• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2291-2295
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• 2014

Although nucleolar protein nucleostemin (NS) is essential for cell proliferation and early embryogenesis and expression has been observed in some types of human cancer and stem cells, the molecular mechanisms involved in mediation of cell proliferation and cell cycling remains largely elusive. The aim of the present study was to evaluate NS as a potential target for gene therapy of human breast carcinoma by investigating NS gene expression and its effects on SKBR-3 cell proliferation and apoptosis. NS mRNA and protein were both found to be highly expressed in all detected cancer cell lines. The apoptotic rate of the pcDNA3.1-NS-Silencer group ($12.1-15.4{\pm}3.8%$) was significantly higher than those of pcDNA3.1-NS ($7.2-12.0{\pm}1.7%$) and non-transfection groups ($4.1-6.5{\pm}1.8%$, P<0.01). MTT assays showed the knockdown of NS expression reduced the proliferation rate of SKBR-3 cells significantly. Matrigel invasion and wound healing assays indicated that the number of invading cells was significantly decreased in the pcDNA3.1-NS-siRNA group (P<0.01), but there were no significant difference between non-transfected and over-expression groups (P>0.05). Moreover, RNAi-mediated NS down-regulation induced SKBR-3 cell G1 phase arrest, inhibited cell proliferation, and promoted p53 pathway-mediated cell apoptosis in SKBR-3 cells. NS might thus be an important regulator in the G2/M check point of cell cycle, blocking SKBR-3 cell progression through the G1/S phase. On the whole, these results suggest NS might be a tumor suppressor and important therapeutic target in human cancers.

• The Journal of Korean Orthopaedic Ultrasound Society
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• v.4 no.2
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• pp.111-122
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• 2011

Platelet rich plasma (PRP) has been widely used nowadays for several common orthopaedic-related sports medicine conditions with the theoretical basis that PRP supplies numerous autologous growth factors from concentrated platelets needed to promote the healing process of injured tissue. Even though there are many basic sciences, animal studies and some clinical studies regarding PRP injections for musculoskeletal injuries which suggested good results, it is difficult to compare these various studies due to marked methodological differences such as PRP preparation method, the timing, volume and number of injection, and the outcome measurement tool. In addition, many studies have no control groups or a limited sample size, and there are few prospective randomized controlled trials assessing the efficacy of PRP injections. Therefore, well designed high-quality randomized studies are required to confirm the preliminary results until now and provide scientific evidence to support its use, and the paucity of scientific clinical evidence suggest that the administration of PRP on humans for musculoskeletal injuries should be performed with caution.

• Korean Journal of Veterinary Research
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• v.39 no.2
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• pp.247-256
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• 1999

A disease of young Holstein calves characterized by recurrent pneumonia, ulcerative and granulomatous stomatitis, enteritis with bacterial overgrowth, periodontitis, delayed wound healing, persistent neutrophilia and death at an early age had been originally described in 1983 and again in 1987. Most of these calves had stunted growth and a persistent, progressive neutrophilia (often exceeding 100,000/ml). By investigation of pedigrees, all of the affected calves have now been traced to a common sire and confirmed by polymerase chain reaction (PCR) diagnostic DNA testing to be homozygous carriers of a defective allele for bovine CD18. Neutrophils from these calves have several functional deficits and, most importantly, fail to adhere in a ${\beta}_2$-integrin dependent manner. The ${\beta}_2$-integrins represent a family of glycoproteins which participate in various leukocyte adhesion reactions during host defense. The presence or absence of ${\beta}_2$-integrin molecules can be demonstrated on the surface of neutrophils, monocytes and lymphocytes from normal or affected calves using specific monoclonal antibodies and flow cytometry, or by colloidal gold immunolabeling and scanning electron microscopy in backscatter mode. Deficiency of the ${\beta}_2$-integrins on all leukocyte types in Holstein calves is analogous to leukocyte adhesion deficiency (LAD) seen in humans. Neutrophils in bovine (BLAD) and human LAD patients are unable to adhere to the endothelial lining of the cardiovascular system thus interrupting egression of neutrophils into infected tissues. Other leukocytes, while still deficient in expression of the ${\beta}_2$-integrins, are still able to efficiently egress from the blood stream due to interactions of other adhesion molecules that are not as highly expressed on neutrophils. Both BLAD cattle and LAD children (who do not receive bone marrow transplants) often die at an early age as a result of the failure of neutrophils to extravasate into infected tissues. In 1991, Shuster, et $al^{27}$, identified two point mutations within the alleles encoding bovine CD18 in a Holstein calf afflicted with leukocyte adhesion deficiency. One mutation causes an aspartic acid to glycine substitution at amino acid 128 (D128G) in an extracellular region of this adhesion glycoprotein that is highly conserved (> 95% identity) between humans, cattle and mice. The other mutation is silent. Numerous calves with clinical symptoms of leukocyte adhesion deficiency have since been tested and all have been found homozygous for the D128G allele. In addition, calves homozygous far the D128G allele have been identified during widespread DNA testing in the United States. All cattle with the mutant allele are related to one bull, who through artificial insemination (A.I.), sired many calves in the 1950's and 1960's. The carrier frequency of the D128G CD18 allele among U.S. Holstein cattle had reached approximately 15% among active A.I. bulls and 8% among cows. By 1993, the organization of the dairy industry and the diagnostic test developed to genotype cattle, enabled virtually complete eradication of bovine leukocyte adhesion deficiency among current and future A.I. bulls.

