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.
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.
This study selected major drought events that occurred in the Jeonnam region from 1991 to 2023, examining both meteorological and hydrological drought occurrence mechanisms. The daily drought index was calculated using rainfall and dam storage as input data, and the drought propagation characteristics from meteorological drought to hydrological drought were analyzed. The characteristics of the 2022-23 drought, which recently occurred in the Jeonnam region and caused serious damage, were evaluated. Compared to historical droughts, the duration of the hydrological drought for 2022-2023 lasted 334 days, the second longest after 2017-2018, the drought severity was evaluated as the most severe at -1.76. As a result of a linked analysis of SPI (StandQardized Precipitation Index), and SRSI (Standardized Reservoir Storage Index), it is possible to suggest a proactive utilization for SPI(6) to respond to hydrological drought. Furthermore, by confirming the similarity between SRSI and SPI(12) in long-term drought monitoring, the applicability of SPI(12) to hydrological drought monitoring in ungauged basins was also confirmed. Through this study, it was confirmed that the long-term dryness that occurs during the summer rainy season can transition into a serious level of hydrological drought. Therefore, for preemptive drought response, it is necessary to use real-time monitoring results of various drought indices and understand the propagation phenomenon from meteorological-agricultural-hydrological drought to secure a sufficient drought response period.
Yi, Na-Hyun;Lee, Sang-Won;Lee, Seung-Jae;Kim, Jang-Ho Jay
Journal of the Korea Concrete Institute
/
v.25
no.5
/
pp.485-496
/
2013
In recent years, frequent terror or military attacks by explosion or impact accidents have occurred. Examplary case of these attacks were World Trade Center collapse and US Department of Defense Pentagon attack on Sept. 11 of 2001. These attacks of the civil infrastructure have induced numerous casualties and property damage, which raised public concerns and anxiety of potential terrorist attacks. However, a existing design procedure for civil infrastructures do not consider a protective design for extreme loading scenario. Also, the extreme loading researches of prestressed concrete (PSC) member, which widely used for nuclear containment vessel, gas tank, bridges, and tunnel, are insufficient due to experimental limitations of loading characteristics. To protect concrete structures against extreme loading such as explosion and impact with high strain rate, understanding of the effect, characteristic, and propagation mechanism of extreme loadings on structures is needed. Therefore, in this paper, to evaluate the impact resistance capacity and its protective performance of bi-directional unbonded prestressed concrete member, impact tests were carried out on $1400mm{\times}1000mm{\times}300mm$ for reinforced concrete (RC), prestressed concrete without rebar (PS), prestressed concrete with rebar (PSR, general PSC) specimens. According to test site conditions, impact tests were performed with 14 kN impactor with drop height of 10 m, 5 m, 4 m for preliminary tests and 3.5 m for main tests. Also, in this study, the procedure, layout, and measurement system of impact tests were established. The impact resistance capacity was measured using crack patterns, damage rates, measuring value such as displacement, acceleration, and residual structural strength. The results can be used as basic research references for related research areas, which include protective design and impact numerical simulation under impact loading.
Journal of the Korean Society of Food Science and Nutrition
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v.46
no.5
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pp.562-571
/
2017
In this study, we investigated the anti-oxidant activities [electron-donating ability (EDA), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging ability, and reactive oxygen species (ROS) inhibitory activity], anti-wrinkle activities [collagenase inhibitory activity, suppression and/or phosphorylation of matrix metalloproteinases (MMPs), and mitogen-activated protein (MAP) kinase activity], and mRNA expression levels using reverse transcription-polymerase chain reaction (RT-PCR) assay in ultraviolet (UV) B ray ($50mJ/cm^2$)-irradiated human keratinocyte HaCaT cells. Josaengheugchal, Sinneungheugchal (SE), Shintoheug rice, Heugjinju rice, and Heugseol (HE) among colored rice varieties were reported to have excellent antioxidant properties. In the EDA and ABTS radical scavenging assays, extracts of the five colored rice varieties had scavenging activities of 72% at concentrations higher $50{\mu}g/mL$. In the collagenase inhibition assay, ethanol extracts of the five colored rice varieties showed high inhibitory effects of about 60% at concentrations higher $25{\mu}g/mL$. In the ROS inhibition assay, ethanol extracts of HE and SE showed very excellent inhibition efficacies at all concentrations. We determined molecular biological mechanisms of MMPs (MMP-1, -3, -8, and -13) and mitogen-activated protein kinase (MAPK) with HE, and the results show that HE suppressed expression of MMPs and phosphorylation of MAPK and increased expression of pro-collagen type I in UVB-irradiated cells. It was also confirmed by RT-PCR that HE reduced expression of MMPs mRNA. Therefore, these results suggest that HE has anti-wrinkle and collagen production effects and may be used as a material in the development of functional food and cosmetic industries.
