• Molecules and Cells
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• 제42권10호
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• pp.702-710
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• 2019

Neuroinflammation is an important contributor to the pathogenesis of neurodegenerative disorders including Parkinson's disease (PD). We previously reported that our novel synthetic compound KMS99220 has a good pharmacokinetic profile, enters the brain, exerts neuroprotective effect, and inhibits $NF{\kappa}B$ activation. To further assess the utility of KMS99220 as a potential therapeutic agent for PD, we tested whether KMS99220 exerts an anti-inflammatory effect in vivo and examined the molecular mechanism mediating this phenomenon. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice, oral administration of KMS99220 attenuated microglial activation and decreased the levels of inducible nitric oxide synthase and interleukin 1 beta ($IL-1{\beta}$) in the nigrostriatal system. In lipopolysaccharide (LPS)-challenged BV-2 microglial cells, KMS99220 suppressed the production and expression of $IL-1{\beta}$. In the activated microglia, KMS99220 reduced the phosphorylation of $I{\kappa}B$ kinase, c-Jun N-terminal kinase, and p38 MAP kinase; this effect was mediated by heme oxygenase-1 (HO-1), as both gene silencing and pharmacological inhibition of HO-1 abolished the effect of KMS99220. KMS99220 induced nuclear translocation of the transcription factor Nrf2 and expression of the Nrf2 target genes including HO-1. Together with our earlier findings, our current results show that KMS99220 may be a potential therapeutic agent for neuroinflammation-related neurodegenerative diseases such as PD.

• KSII Transactions on Internet and Information Systems (TIIS)
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• 제15권4호
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• pp.1317-1341
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• 2021

Nowadays, the Internet of Things (IoT) is adopted to enable effective and smooth communication among different networks. In some specific application, the Wireless Sensor Networks (WSN) are used in IoT to gather peculiar data without the interaction of human. The WSNs are self-organizing in nature, so it mostly prefer multi-hop data forwarding. Thus to achieve better communication, a cross-layer routing strategy is preferred. In the cross-layer routing strategy, the routing processed through three layers such as transport, data link, and physical layer. Even though effective communication achieved via a cross-layer routing strategy, energy is another constraint in WSN assisted IoT. Cluster-based communication is one of the most used strategies for effectively preserving energy in WSN routing. This paper proposes a Bio-inspired cross-layer routing (BiHCLR) protocol to achieve effective and energy preserving routing in WSN assisted IoT. Initially, the deployed sensor nodes are arranged in the form of a grid as per the grid-based routing strategy. Then to enable energy preservation in BiHCLR, the fuzzy logic approach is executed to select the Cluster Head (CH) for every cell of the grid. Then a hybrid bio-inspired algorithm is used to select the routing path. The hybrid algorithm combines moth search and Salp Swarm optimization techniques. The performance of the proposed BiHCLR is evaluated based on the Quality of Service (QoS) analysis in terms of Packet loss, error bit rate, transmission delay, lifetime of network, buffer occupancy and throughput. Then these performances are validated based on comparison with conventional routing strategies like Fuzzy-rule-based Energy Efficient Clustering and Immune-Inspired Routing (FEEC-IIR), Neuro-Fuzzy- Emperor Penguin Optimization (NF-EPO), Fuzzy Reinforcement Learning-based Data Gathering (FRLDG) and Hierarchical Energy Efficient Data gathering (HEED). Ultimately the performance of the proposed BiHCLR outperforms all other conventional techniques.

• 대한본초학회지
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• 제36권2호
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• pp.31-42
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• 2021

