• Journal of Life Science
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• v.19 no.8
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• pp.1023-1032
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• 2009

Despite the fact that many cancer cells are sensitive to TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis, some cancer cells show either partial or complete resistance to TRAIL. Human leukemic K562 and CEM cells also show resistance to TRAIL-induced apoptosis. Novel molecular target and treatment strategies are required to overcome TRAIL resistance of human leukemia cells. Therefore, the purpose of this study was to target key anti-apoptotic molecules deciding TRAIL resistance for sensitization of TRAIL-resistant K562 and CEM cells, and to evaluate the effect of quercetin as a TRAIL sensitizer on these TRAIL-resistant cells. We found that quercetin acted in synergy with TRAIL to enhance TRAIL-induced apoptosis in K562 cells by inhibition of the DNA-PK/Akt signaling pathway, which leads to enhancement of TRAIL-mediated activation of caspases and concurrent cleavage of PARP and up-regulation of Bax. The findings suggest that the DNA-PK/Akt signaling pathway plays an essential role in regulating cells to escape from TRAIL-induced apoptosis, and quercetin could act in synergy with TRAIL to increase apoptosis by inhibition of the DNA-PK/Akt signaling pathway, which overcomes TRAIL-resistance of K562 and CEM cells. This study suggests that DNA-PK might interfere with TRAIL-induced apoptosis in human leukemic cells through activation of the Akt signaling pathway.

• Journal of Digital Convergence
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• v.15 no.7
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• pp.139-146
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• 2017

This study was an attempt to review of tuberculosis control projects supported by(Official Development Assistance: ODA) and to describe the meaning of the influencing factors. Also, the study aims to determine the exit strategies of donor countries to sustain these projects. The research was conducted reviewing of tuberculosis-related reports and documents, and understood the tuberculosis control projects in Philippines. There were 14 people who participated, and explored the sustainability limits using in-depth interviewing and observation method. Data from interviews and participant observations were analyzed to the phenomenological method by Colaizzi(1978). A total 4 categories were grouped on the final. The finding shows factors that affect the sustainability of these tuberculosis control projects within Philippines supported by ODA have been divided and explained as follow; "limit of workforce", "limit of finance", "limit of facility and equipment", "limit of participation". To sustain these projects, the following alternative plans have been exemplified; "strengthening professionalism", "strengthening education and public relations", "activated strategy for community involvement", "matching funds for financing". Furthermore, the study of integrated tuberculosis control projects will be needed.

• Journal of Genetic Medicine
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• v.4 no.1
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• pp.22-37
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• 2007

The autosomal dominant spinocerebellar ataxias (SCAs) are a group of neurodegenerative diseases, clinically and genetically heterogeneous, characterized by degeneration of spinocerebellar pathways with variable involvement of other neural systems. At present, 27 distinct genetic forms of SCAs are known: SCA1-8, SCA10-21, SCA23, SCA25-28, DRPLA (dentatorubral-pallidoluysian atrophy), and 16q-liked ADCA (autosomal dominant cerebellar ataxia). Epidemiological data about the prevalence of SCAs are restricted to a few studies of isolated geographical regions, and most do not reflect the real occurrence of the disease. In general a prevalence of about 0.3-2 cases per 100,000 people is assumed. As SCA are highly heterogeneous, the prevalence of specific subtypes varies between different ethnic and continental populations. Most recent data suggest that SCA3 is the commonest subtype worldwide; SCA1, SCA2, SCA6, SCA7, and SCA8 have a prevalence of over 2%, and the remaining SCAs are thought to be rare (prevalence <1%). In this review, we highlight and discuss the SCA7. The hallmark of SCA7 is the association of hereditary ataxia and visual loss caused by pigmentary macular degeneration. Visual failure is progressive, bilateral and symmetrical, and leads irreversibly to blindness. This association represents a distinct disease entity classified as autosomal dominant cerebellar ataxia (ADCA) type II by Harding. The disease affectsprimarily the cerebellum and the retina by the moderate to severe neuronal loss and gliosis, but also many other central nervous system structures as the disease progresses. SCA7 is caused by expansion of an unstable trinucleotide CAG repeat in the ATXN7 gene encoding a polyglutamine (polyQ) tract in the corresponding protein, ataxin-7. Normal ATXN7 alleles contain 4-35 CAG repeats, whereas pathological alleles contain from 36->450 CAG repeats. Immunoblott analysis demonstrated that ataxin-7 is widely expressed but that expression levels vary among tissues. Instability of expanded repeats is more pronounced in SCA7 than in other SCA subtypes and can cause substantial lowering of age at onset in successive generations termed ‘anticipation’ so that children may become diseased even before their parents develop symptoms. The strong anticipation in SCA7 and the rarity of contractions should have led to its extinction within a few generations. There is no specific drug therapy for this neurodegenerative disorder. Currently, therapy remains purely symptomatic. Cellular models and SCA7 transgenic mice have been generated which constitute valuable resources for studying the disease mechanism. Understanding the pathogenetic mechanisms of neurodegeneration in SCAs should lead to the identification of potential therapeutic targets and ultimately facilitate drug discovery. Here we summarize the clinical, pathological, and genetic aspects of SCA7, and review the current understanding of the pathogenesis of this disorder. Further, we also review the potential therapeutic strategies that are currently being explored in polyglutamine diseases.

