• Journal of Life Science
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• v.29 no.2
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• pp.256-264
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• 2019

Lymphotoxin ${\beta}$ receptor ($LT{\beta}R$), a member of the tumor necrosis factor receptor family, plays an important role in lymphoid tissue's architecture and organogenesis. In contrast, MLCK and ROCK play critical roles in the regulation of stress fiber (SF) formation in cells. To determine whether $LT{\beta}R$ stimulation in fibroblastic reticular cells (FRCs) is involved in these signaling pathways, myosin light chain kinase inhibitor-7 (ML-7) was used to inhibit them. ML7-treated FRCs completely blocked SFs and showed retraction and shrinkage processes comparable to those observed in agonistic anti-$LT{\beta}R$ antibody-treated cells. The inhibition of ROCK activity with Y27632-induced changes in actin cytoskeleton organization and cell morphology in FRCs. Actin bundles rearranged into SFs, and phospho-myosin light chain (p-MLC) co-localized in FRCs. We checked the level of Rho-guanosine diphosphate (RhoGDP)/guanosine triphosphate (GTP) exchange activity using FRC lysate. When $LT{\beta}R$ was stimulated with agonistic anti-$LT{\beta}R$ antibodies, Rho-GDP/GTP exchange activity was markedly reduced. Regarding $LT{\beta}R$ signaling with a focus on MLCK inhibition, we showed that the phosphorylation of MLCs was reduced by $LT{\beta}R$ stimulation in FRCs. Cytoskeleton components, such as tubulin, b-actin, and phospho-ezrin proteins acting as membrane-cytoskeleton linkers, were produced in de-phosphorylation, and they reduced expression in agonistic anti-$LT{\beta}R$ antibody-treated FRCs. Collectively, the results suggested that MLCK and ROCK were simultaneously responsible for SF regulation triggered by $LT{\beta}R$ signaling in FRCs.

• Animal Bioscience
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• v.34 no.7
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• pp.1116-1122
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• 2021

Objective: The aim was to characterize the genetic diversity evolution of the registered Mexican Charolais cattle population by pedigree analysis. Methods: Data consisted of 331,390 pedigree records of animals born from 1934 to 2018. Average complete generation equivalent, generation interval, effective population size (N_e), and effective numbers of founders (f_e), ancestors (f_a), and founder genomes (N_g) were calculated for seven five-year periods. The inbreeding coefficient was calculated per year of birth, from 1984 to 2018, whereas the gene contribution of the most influential ancestors was calculated for the latter period. Results: Average complete generation equivalent consistently increased across periods, from 4.76, for the first period (1984 through 1988), to 7.86, for the last period (2014 through 2018). The inbreeding coefficient showed a relative steadiness across the last seventeen years, oscillating from 0.0110 to 0.0145. During the last period, the average generation interval for the father-offspring pathways was nearly 1 yr. longer than that of the mother-offspring pathways. The effective population size increased steadily since 1984 (105.0) and until 2013 (237.1), but showed a minor decline from 2013 to 2018 (233.2). The population displayed an increase in the f_a since 1984 and until 2008; however, showed a small decrease during the last decade. The effective number of founder genomes increased from 1984 to 2003, but revealed loss of genetic variability during the last fifteen years (from 136.4 to 127.7). The f_a:f_e ratio suggests that the genetic diversity loss was partially caused by formation of genetic bottlenecks in the pedigree; in addition, the N_g:f_a ratio indicates loss of founder alleles due to genetic drift. The most influential ancestor explained 1.8% of the total genetic variability in the progeny born from 2014 to 2018. Conclusion: Inbreeding, N_e, f_a, and N_g are rather beyond critical levels; therefore, the current genetic status of the population is not at risk.

• Journal of Food Hygiene and Safety
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• v.35 no.6
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• pp.587-601
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• 2020

Exposure to hazardous substances occurs through multiple pathways. Aggregated risk assessment, which includes all potential exposure pathways to a single toxicant, is necessary to prevent exposure to harmful substances. We aimed to estimate cadmium and lead exposure through various media, such as food, water, air, smoking, cosmetics, and female hygiene products. This study covered 10,733 subjects from the Seventh Korea National Health and Nutrition Examination Survey(2016, 2017). Dietary exposure was estimated using 24-hour recall data. For water and inhalational exposure, regional variations were considered. Water was classified as tap, bottled, and public water. Inhalational exposure was estimated using the '2014 Time Use Survey' based on daily lifestyle and social status. The frequency and volume of cosmetic usage were randomly approximated by sex and age. Post-menarcheal and premenopausal women were assumed to use feminine hygiene products. Non-carcinogenic aggregated risks were estimated using the Aggregate Risk Index from EPAs and the Total Exposure Hazard Index from Korean government guidelines. For carcinogenic risk assessment, excessive cancer risk was estimated. Ingestion, especially food, was the major route for both cadmium and lead exposure. Smoking was also associated with high cadmium exposure. Exposure to lead from cosmetics was remarkable but not critical. In aggregate risk assessments, median cadmium and lead exposure did not exceed the reference value. Sex, age, smoking status, and income affected exposure levels, unlike to regional variations.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.5
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• pp.457-470
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• 2023

