• Title/Summary/Keyword: cell cycle

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G-Protein-Coupled Receptor 120 Mediates DHA-Induced Apoptosis by Regulating IP3R, ROS and, ER Stress Levels in Cisplatin-Resistant Cancer Cells

  • Shin, Jong-Il;Jeon, Yong-Joon;Lee, Sol;Lee, Yoon Gyeong;Kim, Ji Beom;Lee, Kyungho
    • Molecules and Cells
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    • v.42 no.3
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    • pp.252-261
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    • 2019
  • The omega-3 fatty acid docosahexaenoic acid (DHA) is known to induce apoptosis and cell cycle arrest via the induction of reactive oxygen species (ROS) production and endoplasmic reticulum (ER) stress in many types of cancers. However, the roles of DHA in drug-resistant cancer cells have not been elucidated. In this study, we investigated the effects of DHA in cisplatin-resistant gastric cancer SNU-601/cis2 cells. DHA was found to induce ROS-dependent apoptosis in these cells. The inositol 1,4,5-triphosphate receptor ($IP_3R$) blocker 2-aminoethyl diphenylboninate (2-APB) reduced DHA-induced ROS production, consequently reducing apoptosis. We also found that G-protein-coupled receptor 120 (GPR120), a receptor of long-chain fatty acids, is expressed in SNU-601/cis2 cells, and the knockdown of GPR120 using specific shRNAs alleviated DHA-mediated ROS production and apoptosis. GPR120 knockdown reduced the expression of ER stress response genes, similar to the case for the pre-treatment of the cells with N-acetyl-L-cysteine (NAC), an ROS scavenger, or 2-APB. Indeed, the knockdown of C/EBP homologous protein (CHOP), a transcription factor that functions under ER stress conditions, markedly reduced DHA-mediated apoptosis, indicating that CHOP plays an essential role in the anti-cancer activity of DHA. These results suggest that GPR120 mediates DHA-induced apoptosis by regulating $IP_3R$, ROS, and ER stress levels in cisplatin-resistant cancer cells, and that GPR120 is an effective chemotherapeutic target for cisplatin resistance.

Mitophagy Improves Ethanol Tolerance in Yeast: Regulation by Mitochondrial Reactive Oxygen Species in Saccharomyces cerevisiae

  • Jing, Hongjuan;Liu, Huanhuan;Lu, Zhang;Cui, liuqing;Tan, Xiaorong
    • Journal of Microbiology and Biotechnology
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    • v.30 no.12
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    • pp.1876-1884
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    • 2020
  • Ethanol often accumulates during the process of wine fermentation, and mitophagy has critical role in ethanol output. However, the relationship between mitophagy and ethanol stress is still unclear. In this study, the expression of ATG11 and ATG32 genes exposed to ethanol stress was accessed by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The result indicated that ethanol stress induced expression of the ATG11 and ATG32 genes. The colony sizes and the alcohol yield of atg11 and atg32 were also smaller and lower than those of wild type strain under ethanol whereas the mortality of mutants is higher. Furthermore, compared with wild type, the membrane integrity and the mitochondrial membrane potential of atg11 and atg32 exhibited greater damage following ethanol stress. In addition, a greater proportion of mutant cells were arrested at the G1/G0 cell cycle. There was more aggregation of peroxide hydrogen (H2O2) and superoxide anion (O2•-) in mutants. These changes in H2O2 and O2•- in yeasts were altered by reductants or inhibitors of scavenging enzyme by means of regulating the expression of ATG11 and ATG32 genes. Inhibitors of the mitochondrial electron transport chain (mtETC) also increased production of H2O2 and O2•- by enhancing expression of the ATG11 and ATG32 genes. Further results showed that activator or inhibitor of autophagy also activated or inhibited mitophagy by altering production of H2O2 and O2•. Therefore, ethanol stress induces mitophagy which improves yeast the tolerance to ethanol and the level of mitophagy during ethanol stress is regulated by ROS derived from mtETC.