• Korean Journal of Applied Biomechanics
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• v.29 no.3
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• pp.157-166
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• 2019

Objective: This study examined the effects of stimulating fingertip temperature on the patterns of force sharing and stability properties during multi-finger force production tasks. Method: 9 adult subjects (male: 3, female: 6, age: $26.11{\pm}4.01yrs$, height: $169.22{\pm}5.97cm$, weight: $61.44{\pm}11.27kg$) participated in this study. The experiment consisted of three blocks: 1) maximal voluntary contraction (MVC) task, 2) single-finger ramp task to quantify enslaving (i.e., unintended force production by non-task fingers), and 3) 12 trials of multi-finger steady-state force production task at 20% MVC. There were three temperature conditions including body-temperature (i.e., control condition), $40^{\circ}C$, and $43^{\circ}C$, and the stimulation was given to the index finger only for all experimental conditions. Results: There were no significant differences in the MVC forces, enslaving, and the accuracy of performance during the steady-state task between the conditions. However, the share of stimulated index finger force increased with the index fingertip temperature, while the share of middle finger force decreased. Also, the coefficient of variation of both index and middle finger forces over repetitive trials increased with the index fingertip temperature. Under the framework of the uncontrolled manifold (UCM) hypothesis used to quantify indices of multi-finger synergies (i.e., stability property) stabilizing total force during the steady-state task, the two variance components within the UCM analysis increased together with the fingertip temperature, while no changes in the synergy indices between the conditions. Conclusion: The current results showed that fingertip temperature stimulation only to index finger does not affect to muscle force production capability of multi-finger, independence of individual fingers, and force production accuracy by the involvement of all four fingers. The effect of fingertip temperature on the sharing pattern and force variation may be due to diffuse reflex effects of the induced afferent activity on alpha-motoneuronal pools. However, the unchanged stability properties may be the reflection of the active error compensation strategies by non-stimulated finger actions.

• Journal of The Korean Association For Science Education
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• v.42 no.2
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• pp.253-264
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• 2022

The purpose of this study is to examine the practice of scientists from the perspective of Ian Hacking's 'creation of phenomena'. Scientific phenomena, according to Hacking, are regular and do not exist in nature without the intervention of scientists or experimental tools. This study tries to derive scientific educational meaning by analyzing the thoughts and episodes of the 'Sontanda (inter-individual variability)' phenomenon experienced by four life scientists. The Sontanda phenomenon is a common term used by scientists to describe phenomena in which findings do not appear consistently even when studies are carried out using the same experimental procedure and materials. The following four educational implications were discovered as a result of the research. First, we confirmed the importance of embodied knowledge, or non-verbal knowledge, which solves issues by making appropriate judgments and reactions at all times, rather than simply becoming accustomed to the experimental method. This argues that propositional knowledge and non-verbal knowledge should be handled equally in order to provide students with a practical scientific inquiry. Second, we tried to reconsider the picture of the experiment. The phenomenon revealed in the interviews of scientists is rare, and it takes a long time to stabilize the phenomenon. On the other hand, the image of school experiments is always positive and consistent, necessitating a shift in perspective. Third, the precise meaning of scientific practice could be confirmed. This study confirms that scientists use their knowledge effectively in line with the circumstances, and we examined strategies to apply scientific practice to school instruction based on this. Finally, by provoking uncertainty, the Sontanda phenomena may give students with an opportunity to engage in meaningful scientific involvement. By breaking away from the cookbook experiment, this study expects school experimental education to help in efforts to experience scientific practice.

• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.73-81
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• 2023

Sirtuins (SIRTs) belong to the nicotinamide adenine dinucleotide (NAD+)-dependent class III histone deacetylase family. They are key regulators of cellular and physiological processes, such as cell survival, senescence, differentiation, DNA damage and stress response, cellular metabolism, and aging. SIRTs also influence carcinogenesis, making them potential targets for anticancer therapeutic strategies. In this study, we investigated the anticancer properties and underlying molecular mechanisms of a novel SIRT1 inhibitor, MHY2251, in human colorectal cancer (CRC) cells. MHY2251 reduced the viability of various human CRC cell lines, especially those with wild-type TP53. MHY2251 inhibited SIRT1 activity and SIRT1/2 protein expression, while promoting p53 acetylation, which is a target of SIRT1 in HCT116 cells. MHY2251 treatment triggered apoptosis in HCT116 cells. It increased the percentage of late apoptotic cells and the sub-G1 fraction (as detected by flow cytometric analysis) and induced DNA fragmentation. In addition, MHY2251 upregulated the expression of FasL and Fas, altered the ratio of Bax/Bcl-2, downregulated the levels of pro-caspase-8, -9, and -3 proteins, and induced subsequent poly(ADP-ribose) polymerase cleavage. The induction of apoptosis by MHY2251 was related to the activation of the caspase cascade, which was significantly attenuated by pre-treatment with Z-VAD-FMK, a pan-caspase inhibitor. Furthermore, MHY2251 stimulated the phosphorylation of c-Jun N-terminal kinase (JNK), and MHY2251-triggered apoptosis was blocked by pre-treatment with SP600125, a JNK inhibitor. This finding indicated the specific involvement of JNK in MHY2251-induced apoptosis. MHY2251 shows considerable potential as a therapeutic agent for targeting human CRC via the inhibition of SIRT1 and activation of JNK/p53 pathway.

