• 대한한의학회지
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• 제35권2호
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• pp.12-18
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• 2014

Objectives: This was a retrospective case series about the clinical effect of integrated approach with behavior therapy for obstructive sleep apnea (OSA). Methods: Medical records of twelve patients with OSA who were treated with behavior modification including nasal breathing with oral appliances and sleep in lateral position, oral administration of herbal medicines and acupuncture treatment between January and September of 2013 were reviewed. Apnea-hypopnea index (AHI), day time sleepiness, apneas and hypopneas counts during sleep, risk indicator (RI), oxygen desaturation index, average saturation during sleep, lowest desaturation, lowest saturation, snoring events ratio and number of desaturations (%) were assessed before and after treatments with the ApneaLink device, which is a portable diagnostic apparatus for monitoring airflows of the patient's breath at home. Results: After an average 62.67 (SD 37.16) days of treatment, AHI (from 17.67, 12.79 to 8.75, 8.25, p=0.007), RI (from 22.00, 13.26 to 12.09, 8.03, p=0.004), oxygen desaturation index (from 17.33, 12.17 to 8.17, 7.86, p=0.005), and number of desaturations (from 7.00 times, 9.79 to 0.92 times, 1.39, p=0.044) showed significant improvement. Daytime sleepiness improved from 6.5 (3.2) to 3.8 (1.8) but there was no significant difference after treatment (p=0.17). No adverse events related to treatment were observed during participation in the treatment. Conclusion: From this case series, we found that behavior modification with herbal medication and acupuncture may be effective for improving sleep apnea without serious adverse events. Future randomized controlled trials with larger sample size will be necessary for concrete evidence on the benefit of this integrated treatment for OSA.

• Biomolecules & Therapeutics
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• 제25권4호
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• pp.404-410
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• 2017

Benzylideneacetophenone derivative (1E)-1-(4-hydroxy-3-methoxyphenyl) hept-1-en-3-one (JC3) elicited cytotoxic effects on MDA-MB 231 human breast cancer cells-radiation resistant cells (MDA-MB 231-RR), in a dose-dependent manner, with an $IC_{50}$ value of $6{\mu}M$ JC3. JC3-mediated apoptosis was confirmed by increase in sub-G1 cell population. JC3 disrupted the mitochondrial membrane potential, and reduced expression of anti-apoptotic B cell lymphoma-2 protein, whereas it increased expression of pro-apoptotic Bcl-2-associated X protein, leading to the cleavage of caspase-9, caspase-3 and poly (ADP-ribose) polymerase. In addition, JC3 activated mitogen-activated protein kinases, and specific inhibitors of these kinases abrogated the JC3-induced increase in apoptotic bodies. JC3 increased the level of intracellular reactive oxygen species and enhanced oxidative macromolecular damage via lipid peroxidation, protein carbonylation, and DNA strand breakage. Considering these findings, JC3 is an effective therapy against radiation-resistant human breast cancer cells.

• Toxicological Research
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• 제29권1호
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• pp.35-42
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• 2013

Quantum dots (QDs) have received considerable attention due to their potential role in photosensitization during photodynamic therapy. Although QDS are attractive nanomaterials due to their novel and unique physicochemical properties, concerns about their toxicity remain. We suggest a combination strategy, CdSe/ZnS QDs together with curcumin, a natural yellow pigment from turmeric, to reduce QD-induced cytotoxicity. The aim of this study was to explore a potentially effective cancer treatment: co-exposure of HL-60 cells and human normal lymphocytes to CdSe/ZnS QDs and curcumin. Cell viability, apoptosis, reactive oxygen species (ROS) generation, and DNA damage induced by QDs and/or curcumin with or without ultraviolet A (UVA) irradiation were evaluated in both HL-60 cells and normal lymphocytes. In HL-60 cells, cell death, apoptosis, ROS generation, and single/double DNA strand breaks induced by QDs were enhanced by treatment with curcumin and UVA irradiation. The protective effects of curcumin on cell viability, apoptosis, and ROS generation were observed in normal lymphocytes, but not leukemia cells. These results demonstrated that treatment with QD combined with curcumin increased cell death in HL-60 cells, which was mediated by ROS generation. However, curcumin acted as an antioxidant in cultured human normal lymphocytes.

• 대한임상독성학회지
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• 제11권1호
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• pp.41-45
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• 2013

Following are brief statements about the delayed encephalopathy of a patient who recovered without disturbance of consciousness after acute carbon monoxide poisoning. A 72-year-old male was found without consciousness at home and then visited the ER center. Later we learned that the patient was using briquettes as a household heating source. Blood carbon monoxide hemoglobin level was 17.5%. As carbon monoxide poisoning was uncertain after the first interview with the patient, hyperbaric oxygen therapy was not administered at the early stage. After supplying 100% oxygen, the patient recovered consciousness, however, the strength of the lower limb muscle had decreased to class II. The patient showed continued weakening of the lower limb muscle and an increase of CPK; therefore, he was diagnosed as carbon monoxide intoxication and rhabdomyolysis and then admitted to the intensive care unit (ICU) for conservative treatment. During the hospitalization period, continued weakening of the lower limb muscle was observed and he was diagnosed as myopathy after EMG/MCV. However, he suddenly showed altered mentality on the 20th day of hospitalization, and underwent brain MRI. T2 weighted MRI showed typically high signal intensity of both globus pallidus and periventricular white matter; therefore, he was diagnosed as delayed carbon monoxide encephalopathy. This case showed delayed encephalopathy accompanied by rhabdomyolysis and myopathy of a patient who recovered without disturbance of consciousness.

• BMB Reports
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• 제53권6호
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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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• 제10권5호
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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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• 제44권10호
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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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• 제84권3호
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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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• 제27권5호
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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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• 제55권3호
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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.