• Clinical and Experimental Reproductive Medicine
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• 제38권4호
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• pp.193-202
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• 2011

Objective: We found previously that $interferon$ $regulatory$ factor ($Irf$)-1 is a germinal vesicle (GV)-selective gene that highly expressed in GV as compared to metaphase II oocytes. To our knowledge, the function of $Irf-1$ in oocytes has yet to be examined. The present study was conducted to determine the relationship between retinoic acid (RA) and RA-mediated expression of $Irf-1$ and the mouse oocyte maturation. Methods: Immature cumulus-oocyte-complexes (COCs) were collected from 17-day-old female mice and cultured $in$ $vitro$ for 16 hours in the presence of varying concentrations of RA (0-10 ${\mu}M$). Rate of oocyte maturation and activation was measured. Gene expression was measured by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and cytokine secretion in the medium was measured by Bio-Plex analysis. Apoptosis was analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Results: The rates of oocyte maturation to metaphase II and oocyte activation increased significantly with RA treatment (10 nM-1 ${\mu}M$). With 100 nM RA treatment, lowest level of $Irf-1$ mRNA and cumulus cell's apoptosis was found. Among 23 cytokines measured by Bio-Plex system, the substantial changes in secretion of tumor necrosis factor-${\alpha}$, macrophage inflammatory protein-$1{\beta}$, eotaxin and interleukin-12 (p40) from COCs in response to RA were detected. Conclusion: We concluded that the maturation of oocytes and $Irf-1$ expression are negatively correlated, and RA enhances the developmental competence of mouse immature oocytes $in$ $vitro$ by suppressing apoptosis of cumulus cells. Using a mouse model, results of the present study provide insights into improved culture conditions for $in$ $vitro$ oocyte maturation and relevant cytokine production and secretion in assisted reproductive technology.

• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9511-9515
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• 2014

Cholangiocarcinoma (CCA) is a cancer of the bile duct epithelial cells. The highest incidence rate of CCA with a poor prognosis and poor response to chemotherapy is found in Southeast Asian countries, especially in northeastern Thailand and Lao PDR. Cathepsin B is a lysosomal cysteine protease which is regulated by cysteine proteinase inhibitors such as cystatin C. Elevation of cathepsin B levels in biological fluid has been observed in patients with inflammatory diseases and many cancers. We aimed to investigate the serum cathepsin B and cystatin C levels of CCA patients to evaluate the feasibility of using cathepsin B and cystatin C as markers for the diagnosis of CCA. Fifty-six sera from CCA patients, 17 with benign biliary diseases (BBD) and 13 from controls were collected and the cathepsin B and cystatin C levels were determined. In addition, cathepsin B expression was investigated immunohistochemically for 9 matched-pairs of cancerous and adjacent tissues of CCA patients. Serum cathepsin B, but not cystatin C, was significantly higher in CCA and BBD patient groups compared to that in the control group. Consistently, all cancerous tissues strongly expressed cathepsin B while adjacent tissues were negative in 7 out of 9 cases. In contrast, serum cystatin C levels were comparable between CCA and control groups, although serum cystatin C levels in the BBD group was higher than that in the control or CCA groups. When the serum cathepsin B to cystatin C ratio was calculated, that of the CCA group was significantly higher than that of the control group, and, although statistically not significant, the ratio of CCA group showed a trend to be higher than that of the BBD group. Thus, the cathepsin B to cystatin C ratio might be used as an alternative marker for aiding diagnosis of CCA.

