• Journal of Microbiology and Biotechnology
• /
• v.31 no.1
• /
• pp.25-32
• /
• 2021

Inflammatory reactions activated by lipopolysaccharide (LPS) of gram-negative bacteria can lead to severe septic shock. With the recent emergence of multidrug-resistant gram-negative bacteria and a lack of efficient ways to treat resulting infections, there is a need to develop novel anti-endotoxin agents. Antimicrobial peptides have been noticed as potential therapeutic molecules for bacterial infection and as candidates for new antibiotic drugs. We previously designed the 9-meric antimicrobial peptide Pro9-3 and it showed high antimicrobial activity against gram-negative bacteria. Here, to further examine its potency as an anti-endotoxin agent, we examined the anti-endotoxin activities of Pro9-3 and elucidated its mechanism of action. We performed a dye-leakage experiment and BODIPY-TR cadaverine and limulus amebocyte lysate assays for Pro9-3 as well as its lysine-substituted analogue and their enantiomers. The results confirmed that Pro9-3 targets the bacterial membrane and the arginine residues play key roles in its antimicrobial activity. Pro9-3 showed excellent LPS-neutralizing activity and LPS-binding properties, which were superior to those of other peptides. Saturation transfer difference-nuclear magnetic resonance experiments to explore the interaction between LPS and Pro9-3 revealed that Trp3 and Tlr7 in Pro9-3 are critical for attracting Pro9-3 to the LPS in the gram-negative bacterial membrane. Moreover, the anti-septic effect of Pro9-3 in vivo was investigated using an LPS-induced endotoxemia mouse model, demonstrating its dual activities: antibacterial activity against gram-negative bacteria and immunosuppressive effect preventing LPS-induced endotoxemia. Collectively, these results confirmed the therapeutic potential of Pro9-3 against infection of gram-negative bacteria.

• Biomolecules & Therapeutics
• /
• v.29 no.5
• /
• pp.506-518
• /
• 2021

The imprinted tumour suppressor NOEY2 is downregulated in various cancer types, including ovarian cancers. Recent data suggest that NOEY2 plays an essential role in regulating the cell cycle, angiogenesis and autophagy in tumorigenesis. However, its detailed molecular function and mechanisms in ovarian tumours remain unclear. In this report, we initially demonstrated the inhibitory effect of NOEY2 on tumour growth by utilising a xenograft tumour model. NOEY2 attenuated the cell growth approximately fourfold and significantly reduced tumour vascularity. NOEY2 inhibited the phosphorylation of the signalling components downstream of phosphatidylinositol-3'-kinase (PI3K), including phosphoinositide-dependent protein kinase 1 (PDK-1), tuberous sclerosis complex 2 (TSC-2) and p70 ribosomal protein S6 kinase (p70S6K), during ovarian tumour progression via direct binding to vascular endothelial growth factor receptor-2 (VEGFR-2). Particularly, the N-terminal domain of NOEY2 (NOEY2-N) had a potent anti-angiogenic activity and dramatically downregulated VEGF and hypoxia-inducible factor-1α (HIF-1α), key regulators of angiogenesis. Since no X-ray or nuclear magnetic resonance structures is available for NOEY2, we constructed the three-dimensional structure of this protein via molecular modelling methods, such as homology modelling and molecular dynamic simulations. Thereby, Lys15 and Arg16 appeared as key residues in the N-terminal domain. We also found that NOEY2-N acts as a potent inhibitor of tumorigenesis and angiogenesis. These findings provide convincing evidence that NOEY2-N regulates endothelial cell function and angiogenesis by interrupting the VEGFR-2/PDK-1/GSK-3β signal transduction and thus strongly suggest that NOEY2-N might serve as a novel anti-tumour and anti-angiogenic agent against many diseases, including ovarian cancer.

• Korean Journal of Materials Research
• /
• v.31 no.6
• /
• pp.345-352
• /
• 2021

In this study, Ni nanoparticle supported by graphene oxide (GO) (Ni-GO) is successfully synthesized through hydrothermal synthesis and calcination, and Cr(VI) is extracted from aqueous solution. The morphology and structure of Ni-GO composites are characterized by scanning electron microscopy (SEM), trans mission electron microscopy (TEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). High-resolution transmission electron microscopy (HRTEM) and XRD confirms the high dispersion of Ni nanoparticle after support by GO. Loading Ni on GO can obviously enhance the stability of Ni-GO composites. It can be calculated from TGA that the mass percentage of Ni is about 60.67 %. The effects of initial pH and reaction time on Cr(VI) removal ability of Ni-GO are investigated. The results indicate that the removal efficiency of Cr(VI) is greater than that of bared GO. Ni-GO shows fast removal capacity for Cr(VI) (<25 min) with high removal efficiency. Dynamic experiments show that the removal process conforms to the quasi-second order model of adsorption, which indicates that the rate control step of the removal process is chemical adsorption. The removal capacity increases with the increase of temperature, indicating that the reaction of Cr(VI) on Ni-GO composites is endothermic and spontaneous. Combined with tests and characterization, the mechanism of Cr(VI) removal by rapidly adsorption on the surface of Ni-GO and reduction by Ni nanoparticle is investigated. The above results show that Ni-GO can be used as a potential remediation agent for Cr(VI)-contaminated groundwater.

