• BMB Reports
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• 제33권5호
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• pp.396-401
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• 2000

A differential display method is used to identify novel genes whose expression is affected by treatment with ferric ammonium citrate (FAC) or desferrioxamine (DFO), an iron chelating agent in the human hepatoblastoma cell line (HepG2). These chemicals are known to deplete or increase the intracellular concentration of iron, respectively. Initially, we isolated seventeen genes whose expressions are down- or up regulated by the treatment of the chemicals, as well as their four differentially expressed genes that are designated as clone-1, -2, -3, and -4. These are further characterized by cDNA sequencing and Northern blot analysis. Through the cDNA sequencing, as well as comparing them to genes published using the NCBI BLAST program, we identified the sequence of the clone-1 that is up-regulated by the treatment of DFO. It is identical to the human insulin-like growth factor binding protein-1 (IGFBP-1). This suggests that the IGFBP-1 gene in the HepG2 cell is up-regulated by an iron depletion condition. Also, the expression of the clone-3 and -4 is up-regulated by FAC treatment and their eDNA sequences are identical to the human ferritin-fight chain and human NADH-dehydrogenase, respectively. However, the sequence of the clone-2 has no significant homology to any other known gene. Therefore, we suggest that changes of the cellular iron level in the HepG2 cell affects the transcription of cellular genes. This includes human IGFBP-1, ferritin-fight chain, and NADH-dehydrogenase. Regulation of these gene expressions may have an important role in cellular functions that are related to cellular iron metabolism.

• 한국임상약학회지
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• 제22권3호
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• pp.202-210
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• 2012

Methoxy polyethylene glycol-epoetin beta (MPG-EPO), a continuous erythropoietin receptor activator, is a new erythropoiesis-stimulating agent with a long half-life. The purpose of this prospective study is to assess the effects of once-monthly subcutaneous MPG-EPO on hematological responses and nutritional status in peritoneal dialysis patients. Forty four patients undergoing stable peritoneal dialysis were enrolled into the study. Darbepoetin alfa therapy, in peritoneal dialysis patients, was converted to the monthly administration of subcutaneous MPG-EPO for 6 months. The starting dose of MPG-EPO was based on the previous weekly dose of darbepoetin alfa. The dose adjustments were performed to maintain the hemoglobin (Hb) levels in a target range of 10.5-11.0 g/dL. If the Hb levels exceeded 11.0 g/dL, MPG-EPO was temporarily interrupted for 1 month. The mean Hb levels were stable with the values of $9.5{\pm}1.1$ g/dL at baseline, and $10.4{\pm}0.9$ g/dL at the 6th month after conversion. The mean differences in the changes of Hb levels between the baseline and the 6th month were $0.9{\pm}1.4$ g/dL, which was statistically significant. However, the mean differences of iron, transferrin saturation and ferritin concentrations were not significant. It did not show significant differences in the changes of the nutritional parameters. These results suggest that the once-monthly subcutaneous administration of MPG-EPO for 6 months effectively maintains the Hb levels and nutritional status in peritoneal dialysis patients. Taken together, the once-monthly subcutaneous administration of MPG-EPO was practical and might improve the clinical compliance for the management of renal anemia in peritoneal dialysis patients.

• 한국동물학회지
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• 제31권3호
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• pp.207-217
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• 1988

배양 계배 근원세포의 분화에 미치는 계배추출물의 영향을 조사하고, 이 추출물로부터 근워세포의 분화에 필수적인 myotrophic protein(MP)를 순수분리하였다. 그리고 이 MP는 철 운반 단백질인 trsnaferrin과 동일하거나 또는 대단히 유사한 단백질임을 알 수 있었다. 이 단백질은 철을 근원세포에 공급하고 이 철근이 근원세포의 융합에 필수적인 역할을 하는 것으로 보인다. 또 계배추출물속에는 이 MP이외에 근원세포의 융합을 억제하는, 그리고 열에 비교적 안정한 단백질이 존재하다고 생각된다. 이 MP의 수용체(receptor)분석을 한 결과, 수용체의 수는 근원세포가 융합을 하고 나면 급속히 감소하는 것으로 나타났다. 그리고 근원세포의 내로의 철과 MP의 수송에는 약 10분이 소요되는 것으로 나타났다.

