• Molecules and Cells
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• v.43 no.3
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• pp.222-227
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• 2020

Inositol polyphosphate multikinase (IPMK) is required for the biosynthesis of inositol phosphates (IPs) through the phosphorylation of multiple IP metabolites such as IP3 and IP4. The biological significance of IPMK's catalytic actions to regulate cellular signaling events such as growth and metabolism has been studied extensively. However, pharmacological reagents that inhibit IPMK have not yet been identified. We employed a structure-based virtual screening of publicly available U.S. Food and Drug Administration-approved drugs and chemicals that identified the antidepressant, vilazodone, as an IPMK inhibitor. Docking simulations and pharmacophore analyses showed that vilazodone has a higher affinity for the ATP-binding catalytic region of IPMK than ATP and we validated that vilazodone inhibits IPMK's IP kinase activities in vitro. The incubation of vilazodone with NIH3T3-L1 fibroblasts reduced cellular levels of IP5 and other highly phosphorylated IPs without influencing IP4 levels. We further found decreased Akt phosphorylation in vilazodone-treated HCT116 cancer cells. These data clearly indicate selective cellular actions of vilazodone against IPMK-dependent catalytic steps in IP metabolism and Akt activation. Collectively, our data demonstrate vilazodone as a method to inhibit cellular IPMK, providing a valuable pharmacological agent to study and target the biological and pathological processes governed by IPMK.

• Biomolecules & Therapeutics
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• v.29 no.6
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• pp.630-636
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• 2021

Eupafolin, a constituent of the aerial parts of Phyla nodiflora, has neuroprotective property. Because reducing the synaptic release of glutamate is crucial to achieving pharmacotherapeutic effects of neuroprotectants, we investigated the effect of eupafolin on glutamate release in rat cerebrocortical synaptosomes and explored the possible mechanism. We discovered that eupafolin depressed 4-aminopyridine (4-AP)-induced glutamate release, and this phenomenon was prevented in the absence of extracellular calcium. Eupafolin inhibition of glutamate release from synaptic vesicles was confirmed through measurement of the release of the fluorescent dye FM 1-43. Eupafolin decreased 4-AP-induced [Ca²⁺]_i elevation and had no effect on synaptosomal membrane potential. The inhibition of P/Q-type Ca²⁺ channels reduced the decrease in glutamate release that was caused by eupafolin, and docking data revealed that eupafolin interacted with P/Q-type Ca²⁺ channels. Additionally, the inhibition of calcium/calmodulin-dependent protein kinase II (CaMKII) prevented the effect of eupafolin on evoked glutamate release. Eupafolin also reduced the 4-AP-induced activation of CaMK II and the subsequent phosphorylation of synapsin I, which is the main presynaptic target of CaMKII. Therefore, eupafolin suppresses P/Q-type Ca²⁺ channels and thereby inhibits CaMKII/synapsin I pathways and the release of glutamate from rat cerebrocortical synaptosomes.

• Journal of Ginseng Research
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• v.43 no.3
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• pp.442-451
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• 2019

Background: Ginseng has a wide range of beneficial effects on health, such as the mitigation of minor and major inflammatory diseases, cancer, and cardiovascular diseases. There are abundant data regarding the health-enhancing properties of whole ginseng extracts and single ginsenosides; however, no study to date has determined the receptors that mediate the effects of ginseng extracts. In this study, for the first time, we explored whether the antiinflammatory effects of Rg3-enriched red ginseng extract (Rg3-RGE) are mediated by retinoid X receptor ${\alpha}$-peroxisome-proliferating receptor ${\gamma}$ ($RXR{\alpha}-PPAR{\gamma}$) heterodimer nuclear receptors. Methods: Nitric oxide assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay, quantitative reverse transcription polymerase chain reaction, nuclear hormone receptor-binding assay, and molecular docking analyses were used for this study. Results: Rg3-RGE exerted antiinflammatory effects via nuclear receptor heterodimers between $RXR{\alpha}$ and $PPAR{\gamma}$ agonists and antagonists. Conclusion: These findings indicate that Rg3-RGE can be considered a potent antiinflammatory agent, and these effects are likely mediated by the nuclear receptor $RXR{\alpha}-PPAR{\gamma}$ heterodimer.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.20 no.5
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• pp.7-12
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• 2019

