• Title/Summary/Keyword: Iron-overload

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Polyploidization of Hepatocytes: Insights into the Pathogenesis of Liver Diseases

  • Kim, Ju-Yeon;Choi, Haena;Kim, Hyeon-Ji;Jee, Yelin;Noh, Minsoo;Lee, Mi-Ock
    • Biomolecules & Therapeutics
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    • v.30 no.5
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    • pp.391-398
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    • 2022
  • Polyploidization is a process by which cells are induced to possess more than two sets of chromosomes. Although polyploidization is not frequent in mammals, it is closely associated with development and differentiation of specific tissues and organs. The liver is one of the mammalian organs that displays ploidy dynamics in physiological homeostasis during its development. The ratio of polyploid hepatocytes increases significantly in response to hepatic injury from aging, viral infection, iron overload, surgical resection, or metabolic overload, such as that from non-alcoholic fatty liver diseases (NAFLDs). One of the unique features of NAFLD is the marked heterogeneity of hepatocyte nuclear size, which is strongly associated with an adverse liver-related outcome, such as hepatocellular carcinoma, liver transplantation, and liver-related death. Thus, hepatic polyploidization has been suggested as a potential driver in the progression of NAFLDs that are involved in the control of the multiple pathogenicity of the diseases. However, the importance of polyploidy in diverse pathophysiological contexts remains elusive. Recently, several studies reported successful improvement of symptoms of NAFLDs by reducing pathological polyploidy or by controlling cell cycle progression in animal models, suggesting that better understanding the mechanisms of pathological hepatic polyploidy may provide insights into the treatment of hepatic disorders.

Suppressive Effect of Zinc on the Formation of Colonic Preneoplastic Lesions in the Mouse Fed High Levels of Dietary Iron

  • Park, Hyun-Ji;Kang, Bong-Su;Kim, Dang-Young;Yoon, Ja-Seon;Jeong, Jae-Hwang;Nam, Sang-Yoon;Yun, Young-Won;Kim, Jong-Soo;Lee, Beom-Jun
    • Toxicological Research
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    • v.28 no.1
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    • pp.39-49
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    • 2012
  • We investigated the effect of zinc on the formation of colonic aberrant crypt foci induced by azoxymethane (AOM) followed by dextran sodium sulfate (DSS) in mice with high iron diet (HFe; 450 ppm iron). Sixweek old ICR mice were fed on high iron diets with combination of three different levels of zinc in diets, low-zinc (LZn; 0.01 ppm), medium-zinc (MZn; 0.1 ppm), and high-zinc (HZn; 1 ppm) for 12 weeks. Animals were received weekly intraperitoneal injections of AOM (10 mg/kg B.W. in saline) for 3 weeks followed by 2% DSS (molecular weight 36,000~50,000) in the drinking water for a week. To confirm the iron storage in the body, the hepatic iron concentration has been determine chemically and compared with histological assessment visualized by Prussian blue reaction. Aberrant crypt (AC) and aberrant crypt foci (ACF) were analyzed in the colonic mucosa of mouse fed high dietary iron. Superoxide dismutase (SOD) activity and thiobarbituric acid-reactive substances (TBARS) level were also investigated. Apoptosis in the preneoplastic lesion was determined by terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling (TUNEL). In addition, immunohistochemistry of ${\beta}$-catenin was also performed on the mucous membrane of colon. The number of large ACF (${\geq}4$ AC/ACF), which possess greater tumorigenic potential, was significantly lower in MZn and HZn groups compared with LZn group. Cytosolic SOD activity in the liver was significantly higher in HZn group compared with LZn group. Hepatic MDA level was decreased significantly in HZn group compared with MZn and LZn groups. Apoptotic index was significantly higher in HZn group. Taken together, these findings indicate that dietary zinc might exert a protective effect against colonic preneoplastic lesion induced by AOM/DSS in ICR mice with high iron status, and suggest that dietary supplement of zinc might play a role in suppressing colon carcinogenesis in mice.