• 대한지역사회영양학회지
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• 제9권2호
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• pp.142-150
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• 2004

To increase both iron and enhancers for iron absorption through diets should be a basic strategy to sufficiently provide increased iron for pregnancy. Previous studies reported that iron intakes of Korean pregnant women were short and their iron status deteriorated as pregnancy progressed. However, there is little data about the bioavailability of dietary iron during pregnancy. Therefore, this study was conducted to determine the changes of dietary iron intakes, its bioavailability and iron status during pregnancy longitudinally in Korean women. A total of 151 pregnant women in their first trimester of pregnancy voluntarily participated. Among them, 72 women finished the research protocol during the second trimester and 55 did it during the third trimester. Dietary intakes of total iron, both non-heme and heme iron, as well as enhancers, both MPF (meat, poulty, and fish) and vitamin C, increased significantly as pregnancy progressed. As the results, bioavailability of dietary iron and iron absorbed increased significantly as pregnancy progressed. However, the amount of iron absorbed at each trimester did not meet considerably the iron needed during pregnancy. All five indices examined in the study, Hb level, Hct, serum concentrations of ferritin and sTfR (soluble transferrin receptor), and sTfR: ferritin ratio, showed that iron status of the subjects deteriorated as pregnancy progressed. The rate of anemia of the subjects increased as pregnancy progressed although more than 80% of the subjects took iron supplements after the 20th week of pregnancy. These results imply that it is needed to provide more iron especially, heme iron and dietary enhancers to prevent the deterioration of iron status during pregnancy. Future research on bioavailability of supplemental iron should be performed to determine the iron balance precisely.

• Molecular Medicine Reports
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• 제20권4호
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• pp.3933-3941
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• 2019

The microbiome has recently attracted research interest in a variety of subjects, including cancer. In the present study, it was determined that reinforced clostridium media (RC M) for microbiome culture, exerts antitumor effects on renal cell carcinoma cells when compared to the microbiome 'X'. The antitumor effects of RC M were investigated for all ingredients of RC M, and the results revealed that yeast extract could be a candidate for the ingredient driving this phenomenon. Further experiments including MTT assay, cell counting, cell death analysis, cell cycle analysis and western blotting were conducted with yeast extract on renal cell carcinoma cells (Caki-1 and Caki-2) and normal human proximal tubular cells (HK-2). As a result, yeast extract exhibited dose-dependent antitumor effects on Caki-1 and Caki-2, but only slight effects on HK-2. In addition, yeast extract only exhibited slight effects on necrosis, autophagy, or apoptosis of Caki-1 and Caki-2. Yeast extract produced cell cycle arrest with an increased G0/G1 fraction and a decreased S fraction, and this was considered to be related to the decreased cyclin D1. Although yeast extract treatment increased anti-oxidant activities, the antitumor effects of yeast extract were also related to iron metabolism, based on the decreased transferrin receptor and increased ferritin. In addition, decreased GPX4 may be related to iron-dependent cell death, particularly in Caki-2. These results revealed that yeast extract may inhibit proliferation of renal cell carcinoma cells by regulating iron metabolism. Since an increased iron requirement is a classic phenomenon of cancer cells, yeast extract may be a candidate for adjuvant treatment of renal cell carcinoma.

• 한국미생물학회:학술대회논문집
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• 한국미생물학회 2004년도 International Meeting of the Microbiological Society of Korea
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• pp.141-146
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• 2004