The aim of this study was to investigate the role of kinesin superfamily member 15 (KIF15) in nasopharyngeal carcinogenesis (NPC) and explore its underlying mechanisms. We employed various assays, including the CCK-8 assay, flow cytometry, the Transwell and scratch assay, Western blotting, and nude mice transplantation tumor, to investigate the impact of KIF15 on NPC. Our findings demonstrate that KIF15 plays a critical role in the proliferation, apoptosis, migration, and invasion of NPC cells. Furthermore, we discovered that silencing KIF15 inhibits cell proliferation, migration, and invasion while promoting apoptosis, and that KIF15's effect on NPC cell growth is mediated through the PI3K/AKT and P53 signaling pathways. Additionally, we showed that KIF15 promotes nasopharyngeal cancer cell growth in vivo. Our study sheds light on the significance of KIF15 in NPC by revealing that KIF15 knockdown inhibits NPC cell growth through the regulation of AKT-related signaling pathways. These findings suggest that KIF15 represents a promising therapeutic target for the prevention and treatment of NPC.

• Journal of Life Science
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• v.34 no.7
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• pp.520-530
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• 2024

Tumor suppressor genes (TSGs) play a crucial role in maintaining cellular homeostasis. When the function of these genes is lost, it can lead to cellular plasticity that drives the development of various cancers, including small-cell lung cancer (SCLC), which is known for its aggressive nature. SCLC is primarily driven by numerous loss-of-function mutations in TSGs, often involving genes that encode epigenetic regulators. These mutations pose a significant therapeutic challenge as they are not directly targetable. However, understanding the molecular changes resulting from these mutations might provide insights for developing tumor intervention strategies. We propose that despite the heterogeneous genomic landscape of SCLC, the effects of mutations in patient tumors converge on a few critical pathways that drive malignancy. Specifically, alterations in epigenetic regulators lead to transcriptional dysregulation, pushing mutant cells toward a highly plastic state that makes them immune evasive and highly metastatic. This review will highlight studies showing how an imbalance of epigenetic regulators with opposing functions leads to the loss of immune recognition markers, effectively hiding tumor cells from the immune system. Additionally, we will discuss the role of epigenetic regulators in maintaining neuroendocrine features and how aberrant transcriptional control promotes epithelial-to-mesenchymal transition during tumor development. Although these pathways seem distinct, we emphasize that they often share common molecular drivers and mediators. Understanding the connection among frequently altered epigenetic regulators will provide valuable insights into the molecular mechanisms underlying SCLC development, potentially revealing preventive and therapeutic vulnerabilities for SCLC and other cancers with similar mutations.

• Quality Improvement in Health Care
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• v.30 no.1
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• pp.120-131
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• 2024

Purpose: This study aimed to evaluate the impact of implementing a clinical pathways (CPs) on the clinical outcomes and costs of patients undergoing breast cancer surgery. Methods: This retrospective cohort study included patients who were newly diagnosed with primary breast cancer at the Samsung Medical Center between 2014 and 2019 (N=8482; 2931 patients in the pre-path and 5551 patients in the post-path). Clinical outcomes included reoperation during hospitalization, readmission, and emergency room visits within 30 days of discharge. The cost data for each unit were obtained from an activity-based management accounting system. We performed an interrupted time series analysis. Results: The post-path period showed a significantly shorter hospital length of stay (LOS) than the pre-path period (6.3 days in pre-path vs. 5.0 days in post-path; -1.3 days' difference; p=.001), and fewer reoperations during hospitalization and within 30 days after discharge than the pre-path period. After adjusting for inflation rates and relative value scores, the model demonstrated savings of $146 per patient in the post-path for total costs, and $537 per patient for patient out-of-pocket costs (p=.001). Conclusion: CPs can help reduce costs without compromising the quality of care by reducing the number of reoperations, readmissions, and complications.

