• Biomolecules & Therapeutics
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• v.30 no.5
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• pp.455-464
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• 2022

Efonidipine, a calcium channel blocker, is widely used for the treatment of hypertension and cardiovascular diseases. In our preliminary study using structure-based virtual screening, efonidipine was identified as a potential inhibitor of c-Jun N-terminal kinase 3 (JNK3). Although its antihypertensive effect is widely known, the role of efonidipine in the central nervous system has remained elusive. The present study investigated the effects of efonidipine on the inflammation and cell migration induced by lipopolysaccharide (LPS) using murine BV2 and human HMC3 microglial cell lines and elucidated signaling molecules mediating its effects. We found that the phosphorylations of JNK and its downstream molecule c-Jun in LPS-treated BV2 cells were declined by efonidipine, confirming the finding from virtual screening. In addition, efonidipine inhibited the LPS-induced production of pro-inflammatory factors, including interleukin-1β (IL-1β) and nitric oxide. Similarly, the IL-1β production in LPS-treated HMC3 cells was also inhibited by efonidipine. Efonidipine markedly impeded cell migration stimulated by LPS in both cells. Furthermore, it inhibited the phosphorylation of inhibitor kappa B, thereby suppressing nuclear translocation of nuclear factor-κB (NF-κB) in LPS-treated BV2 cells. Taken together, efonidipine exerts anti-inflammatory and anti-migratory effects in LPS-treated microglial cells through inhibition of the JNK/NF-κB pathway. These findings imply that efonidipine may be a potential candidate for drug repositioning, with beneficial impacts on brain disorders associated with neuroinflammation.

• Journal of Korean Neurosurgical Society
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• v.66 no.3
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• pp.228-238
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• 2023

Intraventricular hemorrhage (IVH) is a serious concern for preterm infants and can predispose such infants to brain injury and poor neurodevelopmental outcomes. IVH is particularly common in preterm infants. Although advances in obstetric management and neonatal care have led to a lower mortality rate for preterm infants with IVH, the IVH-related morbidity rate in this population remains high. Therefore, the present review investigated the pathophysiology of IVH and the evidence related to interventions for prevention. The analysis of the pathophysiology of IVH was conducted with a focus on the factors associated with cerebral hemodynamics, vulnerabilities in the structure of cerebral vessels, and host or genetic predisposing factors. The findings presented in the literature indicate that fluctuations in cerebral blood flow, the presence of hemodynamic significant patent ductus arteriosus, arterial carbon dioxide tension, and impaired cerebral venous drainage; a vulnerable or fragile capillary network; and a genetic variant associated with a mechanism underlying IVH development may lead to preterm infants developing IVH. Therefore, strategies focused on antenatal management, such as routine corticosteroid administration and magnesium sulfate use; perinatal management, such as maternal transfer to a specialized center; and postnatal management, including pharmacological agent administration and circulatory management involving prevention of extreme blood pressure, hemodynamic significant patent ductus arteriosus management, and optimization of cardiac function, can lower the likelihood of IVH development in preterm infants. Incorporating neuroprotective care bundles into routine care for such infants may also reduce the likelihood of IVH development. The findings regarding the pathogenesis of IVH further indicate that cerebrovascular status and systemic hemodynamic changes must be analyzed and monitored in preterm infants and that individualized management strategies must be developed with consideration of the risk factors for and physiological status of each preterm infant.

• The Korean Journal of Franchise Management
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• v.7 no.2
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• pp.5-14
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• 2016

