• The Journal of Korean Physical Therapy
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• v.20 no.3
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• pp.53-59
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• 2008

Purpose: The non-receptor-type protein tyrosine kinase Syk (636 amino acids, 72 kDa) is ubiquitously expressed in hematopoietic stem cells and has been widely studied as a regulator and effector of B cell receptor signaling that occurs in processes such as differentiation, proliferation and apoptosis. However, the mechanism relating Syk and p38 mitogen-activated protein kinases (p38MAPK) by endothelin-1 (ET-1, 21 amino acids) stimulation in muscle cells, especially in the volume-dependent hypertensive state, remains unclear. Methods: In this study, we investigated the relationship between Syk and p38MAPK for isometric contraction and enzymatic activity by ET-1 from rat aortic smooth muscle cells and aldosterone-analogue deoxycorticosterone acetate (DOCA) hypertensive state rats (ADHR). Results: The systolic blood pressure was significantly increased in ADHR than in a control group of animals. ET-1 induced isometric contraction and phosphorylation of p38MAPK, which was increased in muscle strips from ADHR. Increased vasoconstriction and phosphorylation of p38MAPK induced by treatment with 30 nM ET-1 were inhibited by the use of 10${\mu}M$ SB203580, an inhibitor of p38MAPK from ADHR. Furthermore, ET-1 induced isometric contraction and phosphorylation of Syk and p38MAPK, which were increased in the aortic smooth muscle cells. Increased tension and phosphorylation of Syk and p38MAPK induced by ET-1 were inhibited by SB203580 from rat aortic smooth muscle cells. Conclusion: These results, suggest that the Syk activity affects ET-1-induced contraction through p38MAPK in smooth muscle cells and that the same pathway directly or indirectly is associated with volume dependent hypertension. The findings suggest the need to develop cardiovascular disease-specialized physical therapy.

• Journal of Life Science
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• v.33 no.6
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• pp.512-522
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• 2023

Cancer with unlimited cell growth is a leading cause of death globally. Various cancer treatments, including surgery, chemotherapy, radiation therapy, immunotherapy, and targeted therapy, can be applied alone or in combination depending on the cancer type and stage. New treatments with fewer side effects than previous cancer treatments are continually under development and in demand. Undifferentiated stem cells with unlimited cell growth are gradually changed via cellular differentiation to arrest cell growth. In this study, we reviewed the possibility of treating cancer by using cellular differentiation into the adipocytes in cancer cells. In previous in vitro studies, oral antidiabetic drugs of the thiazolidinedione (TDZ) class, such as rosiglitazone and pioglitazone, were induced into the adipocytes in various cancer cell lines via increased peroxisome proliferator-activated receptor-γ (PPAR γ) expression and glucose uptake, which is the key regulator of adipogenesis and the energy metabolism pathway. The differentiated adipogenic cancer cells treated with TDZ inhibited cell growth and had a less cellulotoxic effect. This adipogenic differentiation treatment suggests a possible chemotherapy option in cancer cells with high and abnormal glucose metabolism levels. However, the effects of the in vivo adipogenic differentiation treatment need to be thoroughly investigated in different types of stem and normal cells with other side effects.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.20 no.8
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• pp.618-626
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• 2019

Stem cell therapy is not expected to bestow any therapeutic benefit because of the low engraftment rates after transplantation.Various cell-carrying scaffolds have been developed in order to overcome this problem. When the scaffold is formed by 3-dimensional (3D) printing, it is possible to create various shapes of scaffolds for specific regions of injury. At the same time, scaffolds provide stem cells as therapeutic-agents and mechanically support an injured region. PCL is not only cost effective, but it is also a widely used material for 3D printing. Therefore, rapid and economical technology development can be achieved when PCL is printed and used as a cell carrier. Yet PCL materials do not perform well as cell carriers, and only a few cells survive on the PCL surface. In this study, we tried to determine the conditions that maximize the cell-loading capacity on the PCL surface to overcome this issue. By applying a plasma treated condition and then collagen coating known to improve the cell loading capacity, it was confirmed that the 3% collagen coating after plasma treatment showed the best cell engraftment capacity during 72 hours after cell loading. By applying the spheroid cell culture method and scaffold structure change, which can affect the cell loading ability, the spheroid cell culture methods vastly improved cell engraftment, and the scaffold structure did not affect the cell engraftment properties. We will conduct further experiments using PCL material as a cell carrier and as based the excellent results of this study.

