• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.37 no.1
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• pp.30-35
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• 2011

Introduction: Dental implants are used routinely with high success rates in generally healthy individuals. By contrast, their use in patients with diabetes mellitus is controversial because altered bone healing around implants has been reported. This study examined the bone healing response around titanium implants placed immediately in rats with controlled and uncontrolled diabetes. Materials and Methods: Twenty rats were divided into the control, insulin-treated and diabetic groups. The rats received streptozotocin (60 mg/kg) to induce diabetes; animals in the insulin-treated group also received three units of subcutaneous slow-release insulin. A titanium implant ($1.2{\times}3\;mm$) was placed in the extraction socket of the maxillary first molar and bone block was harvested at 1, 2 and 4 weeks. Results: Bone formation around the implants was consistently (from 1 to 4 week post-implantation) slower for the diabetic group than the control and insulin-treated group. Bone morphogenesis in the diabetic rats was characterized by fragmented bone tissues and extensive soft tissue intervention. Conclusion: The immediate placement of titanium implants in the maxilla of diabetic rats led to an unwanted bone healing response. These results suggest that immediate implant insertion in patients with poorly controlled diabetes might be contraindicated.

• Archives of Reconstructive Microsurgery
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• v.13 no.2
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• pp.101-106
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• 2004

Purpose : This study evaluated the effect of VEGF in the arterial anastomosis by using light and electron microscopy. Marerials and method : Rats underwent femoral arterial end-to-end anastomosis after transection and topical VEGF treatment. The proximal and distal segments of the femoral arteries was drenched with 1 drop of VEGF $(100ng/100{\mu}l/bottle)$. and when half of the repair was finished, the other 1 drop was drenched and then the repair was continued to complete the anastomosis. Gross and histologic characteristics of arterial wall were assessed after 3 days, 1, 3 and 5 weeks. In the control group, normal saline solution instead of VEGF was dropped with the same method in the anastomosis. Results : The histologic findings of the arterial wall were the vascular remodeling with the infiltration of inflammatory cells at early stages and the tissue fibrosis at lately stages in the anastomotic sites of the control and the VEGF-treated groups. The scanning electron microscopic results were; (1) the anastomotic sites were covered by many irregular cells with long cytoplasmic processes at the early stages. (2) After 1 week, endothelial cells started to cover the anastomotic sites. (3) After 3 weeks, the anastomotic sites were partially covered by endothelial cells in the control group. (4) After 5 weeks, the anastomotic sites were completely covered by endothelial cells in the control and VEGF-treated groups. (5) In the VEGF-treated group, the anastomotic site was completely covered by endothelial cells which directed parallel to longitudinal axis of arteries after 3 weeks. Conclusion : Topical VEGF maintained luminal integrity by decreasing fibrosis and increasing re-endothelialization. These findings suggest that topical VEGF may be a promising new strategy to enhance healing and improve the outcome of vascular anastomosis.

• Journal of Life Science
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• v.15 no.2 s.69
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• pp.231-235
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• 2005

Matrix metalloproteinases (MMPs) are a family of structurally and functionally related zinc-dependent enzymes responsible for proteolytic degradation of extracellular matrix components such as base membrane or interstitial stroma. MMPs play an important role in a variety of physiological and pathological tissue remodeling processes, including wound healing, embryo implantation, tumor invasion and metastasis. Since MMP-9 (gelatinase B) has unique ability to cleave type IV collagen, gene expression of MMP-9 has been focused on as a pharmacological target. Flavonoids are a class of compounds that are widely spread in plants. In the coures of screening for the suppressors of MMP-9 gene expression from natural products, Metasequoia glyptostroboides was selected. Six flavonoids, sciadopitysin, isoginkgetin, bilobetin, 2,3-dihydrohinokiflavone, luteolin and apigenin were purified as suppressors of MMP-9 gene expression from M. glyptostroboides. The suppressing activity of the isolated flavinoids on the MMP-9 gene expression was measured by gelatin zymography and Nothern blot analysis.

