• Archives of Plastic Surgery
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• v.40 no.3
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• pp.181-186
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• 2013

Background Partial or complete necrosis of a skin flap is a common problem. Polydeoxyribonucleotide (PDRN) can be extracted from trout sperm and used as a tissue repair agent. The aim of this study was to investigate whether PDRN could improve the survival of random pattern skin flaps in rats. Methods Twenty-two male Sprague-Dawley rats were randomly divided into two groups: the PDRN treatment group (n=11) and the control group (n=11). Caudally pedicled random pattern skin flaps were elevated on their dorsal skin and resutured. The treatment group received daily intraperitoneal administration of PDRN (8 mg/kg/day), and the control group received fluid vehicle (NaCl 0.9%, 8 mg/kg/day) from day 0 to day 6. On day 7, the flap survival was evaluated and the harvested tissue surrounding the demarcation line of the necrotic area was stained with H&E, anti-rat vascular endothelial cell growth factor (VEGF) antibody, and PECAM-1/CD31 antibody. Results The average necrotic area of the flap in the PDRN group was significantly smaller when compared with that of the control group. Histologic and immunohistochemical evaluation showed that granulation thickness score and VEGF-positive staining cells were marked higher in the PDRN group than in the control group. PECAM-1/CD31-positive microvascular densities were significantly higher in the PDRN group when compared with the control group. Conclusions This study confirms that PDRN improves the survival of random pattern skin flaps in rats. These results may represent a new therapeutic approach to enhancing flap viability and achieving faster wound repair.

• Biomolecules & Therapeutics
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• v.21 no.4
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• pp.313-322
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• 2013

Previous studies have demonstrated that repeated administration of the exogenous stress hormone corticosterone (CORT) induces dysregulation in the hypothalamic-pituitary-adrenal (HPA) axis and results in depression and anxiety. The current study sought to verify the impact of catechin (CTN) administration on chronic CORT-induced behavioral alterations using the forced swimming test (FST) and the elevated plus maze (EPM) test. Additionally, the effects of CTN on central noradrenergic systems were examined by observing changes in neuronal tyrosine hydroxylase (TH) immunoreactivity in rat brains. Male rats received 10, 20, or 40 mg/kg CTN (i.p.) 1 h prior to a daily injection of CORT for 21 consecutive days. The activation of the HPA axis in response to the repeated CORT injections was confirmed by measuring serum levels of CORT and the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. Daily CTN administration significantly decreased immobility in the FST, increased open-arm exploration in the EPM test, and significantly blocked increases of TH expression in the locus coeruleus (LC). It also significantly enhanced the total number of line crossing in the open-field test (OFT), while individual differences in locomotor activities between experimental groups were not observed in the OFT. Taken together, these findings indicate that the administration of CTN prior to high-dose exogenous CORT significantly improves helpless behaviors, possibly by modulating the central noradrenergic system in rats. Therefore, CTN may be a useful agent for the treatment or alleviation of the complex symptoms associated with depression and anxiety disorders.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.3
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• pp.446-451
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• 2010

We investigated whether oral administration with capsicum extract (Capsicum annuum var. cheongyang) would affect the immune system by examining the immune cells of Peyer's patch (PP), a gut associated lymphoid tissue, ex vivo. The mice were orally administrated with capsicum extract (100 mg/kg/day), capsaicin (10 mg/Kg), and the vehicle for four consecutive days, and PPs were isolated from intestines 2 days later. When the PP cells were cultured in the presence of Concanavalin A for 72 hr, the levels of cytokines, including IL-2 and IFN-${\gamma]$, were dramatically increased, while the levels of IL-4 remained unchanged compared with the control. Data from the FACS analysis of PP cells indicated that capsicum extract significantly increased the number of CD3+ and CD4+ T cells as well as CD 19+ B cells compared with the control but not CD11b+ cells. Furthermore, the percentages of IL-2+ /CD4+ cells and IFN-${\gamma}+$/CD4+ were greatly increased. These data suggested that oraladministration with capsicum extract might activate the CD4+ T cells leading to cytokine production as well as CD19+ B cells in Peyer's patches. As such, capsicum extract might have potential as an immune modulating agent.

• Journal of Microbiology and Biotechnology
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• v.22 no.5
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• pp.708-720
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• 2012