• Journal of Life Science
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• v.26 no.1
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• pp.91-100
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• 2016

Angiogenesis is essential for the pathophysiological processes of embryogenesis, tissue growth, diabetic retinopathy, psoriasis, wound healing, rheumatoid arthritis, cardiovascular diseases, and tumor growth. Inhibition of angiogenesis represents an attractive therapeutic approach for the treatment of angiogenic diseases such as cancer. However, uncontrolled angiogenesis is also necessary for tumor development and metastasis. Inhibition of vascular endothelial growth factor (VEGF) signaling, a critical factor in the induction of angiogenesis, cause robust and rapid changes in blood vessels of tumors and therefore VEGF constitutes a target for such anti-angiogenic therapy. Recently, since natural compounds pose significantly less risk of deleterious side effects than synthetic compounds, a great many natural resources have been assessed for useful substance for anti-angiogenic treatment. Here we evaluated the anti-angiogenic effects of a hot water extract of Scutellaria baicalensis (SBHWE) using in vitro assays and ex vivo animal experiments. Our results show that SBHWE dose-dependently abrogated vascular endothelial responses by inhibiting VEGF-stimulated migration and invasion as well as tube formation in a human umbilical vein endothelial cell (HUVEC) model, without cytotoxicity, as determined by a cell viability assay. Further study revealed that SBHWE prevented VEGF-induced neo-vascularization in a rat aortic ring sprouting model. Taken together, our findings reveal an anti-angiogenic activity of Scutellaria baicalensis and suggest that SBHWE is a novel candidate inhibitor of VEGF-induced angiogenesis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.33 no.2
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• pp.131-138
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• 2007

The purpose of this study was to observe the effect of calcium and vitamin D to the titanium implant osseointegration in animal model. 32 rats, 10 weeks of age, were divided into two group: additional calcium and vitamin D supplementation group and a control group. Titanium screw implant(diameter, 2.0mm; length, 3.5mm; pitch-height 0.4mm) were placed into tibia of 32 rats, 16 in the control group and 16 in the experimental group. The rats were sacrificed at different time interval(1, 2, 4, and 8 weeks after implantation) for histopathologic observation, histomorphometric analysis and immunohistochemistry with osteocalcin and osteopontin antibody. Histopathologically findings, newly formed bone was seen at 1 weeks and became lamellar bone at 2 weeks, and mature trabecullar bone was seen at 4 weeks experimental group. In control group, thickness of regenerated bone increased till 4 weeks gradually and trabecullar bone was seen at 8 weeks. By histomorphometric analysis, bone marrow density was increased significantly at 1 and 2 weeks in experimental group compared to control group. Osteocalcin immunoreactivity was strong at 1 week experimental group and reduced after 4 weeks gradually. But it was continuously weakly from 1 to 4 weeks in control group. Osteopontin immunoreactivity was very strong in newly formed bone from 2 to 8 weeks experimental group. And the amount of osteopontin expression was more abundant in experimental group. The results of this study suggest that calcium and vitamin D supplementation promotes bone healing around dental implants

• The Journal of Korean Academy of Prosthodontics
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• v.43 no.1
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• pp.78-94
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• 2005