The naval surface vessels, which were often exposed to harsh marine environment, tended to be corrosive due to military operations on various sea-areas and courses. Although R.O.K Navy applied various methods to protect further corrosion, the hull corrosion occurred due to cavitation were found on the naval surface vessels at regular and occasional docking. Hull corrosion was a critical factor directly to affect the lifetime of ships and their operational capabilities adversely. In this paper, EH 2350, which was the main anticorrosion paint used by R.O.K. Navy, was compared with DuraTough DL by used by the U.S Navy to collect materials related to anti-corrosion paint. In addition, the paint compatibility verification was conducted through wear abrasion test. Assuming that it was exposed to sea-environment various both abrasion cycle and weight for objective verification. by varying both the abrasion cycles and weights. In this study, the reliability of the EH 2350 conformity, which was used in Naval surface vessels, was secured.

• BMB Reports
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• v.56 no.6
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• pp.359-364
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• 2023

KAI1/CD82, a membrane tetraspanin protein, can prevent various cancers and retinal disorders through its anti-angiogenic and anti-metastatic capacity. However, little is known about its anti-inflammatory effect and molecular mechanism. Therefore, the present study aimed to inLPSvestigate effect of a recombinant protein of the large extracellular domain of human KAI1 (Gly 111-Leu 228, rhKAI1) on lipopolysaccharides (LPS)-stimulated RAW264.7 macrophage-like cells and mouse bone marrow-derived macrophages (BMDM) and to identify its underlying mechanism. Our data showed that rhKAI1 suppressed expression levels of classically macrophages (M1) phenotype-related surface markers F4/80+CD86+ in LPS-stimulated BMDM and RAW264.7 cells. In addition, LPS markedly increased mRNA expression and release levels of pro-inflammatory cytokines and mediators such as interleukin (IL)-1β, IL-6, tumor necrosis factor-α, cyclooxygenase-2, nitric oxide and prostaglandin E2, whereas these increases were substantially down-regulated by rhKAI1. Furthermore, LPS strongly increased expression of NF-κB p65 in the nuclei and phosphorylation of ERK, JNK, and p38 MAPK. However, nuclear translocation of NF-κB p65 and phosphorylation of JNK were greatly reversed in the presence of rhKAI1. Especially, rhKAI1 markedly suppressed expression of toll-like receptor (TLR4) and prevented binding of LPS with TLR4 through molecular docking predict analysis. Importantly, Glu 214 of rhKAI1 residue strongly interacted with Lys 360 of TLR4 residue, with a binding distance of 2.9 Å. Taken together, these findings suggest that rhKAI1 has an anti-inflammatory effect on LPS-polarized macrophages by interacting with TLR4 and down-regulating the JNK/NF-κB signaling pathway.

• Journal of Advanced Marine Engineering and Technology
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• v.33 no.8
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• pp.1203-1211
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• 2009

The dynamics of underwater vehicles can be greatly influenced by the dynamics of the vehicle thrusters. The control of the state of the hovering or very slow motion of the underwater vehicle is most important for automatic docking or control of the manipulator of the vehicle. The dynamics of the thruster based on the electric motor is nonlinear and has uncertain parameters. Since the dynamics of the vehicle coupled with the dynamics of the thruster is nonlinear and has uncertain parameters, a robust control is very effective for a desired motion tracking of the uncertain and nonlinear vehicle. In this paper a study was performed on the robust control scheme of the very slow motion or hovering motion of the underwater vehicle actuated by the electric motor. Also, a concurrent control on the state of the vehicle with nonlinearity and uncertain parameters was performed. A sliding mode control algorithm out of robust controllers was designed and applied, which compensates the nonlinear forces and uncertain parameters of the vehicle and actuator. Through a computer simulation, the proposed control scheme was compared with a linear PD controller and its superior performance was validated.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.179-184
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• 2014

