1.Splitomicin, a SIRT1 Inhibitor, Enhances Hematopoietic Differentiation of Mouse Embryonic Stem Cells
Jeong A PARK ; Sangkyu PARK ; Woo Youn PARK ; Myung Kwan HAN ; Younghee LEE
International Journal of Stem Cells 2019;12(1):21-30
BACKGROUND AND OBJECTIVES: Embryonic stem (ES) cells have pluripotent ability to differentiate into multiple tissue lineages. SIRT1 is a class III histone deacetylase which modulates chromatin remodeling, gene silencing, cell survival, metabolism, and development. In this study, we examined the effects of SIRT1 inhibitors on the hematopoietic differentiation of mouse ES cells. METHODS AND RESULTS: Treatment with the SIRT1 inhibitors, nicotinamide and splitomicin, during the hematopoietic differentiation of ES cells enhanced the production of hematopoietic progenitors and slightly up-regulated erythroid and myeloid specific gene expression. Furthermore, treatment with splitomicin increased the percentage of erythroid and myeloid lineage cells. CONCLUSIONS: Application of the SIRT1 inhibitor splitomicin during ES cell differentiation to hematopoietic cells enhanced the yield of specific hematopoietic lineage cells from ES cells. This result suggests that SIRT1 is involved in the regulation of hematopoietic differentiation of specific lineages and that the modulation of the SIRT1 activity can be a strategy to enhance the efficiency of hematopoietic differentiation.
Animals
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Cell Differentiation
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Cell Survival
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Chromatin Assembly and Disassembly
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Gene Expression
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Gene Silencing
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Histone Deacetylases
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Metabolism
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Mice
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Mouse Embryonic Stem Cells
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Niacinamide
2.Inhibition of MUC1-C Increases ROS and Cell Death in Mouse Embryonic Stem Cells
Jeong-A PARK ; Sangkyu PARK ; Jun-Kyu CHOI ; Myung-Kwan HAN ; Younghee LEE
International Journal of Stem Cells 2021;14(2):180-190
Background and Objectives:
Embryonic stem (ES) cells have the capacity to self-renew and generate all types of cells.MUC1-C, a cytoplasmic subunit of MUC1, is overexpressed in various carcinomas and mediates signaling pathways to regulate intracellular metabolic processes and gene expression involved in the maintenance of cancer cells. However, the functional role of MUC1-C in ES cells is not well understood. In this study, we investigated the role of MUC1-C on growth, survival,: and differentiation of mouse ES (mES) cells.
Methods:
and Results: Undifferentiated mES cells expressed the MUC1-C protein and the expression level was decreased during differentiation. Inhibition of MUC1-C, by the specific inhibitor GO201, reduced proliferation of mES cells.However, there was no prominent effect on pluripotent markers such as Oct4 expression and STAT3 signaling, and MUC1-C inhibition did not induce differentiation. Inhibition of MUC1-C increased the G1 phase population, decreased the S phase population, and increased cell death. Furthermore, inhibition of MUC1-C induced disruption of the ROS balance in mES cells.
Conclusions
These results suggest that MUC1-C is involved in the growth and survival of mES cells.
3.Inhibition of MUC1-C Increases ROS and Cell Death in Mouse Embryonic Stem Cells
Jeong-A PARK ; Sangkyu PARK ; Jun-Kyu CHOI ; Myung-Kwan HAN ; Younghee LEE
International Journal of Stem Cells 2021;14(2):180-190
Background and Objectives:
Embryonic stem (ES) cells have the capacity to self-renew and generate all types of cells.MUC1-C, a cytoplasmic subunit of MUC1, is overexpressed in various carcinomas and mediates signaling pathways to regulate intracellular metabolic processes and gene expression involved in the maintenance of cancer cells. However, the functional role of MUC1-C in ES cells is not well understood. In this study, we investigated the role of MUC1-C on growth, survival,: and differentiation of mouse ES (mES) cells.
Methods:
and Results: Undifferentiated mES cells expressed the MUC1-C protein and the expression level was decreased during differentiation. Inhibition of MUC1-C, by the specific inhibitor GO201, reduced proliferation of mES cells.However, there was no prominent effect on pluripotent markers such as Oct4 expression and STAT3 signaling, and MUC1-C inhibition did not induce differentiation. Inhibition of MUC1-C increased the G1 phase population, decreased the S phase population, and increased cell death. Furthermore, inhibition of MUC1-C induced disruption of the ROS balance in mES cells.