Design of AES Cryptographic Processor with Modular Round Key Generator (모듈화된 라운드 키 생성회로를 갖는 AES 암호 프로세서의 설계)

  • 최병윤;박영수;전성익
    • Journal of the Korea Institute of Information Security & Cryptology
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    • v.12 no.5
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    • pp.15-25
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    • 2002
  • In this paper a design of high performance cryptographic processor which implements AES Rijndael algorithm is described. To eliminate performance degradation due to round-key computation delay of conventional processor, the on-the-fly precomputation of round key based on modified round structure is adopted. And on-the-fly round key generator which supports 128, 192, and 256-bit key has modular structure. The designed processor has iterative structure which uses 1 clock cycle per round and supports three operation modes, such as ECB, CBC, and CTR mode which is a candidate for new AES modes of operation. The cryptographic processor designed in Verilog-HDL and synthesized using 0.251$\mu\textrm{m}$ CMOS cell library consists of about 51,000 gates. Simulation results show that the critical path delay is about 7.5ns and it can operate up to 125Mhz clock frequency at 2.5V supply. Its peak performance is about 1.45Gbps encryption or decryption rate under 128-bit key ECB mode.

A study on the maturation of cardiomyocytes by continuous supply of culture media (세포 배양액의 연속 공급기 제작을 통한 심근세포의 성숙개선에 관한 연구)

  • Kwon, WooJin;Kim, Geun Woo;Jeong, Unseon;Kim, Jongyun;Lee, Dong-Weon
    • Journal of Sensor Science and Technology
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    • v.30 no.2
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    • pp.109-113
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    • 2021
  • In this study, an automated culture media replacement system was developed to analyze changes in the contraction characteristics of cardiomyocytes according to the state of the culture media. For the long-term storage of culture media, a Peltier refrigerator with a temperature of 5 to 8℃ was provided and a pH of 7.4 was maintained. The cell culture media of the cardiomyocytes was continuously replaced using interlocking pumps at a flow rate of 0.83 μl/h. The cardiomyocytes in which the culture media was replaced automatically demonstrated lower heartbeats per minute compared to samples in which there was no replacement. However, these cardiomyocytes moved more uniformly and produced greater displacement in one heartbeat cycle. It was observed that the sarcomere length of the cardiomyocytes increased due to the automated culture media replacement system. These cardiomyocytes were found to demonstrate better maturation compared to the control group. The maturation of cardiomyocytes was verified through staining images. The proposed automated culture media replacement system generates a uniform heart rate and improvements in contraction force. Based on the study, patient-specific drug toxicity assessments can be conducted using differentiated cardiomyocytes in induced pluripotent stem cells.

A Study of 100 tonf Tensile Load for SMART Mooring Line Monitoring System Considering Polymer Fiber Creep Characteristics

  • Chung, Joseph Chul;Lee, Michael Myung-Sub;Kang, Sung Ho
    • Journal of Ocean Engineering and Technology
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    • v.35 no.4
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    • pp.266-272
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    • 2021
  • Mooring systems are among the most important elements employed to control the motion of floating offshore structures on the sea. Considering the use of polymer material, a new method is proposed to address the creep characteristics rather than the method of using a tension load cell for measuring the tension of the mooring line. This study uses a synthetic mooring rope made from a polymer material, which usually consists of three parts: center, eye, and splice, and which makes a joint for two successive ropes. We integrate the optical sensor into the synthetic mooring ropes to measure the rope tension. The different structure of the mooring line in the longitudinal direction can be used to measure the loads with the entire mooring configuration in series, which can be defined as SMART (Smart Mooring and Riser Truncation) mooring. To determine the characteristics of the basic SMART mooring, a SMART mooring with a diameter of 3 mm made of three different polymer materials is observed to change the wavelength that responds as the length changes. By performing the longitudinal tension experiment using three different SMART moorings, it was confirmed that there were linear wavelength changes in the response characteristics of the 3-mm-diameter SMART moorings. A 54-mm-diameter SMART mooring is produced to measure the response of longitudinal tension on the center, eye, and splice of the mooring, and a longitudinal tension of 100 t in step-by-step applied for the Maintained Test and Fatigue Cycle Test is conducted. By performing a longitudinal tension experiment, wavelength changes were detected in the center, eye, and splice position of the SMART moorings. The results obtained from each part of the installed sensors indicated a different strain measurement depending on the position of the SMART moorings. The variation of the strain measurement with the position was more than twice the result of the difference measurement, while the applied external load increased step-by-step. It appears that there is a correlation with an externally generated longitudinal tensional force depending on the cross-sectional area of each part of the SMART mooring.

