• Title/Summary/Keyword: Target degradation

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Simulation of Water Quality Changes in the Saemangeum Reservoir Induced by Dike Completion (방조제 완공에 따른 호내부 수질변화 모의)

  • Suh, Seung-Won;Lee, Hwa-Young;Yoo, Sang-Cheol
    • Journal of Korean Society of Coastal and Ocean Engineers
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    • v.22 no.4
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    • pp.258-271
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    • 2010
  • In order to figure out hydrodynamic and water quality changes after completion of dike construction of the Saemangeum, which behaves as a semi-enclosed estuarine lake, numerical simulations based on fine grid structure by using EFDC were intensively carried out. In this study some limitations of precedent study has been improved and gate operation were considered. Also 3 phases such as air-water-sediment interaction modeling was considered. It is clear that inner mixing of the Saemangeum is dominated by Mankyeong and Dongjin riverine discharges rather than the gate opening influence through the Lagrangian particle tracking simulations. Vertical DO structure after the dike completion shows steep gradient especially at Dongjin river estuary due to lessen of outer sea water exchange. Increasing SOD at stagnantly changed man-made reservoir might cause oxygen deficiency and accelerating degradation of water quality. According to TSI evaluation test representing eutrophication status, it shows high possibility of eutrophication along Mankyeong waterway in spite of dike completion, while the index is getting high after final closing along Dongjin waterway. Numerical tests with gate operations show significant differences in water quality. Thus it should be noted that proper gate operation plays a major role in preserving target water quality and management for inner development plan.

Distribution of Protease Inhibitors from Fish Eggs as Seafood Processing Byproducts (어류 알의 Protease Inhibitor 활성 분포)

  • Ji, Seong-Jun;Lee, Ji-Sun;Shin, Joon-Ho;Park, Kwon-Hyun;Kim, Jin-Soo;Kim, Kyoung-Sub;Heu, Min-Soo
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.44 no.1
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    • pp.8-17
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    • 2011
  • To identify and examine the distribution of proteolytic inhibitory activity in crude extracts from fish eggs, and to determine the applicability of these protease inhibitors as anti-degradation agents in surimi-based products and fish meat, we compared the inhibitory activities of various extracts from fish eggs to those of commercial proteases, such as trypsin and papain. We used the optimal conditions for the screening of trypsin activity: 30 ug/uL of 0.1% trypsin and 0.6 mM Na-benzoyl-L-arginine-p-nitroanilide (BAPNA) with a pH of 8.0 at $40^{\circ}C$ for 60 min. The activities of papain and four commercial proteases were investigated after mixing with 100 ug/uL enzymes and 0.3% casein with a pH of 8.0 at $40^{\circ}C$ for 60 min. We performed a screening assay to detect the inhibitory activity (%) of crude extracts from eight species of fish eggs against the target proteases trypsin and papain. The assay revealed a wide distribution of trypsin and papain inhibitors in fish eggs. The specific inhibitory activities (11.6.28.6 U/mg) of crude extracts from fish eggs against trypsin and BAPNA substrate were higher than that (0.64 U/mg) of egg whites, used as a commercial inhibitor. The inhibitory activities of crude extracts from fish eggs against trypsin, and of egg whites against casein substrate (1.94.4.51 U/mg), were higher than those of papain (0.24.1.57 U/mg) and commercial protease (0.04.0.32 U/mg). The extracts from fish eggs were rich in protease inhibitors that exhibited strong inhibitory activity against trypsin, a serine protease, and papain, a cysteine protease.

Effects of Pesticide Formulations on the Residues in Paddy Rice (농약(農藥)의 제형(劑型)이 수도체중(水稻體中) 잔류량(殘留量)에 미치는 영향(影響))

  • Oh, Byung-Youl;Kim, Young-Ku;Park, Young-Sun
    • Korean Journal of Environmental Agriculture
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    • v.3 no.2
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    • pp.1-8
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    • 1984
  • The present study was performed to elucidate pesticide residues in paddy rice applied with different application schedules and frequencies of pesticide formulations. Pungsanbyeo($Japonica{\times}Indica hybrid$) of rice(Oryza sativa L.) was chosen as target crop. Isoprothiolane(diisopropyl-l,3-dithiolan-2-ylidene malonate) 40EC (emulsifiable concentrates), 12G (granular), and chlorpyriphosmethyl [0,0-dimethyl 0-(3,5,6-trichloro-2-pyridyl) phosphorothioate] 25EC, 3G were selected as pesticide formulations. The closer the isoprothiolane EC application to harvest, the higher the residues in rice straw retained at harvest; however the G application on 30 days before harvest resulted in highest residue. Chlorpyriphosmethyl residues were higher as it was applied nearby to harvest. Degradation rate of chlorpyriphos-methyl in husked rice was quite similar to in rice straw, on the other hand isoprothiolane in the rice was more stable than that in rice straw. Translocated amount of applied G formulation to husked rice was meager irrespective to the chemicals. Percent reduction of isoprothiolane residues in husked rice by polishing was not related to application frequencies but to application date before harvest. Residual portions in rice straw, husked rice and polished rice of total input amount during rice cultivation were ranged from 0.19% to 0.99%, 0.01% to 0.48%, and 0.15%, respectively.

