• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.2
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• pp.119-130
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• 2008

Absorbable atelo-collagen sponge $TERUPLUG^{(R)}$, Termo Co. Tokyo, Japan) is inserted in the extraction wound where alveolar bone is exposed. It protects wounds and promotes the formation of granulation. This is made of atelo-collagen, to minimize antigenicity, which is cross-linked by heat treatment for biocompatibility. $TERUPLUG^{(R)}$ consists of between 85 and 95 % of collagen type I and between 5 to 15 % of collagen type III. The raw material for the collagen is derived from bovine skin. It features a sponge block design and is shaped for easy insertion in the extraction wound. This study was designed to find out the bone healing capacity of $TERUPLUG^{(R)}$. We implanted $TERUPLUG^{(R)}$ (experimental group I) and $TERUPLUG^{(R)}$ with rhBMP-2 (experimental group II) in the rabbit cranium defect and then histologically analysed the specimen. The results were as follows. 1. In the 4 weeks, a lot of the newly formed collagen fibers around material of the experimental group I implanted $TERUPLUG^{(R)}$ were observed. But, in the experimental group II implanted $TERUPLUG^{(R)}$ with rhBMP-2, a little of newly formed collagen fibers around material were observed. The cell proliferating activity and apoptosis of the experimental group I, II was positive in and around the implanted material. 2. In the 8 weeks, the amount of newly formed and matured bone in the experimental group II was more observed than the experimental group I and control group. The results of this study indicate that absorbable atelo-collagen sponge ($TERUPLUG^{(R)}$) is relatively favorable bone void filler with biocompatibility and has the better bone healing capacity in case of application with rhBMP-2.

• BMB Reports
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• v.39 no.6
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• pp.649-655
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• 2006

The NSAID activated gene (NAG-1), a member of the TGF-$\beta$ superfamily, is involved in tumor progression and development. The over-expression of NAG-1 in cancer cells results in growth arrest and increase in apoptosis, suggesting that NAG-1 has anti-tumorigenic activity. This conclusion is further supported by results of experiments with transgenic mice that ubiquitously express human NAG-1. These transgenic mice are resistant to the development of intestinal tumors following treatment with azoxymethane or by introduction of a mutant APC gene. In contrast, other data suggest a pro-tumorigenic role for NAG-1, for example, high expression of NAG-1 is frequently observed in tumors. NAG-1 may be like other members of the TGF-$\beta$ superfamily, acting as a tumor suppressor in the early stages, but acting pro-tumorigenic at the later stages of tumor progression. The expression of NAG-1 can be increased by treatment with drugs and chemicals documented to prevent tumor formation and development. Most notable is the increase in NAG-1 expression by the inhibitors of cyclooxygenases that prevent human colorectal cancer development. The regulation of NAG-1 is complex, but these agents act through either p53 or EGR-1 related pathways. In addition, an increase in NAG-1 is observed in inhibition of the AKT/GSK-$3{\beta}$ pathway, suggesting NAG-1 alters cell survival. Thus, NAG-1 expression is regulated by tumor suppressor pathways and appears to modulate tumor progression.

• Korean Journal of Medicinal Crop Science
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• v.21 no.2
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• pp.136-141
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• 2013

Chelidonium majus (CM) contains several isoquinoline alkaloids that have been reported to have various biological activities such as anti-inflammatory, antimicrobial, antioxidant, immune-modulatory, and antitumoral. It has been reported that the extract of CM had an antioxidant potential, however the mechanism has not been verified. In this study, we found that CM extract activated FOXO3a. FOXO3a is a transcription factor that involved in various biological processes such as cell cycle arrest, apoptosis, DNA repair, and ROS detoxification. Transcriptional activities of FOXO3a were regulated by post-translational modifications including phosphorylation, acetylation, and ubiquitination. Protein level of FOXO3a was increased by CM extract. Promoter activities of FOXO-transcriptional target genes such as MnSOD, p27 and GADD45 were activated by CM extract in a dose dependent manner. In addition, protein level of MnSOD, major antioxidant enzyme, was increased by CM extract. Thereby ROS level was decreased by CM in old HEF cells. These results suggest that CM extract has an antioxidant activity through FOXO activation.

• The Journal of Internal Korean Medicine
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• v.34 no.3
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• pp.298-311
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• 2013

