• Biomolecules & Therapeutics
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• v.29 no.4
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• pp.410-418
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• 2021

Helicobacter pylori causes chronic gastritis through cag pathogenicity island (cagPAI), vacuolating cytotoxin A (VacA), lipopolysaccharides (LPS), and flagellin as pathogen-related molecular patterns (PAMPs), which, in combination with the pattern recognition receptors (PRRs) of host cells promotes the expression and secretion of inflammation-causing cytokines and activates innate immune responses such as inflammasomes. To identify useful compounds against H. pylori-associated gastric disorders, the effect of chalcone derivatives to activate the nucleotide-binding oligomerization domain (NOD)-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome was examined in an H. pylori-infected human monocytic THP-1 cell line in this study. Among the five synthetic structurally-related chalcone derivatives examined, 2'-hydroxy-4',6'-dimethoxychalcone (8) and 2'-hydroxy-3,4,5-trimethoxychalcone (12) strongly blocked the NLRP3 inflammasome in H. pylori-infected THP-1 cells. At 10 μM, these compounds inhibited the production of active IL-1β, IL-18, and caspase-1, and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) oligomerization, but did not affect the expression levels of NLRP3, ASC, and pro-caspase-1. The interruption of NLRP3 inflammasome activation by these compounds was found to be mediated via the inhibition of the interleukin-1 receptor-associated kinase 4 (IRAK4)/IκBα/NF-κB signaling pathway. These compounds also inhibited caspase-4 production associated with non-canonical NLRP3 inflammasome activation. These results show for the first time that certain chalcones could interrupt the activation of the NLRP3 inflammasome in H. pylori-infected THP-1 cells. Therefore, these chalcones may be helpful in alleviating H. pylori-related inflammatory disorders including chronic gastritis.

• The Journal of the Korea institute of electronic communication sciences
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• v.17 no.5
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• pp.995-1002
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• 2022

Global Navigation Satellite System(GNSS) is a convenient system that acquires position and time information of a receiver if only satellite signals can be received anywhere in the world. However navigation signals include errors and a position error occurs according to the reception state of the signal. Also, a position error is affected by the geometric arrangement of the satellites. Therefore a receiver position performance varies by the number and status of visible satellites The condition of satellite signals is not good when the satellite rises or sets and the position change of receiver occurs when the signal is blocked by an obstacle such as a building in the urban area. In this paper, we proposed methods to improve the GNSS performance by using pseudorange correction method estimating the correction amount and the visible satellites selection method. By applying the proposed methods to an environment in which the number of visible satellites changes variously, the performance enhancement was verified.

• Proceedings of the SCSK Conference
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• 2003.09b
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• pp.73-86
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• 2003

Endothelins secreted from keratinocytes are intrinsic madiators for human melanocytes in UVB-induced pigmentation. Antimelanogenic ingredient, 1,2-Ο-diferulylglycerol(SM709) isolated from bamboo extract inhibited the melanin synthesis of Bl6F10 melanoma cells by 62%. To understand the cellular mechanism of antimelanogenic activity of SM709 in human melanocytes, the effects of SM709 on the ET-l-induced $Ca^{2+}$ mobilization were investigated. ET-l receptors in human melanocytes were characterized by using specific antagonist and found that ET-l increased intracellular $Ca^{2+}$ by activating ET-B receptor. SM709 completely blocked the ET-l-induced intracellular $Ca^{2+}$ increase and its inhibitory effect showed dose- and time- dependent manners. To investigate the role of SM709 on intracellular $Ca^{2+}$ store, when the $Ca^{2+}$ store was partially depleted by thapsigargin; a specific inhibitor of ER-type $Ca^{2+}$-ATPase, caffeine-induced $Ca^{2+}$ mobilization did not changed in the presence or absence of SM709, suggesting that SM709 has no effect on the $Ca^{2+}$ store. It is known that LPA receptor and P$_2$ receptor are linked to InsP$_3$ second messenger system. When these receptors in melanocytes were activated by LPA and ATP, the intracellular $Ca^{2+}$ signaling was observed even in the presence of SM709. From the above results, it can be suggested that SM709 has an antimelanogenic activity by antagonizing the ET-B receptor, resulting in subsequent intracellular $Ca^{2+}$ signaling, in UV induced pigmentation.nduced pigmentation.