SPIN90 was identified to farm molecular complex with $\betaPIX$, WASP and Nck. This complex shows that SPIN90 interacts with Nck in a manner dependent upon cell adhesion to extracellular matrix, but $SPIN90{\cdot}{\beta}PIX{\cdot}WASP$ complex was stable even in suspended cells. This suggests that SPIN90 serves as an adaptor molecule to recruit other proteins to Nck at focal adhesions. SPIN90 was phosphorylated by ERK1, which was, itself, activated by cell adhesion and platelet-derived growth factor. Such phosphorylation of SPIN90 likely promotes the interaction of the $SPIN90{\cdot}{\beta}PIX{\cdot}WASP$ complex and Nck. It thus appears that the interaction of the $SPIN90{\cdot}{\beta}PIX{\cdot}WASP$ complex with Nck is crucial for stable cell adhesion and can be dynamically modulated by SPIN90 phosphorylation that is dependent on cell adhesion and ERX activation. SPIN90 directly binds syndapin I, syndapin isoform II-1 and II-s via its PRD region in vitro, in vivo and also associates with endocytosis core components such as clathrin and dynamin. In neuron and fibroblast, SPIN90 colocalizes with syndapins as puntate form, consistent with a role for SPIN90 in clathrin-mediated endocytosis pathway. Overexpression of SPIN90 N-term inhibits receptor-mediated endocytosis. Interestingly, SPIN90 PRD, binding interface of syndapin, significantly blocks internalization of transferrin, demonstrating SPIN90 involvement in endocytosis in vivo by interacting syndapin. Depletion of endogenous SPIN90 by introducing $\alpha-SPIN90$ also blocks receptor-mediated endocytosis. Actin polymerization could generate farce facilitating the pinch-out event in endocytosis, detach newly formed endocytic vesicle from the plasma membrane or push out them via the cytosol on actin tails. Here we found that SPIN90 localizes to high actin turn over cortical area, actin-membrane interface and membrane ruffle in PDGF treated cells. Overexpression of SPIN90 has an effect on cortical actin rearrangement as filopodia induction and it is mediated by the Arp2/3 complex at cell periphery. Consistent with a role in actin organization, CFP-SPIN90 present in actin comet tail generated by PIP5 $kinase\gamma$ overexpression. Therefore this study suggests that SPIN90 is functional linker between endocytosis and actin cytoskeleton.

• 대한약침학회지
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• 제7권3호
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• pp.5-25
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• 2004

Objectives : To observe changes in the serum proteins before and after intravenous injection of wild ginseng herbal acupuncture. Methods : Blood was collected before and after the administration of wild ginseng herbal acupuncture and only the serum was centrifuged. Then differences in the spots on the scanned image after running 2-Dimensionl electrophoresis were located and conducted mass analysis and protein identification. Results : Following results were obtained from the comparative analysis of serum proteins before and after the administration of wild ginseng herbal acupuncture. 1. 28 spots were identified before and after the administration. 2. In confirming manifestation degree, spots with more than two-times increase were 204, 803, 1505, 2205, 3105, 7104, 9001 spots, with more than one-time increase were 1101, 1302, 2013, 3009, 3010, 4002, 4009, 6706, 7103, 8006, 8101, and spots with decrease were 205, 801, 3205, 5202, 6105. 3. After conducting protein identification, proteins 205, 804, 1302, 4009, 6105, 6106 are unidentified yet, and 1101 is unnamed protein. Protein 204 is identified as complement receptor CR2-C3d, 801 as YAP1 protein, 803 as antitrypsin polymer, 1505 as PRO0684, 2013 and 3010 as proapolipoprotein, 2205 as USP48, 2403 as vitamin D binding protein, 3009 as complement component 4A preprotein, 3105 as immunoglobulin lambda chain, 3205 as transthyretin, 4002 as Ras-related protein Ral-A, 4204 as beta actin, 5202 and 7104 as apolipoprotein L1, 6704 as alpha 2 macroglobulin precursor, 7103 as complement component 3 precursor, 8006 as testis-specific protein Y, 8101 as Transferrin, 9001 as(Alpha-Oxy, Beta-(C112g)deoxy) T-State Human Hemoglobin, and 9003 as human hemoglobin. 4. Immune protein CR2-C3d, which acts against microbes and pathogenic organisms, and Antitrypsin(803), which is secreted with inflammatory response in the lungs, were increased by more than 200% after the administration of herbal acupuncture. 5. Immunoglobulin lambda chain(3105), Alpha-Oxy, Beta-(C112g)deoxy T-State Human Hemoglobin(9001), and human hemoglobin(9003) were increased by more than two-times after the administration of herbal acupuncture. 6. Proapolipoprotein(2013, 3010) and apolipoprotein(7104), key components of the HDL-cholesterol which plays an important role in preventing arteriosclerosis, were increased after the administration of herbal acupuncture. 7. Vitamin D binding protein(DBP, 2403), protecting the lung at the time of inflammatory response, was increased after the administration of herbal acupuncture. 8. Transthyretin(TTR, 3205), which is the main protein causing familial aimyloid polyneuropathy(FAP), was decreased after the administration of herbal acupuncture. 9. Ras-related protein Ral-A(4002) that controls phospholipid metabolism, cytoskeletal formation, and membrane traffic, was increased after the administration of herbal acupuncture. 10. Testis-specific protein Y(8006), which takes part in determination of the gender, was increased by more than two-times after the administration of herbal acupuncture. 11. Transferrin(8101), T-State Human Hemoblobin(9001), and Human Hemoblobin(9003) which balances the iron level in the body, were increased after the administration of herbal acupuncture. Conousion : Above results support the notion that intravenous injection of cultivated wild ginseng herbal acupuncture induce changes in serum proteins and this research can be a pioneer work in finding biomarkers.