Objectives : In this study, we aimed to investigate the effect of Eunhoebanchong-san (EBS) on caerulein-induced acute pancreatitis (AP) by detecting oxidative stress markers and performing histopathological examination. Methods : Thirty adult male Sprague-Dawley rats were divided into five groups as follows: normal (NOR), caerulein-induced (CON), caerulein+EBS (130 mg/kg, EA), caerulein+EBS (260 mg/kg, EB) and caerulein+EBS (520 mg/kg, EC) groups. Pancreatic tissues of rats from all groups were removed for apoptosis, and light, and electron microscopic examination. Blood of rats from all groups was obtained for oxidative stress markers and pathological examination. Pancreatic oxidative stress markers were evaluated by the measurements of serum amylase, and interleukin-6 (IL-6) levels were determined spectrophotometrically. Results : The ratio of pancreas/body weight increased significantly in the CON compared with the NOR, but decreased significantly in the EA, the EB, the EC groups compared with the CON. Caerulein administration resulted in a significant increase in amylase, but EBS reduced the levels of these enzymes. Interleukin-6 (IL-6) levels increased significantly in CON compared with NOR, but reduced in EA, EB, and EC group at 24 hrs. In the observations of optical microscopy and electron microscopy, the experimental groups showed significant decreases in pancreatic tissue inflammation, edema, vacuolization, necrosis compared to the control group. Altogether, this indicates EBS is potentially capable of limiting pancreatic damage produced during AP by restoring the fine structure of acinar cells and tissue. Conclusions : We concluded that EBS may have beneficial effects in the treatment of caerulein-induced AP.

• Biomolecules & Therapeutics
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• v.16 no.4
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• pp.336-342
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• 2008

The resveratrol analogue piceatannol (3,5,3',4'-tetrahydroxy-trans-stilbene) is a polyphenol present in grapes and wine and reported to have anti-carcinogenic activities. To investigate the mechanism of anticarcinogenic activities of piceatannol, the effects on CYP 1 enzymes were determined in Escherichia coli membranes coexpressing recombinant human CYP1A1, CYP1A2 or CYP1B1 with human NADPH-P450 reductase. Piceatannol showed a strong inhibition of CYP1A1 and CYP1B1 in a concentration-dependent manner, and $IC_{50}$ of human CYP1A1 and CYP1B1 was 5.8 ${\mu}M$ and 16.6 ${\mu}M$, respectively. However, piceatannol did not inhibit CYP1A2 activity in the concentration of up to 100 ${\mu}M$. Piceatannol exhibited 3-fold selectivity for CYP1B1 over CYP1A1. The mode of inhibition of piceatannol was non-competitive for CYP1A1 and CYP1B1. The result that piceatannol did not inhibit CYP1B1-mediated $\alpha$-naphthoflavone ($\alpha$-NF) metabolism suggests piceatannol may act as a non-competitive inhibitor as well. In human prostate carcinoma PC-3 cells, piceatannol induces apoptosis and prevents Aktmediated signal pathway. Taken together, abilities of piceatannol to induce apoptotic cell death as well as CYP1 enzyme inhibition make this compound a useful tool for cancer chemoprevention.

• Journal of Applied Biological Chemistry
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• v.62 no.4
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• pp.347-353
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• 2019

Stings of jellyfish, which frequently occur in a warm season, cause severe pain, inflammation and sometimes irreversible results such as the death. Harmful venoms from jellyfish, therefore, have been studied for finding the therapeutic agents to relieve pain or to neutralize toxic components. However, it is still unclear if and how jellyfish venom reveal neuronal toxicity even though pain induction seems to result from the activation of nociceptors such as nerve endings. In this study, using HT-22 cell line, we investigated neurotoxic effects of the venom of Chrysaora pacifica (CpV) which appears in South-East ocean of Korea. In 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, CpV significantly reduced the viability of HT-22 cells in a dose-dependent manner. Additionally, in 2',7'-Dichlorofluorescin diacetate fluorescence test under the culture condition lacking dominant inflammatory factors, CpV remarkably increased the production of intracellular reactive oxygen species (ROS). Reduced responsive fluorescence to Rhodamine123 and increased expression of intracellular cytochrome c were also observed in HT-22 cells treated with CpV. These indicate that CpV-reduced viability of HT-22 cells may be due to the activation of apoptotic signalings mediated with oxidative stress and mitochondrial dysfunction. Furthermore, removing Ca²⁺ ion or adding N-acetyl-Lcystein remarkably blocked the CpV effect to reduce the viability of HT-22 cells. The findings in this study clearly demonstrate that CpV may activate Ca²⁺-mediated ROS signalings and mitochondrial dysfunction resulting in neuronal damage or death, and suggest that blocking Ca²⁺ pathway is a therapeutic approach to possibly block toxic effects of jellyfish venoms.

• Reproductive and Developmental Biology
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• v.37 no.2
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• pp.79-83
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• 2013

Matrix metalloproteinases (MMPs) have been known to affect to cell migration, proliferation, morphogenesis and apoptosis by degrading the extracellular matrix. In the previous studies, undifferentiated mouse embryonic stem cells (ESCs) were successfully proliferated inside the extracellular matrix (ECM) analog-conjugated three-dimensional (3D) poly ethylene glycol (PEG)-based hydrogel. However, there is no report about MMP secretion in ESCs, which makes it difficult to understand and explain how ESCs enlarge space and proliferate inside 3D PEG-based hydrogel constructed by crosslinkers containing MMP-specific cleavage peptide sequence. Therefore, we investigated what types of MMPs are released from undifferentiated ESCs and how extracellular signals derived from various niche conditions affect MMP expression of ESCs at the transcriptional level. Results showed that undifferentiated ESCs expressed specifically MMP2 and MMP3 mRNAs. Transcriptional up-regulation of MMP2 was caused by the 3D scaffold, and activation of integrin inside the 3D scaffold upregulated MMP2 mRNAs synergistically. Moreover, mouse embryonic fibroblasts (MEFs) on 2D matrix and 3D scaffold induced upregulation of MMP3 mRNAs, and activation of integrins through conjugation of extracellular matrix (ECM) analogs with 3D scaffold upregulated MMP3 mRNAs synergistically. These results suggest that successful proliferation of ESCs inside the 3D PEG-based hydrogel may be caused by increase of MMP2 and MMP3 expression resulting from 3D scaffold itself as well as activation of integrins inside the 3D PEG-based scaffold.

