, the exact mechanism for the various effects of FA is not clearly understood. Based on results demonstrating anti-proliferation effects on human cancer, we investigated whether FA has similar effects on lung cancer in this study. Firstly, the anti-cancer effect of FA in pulmonary epithelial tumor cell lines (TC-1 cells) was examined by confirming its inhibitory effect on the cell proliferation of TC-1 cells. TC-1 cell proliferation was reduced by FA on a dose-dependent and time-dependent manner. After 24 hours of FA treatment, cell morphological changes such as cell volume decrease, non-adherence and increased number of apoptotic cells were clearly observed. In addition, FA induced a DNA ladder pattern by increased of DNA fragments in TC-1 cells. In the intracellular regulatory pathway by FA, we confirmed that FA induced the reduction of the anti-apoptotic protein, Bcl-2 protein levels. These results indicate that FA has anticancer effect by inducing intracellular apoptotic pathway. Further research on the mechanism of anticancer effects will be basic data for the development of potential anticancer drugs.

HoAaRO: Home Agent-Assisted Route Optimization Protocol for Nested Network

  • Sun, Shi-Min;Lee, Sang-Min;Nam, Ki-Ho;Kim, Jong-Wan;Yoo, Jae-Pil;Kim, Kee-Cheon
    • Proceedings of the Korea Information Processing Society Conference
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    • 2008.05a
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    • pp.1035-1038
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    • 2008
  • Network mobility (NEMO) has been studied extensively due to its potential applications in military and public transportation. NEMO Basic Support Protocol (NBSP) [1], the current NEMO standard based on mobile IPv6, can be readily deployed using the existing mobile IPv6 infrastructure. However, for Nested network mobility, multi-level tunnel and too many Binding Update packets results in substantial performance overhead, generally known as route sub-optimality, especially in the bottleneck root mobile router (root-MR) and Access Router. In this paper, we propose a route optimization mechanism for nested network mobility management to reduce the overhead of root-MR. In this system, Mobile Router (MR) has a cache that stores Mobile Network Nodes' (MNN) information, Correspondent Nodes' (CN) information for every MNN,and the attachments information with its subnet MRs. Home Agent performs Binding Update with CNs responsible for MRs. Through this mechanism, the number of tunnel is limited between CN and MR and the overhead of root-MR is reduced obviously.

Study of hepatoprotective effect of Haegan-jeon through activation of nuclear factor erythroid 2-related factor 2 and optimization of herbal composition based on molecular mechanism (Nuclear factor erythroid 2-related factor 2 활성화를 통한 해간전(解肝煎)의 간세포 보호 효능 및 분자기전을 활용한 해간전(解肝煎) 구성 약물의 최적화 연구)

  • Kim, Jae Kwang;Jung, Ji Yun;Park, Sang Mi;Park, Chung A;Ku, Sae Kwang;Byun, Sung Hui;Cho, Il Je;Kim, Sang Chan
    • Herbal Formula Science
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    • v.26 no.3
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    • pp.207-221
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    • 2018
  • Objectives : Present study investigated hepatoprotective effect of Haegan-jeon extract (HE) and tried to elucidate molecular mechanism involved. According to molecular mechanism, present study optimized herbal composition of HE (op-HE) and compared in vitro and in vivo hepatoprotective effects of op-HE to HE. Methods : For in vitro experiments, HepG2 cells were exposed to arachidonic acid (AA, $10{\mu}M$) and iron ($5{\mu}M$) for inducing oxidative stress. Cell viability, GSH contents, $H_2O_2$ production, mitochondrial membrane potential, immunoblot and reporter gene assay were performed to investigate cytoprotective effects and responsible molecular mechanisms. For in vivo experiments, hepatoprotective effect of HE and op-HE were assessed on $CCl_4-induced$ liver injury mice model. Results : HE pretreatment prevented AA+iron-mediated hepatocytes apoptosis. In addition, AA+iron-induced mitochondrial dysfunction, $H_2O_2$ production, glutathione depletion were reduced by HE pretreatment. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation, antioxidant response element (ARE)-driven reporter gene activity, and antioxidant genes expression were increased by HE. Based on reporter gene and MTT assays, we found that op-HE consisting three medicinal herbs also significantly increased transactivation of Nrf2 and reduced the AA+iron-mediated cytotoxicity. Moreover, in $CCl_4-induced$ liver injury mice model, HE-op had an ability to ameliorate $CCl_4-mediated$ increases in serum alanine transferase and aspartate aminotransferase activity, hepatic degeneration, inflammatory cell infiltration, and collagen deposition. Hepatoprotective effects of op-HE were comparable to those of HE. Conclusions : Present study suggests that op-HE as well as HE exhibit hepatoprotective effect against oxidative stress-mediated liver injury via Nrf2 activation.

Application of Remote Sensing Technology for Developing REDD+ Monitoring Systems (REDD+ 모니터링 시스템 구축을 위한 원격탐사기술의 활용방안)

  • Park, Taejin;Lee, Woo-Kyun;Jung, Raesun;Kim, Moon-Il;Kwon, Tae-Hyub
    • Journal of Korean Society of Forest Science
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    • v.100 no.3
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    • pp.315-326
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    • 2011
  • In recent years, domestic and international interests focus on climate change, and importance of forest as carbon sink have been also increased. Particularly REDD+ mechanism expanded from REDD (Reduced Emissions from Deforestation and Degradation) is expected to perform a new mechanism for reducing greenhouse gas in post 2012. To conduct this mechanism, countries which try to get a carbon credit have to certify effectiveness of their activities by MRV (Measuring, Reporting and Verification) system. This study analyzed the approaches for detecting land cover change and estimating carbon stock by remote sensing technology which is considered as the effective method to develop MRV system. The most appropriate remote sensing for detection of land cover change is optical medium resolution sensors and satellite SAR (Synthetic Aperture Radar) according to cost efficiency and uncertainty assessment. In case of estimating carbon stock, integration of low uncertainty techniques, airborne LiDAR (Light Detection and Ranging), SAR, and cost efficient techniques, optical medium resolution sensors and satellite SAR, could be more appropriate. However, due to absence of certificate authority, guideline, and standard of uncertainty, we should pay continuously our attention on international information flow and establish appropriate methods. Moreover, to apply monitoring system to developing countries, close collaboration and monitoring method reflected characteristics of each countries should be considered.