• Biomolecules & Therapeutics
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• v.31 no.2
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• pp.200-209
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• 2023

Patients with non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) amplification or sensitive mutations initially respond to the tyrosine kinase inhibitor gefitinib, however, the treatment becomes less effective over time by resistance mechanism including mesenchymal-epithelial transition (MET) overexpression. A therapeutic strategy targeting MET and EGFR may be a means to overcoming resistance to gefitinib. In the present study, we found that picropodophyllotoxin (PPT), derived from the roots of Podophyllum hexandrum, inhibited both EGFR and MET in NSCLC cells. The antitumor efficacy of PPT in gefitinib-resistant NSCLC cells (HCC827GR), was confirmed by suppression of cell proliferation and anchorage-independent colony growth. In the targeting of EGFR and MET, PPT bound with EGFR and MET, ex vivo, and blocked both kinases activity. The binding sites between PPT and EGFR or MET in the computational docking model were predicted at Gly772/Met769 and Arg1086/Tyr1230 of each ATP-binding pocket, respectively. PPT treatment of HCC827GR cells increased the number of annexin V-positive and subG1 cells. PPT also caused G2/M cell-cycle arrest together with related protein regulation. The inhibition of EGFR and MET by PPT treatment led to decreases in the phosphorylation of the downstream-proteins, AKT and ERK. In addition, PPT induced reactive oxygen species (ROS) production and GRP78, CHOP, DR5, and DR4 expression, mitochondrial dysfunction, and regulated involving signal-proteins. Taken together, PPT alleviated gefitinib-resistant NSCLC cell growth and induced apoptosis by reducing EGFR and MET activity. Therefore, our results suggest that PPT can be a promising therapeutic agent for gefitinib-resistant NSCLC.

• Atmosphere
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• v.33 no.1
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• pp.49-59
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• 2023

Blocking refers to a class of weather phenomena appearing in the mid and high latitudes, whose characteristics are blocked airflow of persistence. Frequently found over the Pacific and Atlantic regions of the Northern Hemisphere, blocking affects severe weather in the surrounding areas with different mechanisms depending on the type of blocking patterns. Along with lots of studies about persistent weather extremes focusing on the specific types of blocking, a new categorization using Rossby wave breaking has emerged. This study aims to apply this concept to the classification of blockings over the Pacific and examine how different wave breakings specify the associated cold weather in the Korean peninsula. At the same time, we investigate a strongly developing ridge around the Pacific by designing a new detection algorithm, where a reversal method is modified to distinguish ridge-type blocking patterns. As result, Kamchatka blocking (KB) and strong ridge over the Central Pacific are observed the most frequently during 20 years (2001~2020) of the studied period, and anomalous low pressures with cold air over the Korean Peninsula are accompanied by blocking events. When it considers the Rossby wave breaking, cyclonic wave-breaking is dominant in KB, which generates low-pressure anomalies over the Korean Peninsula. However, KB with anticyclone wave breaking appears with the high-pressure anomalies over the Korean Peninsula and it generates the warm temperature anomaly. Lastly, the low-pressure anomalies are also generated by the strong ridge over the Central Pacific, which persists for approximately three days and give a significant impact on cold surge on the Korean Peninsula.

• Korean Circulation Journal
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• v.53 no.6
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• pp.387-403
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• 2023

Background and Objectives: Myocardial ischemia and reperfusion injury (MIRI) has high morbidity and mortality worldwide. We aimed to explore the role of long noncoding RNA lysyl oxidase like 1 antisense RNA 1 (LOXL1-AS1) in cardiomyocyte pyroptosis. Methods: Hypoxia/reoxygenation (H/R) injury was constructed in human cardiomyocyte (HCM). The level of LOXL1-AS1, miR-761, phosphatase and tensin homolog (PTEN) and pyroptosis-related proteins was monitored by quantitative real-time polymerase chain reaction or western blot. Flow cytometry examined the pyroptosis level. Lactate dehydrogenase (LDH), creatine kinase-MB and cardiac troponin I levels were detected by test kits. Enzyme-linked immunosorbent assay measured the release of inflammatory cytokines. Dual-luciferase assay validated the binding relationship among LOXL1-AS1, miR-761, and PTEN. Finally, ischemia/reperfusion (I/R) animal model was constructed. Hematoxylin and eosin staining assessed morphological changes of myocardial tissue. NOD-like receptor pyrin domain-containing protein 3 (NLRP3) and casepase-1 expression was determined by immunohistochemistry. Results: After H/R treatment, LOXL1-AS1 and PTEN were highly expressed but miR-761 level was suppressed. LOXL1-AS1 inhibition or miR-761 overexpression increased cell viability, blocked the release of LDH and inflammatory cytokines (interleukin [IL]-1β, IL-18), inhibited pyroptosis level, and downregulated pyroptosis-related proteins (ASC, cleaved caspase-1, gasdermin D-N, NLRP3, IL-1β, and IL-18) levels in HCMs. LOXL1-AS1 sponged miR-761 to up-regulate PTEN. Knockdown of miR-761 reversed the effect of LOXL1-AS1 down regulation on H/R induced HCM pyroptosis. LOXL1-AS1 aggravated the MIRI by regulating miR-761/PTEN axis in vivo. Conclusions: LOXL1-AS1 targeted miR-761 to regulate PTEN expression, then enhance cardiomyocyte pyroptosis, providing a new alternative target for the treatment of MIRI.

