• BMB Reports
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• v.53 no.6
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• pp.291-298
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• 2020

Tumor angiogenesis is an essential process for growth and metastasis of cancer cells as it supplies tumors with oxygen and nutrients. During tumor angiogenesis, many pro-angiogenic factors are secreted by tumor cells to induce their own vascularization via activation of pre-existing host endothelium. However, accumulating evidence suggests that vasculogenic mimicry (VM) is a key alternative mechanism for tumor vascularization when tumors are faced with insufficient supply of oxygen and nutrients. VM is a tumor vascularization mechanism in which tumors create a blood supply system, in contrast to tumor angiogenesis mechanisms that depend on pre-existing host endothelium. VM is closely associated with tumor progression and poor prognosis in many cancers. Therefore, inhibition of VM may be a promising therapeutic strategy and may overcome the limitations of anti-angiogenesis therapy for cancer patients. In this review, we provide an overview of the current anti-angiogenic therapies for ovarian cancer and the current state of knowledge regarding the links between microRNAs and the VM process, with a focus on the mechanism that regulates associated signaling pathways in ovarian cancer. Moreover, we discuss the potential for VM as a therapeutic strategy against ovarian cancer.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.5
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• pp.263-271
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• 2006

Since astrocytes were shown to play a central role in maintaining neuronal viability both under normal conditions and during stress such as ischemia, studies of the astrocytic response to stress are essential to understand many types of brain pathology. The micro array system permitted screening of large numbers of genes in biological or pathological processes. Therefore, the gene expression patterns in the in vitro model of astrocytes following exposure to oxygen-glucose deprivation (OGD) were evaluated by using the micro array analysis. Primary astrocytic cultures were prepared from postnatal Swiss Webster mice. The cells were exposed to OGD for 4 hrs at $37^{\circ}C$ prior to cell harvesting. From the cultured cells, we isolated mRNA, synthesized cDNA, converted to biotinylated cRNA and then reacted with GeneChips. The data were normalized and analyzed using dChip and GenMAPP tools. After 4 hrs exposure to OGD, 4 genes were increased more than 2 folds and 51 genes were decreased more than 2 folds compared with the control condition. The data suggest that the OGD has general suppressive effect on the gene expression with the exception of some genes which are related with ischemic cell death directly or indirectly. These genes are mainly involved in apoptotic and protein translation pathways and gap junction component. These results suggest that microarray analysis of gene expression may be useful for screening novel molecular mediators of astrocyte response to ischemic injury and making profound understanding of the cellular mechanisms as a whole. Such a screening technique should provide insights into the molecular basis of brain disorders and help to identify potential targets for therapy.

• Molecules and Cells
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• v.44 no.10
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• pp.710-722
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• 2021

Hypoxia, or low oxygen tension, is a hallmark of the tumor microenvironment. The hypoxia-inducible factor-1α (HIF-1α) subunit plays a critical role in the adaptive cellular response of hypoxic tumor cells to low oxygen tension by activating gene-expression programs that control cancer cell metabolism, angiogenesis, and therapy resistance. Phosphorylation is involved in the stabilization and regulation of HIF-1α transcriptional activity. HIF-1α is activated by several factors, including the mitogen-activated protein kinase (MAPK) superfamily. MAPK phosphatase 3 (MKP-3) is a cytoplasmic dual-specificity phosphatase specific for extracellular signal-regulated kinase 1/2 (Erk1/2). Recent evidence indicates that hypoxia increases the endogenous levels of both MKP-3 mRNA and protein. However, its role in the response of cells to hypoxia is poorly understood. Herein, we demonstrated that small-interfering RNA (siRNA)-mediated knockdown of MKP-3 enhanced HIF-1α (not HIF-2α) levels. Conversely, MKP-3 overexpression suppressed HIF-1α (not HIF-2α) levels, as well as the expression levels of hypoxia-responsive genes (LDHA, CA9, GLUT-1, and VEGF), in hypoxic colon cancer cells. These findings indicated that MKP-3, induced by HIF-1α in hypoxia, negatively regulates HIF-1α protein levels and hypoxia-responsive genes. However, we also found that long-term hypoxia (>12 h) induced proteasomal degradation of MKP-3 in a lactic acid-dependent manner. Taken together, MKP-3 expression is modulated by the hypoxic conditions prevailing in colon cancer, and plays a role in cellular adaptation to tumor hypoxia and tumor progression. Thus, MKP-3 may serve as a potential therapeutic target for colon cancer treatment.

