• Molecules and Cells
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• 제38권4호
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• pp.336-342
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• 2015

Propyl gallate (PG) used as an additive in various foods has antioxidant and anti-inflammatory effects. Although the functional roles of PG in various cell types are well characterized, it is unknown whether PG has effect on stem cell differentiation. In this study, we demonstrated that PG could inhibit adipogenic differentiation in human adipose tissue-derived mesenchymal stem cells (hAMSCs) by decreasing the accumulation of intracellular lipid droplets. In addition, PG significantly reduced the expression of adipocyte-specific markers including peroxisome proliferator-activated receptor-${\gamma}$ (PPAR-${\gamma}$), CCAAT enhancer binding protein-${\alpha}$ (C/EBP-${\alpha}$), lipoprotein lipase (LPL), and adipocyte fatty acid-binding protein 2 (aP2). PG inhibited adipogenesis in hAMSCs through extracellular regulated kinase (ERK) pathway. Decreased adipogenesis following PG treatment was recovered in response to ERK blocking. Taken together, these results suggest a novel effect of PG on adipocyte differentiation in hAMSCs, supporting a negative role of ERK1/2 pathway in adipogenic differentiation.

• Journal of Ginseng Research
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• 제39권2호
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• pp.105-115
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• 2015

Background: Alcoholic steatosis is the earliest and most common liver disease, and may precede the onset of more severe forms of liver injury. Methods: The effect of Korean Red Ginseng extract (RGE) was tested in two murine models of ethanol (EtOH)-feeding and EtOH-treated hepatocytes. Results: Blood biochemistry analysis demonstrated that RGE treatment improved liver function. Histopathology and measurement of hepatic triglyceride content verified the ability of RGE to inhibit fat accumulation. Consistent with this, RGE administration downregulated hepatic lipogenic gene induction and restored hepatic lipolytic gene repression by EtOH. The role of oxidative stress in the pathogenesis of alcoholic liver diseases is well established. Treatment with RGE attenuated EtOH-induced cytochrome P450 2E1, 4-hydroxynonenal, and nitrotyrosine levels. Alcohol consumption also decreased phosphorylation of adenosine monophosphate-activated protein kinase, which was restored by RGE. Moreover, RGE markedly inhibited fat accumulation in EtOH-treated hepatocytes, which correlated with a decrease in sterol regulatory element-binding protein-1 and a commensurate increase in sirtuin 1 and peroxisome proliferator-activated receptor-a expression. Interestingly, the ginsenosides Rb2 and Rd, but not Rb1, significantly inhibited fat accumulation in hepatocytes. Conclusion: These results demonstrate that RGE and its ginsenoside components inhibit alcoholic steatosis and liver injury by adenosine monophosphate-activated protein kinase/sirtuin 1 activation both in vivo and in vitro, suggesting that RGE may have a potential to treat alcoholic liver disease.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제29권6호
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• pp.499-508
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• 2007

Background and Purpose: Some subtypes of malignant salivary gland tumors such as adenoid cystic carcinoma (ACC) frequently result in distant metastasis of vascular origin, which are main causes of treatment failure. The reasons for the affinity for vascular metastatic potential are unclear. Therefore, molecular characteristics that influence the dissemination of metastatic tumor cells are important for the design of more effective treatment of salivary ACC. Tumor angiogenesis has been known to be essential for the distant metastasis of malignant cells. So, we determined expressions of vascular metastasis related factors in orthotopic (parotid) murine models of parotid ACC and compared with those in ectopic (subcutis) tumors of athymic mice. Experimental Design: Using specimens from murine parotid (orthotopic, experimental group) and subcutaneous (ectopic, control group) tumors, which have developed via transplantation of tumor cells, originated from human parotid ACC, we performed immunohistochemical assays with anti-vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF, FGF2), matrix metalloproteinase (MMP)-9, and interleukin (IL)-8 antibodies. We also performed immunohistochemical assays with VEGF receptor (VEGFR)-1, VEGFR-2, VEGFR-3, and phosphorylated VEGFR-2. Results: Transplantation of human ACC tumor cell $(5{\times}10^5)$ into the parotid and subcutis successfully resulted in orthotopic (parotid) and ectopic (subcutaneous) tumors in athymic mice. Immunohistochemical staining demonstrated higher expression of major angiogenic factors (VEGF, bFGF, MMP-9) in the orthotopic tumors than in ectopic tumors (P<0.05). But the expression level of angiogenic receptors were same in orthotopic and ectopic tumors of parotid ACC. Conclusion: VEGF, bFGF, and MMP-9 could be a good candidates for antiangiogenic therapy for the contol of vascular metastatic lesions of salivary ACC.