• Journal of Music and Human Behavior
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• v.20 no.1
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• pp.99-115
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• 2023

Given the ongoing discussion regarding remote music therapy following the COVID-19 pandemic and the pivotal role of parental involvement in it, this study investigated parents' perceptions on their roles in a synchronous videoconferencing music therapy for their children with developmental disabilities. A total of 32 participants participated in an online survey comprising 68 questions. Descriptive statistics summarized the collected responses, and Pearson's correlation was conducted to examine the relationship between perceived parental roles, psychological burden, and willingness to participate in future remote music therapy. The findings showed that parents of children with developmental disabilities acknowledged the benefits of tele-music therapy and possessed substantial information about its implementation. Furthermore, they reported their roles of providing physical, participatory, and mediating support. As parents exhibited greater satisfaction with their role in supporting their children's participation or managing their off-task behaviors, they perceived reduced psychological burden. These findings hold significant implications for expansion of tele-music therapy strategies to address the unique needs of children with developmental disabilities and support their parents as immediate mediators for their children.

• The Journal of the Convergence on Culture Technology
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• v.9 no.1
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• pp.777-786
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• 2023

Generative AI systems are expected to be more widely utilized. However, relatively little attention has been paid to understanding how users perceive and accept generative AI results. To identify strategies for increasing the future use of generative AI and prepare for potential issues, we organized design workshop for the general user group and the designer group. They created artwork utilizing Novel AI and semi-structured interview was followed to evaluate their attitudes toward generative AI and its copyright. Results indicate that the general public views generative AI positively, while the design-related group views it quite negatively. The participants expressed concerns as to the misuse the system, specifically related to copyright issues. People who are likely to utilize generative AI outcomes have insisted more strongly that copyrights should be their own. Those working in the design field highly evaluated the possibility of using generative AI in their work. Copyright perceptions were not significantly influenced by users' satisfaction or their level of involvement in the creation process. We discuss design implications for interfaces using generative AI based on the findings.

• Asia Marketing Journal
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• v.10 no.2
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• pp.71-98
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• 2008

Considerably many numbers of studies on country-of-origin(hereafter COO) effects have been presented in international business and marketing areas. Recent studies have been included the effects of COO of manufacture, parts, and design, as well as the effects of brand origin, reflected by the accelerating convergent manufacture circumstances and increasingly competitive environments. Moderating constructs such as knowledge of product category and involvement as individual variables, have been also introduced and researched in various angles. In addition, how the effects of COO occur as processes is also argued in previous studies. This research has attempted to explain business corporation's strategic decisions on choosing a domain of its product manufacturing for several critical reasons, for cost reduction or better image. We displayed two constructs of brand and manufacture in a positive and negative country image group to reconfirm the existence of the effects of COO. Additionally, the effects of respondents' regulatory fit between their motivational focus and the contents of product messages, have been declared. Furthermore the respondents' motivational focus moderates the main effect of COO on product evaluations in a positive 'made-in' combination, while, surprisingly, it does not statistically moderate in a negative, except attitude. Based on the results, implications and suggestions on how to plan and execute more effective marketing strategies regarding COO dimensions, especially COO of manufacture, are separately presented for each situations when it has already been determined and when it is to be.

• Journal of Life Science
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• v.34 no.4
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• pp.279-285
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• 2024

The zonula occludens (ZO) protein serves as a scaffolding protein, providing structural support at the junctions between cells and the cytoplasmic surface. It acts as a bridge between integral membrane proteins and the cytoskeleton. Besides its structural role, it also participates in regulating cell growth and proliferation. Recent studies have highlighted the involvement of ZO protein in various diseases, including cancer. Specifically, research has indicated that ZO protein influences the cancer microenvironment surrounding cancer cells, thereby facilitating their growth and development. ZO proteins exert diverse functions in the cancer microenvironment, impacting processes such as angiogenesis, inflammatory responses, the epithelial-mesenchymal transition, and interactions with mesenchymal stem cells. The specific mechanisms vary depending on the type of cancer and environmental conditions. Recent research unveiled several signaling pathways involving ZO protein, which could potentially impede cancer progression in the tumor microenvironment. Consequently, these insights open avenues for novel treatment strategies. While the numerous physiological, structural, and morphological roles of ZO protein have been observed at the cellular and in vivo levels, understanding the signaling mechanisms it operates in vivo and how these mechanisms influence the cancer microenvironment remains a challenge. In this review, we delineate the characteristics and regulatory mechanisms of ZO protein in the context of the cancer microenvironment. Additionally, we propose leveraging the properties of ZO protein to devise defense mechanisms within the cancer cell environment and provide an overview of its in vivo role.