Objectives : This study was undertaken to investigate the hepatoprotective effect of Spatholobi Caulis water extract (SC) to thioacetamide (TAA)-induced acute liver injury (ALI) in rats. Methods : The rats were injected intraperitoneally with TAA (200 mg/kg body weight) and orally administered SC (100 or 200 mg/kg b.w.) daily for 3 days. Liver biomarkers were assessed by serum glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and ammonia levels. Malondialdehyde (MDA) was measured both serum and liver tissue. In addition, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, anti-oxidant, and inflammation-related proteins were investigated by western blot analysis. Histological examination further confirmed though hematoxylin and eosin stain. Results : The SC treatment reduced liver function markers like GOT and GPT and also remarkably decreased ammonia level. Moreover, the elevated MDA level in TAA-induced group was significantly reduced by SC treatment. NADPH oxidase expression associated with oxidative stress including NOX2, NOX4, and p47phox markedly inhibited by SC administration. SC treatment exerted anti-oxidant effect through the increase of anti-oxidant enzyme including superoxide dismutase (SOD), Catalase, and heme oxygenase-1 (HO-1). The protein expressions of inflammatory cytokines such as tumor necrosis factor-�� (TNF-��), IL-6, and IL-1�� induced by nuclear factor-kappa B (NF-��B) activation were modulated through blocking the phosphorylation of inhibitor of nuclear factor ��B�� (I��B)��. SC treatment also improved histological alterations. Conclusion : These findings suggested that SC administration may be a potential candidate for the prevention or treatment of ALI.

• Journal of Microbiology and Biotechnology
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• 제32권3호
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• pp.365-377
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• 2022

Mammalian target of rapamycin (mTOR) is a serine-threonine kinase member of the cellular phosphatidylinositol 3-kinase (PI3K) pathway, which is involved in multiple biological functions by transcriptional and translational control. mTOR is a downstream mediator in the PI3K/Akt signaling pathway and plays a critical role in cell survival. In cancer, this pathway can be activated by membrane receptors, including the HER (or ErbB) family of growth factor receptors, the insulin-like growth factor receptor, and the estrogen receptor. In the present work, we congregated an electronic network of mTORC1 built on an assembly of data using natural language processing, consisting of 470 edges (activations/interactions and/or inhibitions) and 206 nodes representing genes/proteins, using the Cytoscape 3.6.0 editor and its plugins for analysis. The experimental design included the extraction of gene expression data related to five distinct types of cancers, namely, pancreatic ductal adenocarcinoma, hepatic cirrhosis, cervical cancer, glioblastoma, and anaplastic thyroid cancer from Gene Expression Omnibus (NCBI GEO) followed by pre-processing and normalization of the data using R & Bioconductor. ExprEssence plugin was used for network condensation to identify differentially expressed genes across the gene expression samples. Gene Ontology (GO) analysis was performed to find out the over-represented GO terms in the network. In addition, pathway enrichment and functional module analysis of the protein-protein interaction (PPI) network were also conducted. Our results indicated NOTCH1, NOTCH3, FLCN, SOD1, SOD2, NF1, and TLR4 as upregulated proteins in different cancer types highlighting their role in cancer progression. The MCODE analysis identified gene clusters for each cancer type with MYC, PCNA, PARP1, IDH1, FGF10, PTEN, and CCND1 as hub genes with high connectivity. MYC for cervical cancer, IDH1 for hepatic cirrhosis, MGMT for glioblastoma and CCND1 for anaplastic thyroid cancer were identified as genes with prognostic importance using survival analysis.

• 대한한방부인과학회지
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• 제34권3호
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• pp.15-28
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• 2021

Objectives: This study was designed to examine the anti-cancer activity by innate immunomodulating and anti-inflammatory effects of liriopis tuber water extract (LPE). Methods: Cell cytotoxicity was tested with 4T1 mouse mammary carcinoma cells, spleen cells, macrophage, and RAW264.7 cells. To investigate innate immunomodulating effects of LPE on macrophage, we measured tumor necrosis factor-alpha (TNF-α), interleukin-12 (IL-12), and interleukin-10 (IL-10). To investigate innate immunomodulating effects of LPE on RAW264.7 cell, we measured TNF-α, interleukin-6 (IL-6). In addition, TNF-α and nitric oxide (NO) induced by lipopolysaccharide (LPS) were measured after treating with LPE to observe innate immunomodulating effect of LPE on RAW264.7 cell. Also, mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) were examined by western blot analysis. Results: In an in vitro cytotoxicity analysis, LPE affected tumor cell growth above specific concentration. As compared with the control group, the production of TNF-α, IL-12, and IL-10 were increased in macrophage. As compared with the control group, the production of TNF-α and IL-6 were increased in RAW 264.7 cell. The expression of TNF-α and NO induced by LPS after treating LPE was decreased. In addition, treatment of RAW 264.7 cell with LPE increased the phosphorylation levels of p-extracellular signal-regulated kinase (p-ERK), p-Jun N-terminal kinase (p-JNK), and p-p38. Conclusions: LPE might have impact on the anti-cancer effect by activation of innate immune system and inflammation control.