• The Journal of the Korea institute of electronic communication sciences
• /
• v.16 no.6
• /
• pp.1153-1160
• /
• 2021

This paper proposes a routing algorithm that determines the optimal path using deep reinforcement learning in software-defined networks. The deep reinforcement learning model for learning is based on DQN, the inputs are the current network state, source, and destination nodes, and the output returns a list of routes from source to destination. The routing task is defined as a discrete control problem, and the quality of service parameters for routing consider delay, bandwidth, and loss rate. The routing agent classifies the appropriate service class according to the user's quality of service profile, and converts the service class that can be provided for each link from the current network state collected from the SDN. Based on this converted information, it learns to select a route that satisfies the required service level from the source to the destination. The simulation results indicated that if the proposed algorithm proceeds with a certain episode, the correct path is selected and the learning is successfully performed.

• Journal of Periodontal and Implant Science
• /
• v.52 no.5
• /
• pp.383-393
• /
• 2022

Purpose: Aloe-emodin (AE), a natural anthraquinone abundant in aloe plants and rhubarb (Rheum rhabarbarum), has long been used to treat chronic inflammatory diseases. However, AE's underlying mechanisms in periodontal inflammation have not been fully elucidated. Acidic mammalian chitinase (AMCase) is a potential biomarker involved in bone remodeling. This study aimed to evaluate AE's effect on periodontitis in rats and investigate AMCase expression. Methods: Eighteen Sprague-Dawley rats were separated into the following groups: healthy (group 1), disease (group 2), vehicle (group 3), AE high-dose (group 4), and AE low-dose (group 5). Porphyromonas gingivalis ligatures were placed in rats (groups 2-5) for 7 days. Groups 4 and 5 were then treated with AE for an additional 14 days. Saliva was collected from all groups, and probing pocket depth was measured in succession. Periodontal pocket tissues were subjected to histomorphometric analysis after the rats were sacrificed. Bone marrow-derived macrophages and murine macrophages were stimulated with receptor activator of nuclear factor-κB ligand (RANKL) and treated with different concentrations of AE. AMCase expression was detected from the analysis of saliva, periodontal pocket tissues, and differentiated osteoclasts. Results: Among rats with P. gingivalis-induced periodontitis, the alveolar bone resorption levels and periodontal pocket depth were significantly reduced after treatment with AE. AMCase protein expression was significantly higher in the disease group than in the healthy control (P<0.05). However, AE inhibited periodontal inflammation by downregulating AMCase expression in saliva and periodontal pocket tissue. AE significantly reduced RANKL-stimulated osteoclastogenesis by modulating AMCase (P<0.05). Conclusions: AE decreases alveolar bone loss and periodontal inflammation, suggesting that this natural anthraquinone has potential value as a novel therapeutic agent against periodontal disease.

• Biomolecules & Therapeutics
• /
• v.29 no.3
• /
• pp.331-341
• /
• 2021

Liver cancer is a common tumor and currently the second leading cause of cancer-related mortality globally. Liver cancer is highly related to inflammation as more than 90% of liver cancer arises in the context of hepatic inflammation, such as hepatitis B virus and hepatitis C virus infection. Despite significant improvements in the therapeutic modalities for liver cancer, patient prognosis is not satisfactory due to the limited efficacy of current drug therapies in anti-metastatic activity. Therefore, developing new effective anti-cancer agents with anti-metastatic activity is important for the treatment of liver cancer. In this study, SP-8356, a verbenone derivative with anti-inflammatory activity, was investigated for its effect on the growth and migration of liver cancer cells. Our findings demonstrated that SP-8356 inhibits the proliferation of liver cancer cells by inducing apoptosis and suppressing the mobility and invasion ability of liver cancer cells. Functional studies revealed that SP-8356 inhibits the mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways, which are related to cell proliferation and metastasis, resulting in the downregulation of metastasis-related genes. Moreover, using an orthotopic liver cancer model, tumor growth was significantly decreased following treatment with SP-8356. Thus, this study suggests that SP-8356 may be a potential agent for the treatment of liver cancer with multimodal regulation.

• The Journal of the Institute of Internet, Broadcasting and Communication
• /
• v.23 no.1
• /
• pp.29-35
• /
• 2023

In this paper, we propose a SW-EDU bot, a chatbot learning model for coding education by using a chatbot system. The same scenario-based models are created on the basis of Dialogflow and Kakao i Open Builder, which are representative chatbot builders. And then a SW-EDU bot is designed and implemented by selecting the builder more appropriate to our purpose. The implemented chatbot system aims to learn effective learning methods while encouraging self-direction of users by providing learning type selection, concept learning, and problem solving by difficulty level. In order to compare the usability of chatbot builders, five indicators are selected, and based on these, a builder with a comparative advantage is selected, and SW-EDU bot is implemented based on these. Through usability evaluation, we analyze the feasibility of SW-EDU bot as a learning support tool and confirm the possibility of using it as a new coding education learning tool.

