• Communications for Statistical Applications and Methods
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• v.29 no.4
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• pp.453-469
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• 2022

The study of immune cellular composition has been of great scientific interest in immunology because of the generation of multiple large-scale data. From the statistical point of view, such immune cellular data should be treated as compositional. In compositional data, each element is positive, and all the elements sum to a constant, which can be set to one in general. Standard statistical methods are not directly applicable for the analysis of compositional data because they do not appropriately handle correlations between the compositional elements. In this paper, we review statistical methods for compositional data analysis and illustrate them in the context of immunology. Specifically, we focus on regression analyses using log-ratio transformations and the alternative approach using Dirichlet regression analysis, discuss their theoretical foundations, and illustrate their applications with immune cellular fraction data generated from colorectal cancer patients.

• International Journal of Oral Biology
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• v.45 no.1
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• pp.1-7
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• 2020

Oral lichen planus (OLP) is a chronic inflammatory disease observed in approximately 0.5-2.2% of the population, and it is recognized as a premalignant lesion that can progress into oral squamous cell carcinoma (OSCC). The rate of malignant transformation is approximately 1.09-2.3%, and the risk factors for malignant transformation are age, female, erosive type, and tongue site location. Malignant transformation of OLP is likely related to the low frequency of apoptotic phenomena. Therefore, apoptosis-related genetic factors, like p53, BCL-2, and BAX are reviewed. Increased p53 expression and altered expression of BCL-2 and BAX were observed in OLP patients, and the malignant transformation rate in these patients was relatively higher. The involvement of microRNA (miRNA) in the malignant transformation of OLP is also reviewed. Because autophagy is involved in cell survival and death through the regulation of various cellular processes, autophagy-related genetic factors may function as factors for malignant transformation. In OLP, decreased levels of ATG9B mRNA and a higher expression of IGF1 were observed, suggesting a reduction in cell death and autophagic response. Activated IGF1-PI3K/AKT/mTor cascade may play an important role in a signaling pathway related to the malignant transformation of OLP to OSCC. Recent research has shown that miRNAs, such as miR-199 and miR-122, activate the cascade, increasing the prosurvival and proproliferative signals.

• Archives of Pharmacal Research
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• v.28 no.1
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• pp.1-15
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• 2005

Cancer is still a major global health concern even after an everlasting strive in conquering this dread disease. Emphasis is now given to chemoprevention to reduce the risk of cancer and also to improve the quality of life among cancer afflicted individuals. Recent progress in molecular biology of cancer has identified key components of the cellular signaling network, whose functional abnormality results in undesired alterations in cellular homeostasis, creating a cellular microenvironment that favors premalignant and malignant transformation. Multiple lines of evidence suggest an elevated expression of cyclooxygenase-2 (COX-2) is causally linked to cancer. In response to oxidative/pro-inflammatory stimuli, turning on unusual signaling arrays mediated through diverse classes of kinases and transcription factors results in aberrant expression of COX-2. Population-based as well as laboratory studies have explored a broad spectrum of chemopreventive agents including selective COX-2 inhibitors and a wide variety of anti-inflammatory phytochemicals, which have been shown to target cellular signaling molecules as underlying mechanisms of chemoprevention. Thus, unraveling signaling pathways regulating aberrant COX-2 expression and targeted blocking of one or more components of those signal cascades may be exploited in searching chemopreventive agents in the future.

• Structural Engineering and Mechanics
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• v.50 no.5
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• pp.605-616
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• 2014

When the periodic cellular structure is loaded or swelling beyond the critical value, the structure may undergo a pattern transformation owing to the local elastic instabilities, thus leading to structural collapse and the structure changing to a new configuration. Based on this deformation-triggered pattern, we have proposed the novel composite gel materials. This designed material is a type of architectural material possessing special mechanical properties. In this study, the mechanical behavior of the composite gel periodic structure with various gel inclusions is studied further through numerical simulations. When pattern transformation occurs, it results in a different elastic relationship compared with the material at untransformed state. Based on the obtained nominal stress versus nominal strain behavior, the Poisson's ratio and corresponding deformed structure patterns, we investigate the performance of designed composite materials and the effects of the uniformly distributed gel inclusions on composite materials. A better understanding of the characteristics of these composite gel materials is a key to develop its potential applications on new soft machines.

