• Biomolecules & Therapeutics
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• v.31 no.4
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• pp.456-465
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• 2023

Cervical tumors represent a prevalent form of cancer affecting women worldwide; current treatment options involve surgery, radiotherapy, and chemotherapy. Angiogenesis, the process of new blood vessel formation, is a crucial factor in cervical tumor growth. The molecular mechanisms underlying the effects of the liver kinase B1 (LKB1/STK11) tumor suppressor protein on tumor angiogenesis have not been elucidated. Therefore, we investigated the role of LKB1 in cervical tumor angiogenesis both in vitro and in vivo in this study. Our results demonstrated that LKB1 inhibited cervical tumor angiogenesis by suppressing the expression of angiogenesis-related factors such as vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1α. LKB1 directly affected both carcinoma and vascular endothelial cells, resulting in a significant reduction in tumor growth and angiogenesis. Furthermore, LKB1 was found to bind to VEGF receptor 2 (VEGFR-2) and target the VEGFR-2-mediated protein kinase B/mechanistic target of rapamycin signaling pathway in endothelial cells, thereby reducing cervical tumor growth and angiogenesis. Our study provides new insights into the molecular mechanisms underlying the anti-tumor and anti-angiogenic effects of LKB1 in cervical cancer. These findings will help develop new therapeutic strategies for cervical cancer.

• Steel and Composite Structures
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• v.49 no.1
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• pp.91-107
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• 2023

An effective approach to promoting sustainability within the construction industry is the use of recycled aggregate concrete (RAC) as a substitute for natural aggregates. Ensuring the frost resilience of RAC technologies is crucial to facilitate their adoption in regions characterized by cold temperatures. The main aim of this study was to use the Random Forests (RF) approach to forecast the frost durability of RAC in cold locations, with a focus on the durability factor (DF) value. Herein, three optimization algorithms named Sine-cosine optimization algorithm (SCA), Black widow optimization algorithm (BWOA), and Equilibrium optimizer (EO) were considered for determing optimal values of RF hyperparameters. The findings show that all developed systems faithfully represented the DF, with an R² for the train and test data phases of better than 0.9539 and 0.9777, respectively. In two assessment and learning stages, EO - RF is found to be superior than BWOA - RF and SCA - RF. The outperformed model's performance (EO - RF) was superior to that of ANN (from literature) by raising the values of R² and reducing the RMSE values. Considering the justifications, as well as the comparisons from metrics and Taylor diagram's findings, it could be found out that, although other RF models were equally reliable in predicting the the frost durability of RAC based on the durability factor (DF) value in cold climates, the developed EO - RF strategy excelled them all.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.39
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• pp.8.1-8.8
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• 2017

Background: For an effective bone graft for reconstruction of the maxillofacial region, an adequate vascular network will be required to supply blood, osteoprogenitor cells, and growth factors. We previously reported that the secretomes of bone marrow-derived mesenchymal stem cells (MSC-CM) contain numerous growth factors such as insulin-like growth factor (IGF)-1, transforming growth factor $(TGF)-{\beta}1$, and vascular endothelial growth factor (VEGF), which can affect the cellular characteristics and behavior of regenerating bone cells. We hypothesized that angiogenesis is an important step for bone regeneration, and VEGF is one of the crucial factors in MSC-CM that would enhance its osteogenic potential. In the present study, we focused on VEGF in MSC-CM and evaluated the angiogenic and osteogenic potentials of MSC-CM for bone regeneration. Methods: Cytokines in MSC-CM were measured by enzyme-linked immunosorbent assay (ELISA). Human umbilical vein endothelial cells (HUVECs) were cultured with MSC-CM or MSC-CM with anti-VEGF antibody (MSC-CM + anti-VEGF) for neutralization, and tube formation was evaluated. For the evaluation of bone and blood vessel formation with micro-computed tomography (micro-CT) and for the histological and immunohistochemical analyses, a rat calvarial bone defect model was used. Results: The concentrations of IGF-1, VEGF, and $TGF-{\beta}1$ in MSC-CM were $1515.6{\pm}211.8pg/mL$, $465.8{\pm}108.8pg/mL$, and $339.8{\pm}14.4pg/mL$, respectively. Tube formation of HUVECs, bone formation, and blood vessel formation were increased in the MSC-CM group but decreased in the MSC-CM + anti-VEGF group. Histological findings suggested that new bone formation in the entire defect was observed in the MSC-CM group although it was decreased in the MSC-CM + anti-VEGF group. Immunohistochemistry indicated that angiogenesis and migration of endogenous stem cells were much more abundant in the MSC-CM group than in the MSC-CM + anti-VEGF group. Conclusions: VEGF is considered a crucial factor in MSC-CM, and MSC-CM is proposed to be an adequate therapeutic agent for bone regeneration with angiogenesis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.6
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• pp.1613-1616
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• 2004

