• Biomedical Science Letters
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• v.3 no.1
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• pp.11-20
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• 1997

A regulation of differentiation in human neuroblastoma cells remains poorly understood, although it is of great importance in the clinical therapy of neuroblastoma. This study was aimed to elucidate effects of DNA synthesis inhibitors on the differentiation of neuroblastoma cells on the basis of morphological, biochemical and molecular respects. Three DNA synthesis inhibitors, sodium butyrate, hydroxyurea, cytosine arabinoside were used to explore their effects on the cellular morphology, the expression of c-myc and the elevation of choline acetyltransferase activity. They led to the extension or neurite-like processes reflecting differentiation or IMR-32 cells. In addition, the treatment of three DNA synthesis inhibitors resulted in the remarkable increases in the expression of c-myc as well as the stimulation of choline acetyltransferase activity which is involved in the synthesis of acetylcholine in the differentiated cholinergic neurons. Taken together, these results indicate that DNA synthesis inhibitors play an important role in the induction of cellular differentiation in IMR-32 cells. Furthermore these DNA synthesis inhibitors seem to be future useful to give an important clue (for the treatment of neuroblastoma).

• Korean Journal of Clinical Laboratory Science
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• v.47 no.3
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• pp.117-124
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• 2015

Mesenchymal stem cells (MSCs) are an attractive tool in tissue engineering as they have the required potential to treat injured articular cartilage. UV-exposed DTOPV (S-triazine bridged p-phenylene vinylene) is a biocompatible and fluorescent polymer with a hydrophilic surface. Previous studies have demonstrated that the surface wettability and hydrophilicity play critical roles in regulating cell adhesion and proliferation. The objective of this study was to improve the potential of in vitro MSC differentiation into Chondrocytes using DTOPV. MSCs were cultured on two different substrates: (1) tissue culture polystyrene (TCPS) as a reference and (2) UV-exposed and patterned DTOPV films. Chondrogenesis of MSCs was induced for two weeks on TCPS and DTOPV in the presence of an induction medium containing transforming growth factor (TGF)-${\beta}3$. Interestingly, the MSCs on TCPS adhered and spread, while those on DTOPV tended to form aggregates within several days. The cells cultured on DTOPV for two weeks had a round morphology, with stronger Safranine O staining of the extracellular matrix than that of the cells cultured on TCPS. Also, Type II collagen gene was significantly expressed in cells induced on DTOPV. These results indicate that chondrogenic differentiation of MSCs proceeds more rapidly on DTOPV than on TCPS. Therefore, in cartilage tissue engineering, DTOPV could be used to induce effective chondrogenic differentiation of MSCs.

• Journal of Gastric Cancer
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• v.15 no.4
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• pp.246-255
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• 2015

Purpose: The importance of Helicobacter pylori eradication after endoscopic resection (ER) of gastric neoplasms remains controversial. In this study, we clarified the importance of H. pylori eradication for metachronous lesions after ER. Materials and Methods: This study included 3,882 patients with gastric neoplasms who underwent ER. We included patients infected with H. pylori who received eradication therapy. Among them, 34 patients with metachronous lesions after ER and 102 age- and sex-matched patients (nonmetachronous group) were enrolled. Background mucosal pathologies such as atrophy and intestinal metaplasia (IM) were evaluated endoscopically. The expression levels of CDX1, CDX2, Sonic hedgehog (SHH), and SOX2 were evaluated based on H. pylori eradication and the development of metachronous lesions. Results: The eradication failure rate was higher in the metachronous group than in the nonmetachronous group (P=0.036). Open-type atrophy (P=0.003) and moderate-to-severe IM (P=0.001) occurred more frequently in the metachronous group. In patients with an initial diagnosis of dysplasia, the eradication failure rate was higher in the metachronous group than in the nonmetachronous group (P=0.002). In addition, open-type atrophy was more frequent in the metachronous group (P=0.047). In patients with an initial diagnosis of carcinoma, moderate-to-severe IM occurred more frequently in the metachronous group (P=0.003); however, the eradication failure rate was not significantly different between the two groups. SHH and SOX2 expression was increased, and CDX2 expression was decreased in the nonmetachronous group after eradication (P<0.05). Conclusions: Open-type atrophy, moderate-to-severe IM, and H. pylori eradication failure were significantly associated with metachronous lesions. However, eradication failure was significantly associated with dysplasia, but not carcinoma, in the metachronous group. Thus, H. pylori eradication may play an important role in preventing metachronous lesions after ER for precancerous lesions before carcinomatous transformation.