• Biomolecules & Therapeutics
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• v.20 no.1
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• pp.57-61
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• 2012

The matrix metalloproteinase (MMP) family is involved in the breakdown of the extracellular matrix during normal physiological processes such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes such as pathological aging, arthritis, and metastasis. Oxidative conditions generate reactive oxygen species (ROS) (e.g., hydrogen peroxide [$H_2O_2$]) in cells, which subsequently induce the synthesis of matrix metalloproteinase-1 (MMP-1). MMP-1, an interstitial collagenase, in turn stimulates an aging phenomenon. In this study, baicalein (5,6,7-trihydroxyfl avone) was investigated for its in vitro activity against $H_2O_2$-induced damage using a human skin keratinocyte model. Baicalein pretreatment signifi cantly inhibited $H_2O_2$-induced up-regulation of MMP-1 mRNA, MMP-1 protein expression and MMP-1 activity in cultured HaCaT keratinocytes. In addition, baicalein decreased the transcriptional activity of activator protein-1 (AP-1) and the expression of c-Fos and c-Jun, both components of the heterodimeric AP-1 transcription factor. Furthermore, baicalein reduced phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun-N-terminal kinase (JNK), which are upstream of the AP-1 transcription factor. The results of this study suggest that baicalein is involved in the inhibition of oxidative stress-induced expression of MMP-1 via inactivation of the ERK/JNK/AP-1 signaling pathway.

• Applied Microscopy
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• v.43 no.4
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• pp.133-139
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• 2013

This study was carried out to investigate the effects of pycnogenol (PYC) on the cutaneous wound healing of the mice. The wounds were extracted on days 1, 3, 5, and 7 post-injury for histomorphometrical analysis including wound area, infiltrating inflammatory cells, wound contracture including collagen deposition. As the result, the wound area of PYC-treated group was larger than the control group on days 1 to 7. Inflammatory cells in the PYC-treated wounds were decreased at day 1 compared to the control wound tissue. From day 3 to 7, there was no significant difference between the control and the PYC-treated skin wounds. Though the degree of contraction in the PYC-treated group was lower than that of the control group from days 1 to 5, but appeared significantly higher on day 7. Compared to the control group, collagen accumulation in the PYC-treated group was higher than that of the control group from days 5 to 7. From this result, it may support the possibility that PYC would be useful agent for early inflammatory response and matrix remodeling phase of the skin wounds.

• Journal of Embryo Transfer
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• v.33 no.2
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• pp.61-68
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• 2018

The major focus of this study is to analyze the expression of bovine MMPs and to monitor their activity during the estrus cycle and pregnancy. During pregnancy, MMP-2 expression was detectable around 30 days but became insignificant by 60 days, then started to increase again around 90 days and reached the maximum at 250 days. The activity of MMP-2 protein changed in accordance with its expression level. As expected, the level of TIMP-2 exhibited a reverse pattern. About MMP-9, high level expression was observed as early as 30 days and gradually increase until 90 days. Then started to decrease after 250 days. Again, the sites of MMP-9 expression were similar to those of MMP-2. On the other hand, expression of TIMP-3 remained low until 90 days but showed a small and temporal increase around 250 days. In summary, expression of different MMPs were differentially regulated during estrus cycle and pregnancy. While the expression of MMP-2 was high in estrus cycle, MMP-9 slowly takes over with the progression of pregnancy. These results indicated that the luteal tissue perform distinct functions during pregnancy and estrus. Perhaps the activity of MMP-2 is required for the structural remodeling of luteum, resulting the suppression of P4 inflow from blood. On the other hand, steady maintenance of MMP-9 throughout luteal development is important for the activation of cell proliferation, maturation and angiogenesis.

• Journal of Korean Academy of Oral and Maxillofacial Radiology
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• v.29 no.1
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• pp.119-147
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• 1999

The purpose of this study was to investigate the effects of the Co-60 γ irradiation on the osseointegration. 2.0 mm titanium alloy screw implants(Sankin Industry Co. Ltd., Japan) were placed in the tibial metaphysis of the rabbits, bilaterally. The mean length of the implants was 6.0 mm. The right tibia was irradiated with a single dose of 15Gy from 60Co teletherapic machine at 5th postoperative day. The experimental group was irradiated tibia. The control group was non­irradiated tibia. To observe the phase of bone formation, the bone labeling by intramuscular injection of 20mg/Kg of Tetracycline, Calcein, Alizarin red S, was performed. The rabbits were sacrificed on the 1st, 2nd, 4th, 6th, 8th week and the tibia including implants were taken, and then the specimens were examined by the microradiography, light microscopy, and fluorescent microscopy. The obtained results were as follows: 1. There were connective tissue between bone and titanium at 1st week, in both group. Especially, the many empty lacunae without nucleus and obscure cytoplasm in experimental group, were observed. 2. The osteons were observed at 4th week in control group, and at 6th week in experimental group. The bone formation in experimental group was retarded as compared to the control group. 3. In fluorescent microscopy, bone labelling band was observed as linear, arc or concentric shape. Occasionary interrupted labelling band was observed, which is demonstrated bone remodeling. 4. In microradiographic examination, the radiolucent image was found between bone and implant with widening of bone marrow spaces as compared to the control group.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.42 no.1
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• pp.20-30
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• 2016

