• Title/Summary/Keyword: toxic mechanism

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Melatonin Protects Chronic Kidney Disease Mesenchymal Stem/Stromal Cells against Accumulation of Methylglyoxal via Modulation of Hexokinase-2 Expression

  • Go, Gyeongyun;Yoon, Yeo Min;Yoon, Sungtae;Lee, Gaeun;Lim, Ji Ho;Han, Su-Yeon;Lee, Sang Hun
    • Biomolecules & Therapeutics
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    • v.30 no.1
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    • pp.28-37
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    • 2022
  • Treatment options for patients with chronic kidney disease (CKD) are currently limited; therefore, there has been significant interest in applying mesenchymal stem/stromal cell (MSC)-based therapy to treat CKD. However, MSCs harvested from CKD patients tend to show diminished viability and proliferation due to sustained exposure to uremic toxins in the CKD environment, which limits their utility for cell therapy. The application of melatonin has been demonstrated to improve the therapeutic efficacy of MSCs derived from and engrafted to tissues in patients suffering from CKD, although the underlying biological mechanism has not been elucidated. In this study, we observed overexpression of hexokinase-2 (HK2) in serum samples of CKD patients and MSCs harvested from an adenine-fed CKD mouse model (CKD-mMSCs). HK2 upregulation led to increased production levels of methylglyoxal (MG), a toxic metabolic intermediate of abnormal glycolytic processes. The overabundance of HK2 and MG was associated with impaired mitochondrial function and low cell proliferation in CKD-mMSCs. Melatonin treatment inhibited the increases in HK2 and MG levels, and further improved mitochondrial function, glycolytic metabolism, and cell proliferation. Our findings suggest that identifying and characterizing metabolic regulators such as HK2 in CKD may improve the efficacy of MSCs for treating CKD and other kidney disorders.

Advancement of Clay and Clay-based Materials in the Remediation of Aquatic Environments Contaminated with Heavy Metal Toxic Ions and Micro-pollutants

  • Lalhmunsiama, Lalhmunsiama;Malsawmdawngzela, Ralte;Vanlalhmingmawia, Chhakchhuak;Tiwari, Diwakar;Yoon, Yiyong
    • Applied Chemistry for Engineering
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    • v.33 no.5
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    • pp.502-522
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    • 2022
  • Clay minerals are natural materials that show widespread applications in various branches of science, including environmental sciences, in particular the remediation of water contaminated with various water pollutants. Modified clays and minerals have attracted the attention of researchers in the recent past since the modified materials are seemingly more useful and efficient for removing emerging water contaminants. Therefore, modified engineered materials having multi-functionalities have received greater interest from researchers. The advanced clay-based materials are highly effective in the remediation of water contaminated with organic and inorganic contaminants, and these materials show enhanced selectivity towards the specific pollutants. The review inherently discusses various methods employed in the modification of clays and addresses the challenges in synthesizing the advanced engineered materials precursor to natural clay minerals. The changes in physical and chemical properties, as investigated by various characterization techniques before and after the modifications, are broadly explained. Further, the implications of these materials for the decontamination of waterbodies as contaminated with potential water pollutants are extensively discussed. Additionally, the insights involved in the removal of organic and inorganic pollutants are discussed in the review. Furthermore, the future perspectives and specific challenges in the scaling up of the treatment methods in technology development are included in this communication.

Cloning and Sequencing of a Gene Cluster for the Resistance to Doxorubicin from Streptomyces peucetius subsp. caesius ATCC 27952

  • Hong, Young-Soo;Hwang, Cheol-Kyu;Hwang, Dong-Youn;Kim, Young-Ho;Kim, Sung-Jun;Lee, Jung-Joon
    • Journal of Microbiology and Biotechnology
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    • v.2 no.3
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    • pp.153-160
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    • 1992
  • The doxorubicin resistance locus from Streptomyces peucetius subsp. caesius (the doxorubicin producer, ATCC 27952) has been cloned. The sequence data over 4.4 kb regions reveals the presence of four possible open reading frames (ORFs). ORF2 and ORF3 would encode proteins containing 329 and 283 amino acids, respectively. The protein encoded by ORF2 has two almost identical ATP binding domains with p-glycoprotein, the product of a multidrug resistance gene from tumor cells, and that encoded by ORF3 has several hydrophobic domains suggesting that it is located in the bacterial membrane. These two remarkable similarities of the gene product to p-glycoprotein of mammalian tumor cells suggest that the two proteins may enable bacteria to extrude a variety of toxic agents, including daunorubicin and doxorubicin, by an ATP dependent efflux mechanism analogous to the multidurg resistance protein of cancer cells.