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Anticancer Activities of the Methanolic Extract from Lemon Leaves in Human Breast Cancer Stem Cells (인간 유방암 줄기세포에서 레몬잎 메탄올 추출물의 항암 효능)

  • Moon, Jeong Yong;Nguyen, Linh Thi Thao;Hyun, Ho Bong;Osman, Ahmed;Cho, Minwhan;Han, Suyeong;Lee, Dong-Sun;Ahn, Kwang Seok
    • Journal of Applied Biological Chemistry
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    • v.58 no.3
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    • pp.219-226
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    • 2015
  • The anticancer activity of a methanolic extract from lemon leaves (MLL) was assessed in MCF-7-SC human breast cancer stem cells. MLL induced apoptosis in MCF-7-SC, as evidenced by increased apoptotic body formation, sub-G1 cell population, annexin V-positive cells, Bax/Bcl-2 ratio, as well as proteolytic activation of caspase-9 and caspase-3, and degradation of poly (ADP-ribose) polymerase (PARP) protein. Concomitantly, MLL induced the formation of acidic vesicular organelles, increased LC3-II accumulation, and reduced the activation of Akt, mTOR, and p70S6K, suggesting that MLL initiates an autophagic progression in MCF-7-SC via the Akt/mTOR pathway. Epithelial-mesenchymal transition (EMT), a critical step in the acquisition of the metastatic state, is an attractive target for therapeutic interventions directed against tumor metastasis. At low concentrations, MLL induced anti-metastatic effects on MCF-7-SC by inhibiting the EMT process. Exposure to MLL also led to an increase in the epithelial marker E-cadherin, but decreased protein levels of the mesenchymal markers Snail and Slug. Collectively, this study provides evidence that lemon leaves possess cytotoxicity and anti-metastatic properties. Therefore, MLL may prove to be beneficial as a medicinal plant for alternative novel anticancer drugs and nutraceutical products.

Structural basis of novel TRP14, thioredoxin-related protein that regulates TNE-$\alpha$ signaling pathways

  • Woo, Joo-Rang;Jeong, Woo-Jin;Rhee, Sue-Goo;Ryu, Seong-Eon
    • Proceedings of the Korea Crystallographic Association Conference
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    • 2003.05a
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    • pp.18-18
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    • 2003
  • Thioredoxin (Trx) is a small redox protein that is ubiquitously distributed from achaes to human. In diverse organisms, the protein is involved in various physiological roles by acting as electron donor and regulators of transcription and apoptosis as well as antioxidants. Sequences of Trx within various species are 27~69% identical to that of E. coli and all Trx proteins have the same overall fold, which consists of central five β strands surrounded by four α helices. The N-terminal cysteine in WCGPC motif of Trx is redox sensitive and the motif is highly conserved. Compared with general cysteine, the N-terminal cysteine has low pKa value. The result leads to increased reduction activity of protein. Recently, novel thio.edoxin-related protein (TRP14) was found from rat brain. TRP14 acts as disulfide reductase like Trx1, and its redox potential and pKa are similar to those of Trx1. However, TRP14 takes up electrons from cytosolic thioredoxin reductase (TrxR1), not from the mitochondrial thioredoxin reductase (TrxR2). Biological roles of TES14 were reported to be involved in regulating TNF-α induced signaling pathways in different manner with Trx1. In depletion experiments, depletion of TRP14 increased TNF-α induced phosphorylation and degradation of IκBα more than the depletion Trx1 did. It also facilitated activation of JNK and p38 MAP kinase induced by TNF-α. Unlike Trx1, TRP14 shows neither interaction nor interference with ASK1. Here, we determined three-dimensional crystal structure of TRP14 by MAD method at 1.8Å. The structure reveals that the conserved cis-Pro (Pro90) and active site-W-C-X-X-C motif, which may be involved in substrate recognition similar to Trx1 , are located at the beginning position of strand β4 and helix α2, respectively. The TRP14 structure also shows that surface of TRP14 in the vicinity of the active site, which is surrounded by an extended flexible loop and an additional short a helix, is different from that of Trx1. In addition, the structure exhibits that TRP14 interact with a distinct target proteins compared with Trx1 and the binding may depend mainly on hydrophobic and charge interactions. Consequently, the structure supports biological data that the TRP14 is involved in regulating TNF-α induced signaling pathways in different manner with Trx1.

