• Title/Summary/Keyword: stress-related chemicals

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Molecular Basis of the KEAP1-NRF2 Signaling Pathway

  • Takafumi Suzuki;Jun Takahashi;Masayuki Yamamoto
    • Molecules and Cells
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    • v.46 no.3
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    • pp.133-141
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    • 2023
  • Transcription factor NRF2 (NF-E2-related factor 2) is a master regulator of cellular responses against environmental stresses. NRF2 induces expression of detoxification and antioxidant enzymes and suppresses inductions of pro-inflammatory cytokine genes. KEAP1 (Kelch-like ECH-associated protein 1) is an adaptor subunit of CULLIN 3 (CUL3)-based E3 ubiquitin ligase. KEAP1 regulates the activity of NRF2 and acts as a sensor for oxidative and electrophilic stresses. NRF2 has been found to be activated in many types of cancers with poor prognosis. Therapeutic strategies to control NRF2-overeactivated cancers have been considered not only by targeting cancer cells with NRF2 inhibitors or NRF2 synthetic lethal chemicals, but also by targeting host defense with NRF2 inducers. Understanding precise molecular mechanisms how the KEAP1-NRF2 system senses and regulates the cellular response is critical to overcome intractable NRF2-activated cancers.

Comparative Proteome Analysis of Two Antagonist Bacillus subtilis Strains

  • Zhang, C.X.;Zhao, X.;Han, F.;Yang, M.F.;Chen, H.;Chida, T.;Shen, S.H.
    • Journal of Microbiology and Biotechnology
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    • v.19 no.4
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    • pp.351-357
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    • 2009
  • Natural wild-type strains of Bacillus subtilis are extensively used in agriculture as biocontrol agents for plants. This study examined two antagonist B. subtilis strains, KB-1111 and KB-1122, and the results illustrated that KB-1122 was a more potent inhibitor of the indicator pathogen than KB-1111. Thus, to investigate the intrinsic differences between the two antagonist strains under normal culture conditions, samples of KB-1111 and KB-1122 were analyzed using MALDI-TOF-MS. The main differences were related to 20 abundant intracellular and 17 extracellular proteins. When searching the NCBI database, a number of the differentially expressed proteins were identified, including 11 cellular proteins and 10 secretory proteins. Among these proteins, class III stress-response-related ATPase, aconitate hydratase, alpha-amylase precursor, and a secretory protein, endo-l, 4-beta-glucanase, were differentially expressed by the two strains. These results are useful to comprehend the intrinsic differences between the antagonism of KB-1111 and KB-1122.

Molecular Cloning and Characterization of a Peroxiredoxin cDNA from Cell Cultures of Sweetpotato (고구마 배양세포에서 Peroxiredoxin cDNA의 분리 및 발현 특성)

  • Park, Soo-Young;Ryu, Sun-Hwa;Kwon, Suk-Yoon;Kim, Jong-Guk;Kwak, Sang-Soo
    • Journal of Plant Biotechnology
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    • v.30 no.2
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    • pp.135-141
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    • 2003
  • Peroxiredoxin(Pix) are large family of peroxidases that reduce alkyl hydroperoxides and hydrogen peroxide. A cDNA clone (referred to as swPrxl) encoding Pix was from a sweetpotato cDNA library constructed from suspension-sultured cells, and its expression was investigated in terms of stress. The swPrxl contained an open reading frame (ORF) encoding mature protein of 193 amino acids with calculated molecular mass of 20.8kDa. The predicted amino acid sequence of swPrxl has two conserved cysteines that are essential resicues for the reduction of peroxides. It showed high amino acid sequence homology ot PixIIF of Arabidopsis (77%) and putative Prx of rice(72%). RNA gel-blot analysis showed that swPrxl gene was expressed dominantly in leave among intact tissues, and also highly detect in suspension-cultured cells. Interestingly, the level of swPrxl transcripts was almost the same regardless of the growth stage in suspension culture. Furthermore, the transcription level of swPrxl gene was not significantly changed in response to various stress treatments such as wounding, extreme temperature and stress-related chemicals RT-PCR analyses.