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Influence of oil pipe corrosion defects on the sealing performance of annular BOP

  • Dong, Liangliang;Tang, Yuan;Wang, Liuyang
    • Structural Engineering and Mechanics
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    • v.84 no.3
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    • pp.337-344
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    • 2022
  • Due to corrosion defects on the surface of the oil pipe, the sealing performance of the annular blowout preventer (BOP) decreases, and the leakage of toxic and harmful gases such as H2S and SO2 will threaten the safety of operators on the well. Therefore, this paper establishes the FE model for evaluating the sealing performance of BOP-oil pipe corrosion defects, which is based on the rubber large deformation theory and rubber core sealing mechanism, and designs the experiment of BOP sealing performance to verify the accuracy of the FE model. The sealing performance of BOP sealing oil pipe with corrosion defects is studied. The research results show that the sealing performance of BOP is more sensitive to the axial size of corrosion defects. With the increase of oil pipe outer diameter, the critical size of defects increases continuously. The sensitivity of radial and depth dimensions is low, When for 88.9 mm outer diameter oil pipe, the axial critical size of corrosion defect is 20 mm, the radial critical size is 16 mm and the critical depth is 2 mm. Fit the formula between the outer diameter of oil pipe and the piston increment. According to the formula, the operator can calculate the piston stroke increment required by the BOP to complete the sealing when the oil pipe is corroded.

Fermented sea tangle (Laminaria japonica Aresch) Accelerates Osteoblast Differentiation in murine osteoblastic MC3T3-E1 Cells (MC3T3-E1 골아세포에서 발효 다시마 추출물에 의한 조골세포 분화의 촉진)

  • Nara Jeong;Yung Hyun Choi
    • Journal of Marine Bioscience and Biotechnology
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    • v.15 no.1
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    • pp.24-32
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    • 2023
  • The Laminaria japonica Aresch (Sea tangle) belongs to the brown algae and has a long history as a food material in Asia, including Korea. Recent studies have found that the fermented Sea tangle extract (FST) inhibited the differentiation of osteoclasts and protected osteoblasts from oxidative damage. This study aims to explore the possibility that FST can induce the differentiation of osteoblasts and identify the responsible mechanism. According to our results, FST induced differentiation into osteogenic cells in the presence of osteoblastic MC3T3-E1 cells under non-toxic conditions.. This finding was confirmed by phalloidin staining, increased alkaline phosphatase activity, and calcium deposition. Additionally, it was found that this process was achieved by increasing the expression of key factors involved in osteoblast differentiation, such as runt-related transcription factor-2, osterix, β-catenin, and bone morphogenetic protein-2. Moreover, FST increased autophagy, which may contribute to the maintenance of the bone formation homeostasis, and is associated with the activation of the phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase signaling pathways. Although further research about the bioactive substances contained in FST and the tests of their efficacy are required, the results of this study indicate that FST has incredible applicability as a functional material for maintaining the bone homeostasis.

Adsorption of Azocarmine G dye on H2SO4-modified acacia sawdust

  • Celal Duran;Sengul Tugba Ozeken;Aslihan Yilmaz Camoglu;Duygu Ozdes
    • Membrane and Water Treatment
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    • v.15 no.1
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    • pp.41-50
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    • 2024
  • Presence of hazardous dyes in water cause considerable risks to the human health and environment due to their potential toxicity and ecological disruptions. Therefore, in the present research, to suggest an alternative method for the retention of toxic Azocarmine G (ACG) dye from aqueous media, natural and H2SO4-modified acacia sawdust were performed for the first time as low-cost and efficient adsorbents. Based on batch experiments, it was determined that the best conditions for the developed dye retention process were an initial pH of 2.0 and an equilibrium time of 240 min. Analysis of the data using both pseudo-first order and pseudo-second order kinetic models showed that the retention of ACG onto the adsorbents predominantly occurred through chemical adsorption. Langmuir, Freundlich, and Dubinin-Radushkevich isotherm models were employed to provide insights into the interaction between the adsorbate and adsorbent and the mechanism of the adsorption process. Maximum monolayer adsorption capacities of natural and H2SO4-modified acacia sawdust were determined as 28.01 and 64.90 mg g-1, respectively by Langmuir isotherm model. Results of the study clearly indicated that the modification of acacia sawdust with H2SO4 leads to a substantial increase in the adsorption performance of anionic dyes.