Purpose. The purpose of this study was to compare the effects of various surface treatments by measuring resonance frequency and histomorphometric analyses. Material and methods. In 5 adult dogs, the mandibular premolar were extracted. Six months later, 30 screw titanium implants (Dentium Co., Seoul, Korea) 6mm in length and 3.4mm in diameter, were placed in the mandibles of 5 dogs. Implants were divided into five groups following to surface treatment methods ; Group 1 is machined controls, Group 2 is sandblasted with large grit and acid-etched (SLA), Group 3 is anodized (Autoelectric Co., Korea, 660Hz, Duty10), Group 4 is hydroxyapatite(HA) coated by ion beam assisted deposition(E-beam), Group 5 is hydroxyapatite(HA) coated with Sol-gel coating process. Resonance frequency was measured implant placement immediately, and 3, 6 weeks and 10 weeks of healing perods. With the animal subject's sacrifice 10 weeks after implantation, implants were removed on bloc and histologic and computer-based histomorphometric analyses were performed. Histomorphometric analysis involved quantification of the entire bone to metal contact around the implants. Statistical analyses were performed using the SPSS for Windows (ver. 9.0 SPSS Inc.) Statistical differences were considered significant at P<0.05. Results. The results were as follows : 1) In five groups, mean value of resonance frequency analysis(RFA) were highest in group 5 (Sol-gel implant) at implantation and those of group 4 (E-beam)was highest at 10 weeks . but there was no correlation between surface treatments and RFA. 2) In all surface treatment groups, the RFA values of implants decreased until 3 weeks and increased to 10 weeks. 3) The percentage of direct bone-to-implant contact (BIC) had statistical significance between five groups in cancellous bone, (P<0.05) the percentage of bone density inside the thread had no statistical significance between five groups. (P>0.05) 4) There was a significant difference between cortical bone and cancellous bone in BIC. (P<0.05) and bone density. (P<0.05) 5) There was a correlation between the RFA value of implants at 10 weeks and BIC in cancellous bone, and between the RFA value of implants at 10 weeks and bone density in cortical bone. (P<0.05). Conclusions. These results indicate that surface treatment does not affect the implant stability in case of good bone quality.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.2
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• pp.151-159
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• 2019

Pruritus (itching) is classically defined as an unpleasant cutaneous sensation that leads to scratching behavior. Although the scientific criteria of classification for pruritic diseases are not clear, it can be divided as acute or chronic by duration of symptoms. In this study, we investigated whether skin injury caused by chemical (contact hypersensitivity, CHS) or physical (skin-scratching stimulation, SSS) stimuli causes initial pruritus and analyzed gene expression profiles systemically to determine how changes in skin gene expression in the affected area are related to itching. In both CHS and SSS, we ranked the Gene Ontology Biological Process terms that are generally associated with changes. The factors associated with upregulation were keratinization, inflammatory response and neutrophil chemotaxis. The Kyoto Encyclopedia of Genes and Genomes pathway shows the difference of immune system, cell growth and death, signaling molecules and interactions, and signal transduction pathways. Il1a, Il1b and Il22 were upregulated in the CHS, and Tnf, Tnfrsf1b, Il1b, Il1r1 and Il6 were upregulated in the SSS. Trpc1 channel genes were observed in representative itching-related candidate genes. By comparing and analyzing RNA-sequencing data obtained from the skin tissue of each animal model in these characteristic stages, it is possible to find useful diagnostic markers for the treatment of itching, to diagnose itching causes and to apply customized treatment.

• Journal of The Korean Society of Integrative Medicine
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• v.10 no.4
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• pp.121-136
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• 2022

Purpose : Marine therapy is an activity that promotes public health such as constitution improvement, immunity improvement, and anti-aging by utilizing marine therapeutic resources such as seawater, mud, seaweed, salt and sea climate. In Europe developed countries, the marine therapy industry has been developing for centuries, with France, Germany, and Israel leading the way. Currently, it has achieved great industrial achievements and is of great help in improving the human health. The purpose of this study is to investigate how marine therapeutic resources benefit to human health, as well as how to study and utilize their efficacy. We analyzed previous research articles related to the effects of marine therapeutic resources. Methods : The study included a total of 830 published literatures in the last 20 years from the Republic of Korea and other contries. PubMed and Google Scholar were utilized to collect the foreign source while the local scientific publications were accessed through the Korean Education and research Information Service (KERIS) and Korean studies Information Service System (KISS). The keywords used to search foreign literature were "marine therapy", "Thalassotherapy", "seawater", "deep seawater", "saline groundwater", "sand therapy", "mud therapy", "hydrotherapy", "seaweed", "Sun light", "sea salt", "marine animal", and "marine microorganisms" were combined, and for the domestic literature, the keywords were "marine therapy", "marine therapeutic resources", "seawater", and "sand". Results : A total of 830 research papers were found as a result of searching for domestic and international papers related to marine therapeutic resources. The collected documents were classified into 175 seawater resources, 259 marine mineral resources, 41 marine environment, and 355 marine organisms. The efficacy of each marine therapeutic resources was analyzed. By resources type, there were about 213 papers on the efficacy of seaweed, followed by about 175 papers on seawater, 142 on microorganisms, 124 on mud/peat, and sand, salt, minerals and others are appeared in order (Table 1). Conclusion : Korea has the highest marine biodiversity index, excellent tidal flats, four distinct seasons, and various sea environments of the East sea, Yellow sea, South sea and Jeju sea. For this reason, Korea has a much more diverse marine therapeutic resources than other advanced countries in the marine therapy industry. prebiously, we thought that the sea was only valuable as a shipping port and fishery industry. But now, it been shown that the ocean can become a new industrial field which can contribute to human health and well-being by providing healing and therapy to people through the gift of marine resources.