The cellular response to hypoxia is controlled to a large degree by the transcription factor Hypoxia-inducible factor-1(HIF-1). HIF-1 is a transcription factor that is activated by hypoxia and plays a critical role in the development of the cancer phenotype. HIF-1 regulates transcription of a number of genes crucial for tumor survival under hypoxic conditions, including vascular endothelial growth factor(VEGF), erythropoietin(Epo) and several glycolytic enzymes. Tumors in which hypoxia can not induce HIF-1 transcriptional activity remain small and fail to metastasize. In this study, we examined whether aqueous root extract of Ailanthus altissima (REA) downregulate HIF-1, VEGF and p53, and raise the possibility that depletion of these proteins and the anti proliferative activities of REA have any effects on inhibition of angiogenesis in MCF-7 cells. Pharmacologic targeting of specific signal transduction pathways related to oncogenic transformation is a promising approach in cancer treatment. Therefore, REA could be a candidate drug for further clinical development.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.28 no.6
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• pp.549-558
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• 2006

During distraction osteogenesis, the angiogenic activity is crucial factor in the new bone formation. The aim of this study was to detect the autocrine growth activity in the cellular components of the distracted periosteum with observation of the expression of vascular endothelial growth factor (VEGF) and its receptors following the mandibular distraction osteogenesis. Unilateral mandibular distraction (0.5 mm twice per day for 10 days) was performed in six mongrel dogs. Two animals were sacrificed at 7, 14, and 28 days after completion of distraction, respectively. The distracted lingual periosteum was harvested and processed for immunohistochemical examinations. After then, we observed the expression of VEGF, Flt-1 (VEGFR-1), and Flk-1 (VEGFR-2) in the osteoblasts and immature mesenchymal cells of the distracted periosteum. At 7 days after distraction, the expression of VEGF and its receptors were significantly increased in the cellular components of the distracted periosteum. Up to 14 days following distraction, the increased expressions were maintained in the osteoblastic cells. At 28 days after distraction, the expression of VEGF and its receptors decreased, but VEGF was still expressed weak or moderate in the osteoblastic cells of distracted periosteum. The expression pattern of VEGF and its receptors shown here suggested that VEGF play an important role in the osteogenesis, and these osteoblastic cell-derived VEGF might act as autocrine growth factor during distraction osteogenesis. In the other word, the cellular components in the distracted periosteum, such as osteoblasts and immature mesenchymal cells, might have autocrine growth activity during distraction osteogenesis.

• BMB Reports
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• v.38 no.5
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• pp.602-608
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• 2005

