• Korean Journal of Veterinary Pathology
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• v.3 no.1
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• pp.15-25
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• 1999

To elucidate the mechanism of age-related development in FGS/NgaKIST mice with spontaneous glomerulosclerotic lesion, we examined expression and localization of various cytokine mRNA in the kidney in the progression of diseases. This mouse model is the first to develop spontanously occuring glomerosclerotic lesion in the kidney. In this study, we detected the up-regulation of local cytokine genes such as IL-1$\beta$, IL-2, IL-6, IL-10, TNF-$\alpha$, TGF-$\beta$, and IFN- $\gamma$ in the kidneys. In RT-PCR and Southern blot analysis, we detected gradual expressions of cytokine mRNA of IL-1$\beta$, IL-2, IL-6, IFN- $\gamma$, and TNF $\alpha$ mRNA during the course of disease. Other cytokines including IL -10 and TGF -$\beta$ were found to be appeared the slightly expressed level at 3 to 12 weeks before onset of inflammatory lesion but they are highly expressed at the end-stage of the disease accompaning high proteinurea and wasting. In situ RT-PCR, each cytokine mRNA were specifically localized in a variety of cells including mesangial, endothelial, parietal epithelial, tubular epithelial, arterial muscle cell, and infiltrated inflammatory cells. In addition, TNF - $\alpha$was detected moderately in the visceral and parietal epithelial cell, but weakly in endothelial and mesangial cells, whereas IL-1 $\beta$ and IL -6 were strong in mesangial regions. IL-6 and TNF- $\alpha$ was highly localized in the damaged proximal and collecting tubules. Especially, TGF -$\beta$ mRNA was highly found in mesangial cells within glomerulus and interstitium during the end-stage of this disease.. These results indicate that pro inflammatory cytokines such as IL-1 $\beta$, IL-2, IL-6, and TNF- $\alpha$ were gradually expressed from the early stage of this disease to the end-stage, and that IL-10 and TGF-$\beta$ may be important in the accumulation of extracellular matrix(ECM) within glomerulus and periglomerular fibrosis in the progression of this disease as well as tissue destruction in end-stage of this disease.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6145-6150
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• 2014

Toll-like receptors (TLRs) are expressed in immune and tumor cells and recognize pathogen-associated molecular patterns. Cervical cancer (CC) is directly linked to a persistent infection with high risk human papillomaviruses (HR-HPVs) and could be associated with alteration of TLRs expression. TLR9 plays a key role in the recognition of DNA viruses and better understanding of this signaling pathway in CC could lead to the development of novel immunotherapeutic approaches. The present study was undertaken to determine the level of TLR9 expression in cervical neoplasias from Tunisian women with 53 formalin-fixed and paraffin-embedded specimens, including 22 samples of invasive cervical carcinoma (ICC), 18 of cervical intraepithelial neoplasia (CIN), 7 of condyloma and 6 normal cervical tissues as control cases. Quantification of TLR9 expression was based on scoring four degrees of extent and intensity of immunostaining in squamous epithelial cells. TLR9 expression gradually increased from CIN1 (80% weak intensity) to CIN2 (83.3% moderate), CIN3 (57.1% strong) and ICC (100% very strong). It was absent in normal cervical tissue and weak in 71.4% of condyloma. The mean scores of TLR9 expression were compared using the Kruskall-Wallis test and there was a statistical significance between normal tissue and condyloma as well as between condyloma, CINs and ICC. These results suggest that TLR9 may play a role in progression of cervical neoplasia in Tunisian patients and could represent a useful biomarker for malignant transformation of cervical squamous cells.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3613-3618
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• 2014