In this study, we assessed the effects of ginsenoside Re (GRe) administration on repeated immobilization stress-induced behavioral alterations using the forced swimming test (FST), the elevated plus maze (EPM), and the active avoidance conditioning test (AAT). Additionally, we examined the effect of GRe on the central adrenergic system by observing changes in neuronal tyrosine hydroxylase (TH) immunoreactivity and brain-derived neurotrophic factor (BDNF) mRNA expression in the rat brain. Male rats received 10, 20, or 50 mg/kg GRe (i.p.) 30 min before daily exposures to repeated immobilization stress (2 h/day) for 10 days. Activation of the hypothalamic-pituitary-adrenal (HPA) axis in response to repeated immobilization was confirmed by measuring serum levels of corticosterone (CORT) and the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. Repeated immobilization stress increased immobility in the FST and reduced open-arm exploration in the EPM test. It also increased the probability of escape failures in the AAT test, indicating a reduced avoidance response. Daily administration of GRe during the repeated immobilization stress period significantly inhibited the stress-induced behavioral deficits in these behavioral tests. Administration of GRe also significantly blocked the increase in TH expression in the locus coeruleus (LC) and the decrease in BDNF mRNA expression in the hippocampus. Taken together, these findings indicate that administration of GRe prior to immobilization stress significantly improved helpless behaviors and cognitive impairment, possibly through modulating the central noradrenergic system in rats. These findings suggest that GRe may be a useful agent for treating complex symptoms of depression, anxiety, and cognitive impairment.

• Journal of Periodontal and Implant Science
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• v.30 no.4
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• pp.747-757
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• 2000

Cyclosporin A(CsA) is an immunosuppressive agent widely used for preventing graft rejecting response in organ transplantation. The basic properties of CsA to osteoblast has not been well known yet. A better understanding of the mechanisms of CsA function on bone could provide valuable information regarding basic properties of bone remodeling, pharmacotherapeutic intervention in metabolic bone disease, and the consequences of immunosuppression in bone physiology. The purpose of this study was to investigate the effect of CsA on osteoblast by evaluating parameters of proliferation, collagen synthetic activity, alkaline phosphatase activity, and ALP mRNA expression in mouse calvarial cell. 1. CsA ($3{\mu}g/m{\ell}$) treated mouse calvarial cell showed statistically significant increase in cell proliferation.(P<0.05) 2. CsA($1,\; 3{\mu}g/m{\ell}$) treated MC3T3 cell line showed statistically significant increase in cell proliferation. 3. The amount of collagen of CsA($3{\mu}g/m{\ell}$) treated mouse calvarial cell was decreased statistically significantly. 4. Alkaline phosphatase activity was increased statistically significantly in CsA treated group($1{\mu}g/m{\ell}$). 5. mRNA expression of ALP was increased in CsA treated group These results suggest that CsA could affect bone remodeling by modulating proliferation & differentiation of osteoblast.

• Journal of Ginseng Research
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• v.41 no.1
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• pp.96-102
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• 2017

Background: Korean ginseng, Panax ginseng Meyer, has been used as a traditional oriental medicine to treat illness and promote health for several thousand years. Ginsenosides are the main constituents for the pharmacological effects of P. ginseng. Since several ginsenosides, including ginsenoside (G)-Rg3 and G-Rp1, have reported antiplatelet activity, here we investigate the ability of G-Rp4 to modulate adenosine diphosphate (ADP)-induced platelet aggregation. The ginsenoside Rp4, a similar chemical structure of G-Rp1, was prepared from G-Rg1 by chemical modification. Methods: To examine the effects of G-Rp4 on platelet activation, we performed several experiments, including antiplatelet ability, the modulation of intracellular calcium concentration, and P-selectin expression. In addition, we examined the activation of integrin ${\alpha}IIb{\beta}_3$ and the phosphorylation of signaling molecules using fibrinogen binding assay and immunoblotting in rat washed platelets. Results: G-Rp4 inhibited ADP-induced platelet aggregation in a dose-dependent manner. We found that G-Rp4 decreased calcium mobilization and P-selectin expression in ADP-activated platelets. Moreover, fibrinogen binding to integrin ${\alpha}IIb{\beta}_3$ by ADP was attenuated in G-Rp4-treated platelets. G-Rp4 significantly attenuated phosphorylation of extracellular signal-regulated protein kinases 1 and 2, p38, and c-Jun N-terminal kinase, as well as protein kinase B, phosphatidylinositol 3-kinase, and phospholipase C-${\gamma}$ phosphorylations. Conclusion: G-Rp4 significantly inhibited ADP-induced platelet aggregation and this is mediated via modulating the intracellular signaling molecules. These results indicate that G-Rp4 could be a potential candidate as a therapeutic agent against platelet-related cardiovascular diseases.

• Molecules and Cells
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• v.27 no.2
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• pp.149-157
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• 2009

In both gram-positive and several gram-negative bacteria, the transcription of dnaK and groE operons is negatively regulated by HrcA; however, the mechanism modulating HrcA protein activity upon thermal stress remains elusive. Here, we demonstrate that HrcA is modulated via reduction and oligomerization in vitro. Native-PAGE analysis was used to reveal the oligomeric structure of HrcA. The oligomeric HrcA structure became monomeric following treatment with the reducing agent dithothreitol, and this process was reversed by treatment with hydrogen peroxide. Moreover, the mutant HrcA C118S exhibited reduced binding to CIRCE elements and became less oligomerized, suggesting that cysteine residue 118 is important for CIRCE element binding as well as oligomerization. Conversely, HrcA mutant C280S exhibited increased oligomerization. An HrcA double mutant (C118S, C280S) was monomeric and exhibited a level of oligomerization and CIRCE binding similar to wild type HrcA, suggesting that cysteine residues 118 and 280 may function as checks to one another during oligomer formation. Biochemical fractionation of E. coli cells overexpressing HrcA revealed the presence of HrcA in the membrane fraction. Together, these results suggest that the two HrcA cysteine residues at positions 118 and 280 function as reduction sensors in the membrane and mediate oligomerization upon stress.

