• Molecules and Cells
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• v.46 no.3
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• pp.133-141
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• 2023

Transcription factor NRF2 (NF-E2-related factor 2) is a master regulator of cellular responses against environmental stresses. NRF2 induces expression of detoxification and antioxidant enzymes and suppresses inductions of pro-inflammatory cytokine genes. KEAP1 (Kelch-like ECH-associated protein 1) is an adaptor subunit of CULLIN 3 (CUL3)-based E3 ubiquitin ligase. KEAP1 regulates the activity of NRF2 and acts as a sensor for oxidative and electrophilic stresses. NRF2 has been found to be activated in many types of cancers with poor prognosis. Therapeutic strategies to control NRF2-overeactivated cancers have been considered not only by targeting cancer cells with NRF2 inhibitors or NRF2 synthetic lethal chemicals, but also by targeting host defense with NRF2 inducers. Understanding precise molecular mechanisms how the KEAP1-NRF2 system senses and regulates the cellular response is critical to overcome intractable NRF2-activated cancers.

• Journal of Microbiology and Biotechnology
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• v.34 no.6
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• pp.1197-1205
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• 2024

Filamentous fungi are important cell factories for the production of high-value enzymes and chemicals for the food, chemical, and pharmaceutical industries. Under submerged fermentation, filamentous fungi exhibit diverse fungal morphologies that are influenced by environmental factors, which in turn affect the rheological properties and mass transfer of the fermentation system, and ultimately the synthesis of products. In this review, we first summarize the mechanisms of mycelial morphogenesis and then provide an overview of current developments in methods and strategies for morphological regulation, including physicochemical and metabolic engineering approaches. We also anticipate that rapid developments in synthetic biology and genetic manipulation tools will accelerate morphological engineering in the future.

• Development and Reproduction
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• v.20 no.1
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• pp.51-61
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• 2016

Neurokinin B (NKB) and neurokinin B related peptide (NKBRP) belong to tachykinin peptide family. They act as a neurotransmitter and/or neuromodulator. Mutation of NKB and/or its cognate receptor, NK3R resulted in hypogonadotropic hypogonadism in mammals, implying a strong involvement of NKB/NK3R system in controlling mammalian reproduction. Teleosts possess NKBRP as well as NKB, but their roles in fish reproduction need to be clarified. In this study, NKB and NKBRP coding gene (tac3) was cloned from Nile tilapia and sequenced. Based on the sequence, Nile tilapia NKB and NKBRP peptide were synthesized and their biological potencies were tested in vitro pituitary culture. The synthetic NKBRP showed direct inhibitory effect on the expression of GTH subunits at the pituitary level. This inhibitory effect was confirmed in vivo by means of intraperitoneal (ip) injection of synthetic NKB and NKBRP to mature female tilapia (20 pmol/g body weight [BW]). Both NKB and NKBRP had no effect on the plasma level of sex steroids, E2 and 11-KT. However, NKBRP caused declines of expression level of GnRH I, Kiss2 and tac3 mRNAs in the brain while NKB seemed to have no distinct effect. These results indicate some inhibitory roles of NKBRP in reproduction of mature female Nile tilapia, although their exact functions are not clear at the moment.

• BMB Reports
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• v.32 no.6
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• pp.561-566
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• 1999

CA(1-8)-ME(1-12) [CA-ME], composed of cecropin A(1-8) and melittin(1-12), is a synthetic antimicrobial peptide having potent antibacterial and antitumor activities with minimal hemolytic activity. In order to investigate the effects of the flexible hinge sequence, Gly-Ile-Gly, of CA-ME on antibiotic activity, CA-ME and three analogues, CA-ME1, CA-ME2, and CA-ME3, were synthesized. The Gly-Ile-Gly sequence of Ca-ME was deleted in CA-ME1 and replaced with Pro and Gly-Pro-Gly in CA-ME2 and CA-ME3, respectively. CA-ME1 and CA-ME3 showed a significant decrease in antitumor activity and phospholipid vesicle-disrupting ability. However, CA-ME2 showed similar antitumor and vesicle-disrupting activities, as compared with CA-ME. These results suggest that the flexibility or ${\beta}$-turn induced by Gly-Ile-Gly or Pro in the central part of CA-ME may be important in the electrostatic interaction of the N-terminus cationic ${\alpha}$-helical region with the cell membrane surface and the hydrophobic interaction of the C-terminus amphipathic ${\alpha}$-helical region with the hydrophobic acyl chains in the cell membrane. CA-ME3 exhibited lower antitumor and vesicle-disrupting activities than CA-ME and CA-ME2. This result suggests that the excessive ${\beta}$-turn structure caused by the Gly-Pro-Gly sequence in CA-ME3 seems to interrupt ion channel/pore formation in the lipid bilayer. We concluded that the appropriate flexibility or bilayer. We concluded that the appropriate flexibility or ${\beta}$-turn structure provided by the central hinge is responsible for the effective antibiotic activity of the antimicrobial peptides with the helix-hinge-helix structure.