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Apoptotic Cell Death of Human Leukemia U937 Cells by Essential Oil purified from Schisandrae Semen (오미자 종자 정유에 의한 인체백혈병 U937 세포의 apoptosis 유도)

  • Choi, Yung Hyun
    • Journal of Life Science
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    • v.25 no.2
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    • pp.249-255
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    • 2015
  • Schisandrae fructus [Schizandra chinensis (Turcz.) Baillon] is a medicinal herb widely used for treating various inflammatory and immune diseases in East Asian countries. The Schisandrae Semen essential oil (SSeo) from this plant has pharmacological activities, including antioxidant, antimicrobial, and antitumoral activities. Nevertheless, the biological activities and underlying molecular mechanisms of the potential anti-cancer effects of this oil remain unclear. In the present study, we investigated the potential inhibition of apoptosis signaling pathways by SSeo in human leukemia U937 cells and evaluated the underlying molecular mechanism. Exposure to SSeo resulted in a concentration-dependent growth inhibition due to apoptosis, which was verified by DNA fragmentation, the presence of apoptotic bodies, and an increase in the sub-G1 ratio. Induction of apoptotic cell death by SSeo was correlated with the down-regulation of members of the inhibitor of apoptosis protein (IAP) family (including X-linked inhibitor of apoptosis protein (XIAP), cIAP-1, and surviving) and anti-apoptotic Bcl-2, and with up-regulation of death receptor (DR) 4 and DR5, depending on dosage. SSeo treatment also induced Bid truncation, mitochondrial dysfunction, proteolytic activation of caspase-3, -8 and -9, and concomitant degradation of activated caspase-3 target proteins such as poly (ADP-ribose) polymerase. Taken together, these findings suggest that SSeo may be a potential chemotherapeutic agent for use in the control of human leukemia cells. Further studies are needed to identify its active compounds.

Forward rate control of MPEG-2 video based on distortion-rate estimation (왜곡-비트율 추정에 근거한 MPEG-2 비디오의 순방향 비트율 제어)

  • 홍성훈;김성대;최재각;홍성용
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.23 no.8
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    • pp.2010-2024
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    • 1998
  • In video coding, it is important to improve the average picture quality as well as to maintain cosistent picture quality between consecutive pictures. In this paper, we propose a distortion-rate estimation method for MPEG-2 video and a forward rate control method, using the proposed estimation result, to be able to obtain the improved and consistent picture quality of CBR (Constant Bit Rate) encoded MPEG-2 video. The proposed distortion-rate estimation enable us to predict the distortion and the bits generated from an encoded picture at a given quantization step size and vice versa. The most attactive features of proposed distortion-rate estimation are its accuracy and low computational complexity enough to be applied to the practical video coding. In addition, the proposed rate control first determined a quantization parameter per frame by following procedure: distortion-rate estimation, target bit allocation, distortion constraint and VBV(Video Buffer Verification) constraint. And then this quantization parameter is applied to the encoding so that improved and consisten picture quality can be obtained. Furthermore the proposed rate control method can solve the error propagation problem caused by scene change or anchor picture degradation by using the B-picture skipping and the guarantee of the minimum bit allocation for the anchor picture. Experimental results, comparing the proposed forward rate control method with TM5 method, show that the proposed method makes more improed and consistent picture quality than TM5.

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Transcription factor EGR-1 transactivates the MMP1 gene promoter in response to TNFα in HaCaT keratinocytes