Stathmin, also called oncoprotein 18, is a founding member of the family of microtubule-destabilizing proteins that play a critical role in the regulation of mitosis. At the same time stathmin has been recognized as one of responsible factors in cancer cells. The aim of this study was to assess stathmin status, its correlations with clinicopathological parameters and its role as a progosnostic marker in EC patients. The protein and mRNA levels of stathmin were examined byimmunohistochemistry (IHC) and in situ hybridization in 100EC tissues and adjacent noncancerous tissues. mRNA and protein expression of stathmin in three EC cell lines(EC9706, ECa109, EC1 commonly used in research) were also analyzed using immunocytochemistry, western blot and in situ hybridization. The prognostic value of Stathmin expression within the tumor tissues were assessed by Cox regression and Kaplan-Meier analysis. We showed that stathmin expression was significantly higher in EC tissues than in adjacent noncancerous tissues. High stathmin immunostaining score in the EC was positively correlated with tumor differentiation, Tumor invasion, Lymph node metastases, and TNM stage. In addition, we demonstrated that three EC cell lines examined, were constitutively expressing a high level of stathmin. Of those, EC-1 showed the strongest mRNA and protein expression for the stathmin analyzed. Kaplan-Meier analysis showed that significantly longer 5-year survival rate was seen in EC patients with high Stathmin expression, compared to those with low expression of Stathmin expression. Furthermore, multivariate Cox proportional hazard analyses revealed that Stathmin was an independent factors affecting the overall survival probability. In conclusion, our data provide a basis for the concept that stathmin might be associated with EC development and progression. High levels of Stathmin expression in the tumor tissues may be a good prognostic marker for patients with EC.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.46 no.4
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• pp.240-249
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• 2020

Objectives: Although the side effects of radiation therapy vary from mucositis to osteomyelitis depending on the dose of radiation therapy, to date, an experimental animal model has not yet been proposed. The aim of this study was to develop an animal model for assessing complications of irradiated bone, especially to quantify the dose of radiation needed to develop a rat model. Materials and Methods: Sixteen Sprague-Dawley rats aged seven weeks with a mean weight of 267.59 g were used. Atraumatic extraction of a right mandibular first molar was performed. At one week after the extraction, the rats were randomized into four groups and received a single dose of external radiation administered to the right lower jaw at a level of 14, 16, 18, or 20 Gy, respectively. Clinical alopecia with body weight changes were compared and bony volumetric analysis with micro-computed tomography (CT), histologic analysis with H&E were performed. Results: The progression of the skin alopecia was different depending on the irradiation dose. Micro-CT parameters including bone volume, bone volume/tissue volume, bone mineral density, and trabecular spaces, showed no significant differences. The progression of osteoradionecrosis (ORN) along with that of inflammation, fibrosis, and bone resorption, was found with increased osteoclast or fibrosis in the radiated group. As the radiation dose increases, osteoclast numbers begin to decrease and osteoclast tends to increase. Osteoclasts respond more sensitively to the radiation dose, and osteoblasts are degraded at doses above 18 Gy. Conclusion: A standardized animal model clinically comparable to ORN of the jaw is a valuable tool that can be used to examine the pathophysiology of the disease and trial any potential treatment modalities. We present a methodology for the use of an experimental rat model that incorporates a guideline regarding radiation dose.

• Journal of the Korean Institute of Intelligent Systems
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• v.25 no.6
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• pp.529-535
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• 2015

Biological networks have been handled with the static concept. However, life phenomena in cells occur depending on the cellular state and the external environment, and only a few proteins and their interactions are selectively activated. Therefore, we should adopt the dynamic network concept that the structure of a biological network varies along the flow of time. This concept is effective to analyze the progressive transition of the disease. In this paper, we applied the proposed method to Alzheimer's disease to analyze the structural and functional characteristics of the disease network. Using gene expression data and protein-protein interaction data, we constructed the sub-networks in accordance with the progress of disease (normal, early, middle and late). Based on this, we analyzed structural properties of the network. Furthermore, we found module structures in the network to analyze the functional properties of the sub-networks using the gene ontology analysis (GO). As a result, it was shown that the functional characteristics of the dynamics network is well compatible with the stage of the disease which shows that it can be used to describe important biological events of the disease. Via the proposed approach, it is possible to observe the molecular network change involved in the disease progression which is not generally investigated, and to understand the pathogenesis and progression mechanism of the disease at a molecular level.