• Journal of Periodontal and Implant Science
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• 제33권1호
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• pp.13-26
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• 2003

Periodontal regeneration therapy with bone-substituting materials has gained favorable clinical efficacy by enhancing osseous regeneration in periodontal bony defect. As bone-substituting materials, bone powder, calcium phosphate ceramic, modified forms of hydroxyapatite, and hard tissue replacement polymer have demonstrated their periodontal bony regenerative potency. Bone-substituting materials should fulfill several requirements such as biocompatibility, osteogenecity, malleability, biodegradability. The purpose of this study was to investigate biocompatibility, osteo-conduction capacity and biodegradability of $Na_2O$, $K_2O$ added calcium metaphosphate(CMP). Beta CMP was obtained by thermal treatment of anhydrous $Ca_2(H_2PO_4)_2$. $Na_2O$ and $K_2O$ were added to CMP. The change of weight of pure CMP, $Na_2O$-CMP, and $K_2O$-CMP in Tris-buffer solution and simulated body fluid for 30 days was measured. Twenty four Newzealand white rabbits were used in negative control, positive control(Bio-Oss), pure CMP group, 5% $Na_2$-CMP group, 10% $Na_2O$-CMP goup, and 5% $K_2O$-CMP group. In each group, graft materials were placed in right and left parietal bone defects(diameter 10mm) of rabbit. The animals were sacrificed at 3 months and 6 months after implantation of the graft materials. Degree of biodegradability of $K_2O$ or $Na_2O$ added CMP was greater than that of pure CMP in experimental condition. All experimental sites were healed with no clinical evidence of inflammatory response to all CMP implants. Histologic observations revealed that all CMP grafts were very biocompatible and osseous conductive, and that in $K_2O$-CMP or $Na_2O$-CMP implanted sites, there was biodegradable pattern, and that in site of new bone formation, there was no significant difference between all CMP group and DPBB(Bio-Oss) group. From this result, it was suggested that all experimental CMP group graft materials were able to use as an available bone substitution.

• Tuberculosis and Respiratory Diseases
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• 제78권3호
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• pp.218-226
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• 2015

Background: Eph receptors and ephrin ligands have several functions including angiogenesis, cell migration, axon guidance, fluid homeostasis, oncogenesis, inflammation and injury repair. The EphA2 receptor potentially mediates the regulation of vascular permeability and inflammation in response to lung injury. Methods: Mice were divided into 3 experimental groups to study the role of EphA2 signaling in the lipopolysaccharide (LPS)-induced lung injury model i.e., IgG+phosphate-buffered saline (PBS) group (IgG instillation before PBS exposure), IgG+LPS group (IgG instillation before LPS exposure) and EphA2 monoclonal antibody (mAb)+LPS group (EphA2 mAb pretreatment before LPS exposure). Results: EphA2 and ephrinA1 were upregulated in LPS-induced lung injury. The lung injury score of the EphA2 mAb+LPS group was lower than that of the IgG+LPS group ($4.30{\pm}2.93$ vs. $11.45{\pm}1.20$, respectively; p=0.004). Cell counts (EphA2 mAb+LPS: $11.33{\times}10^4{\pm}8.84{\times}10^4$ vs. IgG+LPS: $208.0{\times}10^4{\pm}122.6{\times}10^4$; p=0.018) and total protein concentrations (EphA2 mAb+LPS: $0.52{\pm}0.41mg/mL$ vs. IgG+LPS: $1.38{\pm}1.08mg/mL$; p=0.192) were decreased in EphA2 mAb+LPS group, as compared to the IgG+LPS group. In addition, EphA2 antagonism reduced the expression of phospho-p85, phosphoinositide 3-kinase $110{\gamma}$, phospho-Akt, nuclear factor ${\kappa}B$, and proinflammatory cytokines. Conclusion: This results of the study indicated a role for EphA2-ephrinA1 signaling in the pathogenesis of LPS-induced lung injury. Furthermore, EphA2 antagonism inhibits the phosphoinositide 3-kinase-Akt pathway and attenuates inflammation.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제31권6호
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• pp.478-484
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• 2009

