• International Journal of Stem Cells
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• v.16 no.3
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• pp.304-314
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• 2023

Background and Objectives: Ear cartilage malformations are commonly encountered problems in reconstructive surgery, since cartilage has low self-regenerating capacity. Malformations that impose psychological and social burden on one's life are currently treated using ear prosthesis, synthetic implants or autologous flaps from rib cartilage. These approaches are challenging because not only they request high surgical expertise, but also they lack flexibility and induce severe donor-site morbidity. Through the last decade, tissue engineering gained attention where it aims at regenerating human tissues or organs in order to restore normal functions. This technique consists of three main elements, cells, growth factors, and above all, a scaffold that supports cells and guides their behavior. Several studies have investigated different scaffolds prepared from both synthetic or natural materials and their effects on cellular differentiation and behavior. Methods and Results: In this study, we investigated a natural scaffold (alginate) as tridimensional hydrogel seeded with progenitors from different origins such as bone marrow, perichondrium and dental pulp. In contact with the scaffold, these cells remained viable and were able to differentiate into chondrocytes when cultured in vitro. Quantitative and qualitative results show the presence of different chondrogenic markers as well as elastic ones for the purpose of ear cartilage, upon different culture conditions. Conclusions: We confirmed that auricular perichondrial cells outperform other cells to produce chondrogenic tissue in normal oxygen levels and we report for the first time the effect of hypoxia on these cells. Our results provide updates for cartilage engineering for future clinical applications.

• Nutrition Research and Practice
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• v.4 no.6
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• pp.455-461
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• 2010

The tumor microenvironment, particularly sufficient nutrition and oxygen supply, is important for tumor cell survival. Nutrition deprivation causes cancer cell death. Since apoptosis is a major mechanism of neuronal loss, we explored neuronal apoptosis in various microenvironment conditions employing neuroblastoma (NB) cells. To investigate the effects of tumor malignancy and differentiation on apoptosis, the cells were exposed to poor microenvironments characterized as serum-free, low-glucose, and hypoxia. Incubation of the cells in serum-free and low-glucose environments significantly increased apoptosis in less malignant and more differentiated N-type IMR32 cells, whereas more malignant and less differentiated I-type BE(2)C cells were not affected by those treatments. In contrast, hypoxia (1 % $O_2$) did not affect apoptosis despite cell malignancy. It is suggested that DLK1 constitutes an important stem cell pathway for regulating self-renewal, clonogenicity, and tumorigenicity. This raises questions about the role of DLK1 in the cellular resistance of cancer cells under poor microenvironments, which cancer cells normally encounter. In the present study, DLK1 overexpression resulted in marked protection from apoptosis induced by nutrient deprivation. This in vitro model demonstrated that increasing severity of nutrition deprivation and knock-down of DLK1 caused greater apoptotic death, which could be a useful strategy for targeted therapies in fighting NB as well as for evaluating how nutrient deprived cells respond to therapeutic manipulation.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.31 no.3
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• pp.343-352
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• 1998

The relationship between summer hypoxia in bottom water layer and benthic community structure was discussed at forty sampling stations in semi-enclosed Youngsan River estuarine bay, Korea. The oxygen deficient layer less than $2.0 mg/\ell$ was widely developed in the inner estuarine stations in summer due to the summer stratification. A total of 141 species was occurred, with a mean density of $1,923 ind./m^2$ and biomass of $79.44\;g/m^2$ in summer season. The species number was significantly increased with the increment of the bottom dissolved oxygen, whereas density and biomass were partially correlated within the low oxygen level of $2.0\;mg/\ell$. These results imply that benthic community structures are affected by bottom oxygen depletion in summer. Cluster analysis showed that the benthic community could be classified into three station groups. These station groups from the species composition coincided with the groups based on the environmental factors. This fact suggests that the overall spatial distribution of macrozoobenthos in Youngsan River estuarine bay in summer should be controlled by the summer hypoxia and clay content of the area. Group-I was located the innermost estunrine bay from Mokpo Harbour to near the dike, where summer hypoxia was developed and one bivalve Theora fragilis, two polychaetes, Tharyx sp. and Lumbrineris longifolia were dominated. Group-II, the central transitory area of the estuarine bay between two another stational groups, where two bivalves Theora fragilis, Raetellops pulchella and a polychaete Tharyx sp. predominated with relatively low density compared to that of Group-I. Group-III, the mouth part of the estunrine bay exposed to the open sea, where a polychaetes Poecilochaetus johnsoni and a bivalve Yoldia Johanni predominated.