• Communications of Mathematical Education
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• v.37 no.4
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• pp.635-652
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• 2023

This study conducts a comprehensive analysis of the curricular progression of the concepts and learning sequences of 'lines', specifically, 'line segments', 'straight lines', and 'rays', at the elementary school level. By examining mathematics curricula and textbooks, spanning from 2nd to 7th and 2007, 2009, 2015, and up to 2022 revised version, the study investigates the timing and methods of introducing these essential geometric concepts. It also explores the sequential delivery of instruction and the key focal points of pedagogy. Through the analysis of shifts in the timing and definitions, it becomes evident that these concepts of lines have predominantly been integrated as integral components of two-dimensional plane figures. This includes their role in defining the sides of polygons and the angles formed by lines. This perspective underscores the importance of providing ample opportunities for students to explore these basic geometric entities. Furthermore, the definitions of line segments, straight lines, and rays, their interrelations with points, and the relationships established between different types of lines significantly influence the development of these core concepts. Lastly, the study emphasizes the significance of introducing fundamental mathematical concepts, such as the notion of straight lines as the shortest distance in line segments and the concept of lines extending infinitely (infiniteness) in straight lines and rays. These ideas serve as foundational elements of mathematical thinking, emphasizing the necessity for students to grasp concretely these concepts through visualization and experiences in their daily surroundings. This progression aligns with a shift towards the comprehension of Euclidean geometry. This research suggests a comprehensive reassessment of how line concepts are introduced and taught, with a particular focus on connecting real-life exploratory experiences to the foundational principles of geometry, thereby enhancing the quality of mathematics education.

• International Journal of Oncology
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• v.54 no.6
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• pp.2169-2178
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• 2019

Forkhead box A1 (FOXA1) functions as a tumor suppressor gene or an oncogene in various types of cancer; however, the distinct function of FOXA1 in colorectal cancer is unclear. The present study aimed to evaluate whether FOXA1 affects the oncogenic behavior of colorectal cancer cells, and to investigate its prognostic value in colorectal cancer. The impact of FOXA1 on tumor cell behavior was investigated using small interfering RNA and the pcDNA6-myc vector in human colorectal cancer cell lines. To investigate the role of FOXA1 in the progression of human colorectal cancer, an immunohistochemical technique was used to localize FOXA1 protein in paraffin-embedded tissue blocks obtained from 403 patients with colorectal cancer. Tumor cell apoptosis and proliferation were evaluated using a terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay and Ki-67 immunohistochemical staining, respectively. FOXA1 knockdown inhibited tumor cell invasion in colorectal cancer cells, and induced apoptosis and cell cycle arrest. FOXA1 knockdown activated cleaved caspase-poly (ADP-ribose) polymerase, upregulated the expression of p53 upregulated modulator of apoptosis, and downregulated BH3 interacting domain death agonist and myeloid cell leukemia-1, leading to the induction of apoptosis. FOXA1 knockdown increased the phosphorylation level of signal transducer and activator of transcription-3. By contrast, these results were reversed following the overexpression of FOXA1. The overexpression of FOXA1 was associated with differentiation, lymphovascular invasion, advanced tumor stage, depth of invasion, lymph node metastasis and poor survival rate. The mean Ki-67 labeling index value of FOXA1-positive tumors was significantly higher than that of FOXA1-negative tumors. However, no significant association was observed between the expression of FOXA1 and the mean apoptotic index value. These results indicate that FOXA1 is associated with tumor progression via the modulation of tumor cell survival in human colorectal cancer.

• Journal of Periodontal and Implant Science
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• v.32 no.2
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• pp.415-428
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• 2002