• Genomics & Informatics
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• 제12권2호
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• pp.58-63
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• 2014

The tyrosine-protein kinase Tec (TEC) is a member of non-receptor tyrosine kinases and has critical roles in cell signaling transmission, calcium mobilization, gene expression, and transformation. TEC is also involved in various immune responses, such as mast cell activation. Therefore, we hypothesized that TEC polymorphisms might be involved in aspirin-exacerbated respiratory disease (AERD) pathogenesis. We genotyped 38 TEC single nucleotide polymorphisms in a total of 592 subjects, which comprised 163 AERD cases and 429 aspirin-tolerant asthma controls. Logistic regression analysis was performed to examine the associations between TEC polymorphisms and the risk of AERD in a Korean population. The results revealed that TEC polymorphisms and major haplotypes were not associated with the risk of AERD. In another regression analysis for the fall rate of forced expiratory volume in 1 second ($FEV_1$) by aspirin provocation, two variations (rs7664091 and rs12500534) and one haplotype (TEC_BL2_ht4) showed nominal associations with $FEV_1$ decline (p=0.03-0.04). However, the association signals were not retained after performing corrections for multiple testing. Despite TEC playing an important role in immune responses, the results from the present study suggest that TEC polymorphisms do not affect AERD susceptibility. Findings from the present study might contribute to the genetic etiology of AERD pathogenesis.

• Korean Journal of Oriental Medicine
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• 제8권1호
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• pp.109-126
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• 2002

The herbal extract (YMT_02) is a modified herbal extracts from Yukmijihwangtang (YMJ) to promote memory-enhancing. The YMJ extracts has been widely used as an anti-aging herbal medicine for hundred years in Asian countries. The purpose of this study is to; 1) quantitatively evaluate the memory-enhancing effect of YMT_02 by hehavior task, 2) identify candidate genes responsible for enhancing memory by cDNA microarray and 3) assess the anti-oxidant effect of YMT_02 on PC12 cell. Memory retention abilities are addressed by passive avoidance task with Sprague-Dawley (SD) male rat. Before the training session, the rats are subdivided into four groups and administrated with YMT_02, Ginkgo biloba, Soya lecithin and normal saline for 10 days. The retention test was performed. 24 hours after the training session. The retention time of the YMT_02 group was significantly (p<0.05) delayed $({\sim}100%)$, whereas Ginkgo biloba and Soya lecithin treatment delayed 20% and 10% respectively. The hippocampi of YMT_02 and control group were dissected and mRNA was further purified. After synthesizing cDNA using oligo-dT primer, the cDNA were applied and mRNA was further purified. After synthesizing cDNA using oligo-dT primer, the cDNA were applied to Incyte rat GEMTM 2 cDNA microarray. The microarray results show that prealbumin(transthyretin), phosphotidy lethanolamine N-methyltransferase, and PEP-19 are expressed abundantly in the YMT_02 treated group. Especially, PEP-19 is a neuron-specific protein, which inhibits apoptotic processes in neuronal cell. On the other hand, transcripts of RAB15, glutamate receptor subunit 2 and CDK 108 are abundant in control group. Besides, neuronal genes involved in neuronal death or neurodegeneration such as neuronal-pentraxin and spectrin are abundantly expressed in control group. Additionally, the YMT_02 shows an anti oxidative effect in the PC12 cell. The list of differentially expressed genes may implicate further insight on the action and mechanism behind the memory-enhancing effect of herbal extracts YMT_02, for example, anti-apoptotic, anti-oxidative, and neuroprotective effects.