• 한국균학회소식:학술대회논문집
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• 2015.05a
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• pp.15-15
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• 2015

Aspergillus fumigatus is a major cause of invasive aspergillosis (IA), a significant health issue worldwide with high mortality rates up to 95%. Our lab is interested in how A. fumigatus adapts to low oxygen conditions 'hypoxia', which is one of the important host microenvironments. A. fumigatus SrbA is a basic helix-loop-helix (bHLH) transcriptional regulator and belongs to sterol regulatory element binding protein (SREBP) family members. Loss of SrbA completely blocks growth in hypoxia and results in avirulence in murine models of IA suggesting an essential role of SrbA in hypoxia adaptation and virulence in A. fumigatus. We conducted chromatin immunoprecipitation sequencing (ChIP-seq) with A. fumigatus wild type using a SrbA specific antibody, and 97 genes were revealed as SrbA direct targets. One of the 'SrbA regulons' (AFUB_099590) was a putative bHLH transcriptional regulator whose sequence contained a characteristic tyrosine substitution in the basic portion of the bHLH domain of SREBPs. Therefore, we designated AFUB_099590 SrbB. Further characterization of SrbB demonstrated that SrbB is important for radial growth, biomass production, and biosynthesis of heme intermediates in hypoxia and virulence in A. fumigatus. A series of quantitative real time PCR showed that transcription of several SrbA regulons is coordinately regulated by two SREBPs, SrbA and SrbB in hypoxia. This suggests that SrbA and SrbB have both dependent and independent functions in regulation of genes responsible for hypoxia adaptation in A. fumigatus. Together, our data provide new insights into complicated roles of SREBPs in adaptation of host environments and virulence in pathogenic fungi.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.5
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• pp.509-518
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• 2017

Glioblastoma multiforme (GBM) is the most common primary intracranial tumor in adults and has poor prognosis. The GBM-specific tumor microenvironment (TME) plays a crucial role in tumor progression, immune escape, local invasion, and metastasis of GBM. Here, we demonstrate that hypoxia, reactive oxygen species (ROS), and differential concentration of glucose influence the expression of cytokines and chemokines, such as IL-6, IL-8, and IP-10, in human glial cell lines. Treatment with cobalt chloride ($CoCl_2$) and hydrogen peroxide ($H_2O_2$) significantly increased the expression levels of IL-6, IL-8, and IP-10 in a dose-dependent manner in CRT-MG and U251-MG astroglioma cells, but not in microglia cells. However, we found strikingly different patterns of expression of cytokines and chemokines between $H_2O_2$-treated CRT-MG cells cultured in low- and high-glucose medium. These results suggest that astroglioma and microglia cells exhibit distinct patterns of cytokine and chemokine expression in response to $CoCl_2$ and $H_2O_2$ treatment, and different concentrations of glucose influence this expression under either hypoxic or oxidant-enriched conditions.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.1
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• pp.53-62
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• 2016

Mesenchymal stem cells (MSCs) in the bone marrow and other somatic tissues reside in an environment with relative low oxygen tension. Cobalt chloride ($CoCl_2$) can mimic hypoxic conditions through transcriptional changes of some genes including hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) and vascular endothelial growth factor (VEGF). This study evaluated the potential role of $CoCl_2$ preconditioning on multi-lineage differentiation of C3H/10T1/2, a murine MSC line to understand its possible molecular mechanisms in vitro. $CoCl_2$ treatment of MSCs markedly increased HIF-$1{\alpha}$ and VEGF mRNA, and protein expression of HIF-$1{\alpha}$. Temporary preconditioning of MSCs with $CoCl_2$ induced up-regulation of osteogenic markers including alkaline phosphatase, osteocalcin, and type I collagen during osteogenic differentiation, followed by enhanced mineralization. $CoCl_2$ also increased chondrogenic markers including aggrecan, sox9, and type II collagen, and promoted chondrocyte differentiation. $CoCl_2$ suppressed the expression of adipogenic markers including $PPAR{\gamma}$, aP2, and $C/EBP{\alpha}$, and inhibited adipogenesis. Temporary preconditioning with $CoCl_2$ could affect the multi-lineage differentiation of MSCs.