• IMMUNE NETWORK
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• v.2 no.1
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• pp.53-59
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• 2002

Background: Clinical observations and laboratory studies have supported an immune basis for most acquired aplastic anemias, with the majority of patients responding to immunosuppressive therapy. Fas, a member of the tumor necrosis factor (TNF) receptor superfamily is a critical downregulator of cellular immune responses. Proinflammatory cytokines like interferon gamma (IFN-${\gamma}$) and TNF-${\alpha}$ can induce Fas expression and render hematopoietic progenitor cells susceptible to Fas-induced growth suppression and apoptosis. Methods: In order to investigate the involvement of apoptosis in the pathogenesis of aplastic anemia (AA), we measured the expression of Fas antigen and caspase-3 on bone marrow (BM) mononuclear cells (MNCs) of AA in the presence or absence of IFN-${\gamma}$, TNF-${\alpha}$, or macrophage inflammatory protein 1-${\alpha}$ (MIP-$1{\alpha}$). Results: We confirmed that AA BM MNCs were more apoptotic and highly expressed Fas antigen than normal donors. Stimulation by IFN-${\gamma}$, TNF-${\alpha}$, or MIP-$1{\alpha}$ increased Fas antigen and caspase-3 expression in AA BM MNCs than BM MNCs of normal donors. Anti-Fas monoclonal antibody enhanced IFN-${\gamma}$, TNF-${\alpha}$, or MIP$1{\alpha}$ mediated caspase-3 expression in BM MNCs of normal donors. Among these three cytokines, IFN-${\gamma}$ enhanced apoptosis most strongly via Fas-caspase-3 pathway. Conclusion: These results suggest that Fas signal pathway may play a role in the pathophysiology of aplastic anemia and negative hematopoietic regulators like IFN-${\gamma}$ can induce apoptosis of bone marrow progenitors in part by Fas induction.

• Journal of Periodontal and Implant Science
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• v.23 no.3
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• pp.359-373
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• 1993

The ultimate objective of periodontal therapy is not only stopping the progression of periodontal disease, but also promoting the regeneration of lost periodontal tissue. Guided Tissue Regeneration, which is based on the principle that the goal of periodontal regeneration can be achieved by preventing apical migration of gingival epithelium and blocking cells originating from connective tissue, has been developed and used as a clinical procedure, and although it has shown excellent results in connective tissue healing, there have not been many studies showing its effect on the regeneration of alveolar bone loss due to periodontal disease. The objectives of this study are to investigate the result of 12 months-long treatment following guided tissue regeneration using expanded polytetrafluoroehylene membrane, and to observe the presence of regenerated alveolar bone. Forty-one teeth from 28 patients with clinical diagnosis of periodontitis has been selected. In fifteen of those interproximal intrabony defects, only flap operation had been carried out, and designated as the control group. Twenty-six intrabony defects received e-PTFE membrane following flap operation, and designated as the experimental group. Eleven teeth whose membrane had been exposed were excluded from the experiment. Various measurements including probing depth, loss of attachment, probing bone level and gingival recession have been recorded at 6th month and 12th month, and the significance of the changes has been analyzed. The results are as follows: 1. Probing depth at 6th and 12th month has shown a significant decrease in both groups (p<0.01), but significantly higher decrease was found in the experimental group compared to the control at the month(p<0.05). 2. Loss of attachment at 6th and 12th month has shown a significant decrease in both groups, but significantly higher decrease was found in the experimental group compared to the control (p<0.05). 3. Probing bone level at 6th and 12th month has shown a insignificant decrease in the control group and significant decrease in the experimental group (p<0.01). Significantly higher decrease in probing bone level was found in the experimental group (p<0.05). 4. Gingival recession at 6th and 12th month has shown a statistically significant increase (p<0.05), and the control group showed higher increase compared to the experimental group although no statistical significance was found. As these results have shown, the use of e-PTFE membrane in intrabony pockets results in marked decrease in the loss of attachment and probing bone level. This seems to indicate that e-PTFE membrane may play a role in alveolar bone regeneration in intrabony defects.