Resistance Function of Woody Landscape Plants to Air Pollutants(II) - POD Activity - (조경수목(造景樹木)의 대기오염물질(大氣汚染物質)에 대한 방어기능(防禦機能)(II) - POD 활성(活性)을 중심으로 -)

  • Kim, Myung Hee;Lee, Soo Wook
    • Journal of Korean Society of Forest Science
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    • v.81 no.3
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    • pp.234-246
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    • 1992
  • This study was conducted to determine the toxic effects of air pollutants on landscaping tress, Pinus densiflora, Pinus koraiensis, Ginkgo biloba, Liriodendron tulipifera, Platanus occidentalis and their resistance to the pollutant toxicity in urban and industrial regions of Seoul and Taejon, Korea. Total sulfur contents and enzyme activities such as superoxide dismutase and peroxidase were analyzed in tree foliage of Pinus densiflora, Pinus koraiensis, Ginkgo biloba, Liriodendron tulipifera, Platanus occidentalis. In addition, POD activity was analyzed in the foliage on tree seedlings, i.e. Pinus densiflora, Pinus koraiensis, Ginkgo biloba, Lirioderdron tulipifera, with the fumigation of $SO_2$ in gas chamber 4 hours a day for six days. In Ginkgo biloba total sulfur content and POD activity had a negative correlation while other species had a positive relationship in total sulfur content and enzyme activity. Air pollutants accumulated in tree tissues were supposed to enhance the enzyme activity like POD providing the resistance mechanisms. Especially Pinus koraiensis and Platanus occidentalis had higher POD activity than other species. The increase of temporary POD activity against environmental stress appeared in sensitive trees and prolonged increase of POD activity played an important role in resistance mechanism. SOD and POD activities in all species had a positive correlation except Ginkgo biloba. Changes of SOD and POD activities were different between species and in most species SOD as well as POD seemed to participate in resistance mechanism.

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A Study on the Protective Effect and Its Mechanism of Zinc against Immuno-cytotoxicity of Methylmercury (유기수은의 세포면역독성과 이에 대한 아연의 방어효과 및 기전)

  • 고대하;염정호;오경재
    • Journal of Environmental Health Sciences
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    • v.27 no.2
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    • pp.82-91
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    • 2001
  • This study was carried out to elucidate the protective effect of zinc chloride(ZnCl$_2$) and its mechanism against the immuno-cytotoxicity of methylmercury chloide($CH_3$HgCl). This study was observed in the culture of EMT-6 cells which are originated from mammary adenocarcinoma of Balb/c mouse. Cytotoxicity of metals was measured by cell viability and NO$_2$$^{[-10]}$ , and mitochondrial function was evaluated by adenosine triphosohate (ATP) production. $CH_3$HgCl significantly decreased the sythesis of nitric oxide(NO), ATP and glutathione(GSH) in a dose-dependent manner. ZnCl$_2$ significantly increased the synthesis of GSH in a dose-dependent manner, but synthesis of NO and ATP were not changed. The immuno-cytotoxicity of $CH_3$HgCl was not fully protected when combined addition of ZnCl$_2$, whereas ZnCl$_2$ prior to addition of $CH_3$HgCl completly protected the Hg-induced immuno-cytotoxicity. Similarly, intracellular accumulation of mercury significantly decreased by ZnCl$_2$. Degree of diminution of intracellular mercury was larger in ZnCl$_2$ prior to addition of $CH_3$HgCl than in combined addition of ZnCl$_2$ and $CH_3$HgCl.. Dithiothreitol(DTT) or buthionine sulfoximine(BSO) addition at 50$\mu$M or less, which was not toxic to the cells, did not affect synthesis of NO and ATP. DTT increased intracellular GSH level and DTT pretreatment protected toxicity induced by $CH_3$HgCl as shown complete recover in the NO and ATP values. BSO decreased intracellular GSH level and BSO pretreatment exaggerated toxicity induced by $CH_3$HgCl as shown synergistic reduction in the NO and ATP values. These results indicated that the protective effects of zinc against immuno-cytotoxicity of methylmercury associated with increasing cellular level of GSH. Increased intracellular GSH transports methylmercury to out of cells. In accordance with intracellular level of mercury decreased, immuno-cytotoxicity of methylmercury decreased. These result also suggest that the protective mechanism of zinc against the mercury toxicity would be exerted in the immune system in vivo.