Review and Strategy for Study on Korean Buffer Characteristics Under the Elevated Temperature Conditions: Mineral Transformation and Radionuclide Retardation Perspective

  • Park, Tae-Jin;Yoon, Seok;Lee, Changsoo;Cho, Dong Keun
    • Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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    • v.19 no.4
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    • pp.459-467
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    • 2021
  • In the majority of countries, the upper limit of buffer temperature in a repository is set to below 100℃ due to the possible illitization. This smectite-to-illite transformation is expected to be detrimental to the swelling functions of the buffer. However, if the upper limit is increased while preventing illitization, the disposal density and cost-effectiveness for the repository will dramatically increase. Thus, understanding the characteristics and creating a database related to the buffer under the elevated temperature conditions is crucial. In this study, a strategy to investigate the bentonite found in Korea under the elevated temperatures from a mineral transformation and radionuclides retardation perspective was proposed. Certain long-term hydrothermal reactions generated the bentonite samples that were utilized for the investigation of their mineral transformation and radionuclide retardation characteristics. The bentonite samples are expected to be studied using in-situ synchrotron-based X-Ray Diffraction (XRD) technique to determine the smectite-to-illite transformation. Simultaneously, the 'high-temperature and high-pressure mineral alteration measurement system' based on the Diamond Anvil Cell (DAC) will control and provide the elevated temperature and pressure conditions during the measurements. The kinetic models, including the Huang and Cuadros model, are expected to predict the time and manner in which the illitization will become detrimental to the performance and safety of the repository. The sorption reactions planned for the bentonite samples to evaluate the effects on retardation will provide the information required to expand the current knowledge of repository optimization.

Effects of Micro-current Stimulation on lipid metabolism in Oleic Acid-Induced Non-Alcoholic Fatty Liver disease in FL83B cells (올레산으로 유도된 비알코올성 지방간 세포 모델에서의 미세전류 자극의 지질 대사 조절 효능 평가)

  • Lee, Hana;Lee, Minjoo;Kim, Han Sung
    • Journal of Biomedical Engineering Research
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    • v.43 no.1
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    • pp.1-10
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    • 2022
  • Non-alcoholic fatty liver disease(NAFLD) is excessive hepatic lipid accumulation mainly caused by obesity. This study aimed to evaluate whether micro-current stimulation(MCS) could modulate lipid metabolism regarding the Sirt1/AMPK pathway, fatty acid β-oxidation pathway, and lipolysis and lipogenesis-related factors in FL83B cells. For the NAFLD cell model, FL83B cells were treated with oleic acid for lipid accumulation. MCS were stimulated for 1 hr and used frequency 10 Hz, duty cycle 50%, and biphasic rectangular current pulse. The intensity of MCS was divided into 50, 100, 200, and 400 ㎂. Through the results of Oil red O staining, it was confirmed that MCSs with the intensity of 200 ㎂ and 400 ㎂ significantly reduced the degree of lipid droplet formation. Thus, these MCS intensities were applied to western blot analysis. Western blot analysis was performed to analyze the effects of MCS on lipid metabolism. MCS with the intensity of 400 ㎂ showed that significantly activated the Sirt1/AMPK pathway, a key pathway for regulating lipid metabolism in hepatocytes, and fatty acid β-oxidation-related transcription factors. Moreover, it activated the lipolysis pathway and suppressed lipogenesis-related transcription factors such as SREBP-1c, FAS, and PPARγ. In the case of MCS with the intensity of 200 ㎂, only PGC1α and SREBP-1c showed significant differences compared to cells treated only with oleic acid. Taken together, these results suggested that MCS with the intensity of 400 ㎂ could alleviate hepatic lipid accumulation by modulating lipid metabolism in hepatocytes.

Potential biomarkers and signaling pathways associated with the pathogenesis of primary salivary gland carcinoma: a bioinformatics study

  • Bayat, Zeynab;Ahmadi-Motamayel, Fatemeh;Salimi Parsa, Mohadeseh;Taherkhani, Amir
    • Genomics & Informatics
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    • v.19 no.4
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    • pp.42.1-42.17
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    • 2021
  • Salivary gland carcinoma (SGC) is rare cancer, constituting 6% of neoplasms in the head and neck area. The most responsible genes and pathways involved in the pathology of this disorder have not been fully understood. We aimed to identify differentially expressed genes (DEGs), the most critical hub genes, transcription factors, signaling pathways, and biological processes (BPs) associated with the pathogenesis of primary SGC. The mRNA dataset GSE153283 in the Gene Expression Omnibus database was re-analyzed for determining DEGs in cancer tissue of patients with primary SGC compared to the adjacent normal tissue (adjusted p-value < 0.001; |Log2 fold change| > 1). A protein interaction map (PIM) was built, and the main modules within the network were identified and focused on the different pathways and BP analyses. The hub genes of PIM were discovered, and their associated gene regulatory network was built to determine the master regulators involved in the pathogenesis of primary SGC. A total of 137 genes were found to be differentially expressed in primary SGC. The most significant pathways and BPs that were deregulated in the primary disease condition were associated with the cell cycle and fibroblast proliferation procedures. TP53, EGF, FN1, NOTCH1, EZH2, COL1A1, SPP1, CDKN2A, WNT5A, PDGFRB, CCNB1, and H2AFX were demonstrated to be the most critical genes linked with the primary SGC. SPIB, FOXM1, and POLR2A significantly regulate all the hub genes. This study illustrated several hub genes and their master regulators that might be appropriate targets for the therapeutic aims of primary SGC.