• Tuberculosis and Respiratory Diseases
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• v.84 no.3
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• pp.217-225
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• 2021

Background: Despite the proven benefits of dexamethasone in hospitalized coronavirus disease 2019 (COVID-19) patients, the optimum time for the administration of dexamethasone is unknown. We investigated the progression of COVID-19 pneumonia based on the timing of dexamethasone administration. Methods: A single-center, retrospective cohort study based on medical record reviews was conducted between June 10 and September 21, 2020. We compared the risk of severe COVID-19, defined as the use of a high-flow nasal cannula or a mechanical ventilator, between groups that received dexamethasone either within 24 hours of hypoxemia (early dexamethasone group) or 24 hours after hypoxemia (late dexamethasone group). Hypoxemia was defined as room-air SpO₂ <90%. Results: Among 59 patients treated with dexamethasone for COVID-19 pneumonia, 30 were in the early dexamethasone group and 29 were in the late dexamethasone group. There was no significant difference in baseline characteristics, the time interval from symptom onset to diagnosis or hospitalization, or the use of antiviral or antibacterial agents between the two groups. The early dexamethasone group showed a significantly lower rate of severe COVID-19 compared to the control group (75.9% vs. 40.0%, p=0.012). Further, the early dexamethasone group showed a significantly shorter total duration of oxygen supplementation (10.45 days vs. 21.61 days, p=0.003) and length of stay in the hospital (19.76 days vs. 27.21 days, p=0.013). However, extracorporeal membrane oxygenation and in-hospital mortality rates were not significantly different between the two groups. Conclusion: Early administration of dexamethasone may prevent the progression of COVID-19 to a severe disease, without increased mortality.

• Biomolecules & Therapeutics
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• v.27 no.5
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• pp.442-449
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• 2019

This study sought to evaluate the effects of Asiatic acid in LPS-induced BV2 microglia cells and 1-methyl-4-phenyl-pyridine ($MPP^+$)-induced SH-SY5Y cells, to investigate the potential anti-inflammatory mechanisms of Asiatic acid in Parkinson's disease (PD). SH-SY5Y cells were induced using $MPP^+$ to establish as an in vitro model of PD, so that the effects of Asiatic acid on dopaminergic neurons could be examined. The NLRP3 inflammasome was activated in BV2 microglia cells to explore potential mechanisms for the neuroprotective effects of Asiatic acid. We showed that Asiatic acid reduced intracellular production of mitochondrial reactive oxygen species and altered the mitochondrial membrane potential to regulate mitochondrial dysfunction, and suppressed the NLRP3 inflammasome in microglia cells. We additionally found that treatment with Asiatic acid directly improved SH-SY5Y cell viability and mitochondrial dysfunction induced by $MPP^+$. These data demonstrate that Asiatic acid both inhibits the activation of the NLRP3 inflammasome by downregulating mitochondrial reactive oxygen species directly to protect dopaminergic neurons from, and improves mitochondrial dysfunction in SH-SY5Y cells, which were established as a model of Parkinson's disease. Our finding reveals that Asiatic acid protects dopaminergic neurons from neuroinflammation by suppressing NLRP3 inflammasome activation in microglia cells as well as protecting dopaminergic neurons directly. This suggests a promising clinical use of Asiatic acid for PD therapy.

• BMB Reports
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• v.55 no.3
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• pp.148-153
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• 2022

Etoposide is a chemotherapeutic medication used to treat various types of cancer, including breast cancer. It is established that pulsed electromagnetic field (PEMF) therapy can enhance the effects of anti-cancer chemotherapeutic agents. In this study, we investigated whether PEMFs influence the anti-cancer effects of etoposide in MCF-7 cells and determined the signal pathways affected by PEMFs. We observed that co-treatment with etoposide and PEMFs led to a decrease in viable cells compared with cells solely treated with etoposide. PEMFs elevated the etoposide-induced PARP cleavage and caspase-7/9 activation and enhanced the etoposide-induced down-regulation of survivin and up-regulation of Bax. PEMF also increased the etoposide-induced activation of DNA damage-related molecules. In addition, the reactive oxygen species (ROS) level was slightly elevated during etoposide treatment and significantly increased during co-treatment with etoposide and PEMF. Moreover, treatment with ROS scavenger restored the PEMF-induced decrease in cell viability in etoposide-treated MCF-7 cells. These results combined indicate that PEMFs enhance etoposide-induced cell death by increasing ROS induction-DNA damage-caspase-dependent apoptosis.

• Fisheries and Aquatic Sciences
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• v.26 no.2
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• pp.133-144
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• 2023