  • Yeo, Hyunjin;Lee, Jeong Yeon;Kim, JuHwan;Ahn, Sung Shin;Jeong, Jeong You;Choi, Ji Hye;Lee, Young Han;Shin, Soon Young
    • BMB Reports
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    • v.53 no.6
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    • pp.323-328
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    • 2020
  • Matrix metalloproteinase 1 (MMP-1), a calcium-dependent zinccontaining collagenase, is involved in the initial degradation of native fibrillar collagen. Tissue necrosis factor-alpha (TNFα) is a pro-inflammatory cytokine that is rapidly produced by dermal fibroblasts, monocytes/macrophages, and keratinocytes and regulates inflammation and damaged-tissue remodeling. MMP-1 is induced by TNFα and plays a critical role in tissue remodeling and skin aging processes. However, the regulation of the MMP1 gene by TNFα is not fully understood. We aimed to find additional cis-acting elements involved in the regulation of TNFα-induced MMP1 gene transcription in addition to the nuclear factor-kappa B (NF-κB) and activator protein 1 (AP1) sites. Assessments of the 5'-regulatory region of the MMP1 gene, using a series of deletion constructs, revealed the requirement of the early growth response protein 1 (EGR-1)-binding sequence (EBS) in the proximal region for proper transcription by TNFα. Ectopic expression of EGR-1, a zinc-finger transcription factor that binds to G-C rich sequences, stimulated MMP1 promoter activity. The silencing of EGR-1 by RNA interference reduced TNFα-induced MMP-1 expression. EGR-1 directly binds to the proximal region and transactivates the MMP1 gene promoter. Mutation of the EBS within the MMP1 promoter abolished EGR-1-mediated MMP-1 promoter activation. These data suggest that EGR-1 is required for TNFα-induced MMP1 transcriptional activation. In addition, we found that all three MAPKs, ERK1/2, JNK, and p38 kinase, mediate TNFα-induced MMP-1 expression via EGR-1 upregulation. These results suggest that EGR-1 may represent a good target for the development of pharmaceutical agents to reduce inflammation-induced MMP-1 expression.

Tristetraprolin Inhibits the Growth of Human Glioma Cells through Downregulation of Urokinase Plasminogen Activator/Urokinase Plasminogen Activator Receptor mRNAs

  • Ryu, Jinhyun;Yoon, Nal Ae;Lee, Yeon Kyung;Jeong, Joo Yeon;Kang, Seokmin;Seong, Hyemin;Choi, Jungil;Park, Nammi;Kim, Nayoung;Cho, Wha Ja;Paek, Sun Ha;Cho, Gyeong Jae;Choi, Wan Sung;Park, Jae-Yong;Park, Jeong Woo;Kang, Sang Soo
    • Molecules and Cells
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    • v.38 no.2
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    • pp.156-162
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    • 2015
  • Urokinase plasminogen activator (uPA) and urokinase plasminogen activator receptor (uPAR) play a major role in the infiltrative growth of glioblastoma. Downregulatoion of the uPA and uPAR has been reported to inhibit the growth glioblastoma. Here, we demonstrate that tristetraprolin (TTP) inhibits the growth of U87MG human glioma cells through downregulation of uPA and uPAR. Our results show that expression level of TTP is inversely correlated with those of uPA and uPAR in human glioma cells and tissues. TTP binds to the AU-rich elements within the 3' untranslated regions of uPA and uPAR and overexpression of TTP decreased the expression of uPA and uPAR through enhancing the degradation of their mRNAs. In addition, overexpression of TTP inhibited the growth and invasion of U87MG cells. Our findings implicate that TTP can be used as a promising therapeutic target to treat human glioma.

Tristetraprolin Overexpression in Gastric Cancer Cells Suppresses PD-L1 Expression and Inhibits Tumor Progression by Enhancing Antitumor Immunity

  • Guo, Jian;Qu, Huiheng;Shan, Ting;Chen, Yigang;Chen, Ye;Xia, Jiazeng
    • Molecules and Cells
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    • v.41 no.7
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    • pp.653-664
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    • 2018
  • The RNA-binding protein tristetraprolin (TTP) binds to adenosine-uridine AU-rich elements in the 3'-untranslated region of messenger RNAs and facilitates rapid degradation of the target mRNAs. Therefore, it regulates the expression of multiple cancer and immunity-associated transcripts. Furthermore, a lack of TTP in cancer cells influences cancer progression and predicts poor survival. Although the functions of TTP on cancer cells have previously been researched, the mechanism of TTP on the interaction between cancer cells with their micro-environment remains undiscovered. In this study, we admed to determine the role of cancer cell TTP during the interaction between tumor and immune cells, specifically regulatory T cells (Tregs). We evaluate the capability of TTP to modulate the antitumor immunity of GC and explored the underlying mechanism. The overexpression of TTP in GC cells dramatically increased peripheral blood mononuclear lymphocyte (PBML) -mediated cytotoxicity against GC cells. Increased cytotoxicity against TTP-overexpressed GC cells by PBMLs was determined by Treg development and infiltration. Surprisingly, we found the stabilization of programmed death-ligand 1 (PD-L1) mRNA was declining while TTP was elevated. The PD-L1 protein level was reduced in TTP-abundant GC cells. PD-L1 gas been found to play a pivotal role in Treg development and functional maintenance in immune system. Taken together, our results suggest the overexpression of TTP in GC cells not only affects cell survival and apoptosis but also increases PBMLs -mediated cytotoxicity against GC cells to decelerate tumor progression. Moreover, we identified PD-L1 as a critical TTP-regulated factor that contributes to inhibiting antitumor immunity.