Purpose - Competitive industry structure and recent economic depression challenge a survival of Korean small- and medium-sized food franchising companies (SMFCs), albeit the explosive growth of the Korean food service industry for last few decades. Against this backdrop, it examines how these SMFCs overcome liabilities of smallness and resource scarcity to strengthen competitive advantage in the market. To tackle this, in this article we focus on corporate entrepreneurship and human resources as a knowledge-based asset for these SMFCs. Furthermore, the ratio of employee turnover is high in SMFCs. We view that such brain-drain may result in poor performance of the Korean SMFCs. As such, we pay attention to the role of organizational commitment to an organization as a solution for enhancing individual-level employees' loyalty toward their organization. Research design, data, and methodology - Our research question is to what extent corporate entrepreneurship (i.e., innovative organizational culture, organizational autonomy, and administrative innovation) affects an individual-level attitude toward the organization and, in turn, employee creativity and satisfaction in the Korean SMFCs context. We collected data from employees in SMFCs for three months. A total of 126 valid questionnaires were collected, and analyzed the data using partial least squares path modeling. Results - The reliable and valid measurement model feed into testing the structural model. Our findings suggest that innovative organizational culture and organizational autonomy positively affect employee commitment. Particularly, organizational autonomy has a greater effect than innovative culture on employee commitment. However, the relationship between administrative innovation and employee commitment is not significant. We also find that employee commitment positively affects both employee creativity and satisfaction. Conclusions - Our contribution to the existing franchising business and management literature is twofold. First, the conceptual model includes three antecedents in the organizational entrepreneurship dimension to organizational commitment. Second, we conceptualize organizational commitment as employee commitment, and validate its impact on employee creativity and job satisfaction at an individual performance level. Overall, this article suggests that it is critically important for the Korean SMFCs to develop corporate entrepreneurship in order to facilitate employees' positive attitudes toward their organizations.

• Journal of Sensor Science and Technology
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• v.32 no.5
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• pp.290-294
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• 2023

Among various types of harmful gases, hydrogen sulfide is a strong toxic gas that is mainly generated during spillage and wastewater treatment at industrial sites. Hydrogen sulfide can irritate the conjunctiva even at low concentrations of less than 10 ppm, cause coughing, paralysis of smell and respiratory failure at a concentration of 100 ppm, and coma and permanent brain loss at concentrations above 1000 ppm. Therefore, rapid detection of hydrogen sulfide among harmful gases is extremely important for our safety, health, and comfortable living environment. Most hydrogen sulfide gas sensors that have been reported are electrical resistive metal oxide-based semiconductor gas sensors that are easy to manufacture and mass-produce and have the advantage of high sensitivity; however, they have low gas selectivity. In contrast, the electrochemical sensor measures the concentration of hydrogen sulfide using an electrochemical reaction between hydrogen sulfide, an electrode, and an electrolyte. Electrochemical sensors have various advantages, including sensitivity, selectivity, fast response time, and the ability to measure room temperature. However, most electrochemical hydrogen sulfide gas sensors depend on imports. Although domestic technologies and products exist, more research is required on their long-term stability and reliability. Therefore, this study includes the processes from electrode material synthesis to sensor fabrication and characteristic evaluation, and introduces the sensor structure design and material selection to improve the sensitivity and selectivity of the sensor. A sensor case was fabricated using a 3D printer, and an Ag reference electrode, and a Pt counter electrode were deposited and applied to a Polytetrafluoroethylene (PTFE) filter using PVD. The working electrode was also deposited on a PTFE filter using vacuum filtration, and an electrochemical hydrogen sulfide gas sensor capable of measuring concentrations as low as 0.6 ppm was developed.

• Journal of Life Science
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• v.28 no.3
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• pp.284-292
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• 2018

The melanin-concentrating hormone (MCH), a cyclic hypothalamic peptide composed of 17 amino acids, was initially identified in chum salmon (Oncorhynchus keta) as a regulator of pigmentation. Mammalian MCHs are cyclic hypothalamic peptides composed of 19 amino acids that regulate food intake and energy homeostasis. The present study examined not only MCH expression of different tissues but also the melanohore aggregation and intracellular $Ca^{2+}$ influx of fMCH and the other MCH. Real-time qPCR showed that MCH expressed specially in the brain, gonad, and ovary, and expression of MCH was observed during the developmental stages. In the application of synthetic fMCH and both types of synthetic fMCH, dN-fMCH and dC-fMCH, scale melanophore induced significant changes in aggregation activity with various concentrations of MCH. Also, compared to hMCH and sMCH, fMCH exhibited a 36~99.85% increase in relative potency (%), whereas aggregation of dN-fMCH and dC-fMCH remained in a high concentration. However, dispersion was induced rapidly according to be low concentration of dN-fMCH and dC-fMCH. We show that fMCH and its derivates were bound human MCHR1 and rat MCHR expressed in HEK293T cells with nano-molar affinity and are likely to be ligand-induced to mobilize intracellular $Ca^{2+}$. These results may provide new ligands for binding assay with MCHew ligands, as a structure similar to the mammalian MCH structure was discovered in fish. Once the fMCH receptor system is in place, it can be compared to the MCH system of mammals in terms of MCH function.