Ferritin Overload Suppresses Male Fertility Via altered Acrosome Reaction

  • Kwon, Woo-Sung;Rahman, Md Saidur;Kim, Ye-Ji;Ryu, Do-Yeol;Kahtun, Amena;Pang, Myung-Geol
    • Reproductive and Developmental Biology
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    • v.39 no.4
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    • pp.117-125
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    • 2015
  • Iron is required for cell viability but is toxic in excess. While the iron-mediated malfunction of testicular cells is well appreciated, the underlying mechanism(s) of this effect and its relationship with fertility are poorly understood. Ferritin is a ubiquitous intracellular protein that controls iron storage, ferroxidase activity, immune response, and stress response in cells. Ferritin light chain protein (FTL) is the light subunit of the Ferritin. Previously, we had identified the FTL in bovine spermatozoa following capacitation. In present study, to investigate the role of Ferritin in sperm function, mice spermatozoa were incubated with multiple doses (1, 10 and $100{\mu}M$) of sodium nitroprusside (SNP), an iron donor. SNP was increased Ferritin levels in a dose-dependent manner. The Ferritin was detected on the acrosome in spermatozoa by immunocytochemistry. Short-term exposure of spermatozoa to SNP increased tyrosine phosphorylation and the acrosome reaction (AR). Finally, SNP affected a significant decrease in the rate of fertilization as well as blastocyst formation during early embryonic development. On the basis of these results, we propose that the effects of Ferritin on the AR may reduce overall sperm function leads to poor fertility in males and compromised embryonic development.

The Relationship between Serum Ferritin and Bone Mineral Density

  • Jo, Yoon-Kyung;Seok, Ju-Won;Kim, Jung-Ha
    • Biomedical Science Letters
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    • v.16 no.4
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    • pp.293-298
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    • 2010
  • Several risk factors for osteoporosis are known relatively well. Some nutrients are directly or indirectly needed for metabolic processes related to bone. Recently, an increased prevalence of osteoporosis has been reported in patients with hemochromatosis, an iron overload disease. Thus, the aim of this study was to find out if there was any relationship between serum ferritin and T-score of bone mineral density in healthy women. We recruited 1,101 subjects females aged between 39 and 85 years. We measured serum ferritin, glucose tolerance indices, lipid profiles, inflammatory indices, hormones, calcium, alkaline phosphatase. Also, anthropometric, blood pressure, and bone mineral density measurements were performed. T-score was negatively correlated with age (r=-0.425; P<0.01), systolic (r=-0.109; P<0.01) and diastolic (r=-0.093; P<0.01) pressure, follicular stimulation hormone (r=-0.190; P<0.01), alkaline phosphatase (r=-0.235; P<0.01), and serum ferritin (r=-0.090; P<0.05) and positively with body mass index (r=0.050; P=0.01), HDL-cholesterol (r=0.314; P<0.01), and estradiol (r=0.200; P<0.01). After adjustment for age, alkaline phosphatase, body mass index, HDL-cholesterol, estradiol, and follicular stimulation hormone, serum ferritin was independently inversely correlated with T-score (${\beta}$=-0.001; P<0.05). It is possible that an increase of serum ferritin in females be risk to osteoporosis.