• Journal of Ginseng Research
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• 제46권1호
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• pp.79-90
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• 2022

Background: Herbal medicines are popular approaches to capably prevent and treat obesity and its related diseases. Excessive exposure to dietary lipids causes oxidative stress and inflammation, which possibly induces cellular senescence and contribute the damaging effects in brain. The potential roles of selective enhanced ginsenoside in regulating high fat diet (HFD)-induced brain damage remain unknown. Methods: The protection function of Ginsenoside F1-enhanced mixture (SGB121) was evaluated by in vivo and in vitro experiments. Human primary astrocytes and SH-SY5Y cells were treated with palmitic acid conjugated Bovine Serum Albumin, and the effects of SGB121 were determined by MTT and lipid uptake assays. For in vivo tests, C57BL/6J mice were fed with high fat diet for 3 months with or without SGB121 administration. Thereafter, immunohistochemistry, western blot, PCR and ELISA assays were conducted with brain tissues. Results and conclusion: SGB121 selectively suppressed HFD-induced oxidative stress and cellular senescence in brain, and reduced subsequent inflammation responses manifested by abrogated secretion of IL-6, IL-1β and TNFα via NF-κB signaling pathway. Interestingly, SGB121 protects against HFD-induced damage by improving mitophagy and endoplasmic reticulum-stress associated autophagy flux and inhibiting apoptosis. In addition, SGB121 regulates lipid uptake and accumulation by FATP4 and PPARα. SGB121 significantly abates excessively phosphorylated tau protein in the cortex and GFAP activation in corpus callosum. Together, our results suggest that SGB121 is able to favor the resistance of brain to HFD-induced damage, therefore provide explicit evidence of the potential to be a functional food.

• 운동영양학회지
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• 제25권4호
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• pp.45-53
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• 2021

[Purpose] In this study, we investigated whether a 70% ethanolic (EtOH) extract of Sargassum horneri had antioxidant and anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated macrophage-like RAW 264.7 cells. [Methods] The proximate composition, fatty acids, amino acids, and dietary fiber of S. horneri, various biologically active compounds, and antioxidant activity were analyzed. [Results] The DPPH and ABTS free radical scavenging activities, as well as the reduction power, of the S. horneri extract used here were significantly increased in a concentration-dependent manner. This indicates that S. horneri contains bioactive compounds, such as phenols and flavonoids, that have excellent antioxidant activity. The cellular viability and metabolic activity results confirmed that the extract had no discernible toxicity at concentrations up to 100 ㎍/mL. The levels of nitrites and cytokines (PGE₂, TNF-α and IL-6), which mediate pro-inflammatory effect, were significantly inhibited by treatment with either 50 or 100 ㎍/mL S. horneri extract, whereas that of IL-1β was significantly inhibited by treatment with 100 ㎍/mL of the extract. Similarly, the expression of iNOS and COX-2 proteins also decreased according to 50 or 100 ㎍/mL extract concentrations. NF-κB binding to DNA was also significantly inhibited by treatment with 100 ㎍/mL of extract. [Conclusion] These results suggest that 70% EtOH extracts of S. horneri can relieve inflammation caused by disease or high intensity exercise.