Treatment with Phytoestrogens Reversed Triclosan and Bisphenol A-Induced Anti-Apoptosis in Breast Cancer Cells

  • Lee, Geum-A;Choi, Kyung-Chul;Hwang, Kyung-A
    • Biomolecules & Therapeutics
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    • v.26 no.5
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    • pp.503-511
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    • 2018
  • Triclosan (TCS) and bisphenol A (BPA) are endocrine-disrupting chemicals that interfere with the hormone or endocrine system and may cause cancer. Kaempferol (Kaem) and 3,3'-diindolylmethane (DIM) are phytoestrogens that play chemopreventive roles in the inhibition of carcinogenesis and cancer progression. In this study, the influence of TCS, BPA, Kaem, and DIM on proliferation and apoptotic abilities of VM7Luc4E2 breast cancer cells were examined. MTT assay revealed that TCS ($0.1-10{\mu}M$), BPA ($0.1-10{\mu}M$) and E2 ($0.01-0.0001{\mu}M$) induced significant cell proliferation of VM7Luc4E2 cells, which was restored to the control (0.1% DMSO) by co-treatment with Kaem ($30{\mu}M$) or DIM ($15{\mu}M$). Reactive oxygen species (ROS) production assays showed that TCS and BPA inhibited ROS production of VM7Luc4E2 cells similar to E2, but that co-treatment with Kaem or DIM on VM7Luc4E2 cells induced increased ROS production. Based on these results, the effects of TCS, BPA, Kaem, and DIM on protein expression of apoptosis and ROS production-related markers such as Bax and Bcl-xl, as well as endoplasmic reticulum (ER) stress-related markers such as $eIF2{\alpha}$ and CHOP were investigated by Western blot assay. The results revealed that TCS, and BPA induced anti-apoptosis by reducing ROS production and ER stress. However, Kaem and DIM effectively inhibited TCS and BPA-induced anti-apoptotic processes in VM7Luc4E2 cells. Overall, TCS and BPA were revealed to be distinct xenoestrogens that enhanced proliferation and anti-apoptosis, while Kaem and DIM were identified as natural chemopreventive compounds that effectively inhibited breast cancer cell proliferation and increased anti-apoptosis induced by TCS and BPA.

A Review on the Pain and Depression Comorbidity Animal Models (통증과 우울증의 병합 동물모델에 대한 최신 연구 동향 분석)

  • Song, Ji-Hye;Kook, Hye-Jung;Park, Byung-Jin;Kim, Song-Yi;Park, Ji-Yeun
    • Korean Journal of Acupuncture
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    • v.38 no.2
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    • pp.75-99
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    • 2021
  • Objectives : The purpose of this study is to analyze animal behavioral changes and related neurobiological mechanisms in recent studies using animal models with pain and depression. Methods : We conducted database search in Pubmed, NDSL, and EMBASE up to January 2021. Included studies were classified as depression-like behavior observed in pain model, pain-like behavior observed in depression model, and pain and depression comorbidity model. The results of pain- and depression-like behaviors, the changes of neurobiological mechanisms, and the treatment methods such as drugs, natural substance-derived chemicals, or acupuncture were analyzed. Results : We included 124 studies (81 studies in depression-like behavior observed in pain model, 19 studies in pain-like behavior observed in depression model, and 24 studies in pain and depression comorbidity model). Pain and depression comorbidity animal models were induced using various methods by drugs or surgery. Von frey test, a method for evaluating mechanical allodynia was the most commonly used for measuring pain-like behavior and the forced swimming test was the most commonly used for measuring depression-likes behavior. The changes of neurobiological factors, such as decrease of 5-hydroxytryptamine and increase of oxidative stress and pro-inflammation cytokines were generally changed in the frontal cortex, hippocampus, thalamus, and spinal cord in all types of models. For treating pain and depression-like behaviors, various types of drugs such as antidepressant, tranquilizer, analgesic, and natural substance-derived chemicals were used. Acupuncture treatment was used in 4 studies. Conclusions : In the future, more diverse studies on the combined model of pain and depression need to be conducted. In addition, it is necessary to establish a mechanistic basis for the development of various treatments by identifying the common mechanisms of pain and depression.