Conclusions
These results suggest that MUC1-C is involved in the growth and survival of mES cells.
4.Effects of Dental Sound Insulation System on Stress and Dental Fear Reduction in Pediatric Patients
Sangkyu HAN ; Jaeho LEE ; Eun LEE ; Taeyang LEE ; Wonse PARK ; Je Seon SONG
Journal of Korean Academy of Pediatric Dentistry 2024;51(4):380-391
This study aimed to assess the effectiveness of dental sound insulation in alleviating stress and fear during dental scaling in pediatric patients. It also examined the influence of a noise-canceling application on dentist-patient communication and convenience of dental procedures. This study included 60 children and adolescents aged 7 - 16 years between April 2022 and March 2023. All participants underwent dental plaque control using an ultrasonic scaler on the maxilla first, followed by plaque control on the mandible. Dental sound insulation with active noise canceling was randomly applied to either the maxilla or mandible. Findings revealed that the stress index was significantly reduced when the application was used, with a score of 5.85 compared to 8.43 without it (p < 0.0001). Similarly, the dental fear score was significantly reduced to 1.17 with the application, as opposed to 2.97 without it (p < 0.0001). The dental sound insulation did not affect the communication between dentists and patients or the convenience of treatment. This study demonstrated that active noise canceling during pediatric dental care significantly reduced stress and fear, suggesting that it could be a valuable behavior guidance tool, particularly for children who find dental visits challenging.
5.Effects of Dental Sound Insulation System on Stress and Dental Fear Reduction in Pediatric Patients
Sangkyu HAN ; Jaeho LEE ; Eun LEE ; Taeyang LEE ; Wonse PARK ; Je Seon SONG
Journal of Korean Academy of Pediatric Dentistry 2024;51(4):380-391
This study aimed to assess the effectiveness of dental sound insulation in alleviating stress and fear during dental scaling in pediatric patients. It also examined the influence of a noise-canceling application on dentist-patient communication and convenience of dental procedures. This study included 60 children and adolescents aged 7 - 16 years between April 2022 and March 2023. All participants underwent dental plaque control using an ultrasonic scaler on the maxilla first, followed by plaque control on the mandible. Dental sound insulation with active noise canceling was randomly applied to either the maxilla or mandible. Findings revealed that the stress index was significantly reduced when the application was used, with a score of 5.85 compared to 8.43 without it (p < 0.0001). Similarly, the dental fear score was significantly reduced to 1.17 with the application, as opposed to 2.97 without it (p < 0.0001). The dental sound insulation did not affect the communication between dentists and patients or the convenience of treatment. This study demonstrated that active noise canceling during pediatric dental care significantly reduced stress and fear, suggesting that it could be a valuable behavior guidance tool, particularly for children who find dental visits challenging.
6.Effects of Dental Sound Insulation System on Stress and Dental Fear Reduction in Pediatric Patients
Sangkyu HAN ; Jaeho LEE ; Eun LEE ; Taeyang LEE ; Wonse PARK ; Je Seon SONG
Journal of Korean Academy of Pediatric Dentistry 2024;51(4):380-391
This study aimed to assess the effectiveness of dental sound insulation in alleviating stress and fear during dental scaling in pediatric patients. It also examined the influence of a noise-canceling application on dentist-patient communication and convenience of dental procedures. This study included 60 children and adolescents aged 7 - 16 years between April 2022 and March 2023. All participants underwent dental plaque control using an ultrasonic scaler on the maxilla first, followed by plaque control on the mandible. Dental sound insulation with active noise canceling was randomly applied to either the maxilla or mandible. Findings revealed that the stress index was significantly reduced when the application was used, with a score of 5.85 compared to 8.43 without it (p < 0.0001). Similarly, the dental fear score was significantly reduced to 1.17 with the application, as opposed to 2.97 without it (p < 0.0001). The dental sound insulation did not affect the communication between dentists and patients or the convenience of treatment. This study demonstrated that active noise canceling during pediatric dental care significantly reduced stress and fear, suggesting that it could be a valuable behavior guidance tool, particularly for children who find dental visits challenging.
7.Lipofundin(R) MCT/LCT 20% increase left ventricular systolic pressure in an ex vivo rat heart model via increase of intracellular calcium level.