Objectives: To validate a critical-size mandibular bone defect model in miniature pigs. Materials and Methods: Bilateral notch defects were produced in the mandible of dentally mature miniature pigs. The right mandibular defect remained untreated while the left defect received an autograft. Bone healing was evaluated by computed tomography (CT) at 4 and 16 weeks, and by micro-CT and non-decalcified histology at 16 weeks. Results: In both the untreated and autograft treated groups, mineralized tissue volume was reduced significantly at 4 weeks post-surgery, but was comparable to the pre-surgery levels after 16 weeks. After 16 weeks, CT analysis indicated that significantly greater bone was regenerated in the autograft treated defect than in the untreated defect (P=0.013). Regardless of the treatment, the cortical bone was superior to the defect remodeled over 16 weeks to compensate for the notch defect. Conclusion: The presence of considerable bone healing in both treated and untreated groups suggests that this model is inadequate as a critical-size defect. Despite healing and adaptation, the original bone geometry and quality of the pre-injured mandible was not obtained. On the other hand, this model is justified for evaluating accelerated healing and mitigating the bone remodeling response, which are both important considerations for dental implant restorations.

• Genomics & Informatics
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• v.14 no.3
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• pp.78-84
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• 2016

Extranodal natural killer (NK)/T-cell lymphoma, nasal type (NKTCL), is a malignant disorder of cytotoxic lymphocytes of NK or T cells. It is an aggressive neoplasm with a very poor prognosis. Although extranodal NKTCL reportedly has a strong association with Epstein-Barr virus, the molecular pathogenesis of NKTCL has been unexplored. The recent technological advancements in next-generation sequencing (NGS) have made DNA sequencing cost- and time-effective, with more reliable results. Using the Ion Proton Comprehensive Cancer Panel, we sequenced 409 cancer-related genes to identify somatic mutations in five NKTCL tissue samples. The sequencing analysis detected 25 mutations in 21 genes. Among them, KMT2D, a histone modification-related gene, was the most frequently mutated gene (four of the five cases). This result was consistent with recent NGS studies that have suggested KMT2D as a novel driver gene in NKTCL. Mutations were also found in ARID1A, a chromatin remodeling gene, and TP53, which also recurred in recent NGS studies. We also found mutations in 18 novel candidate genes, with molecular functions that were potentially implicated in cancer development. We suggest that these genes may result in multiple oncogenic events and may be used as potential bio-markers of NKTCL in the future.

• IMMUNE NETWORK
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• v.9 no.3
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• pp.90-97
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• 2009

Background: CD147, as a cellular receptor for cyclophilin A (CypA), is a multifunctional protein involved in tumor invasion, inflammation, tissue remodeling, neural function, and reproduction. Recent observations showing the expression of CD147 in leukocytes indicate that this molecule may have roles in inflammation. Methods: In order to investigate the role of CD147 and its ligand in the pathogenesis of atherosclerosis, human atherosclerotic plaques were analyzed for the expression pattern of CD147 and CypA. The cellular responses and signaling molecules activated by the stimulation of CD147 were then investigated in the human macrophage cell line, THP-1, which expresses high basal level of CD147 on the cell surface. Results: Staining of both CD147 and CypA was detected in endothelial cell layers facing the lumen and macrophage-rich areas. Stimulation of CD147 with its specific monoclonal antibody induced the expression of matrix metalloproteinase (MMP)-9 in THP-1 cells and it was suppressed by inhibitors of both ERK and NF-${\kappa}B$. Accordingly, the stimulation of CD147 was observed to induce phosphorylation of ERK, phosphorylation-associated degradation of $I{\kappa}B$, and nuclear translocation of NF-${\kappa}B$ p65 and p50 subunits. Conclusion: These results suggest that CD147 mediates the inflammatory activation of macrophages that leads to the induction of MMP-9 expression, which could play a role in the pathogenesis of inflammatory diseases such as atherosclerosis.