Auranofin is a US Food and Drug Administration (FDA)-approved anti-arthritis medication that functions as a thioredoxin reductase inhibitor. Spermidine, a polyamine present in marine algae, can exert various physiological functions. Herein, we examined the synergistic anticancer activity of auranofin and spermidine in hepatocellular carcinoma (HCC). Combined treatment with auranofin and spermidine suppressed cell viability more efficiently than either treatment alone in HCC Hep3B cells. The isobologram plotted by calculating the half maximal inhibitory concentration (IC₅₀) values of each drug indicated that the two drugs exhibited a synergistic effect. Based on the analysis of annexin V and cell cycle distribution, auranofin and spermidine markedly induced apoptosis in Hep3B cells. Moreover, auranofin and spermidine increased mitochondria-mediated apoptosis by promoting mitochondrial membrane potential (Δψm) loss. Auranofin and spermidine significantly increased reactive oxygen species (ROS) production in Hep3B cells, and the blocking ROS suppressed apoptosis induced by spermidine and auranofin. In addition, auranofin and spermidine reduced the expression of phosphorylated phosphatidylinositol-3 kinase (PI3K) and protein kinase B (Akt), and PI3K inhibitor accelerated auranofin- and spermidine-induced apoptosis. Using ROS scavenger and PI3K inhibitor, we revealed that ROS acts upstream of auranofin- and spermidine-induced apoptosis. Collectively, our study suggests that combination treatment with auranofin and spermidine could afford synergistic anticancer activity via ROS overproduction and reduced PI3K/Akt signaling pathway.

• Tuberculosis and Respiratory Diseases
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• v.47 no.5
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• pp.650-659
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• 1999

Background/Aims: It is well recognized that all aerobic cells have the protective mechanisms in order to minimize the tissue damage induced by various reactive oxygen species(ROS). Thioredoxin peroxidase(TPX) which has been recently identified and characterized functions to convert peroxide to water. The protein is also found in various subtypes(TPX-A & B, MER5, HS22 and HORF-06) and is known to be ubiquitous in most human cells. Especially, ischemic brain injuries, partial hepatectomy and radiation induced DNA damages. In treating lung cancer, radiation therapy has a major place in the local control and the relief of symptoms, but radiation induced free radical injury and resulting pulmonary fibrosis has been the major drawback of the therapy. However, little is known about the protective mechanisms and biologic modulations against radiation-induced tissue damages. Methods: Eighteen mice were divided into six groups, 3 in each group, and fifteen had received 900cGy of radiation. The mice were sacrificed according to the pre determined time schedule; immediate, 1, 2, 3 and 6 weeks after irradiation. Extracts were made from the lungs of each mice, Western blot analysis of various subtypes of TPX were done after SDS-P AGE. Examination of H & E stained slides from the same irradiated specimens and the control specimens were also performed. Results: No difference in the intensity of the immunoreactive bands in the irradiated lung samples of the mice compared to the unirradiated control was observed regardless of the time intervals, although H & E examination of the sample specimens demonstrated progressive fibrotic changes of the irradiated lung samples. Conclusion: In conclusion, according to our data, it is suggested that various thioredoxin peroxidase subtypes and catalase which are known to be increased in many repair processes may not be involved in the repair of the radiation injury to the lung and subsequent fibrosis.

• Journal of the Korean Society of Radiology
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• v.6 no.2
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• pp.83-91
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• 2012

The obesity is a medical condition in which excess body fat has accumulated to the extent. It may have an adverse effect on health, leading to reduced life expectancy and increased health problems such as lifestyle disease, hypertension, and diabetes. Furthermore, it may cause the mental illness such as depression, bipolar disorder, anorexia, hyperphagia, and so on by shrinking psychologically. So, it is regarded as the serious worldwide social problem. Recently, although there are many general obesity care methods with various approaches, these can't be the radical obesity care because of the side effects such as surgery aftereffect, drug addiction, and so on. For these reasons, a methodical approach with a consideration of individual obesity pattern is strongly demanded. In this study, complex obesity care and management system which is overcome the weakness of non-surgical obesity treatment is proposed. And the individually adapted obesity treatment system with the far-infrared therapy module, oxygen therapy module, color therapy module, and microwave therapy module was developed. The complex obesity treatment system which is proposed in this study, could improve the efficiency of treatment by suggesting the various treatment protocols. And proposed system could be the foundation of the high quality obesity treatment system.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.21 no.10
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• pp.127-136
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• 2020

Purpose: This study aimed to establish a basis for application time and cold therapy interval by checking the physiological changes after applying a cold-gel and ice pack, commonly applied to cold therapy, and after passive rewarming. Method: A total of 22 healthy adults used cold-gel packs and ice packs in a Randomized control group repeated measurement study, and passive rewarming was performed for 40 minutes after 30 minutes of cold therapy. After applying to the right axilla, StO₂, SpO₂, peripheral blood flow, skin and body temperature were measured 15 times every 5 minutes. Result: In the cold-gel pack group, StO₂ decreased from 69.43% to 61.06% after 30 minutes application, and in the ice pack group, StO₂ decreased from 67.66% to 64.80% (p <001). In the cold-gel pack group, skin temperature decreased from 33.57℃ to 29.15℃ after 30 minutes application, and in the ice pack group, skin temperature decreased from 32.64℃ to 28.90℃ (p <.001). Only skin temperature recovered completely after 40 minutes of rewarming. There were insignificant differences between the cold-gel pack and ice pack. Conclusion: When applying cold therapy to the axillary, at least 40 minutes for passive rewarming is necessary after 30 minutes of application.