• Journal of Life Science
• /
• v.27 no.2
• /
• pp.149-154
• /
• 2017

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-hodgkin lymphoma. Advances in the chemotherapeutic treatment of this disease have improved the outcomes of DLBCL; nonetheless, many patients still die of DLBCL, and therefore, a better understanding of this disease and identification of novel therapeutic targets are urgently required. In a recent gene expression profiling study, PDE (phosphodiesterase) 4B was found to be overexpressed in chemotherapy-resistant tumors. The major function of PDE4B is to inactivate the second messenger cyclic 3',5' monophosphate (cAMP) by catalyzing the hydrolysis of cAMP to 5'AMP. It is known that cAMP induces cell cycle arrest and/or apoptosis in B cells, and PDE4B abolishes cAMP's effect on B cells. However, the mechanism by which PDE4B is overexpressed remains unclear. Here, we show that the aberrant expression of miRNA may be associated with the overexpression of this gene. The PDE4B 3' untranslated region (UTR) has three functional binding sites of miR-23b, as confirmed by luciferase reporter assays. Interestingly, miR-23b-binding sites were evolutionarily conserved from humans to lizards, implying the critical role of PDE4B-miR-23b interaction in cellular physiology. The ectopic expression of miR-2 3b repressed PDE4B mRNA levels and enhanced intracellular cAMP concentrations. Additionally, miR-23b expression inhibited cell proliferation and survival of DLBCL cells only in the presence of forskolin, an activator of adenylyl cyclase, suggesting that miR-23b's effect is via the downregulation of PDE4B. These results together suggest that miR-23b could be a therapeutic target for overcoming drug resistance by repressing PDE4B in DLBCL.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.27 no.5
• /
• pp.373-384
• /
• 2001

Cellular proliferation is an intricately regulated process mediated by the coordinated interactions of critical growth control genes. Two of these factors in mammalian cells are the p53 and mdm-2 genes. A protein product of the mem-2 oncogene has been recently shown to associate with the protein encoded by the tumor suppressor gene p53. The p53 tumor suppressor protein is stabilized in response to DNA damage and other stress signals and causes the cell to undergo growth arrest or apoptosis, thus preventing the establishment of mutations in future cellular generations. Mutation or loss of p53 is a very common event in tumor progression. It occurs in about 50% of all tumors analysed including of colon, lung, breast and liver. The cellular mdm-2 gene, which has potential transforming activity that can be activated by overexpression, is amplified in a significant percentage of human sarcoma and in other mammalian tumors. Proteins encoded by the mdm-2 gene are able to bind to the p53 protein and, when overexpressed, can inhibit p53's transcriptional activation function, thus mdm-2 can act as a negative regulator of p53 function. Experimental study was performed to observe the relationship between p53 gene mutation and mdm-2 protein expression and apply the results to the clinical activity. 36 golden syrian hamster each weighing $60{\sim}80g$ were used and painted with 0.5% DMBA by 3 times weekly on the right buccal cheek(experimental side) for 6, 8, 10, 12, 14 and 16 weeks. Left buccal cheek(control side) was treated with mineral oil as the same manner to the right side. The hamsters were sacrificed on the 6, 8, 10, 12, 14 & 16 weeks. Normal and tumor tissues from paraffin block were examined for histology and immunohistochemistry observation, and were completely dissected by microdissection and DNA from both tissue were isolated by proteins K/phenol/chloroform extraction. Segments of the hamster p53 exons 5, 6, 7 and 8 were amplified by PCR using the oligonucleotide primers, and then confirmational change was observed by SSCP respectively. The results were as follows : 1. Dysplasia at 6 weeks, carcinoma in situ at 8 weeks and invasive carcinoma from 10 weeks could be observed in experimental groups. 2. p53 mutations were detected in 10 of the 36(28%) and the exons 6(6 of the 10 : 60%) was the most hot spot area among the highy conserved region(exons 5, 6, 7 & 8). 3. Immunohistochemical study confirmed 22 of the 36(61%) of p53 expression involving 10 of p53 mutations. 4. mdm-2 expression of was showed in 3 of the 36(8%) involving 1 of the 22 of p53 expression and 2 of the 14 of p53 non-expression. From the above results, mutation of p53 gene or expression of p53 protein may have the influence of the DMBA induced carcinoma of hamster buccal pouch but the expression of mdm-2 protein may not have relationship with tumorigenesis.