Three-dimensional porous scaffolds play an important role in tissue engineering strategies. They provide a void volume in which vascularization, new tissue formation, and remodeling can occur. Like any grafted materials, the ideal scaffold for bone tissue engineering should be biocompatible without causing an inflammatory response. It should also possess biodegradability, which provides a suitable three-dimensional environment for the cell function together with the capacity for gradual resorption and replacement by host bone tissue. Various scaffolds have already been developed for bone tissue engineering applications, including naturally derived materials, bioceramics, and synthetic polymers. The advantages of biodegradable synthetic polymers include the ability to tailor specific functions. The purpose of this study was to examine the osteogenic activity of periosteal-derived cells in a polydioxanone/pluronic F127 scaffold. Periosteal-derived cells were successfully differentiated into osteoblasts in the polydioxanone/pluronic F127 scaffold. ALP activity showed its peak level at 2 weeks of culture, followed by decreased activity during the culture period. Similar to biochemical data, the level of ALP mRNA in the periosteal-derived cells was also largely elevated at 2 weeks of culture. The level of osteocalcin mRNA was gradually increased during entire culture period. Calcium content was detactable at 1 week and increased in a time-dependent manner up to the entire duration of culture. Our results suggest that polydioxanone/pluronic F127 could be a suitable scaffold of periosteal-derived cells for bone tissue engineering.

• 대한치과보철학회지
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• 제28권2호
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• pp.1-28
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• 1990

The severe atrophic edentulism with poor neuromuscular control militates against successful conventional denture therapy. To such situation, a prescribing of dental implant treatment has been considered with some probability. Implant materials used as a trial for dental implants includes metals, plastic polymers and ceramics. The purpose of this study was to observe histologic response in osseointegration process at titanium implant-tissue interface based on biocompatibility at specific period of sequential natures which were divided into a half month, one, month, two months, three months and immediate as a base line. In this study, unilateral lower left premolar and molar teeth were extraced in three dogs. After allowing to heal for 6 months, three kinds of osseointegrated implant, $Br{\aa}nemark$, Corevent and kimplant(a prototype of SNU implant study)were inserted in each dog respectively according to the above sequence from front to back. The specimens were taken from those dogs at the same time since implant were inserted quite reverse order of the specified periods, and decalcified and processed for histologic examination for the light microscopy and the electron microscopy. The microscopic histologic findings at the interface between titanium implants and tissue were interpretated as follows : A. Light microscopic findings : a. Immediate : Implant were surrounded by compact bone and spongy bone. Microcrak was observed in the superficial bone tissue. Osteocytes were disappeared and bone lacunae were observed as a vacant space in some parts. In the contacting with the spongy bone, bone trabeculae and bone marrow were in contact with the implant. b. A half Month : Osteoblasts exist as a monolayer in th inner bone trabeculae and do bone additiocn. Osteoblasts&inflammatory cells were observed in some parts. c. One Month : The presence of osteoclasts decreased. Osteoblasts did active bone fromation, and bone marrow was in contact with the implant in the many places. d. Two Months : Bone formation was advanced in comparison with the b and c. The presence of osteoclsts was not observed. e. Three Months : The superficial bone tissue contacted with the implants was entirely composed by the compact bone. B. Electron microscopic findings : a. A half month and one month group : In the parts of the active bone formation, osteoblasts with the well developed endoplasmic reticulum and Golgi apparatus were arranged in the monolayer. In the parts of the bone resorption, ruffled border was well developed and many osteoclasts with the well-developed golgi apparatus, mitochondria, vacuole, vesicle and lysosome were existed. b. Three months group : No osteoblasts were observed in the superficial bone tissue. Bone matrix with collaen fiber was observed. c. No significant dirrerence in the histologic findings was observed in $Br{\aa}nemark$, Core-vent and kimplant.