• The Journal of Internal Korean Medicine
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• v.44 no.3
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• pp.402-417
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• 2023

Objective: Liver fibrosis is a highly conserved wound-healing response and the final common pathway of chronic inflammatory injury. This study aimed to evaluate the potential anti-fibrotic effect of the combination of Rhei Radix et Rhizoma water extract (RW) and silymarin in a thioacetamide (TAA)-induced liver fibrosis model. Methods: The liver fibrosis mouse model was established through the intraperitoneal injection of TAA (1 week 100 mg/kg, 2-3 weeks 200 mg/kg, 4-8 weeks 400 mg/kg) three times per week for eight weeks. Animal experiments were conducted in five groups; Normal, Control (TAA-induced liver fibrosis mice), Sily (silymarin 50 mg/kg), RSL (RW 50 mg/kg+silymarin 50 mg/kg), and RSH (RW 100 mg/kg+silymarin 50 mg/kg). Biochemical analyses were measured in serum, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA), and ammonia levels. Liver inflammatory cytokines and fibrous biomarkers were measured by Western blot analysis, and liver histopathology was evaluated through tissue staining. Results: A significant decrease in the liver function markers AST and ALT and a reduction in ammonia and total bilirubin were observed in the group treated with RSL and RSH. Measurement of reactive oxygen species and MDA revealed a significant decrease in the RSL and RSH administration group compared to the TAA induction group. The expression of extracellular matrix-related proteins, such as transforming growth factor β1, α-smooth muscle actin, and collagen type I alpha 1, was likewise significantly decreased. All drug-administered groups had increased matrix metalloproteinase-9 but a decreasing tissue inhibitor of matrix metalloproteinase-1. RSL and RSH exerted a significant upregulation of NADPH oxidase 2, p22^phox, and p47^phox, which are oxidative stress-related factors. Furthermore, pro-inflammatory proteins such as cyclooxygenase 2 and interleukin-1β were markedly suppressed through the inhibition of nuclear factor kappa B activation. Conclusions: The administration of RW and silymarin suppressed the NADPH oxidase factor protein level and showed a tendency to reduce inflammation-related enzymes. These results suggest that the combined administration of RW and silymarin improves acute liver injury induced by TAA.

• Implantology
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• v.18 no.2
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• pp.120-138
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• 2014

Purpose: The purpose of this study was to review the outcomes of a series of studies on tissue regeneration conducted in multiple institutions including the Department of Periodontology, College of Dentistry, Yonsei University. Materials and Methods: Studies were performed divided into the following three subjects; 1) Development of three-dimensional nano-hydroxyapatite (n-HA) scaffold for facilitating drug release and cell adhesion. 2) Synergistic effects of bone marrow-derived mesenchymal stem cells (BMMSC) application simultaneously with platelet-rich plasma (PRP) on HA scaffolds. 3) The efficacy of silk scaffolds coated with n-HA. Also, all results were analyzed by subjects. Results: Hollow hydroxyapatite spherical granules were found to be a useful tool for the drug release and avidin-biotin binding system for cell attachment. Also, BMMSC simultaneously with PRP applied in an animal bone defect model was seen to be more synergistic than in the control group. But, the efficacy of periodontal ligament cells and dental pulp cells with silk scaffolds could not be confirmed in the initial phase of bone healing. Conclusion: The ideal combination of three elements of tissue engineering-scaffolds, cells and signaling molecules could be substantiated due to further investigations with the potentials and limitations of the suggested list of studies.