• 한국임상약학회지
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• 제21권2호
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• pp.122-130
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• 2011

Objective: Although recombinant human erythropoietin (rhEPO) has revolutionized the treatment of anemia in chronic kidney disease (CKD) receiving hemodialysis (HD) with no need of blood transfusion, some patients have a blunted or appear to be resistant to rhEPO. There is a controversy in the causes of rhEPO resistance in maintenance HD patients with anemia. This study is to examine current anemia treatment outcomes and the factors influencing the rhEPO responsiveness in HD patient with CKD. Methods: The clinical parameters or factors relating to erythrompoietin treatment outcomes and erythropoietin responsiveness were collected from the HD patients in two large dialysis centers for three months. The collected paramenters included serum iron, total iron biding capacity (TIBC), transferrin saturation rate, ferritin, albumin, intact PTH, C-reactive protein (CRP), nPCR and medications such as an angiotensin converting enzyme inhbitor, an angiotension II receptor blocker and an HMG-CoA reductase inhibitor (HMG-CoA RI). The data were analyzed to examine the degree of acheiveing the anemia treatment goal and factors relating to ERI. Results: Among total 111 patients, 42 (42.3%) and 47 (37.8%) patients achieved the target Hct and Hb based on the Health Insurance Review and Assessment Services (HIRA) reimbursement criteria. In the higher ERI group (upper quartile), the patients had higher CRP levels (0.5 mg/dl) (p=0.0096), and lower TIBC score (<$240{\mu}g/dl$) (p=0.0027), and less patients were taking HMG-CoA RI (p=0.0019). Male patients (p=0.0204), patients with high TIBC score ($R^2$=0.084, p=0.0021) and patients taking HMG-CoA RI (p=0.0052) required to administer less dose of rhEPO meaning higher erythropoietin responsiveness. Conclusion: Less than 50% of CKD patients were achieving the goals of anemia by erythropoietin administration in large hospitals in Korea even though the goals were lower than those of NKF-K/DOQI practice guideline. The factors influencing ERI were sex, TIBC and HMG-CoA RI administration status, and neither an ACEI nor an ARB did not influence ERI.

• 한국가정과학회지
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• 제4권1호
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• pp.36-45
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• 2001

This study was performed to determine the changes of maternal iron status during pregnancy cross sectionally, and to evaluate the appropriateness of the cut-off points of hemoglobin (Hb). hematocrit (Hct), serum transferrin receptor (sTfR) and sTfR : ferritin ratio for assessing iron deficiency status based on serum ferritin level (< 12${\mu}g$/L). Serum Hb concentrations in the first trimester were significantly higher (p < 0.05) than those in the second and third trimester. Serum levels of iron and ferritin in the third trimester were significantly lower (p < 0.05) than those in the first and second trimester. On the other hand, sTfR:ferritin ratios in the third trimester were significantly higher (p < 0.05) than those in the first and second trimester. sTfR concentrations did not change significantly during pregnancy. The appropriate cut-off points of Hb were 11.5g/dL for whole period of pregnancy. 12.0g/dL for 1st trimester. and 11.5g/dL for both 2nd and 3rd trimester. The good cut-off points of Hct were 34% for whole period of pregnancy. 36% for 1st trimester. and 34% for both 2nd and 3rd trimester The suitable cut-off points of TIBC were 400${\mu}g$/dL for whole period of pregnancy. 360${\mu}g$/dL for 1st trimester, and 400${\mu}g$/dL for both 2nd and 3rd trimester. Any cut-off point of sTfR could not be selected because of its low sensitivity and specificity. The proper cut-off point of sTfR : ferritin ratio was 600 or 650 for all the periods determined except the first trimester. In conclusion, there were no reliable cut-off levels of sTfR and those of sTfR : ferritin ratio showed low specificity. The cut-off values of Hb and Hct for assessing iron deficiency were slightly higher than the values used to evaluate anemia. Thus, if appropriate cut-off levels were applied, Hb. Hct, or TIBC might be useful indices for evaluating iron deficiency as well as anemia.