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Panax ginseng and its ginsenosides: potential candidates for the prevention and treatment of chemotherapy-induced side effects

  • Wan, Yan;Wang, Jing;Xu, Jin-feng;Tang, Fei;Chen, Lu;Tan, Yu-zhu;Rao, Chao-long;Ao, Hui;Peng, Cheng
    • Journal of Ginseng Research
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    • v.45 no.6
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    • pp.617-630
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    • 2021
  • Chemotherapy-induced side effects affect the quality of life and efficacy of treatment of cancer patients. Current approaches for treating the side effects of chemotherapy are poorly effective and may cause numerous harmful side effects. Therefore, developing new and effective drugs derived from natural nontoxic compounds for the treatment of chemotherapy-induced side effects is necessary. Experiments in vivo and in vitro indicate that Panax ginseng (PG) and its ginsenosides are undoubtedly non-toxic and effective options for the treatment of chemotherapy-induced side effects, such as nephrotoxicity, hepatotoxicity, cardiotoxicity, immunotoxicity, and hematopoietic inhibition. The mechanism focus on anti-oxidation, anti-inflammation, and anti-apoptosis, as well as the modulation of signaling pathways, such as nuclear factor erythroid-2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), P62/keap1/Nrf2, c-jun Nterminal kinase (JNK)/P53/caspase 3, mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinases (ERK), AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase kinase 4 (MKK4)/JNK, and phosphatidylinositol 3-kinase (PI3K)/AKT. Since a systemic review of the effect and mechanism of PG and its ginsenosides on chemotherapy-induced side effects has not yet been published, we provide a comprehensive summarization with this aim and shed light on the future research of PG.

Study on the Regulation of KAP3 Gene Involved in the Brain Sexual Differentiation by DDT during the Critical Period of Fetal and Neonatal Age (출생 전.후 뇌의 성분화 결정시기에 DDT에 의한 KAP3 유전자 조절에 대한 연구)

  • 강한승;전부일;최은정;이병주;이채관;강성구
    • Development and Reproduction
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    • v.4 no.1
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    • pp.95-100
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    • 2000
  • A large number of man-made chemicals that have been released into the environment have the potential to disrupt the endocrine system of animals and humans. There is a critical developmental period during which sexual brain differentiation proceeds irreversibly under the influence of gonadal hormone. Recently we identified KAP3 gene expressed during the critical period of rat brain sexual differentiation. KAP3 functions as a microtubule-based motor that transports membranous organelles anterogradely in cells, including neurons. In the present study, we aimed to investigate the effect of endocrine disrupter, Dichlorodiphenyl trichloroethane (DDT), on the KAP3 gene expression during critical period of rat brain development. Maternal exposure to DDT increased the level of KAP3 mRNA in male and female fetus brains when examined on the gestational day 17 (GDl7). In postnatal day 6, DDT suppressed the expression of KAP3 gene in male and female rat brain. Also, the body weight and fertilization rate were decreased in the DDT exposured rats. These results showed that endocrine disrupter, DDT, can affect the transcriptional level of brain sexual differentiation related gene, KAP3, in the prenatal and the neonatal rat brain and that maternal exposure to endocrine disruptors may lead to a toxic response in embryonic differentiation of brain. And so KAP3 gene may be used a gene maker to analyse the molecular mechanism for toxic response in animal nerve tissues exposed to endocrine disruptors.

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