• Journal of Periodontal and Implant Science
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• 제25권3호
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• pp.497-517
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• 1995

The cells associated with normal defense mechanism in inflammation release free oxygen radicals, hydroxy radicals, and various protease, all of which can damage the surrounding cells(fibroblasts) and matrix molecules(collagen). The objective of this study was to evaluate the effects of "scavenger" enzyme, superoxide dismutase(SOD). to periodontal ligament (PDL) cells. Human PDL cells were cultured from the teeth extracted for non-periodontal reason. Cultured PDL cells in vitro were treated with SOD and LPS according to dosage and culture times. Cellular activity was exaimed by Microtitration(MTT) assay. The quantitative expression of cellular proliferation by proliferating cell nuclear antigen(PCNA), collagen type I and fibronectin by indirect immunocytochemically stain in PDL cells were done. The results were as follows: 1. As only SOD treated group at 2 and 3 days, PDL cell activity was significantly increased at more than 150U(P<0.05). 2. When LPS(0.5, $5{\mu}g/m{\ell}$) and SOD(more than 150U) were added together, it was significantly increased than LPS only treated and control groups at 2 days(P<0.05). 3. When LPS($5{\mu}g/m{\ell}$) and SOD(150, 300U) were added together, PCNA index was significantly increased than LPS only treated and control groups at 2 and 3 days(P<0.05). 4. When LPS($5{\mu}g/m{\ell}$) and SOD(150U) were added together, collagen type I was significantly increased than LPS only treated and control groups at 3 days(P<0.05). 5.When LPS($5{\mu}g/m{\ell}$) and SOD(300U) were added together, fibronectin was significantly increased than LPS only treated and control groups at 3 days(P<0.05). On the above the results, the SOD in association with collagen type I, fibonectin, and PCNA may afford biological protection to oxy-radicals that were typically liberated during normal inflammatory response. Thus, the exogenous application of SOD may be effective in sthe treatment of the localized breakdown associated with chronic periodontal disease.

• Journal of Periodontal and Implant Science
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• 제33권2호
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• pp.301-310
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• 2003

The purpose of this study is to evaluate the biocompatibility and the biorsorbability of several types of calcium polyphosphate made through change of manufacturing process for 12 month. To solve limitation of calcium phosphate, we developed a new ceramic, Calcium Polyphosphate(CPP), and report the biologic response to CPP in extraction sites of beagle dog. Porous CPP blocks were prepared by condensation of anhydrous $Ca(H_2PO_4)_2$ to form non-crystalline $Ca(PO_3)_2$ and then milled to produce CPP powder. CPP powder, CPP block, and CPP granules added with $Na_2O$ were implanted in extraction sockets and histologic observation were performed at 12 months later. Like 3 months results, histologic observation at 12 months revealed that CPP matrix were mingled with and directly apposed to new bone without any adverse tissue reaction, CPP powder show direct bony contact, but new bone formation and fibrous tissue encapsulation showed in CPP block. 10% $Na_2O$ CPP granules show more inflammatory cells infiltration around graft materials compared at 3 month, but 15% $Na_2O$ CPP granules show less. This result revealed that regardless of addition of $Na_2O$, CPP had a high affinity for bone and had been resorbed slowly. From this results, it was suggested that CPP is promising ceramic as a bone substitute and addition of $Na_2O$ help biodegradation but optimal concentration of $Na_2O$ and other additive component to increase degradation rate should be determined in further study.

• 대한의생명과학회지
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• 제12권3호
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• pp.289-301
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• 2006