Periodontal disease is a complex infectious disease caused by bacteria in the oral mucosa, which results in gingival inflammation, breakdown of periodontal tissues, bone resorption, and finally tooth loss. Mechanical plaque control methods-scaling and root planing are effective methods to stop the progression of such periodontal disease. It was reported that subantimicrobial dose of doxycycline(SDD) regimen could improve clinical conditions of periodontal tissues without causing the overgrowth of opportunistic organisms that was a typical antibiotic side effect. Therefore pharmacological therapy, used in conjunction with mechanical therapy could be considered a useful treatment modality in the treatment of chronic periodontal disease. In this study, 30 patients diagnosed as moderate to advanced chronic periodontitis were divided into 2 groups. In this double-blind, placebo-controlled study, the patients were administered 20mg doxycycline capsule or placebo capsule b.i.d. for 4months, after scaling and root planing. Clinical parameters-bleeding on probing, pocket depth and clinical attachment level were compared and evaluated between these groups at periods of first visit, 1 month, 2 months, 3 months, 4 months. The results were as follows ; 1. In case of moderate periodontitis, pocket depth showed significant reduction after treatment in both the control & experiment groups, when compared with the baseline values(p<0.01), but in case of advanced periodontitis, only the experiment group showed significant reduction after treatment when compared with the baseline values(p<0.05). Statistically significant reduction in pocket depth was observed in the experiment group compared to the control group(p<0.05). 2. In case of moderate periodontitis, clinical attachment level showed significant reduction after treatment in both the control & experiment groups, when compared with the baseline values(p<0.01), but in case of advanced periodontitis, only the experiment group showed significant reduction after treatment when compared with the baseline values(p<0.05). Statistically significant reduction in clinical attachment level was observed in the experiment group compared to the control group(p<0.05). 3. Bleeding on probing improved after treatment in both the groups. In case of moderate periodontitis, the experiment group showed statistically significant reduction of bleeding on probing when compared with the control group at 1 and 4 months after treatment(p<0.05). In case of advanced periodontitis, treatment resulted in statistically significant reduction of bleeding on probing in both the groups(p<0.05). These results indicate that the use of subantimicrobial dose of doxycycline is a useful supplement to mechanical treatment for periodontal patients in ameliorating the clinical parameters such as periodontal pocket, attachment level, and bleeding on probing.

• Clinical and Experimental Pediatrics
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• v.61 no.8
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• pp.258-263
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• 2018

Purpose: Macrolide-resistant Mycoplasma pneumoniae pneumonia (MPP) is characterized by prolonged fever and radiological progression despite macrolide treatment. Few studies have examined serum procalcitonin (PCT) level in children with MPP. We aimed to investigate the association of acute inflammation markers including PCT with clinical parameters in children with MPP. Methods: A total of 147 children were recruited. The diagnosis of MPP relied on serial measurement of IgM antibody against mycoplasma and/or polymerase chain reaction. We evaluated the relationships between C-reactive protein (CRP), PCT, and lactate dehydrogenase (LDH) levels and white blood cell (WBC) counts, and clinical severity of the disease. We used multivariate logistic regression analysis to estimate the odds ratio for prolonged fever (>3 days after admission) and hospital stay (> 6 days), comparing quintiles 2-5 of the PCT levels with the lowest quintile. Results: The serum PCT and CRP levels were higher in children with fever and hospital stay than in those with fever lasting ${\leq}3days$ after admission and hospital stay ${\leq}6days$. CRP level was higher in segmental/lobar pneumonia than in bronchopneumonia. The LDH level and WBC counts were higher in children with fever lasting for >3 days before compared to those with fever lasting for ${\leq}3days$. The highest quintile of PCT levels was associated with a significantly higher risk of prolonged fever and/or hospital stay than the lowest quintile. Conclusion: Serum PCT and CRP levels on admission day were associated with persistent fever and longer hospitalization in children with MPP.

• Science of Emotion and Sensibility
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• v.13 no.4
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• pp.761-768
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• 2010

Research from many marketing fields shows that the importance of factors which ultimately reflect customers' satisfaction towards a product or service vary with the progression of time. Likewise, the emotions that users experience from using the product can vary with prolonged interaction with the product itself. Thus, research was conducted under the notion that users' emotions at the initial stage of product usage is likely to vary with that at a later stage, when users would have had more experience with the product. In this research, a comparison was made between the emotions felt by customers with first-hand experience with the iPhone and those felt by long-time iPhone users who already had much more opportunities to familiarize themselves with the product. The results of the research conducted above show that, with first usage of the iPhone, users experience a relatively low level of negative emotions(Uncomfortableness) due to the predominance of the users' positive emotions. Over prolonged usage, however, the level of negative emotions associated with the usage of the iPhone has been shown to increase. Still, it is impossible to state that the Uncomfortableness associated with iPhone usage is high in general. In fact, it has been shown that positive emotions were rather experienced by iPhone users both before and after usage, suggesting that the emotions involved during iPhone usage was generally positive. Although more research would need to be conducted to safeguard this claim, it can be generally deduced from the results of this research that:when using a product, positive emotions in terms of the reflective level accounts for much of the negative emotions(i.e. discomfort) associated with behavioral level with regard to the product itself.