• Reproductive and Developmental Biology
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• 제35권4호
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• pp.503-510
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• 2011

Cellular uptake of nanoparticles for stem cell labeling and tracking is a critical technique for biomedical therapeutic applications. However, current techniques suffer from low intracellular labeling efficiency and cytotoxic effects, which has led to great interest in the development of a new labeling strategy. Using silica-coated nanoparticles conjugated with rhodamine B isothiocyanate (RITC) (SR), we tested the cellular uptake efficiency, biocompatibility, proliferation or differentiation ability with murine bone marrow derived hematopoietic stem/progenitor cells. The bone marrow hematopoietic cells showed efficient uptake with SR with dose or time dependent manner and also provided a higher uptake on hematopoietic stem/progenitor cells. Biocompatibility tests revealed that the SR had no deleterious effects on cell cytotoxicity, proliferation, or multi-differentiation capacities in vitro and in vivo. SR nanoparticles are advantageous over traditional labeling techniques as they possess a high level of cellular internalization without limiting the biofunctionality of the cells. Therefore, SR provides a useful alternative for gene or drug delivery into hematopoietic stem/progenitor cells for basic research and clinical applications.

• Toxicological Research
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• 제30권4호
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• pp.235-242
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• 2014

Cancer cells are known to drastically alter cellular energy metabolism. The Warburg effect has been known for over 80 years as pertaining cancer-specific aerobic glycolysis. As underlying molecular mechanisms are elucidated so that cancer cells alter the cellular energy metabolism for their advantage, the significance of the modulation of metabolic profiles is gaining attention. Now, metabolic reprogramming is becoming an emerging hallmark of cancer. Therapeutic agents that target cancer energy metabolism are under intensive investigation, but these investigations are mostly focused on the cytosolic glycolytic processes. Although mitochondrial oxidative phosphorylation is an integral part of cellular energy metabolism, until recently, it has been regarded as an auxiliary to cytosolic glycolytic processes in cancer energy metabolism. In this review, we will discuss the importance of mitochondrial respiration in the metabolic reprogramming of cancer, in addition to discussing the justification for using mitochondrial DNA somatic mutation as metabolic determinants for cancer sensitivity in glucose limitation.

• 한국환경성돌연변이발암원학회지
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• 제26권1호
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• pp.1-6
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• 2006

To enhance our understanding of toxicity mediated through the pathway by which TCDD stimulates gene expression, we have investigated genes whose expressions are changed after treatment with TCDD and/or MNNG in human Chang liver cell. First, we treated with MNNG and TCDD for two weeks to transform human Chang liver cell. We obtained cell looks like to be transformed and compared the differential gene expression by using cDNA chip (Macrogen) which carrys genes related with signal transduction pathways, oncogenes and tumor suppressor genes, etc. We found that TCDD up- or down-regulated 203 and 111 genes including oncogenes and tumor suppressor genes in human Chang liver cell two fold or more, respectively. Second, we compared the differential gene expression after treatment with TCDD only by using cDNA chip (Superarray) which carrys genes related with cell cycle regulations, and found that TCDD up regulated genes related with cell proliferation as well as cell growth inhibition in human Chang liver cell two fold or more, respectively. These results suggest that toxicity induced by TCDD may reflect sustained alterations in the expression of many genes and that the changes reflect both direct and indirect effects of TCDD.

• 대한약침학회지
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• 제19권4호
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• pp.319-328
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• 2016

Objectives: Advancements in nanotechnology have led to nanoparticle (NP) use in various fields of medicine. Although the potential of NPs is promising, the lack of documented evidence on the toxicological effects of NPs is concerning. A few studies have documented that homeopathy uses NPs. Unfortunately, very few sound scientific studies have explored the toxic effects of homeopathic drugs. Citing this lack of high-quality scientific evidence, regulatory agencies have been reluctant to endorse homeopathic treatment as an alternative or adjunct treatment. This study aimed to enhance our insight into the impact of commercially-available homeopathic drugs, to study the presence of NPs in those drugs and any deleterious effects they might have, and to determine the distribution pattern of NPs in zebrafish embryos (Danio rerio). Methods: Homeopathic dilutions were studied using high-resolution transmission electron microscopy with selected area electron diffraction (SAED). For the toxicity assessment on Zebrafish, embryos were exposed to a test solution from 4 - 6 hours post-fertilization, and embryos/larvae were assessed up to 5 days post-fertilization (dpf ) for viability and morphology. Toxicity was recorded in terms of mortality, hatching delay, phenotypic defects and metal accumulation. Around 5 dpf was found to be the optimum developmental stage for evaluation. Results: The present study aimed to conclusively prove the presence of NPs in all high dilutions of homeopathic drugs. Embryonic zebrafish were exposed to three homeopathic drugs with two potencies (30CH, 200CH) during early embryogenesis. The resulting morphological and cellular responses were observed. Exposure to these potencies produced no visibly significant malformations, pericardial edema, and mortality and no necrotic and apoptotic cellular death. Conclusion: Our findings clearly demonstrate that no toxic effects were observed for these three homeopathic drugs at the potencies and exposure times used in this study. The embryonic zebrafish model is recommended as a well-established method for rapidly assessing the toxicity of homeopathic drugs.