• IMMUNE NETWORK
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• v.16 no.4
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• pp.242-248
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• 2016

Thymic atrophy is a complication that results from exposure to many environmental stressors, disease treatments, and microbial challenges. Such acute stress-associated thymic loss can have a dramatic impact on the host's ability to replenish the necessary naïve T cell output to reconstitute the peripheral T cell numbers and repertoire to respond to new antigenic challenges. We have previously reported that treatment with the orexigenic hormone ghrelin results in an increase in the number and proliferation of thymocytes after dexamethasone challenge, suggesting a role for ghrelin in restraint stress-induced thymic involution and cell apoptosis and its potential use as a thymostimulatory agent. In an effort to understand how ghrelin suppresses thymic T cell apoptosis, we have examined the various signaling pathways induced by receptor-specific ghrelin stimulation using a restraint stress mouse model. In this model, stress-induced apoptosis in thymocytes was effectively blocked by ghrelin. Western blot analysis demonstrated that ghrelin prevents the cleavage of pro-apoptotic proteins such as Bim, Caspase-3, and PARP. In addition, ghrelin stimulation activates the Akt and Mitogen-activated protein kinases (MAPK) signaling pathways in a time/dose-dependent manner. Moreover, we also revealed the involvement of the FoxO3a pathway in the phosphorylation of Akt and ERK1/2. Together, these findings suggest that ghrelin inhibits apoptosis by modulating the stress-induced apoptotic signal pathway in the restraint-induced thymic apoptosis.

• Journal of Ginseng Research
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• v.47 no.5
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• pp.645-653
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• 2023

Background: Changes to work-life balance has increased the incidence of cervical cancer among younger people. A minor ginseng saponin known as ginsenoside Rk1 can inhibit the growth and survival of human cancer cells; however, whether ginsenoside Rk1 inhibits HeLa cell proliferation is unknown. Methods and results: Ginsenoside Rk1 blocked HeLa cells in the G0/G1 phase in a dose-dependent manner and inhibited cell division and proliferation. Ginsenoside Rk1 markedly also activated the apoptotic signaling pathway via caspase 3, PARP, and caspase 6. In addition, ginsenoside Rk1 increased LC3B protein expression, indicating the promotion of the autophagy signaling pathway. Protein processing in the endoplasmic reticulum signaling pathway was downregulated in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, consistent with teal-time quantitative PCR and western blotting that showed YOD1, HSPA4L, DNAJC3, and HSP90AA1 expression levels were dramatically decreased in HeLa cells treated with ginsenoside Rk1, with YOD1 was the most significantly inhibited by ginsenoside Rk1 treatment. Conclusion: These findings indicate that the toxicity of ginsenoside Rk1 in HeLa cells can be explained by the inhibition of protein synthesis in the endoplasmic reticulum and enhanced apoptosis, with YOD1 acting as a potential target for cervical cancer treatment.