• Proceedings of the Microbiological Society of Korea Conference
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• 2003.05a
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• pp.83-86
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• 2003

Major advances in positive-sense RNA virus research have been facilitated by the development of reverse genetics systems. These systems consist of an infectious cDNA clone that encompasses the genome of the virus in question. This clone is then used as a template for the subsequent synthesis of infectious RNA for the generation of synthetic viruses. However, the construction of infectious cDNA for the Japanese encephalitis virus (JEV) has been repeatedly thwarted by the instability of its cDNA. As JEV is an important human pathogen that causes permanent neuropsychiatric sequelae and even fatal disease, a reliable reverse genetics system for this virus is highly desirable. The availability of this tool would greatly and the development of effective vaccines as well as facilitate studies into the basic biology of the virus, including the molecular mechanisms of viral replication, neurovirulence, and pathogenesis. We have successfully constructed a genetically stable infectious JEV cDNA containing full-length viral RNA genome. Synthetic RNA transcripts generated in vitro from the cDNA were highly infectious upon transfection into susceptible cells, and the cDNA remained stable after it had been propagated in E. coli for 180 generations. Using this infectious JEV cDNA, we have successfully expressed a variety of reporter genes from the full-length genomic and various subgenomic RNAs in vitro transcribed from functional JEV cDNAS. In summary, we have developed a reverse genetics system for JEV that will greatly facilitate the research on this virus in a variety of different fields. It will also be useful as a heterologous gene expression vector and aid the development of a vaccine against JEV.

• The Korean Journal of Zoology
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• v.23 no.3
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• pp.149-160
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• 1980

The effects of mutagens, MMS and captan, on the patterns of proteins synthesized during the early developmental stages in mice were analyzed using two-dimensional electrophoresis. Three classes of proteins were observed in terms of synthetic pattern during the preimplantation stages. The first class is synthesized from the m-RNA, which was made and preserved throughout oogenesis and activated at the fertilization. The synthesis of these proteins did not seem to be influenced by MMS. The second class, which may be stagespecific proteins synthesized by newly transcribed m-RNA, was selectively inhibited by MMS. The third class, the synthesis of which is also suppressed by MMS, is the proteins synthesized by the m-RNA transcribed in augmented fashion. While MMS inhibits protein synthesis dependent on thenew transcription, this mutagen enhances a synthesis of a few proteins which were not observed in the untreated embryos. Captan did not affect protein synthesis at morula stage.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.11
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• pp.1795-1806
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• 2018

Objective: The study was designed to establish choline deficiency model (CDM) in broilers for evaluating efficacy of polyherbal formulation (PHF) in comparison with synthetic choline chloride (SCC). Methods: A total of 2,550 one-day-old Cobb 430 broiler chicks were randomly assigned to different groups in three experiments. In experiment 1, G1 and G2 served as normal controls and were fed a basal diet with 100% soybean meal (SBM) as a major protein source supplemented with and without SCC, respectively. In G3, G4, G5, and G6 groups, SBM was replaced at 25%, 50%, 75%, and 100% by soy protein isolate (SPI) to induce a graded level of choline deficiency. In experiment 2, PHF (500 and 1,000 g/ton) in comparison with SCC (1,000 g/ton) were evaluated. In experiment 3, dose-response of PHF (200, 400, and 500 g/ton) with SCC (400 g/ton) was determined. Results: Replacement of SBM by SPI produced a linear decrease in body weight gain (BWG) with a poor feed conversion ratio (FCR). 25% SBM replacement by SPI yielded an optimum negative impact on BWG and FCR; hence, it is considered for further studies. In experiment 2, PHF (500 and 1,000 g/ton) and SCC (1,000 g/ton) showed a similar performance in BWG, FCR and relative liver weight. In experiment 3, PHF produced an optimum efficacy at 400 g/ton and was comparable to SCC in the restoration of serum aspartate aminotransferase activity, abdominal fat, breast muscle lipid content and liver histopathological abnormalities. Conclusion: Replacement of SBM by SPI caused choline deficiency characterised by worsening of BWG, FCR, elevation in liver enzymes and histopathological changes indicating fatty liver. CDM was found valid for evaluating SCC and PHF. It is concluded that PHF has the potential to mimic biological activities of SCC through the restoration of negative effects caused by CDM.