• Journal of Pharmaceutical Investigation
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• 제34권6호
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• pp.483-489
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• 2004

Fexofenadine HCl is non-sedating histamine H1 receptor antagonist that can be used for the treatment of seasonal allergic rhinitis. The objective of this study was to investigate whether the carriers of deformable liposomes can enhance the transepithelial permeability of fexofenadine HCl across the in vitro ALI human nasal monolayer model. Characterization of this model was achieved by bioelectric measurements and morphological studies. The passage 2 and 3 of cell monolayers exhibited the TEER value of $2852\;{\pm}\;482\;ohm\;{\times}\;cm^2$ on 11 days of seeding and maintained high TEER value for 5 days. The deformable liposome of fexofenadine HCl was prepared with phosphatidylcholine (PC) and cholic acid using extruder method. The mean particle size was about 200 nm and the maximum entrapment efficiency of 33.0% was obtained in the formulation of 1% PC and $100\;{\mu}g/ml$ fexofenadine HCl. The toxicity of the deformable liposome to human nasal monolayers was evaluated by MTT assay and TEER value change. MTT assay showed that it has no toxic effect on the nasal epithelial cells in 2-hour incubation when the PC concentration was below 1%. However, deformable liposome could not enhance the transepithelial permeability $(P_{app})$ and cellular uptake of fexofenadine HCl. In conclusion, the in vitro model could be used in nasal drug transport studies and evaluation of transepithelial permeability of formulations.

• The Korean Journal of Physiology and Pharmacology
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• 제22권3호
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• pp.269-275
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• 2018

$Na^+/H^+$ exchangers (NHEs) have been shown to be involved in regulating cell volume and maintaining fluid and electrolyte homeostasis. Pooled evidences have suggested that loss of $Na^+/H^+$ exchanger isoform 8 (NHE8) impairs intestinal mucosa. Whether NHE8 participates in the pathology of infectious colitis is still unknown. Our previous study demonstrated that somatostatin (SST) could stimulate the expression of intestinal NHE8 so as to facilitate $Na^+$ absorption under normal condition. This study further explored whether NHE8 participates in the pathological processes of infectious colitis and the effects of SST on intestinal NHE8 expression in the setting of infectious colitis. Our data showed that NHE8 expression was reduced in Citrobacter rodentium (CR) infected mice. Up-regulation of NHE8 improved diarrhea symptom and mucosal damage induced by CR. In vitro, a similar observation was also seen in Enteropathogenic E. coli (EPEC) infected Caco-2 cells. Seglitide, a SST receptor (SSTR) 2 agonist, partly reversed the inhibiting action of EPEC on NHE8 expression, but SSTR5 agonist (L-817,818) had no effect on the expression of NHE8. Moreover, SST blocked the phosphorylation of p38 in EPEC-infected Caco-2 cells. Taken together, these results suggest that enhancement of intestinal NHE8 expression by SST could ameliorate the symptoms of mice with infectious colitis.

• Journal of Chest Surgery
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• 제36권1호
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• pp.15-20
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• 2003

Myasthenia gravis is a rare autoimmune disease involving acetylcholine receptor and its autoantibody on neuromuscular junction. The methods of treatment are medical treatment and surgical thymectomy. In this paper we analyzed the result of thymectomy and the factors affecting the postoperative symptom improvement. Material and method : This study obtained medical records of 37 patients who received the thymectomy for myasthenia gravis from March 1986 to December 1998. Result Out of 37 cases, 21 cases(57%) showed improvement, of which 8 cases (50%) in the group of thymoma(n=16), and 13 cases (62%) in the group of thymic hyperplasia(n=21) showed the improvement of symptoms. Postoperative complications were respiratory insufficiency due to aggravation of symptoms after operation, including tracheal intubation for ventilator support in 9 cases, pneumonia in 3 cases, pneumothorax in 2 cases and left vocal cord palsy in 1 case. There was one postoperative mortality. The relation between postoperative improvement and sex(P=0.3222), age(P=0.7642), thymic pathologic variants,(P=0.4335) and classification of thymoma(P=0.20) showed no statistically significant correlation. However, the lower grade of preoperative symptoms can predict the lower grade of postoperative symptoms significantly(P=0.0032). Follow up study to 36 postoperative survivors was performed in October 2002 based on the out-patient records and call with patients. Out of 36 cases, 33 cases(91.7%) could be investigated and 3 cases could not. Mean follow up period was 83.2 months. Out of 33 cases, 25 cases(75.8%) showed symptomatic improvement, of which 8 cases(53.3%) in the group of thymoma(n=15) and 17 cases(94.4%) in the group of thymic hyperplasia(n=18) showed the improvement of$\boxUl$ symptoms. Conclusion : In myasthenia gravis, thymectomy showed the good improvement, and more important factor affecting the improvement of symptoms was the grdae of preoperative symptoms. Also midterm and long term follow up results showed good symptomatic improvement.