Transcriptional regulation of genetic variants in the SLC40A1 promoter

  • Seung Yeon Ha;Jin-Young Kim;Ji Ha Choi
    • The Korean Journal of Physiology and Pharmacology
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    • v.28 no.2
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    • pp.113-120
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    • 2024
  • Solute carrier 40A1 (SLC40A1) encodes ferroportin, which is the only known transmembrane protein that exports elemental iron from mammalian cells and is essential for iron homeostasis. Mutations in SLC40A1 are associated with iron-overload disorders. In addition to ferroportin diseases, SLC40A1 expression is downregulated in various cancer types. Despite the clinical significance of the SLC40A1 transporter, only a few studies have investigated genetic variants in SLC40A1. The present study was performed to identify genetic variations in the SLC40A1 promoter and functionally characterize each variant using in vitro assays. We investigated four haplotypes and five variants in the SLC40A1 promoter. We observed that haplotype 3 (H3) had significantly lower promoter activity than H1, whereas the activity of H4 was significantly higher than that of H1. Luciferase activity of H2 was comparable to that of H1. In addition, four variants of SLC40A1, c.-1355G>C, c.-662C>T, c.-98G>C, and c.-8C>G, showed significantly increased luciferase activity compared to the wild type (WT), whereas c.-750G>A showed significantly decreased luciferase activity compared to the WT. Three transcription factors, cAMP response element-binding protein-1 (CREB-1), chicken ovalbumin upstream promoter transcription factor 1, and hepatic leukemia factor (HLF), were predicted to bind to the promoter regions of SLC40A1 near c.-662C>T, c.-98G>C, and c.-8C>G, respectively. Among these, CREB1 and HLF bound more strongly to the variant sequences than to the WT and functioned as activators of SLC40A1 transcription. Collectively, our findings indicate that the two SLC40A1 promoter haplotypes affect SLC40A1 transcription, which is regulated by CREB-1 and HLF.

An examples of a 6-inch GTO inverter drive system applied for rougher mills

  • Kawasaki, Muneo;Okayama, Hideo;Koyama, Masato;Mitsuhashi, Masamichi;Masuda, Hiroyuki
    • 제어로봇시스템학회:학술대회논문집
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    • 1996.10a
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    • pp.25-28
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    • 1996
  • Recently, AC variable-speed motors are used for many steel rolling mill drive systems, because of their low maintenance and enhanced control performance. We have been applied GTO inverters for these AC motor drive systems since 1993. We have developed world largest 6-inch diameter GTO and large capacity 3-level GTO inverter up to 20000(kVA). As an example, in this paper, we describe the main circuit, system arrangement and control features of the 6-inches GTO inverters to drive rougher mills for hot strip mill of Pohang Iron & Steel Co., Ltd. The motor capacity is 6000(kW), and it's overload is 250(%).

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A Study on Electrical Fire of Small Ventilators due to Aged Degradation (경년열화에 의한 소형 환풍기의 전기화재에 관한 연구)

  • Lim, Jong Yong;Lee, Sung Ill
    • Journal of the Korean Society of Safety
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    • v.31 no.4
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    • pp.22-26
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    • 2016
  • "Always-on" small ventilators are likely to experience thermal decomposition of insulating material due to thermal, electrical, mechanical and environmental influences, and lose insulating properties by the process of oxidation and physiochemical reaction. This increases the risk of electrical fire because of layer short, short circuit, overload and Plastics are usually used to make ventilator and ventilator enclosures since they make less noise and are cheaper. Although more preferred than iron, plastic, a combustible material, has a higher risk of fire. In this study, several experiments were carried out to find out how RCD(Residual Current Protective Device) and Thermal fuses, which are electric motor protection devices, work and what needs to be done to reduce the risk of fire.

Iron chelating agent, deferoxamine, induced apoptosis in Saos-2 osteosarcoma cancer cells (Saos-2 골육종 세포에서 iron chelating agent, deferoxamine에 의한 apoptosis 유도)