As a crucial transcription factor family, heat-shock factors were mainly analyzed and characterized in tomato and Arabidopsis. In this study, we isolated two putative heat shock factors OsHSF6 and OsHSF12 that interact specifically with heat-shock element (HSE) from Oryza sativa L by yeast one-hybrid method. The full-length cDNA of OsHSF6 and OsHSF12 have 1074bp and 920bp open reading frame (ORF), respectively. Analysis of the deduced amino acid sequences revealed that OsHSF6 was a class A heat shock factor (HSF) with all the conserved sequence elements characteristic of heat stress transcription factor, while OsHSF12 was a class B HSF with C-terminal domain (CTD) lacking of AHA motif. Bioinformatic analysis showed that the sequences and structures of two HSFs' DNA binding domain (DBD) had a high similarity with LpHSF24. The results of RT-PCR indicated OsHSF6 gene was expressed immediately after rice plants exposure to heat stress, and the transcription of OsHSF6 gene accumulated primarily in immature seeds, roots and leaves. However, we did not find the transcription of OsHSF12 gene in different organs and growth periods. Our results implied that OsHSF6 might be function as a HSF regulating early expression of stress genes in response to heat shock, and OsHSF12 might be act as a synergistic factor to regulate the expression of down-stream genes.

• The Mathematical Education
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• v.56 no.4
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• pp.407-434
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• 2017

The purpose of this study is to develop and verify the TPACK measurement tool for middle and high school mathematics teachers in the Korean context. Also, by clarifying the relationship between subordinate factors of Mathematics teachers' TPACK, an attempt was made to provide suggestions on the designs and directions for the in-service and pre-service teacher education and the programs for improving mathematics teachers' TPACK in the future. In order to achieve this goal, TPACK factors of mathematics teachers were extracted by reviewing literature on PCK, MKT, and TPACK. Then, content validity, basic statistical survey, reliability verification, exploratory factor analysis, confirmatory factor analysis, and structural equation model verification were conducted sequentially. At first, preliminary analysis was carried out on 79 mathematics teachers, and 76 items excluding the items with extreme value and reliability were included in the basic statistical analysis. And secondly, an exploratory factor analysis was conducted on 376 mathematics teachers, and this instrument consisted of 7 subordinate factors(CK, PK, TK, PCK, TCK, TPK, TPACK) and 61 items. Also by conducting confirmatory factor analysis and structural equation model test with 254 mathematics teachers, the measurement tool was confirmed the validity and reliability through statistically significant analysis. Then, the importance of integrated knowledge was confirmed by looking at the relationship between the TPACK factors of in-service mathematics teachers. The integrated knowledge(PCK, TCK, TPK) has played a crucial role in the formation of TPACK rather than the knowledge of CK, PK, and TK alone. Finally, the validity of TCK was confirmed through the structural equation modeling of TPACK. TCK not only directly affected TPACK, but also indirectly through TPK. According to these affirmative results, this measurement tool is claimed to be suitable for measuring the factors of Mathematics teachers' TPACK, and also the structural equation model can be regarded as a suitable model for analyzing the structural relationship of mathematics teachers' TPACK.

• IMMUNE NETWORK
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• v.24 no.1
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• pp.10.1-10.17
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• 2024

In this review, we will explore the intricate roles of cytokines and vascular endothelial growth factors in autoimmune diseases (ADs), with a particular focus on rheumatoid arthritis (RA) and multiple sclerosis (MS). AD is characterized by self-destructive immune responses due to auto-reactive T lymphocytes and Abs. Among various types of ADs, RA and MS possess inflammation as a central role but in different sites of the patients. Other common aspects among these two ADs are their chronicity and relapsing-remitting symptoms requiring continuous management. First factor inducing these ADs are cytokines, such as IL-6, TNF-α, and IL-17, which play significant roles in the pathogenesis by contributing to inflammation, immune cell activation, and tissue damage. Secondly, vascular endothelial growth factors, including VEGF and angiopoietins, are crucial in promoting angiogenesis and inflammation in these two ADs. Finally, placental growth factor (PlGF), an emerging factor with bi-directional roles in angiogenesis and T cell differentiation, as we introduce as an "angio-lymphokine" is another key factor in ADs. Thus, while angiogenesis recruits more inflammatory cells into the peripheral sites, cytokines secreted by effector cells play critical roles in the pathogenesis of ADs. Various therapeutic interventions targeting these soluble molecules have shown promise in managing autoimmune pathogenic conditions. However, delicate interplay between cytokines, angiogenic factors, and PlGF has more to be studied when considering their complementary role in actual pathogenic conditions. Understanding the complex interactions among these factors provides valuable insights for the development of innovative therapies for RA and MS, offering hope for improved patient outcomes.