• The Journal of the Korean dental association
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• v.48 no.4
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• pp.256-262
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• 2010

bone grafting is indicated in the case of bony defects and is classified into autograft, allograft, and xenograft. Synthetic bone graft is contrasted with these three categories in that it has a different donor source. Autograft is most prominent as it is known as a gold standard of all grafting procedures. Its principles and practices are well established via accumulated informations and clinical experiences, which imposes no regulations or restrictions in its clinical use. On the other hand, other bone graft procedures are under tight control for the safety and effectiveness of each product. Food and Drug Administration of the United States has a system in which the information on the approvals and clearances of bone graft materials on their internet homepage. All the bone graft materials that are under the regulations of the United States are classified into the category of medical devices, which includes allogenic bone, xenogenic bone, and synthetic bone graft materials. Each bone graft material has its own indication and the FDA approvals and clearances of medical devices contain the item of "intended use" to specify the indications of each bone graft materials. US dentists, as users of the specific bone graft materials, are provided with adequate information on the approved materials they are to utilize. As an user of these materials, Korean dentists are less provided with the information on the bone graft materials they want to use. Medical providers of the bone graft materials have to be able to provide their users with the essential information such as the intended use of the regulatory approval. Dentists must also be active in gathering informations on the material of their interest, and the system must be built in which both of the medical providers and users of bone graft materials can be satisfied in providing and getting the information, respectively.

• Molecules and Cells
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• v.44 no.7
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• pp.458-467
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• 2021

GPR43 (also known as FFAR2 or FFA2) is a G-protein-coupled receptor primarily expressed in immune cells, enteroendocrine cells and adipocytes that recognizes short-chain fatty acids, such as acetate, propionate, and butyrate, likely to be implicated in innate immunity and host energy homeostasis. Activated GPR43 suppresses the cAMP level and induces Ca²⁺ flux via coupling to Gα_i and Gα_q families, respectively. Additionally, GPR43 is reported to facilitate phosphorylation of ERK through G-protein-dependent pathways and interacts with β-arrestin 2 to inhibit NF-κB signaling. However, other G-protein-dependent and independent signaling pathways involving GPR43 remain to be established. Here, we have demonstrated that GPR43 augments Rho GTPase signaling. Acetate and a synthetic agonist effectively activated RhoA and stabilized YAP/TAZ transcriptional coactivators through interactions of GPR43 with Gα_q/11 and Gα_12/13. Acetate-induced nuclear accumulation of YAP was blocked by a GPR43-specific inverse agonist. The target genes induced by YAP/TAZ were further regulated by GPR43. Moreover, in THP-1-derived M1-like macrophage cells, the Rho-YAP/TAZ pathway was activated by acetate and a synthetic agonist. Our collective findings suggest that GPR43 acts as a mediator of the Rho-YAP/TAZ pathway.

• BMB Reports
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• v.55 no.12
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• pp.645-650
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• 2022

Epithelial-to-mesenchymal transition (EMT)-subtype gastric cancers have the worst prognosis due to their higher recurrence rate, higher probability of developing metastases and higher chemo-resistance compared to those of other molecular subtypes. Pharmacologically actionable somatic mutations are rarely found in EMT-subtype gastric cancers, limiting the utility of targeted therapies. Here, we conducted a high-throughput chemical screen using 37 gastric cancer cell lines and 48,467 synthetic small-molecule compounds. We identified YK-135, a small-molecule compound that showed higher cytotoxicity toward EMT-subtype gastric cancer cell lines than toward non-EMT-subtype gastric cancer cell lines. YK-135 exerts its cytotoxic effects by inhibiting mitochondrial complex I activity and inducing AMP-activated protein kinase (AMPK)-mediated apoptosis. We found that the lower glycolytic capacity of the EMT-subtype gastric cancer cells confers synthetic lethality to the inhibition of mitochondrial complex I, possibly by failing to maintain energy homeostasis. Other well-known mitochondrial complex I inhibitors (e.g., rotenone and phenformin) mimic the efficacy of YK-135, supporting our results. These findings highlight mitochondrial complex I inhibitors as promising therapeutic agents for EMT-subtype gastric cancers and YK-135 as a novel chemical scaffold for further drug development.