• The Journal of Korean Medicine
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• v.24 no.2
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• pp.166-178
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• 2003

Objectives : Nitric oxide (NO) plays an important role in normal and pathophysiological cells as a messenger molecule, neurotransmitter, microbiological agent, or dilator of blood vessels and arteriosclerosis, respectively. This study was undertaken to understand the mechanism of NO production and effect of Hyeolbuchukeo-tang (Xiefuzhuyu-tang) on NO production in cultured vascular smooth muscle cell (VSMC). Methods and Results : VSMC was isolated from aorta and cultured. Cultured primary cells were identified as VSMC with anti--smooth muscle actin antibody. A large amount of NO was produced in cultured VSMC treated with $IFN-{\gamma}$ plus TNF in a time- and dose-dependent manner. $TNF-{\alpha}$ was a more efficient stimulator than $IFN-{\gamma}$ in NO production of cultured VSMC. iNOS protein wasdetected within 3 hrs and it increased up to 12 hrs in a time-dependent manner. However, accumulated NO in cytokine-treated VSMC was not detected within 3 hrs. NO production in cytokine-treated VSMC showed the dose- and time-dependent manner, and increased up to 48 hrs. The activated VSMC produced a large amount of NO (about 60 uM). Hyeolbuchukeo-tang (Xiefuzhuyu-tang) alone did not induceNO production, but it potentiated the effect of $TNF-{\alpha}$ on NO production and increased NO production by about 20%. Hyeolbuchukeo-tang (Xiefuzhuyu-tang) did not affect the transcriptional activity of iNOS gene, but increased the accumulation of iNOS. These results indicate that Hyeolbuchukeo-tang (Xiefuzhuyu-tang) could modulate the translational level of iNOS. PKC did not modulate NO production, but calcium ionophore A23187 decreased NO production. However, Hyeolbuchukeo-tang (Xiefuzhuyu-tang) elevated the decreased NO production in A23187-treated VSMC by modulating the stability of iNOS transcripts. Half-life of the synthesized transcripts appeared to have about 6 hrs. PDTC, an $NF-{\kappa}B$ inhibitor, blocked the accumulation of iNOS mRNA, indicating that $NF-{\kappa}B$ served as an important modulator in the transcriptional regulation of iNOS. As Hyeolbuchukeo-tang (Xiefuzhuyu-tang) potentiated the effect of the $TNF-{\alpha}$ on NO production but had no additional effect on PDTC-modulated NO production, it is suggested that Hyeolbuchukeo-tang (Xiefuzhuyu-tang) enhances the $TNF-{\alpha}-mediated$ NO production of VSMC by modulating the iNOS activity and the stability of iNOS transcripts in activated VSMC having the elevated intracellular calcium ion. Conclusions : This study suggests that Hyeolbuchukeo-tang (Xiefuzhuyu-tang) has a potential capacity for preventing and treating diseases of the circulation system, including arteriosclerosis.

• Korean Journal of Radiology
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• v.22 no.2
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• pp.179-188
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• 2021

Objective: This study aimed to prospectively compare the efficacy, safety, and mid-term outcomes of dual-switching monopolar (DSM) radiofrequency ablation (RFA) to those of conventional single-switching monopolar (SSM) RFA in the treatment of hepatocellular carcinoma (HCC). Materials and Methods: This single-center, two-arm, parallel-group, randomized controlled study was approved by the Institutional Review Board. Written informed consent was obtained from all patients upon enrollment. A total of 80 patients with 94 HCC nodules were randomized into either the DSM-RFA group or SSM-RFA group in a 1:1 ratio, using a blocked randomization method (block size 2). The primary endpoint was the minimum diameter of the ablation zone per unit time. The secondary endpoints included other technical parameters, complication rate, technique efficacy, and 2-year clinical outcomes. Results: Significantly higher ablation energy per unit time was delivered to the DSM-RFA group than to the SSM-RFA group (1.7 ± 0.2 kcal/min vs. 1.2 ± 0.3 kcal/min; p < 0.001). However, no significant differences were observed between the two groups for the analyzed variables, including primary endpoint, regarding size of the ablation zone and ablation time. Major complication rates were 4.9% in the DSM-RFA group and 2.6% in the SSM-RFA group (p = 1.000). The 2-year local tumor progression (LTP) rates of the HCC nodules treated using DSM-RFA and SSM-RFA were 8.5% and 4.7%, respectively (p = 0.316). The 2-year LTP-free survival rates of patients in the DSM-RFA and SSM-RFA groups were 90.0% and 94.4%, respectively (p = 0.331), and the 2-year recurrence-free survival rates were 54.9% and 75.7%, respectively (p = 0.265). Conclusion: Although DSM-RFA using a separable clustered electrode delivers higher ablation energy than SSM-RFA, its effectiveness failed to show superiority over SSM-RFA in the treatment of HCC.