• Journal of Technologic Dentistry
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• v.39 no.4
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• pp.263-273
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• 2017

Purpose: This study aimed to explore the relations between class distracting factors and class satisfaction of the dental technology students and then provide a primary data to help further related studies and develop educational programs with which instructors can efficiently manage their classroom. Methods: For this study we have conducted a survey started from the beginning of May 2017 to the end of June. The subjects of the survey were Dental Technology students of D-city, K-city, W-city, selected by random sampling method. The questionnaire was self-administrated and 437 valid results were chosen for our analysis among 450 distributed questionnaires. Results: The results of the research was as follows. Firstly, The overall average point of class distracting factors was 2.5 point. The environmental factors were the highest point as 2.59 and as for the subcategories tiredness and drowsiness was the highest point as 2.76. Secondly, The overall average point of class satisfaction turned out 3,88 point and compliance with class and attitude factors gained the highest point as 4.06. Of the subcategories strict roll checking was the highest point as 4.17. Thirdly, As for class distracting factors from general characteristics a statistical significance was shown as follows; 'instructor factor'(p<.01), 'learner factor'(p<.05), 'total class distracting factor'(p<.05) in the area of gender, 'environmental factor'(p<.001), 'total class distracting factor'(p<.01), 'learner factor'(p<.05), 'instructor factor'(p<.05) in the area of gender 'learner factor'(p<.001), 'instructor factor'(p<.001), 'environmental factor'(p<.001), 'total class distracting factor'(p<.01) in the area of class grade, 'environmental factor'(p<.05) in GPA. Fourthly, A statistical significance, a negative correlation (p<.01) were shown between class distracting factors and class satisfaction. Class distracting factor that especially affects the class satisfaction was instructor factor(p<.001) and the explanatory power of the model turned out 14.7%, which was statistically meaningful (p<.001). Conclusion : Results of this study reveal that instructor factor is the key to class satisfaction of the students. So it is crucial that the instructor faithfully prepare for the class to reinforce the students' learning. Additionally further studies should be followed with more subjects and newer perspectives to develop innovative teaching methodology.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.3
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• pp.449-456
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• 2018

Objective: Nanog, a homeodomain protein, has been investigated in humans and mice using embryonic stem cells (ESCs). Because of the limited availability of ESCs, few studies have reported the function and role of Nanog in porcine ESCs. Therefore, in this study, we investigated the location of the porcine Nanog chromosome and its basal promoter activity, which might have potential applications in development of ESCs specific marker as well as understanding its operating systems in the porcine. Methods: To characterize the porcine Nanog promoter, the 5'-flanking region of Nanog was isolated from cells of mini-pig ears. BLAST database search showed that there are two porcine Nanog genomic loci, chromosome 1 and 5, both of which contain an exon with a start codon. Deletion mutants from the 5'-flanking region of both loci were measured using the Dual-Luciferase Reporter Assay System, and a fluorescence marker, green fluorescence protein. Results: Promoter activity was detected in the sequences of chromosome 5, but not in those of chromosome 1. We identified the sequences from -99 to +194 that possessed promoter activity and contained transcription factor binding sites from deletion fragment analysis. Among the transcription factor binding sites, a Sp1 was found to play a crucial role in basal promoter activity, and point mutation of this site abolished its activity, confirming its role in promoter activity. Furthermore, gel shift analysis and chromatin immunoprecipitation analysis confirmed that Sp1 transcription factor binds to the Sp1 binding site in the porcine Nanog promoter. Taken together, these results show that Sp1 transcription factor is an essential element for porcine Nanog basal activity the same as in human and mouse. Conclusion: We showed that the porcine Nanog gene is located on porcine chromosome 5 and its basal transcriptional activity is controlled by Sp1 transcription factor.