Chemoresistance of breast cancer to doxorubicin is mediated mainly through activation of NF-kB and over expression of HER2. Curcumin and its analogues (PGV-0 and PGV-1) exert cytotoxic effects on T47D breast cancer cells. Suppression of NF-kB activation is suggested to contribute to this activity. The present study aimed to explore the effects of curcumin, PGV-0, and PGV-1 singly and in combination with doxorubicin on MCF-7/Dox cells featuring over-expression of HER2. In MTT assays, curcumin, PGV-0, and PGV-1 showed cytotoxicity effects against MCF-7/Dox with IC50 values of $80{\mu}M$, $21{\mu}M$, and $82{\mu}M$ respectively. These compounds increased MCF-7/Dox sensitivity to doxorubicin. Cell cycle distribution analysis exhibited that the combination of curcumin and its analogues with Dox increased sub G-1 cell populations. Curcumin and PGV-1 but not PGV-0 decreased localization of p65 into the nucleus induced by Dox, indicating that activation of NF-kB was inhibited. Molecular docking of curcumin, PGV-0, and PGV-1 demonstrated high affinity to HER2 at ATP binding site. This interaction were directly comparable with those of ATP and lapatinib. These findings suggested that curcumin, PGV-0 and PGV-1 enhance the Dox cytotoxicity to MCF-7 cells through inhibition of HER2 activity and NF-kB activation.

• Journal of Industrial Convergence
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• v.21 no.4
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• pp.165-170
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• 2023

There are cases where the mobility impaired have difficulty moving from the moment they leave the house. If guardians also do not have time to entrust their families, who are socially disadvantaged, to a shelter, the guardian has no choice but to check directly in order to know the location of the guardian. The AI home care solution was designed to relieve the anxiety and labor of caregivers and to provide convenience for protection facility officials and users. If more facilities distribute and use services free of charge to non-profit foundations and protective facilities, the concern of guardians will be reduced, and the burden of facility officials who have to manage facility users will be reduced. In this paper, we provide emergency notification services to guardians in the event of an emergency as well as location and status alarms for guardians, which are all data related to movement, in consideration of the mobility vulnerable. Furthermore, it is necessary to provide a service function that recommends the optimal route using a navigation function to ease the convenience and burden of facility officials. It is necessary to alleviate anxiety by providing necessary information to the guardian, such as the location of the shuttle used by the mobile weak and the time of getting on and off. In addition, while providing services for free, the goal is to improve the quality of service for facility managers and the quality of service for the mobility weak.

• Microbiology and Biotechnology Letters
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• v.37 no.3
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• pp.248-257
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• 2009

The inhibitors against Vibrio harveyi quorum sensing (QS) signaling were developed by modifying the molecular structure of the major signal, N-3-hydroxybutanoyl-L-homoserine lactone (3-OH-$C_4$-HSL). A series of structural derivatives, N-(3-hydroxysulfonyl)-L-homoserine lactones (HSHLs) were synthesized by the solid-phase organic synthesis method. The in vivo QS inhibition by these compounds was measured by a bioassay system using the V. harveyi bioluminescence, and all showed significant inhibitory effects. To analyze the interaction between these compounds and LuxN, a 3-OH-$C_4$-HSL receptor protein of V. harveyi, we tentatively determined the putative signal binding domain of LuxN based on the sequence homology with other acyl-HSL binding proteins, and predicted the partial 3-D structure of the putative signal binding domain of LuxN by using ORCHESTRA program, and further estimated the binding poses and energies (docking scores) of 3-OH-$C_4$-HSL and HSHLs within the domain. In comparison of the result from this modeling study with that of in vivo bioassay, we suggest that the in silica interpretation of the interaction between ligands and their receptor proteins can be a valuable way to develop better competitive inhibitors, especially in the case that the structural information of the protein is limited.

• Journal of Life Science
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• v.23 no.5
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• pp.609-615
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• 2013

Glyceollin I has gained attention as a useful therapy for various dermatological diseases. However, the binding property of glyceollin I to the mammalian adenylyl cyclase (hereafter mAC), a critical target enzyme for the down-regulation of skin melanogenesis, has not been fully explored. To clarify the action mechanism between glyceollin I and mAC, we first investigated the molecular docking property of glyceollin I to mAC and compared with that of SQ22,536, a well-known mAC inhibitor, to mAC. Glyceollin I showed superiority by forming three hydrogen bonds with Asp 1018, Trp 1020, and Asn 1025, which exist in the catalytic site of mAC. However, SQ22,536 formed only two hydrogen bonds with Asp 1018 and Asn 1025. Secondly, we confirmed that glyceollin I effectively inhibits the formation of forskolin-induced cAMP and the phosphorylation of PKA from a cell-based assay. Long term treatment with glyceollin I had little effect on the cell viability. The findings of the present study also suggest that glyceollin I may be extended to be used as an effective inhibitor of hyperpigmentation.