• Biomolecules & Therapeutics
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• v.23 no.1
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• pp.31-38
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• 2015

Histone acetylation plays a critical role in the regulation of transcription by altering the structure of chromatin, and it may influence the resistance of some tumor cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) by regulating the gene expression of components of the TRAIL signaling pathway. In this study, we investigated the effects and molecular mechanisms of trichostatin A (TSA), a histone deacetylase inhibitor, in sensitizing TRAIL-induced apoptosis in Caki human renal carcinoma cells. Our results indicate that nontoxic concentrations of TSA substantially enhance TRAIL-induced apoptosis compared with treatment with either agent alone. Cotreatment with TSA and TRAIL effectively induced cleavage of Bid and loss of mitochondrial membrane potential (MMP), which was associated with the activation of caspases (-3, -8, and -9) and degradation of poly (ADP-ribose) polymerase (PARP), contributing toward the sensitization to TRAIL. Combined treatment with TSA and TRAIL significantly reduced the levels of the cellular Fas-associated death domain (FADD)-like interleukin-$1{\beta}$-converting enzyme (FLICE) inhibitory protein (c-FLIP), whereas those of death receptor (DR) 4, DR5, and FADD remained unchanged. The synergistic effect of TAS and TRAIL was perfectly attenuated in c-$FLIP_L$-overexpressing Caki cells. Taken together, the present study demonstrates that down-regulation of c-FLIP contributes to TSA-facilitated TRAIL-induced apoptosis, amplifying the death receptor, as well as mitochondria-mediated apoptotic signaling pathways.

• Korean Journal of Adult Nursing
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• v.25 no.5
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• pp.527-538
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• 2013

Purpose: The purpose of this study was to develop a model that explains causal relationships between post-menopausal women's osteoporosis general knowledge and awareness of their own bone mass density(BMD) and their osteoporosis health beliefs and preventive behaviors. Methods: Retrospective design using structural equation model tested seven variables by using questionnaires of osteoporosis knowledge test, osteoporosis health belief scale, osteoporosis self-efficacy scale, and osteoporosis preventive behaviors scale. 162 middle age and post-menopausal women were recruited. Results: Mediating effect of health beliefs was not significant in the relationship between BMD awareness and preventive behaviors. Instead, BMD awareness had a direct influence on the preventive behaviors that is strong and significant. Between the relationship of the BMD awareness and health beliefs, direct pathways of perceived threat, relative benefits, and self-efficacy were not significant. However, relative benefits and self-efficacy showed direct influence on the preventive behaviors. Conclusion: Having middle age women get their BMD test done in order for them to be aware of their own BMD results might be a critical strategy to promote osteoporosis preventive behaviors. There is a need to develop diverse strategies to enhance their self-efficacy which has been shown to be important to osteoporosis preventive behaviors.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4405-4409
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• 2014

Reactive oxygen species (ROS), highly reactive molecules, are produced by living organisms as a result of normal cellular metabolism and environmental factors, and can damage nucleic acids and proteins, thereby altering their functions. The human body has several mechanisms to counteract oxidative stress by producing antioxidants. A shift in the balance between oxidants and antioxidants in favor of oxidants is termed as "oxidative stress". Paradoxically, there is a large body of research demonstrating the general effect of oxidative stress on signaling pathways, less is known about the initial and direct regulation of signaling molecules by ROS, or what we term the "oxidative interface." This review focuses on the molecular mechanisms through which ROS directly interact with critical signaling molecules to initiate signaling in a broad variety of cellular processes, such as proliferation and survival (MAP kinases and PI3 kinase), ROS homeostasis, and antioxidant gene regulation (Ref-1 and Nrf-2). This review also deals with classification as well as mechanisms of formation of free radicals, examining their beneficial and deleterious effects on cellular activities and focusing on the potential role of antioxidants in preventing and repairing damage caused by oxidative stress. A discussion of the role of phytochemical antioxidants in oxidative stress, disease and the epigenome is included.

• Proceedings of the Korean Vacuum Society Conference
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• 2016.02a
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• pp.102-102
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• 2016

Water, which is most abundant in Earth surface and very closely related to all forms of living organisms, has a simple molecular structure but exhibits very unique physical and chemical properties. Even though tremendous effort has been paid to understand this nature's core substance, there amazingly still lefts much room for scientist to explore its novel behaviors. Especially, as the scale goes down to nano-regime, water shows extraordinary properties that are not observable in bulk state. One of such interesting features is the formation of nanoscale bubbles showing unusual long-term stability. Nanobubbles can be spontaneously formed in water on hydrophobic surface or by decompression of gas-saturated liquid. In addition, the nanobubbles can be generated during electrochemical reaction at normal hydrogen electrode (NHE), which possibly distorts the standard reduction potential at NHE as the surface nanobubble screens the reaction with electrolyte solution. However, the real-time evolution of these nanobubbles has been hardly studied owing to the lack of proper imaging tools in liquid phase at nanoscale. Here we demonstrate, for the first time, that the behaviors of nanobubbles can be visualized by in situ transmission electron microscope (TEM), utilizing graphene as liquid cell membrane. The results indicate that there is a critical radius that determines the long-term stability of nanobubbles. In addition, we find two different pathways of nanobubble growth: i) Ostwald ripening of large and small nanobubbles and ii) coalescence of similar-sized nanobubbles. We also observe that the nucleation and growth of nanoparticles and the self-assembly of biomolecules are catalyzed at the nanobubble interface. Our finding is expected to provide a deeper insight to understand unusual chemical, biological and environmental phenomena where nanoscale gas-state is involved.