• Journal of Yeungnam Medical Science
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• 제14권1호
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• pp.53-66
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• 1997

Insulin resistance is a prominent feature of diabetic state and has heterogeneous nature. However, the pathogenetic sequence of events leading to the emergence of the defect in insulin action remains controversial. It is well-known that prolonged hyperglycemia and hyperinsulinemia are one of the causes of development of insulin resistance, but both hyperglycemia and hyperinsulinemia stimulate glucose uptake in peripheral tissue. Therefore, it is hypothesized that insulin resistance may be generated by a kind of protective mechanism preventing cellular hypertrophy. In this study, to evaluate whether the acutely increased glucose uptake inhibits further glucose transport stimulated by insulin, insulin sensitivity was measured after preloaded glucose infusion for 2 hours at various conditions in rats. And also, to evaluate the mechanism of decreased insulin sensitivity, insulin receptor binding affinity and glucose transporter 4 (GLUT4) protein of plasma membrane of gastrocnemius muscle were assayed after hyperinsulinemic euglycemic clamp studies. Experimental animals were divided into five groups according to conditions of preloaded glucose infusion: group I, basal insulin ($14{\pm}1.9{\mu}U/ml$) and basal glucose ($75{\pm}0.7mg/dl$), by normal saline infusion; group II, normal insulin ($33{\pm}3.8{\mu}U/ml$) and hyperglycemia ($207{\pm}6.3mg/dl$), by somatostatin and glucose infusion; group III, hyperinsulinemia ($134{\pm}34.8{\mu}U/ml$) and hyperglycemia ($204{\pm}4.6mg/dl$), by glucose infusion; group IV, supramaximal insulin ($5006{\pm}396.1{\mu}U/ml$) and euglycemia ($l00{\pm}2.2mg/dl$), by insulin and glucose infusion; group V, supramaximal insulin ($4813{\pm}687.9{\mu}U/ml$) and hyperglycemia ($233{\pm}3.1mg/dl$), by insulin and glucose infusion. Insulin sensitivity was assessed with hyperinsulinemic euglycemic clamp technique. The amounts of preloaded glucose infusion(gm/kg) were $1.88{\pm}0.151$ in group II, $2.69{\pm}0.239$ in group III, $3.54{\pm}0.198$ in group IV, and $4.32{\pm}0.621$ in group V. Disappearance rates of glucose (Rd, mg/kg/min) at steady state of hyperinsulinemic euglycemic clamp studies were $16.9{\pm}3.88$ in group I, $13.5{\pm}1.05$ in group II, $11.2{\pm}1.17$ in group III, $13.2{\pm}2.05$ in group IV, and $10.4{\pm}1.01$ in group V. A negative correlation was observed between amount of preloaded glucose and Rd (r=-0.701, p<0.001) when all studies were combined. Insulin receptor binding affinity and content of GLUT4 were not significantly different in all experimental groups. These results suggest that increased glucose uptake may inhibit further glucose transport and lead to decreased insulin sensitivity.

• Development and Reproduction
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• 제13권4호
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• pp.353-362
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• 2009

GnRH and its receptor are known to express locally in the ovary and to regulate the ovarian function by affecting on granulosa and lutein cells. It has been reported that GnRH directly causes apoptosis in the granulosa and lutein cells of the ovary. However, whether the apoptosis of the cells by GnRH is recovered by FSH as an anti-apoptotic factor is not yet known. In this study, we evaluated the apoptosis and the production of progesterone $(P_4)$ and estradiol $(E_2)$ after treatment with 5, 50, and 100 ng/$m\ell$ GnRH and 1 IU/ml FSH in the granulosa-lutein cells that are obtained during oocyte-retrieval for IVF-ET. Results of DNA fragment analysis and TUNEL assay demonstrated that DNA fragmentation and the rate of apoptotic cells were increased in a dose-dependent manner showing a significant increase in the cells treated with 100 ng/$m\ell$ GnRH. In addition, we found that FSH suppresses the apoptosis of the cells induced by GnRH. In the results of chemiluminescence assay for $P_4$ and $E_2$, $P_4$ production was decreased by GnRH treatment, whereas $E_2$ production was not changed. We also demonstrated that FSH inhibits the suppressive effect of GnRH on $P_4$ production as the result of apoptosis. The present results suggest that GnRH agonist using in ovarian hyperstimulation protocol might induce the dysfunction of the ovary, but its function could be recovered by FSH. These results also will be expected to use as the basic data to elucidate the physiological role of GnRH and to develop new ovarian hyperstimulation protocols for IVF-ET.