A Comparative Anatomical Study of Saururus chinensis (Lour.) Baill. and Houttuynia cordata Thunb. (Saururaceae) (삼백초와 약모밀의 내부형태 비교 연구)

  • Yang, Sungyu;Choi, Goya
    • The Korea Journal of Herbology
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    • v.33 no.3
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    • pp.11-18
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    • 2018
  • Objectives : Saururus chinensis and Houttuynia cordata (Saururaceae) are perennial herbs using for medicinal purposes in Korea. The objectives of this study are to compare anatomical key characters between two medicinal plants and to provide fundamental information for the identification of two herbal medicines by using anatomical features. Methods : Cross-sections of root, rhizome, stem, petiole, and leaf for each species were observed in this study. Materials were analyzed through dehydration, paraffin embedding and micro-sectioning, and double staining with Safranin O and Fast-Green FCF. Observations of permanent preparation were conducted using light microscope. Results : S. chinensis and H. cordata were distinguished with anatomical differentiations; Idioblasts with essential oil were scattered in the parenchyma cell of cortex, pith, and phloem of S. chinensis, on the other hand, in H. cordata, idioblasts were distributed ring-shaped in the cortex of the root. S. chinensis had two cycles of vascular bundles in the stem while H. cordata had one cycle. Hypodermis layer was conspicuous in a stem of H. cordata, crystals were observed the only parenchyma in a stem of S. chinensis, and epidermal oil cells were developed in the epidermis of H. cordata. S. chinensis had air cavity at the cortex and pith of the stem. The shape of cross-section was polygonal in the stem of S. chinensis and was circular in the stem of H. cordata. Conclusions : We investigated anatomical study of Korean S. chinensis and H. cordata. To identify two herbal medicines, we considered main anatomical features and provided identification key here.

Study of the Antioxidant Effect of Ojayeonjong-hwan (오자연종환(五子衍宗丸) 추출물의 항산화 효과에 관한 연구)

  • Jung, Yu-jin;Park, Sang-eun;Hong, Sang-hoon
    • The Journal of Internal Korean Medicine
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    • v.43 no.3
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    • pp.344-362
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    • 2022
  • Objective: In this study, the antioxidant activity of Ojayeonjong-hwan extracts was compared, and the following results were obtained. Methods: For hydrothermal and ethanol extracts, DPPH free radical and ABTS cationic radical erasing activity and reducing power using the FRAP method were compared, and the association between the antioxidant power of each extract and total phenol content was investigated. Significant results were obtained through in vitro apoptosis analysis through FFITC staining, mitochondrial membrane potential analysis, and ROS level measurement using C2C12 myoblastoma. Results: 1. In a comparison of DPPH free radical and ABTS cationic radical scavenging activity, water, and 70% ethanol extracts of Ojayeonjong-hwan (WEO and EEO) showed superior radical scavenging ability. 2. In the results of reducing power using the FRAP method, WEO and EEO showed antioxidant activity, which was shown to be dependent on the total phenol content contained in the extracts. 3. In comparison to the protective effect against H2O2-induced oxidative stress in C2C12 myoblasts, water extracts had no significant effect, but 70% ethanol extracts inhibited H2O2-mediated cytotoxicity in a concentration-dependent manner. 4. The cytotoxic protective effect of EEO against oxidative stress in C2C12 myoblasts was correlated with its inhibitory effects on H2O2-induced apoptosis and cell-cycle arrest. 5. In H2O2-treated C2C12 myoblasts, the apoptosis inhibitory effects of EEO were associated with the suppression of mitochondrial dysfunction and DNA damage. 6. The protective effects of EEO against H2O2-induced oxidative stress in C2C12 myoblasts were directly related to the inhibition of ROS generation. Conclusions: Ojayeonjong-hwan extracts all have protective potential against oxidative stress.