• Korean Journal of Ichthyology
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• v.23 no.1
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• pp.10-20
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• 2011

Genetic determinant for metallothionein (MT), a cysteine-rich protein playing essential roles in metal detoxification and homeostasis, was characterized in the Korean bitterling (Acheilognathus signifer, Cyprinidae), an endemic fish species. The full-length A. signifer MT (AsMT) cDNA (551 bp) is composed of a single open-reading frame (ORF) to encode a polypeptide of 60 amino acids containing 20 cysteine residues whose positions are conserved in most cypriniform MTs. At the genomic level, the AsMT (2,593 bp spanning the 5'-flanking region to the 3'-untranslated region) represented a conserved tripartite (three exons interrupted by two introns) structure with AT-rich introns. The upstream regulatory region (-1,914 bp from the ATG initiation codon) of AsMT displayed various sites and motifs for transcription factors involved in the metal-mediated regulation and stress/immune responses. The AsMT transcript was ubiquitously detected in various organs with variable expression levels, where the ovary and intestine showed the highest expression, while the heart and skeletal muscle represented the lowest level. During an exposure to copper (immersion in $0.5\;{\mu}M$ Cu for 48 h), the levels of AsMT transcripts were significantly elevated in the liver (more than 3.5-fold), moderately in the gill, kidney, and spleen (ranging from 1.5- to 2.5-fold), and barely in the brain and intestine. Results of this study could form a useful basis to explore the metal-related stress physiology of this endangered fish species.

• The Korean Journal of Nuclear Medicine
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• v.29 no.1
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• pp.110-117
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• 1995

Tc-99m Labeled hexamethylenepropyleneamineoxime ([$^{99m}Tc$]-HMPAO) is a famous amino-oxime compound and is widely used to construct SPECT images of cerebral blood flow. To investigate the relationship between chemical structure and radiolabeling in these kind of diamine-oxime compounds, we synthesized seven compounds by Schiff's base formation and successive reduction with sodium borohydride. They were (RR/SS )-4,8-diaza-3,6,6,9-tetramethylundecane-2,10-dione bisoxime (2), (RR/SS/meso)-4,8-diaza-3,9-dimethy-lundecane-2,10-dione bisoxime (4), (RR/SS/meso)-4,8-diaza-3,10-dimethyldodecane-2,11-dione bisoxime (5), (RR/SS/meso)-4,7-diaza-3,6,6,8-tetramethyldecane-2,9-dione bisoxime (8), (RR/SS/meso)-4,7-diaza-5,6-cyclohexyl-3,8-dimethyldecane-2,9-dione bisoxime (10), (RR/SS/meso)-3,4-bis(1-aza-2-methyl-3-oxime-1-butyl)-benzoic acid (12), and (RR/SS/ meso)-2,3-bis(1-aza-2-methyl-3-oxime-1-butyl) benzophenone (14). Chemical structures of all the synthesized compounds were identified by taking $^1H$ spectrum. Among them, 2 and 4 are propyleneamine oxime (PnAO), 6 is butyleneamine oxime (BnAO) and 8, 10, 12 and 14 are ethyleneamine oxime (EnAO). Each compound (0.5 mg) was incubated with stannous chloride (0.5 g - 8 g), carbonate-bicarbonate buffer (final concentration = 0.1 M, pH 7 - pH 10) and Tc-99m-pertechenate (1 ml). Tc-99m labeling of these compounds were checked by ITLC (acetone), ITLC (normal saline), reverse phase TLC (50 % acetonitrile) and ITLC (ethyl acetate). According to the results, EnAO's were not labeled by Tc-99m in any of above condition. About 11 % of maximum labeling efficiency was obtained with BnAO. However, 4 (PnAO) was labeled with Tc-99m to 85 % which is similar to the labeling efficiency of 2 (HMPAO). Hydrophilic impurity (9 % ) was the most significant problem with the labeling of 4, however, pertechnetate (3 % ) and colloid (3 %) were minor problem. In conclusion, we synthesized seven diamine blsoxlme compounds. Among them, four EnAO compounds were not labeled by Tc-99m. A BnAO was labeled poorly and two PnAO's were labeled well. These labeling can be explained by tertiary structure of their Tc-99m chelate.