Cardiopulmonary bypass (CPB) for cardiac surgery triggers the production and release of numerous chemotactic substances and cytokines, ensuing systemic inflammatory response that leads to postoperative major organ dysfunction. Traditionally, corticosteroids (steroid) have been administered to patients undergoing cardiac surgery to ward off these detrimental physiologic alterations. However, the majority of the studies have been performed on adult patients with high-dose steroid. We carried out a randomized, prospective, double-blind study to compare the efficacy of low-dose steroid with that of high-dose steroid and to determine the adequate dose of pretreated-steroid for prophylactic effects in pediatric cardiac surgery. Thirty pediatric patients scheduled for elective cardiac surgery were randomly assigned to two groups; fifteen patients received low-dose methylprednisolone (10mg/kg intravenously, n=15, low-dose group) and the others received high-dose methylprednisolone (30mg/kg intravenously, n=15, high-dose group) 1 hour prior to CPB. Arterial blood samples were taken before CPB (Pre-CPB), 10 minutes after start of CPB (CPB-10), and immediately after CPB-end (CPB-OFF) for measuring total leukocyte counts (T-WBC) and diff-counts, platelet counts, interleukin-6 (IL-6), myeloperoxidase (MPO), total antioxidant (TAO), neuron-specific enolase (NSE), troponin I (TNI), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and blood urea nitrogen (BUN) levels. Other parameters such as volumes of urine output, pulmonary index $(PI,\;PaO_2/FiO_2)$, mechanical ventilating period, intensive care unit (ICU)-staying period, postoperative complications (fever, wound problem), postoperative 24 hrs and total volumes in blood loss, and hospitalized days were also assessed. All parameters were compared between two groups. There were no significant differences in T-WBC counts, monocyte fraction, platelet counts, TA levels, NSE levels, creatinine levels, BUN levels, the volumes of total urine output, PI, the incidences of fever and wound problem, postoperative 24hrs- and total-blood loss volumes and ICU-staying period between two groups (P>0.05). At CPB-OFF, neutrophil fraction, MPO level, TNI level, and AST level were higher in the high-dose group than in the low-dose group (P<0.05). IL-6 level at CPB-10 was higher in the high dose-group than in the low-dose group (P<0.05). Furthermore, mechanical ventilating periods and hospitalized days of the high-dose group were significantly longer than those of low-dose group (P<0.05). The high-dose group had significantly low lymphocyte fi-action at CPB-OFF compared with the low-dose group (P<0.001). These findings suggest that pretreatment of high-dose steroid is not superior to that of low-dose steroid regrading its potential benefits in pediatric cardiac surgery. Therefore, the conventional strategy of steroid treatment, high-dose pretreatment, should be modified in the cardiac surgery with CPB. However, further studies must be performed on the larger number of patients in as much as small number of patients in this study.

• 동의생리병리학회지
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• 제28권2호
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• pp.146-153
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• 2014

Gami-Sopungsan (GS) is one of the traditional korean remedy. We investigated the anti-inflammation and anti-atopic dermatitis (AD) effect of GS. No cytotoxicity of GS was observed in the range of $1{\sim}100{\mu}g/m{\ell}$ on Raw 264.7 cells. The Inflammatory response of Raw 264.7 cells were induced by lipopolysaccharide (LPS), followed by GS treatment at indicated concentrations (0, 1, 10 and $100{\mu}g/m{\ell}$). At $100{\mu}g/m{\ell}$ concentration, GS showed inhibitory effect on LPS-induced nitric oxide production by 20%. Production of IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ was decreased by approximately 56%, 36% and 79%, respectively upon GS treatment at $100{\mu}g/m{\ell}$. 200 mg/kg of GS was orally administered to NC/Nga mice, where AD was induced by 1-chloro 2,4-dinitrobenzene. There were no significant difference between GS treated group and the control group on body weight and food intake changes during growth. The back skin of GS group showed decrease in erythema, pruritus, dry skin, edema, excoriation, erosion and lichenification level through naked eye observations. In addition, leukocyte infiltration and the thickness of epidermis were significantly decreased in the skin tissues (back and ear). The serum IgE levels were decreased by 28.8% in the GS treated group. The GS treated group showed remarkable inhibition of IL-4 (83%), IL-5 (95%), IL-6 (62%) and TNF-${\alpha}$ (84%) in serum, indicating that GS has similar or higher efficacy than those of the dexamethasone treated group. From the results above, we conclude that GS has significant anti-inflammation and anti-AD effects on Raw 264.7 cells and NC/Nga mice. The results should provide fundamental and valuable data for the research on natural products being developed against atopic dermatitis.