• Molecules and Cells
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• v.37 no.4
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• pp.330-336
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• 2014

Thymosin beta4 (TB4) has multiple functions in cellular response in processes as diverse as embryonic organ development and the pathogeneses of disease, especially those associated with cardiac coronary vessels. However, the specific roles played by TB4 during heart valve development in vertebrates are largely unknown. Here, we identified a novel function of TB4 in endothelial-mesenchymal transformation (EMT) in cardiac valve endocardial cushions in zebrafish. The expressions of thymosin family members in developing zebrafish embryos were determined by whole mount in situ hybridization. Of the thymosin family members only zTB4 was expressed in the developing heart region. Cardiac valve development at 48 h post fertilization was defected in zebrafish TB4 (zTB4) morpholino-injected embryos (morphants). In zTB4 morphants, abnormal linear heart tube development was observed. The expressions of bone morphogenetic protein (BMP) 4, notch1b, and hyaluronic acid synthase (HAS) 2 genes were also markedly reduced in atrio-ventricular canal (AVC). Endocardial cells in the AVC region were stained with anti-Zn5 antibody reactive against Dm-grasp (an EMT marker) to observe EMT in developing cardiac valves in zTB4 morphants. EMT marker expression in valve endothelial cells was confirmed after transfection with TB4 siRNA in the presence of transforming growth factor ${\beta}$ ($TGF{\beta}$) by RT-PCR and immunofluorescent assay. Zn5-positive endocardial AVC cells were not observed in zTB4 morphants, and knockdown of TB4 suppressed TGF-${\beta}$-induced EMT in ovine valve endothelial cells. Taken together, our results demonstrate that TB4 plays a pivotal role in cardiac valve formation by increasing EMT.

• Genomics & Informatics
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• v.4 no.4
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• pp.161-166
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• 2006

The establishment of DNA microarray technology has enabled high-throughput analysis and molecular profiling of various types of cancers. By using the gene expression data from microarray analysis we are able to investigate diagnostic applications at the molecular level. The most important step in the application of microarray technology to cancer diagnostics is the selection of specific markers from gene expression profiles. In order to select markers of Immortalization and transformation we used c-myc and $H-ras^{V12}$ oncogene-transfected NIH3T3 cells as our model system. We have identified 8751 differentially expressed genes in the immortalization/transformation model by multivariate permutation F-test (95% confidence, FDR<0.01). Using the support vector machine algorithm, we selected 13 discriminative genes which could be used to predict immortalization and transformation with perfect accuracy. We assayed $H-ras^{V12}$-transfected 'transformed' cells to validate our immortalization/transformation dassification system. The selected molecular markers generated valuable additional information for tumor diagnosis, prognosis and therapy development.

• Molecules and Cells
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• v.40 no.3
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• pp.163-168
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• 2017

Microglia are the primary resident immune cells of the central nervous system (CNS). They are the first line of defense of the brain's innate immune response against infection, injury, and diseases. Microglia respond to extracellular signals and engulf unwanted neuronal debris by phagocytosis, thereby maintaining normal cellular homeostasis in the CNS. Pathological stimuli such as neuronal injury induce transformation and activation of resting microglia with ramified morphology into a motile amoeboid form and activated microglia chemotax toward lesion site. This review outlines the current research on microglial activation and chemotaxis.

• Molecules and Cells
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• v.21 no.2
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• pp.167-173
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• 2006

The literature provides strong precedent for both pro-tumorigenic and tumor suppressor roles for the c-Jun N-terminal kinases (JNKs) in the setting of oncogenesis. Clearly, JNKs are activated by numerous oncogenes and growth factors and the literature documents a role for these MAP kinases in cell proliferation and transformation. By contrast, JNKs mediate signals from diverse stimuli that result in cell death or differentiation and a role for JNKs as tumor suppressors has emerged. This enigmatic nature of the JNKs in the setting of oncogenesis is considered herein. Further illumination of the complex and context-dependent functions of the JNKs in cancer cells is of obvious importance for the rational use of small molecule JNK inhibitors as therapeutics.

• ALGAE
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• v.33 no.4
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• pp.351-358
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• 2018

The ability to transform the chloroplast of Cyanidioschyzon merolae was limited by lack of confirmed and reliable promoter sequences (among other reasons), capable of delivering stable or modulated DNA transcription followed by protein synthesis. Our research has confirmed the applicability of three selected chloroplast promoters in C. merolae chloroplast overexpression of the exogenous protein (i.e., chloramphenicol acetyltransferase) and genetic transformation. These results might facilitate further research on genetically modified strains of C. merolae to envisage yet unknown aspect of cellular and plastic physiology as well as C. merolae potential applications as bio-factories or sources of useful chemicals.

• Korean Journal of Microbiology
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• v.27 no.1
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• pp.10-15
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• 1989

The plasmid pKOneo, containing SV40 transcriptional promoter, has been used in the mouse tumorigenicity assay for oncogene studies. This assay employs a cotransfection of NIG3T3 fibroblast cells with the desired DNA and the plasmid pKOneo. This oncogene assay, however, has been speculated due to the SV40 transcriptional promoter in the plasmid pKOneo. This research was designed to investigate if the plasmid pKOneo alone is capable of transforming NiH3T3 fibroblast cells. The NIH3T3 subclones were established after the NIH3T3 cells were transfected with the plasmid pKOneo alone. The estabilished NIH3T3 subclones, containing the exogeneous plasmid pKOneo in their chromosomes, were examined for their expression of transformation-associated parameters. The results indicate that this plasmid pKOneo alone has positive effects on transformation of NIH3T3 cells after integration into cellular chromosomes.