Induced monoterpene and lignin production in mechanically stressed and fungal elicited cultured Cupressus lusitanica cells

  • De Alwis, Ransika;Fujita, Koki;Ashitani, Tatsuya;Kuroda, Ken'ichi
    • Plant Biotechnology Reports
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    • v.3 no.1
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    • pp.57-65
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    • 2009
  • Cultured Cupressus lusitanica cells induced by various stresses are thought to produce different complexes of defense chemicals to optimize defense. To compare the induced products of two stimulations, we investigated the emission of monoterpenes, biosynthesis of ${\beta}-thujaplicin$, and accumulation of lignin in mechanically stressed and fungal elicited cultured C. lusitanica cells. Both mechanical stress and fungal elicitor caused emission of qualitatively similar monoterpene blends indicating de novo biosynthesis of these compounds after stimulation, while mechanical stress alone is sufficient to induce fungal elicitor-related monoterpene emission. Sabinene and limonene were the dominant compounds over the time course in both volatile blends. Although the emitted volatile blends were qualitatively similar, the time course and the relative ratios of the constituents of the volatile blends differed with the type of stimulation. While fungal elicited cells produced significant amounts of ${\beta}-thujaplicin$ over the 5-day time course, no ${\beta}-thujaplicin$ was observed in the mechanically stressed cells. The production of ${\beta}-thujaplicin$ was the main dissimilarity of the induced products of these two treatments, suggesting that synthesis of ${\beta}-thujaplicin$ is not a general response to all types of stresses, but is a specific response and serves as a strong toxic compound against already invaded fungus. Significantly higher amounts of lignin accumulations were observed in the fungal elicited and mechanically stressed cells on the 5th day after induction. Based on these results, we suggest the composition of induced products was dependent on the method of stimulation.

Analysis of the Active Compounds and Therapeutic Mechanisms of Yijin-tang on Meniere's Disease Using Network Pharmacology(I) (네트워크 약리학을 활용한 메니에르병에 대한 이진탕(二陳湯)의 활성 성분과 치료 기전 연구(I))

  • SunKyung Jin;Hae-Jeong Nam
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.36 no.1
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    • pp.50-63
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    • 2023
  • Objectives : This study used a network pharmacology approach to explore the active compounds and therapeutic mechanisms of Yijin-tang on Meniere's disease. Methods : The active compounds of Yijin-tang were screened via the TCMSP database and their target proteins were screened via the STITCH database. The GeneCard was used to establish the Meniere's disease-related genes. The intersection targets were obtained through Venny 2.1.0. The related protein interaction network was constructed with the STRING database, and topology analysis was performed through CytoNCA. GO biological function analysis and KEGG enrichment analysis for core targets were performed through the ClueGO. Results : Network analysis identified 126 compounds in five herbal medicines of Yijin-tang. Among them, 15 compounds(naringenin, beta-sitosterol, stigmasterol, baicalein, baicalin, calycosin, dihydrocapsaicin, formononetin, glabridin, isorhamnetin, kaempferol, mairin, quercetin, sitosterol, nobiletin) were the key chemicals. The target proteins were 119, and 7 proteins(TNF, CASP9, PARP1, CCL2, CFTR, NOS2, NOS1) were linked to Meniere's disease-related genes. Core genes in this network were TNF, CASP9, and NOS2. GO/KEGG pathway analysis results indicate that these targets are primarily involved in regulating biological processes, such as excitotoxicity, oxidative stress, and apoptosis. Conclusion : Pharmacological network analysis can help to explain the applicability of Yijin-tang on Meniere's disease.