• Tuberculosis and Respiratory Diseases
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• 제52권5호
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• pp.463-474
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• 2002

배 경 : 전체 폐암의 75%를 차지하고 있는 비소세포폐암의 항암요법은 Cisplatin을 근간으로 하여 최근 여러 가지 새로운 항암제들이 개발되어 사용하고 있다. Cisplatin의 충분한 항암효과를 기대할 수 있는 용량을 결정하는데 중요한 것이 용량 제한성 (dose-limiting) 부작용으로, 결국 악성종양세포와 정상세포를 구분할 수 없어 발생하게 되며 이는 한번의 고용량(single high dose) 및 축적되는 용량(cumulative dose) 모두에서 생길 수 있어 최근 화학적 보호제제들을 사용 하여 이러한 cisplatinn의 용량 제한성 부작용들을 최소화시키면서 고용량의 cisplatin을 시도해 항암효과를 강화시키려는 연구가 많이 시행되고 있다. 방 법 : 비소세포폐암세포주(폐선암과 폐편평상피암)와 정상 폐포상피세포주에서 각각 단계적으로 cisplatin용량을 고용량으로 증량시키면서 세포독성효과를 먼저 비교 하고 다시 glutathione을 함께 투여하였을 때 glutathione이 고용량 cisplatin의 세포독성에 미치는 효과를 각 세포주들에서 비교하였다(SPSS 10.0 ANOVA test p<0.05) 결 과 : 폐선암세포주는 결과의 차이가 심해 비교하기가 힘드나 나타난 결과로 볼 때 glutathione의 투여는 cisplatin의 항암효과를 상쇄시켜 임상에서 투여하는데는 문제가 있을 것으로 생각된다. 폐편평상피암세포 주와 정상폐상피세포주 두가지를 같은 cisplatin 농도와 glutathione 농도에서 비교하였는데 Cisplatin 농도는 0, 30, 60, 125 ${\mu}g$/ml의 4 단계의 농도에서 비교 하였고 결과는 편평상피폐암세포주에서는 glutathione 농도 100 ${\mu}g$/ml 에서 76.6-81.5%, 250 ${\mu}g$/ml에서 80.5-93.2% 정도로 생존율을 나타내고 정상폐상피세포주에서 glutathione농도 100, 250 ${\mu}g$/ml 모두에서 91.5-100%까지 90%이상의 생존율을 유지하였다. (ANOVA test p<0.05) 결 론 : glutathione은 정상폐상피세포주에서 고농도 cisplatin에 의한 세포독성에 대한 보호효과가 크다.

• 대한본초학회지
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• 제26권2호
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• pp.75-81
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• 2011

Objectives : This study aims at examining the anti-inflammatory effects of Scutellariae Radix extract. Methods : Scutellariae Radix was hot water extracted to make the samples(SR) for the experiment. Their effects were examined on the increase of cell viability in mouse macrophage Raw 264.7 cells, the creation of nitric oxide(NO) in lipopolysaccharide(LPS)-induced Raw 264.7 cells, and the creation of cytokines of interleukin(IL)-$1{\beta}$ and others. Results : The results of the experiment are as follows. 1. The MTT assay was carried out to check the cellular toxicity of the water extract of Scutellariae Radix. The results were found no significant toxicity caused to macrophages by the water extract of Scutellariae Radix. 2. The water extract of Scutellariae Radix significantly restricted the increase of NO in the LPS-induced macrophages after 24-hour culture. 3. The water extract of Scutellariae Radix significantly restricted the creation of IL-6, IL-10, IL-12p40, IL-17, interferon-inducible protein(IP)-10, keratinocyte-derived chemokine(KC), and vascular endothelial growth factor(VEGF) in the LPS-induced macrophages at the concentration of $25{\mu}g/mL$ or higher. Conclusion : The samples(SR) of hot water extract of Scutellariae Radix caused no significant cellular toxicity to macrophages and significantly restricted the creation of NO, IL-6, IL-10, IL-12p40, IL-17, IP-10, KC, and VEGF in the LPS-induced macrophages at $25{\mu}g/mL$ or higher, thus demonstrating significant anti-inflammatory effects.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2015-2020
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• 2012

Oleanolic acid (OA) is a naturally occurring triterpenoid in food materials and is a component of the leaves and roots of Olea europaea, Viscum album L., Aralia chinensis L. and more than 120 other plant species. There are several reports validating its antitumor activity against different cancer cells apart from its hepatoprotective activity. However, antitumor activity against skin cancer has not beed studied well thus far. Hence the present study of effects of OA against HaCaT (immortalized keratinocyte) cells - a cell-based epithelial model system for toxicity/ethnopharmacology-based studies - was conducted. Radical scavenging activity ($DPPH{\cdot}$) and FRAP were determined spectrophotometrically. Proliferation was assessed by XTT assay at 24, 48 and 72 hrs with exposure to various concentrations (12.5-200 ${\mu}M$) of OA. Apoptotic induction potential of OA was demonstrated using a cellular DNA fragmentation ELISA method. Morphological studies were also carried out to elucidate its antitumor potential. The results revealed that OA induces apoptosis by altering cellular morphology as well as DNA integrity in HaCaT cells in a dose-dependent manner, with comparatively low cytotoxicity. The moderate toxicity observed in HaCaT cells, with induction of apoptosis, possibly suggests greater involvement of programmed-cell death-mediated mechanisms. We conclude that OA has relatively low toxicity and has the potential to induce apoptosis in HaCaT cells and hence provides a substantial and sound scientific basis for further validation studies.