• KSBB Journal
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• v.29 no.1
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• pp.50-57
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• 2014

NF-${\kappa}B$ is a transcriptional factor which is involved in many biological processes including immunity, inflammation, and cell survival. Many investigators studied on the mechanism involved in activation of NF-${\kappa}B$ signalling pathway via ubiquitination and degradation of $I{\kappa}B$ regarding skin disease. Some specific molecules including Akt, MEK, p38 MAP Kinase, Stat3, et al. represent convergence points and key regulatory proteins in signaling pathways controlling cellular events such as growth and differentiation, energy homeostasis, and the response to stress and inflammation. Ultraviolet (UV) irradiation has many adverse effects on skin, including inflammation, alteration in the extracellular matrix, cellular senescence, apoptosis and skin cancer. Prunus mume, a naturally derived plant extract, has beneficial biological activities as blood fluidity improvement, anti-fatigue action, antioxidative and free radical scavenging activities, inhibiting the motility of Helicobacter pyolri. Previous reports on various beneficial function prompted us to investigate UVB-induced or other immunostimulated biological marker regarding P. mume extract. P. mume extract suppresses UVB-induced cyclooxygenase-2 (COX-2) expression in mouse skin epidermal JB6 P+ cells. The activation of activator protein-1 and nuclear factor-${\kappa}B$ induced by UVB was dose-dependently inhibited by P. mume extract treatment. This results suggest that P. mume extracts might be used as a potential agents for protection of inflammation or UVB induced skin damage.

• KSBB Journal
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• v.28 no.4
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• pp.230-237
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• 2013

Amyloid ${\beta}$ peptide (A${\beta}$) still best known as a molecule to cause Alzheimer's disease (AD). AD is characterized by the accumulation and deposition of A${\beta}$ within the brain, leading to neuronal cell loss and perturbation of synaptic function by causing free radical formation, inflammation and apoptosis. We investigated the inflammatory action of A${\beta}$ on two types of brain cells, neuronal cells (SH-SY5Y) and neuroglia cells (C6), and its mechanism. We measured the production of NO-iNOS, TNF-${\alpha}$, and ICAM-1 using RT-PCR and Western blot analysis less than the concentration of cytotoxic effects (> 70% survivability). A${\beta}$ had no effect on the production of NO and TNF-${\alpha}$, but significantly increases of iNOS and ICAM-1. Based on this, we suggest that the inflammatory effect of A${\beta}$ results from the action of ICAM-1 in neuronal cells, rather than the release of inflammatory mediators such as NO and TNF-${\alpha}$ in neuroglia cells. In addition, we confirmed whether p53 was related to the action of A${\beta}$ by using SH-SY5Y ($p53^{-/-}$) dominant cells. Neither the expression of p53 nor the cytotoxicity of SH-SY5Y ($p53^{-/-}$) cells were directly affected by A${\beta}$. However, ICAM-1 was not expressed in SH-SY5Y ($p53^{-/-}$) cells. This means that p53- independent pathway exists in the expression of ICAM-1 by A${\beta}$ while p53 plays a role as an on-and-off switch.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.7
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• pp.896-902
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• 2017

In this study, we investigated citrus Kombucha (CK) produced by three different bacteria strains (Gluconacetobacter xylinus, Gluconacetobacter medellinensis, and Gluconobacter oxydans; named as CK-MOX) identified from traditional Kombucha. During fermentation, the pH level of CK-MOX was gradually reduced, and total acidity slightly increased. Antioxidant activity, measured by DPPH, ABTS, and oxygen radical absorbance capacity assays, markedly increased after fermentation. Moreover, fermented CK-MOX (Day15) exhibited anti-proliferative and anti-migratory activities against EJ human bladder carcinoma cells. Western immunoblot assays showed that treatment with CK-MOX significantly up-regulated phospho-extracellular signaling kinase (ERK) levels. To distinguish whether or not up-regulation of phospho-ERK is the cause or effect, we investigated the viability of EJ cells in the presence of U0126, a mitogen activated protein kinase/ERK kinase 1/2 inhibitor. Pre-treatment with U0126 rescued cells from CK-MOX-induced cell death, which indicates phospho-ERK may be a key regulator in the mechanism of CK-MOX-induced apoptosis of EJ bladder cancer cells. In conclusion, CK-MOX, fermented by a defined composition of bacterial starters, shows antioxidant capacity and anti-cancer activity against EJ bladder cancer cells.