• Journal of Microbiology and Biotechnology
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• v.21 no.7
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• pp.757-765
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• 2011

Many studies have suggested that the behavioral and reinforcing effects of morphine are induced by hyperactivation of the mesolimbic dopaminergic system, which results in increases in locomotor activity, c-Fos expression in the nucleus accumbens (NAc), and tyrosine hydroxylase (TH) in the ventral tegmental area (VTA). In order to investigate the effect of wild ginseng (WG) on treating morphine addiction, we examined the behavioral sensitization of locomotor activity and c-Fos and TH expression in the rat brain using immunohistochemistry. Intraperitioneal injection of WG (100 and 200 mg/kg), 30 min before administration of a daily injection of morphine (40 mg/kg, s.c.), significantly inhibited morphine-induced increases in c-Fos expression in NAc and TH expression in VTA as well as in locomotor activity, as compared with Panax ginseng. It was demonstrated that the inhibitory effect of WG on the behavioral sensitization after repeated exposure to morphine was closely associated with the reduction of dopamine biosynthesis and postsynaptic neuronal activity. It suggests that WG extract may be effective for inhibiting the behavioral effects of morphine by possibly modulating the central dopaminergic system and that WG might be a useful resource to develop an agent for preventing and treating morphine addiction.

• The Journal of Internal Korean Medicine
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• v.27 no.3
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• pp.653-663
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• 2006

Objective : Graves' disease, the most common cause of hyperthyroidism, is an autoimmune disorder associated with autoantibodies to the TSH receptor. The clinical features of Graves' disease are goiter and hypermetabolic symptoms induced by excessive hormones. Antithyroid drug therapy is the first-line treatment for Graves' disease in Korea, Japan and European countries. Yet in spite of a long period and high-dose of treatment, it is hard to achieve remission because of adverse effects, frequent recurrence and resistance to antithyroid drugs. Recently, it has been reported that the abnormal thyroid hormone and clinical symptoms of Graves' disease were reduced by Ahnjeonbaekho-tang (AJBHT). Methods : To investigate the effectiveness and action mechanism of AJBHT, we studied the influence of AJBHT on FRTL-5 thyroid cell proliferation, DNA synthesis and expression of T4, TSH, cAMP, Tg and TPO mRNA. Results : AJBHT significantly inhibited the FRTL-5 cell proliferation, DNA synthesis, T4 synthesis, cAMP production and the expression of Tg mRNA in comparison with control and MMI. Conclusions : These results suggest that AJBHT may inhibit the cell proliferation and DNA synthesis by regulating the cAMP, and suppress the T4 synthesis by modulating Tg mRNA expression and cAMP synthesis, and that it may be useful agent for treating the goiter and hormone abnormality of Graves' disease.

• Biomolecules & Therapeutics
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• v.20 no.3
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• pp.313-319
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• 2012

In recent years, inhibition of HDACs has emerged as a potential strategy to reverse aberrant epigenetic changes associated with cancer, and several classes of HDAC inhibitors have been found to have potent and specific anticancer activities in preclinical studies. But their precise mechanism of action has not been elucidated. In this study, a novel synthetic inhibitor of HDAC, 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide [IN-2001] was examined for its antitumor activity and the underlying molecular mechanisms of any such activity on human breast cancer cell lines. IN-2001 effectively inhibited cellular HDAC activity ($IC_{50}$ = 0.585 nM) inMDA-MB-231 human breast cancer cells. IN-2001 caused a significant dose-dependent inhibition of cell proliferation in estrogen receptor (ER) negative MDA-MB-231human breast cancer cells. Cell cycle analysis revealed that the growth inhibitory effects of IN-2001 might be attributed to cell cycle arrest at $G_0/G_1$ and/or $G_2$/Mphase and subsequent apoptosis in human breast cancer cells. These events are accompanied by modulating several cell cycle and apoptosis regulatory genes such as CDK inhibitors $p21^{WAF1}$ and $p27^{KIP1}$ cyclin D1, and other tumor suppressor genes such as cyclin D2. Collectively, IN-2001 inhibited cell proliferation and induced apoptosis in human breast cancer cells and these findings may provide new therapeutic approaches, combination of antiestrogen together with a HDAC inhibitor, in the hormonal therapy-resistant ER-negative breast cancers. In summary, our data suggest that this histone deacetylase inhibitor, IN-2001, is a novel promising therapeutic agent with potent antitumor effects against human breast cancers.