• Microbiology and Biotechnology Letters
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• v.47 no.1
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• pp.164-171
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• 2019

Radiation therapy has many side effects, such as digestive mucosal ulcers, without regard to its efficacy. The purpose of this study is to address an alternative method to replace the limitation of radiation therapy using radiomimetic microbial ribotoxins. In the evaluation of cancer therapy, we analyzed the formation of colorectal cancer (CRC) cell spheroids, which can take into account the heterogeneous cellular constitution, tumor stem cells, and the surrounding microenvironment. Ribotoxic stress interfered with the spheroid structure composed of relatively small clusters. Spheroids under ribotoxic stress were structurally sparse and their shrinkage was very slow. In the control group, the clusters of strongly aggregated cells were resistant to physical stress, but the ribotoxic stress-exposed spheroids were easily broken up by the physical stress. Moreover, the ribosome-insulted CRC cells slowly migrated to form clusters and the cell-cell junctional points in the ribosome-insulted spheroids were rarer than those in the control CRC spheroid. Moreover, levels of the cell-to-cell junctional protein E-cadherin were suppressed by ribotoxic stress in both allograft and xenograft spheroids. In conclusion, the radiomimetic microbial ribotoxins induced structural defects in CRC cell spheroids via retardation of migration and cell-cell junction in the formation of three-dimensional structures, and provides a basis for the mechanism of pharmacological radiomimetic anticancer actions as an alternate to radiotherapy against cancer.

• BMB Reports
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• v.34 no.2
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• pp.176-181
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• 2001

Using a retrovirus, foreign genes can be introduced into mammalian cells. The purpose of this study is to produce a retrovirus that can make the infected cells express two genes; the human multidrug resistance gene (MDR1) and the HLA-B7 gene, which is one of the major human histocompatibility complex (MHC) class I genes. For the expression of these genes, the internal ribosome entry site (IRES) was used, which was derived from the encephalomyocarditis (EMC) virus. In order to produce retroviruses, a retroviral vector was transfected into a packaging cell line and the transfected cells were treated with vincristine, which is an anti-cancer drug and a substrate for the MDRI gene product. This study revealed that two genes were incorporated into chromosomes of selected cells and expressed in the same cells. The production of the retrovirus was confirmed by the reverse transcription (RT)-PCR of the viral RNA. The retrovirus that was produced infected mouse fibroblast cells as well as the human U937. This study showed that packaging cells produced the retroviruses, which can infect the target cells. Once the conditions for the high infectivity of retrovirus into human cells are optimized, thus virus will be used to infect hematopoietic stem cells to co-express MDRl and HLA-B7 genes, and develop the lymphocytes that can be used for the immnogene therapy.

• Korean Journal of Pharmacognosy
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• v.46 no.1
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• pp.52-58
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• 2015

Neural stem cells (NSCs), with self-renewal and neuronal differentiation capacity, are a feasible resource in cell-based therapies for various neurodegenerative diseases and neural tissue injuries. In this study, we investigated the effects of Schisandrae Fructus (SF) on proliferation and differentiation of human embryonic NSCs. Treatment with 70% ethanol extract of SF increased the viability of NSCs derived from human embryonic stem cells, which was accompanied by increased mRNA expression of cyclin D1. Whereas 70% ethanol extract of SF also decreased the mRNA expression of nestin, it increased class III ${\beta}$-tublin (Tuj-1) and MAP2 in both growth and differentiation media. Lastly, we found increased mRNA expression of BDNF in SF-treated NSCs. In conclusion, our study demonstrates for the first time that SF induced proliferation and neuronal differentiation of NSCs and increased mRNA expression of BDNF, suggesting its potential as a regulator of NSC fate in NSC-based therapy for neuronal injuries from various diseases.

• Molecules and Cells
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• v.40 no.8
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• pp.550-557
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• 2017

The periodontal ligament (PDL) is the connective tissue between tooth root and alveolar bone containing mesenchymal stem cells (MSC). It has been suggested that human periodontal ligament stem cells (hPDLSCs) differentiate into osteo/cementoblast and ligament progenitor cells. The periodontitis is a representative oral disease where the PDL tissue is collapsed, and regeneration of this tissue is important in periodontitis therapy. Fibroblast growth factor-2 (FGF-2) stimulates proliferation and differentiation of fibroblastic MSCs into various cell lineages. We evaluated the dose efficacy of FGF-2 for cytodifferentiation of hPDLSCs into ligament progenitor. The fibrous morphology was highly stimulated even at low FGF-2 concentrations, and the expression of teno/ligamentogenic markers, scleraxis and tenomodulin in hPDLSCs increased in a dose dependent manner of FGF-2. In contrast, expression of the osteo/cementogenic markers decreased, suggesting that FGF-2 might induce and maintain the ligamentogenic potential of hPDLSCs. Although the stimulation of tenocytic maturation by $TGF-{\beta}1$ was diminished by FGF-2, the inhibition of the expression of early ligamentogenic marker by $TGF-{\beta}1$ was redeemed by FGF-2 treatment. The stimulating effect of BMPs on osteo/cementogenesis was apparently suppressed by FGF-2. These results indicate that FGF-2 predominantly differentiates the hPDLSCs into teno/ligamentogenesis, and has an antagonistic effect on the hard tissue differentiation induced by BMP-2 and BMP-4.