• Journal of the Korean Institute of Landscape Architecture
• /
• v.44 no.6
• /
• pp.98-106
• /
• 2016

This paper has attempted to reexamine current international circumstance and the meaning of regionality and discover the practical design strategy in the process of observing the trend of contemporary landscape architecture from the perspective of regionality. Contemporary landscape architecture has started to discover possibility in the local value and create identity. This tendency can be classified as follows: First, regionality is re-examined as a medium which can integrate nature, culture and city. As a concept which contains time and spatial continuity, landscape is a matter of the identity of land and area. Second, regionality has been reinterpreted and recreated by designers. Landscape designers attempt to restore the past memories and traces instead of adding a new concept after erasing previous physical features. This design attitude has spatialized time continuity. Third, site is seen as a palimpsest, not tabula rasa in contemporary landscape architecture. It has been attempted to visually materialize the natural and ecological processes and spatial features. Fourth, site is approached in a tectonic approach instead of analytical approach. It is attempted to organize and restore the geological and archeological memories and ecological processes. Differentiation has emerged as a critical design strategy in contemporary landscape architecture. However, regionality is also formed through an interaction with continuity as well as through differentiation. In this sense, the following possibilities can be reviewed as practical design strategies to realize regionality: First, a terra-tectonic approach discovers and selects possibility in the site and expresses the site, creating practical possibility which strengthens regionality. If the memory and conditions of the site are different, the identity would different as well. Second, continuity of region itself is a gene pool with comparative advantage. As a rough sketch of design, it acts as a loose conformity on designers' experience and practice. Of course, this approach is not absolute with some limitations. It is necessary to explore practical strategies.

• Tuberculosis and Respiratory Diseases
• /
• v.63 no.2
• /
• pp.128-138
• /
• 2007

Backgrounds: Mutations of katG and inhA (ORF and promoter) are known to be related to isoniazid (INH) resistance of Mycobacterium tuberculosis. Because reports on these mutations in Korean isolates are limited (i.e. only the frequency of katG codon 463 was evaluated.), we tried to know the kinds of mutations of two genes and their frequencies in INH resistant Korean M. tuberculosis strains. Methods: PCR was performed to amplify katG (2,223 bp), inhA ORF (-77~897, 975 bp), and inhA promoter (-168~80, 248 bp) from 29 multidrug resistant M. tuberculosis (MDR-TB) DNAs prepared by bead beater-phenol method. Their sequences were determined and analyzed by ABI PRISM 3730 XL Analyzer and MegAlign package program, respectively. Results: All of the isolates had more than one mutation in katG or inhA gene. Twenty seven (93%) of 29 tested strains had katG mutations, which suggests that katG is a critical gene determining INH resistance of M. tuberculosis. Amino acid substitutions, such as Arg463Leu and Ser315Thr, due to point mutations of the katG were the most frequent (62.1% and 55.2%) mutations. In addition, deletion of the katG gene was frequently observed (17.2%). Analyzed Korean MDR-TB isolates also had variable inhA mutations. Point mutation of inhA promoter region, such as -15 ($C{\rightarrow}T$) was frequently found. Substitution of amino acid (Lsy8Asn) due to point mutation ($AAA{\rightarrow}AAC$) of inhA ORF was found in 1 isolate. Interestingly, 14 point mutated types that were not previously reported were newly found. While four types resulted in amino acid change, the others were silent mutations. Conclusions: Although it is not clear that the relationship of these newly found mutations with INH resistance, they show marked diversity in Korean MDR-TB strains. It also suggests their feasibility as a molecular target to supplement determining the INH resistance of clinical isolates because of the possible existence of low-level INH resistant strains.