Effects of BojungIkkiTang-Gamybang on Protective of Cell Death and Anti-Oxidative in C6 Glioma Cell (보중익기탕가미방(補中益氣湯加味方)이 신경교세포의 세포사멸보호 및 항산화에 미치는 영향)

  • Hwang, Gui-Seong;Kim, Hyung-Woo;Choi, Chan-Hun;Jeong, Hyun-Woo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.24 no.3
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    • pp.401-409
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    • 2010
  • This study was designed to investigate the effects of BojungIkkiTang-Gamybang freeze dried powder (BITG) on proliferauion, protective of cell death induced by chemicals such as paraquat, hydrogen peroxide etc and anti-oxidative effects in C6 glioma cells. In our results, BITC accelerated proliferation rates of C6 cells in vitro. In addition, protective effects on cell death induced by paraquat and hydrogen peroxide. And, BITC did not have effects on SOD and total glutathione activities, but decresed malone dialdehyde activity. In conclusion, these results suggest the possibility of BojungIkkiTang-Gamybang to protect brain cell or neuronal cell from damage induced by oxidative stress. And also suggest that related mechanisms are involved in malone dialdehyde activity.

Relationship between Menstrual Distress and Sleep Disturbance in Middle-school Girls (여자 중학생의 월경불편감과 수면장애와의 관계)

  • Park, Se Yeong;Park, SoMi
    • Women's Health Nursing
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    • v.24 no.4
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    • pp.392-403
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    • 2018
  • Purpose: To identify factors associated with menstrual distress and characterize the relationship between menstrual distress and sleep disturbance in middle-school girls. Methods: Participants in this correlational study were 117 middle-school girls who were recruited through convenience sampling. Data were collected from March 2018 to April 2018 using self-reported structured questionnaires and analyzed using IBM SPSS Statistics 23.0. Factors associated with menstrual distress included physiological, psychological, and situational factors based on the theory of unpleasant symptoms. Results: Age of menarche (${\beta}=-.28$, p<.001), amount of menstruation (${\beta}=.23$, p=.004), lifestyle-related exposure to endocrine-disrupting chemicals (${\beta}=.21$, p=.027), and academic and peer-relationship stress (${\beta}=.19$, p=.025) influenced menstrual distress, explaining 47.4% of the variance in this regression model. The relationship between menstrual distress and sleep disturbance was statistically significant. Sleep disturbance was increased 1.26 folds when dysmenorrhea score increased by one unit (OR=1.26, 95% CI: 1.01~1.58). However, parental support was not a significant moderating factor of sleep disturbance. Conclusion: This study provides basis to develop an intervention strategy to alleviate menstrual discomfort in adolescents and improve their quality of sleep.

A Study on the Resistance of Stress Corrosion Cracking due to Expansion Methods for Steam Generator Tubes in Nuclear Power Plants (원전 증기발생기 전열관의 확관방법에 따른 응력부식균열 저항성 연구)

  • Kim, Young Kyu;Song, Myung Ho
    • Journal of Energy Engineering
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    • v.23 no.2
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    • pp.149-157
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    • 2014
  • The steam generator tubes of nuclear power plants have various types of corrosion failures during the plant operation. The stress corrosion cracking which occurs on the outer surface of tube is called the secondary side stress corrosion cracking and mainly occurs in the expansion-transition area of tube. The causes are the concentration of impurities by the sludge pile-up related to the geometry of its region and the residual stress by tube expansion in the process of steam generator manufacturing. Especially the directionality and sizes of residual stresses are differed according to the tube expansion methods and the direction and the frequency of tube cracks depend on their characteristics. In bases on the plant experiences, it is notified that circumferential cracks of tubes expanded with explosive expansion method are dominantly occurred compared to those of tubes done with hydraulic expansion one. Therefore in this study, according to tube expansion methods frequencies and sizes of tube cracks with specific direction are compared by means of accelerated immersion test and also the crack morphology and the specific chemicals from water-chemistry environment are observed through the fracture surface examination.