Jiyoung PARK ; Yeon A KIM ; Jeong Yeol HAN ; Sangkyu JIN ; Seong Ho OK ; Ju Tae SOHN ; Heon Keun LEE ; Young Kyun CHUNG ; Il Woo SHIN
Korean Journal of Anesthesiology 2016;69(1):57-62
BACKGROUND: Lipid emulsions have been used to treat various drug toxicities and for total parenteral nutrition therapy. Their usefulness has also been confirmed in patients with local anesthetic-induced cardiac toxicity. The purpose of this study was to measure the hemodynamic and composition effects of lipid emulsions and to elucidate the mechanism associated with changes in intracellular calcium levels in myocardiocytes. METHODS: We measured hemodynamic effects using a digital analysis system after Intralipid(R) and Lipofundin(R) MCT/LCT were infused into hearts hanging in a Langendorff perfusion system. We measured the effects of the lipid emulsions on intracellular calcium levels in H9c2 cells by confocal microscopy. RESULTS: Infusion of Lipofundin(R) MCT/LCT 20% (1 ml/kg) resulted in a significant increase in left ventricular systolic pressure compared to that after infusing modified Krebs-Henseleit solution (1 ml/kg) (P = 0.003, 95% confidence interval [CI], 2.4-12.5). Lipofundin(R) MCT/LCT 20% had a more positive inotropic effect than that of Intralipid(R) 20% (P = 0.009, 95% CI, 1.4-11.6). Both lipid emulsion treatments increased intracellular calcium levels. Lipofundin(R) MCT/LCT (0.01%) increased intracellular calcium level more than that of 0.01% Intralipid(R) (P < 0.05, 95% CI, 0.0-1.9). CONCLUSIONS: These two lipid emulsions had different inotropic effects depending on their triglyceride component. The inotropic effect of lipid emulsions could be related with intracellular calcium level.
Animals
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Blood Pressure*
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Calcium*
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Drug-Related Side Effects and Adverse Reactions
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Emulsions
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Heart*
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Hemodynamics
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Humans
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Microscopy, Confocal
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Myocardial Contraction
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Parenteral Nutrition, Total
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Perfusion
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Rats*
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Triglycerides
8.Protective effect of butylated hydroxylanisole against hydrogen peroxide-induced apoptosis in primary cultured mouse hepatocytes.
Geun Hye HWANG ; Yu Jin JEON ; Ho Jae HAN ; Soo Hyun PARK ; Kyoung Min BAEK ; Woochul CHANG ; Joong Sun KIM ; Lark Kyun KIM ; You Mie LEE ; Sangkyu LEE ; Jong Sup BAE ; Jun Goo JEE ; Min Young LEE
Journal of Veterinary Science 2015;16(1):17-23
Butylated hydroxyanisole (BHA) is a synthetic phenolic compound consisting of a mixture of two isomeric organic compounds: 2-tert-butyl-4-hydroxyanisole and 3-tert-butyl-4-hydroxyanisole. We examined the effect of BHA against hydrogen peroxide (H2O2)-induced apoptosis in primary cultured mouse hepatocytes. Cell viability was significantly decreased by H2O2 in a dose-dependent manner. Additionally, H2O2 treatment increased Bax, decreased Bcl-2, and promoted PARP-1 cleavage in a dose-dependent manner. Pretreatment with BHA before exposure to H2O2 significantly attenuated the H2O2-induced decrease of cell viability. H2O2 exposure resulted in an increase of intracellular reactive oxygen species (ROS) generation that was significantly inhibited by pretreatment with BHA or N-acetyl-cysteine (NAC, an ROS scavenger). H2O2-induced decrease of cell viability was also attenuated by pretreatment with BHA and NAC. Furthermore, H2O2-induced increase of Bax, decrease of Bcl-2, and PARP-1 cleavage was also inhibited by BHA. Taken together, results of this investigation demonstrated that BHA protects primary cultured mouse hepatocytes against H2O2-induced apoptosis by inhibiting ROS generation.
Animals
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Apoptosis/*drug effects
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Butylated Hydroxyanisole/chemistry/*pharmacology
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Cell Survival/drug effects
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Cells, Cultured
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Hepatocytes/*drug effects
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Hydrogen Peroxide/*toxicity
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Male
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Mice
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Mice, Inbred ICR
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Molecular Structure