Kim, Kyeongnam;Kim, Chaeeun;Park, Jungeun;Yoo, Jinsung;Kim, Woosung;Jeon, Hwang-Ju;Kim, Jun-Ran;Lee, Sung-Eun
Korean Journal of Environmental Biology
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v.39
no.3
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pp.354-361
/
2021
Understanding the phytotoxic mechanism of methyl bromide (MB), an essential fumigant during the quarantine and pre-shipment process, is urgently needed to ensure its proper use and reduce international economic losses. In a previous study, two main MB-induced toxic mechanisms such as reactive oxygen species (ROS) and auxin distribution were selected by analyzing transcriptomic analysis. In the study, a 3-week-old A. thaliana was supplied with 1 mM ROS scavengers [N-acetyl-L-cysteine (NAC) or L-glutathione (GSH)] and 1µM indole-3-acetic acid(IAA) three times every 12 h, and visual and gene expression assessments were performed to evaluate the reduction in phytotoxicity by supplements. Phytotoxic effects on the MB-4h exposed group were decreased with GSH application compared to the other single supplements and a combination of supplements at 7 days post fumigation. Among these supplements, GSH at a concentration of 1, 2, and 5mM was suppled to A. thaliana with MB-fumigation. During a long-term observation of 2 weeks after the fumigation, 5 mM GSH application was the most effective in minimizing MB-induced phytotoxic effects with up-regulation of HSP70 expression and increase in main stem length. These results indicated that ROS was a main key factor of MB-induced phytotoxicity and that GSH can be used as a supplement to reduce the phytotoxicity of MB.
In recent years, greenhouse gas (GHG) reduction has become high priority issue in international aviation. GHG emissions from the aviation sector only accounts for approximately 2 percent of total GHG emissions in the world. However, as with GHG gases in other sectors, it has been pointed out as a contributing factor to global warming and there is an ongoing conversation in the aviation community to establish international framework for emissions reductions. In the case of international aviation, effects of aviation activities of a State go beyond the airports and airspace of that State. This makes compiling of GHG emissions data very difficult. There are also other legal and technical issues, namely the principle of “Common but Differentiated Responsibility (CBDR)” under the United Nations Framework Convention on Climate Change (UNFCCC) and “Fair Opportunity” principle of the Chicago Convention. For all these reason, it is expected that it will not be an easy job to establish an internationally agreed mechanism for reducing emissions in spite of continuing collaboration among States. UN adopted the UNFCCC in 1990 and the Kyoto Protocol in 1997 to impose common but differentiated responsibility on emissions reductions. In international aviation, ICAO has been taking the lead in measures for the aviation sector. In this role, ICAO held the High-level Meeting on International Aviation and Climate Change on 7 to 9 October 2009 at its Headquarters in Montreal and endorsed recommendations on reducing GHG from international aviation which will also be reported to the 15th Meeting of the Conference of the Parties (COP15). Key items include basic principle in global aviation emissions reduction: aspirational goals and implementation options: strategies and measures to achieve goals: means to measure and monitor the implementation; and financial and human resources. It is very likely that the Republic of Korea will be included among the Parties subject to mandatory limitation or reduction of GHG emissions after 2013. Therefore, it is necessary for Korea to thoroughly analyze ICAO measures to develop comprehensive measures for reducing aviation emissions and to take proactive actions to prepare for future discussions on critical issues after COP15.