• Restorative Dentistry and Endodontics
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• v.48 no.1
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• pp.2.1-2.12
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• 2023

Objectives: In this study, natural substances were introduced as primary dental pulp caps for use in pulp therapy, and the antimicrobial and cytotoxic properties of these substances were investigated. Materials and Methods: In this in vitro study, the antimicrobial properties of calcium-enriched mixture (CEM) cement, propolis, and propolis individually combined with the extracts of several medicinal plants were investigated against Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Then, the cytotoxicity of each substance or mixture against pulp stem cells extracted from 30 primary healthy teeth was evaluated at 4 concentrations. Data were gathered via observation, and optical density values were obtained using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) test and recorded. SPSS software version 23 was used to analyze the data. Data were evaluated using 2-way analysis of variance and the Tukey test. Results: Regarding antimicrobial properties, thyme alone and thyme + propolis had the lowest minimum inhibitory concentrations (MICs) against the growth of S. aureus, E. coli, and P. aeruginosa bacteria. For E. faecalis, thyme + propolis had the lowest MIC, followed by thyme alone. At 24 and 72 hours, thyme + propolis, CEM cement, and propolis had the greatest bioviability in the primary dental pulp stem cells, and lavender + propolis had the lowest bioviability. Conclusions: Of the studied materials, thyme + propolis showed the best results in the measures of practical performance as a dental pulp cap.

• Childhood Kidney Diseases
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• v.14 no.1
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• pp.32-41
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• 2010

Purpose : Glomerulonephropathy (GN) often manifests as proteinuria and progresses to chronic renal failure without specific therapy. Mesenchymal stem cell (MSC) has been tried as a therapeutic agent in experimental GN, and previous studies showed that administration of MSC concomitantly to the insult inducing GN or via intra-renal administration ameliorated proteinuria. The purpose of this study was to test the therapeutic potential of MSC administered via intravenous route at the time of clinically evident proteinuria. Methods : MSCs were administered intravenously via tail vain into the mice with adriamycin (ADR) induced nephropathy (ADR-GN), two weeks after ADR injection when massive proteinuria was evident. To test the capacity of MSC modulate the cytokine production in the inflammatory milieu, the concentrations of IFN-$\gamma$ and IL-10 were measured in the supernatant of in vitro mixed lymphocyte culture (MLC) with or without additional MSC. Results : MSCs administered intravenously into the proteinuric mice with ADR-GN accelerated the recovery of this experimental GN with disappearance of proteinuria in two weeks when the saline treated (control) mice still showed significant proteinuria. The mice treated with MSC also had a tendency of better survival. Addition of MSC decreased IFN-$\gamma$ and increased IL-10 in the supernatant of MLC. Conclusion : This study showed that MSC had a therapeutic potential even when administered in a more clinically relevant setting into a proteinuric glomerulonephropathy model. Further study to verify the mechanism and long-term safety of this phenomenon is required.

• Journal of Veterinary Clinics
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• v.27 no.5
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• pp.533-539
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• 2010

Stem cell-based therapy is under intensive investigation to treat acute renal failure (ARF). The purpose of this study was to evaluate available ARF models, and suggest a model appropriate to therapeutic evaluation of the stem cells in preclinical approach by determining the optimum concentration of nephrotoxic agents and duration of ischemia induction. Three different types of available acute kidney injury (AKI) animal models were analyzed using rats: Cisplatin (saline, 5 and 7.5 mg/kg, IP) or glycerol (saline, 8 and 10 ml/kg, IM)-induced nephrotoxicity as toxic models and ischemia-induced (sham, 35 and 45 minutes) nephropathy as an ischemic model. The relevance and applicability to investigate especially the regenerative ability of stem cells were evaluated regarding morphology, renal function and survival at this time point. In the point of renal function, 10 ml glycerol/kg and 7.5 mg cisplatin/kg model in toxic models and 45 min model in ischemia models showed significant decrease for the longer observation time compared to 8 ml glycerol/kg, 5 mg cisplatin/kg and the 35 min ischemia models, respectively. All groups were observed no mortality except 45 min-ischemia model with 50% survival. Histological significant alterations including cast formation in the tubular lumen, tubular necrosis and apoptosis were revealed on the second day in either ischemiaor glycerol-induced models, and on day 5 in cisplatin-induced models. The results indicate that ischemia 35 min-, cisplatin 7.5 mg/kg- and glycerol 10 ml/kg-induced AKI would be ideal animal models to monitor a outcome parameter related to the therapeutic effects on renal function with noninvasive techniques in the same animal at multiple time points. Our findings also suggest that the best time points for the functional or histological interpretation of renal will be on day 2 in both glycerol- and ischemia-induced AKI models and on day 5 in cisplatin-induced AKI.