• Journal of Periodontal and Implant Science
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• v.35 no.2
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• pp.461-474
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• 2005

The ultimate goal of periodontal therapy is the regeneration of periodontal tissue and the repair of function. For more than a decade there have been many efforts to develop materials and methods of treatment to promote periodontal tissue regeneration. Recently many efforts are concentrated on the regeneration potential of material used in traditional medicine. Safflower(Carthamus tinctorius L.) seed extract(SSE) have long clinically used in Korea to promote bone formation and prevent osteoporosis. The purpose of this study was to examine the effects of SSE on bone formation in human osteoblastic cell line. Human fetal osteoblastic cell line(hFOB 1.19) was cultured with DMEM and SSE($1{\mu}g/ml$, $10{\mu}g/ml$, $100{\mu}g/ml$, $1mg/ml$) at $34^{\cdot}C$ with 5% $CO_2$ in 100% humidity. The proliferation, differentiation of the cell was evaluated by several experiments. Cell proliferation was significantly increased at $10{\mu}g/ml$, $100{\mu}g/ml$, 1mg/ml of SSE after 3 and 7 days incubation(p<0.05). Cell spreading assay was significantly increased at $100{\mu}g/ml$ of SSE after 3 days and $1{\mu}g/ml$, $10{\mu}g/ml$, $100{\mu}g/ml$, 1mg/ml of SSE after 7 days(p<0.05). Alkaline Phosphatase(ALP) level was significantly increased in $10{\mu}g/ml$, $100{\mu}g/ml$, 1mg/ml of SSE(p<0.05). Collagen synthesis was significantly increased at $10{\mu}g/ml$, $100{\mu}g/ml$, 1mg/ml of SSE(p<0.05). A quantified calcium accumulation was significantly increased at $10{\mu}g/ml$, $100{\mu}g/ml$ of SSE(p<0.05). ALP and osteocalcin mRNA was expressed in $100{\mu}g/ml$ of SSE by RT-PCR. These results indicate that SSE are capable of increasing osteoblasts mineralization and may play an important role in bone formation.

• Korean Journal of Plant Resources
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• v.25 no.5
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• pp.578-585
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• 2012

Cytokines released from innate immune cells play key roles in the regulation of the immune response. Red Ginseng (RG, steamed and dried root of Panax ginseng C.A. Meyer) is known to show different pharmacological effects by changed composition of saponins compared with Panax Ginseng. In this study, we examined the immunomodulatory effects of RG on the regulation of cytokine release in mice. RG was injected i.p at doses of 0.5, 5 and 50 mg/kg for 6 weeks. We assessed that the weight index of immune organs such as thymus, and spleen, and the mitogen blastogenesis of splenocytes. We also determined the levels of circulating cytokines in serum from RG-treated mice using ELISA assay. The weight index of thymus and spleen, and proliferation of mitogen response of splenocytes have increased in the RG-injected groups. In addition, the levels of IFN-${\gamma}$, TNF-${\alpha}$, IL-6, IL-12 and IL-2 concentrations have significantly increased in the serum of RG-treated mice, but that of IL-10 has not. These results suggest that RG has immune stimulating effects and could be useful as a immunoregulator of circulating cytokine release in vivo.