This study attempts to analyze how and why Chosun Ilbo and Hankyoreh Shinmun produce particular social discourses about the media reform in different ways. In doing so, this paper attempts to disclose the ideological nature of media reform discourses in social contexts. For the purpose, a content analysis method was applied to the analysis of straight news, while an interpretive discourse analysis was appled to analyze both editorials and columns in newspapers. As a theoretical framework, an articulation theory was applied to explain the relationships among social forces, ideological elements, discourse practices and subjects to produce the media reform discourses. In doing so, I attempted to understand the overall conjuncture of the media reform aspects in social contexts. The period for the analysis was limited from January 10th to August 10th this year. Newspaper articles related to the media reform were obtained from the database of newspaper articles, "KINDS," produced by Korean Press Foundation, in searching the key word, "media reform". Total articles to be analyzed were 765, 429 from Hankyoreh Sinmun and 236 from Chosun Ilbo. The research results, first of all, empirically show that both Chosun Ilbo and Hankure Synmun used straight news for their firms' interests and value judgement, in selecting and excluding events related to media reform or in exaggerating and reducing the meanings of the events, although there are differences in a greater or less degree between two newspaper companies. Accordingly, this paper argues that the monopoly of newspaper subscriber by three major newspapers in Korean society could result in the forming of one-sided social consensus about various social issues through the distorting and unequal reporting by them. Second, this paper's discourse analysis related to the media reform indicates that the discourse of ideology confrontation between the right and the left produced by Chosen Ilbo functioned as a mechanism to realize law enforcement of the right in articulating the request of media reform and the anti-communist ideology. It resulted in the discursive effect of suppressing the request of media reform by civic groups and scholars and made many people to consider the media reform as a ideological matter in Korean society.
Persistent organic pollutants (POPs) can affect epigenetic mechanisms and obesity development. Polybrominated diphenyl ethers (PBDEs)-widely used to make flames-are one of the important POPs. Prenatal exposure to endocrine disrupting chemicals (EDCs), such as POPs, may affect global DNA methylation in long interspersed nuclear elements (LINE-1), increasing the risk of obesity later in life. Therefore, pregnant Sprague-Dawley (SD) rats were used to elucidate whether BDE-47 and BDE-209 transferred through placenta and breast milk cause epigenetic changes in LINE-1 and increase genetic susceptibility to obesity as obesogen during the developmental periods. Global DNA methylation in LINE-1 and gene expression related to obesity were measured in dams and offspring, using a methylation-sensitive high resolution melting analysis (MS-HRM) and direct bisulfite sequencing and quantitative real time polymerase chain reaction (qPCR), respectively. The results of MS-HRM showed global DNA hypomethylation patterns in LINE-1 of exposed offspring (2 of total 4) at PND 4, but bisulfite sequencing showed no difference in both the exposed and non-exposed groups. Gene expression in dams related to ${\beta}$-oxidation pathway and those related to adipokines showed different patterns between the two groups. On the contrary, gene expressions of offspring showed a similar pattern. Gene expressions related to ${\beta}$-oxidation pathway and obesity were significantly increased when compared with 'at birth', but not $PPAR-{\alpha}$. In conclusion, this study demonstrated the possibility that co-exposure to BDE-47 and BDE-209-via the placenta and breast milk-may affect epigenetic changes and modulate gene expression levels related to obesity.
Autophagy is a cellular process whereby cytosolic materials or organelles are taken up in a double-membrane vesicle structure known as an autophagosome and transported into a lysosome for degradation. Although autophagy has been studied at the genetic, cellular, or biochemical level, systematic ultrastructural quantitative analysis of autophagosomes during the autophagy process by using transmission electron microscopy (TEM) has not yet been reported. In this study, we performed ultrastructural analysis of autophagosomes in wild-type (WT) mouse embryonic fibroblasts (MEFs) and autophagy essential gene (atg5) knockout (KO) MEFs. First, we performed ultrastructural analysis of autophagosomes in WT MEFs compared to atg5 KO MEFs in basal autophagy or starvation-induced autophagy. Although we observed phagopore, early, late autophagosomes, or autolysosomes in WT MEFs, atg5 KO MEFs had immature autophagosomes that showed incomplete closure. Upon starvation, late autophagosomes accumulated in WT MEFs while the number of immature autophagosomes significantly increased in atg5 KO MEF indicating that atg5 plays an important role in the maturation of autophagosomes. Next, we examined autophagosomes in the cell model expressing polyQ-expanded N-terminal fragment of huntingtin. Our TEM analysis indicates that the number of late autophagosomes was significantly increased in the cells expressing the mutant huntingtin, indicating that improving the fusion of autophagosome with lysosome may be effective to enhance autophagy for the treatment of Huntington's disease. Taken together, the results of our study indicate that ultrastructural and quantitative analysis of autophagosomes using TEM can be applied to various human cellular disease models, and that they will provide an important insight for cellular pathogenesis of human diseases associated with autophagy.
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