• Journal of Korean Philosophical Society
• /
• v.145
• /
• pp.271-296
• /
• 2018

In this article, I intend to reveal critically both the intrinsic crux and main problems of the politics of hostile exclusion based on the effect of labeling which was designed precisely as an impure political technique and has been operated for too long in Korean society by the conservative ruling class that centered on various negative ideological labels like 'pro-North Korean leftist forces.' Firstly, what is called the 'conservative ruling class' in Korean society is in itself an antinationalistic and antidemocratic pro-Japanese dictatorship group. Secondly, the conservative ruling class as a pro-Japanese dictatorship group has utilized politically the labeling effect which regards antigovernment Korean members as pro-North Korean or rebellious persons. This group's hostile politics, based on the ideological labelling effect, deprives antigovernment persons and groups of the qualification of Korean citizenship, in order to hold and retain their supreme power in Korean society. Thirdly, the conservative ruling class has attempted to stigmatize the citizens who participate in a movement for democracy as a pro-North Korean leftist force, but such a politically impure manner is typically completely unjustified groundless labeling. Fourthly, the attempt to define the conservative ruling class as a pro-Japanese dictatorship force is normatively justified and resonably appraised insofar as such a definition has been proved to be worthy of confidence. Finally, the trial to consider Roh's regime and pro-Roh (pro-Moon) groups as a kind of Yeongnam hegemonism by several critical intellectuals and current politicians from Honam region is not only merely a groundless and unconvincing labelling, but also the failed outcome of the attempt to systemize logically their emotional antipathy and repulsion toward Roh and pro-Roh (pro-Moon) groups.

• Korean Journal of Heritage: History & Science
• /
• v.47 no.2
• /
• pp.114-131
• /
• 2014

The Portrait of Yang Zhuxi(楊竹西小像) at the Palace Museum in Beijing holds important significance as one of the rare portraits from Yuan Period and as a painting with a definite year of creation in 1363. It is also noteworthy in that it is the only remaining work of Wang Yi(王繹), who was one of the critical portrait painters during the second half of Yuan Period and the author of Xiexiang Mijue(寫像秘訣), the first book on the portrait theories, that it was created in conjunction with Ni Zan(倪瓚), one of the utmost landscape painters of the times, and that it was an early case of landscape and figure painting-format portraits. The figure in Portrait of Yang Zhuxi was originally known as Yang Wu(楊瑀), a high official during Yuan Period, but it was a misunderstanding on the part of Li Rihua(李日華), a literary figure from Ming Dynasty. The actual model was Yang Qian(楊謙), a reclusive literary figure in the Songjiang(松江) region. Yang Qian is estimated as one of the central figures with a high reputation in the literary community of Jiangnan those days. Portrait of Yang Zhuxi was depicted by borrowing the icon of such hermits as Su Shih(蘇軾), which seems like a proper choice to express Yang Zhuxi, a reclusive literary figure. Furthermore, the rocks and pine trees described by Ni Zan reinforced the significance of the portrait through their traditional symbolism of man of virtue and man of letters, respectively. Portrait of Yang Zhuxi used the Baimiao Manner(白描法), thus being differentiated from other portraits from the same period. Even though there is no coloring in the painting, it boasts more excellent realism than colored portraits. It expressed the body with the graceful and controlled Li Gonglin(李公麟) and Zhao Mengfu(趙孟?) style Baimiao Manner, raising its dignity further. In terms of functions, Portrait of Yang Zhuxi is strongly characterized by the appreciative function unlike other portraits focused on the ceremonial function. Being created to be viewed and appreciated by the model himself and his friends, the portrait was very significant to promote their friendship. However, there was a great intention to reflect the emotions of the model himself and his friends in the painting beyond the simple appreciation level.