• Molecules and Cells
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• v.41 no.6
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• pp.582-590
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• 2018

Endothelial progenitor cells (EPCs) and outgrowth endothelial cells (OECs) play a pivotal role in vascular regeneration in ischemic tissues; however, their therapeutic application in clinical settings is limited due to the low quality and quantity of patient-derived circulating EPCs. To solve this problem, we evaluated whether three priming small molecules (tauroursodeoxycholic acid, fucoidan, and oleuropein) could enhance the angiogenic potential of EPCs. Such enhancement would promote the cellular bioactivities and help to develop functionally improved EPC therapeutics for ischemic diseases by accelerating the priming effect of the defined physiological molecules. We found that preconditioning of each of the three small molecules significantly induced the differentiation potential of $CD34^+$ stem cells into EPC lineage cells. Notably, long-term priming of OECs with the three chemical cocktail (OEC-3C) increased the proliferation potential of EPCs via ERK activation. The migration, invasion, and tube-forming capacities were also significantly enhanced in OEC-3Cs compared with unprimed OECs. Further, the cell survival ratio was dramatically increased in OEC-3Cs against $H_2O_2$-induced oxidative stress via the augmented expression of Bcl-2, a pro-survival protein. In conclusion, we identified three small molecules for enhancing the bioactivities of ex vivo-expanded OECs for vascular repair. Long-term 3C priming might be a promising methodology for EPC-based therapy against ischemic diseases.

• Korean Journal of Microbiology
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• v.47 no.4
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• pp.342-347
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• 2011

T cells play a key role in viral infection. However, in patients with chronic hepatitis C virus (HCV) infection, HCV-specific T cells are dysfunctional and impaired in the liver, which is the primary site for HCV replication. There are multiple potential mechanisms for HCV-specific T cell dysfunction including induction of immune inhibitory pathways (program death-1; PD-1, cytotoxic t lymphocyte associated antigen-4; CTLA-4) and immune tolerance induced specific for the liver. However, the interaction between hepatocytes and HCV-specific CD8 T cells has not clearly established. In this study, we confirmed huh (human hepatoma) 7.5 cells expressing HLA (human leukocyte antigen) A2 presented antigen to activate HCV-specific CD8 T cells in HLA A2-restricted manner and expression of PD-L (program death ligand) 1 on huh7.5 cells reduced HCV-specific CD8 T cell activation, suggesting an immune modulatory activity. Loss of HCV-specific tetramer responses following antigenic stimulation correlated with increased caspase-3 activity. In addition, PD-L1 on huh7.5 cells rescued HCV-specific CD8 T cells from apoptosis. Our results suggest that the interaction between PD-L1 and PD-1 can recover the function of HCV-specific CD8 T cells in the liver, which could be applied in therapy of HCV chronic infection.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.4
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• pp.902-908
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• 2006

Tetrandra is the root of Stephania tetrandra 5. Moore (family Menispermaceae), or of Aristolochia frangchi Wu (family Aristolochiaceae). It is a Differ-flavored and cold-property herb acting on the urinary bladder, kidney and spleen meridiands. Known biological effects of this herb are expelling wind to relieve pain and inducing diuresis to alleviate edema. This herb also has anti-inflammatory and anti-hypersensitivity actions. Recent studies have shown that Stephanniae Tetrandrae Radix has antimicrobial effects, namely, a protective effect on acute renal failure induce by gentamicin sulfate and a suppressive effect against clostridium perfringes. However, there is a lack of studies concerning the immunological activities of this herb. The present study was conducted to evaluate the immunological activities of Stephanniae Tetrandrae Radix on the regulatory mechanisms of cytokines and nitric oxide (NO) in Raw 264.7 cells. Cell viability was measured by MTT assay after the treatment of Stephanniae Tetrandrae Radix extract (STRE) and NO production was monitored by measuring the nitrite content in culture medium. COX-2 and iNOS were determined by immunoblot analysis, and levels of cytokine were analyzed by sandwich immunoassays. Results provided evidences that STRE inhibited the production of nitrite and nitrate (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$, $interleukin-1{\beta}(IL-1{\beta})$ and interleukin-6 (IL-6) in Raw 264.7 cells activated with lipopolysaccharide (LPS). These findings showed that STRE could produce some anti-inflammatory effects which might play a role in adjunctive therapy in Gram-negative bacterial infections.