• Korean Journal of Materials Research
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• v.10 no.12
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• pp.807-811
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• 2000

CeO$_2$ and SrBi$_2$Ta$_2$O$_{9}$ (SBT) thin films for MFISFET (Metal-ferroelectric-insulator-semiconductor-field effect transistor) were deposited by r.f. sputtering and pulsed laser ablation method, respectively. The effects of sputtering gas ratio(Ar:O$_2$) during deposition for CeO$_2$ films were investigated. The CeO$_2$ thin films deposited on Si(100) substrate at $600^{\circ}C$ exhibited (200) preferred orientation. The preferred orientation, Brain size and surface roughness of films decreased with increasing oxygen to argon gas ratio. The films deposited under the condition of Ar:O$_2$= 1 : 1 showed the best C- V characteristics. The leakage current of films showed the order of 10$^{-7}$ ~10$^{-8}$ A at 100kV/cm. The SBT thin films on CeO$_2$/Si substrate showed dense microstructure of polycrystalline phase. From the C-V characteristics of MFIS structure with SBT film annealed at 80$0^{\circ}C$, the memory window width was 0.9V at 5V The leakage current density of Pt/SBT/CeO$_2$/Si structure annealed at 80$0^{\circ}C$ was 4$\times$10$^{-7}$ /$\textrm{cm}^2$ at 5V.

• Applied Biological Chemistry
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• v.42 no.1
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• pp.68-72
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• 1999

The cytotoxicity of 1,3-diphenylpropenone derivatives known to inhibit the farnesyl protein transferase (FPTase) was examined against various established tumor cell line, A549 (lung cancer), SKMEL-2 (uterine cancer), HCT-15 (skin cancer), SKOV-3 (brain cancer) and XF-498 (colon cancer) of the 1,3-diphenylpropenone derivatives showing farnesyl protein transferase (FPTase) inhibition activity. And the structure-activity relationship (SAR) between structure of 1,3-diphenylpropenone derivatives as substrate and cytotoxicity was investigated by Free-Wilson analysis as well as Hansch method with tumor cell lines. From the result of Free-Wilson analyses, X-substituents on the benzoyl group have a more important role than Y-substituents on the styryl group. The 2,4-dichloro substituent, 15 and 2,4-dimethyl substituent, 16 showed the highest cytotoxicity (average pI_(50)=5.0). Particulary, the cytotoxicity of X-substituents increased with electronic effect $({\sigma})$ due to weak electron withdrawing group with optimum value $({\sigma}_{opt}=0.22{\sim}0.29})$ whereas that of Y-substituent resulted from various factors such as logP, $B_1$ and R constant.

• Journal of Life Science
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• v.28 no.12
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• pp.1536-1544
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• 2018

Depression is a common, serious, and recurring mental disorder. The pathogenesis of depression involves many factors such as environmental factor, genetic factor and alteration of structure and function in neurobiological systems. Increasing evidence supports that epigenetic alteration may be associated with depression. The epigenetics is explained as the mechanisms by which environmental factor causes changes in chromatin structure and alters gene expression without changing DNA base sequence. DNA methylation and histone modification involving histone acetylation and methylation are the main epigenetic mechanisms. Animal studies have shown that stressful environment such as early life stress can leave persistent epigenetic marks in the genome, which alter gene expression and influence neural and behavioral function through adulthood. A potentially important gene in depression is brain-derived neurotrophic factor (BDNF). BDNF plays a central role in depression and antidepressant action. In studies of the rodent, exposure to stress at prenatal, postnatal, and adult stages alters BDNF expression through histone modification and DNA methylation of the BDNF gene which results in anxiety and depressive-like behavior. This review discusses recent advances in the study of the epigenetic mechanisms that contribute to depression, particularly histone modification and DNA methylation of the BDNF gene, that may help in the development of new targets for depression treatment.