• Journal of Life Science
• /
• v.29 no.1
• /
• pp.9-17
• /
• 2019

As tumors develop, they encounter microenvironmental stress, such as hypoxia and glucose depletion, due to poor vascular function, thereby leading to necrosis, which is observed in solid tumors. Necrotic cells are known to release cellular cytoplasmic contents, such as high mobility group box 1 (HMGB1), into the extracellular space. The release of HMGB1, a proinflammatory and tumor-promoting cytokine, plays an important role in promoting inflammation and metabolism during tumor development. Recently, HMGB1 was shown to induce the epithelial-mesenchymal transition (EMT) and metastasis. However, the underlying mechanism of the HMGB1-induced EMT, invasion, and metastasis is unclear. In this study, we showed that noninvasive breast cancer cells MCF-7 formed tightly packed, rounded spheroids and that the cells in the inner regions of a multicellular tumor spheroid (MTS), an in vitro model of a solid tumor, led to necrosis due to an insufficient supply of O2 and glucose. In addition, after 7 d of MTS culture, the EMT was induced via the transcription factor Snail. We also showed that HMGB1 receptors, including RAGE, TLR2, and TLR4, were induced by MTS culture. RAGE, TLR2, and TLR4 shRNA inhibited MTS growth, supporting the idea that RAGE/TLR2/TLR4 play critical roles in MTS growth. They also prevented MTS culture-induced Snail expression, pointing to RAGE/TLR2/TLR4-dependent Snail expression. RAGE, TLR2, and TLR4 shRNA suppressed the MTS-induced EMT. In human cancer tissues, high levels of RAGE, TLR2, and TLR4 were detected. These findings demonstrated that the HMGB-RAGE/TLR2/TLR4-Snail axis played a crucial role in the growth of the MTS and MTS culture-induced EMT.

• Asian-Australasian Journal of Animal Sciences
• /
• v.32 no.7
• /
• pp.922-929
• /
• 2019

Objective: Mutations in low-density lipoprotein receptor (LDLR), which encodes a critical protein for cholesterol homeostasis and lipid metabolism in mammals, are involved in cardiometabolic diseases, such as familial hypercholesterolemia in pigs. Whereas microRNAs (miRNAs) can control LDLR regulation, their involvement in circulating cholesterol and lipid levels with respect to cardiometabolic diseases in pigs is unclear. We aimed to identify and analyze LDLR as a potential target gene of SSC-miR-20a. Methods: Bioinformatic analysis predicted that porcine LDLR is a target of SSC-miR-20a. Wild-type and mutant LDLR 3'-untranslated region (UTR) fragments were generated by polymerase chain reaction (PCR) and cloned into the pGL3-Control vector to construct pGL3 Control LDLR wild-3'-UTR and pGL3 Control LDLR mutant-3'-UTR recombinant plasmids, respectively. An miR-20a expression plasmid was constructed by inserting the porcine premiR-20a-coding sequence between the HindIII and BamHI sites in pMR-mCherry, and constructs were confirmed by sequencing. HEK293T cells were co-transfected with the miR-20a expression or pMR-mCherry control plasmids and constructs harboring the corresponding 3'-UTR, and relative luciferase activity was determined. The relative expression levels of miR-20a and LDLR mRNA and their correlation in terms of expression levels in porcine liver tissue were analyzed using reverse-transcription quantitative PCR. Results: Gel electrophoresis and sequencing showed that target gene fragments were successfully cloned, and the three recombinant vectors were successfully constructed. Compared to pMR-mCherry, the miR-20a expression vector significantly inhibited wild-type LDLR3'-UTR-driven (p<0.01), but not mutant LDLR-3'-UTR-driven (p>0.05), luciferase reporter activity. Further, miR-20a and LDLR were expressed at relatively high levels in porcine liver tissues. Pearson correlation analysis revealed that porcine liver miR-20a and LDLR levels were significantly negatively correlated (r = -0.656, p<0.05). Conclusion: LDLR is a potential target of miR-20a, which might directly bind the LDLR 3'-UTR to post-transcriptionally inhibit expression. These results have implications in understanding the pathogenesis and progression of porcine cardiovascular diseases.

• Journal of the Daesoon Academy of Sciences
• /
• v.40
• /
• pp.243-272
• /
• 2022