• Applied Microscopy
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• 제27권2호
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• pp.165-175
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• 1997

This paper aims to prove the effects of Squalene (SQ) on the cellular toxicity of 5-FU to the mouse which pretreated with SQ and then treated with 5-FU. The results of the group A (treated with only 5-FU) are as follows. The nucleus was destroyed at 24 hours and 48 hours group, however, somewhat repaired at 72 hours group. The dilated inner cavity and the irregular lamellae of the rough surfaced endoplasmic reticulum (RER) were observed continually until 72 hours group. The inner cavity of the smooth surfaced endoplasmic reticulum (SER) were dilated in all groups. However, the destroyed and the normal membrane were observed simultaneously at 72 hours group. The inner membrane of the mitochondria were almost repaired at 96 hours group. The results of the group B (treated with 5-FU and squalene) are as follows. The nucleus was a little influenced by the toxicity of 5-FU at 24 hours and 48 hours, RER were observed to keep the typical lamella structure of cisternae from 24 to 72 hours group, but inner cavity kept on dilating. In SER, inner cavity were also observed to flatten from 24 to 72 hours group. Mitochnodria were always shown normal. All cell organelles were simillar to those of normal groups at 96 hours. Accordingly, it can be said that the treatment of 50 prevents the cytotoxicity of 5-FU on cell organelles of liver cell and that is concerned with the formation of membrane system of cell organelles.

• 대한본초학회지
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• 제28권5호
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• pp.45-52
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• 2013

Objectives : This study aims at examining the immuno-modulating activity in the fermentative extract of the root of Scutellaria baicalensis Georgi (Scutellariae Radix) on the production of inflammatory mediator in LPS-stimulated RAW264.7 mouse macrophages. Method : Measurements were done for the influences on the cell viability, generation of hydrogen peroxide in cells and nitric oxide (NO) generation using the macrophage of mouse with the specimen SBS as the fermentative extract of Scutellariae Radix (SBS) with Saccharomyces cerevisiae STV89. Result : As a result of carrying out MTT assay to check the cellular toxicity of the fermentative extract of Scutellariae Radix, any excessive toxicity to the macrophage did not occur from treatments by concentration for SBS. SBS increased the generation of hydrogen peroxide in the macrophage. SBS suppressed the NO generated in macrophages and SBS concentration higher than $25{\mu}g/mL$ significantly suppressed the increased NO generated in LPS-stimulated macrophages. SBS concentration higher than $25{\mu}g/mL$ significantly suppressed the generation of IL-6, IL-10, IL-12p40 and MCP-1 in LPS-stimulated macrophages. Conclusion : Our findings indicate that SBS has an immuno-modulating activity in macrophage activation through suppressing the generation of inflammatory substances, NO, IL-6, IL-10, IL-12p40 and MCP-1.

• Molecular & Cellular Toxicology
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• 제1권2호
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• pp.137-141
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• 2005

The critical role of folate in the remethylation pathway for methionine synthesis from homocysteine has been well documented. Hyperhomocysteinemia resulting from inadequate folate nutrition has been implicated in increased incidence of macrovascular diseases, colorectal cancer, neural tube defects, etc. Chronic exposure to ethanol impairs folate nutrition and one-carbon metabolism in the liver, which often results in fatty liver due to a defective remetylation process. This study was carried out to investigate the chronic effects of moderate levels of alcohol and dietary folate on plasma homocysteine levels, and on histopathology and biochemical functions of the liver. Rats were raised on experimental diets with three levels of folate (0, 2, 8 mg/kg diet), and 50% ethanol (1.8 ml/kg body weight) was administered intragastically by intubation tubes three times a week for 10 weeks. Plasma homocysteine concentrations were found to be significantly influenced by dietary folate intake and alcohol administration. Among all treatment groups, plasma homocysteine levels were the highest in the animals receiving a combined treatment of folate deficient diet and alcohol administration. Plasma homocysteine concentrations were negatively correlated with folate concentration in the plasma (p<0.01) and liver (p<0.05). Among alcohol treated rats, increase in plasma homocysteine values due to macrovascular and microvascular fatty changes and spotted necrosis were observed more frequently in folate-deficient animals diet than those on folate-adequate and folate supplemented diets in alcohol-treated rats. These results indicate that folate supplementation above the recommended level might be beneficial in the prevention of alcohol-related hyperhomocysteinemia and abnormal histologic changes in the liver.