• Journal of Ginseng Research
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• 제47권2호
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• pp.237-245
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• 2023

Background: Ginsenoside Rg2 (Rg2) has a variety of pharmacological activities and provides benefits during inflammation, cancer, and other diseases. However, there are no reports about the relationship between Rg2 and atherosclerosis. Methods: We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to detect the cell viability of Rg2 in vascular smooth muscle cells (VSMCs) and human umbilical vein endothelial cells (HUVECs). The expression of inflammatory factors in HUVECs and the expression of phenotypic transformation-related marker in VSMCs were detected at mRNA levels. Western blot method was used to detect the expression of inflammation pathways and the expression of phenotypic transformation at the protein levels. The rat carotid balloon injury model was performed to explore the effect of Rg2 on inflammation and phenotypic transformation in vivo. Results: Rg2 decreased the expression of inflammatory factors induced by lipopolysaccharide in HUVECs-without affecting cell viability. These events depend on the blocking regulation of NF-κB and p-ERK signaling pathway. In VSMCs, Rg2 can inhibit the proliferation, migration, and phenotypic transformation of VSMCs induced by platelet derived growth factor-BB (PDGF-BB)-which may contribute to its anti-atherosclerotic role. In rats with carotid balloon injury, Rg2 can reduce intimal proliferation after injury, regulate the inflammatory pathway to reduce inflammatory response, and also suppress the phenotypic transformation of VSMCs. Conclusion: These results suggest that Rg2 can exert its anti-atherosclerotic effect at the cellular level and animal level, which provides a more sufficient basis for ginseng as a functional dietary regulator.

• 대한한의학회지
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• 제43권4호
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• pp.20-32
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• 2022

Objectives: Kyungok-go (KOG) is a traditional multi-herbal medicine commonly used for enforcing weakened immunity for long time. Recently, there are several reports that KOG has anti-inflammatory and immuno-stimulatory activities in many experimental models. However, the protective effects of KOG on neuronal inflammation are still undiscovered. Thus, we investigated the neuro-protective activity of KOG on lipopolysaccharide (LPS)-stimulated mouse microglia cells. To find out KOG's anti-neuroinflammatory effects on microglial cells, we examined the production of nitrite using griess assay, and mRNA expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α using real time RT-PCR. In addition, to examine the regulating mechanisms of KOG, we investigated the protein expression of mitogen-activated protein kinases (MAPKs) and Iκ-Bα by western blot. KOG inhibited the elevation of nitrite, iNOS and COX-2 on LPS-stimulated BV2 cells. Also, KOG significantly inhibited the pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α on LPS-stimulated BV2 microglial cells. Moreover, KOG inhibited the activation of c-Jun N-terminal kinase (JNK), P38 and degradation of Iκ-Bα but not the activation of extracellular signal regulated kinase (ERK) on LPS-stimulated BV2 microglial cells. These results showed KOG has the anti-inflammatory effects through the inhibition on nitrite, iNOS, COX-2, IL-1β, IL-6, and TNF-α via the deactivation of JNK, p38 and nuclear factor (NF)-κB on LPS-stimulated BV2 microglial cells. Thereby, KOG could offer the new and promising treatment for neurodegenerative disease related to neuroinflammation.

• Journal of Ginseng Research
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• 제47권3호
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• pp.420-428
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• 2023

Background: Ginsenoside F2 (GF2), a minor component of Panax ginseng, has been reported to possess a wide variety of pharmacological activities. However, its effects on glucose metabolism have not yet been reported. Here, we investigated the underlying signaling pathways involved in its effects on hepatic glucose. Methods: HepG2 cells were used to establish insulin-resistant (IR) model and treated with GF2. Cell viability and glucose uptake-related genes were also examined by real-time PCR and immunoblots. Results: Cell viability assays showed that GF2 up to 50 μM did not affect normal and IR-HepG2 cell viability. GF2 reduced oxidative stress by inhibiting phosphorylation of the mitogen-activated protein kinases (MAPK) signaling components such as c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), and p38 MAPK, and reducing the nuclear translocation of NF-κB. Furthermore, GF2 activated PI3K/AKT signaling, upregulated the levels of glucose transporter 2 (GLUT-2) and GLUT-4 in IR-HepG2 cells, and promoted glucose absorption. At the same time, GF2 reduced phosphoenolpyruvate carboxykinase and glucose-6-phosphatase expression as well as inhibiting gluconeogenesis. Conclusion: Overall, GF2 improved glucose metabolism disorders by reducing cellular oxidative stress in IR-HepG2 cells via MAPK signaling, participating in the PI3K/AKT/GSK-3β signaling pathway, promoting glycogen synthesis, and inhibiting gluconeogenesis.