Jeongeup, Jeollabuk-do, is an area that requires attention from those who study the history of Korean thought. In addition, Jeongeup is an area wherein many works were recorded for the first time in literary history. This is the case with Jeongeupsa as a style of Baekje songs and the lyrics of the noble families of the Joseon Dynasty, Sangchungok. Jeongeup is likewise the location where Choi Chi-won (857~?) was selected to serve as a local taesu (viceroy) and where a unique tradition of music and style were passed down. In this paper, the relationship between Choi Chi-won's role in the process of establishing a silent Confucian academy in Jeongeup and the emergence of scholar culture was examined. When Choi Chi-won left after his term in office, a birth shrine called Taesansa Temple was built to repay the selection of the villagers, and it became the source that led to the opening of the Confucian academy Museongseowon in the future. Jeongeup will be shown to be the location where Choi Chi-won realized his aspirations and honed his capabilities. In particular, Choi Chi-won's played a crucial role in the mid-Joseon Dynasty by supporting the construction and securing the name of Museongseowon. That is why Choi Chi-won was able to be revived as a symbolic figure in the region. In addition, it can be seen that the shape of Choi Chi-won was more sedentary- in the form of a Confucian scholar- and Confucian scholars emphasized the transfer of portraits at Museongseowon. Through the poetry written by Choi Chi-won, readers can learn about the worries and perceptions of scholars during those times. Although his value in the field of poetry is diverse, he can especially be recognized as a Confucian intellectual. In a large number of his works, he expresses his anxiety, agony, and critical inner consciousness all of which came from his encounter with the realities of his time. In fact, Choi Chi-won showed his qualities as a prominent literary figure of his time who had extraordinary aspirations and an admirable work ethic. However, he failed to overcome his regional and mental alienation as a poet in neighboring countries. Therefore, he internalized a sort of fierceness in terms of his perception of the world. However, it seems that it was rather a factor that made his work exhibit a strong lyrical style. In addition, Choi Chi-won's collection of writings includes a number of works that strongly criticized various forms of pathological phenomena caused by terminal phenomena of the time. He also highlighted the wrong in society by realistically depicting the lives poor and needy people and their eventual sacrifice via distorted relationships. This can be read encapsulating the agony of intellectuals of that time. The dictionary definition of a 'Confucian scholar' is "a Confucian term referring to a person or class that embodies Confucian ideology," and in its contemporary meaning it suggests " ⋯ an example of a personality, but not an identity, and the conscience of one's time period as a source of human morality inwardly and social order outwardly." In this respect, it could even be said that Choi Chi-won could be considered the originator of scholar culture.

• Economic and Environmental Geology
• /
• v.55 no.1
• /
• pp.77-95
• /
• 2022

The Gonamsan gabbroic complex in the Pocheon area, northwestern region of South Korea consists of a variety types of gabbroic rocks and associated Fe-Ti oxide deposits caused by magmatic differentiation. Post-magmatic intrusions (i.e., gabbroic pegmatite and pyroxene-apatite-zircon rocks) partly intruded into the gabbroic rocks. The gabbroic pegmatite occurs in monzodiorite and oxide gabbro of the complex, intimately and spatially associated with high-grade lenticular Fe-Ti oxide mineralization. The pegmatite can be subdivided into plagioclase-amphibole and pyroxene-olivine pegmatite, in which the contact surface is sharp. The plagioclase-amphibole pegmatite comprises plagioclase and amphibole, with lesser amount of pyroxene, ilmenite, sphene, apatite, and biotite. The pegmatite shows plagioclase-amphibole intergranular texture, in which the open space formed by large plagioclase laths (An_2-26Ab_72-98Or_0-2) are infilled by amphibole. The pyroxene-olivine pegmatite is dark gray to black in color and also contains magnetite, ilmenite, spinel, apatite, and calcite as a minor component. The pyroxene (En_35-36Fs_8-9Wo₅₅) and olivine (Fo_84-85Fa_15-16) partly show a poikilitic texture defined by smaller euhedral olivine enclosed by coarser clinopyroxene. Fe-Ti oxide minerals consist mainly of magnetite and ilmenite that are found interstitially to earlier formed silicates. Subsequently, they are encompassed by reaction rim (almost of amphibole and biotite) along the boundary with surrounding silicate minerals. Under the microscope, magnetite contains a lot of oxyexsolved ilmenite (trellis type) and spinel, and thereby is weakly enriched in magnetite-compatible elements such as Ti, Al, Mg, and V. The structure and textures at the contact zone as well as mineralogical disequilibrium between gabbroic pegmatite and the host gabbroic rocks suggest that the pegmatite may form as a result of accumulation from Fe-rich melt (or liquid) that occurred somewhere rather than in situ form from the host gabbroic rock during the magmatic differentiation. Consequently, the preliminary study suggests that further study on the post-magmatic activities can not only help us improve our understanding on magmatic fractionation but also provide critical information on Fe-Ti oxide mineralization in gabbroic rocks resulting from the magmatic differentiation.