  • Park, Eun Hye;Lee, Hyo Jung;Lee, Soo Yeon;Kim, Sun Young;Yi, Ho Keun;Lee, Dae Yeol;Hwang, Pyoung Han
    • Clinical and Experimental Pediatrics
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    • v.52 no.2
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    • pp.213-219
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    • 2009
  • Purpose:Iron is a critical nutritional element that is essential for a variety of important biological processes, including cell growth and differentiation, electron transfer reactions, and oxygen transport, activation, and detoxification. Iron is also required for neoplastic cell growth due to its catalytic effects on the formation of hydroxyl radicals, suppression of host defense cell activities, and promotion of cancer cell multiplication. Chronic transfusion-dependent patients receiving chemotherapy may have iron overload, which requires iron-chelating therapy. We performed this study to demonstrate whether the iron chelating agent deferoxamine induces apoptosis in Saos-2 osteosarcoma cells, and to investigate the underlying apoptotic mechanism. Methods:To analyze the apoptotic effects of an iron chelator, cultured Saos-2 cells were treated with deferoxamine. We analyzed cell survival by trypan blue and crystal violet analysis, apoptosis by nuclear condensation, DNA fragmentation, and cell cycle analysis, and the expression of apoptotic related proteins by Western immunoblot analysis. Results:Deferoxamine inhibited the growth of Saos-2 cell in a time- and dose-dependent manner. The major mechanism for growth inhibition with the deferoxamine treatment was by the induction of apoptosis, which was supported by nuclear staining, DNA fragmentation analysis, and flow cytometric analysis. Furthermore, bcl-2 expression decreased, while bax, caspase-3, caspase-9, and PARP expression increased in Saos-2 cells treated with deferoxamine. Conclusion:These results demonstrated that the iron chelating agent deferoxamine induced growth inhibition and mitochondrial-dependent apoptosis in osteosarcoma Saos-2 cells, suggesting that iron chelating agents used in controlling neoplastic cell fate can be potentially developed as an adjuvant agent enhancing the anti-tumor effect for the treatment of osteosarcoma.

The Comparison of dietary behavior and nutrients intakes with different kinds of Stress at university students of outer region of Seoul (대학생의 스트레스와 식행동 및 영양 섭취 상태 비교 - 수도권 1개 대학 재학생을 중심으로 -)

  • 이승교;이영희
    • The Korean Journal of Community Living Science
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    • v.12 no.2
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    • pp.33-45
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    • 2001
  • This study was performed to investigate the degree of different stresses in university students of outer region of Seoul and to search the influence of food habit and nutrient intakes in stress. The data was collected by questionnaire method for self-diagnosed different stresses, dietary habit, and physical status and 24 hours recall for nutrient intakes. The subjects were 282 students attended at the lecture Food and Health. Diet balance was no difference with gender but food intakes were more diverse in female. Nutrient intake of male students was lower in vitamin A and riboflavin, but that of female was low in vitamin A and iron. The university students outer region of Seoul had more stress situation in frustration, deprivation and self-efface than in the stress of the noise and Type-A behavioral stress. Total self-diagnosed dietary habit score was better in the group of no susceptive overload stress than that of the high susceptive group. Same trend of dietary behavior score was in the group of no noise and anxiety-response stress than that in the susceptive groups. The quantity of nutrient intakes was correlated with different kind of stress. Niacin intake was positively related with the stress from life-events, and food induced stress. Thiamin intake was positively related with food induced stress. But the intake of iron, calcium, niacin and riboflavin were negatively related with the stress of noise. Therefore, we could concluded that different kind of stresses were influenced in dietary behavior and vitamin-mineral nutrient intakes. More research would be needed at the aspects of health promotion in the stressful situation of modern society.

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Lumped-Parameter Thermal Analysis and Experimental Validation of Interior IPMSM for Electric Vehicle

  • Chen, Qixu;Zou, Zhongyue
    • Journal of Electrical Engineering and Technology
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    • v.13 no.6
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    • pp.2276-2283
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    • 2018
  • A 50kW-4000rpm interior permanent magnet synchronous machine (IPMSM) applied to the high-performance electric vehicle (EV) is introduced in this paper. The main work of this paper is that a 2-D T-type lumped-parameter thermal network (LPTN) model is presented for IPMSM temperature rise calculation. Thermal conductance matrix equation is generated based on calculated thermal resistance and loss. Thus the temperature of each node is obtained by solving thermal conductance matrix. Then a 3-D liquid-solid coupling model is built to compare with the 2-D T-type LPTN model. Finally, an experimental platform is established to verify the above-mentioned methods, which obtains the measured efficiency map and current wave at rated load case and overload case. Thermocouple PTC100 is used to measure the temperature of the stator winding and iron core, and the FLUKE infrared-thermal-imager is applied to measure the surface temperature of IPMSM and controller. Test results show that the 2-D T-type LPTN model have a high accuracy to predict each part temperature.