• The Korea Journal of Herbology
• /
• v.28 no.6
• /
• pp.135-143
• /
• 2013

Objectives : The purpose of this study was to determine whether the methanol extract of Cassia mimosoides var. nomame Makino, a naturally growing plant in Korea, could prevent the renal-ischemia/reperfusion injury in a rat model or not. Methods : The radical scavenging activities of the extracts, and ascorbic acid as a positive control, were measured in vitro. At one hour after an intraperitoneal injection of the extract (400 mg/kg), renal ischemia/reperfusion injury was generated by 40 min clamping of the left renal artery in rats. After renal ischemia/reperfusion and 24 hr restoration of blood circulation, the serum creatinine concentration was measured. And the extent of epithelial cell injury and apoptosis was assessed by various staining technologies. The Bax/Bcl-2 ratio and activated caspase-3 were assessed by immunohistochemistry. Results : The extract showed a slightly lower level of radical scavenging activity than that of ascorbic acid. Compared to those of the vehicle-treated group, the extract-treated group displayed a significantly smaller tubular epithelial cell injury of 54% reduction in the outer medulla region and a lower serum creatinine concentration of 50% reduction. It seems that the reduction in cellular injury is due to the attenuation of the Bax/Bcl-2 ratio, and the inhibition of caspase-3 activation by the extract of Cassia mimosoides. Conclusions : Cassia mimosoides var. nomame Makino could be a good candidate for a prophylactic agent against the ischemia/reperfusion/induced kidney injury.

• The Korea Journal of Herbology
• /
• v.34 no.3
• /
• pp.1-7
• /
• 2019

Objectives : Amyloid ${\beta}(A{\beta})$ could induce cognitive deficits through oxidative stress, inflammation, and neuron death in Alzheimer's disease (AD). This study was investigated the effect of Angelica keiskei KOIDZUMI (AK) on memory in $A{\beta}$-induced an AD model. Methods : AK was extracted uses 70% ethanol solvent. Total polyphenol and flavonoids content were obtained by the Folin-Ciocalteu and the Ethylene glycol colorimetric methods, respectively. The antioxidant activities were assessed through free radical scavenging assays using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazolin-6-sulfonic acid) (ABTS) methods. Intracerebroventrical (i.c.v) injection of $A{\beta}$ 1-42 was used to induce AD in male ICR mice, followed by administrations of 5, 10 or 20 mg/kg AK on a daily. Animals were subjected to short and long term memory behavior in Y-maze and passive avoidance test. Results : The total polyphenol and flavonoids contents of the AK extract were $88.73{\pm}6.36mg$ gallic acid equivalent/g, $84.21{\pm}5.04mg$ rutin equivalent/g, respectively. The assays of DPPH and ABTS revealed that AK extract in treated concentrations (31.25, 62.5, 125, 250, 500, $1000{\mu}g/m{\ell}$) increased antioxidant activity in a dose-dependent manner. Oral administration of AK extract significantly reversed the $A{\beta}$ 1-42-induced decreasing of the spontaneous alternation in the Y-maze test and $A{\beta}$ 1-42-induced shorting of the step-through latency in the passive avoidance test. Conclusions : The findings suggest that AK indicated the antioxidant protective effects against $A{\beta}$-induced memory deficits, and therefore a potential lead natural therapeutic drug or agent for AD.

• Biomolecules & Therapeutics
• /
• v.30 no.4
• /
• pp.360-367
• /
• 2022

Tropomyosin receptor kinase A (TrkA) protein is a receptor tyrosine kinase encoded by the NTRK1 gene. TrkA signaling mediates the proliferation, differentiation, and survival of neurons and other cells following stimulation by its ligand, the nerve growth factor. Chromosomal rearrangements of the NTRK1 gene result in the generation of TrkA fusion protein, which is known to cause deregulation of TrkA signaling. Targeting TrkA activity represents a promising strategy for the treatment of cancers that harbor the TrkA fusion protein. In this study, we evaluated the TrkA-inhibitory activity of the benzoxazole compound KRC-108. KRC-108 inhibited TrkA activity in an in vitro kinase assay, and suppressed the growth of KM12C colon cancer cells harboring an NTRK1 gene fusion. KRC-108 treatment induced cell cycle arrest, apoptotic cell death, and autophagy. KRC-108 suppressed the phosphorylation of downstream signaling molecules of TrkA, including Akt, phospholipase Cγ, and ERK1/2. Furthermore, KRC-108 exhibited antitumor activity in vivo in a KM12C cell xenograft model. These results indicate that KRC-108 may be a promising therapeutic agent for Trk fusion-positive cancers.