• The Sea:JOURNAL OF THE KOREAN SOCIETY OF OCEANOGRAPHY
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• v.28 no.3
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• pp.95-120
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• 2023

Methane (CH₄) is a key greenhouse gas in the atmosphere with 85 times greater greenhouse potent relative to carbon dioxide (CO₂). The atmospheric concentration of CH₄ is rapidly increasing due to the intensive usage of CH₄ and the thawing of the cryosphere. Additionally, with the current warming of ocean water, the dissociation of gas hydrates, an ice-like compound and the largest reservoir of CH₄ on Earth, is expected to occur, resulting in the release of CH₄ from the seafloor into the overlying water and atmosphere. Moreover, bottom water hypoxia is another concern that potentially introduces greenhouse gases into the atmosphere. With ongoing global warming and eutrophication, the size and duration of bottom water hypoxia are rapidly increasing. These low-oxygen conditions would relocate the redox zone shallower in sediment or in the water column, causing the release of CH₄ into the atmosphere and thereby intensifying global warming. However, there exists a gap in the understanding of CH₄ dynamics including its generation in relation to bottom water hypoxia. Therefore, this review article aims to understand the relationship between CH₄ and bottom water hypoxia and to draw attention to CH₄ investigation in Korea.

• Neonatal Medicine
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• v.18 no.2
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• pp.320-327
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• 2011

Purpose: To determine the effect of changing practice guidelines designed to avoid hyperoxia or hypoxia in very low birth weight or very preterm infants. Methods: We analyzed a database of <1,500 g birth weight or <32 weeks of gestation infants who were born and admitted to the neonatal intensive care unit of Chungnam National University Hospital from January 2007 to July 2010. First, we defined the relationship between arterial partial pressure of oxygen ($PaO_2$) and pulse oxygen saturation ($SpO_2$). When we evaluated 96 pairs of $PaO_2$ and $SpO_2$ measurements, oxygen saturation was 90-94% at a $PaO_2$ of 43-79 mmHg on the oxyhemoglobin dissociation curve, according to pulse oximetry. Based on this observation, a change in practice was instituted in August 2008 with the objective of avoiding hypoxia and hyperoxia in preterm infants with targeting a $SpO_2$ 90-94% (period II). Before the change in practice, high alarms for $SpO_2$ were set at 100% and low alarms at 95% (period I). Results: Sixty-eight infants the met enrollment criteria and 38 (56%) were born during period II, after the change in $SpO_2$ targets. Demographic characteristics, except gender, were similar between the infants born in both periods. After correcting for the effect of confounding factors, the rates for mortality, severe retinopathy of prematurity, and IVH attended to be lower than those for infants in period II. No difference in the rate of patent ductus arteriosus needed to treat was observed. Conclusion: A change in the practice guidelines aimed at avoiding low oxygen saturation and hyperoxia did not increase neonatal complication rates and showed promising results, suggesting decreased mortality and improvements in short term morbidity. It is still unclear what range of oxygen saturation is appropriate for very preterm infants but the more careful saturation targeting guideline should be considered to prevent hypoxemic events and hyperoxia.

• Journal of Korean Neurosurgical Society
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• v.29 no.8
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• pp.1008-1018
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• 2000

Objective : Glutamate induced excitotoxicity is one of the leading causes of cell death under pathologic condition. However, there is controversy whether excitotoxicity may also participate in the neuronal death under low intensity insult such as simple hypoxia or hypoglycemia. To investigate the role of NMDA receptor in low intensity insult, we chose anoxia as the method of injury and used organotypically cultured hippocampal slice as the material of experiment. Materials & Methods : The hippocampal slices cultured for 2-3 weeks were exposed to 60 minutes of complete oxygen deprivation(anoxia). Neuronal death was assessed with Sytox stain. Corrected optical density of fluorescence in gray scale, used as cellular death indicator, was obtained from pictures taken at 24 and 48 hours following the insult. The well-known in vivo phenomenon of regional difference in susceptibility of hippocampal sub-fields to ischemic insult was reproduced in HOSC(hippocampal organotypic slice culture) by complete oxygen deprivation injury. Results : $CA_1$ was the most vulnerable to complete oxygen deprivation in hippocampus while $CA_3$ was resistant. Oxygen deprivation for 10 and 20 minutes with glucose(6.5g/l) present was insufficient to induce neuronal death in the cultured hippocampal slice. However, after 30 minutes exposure under anoxic condition, neuronal death was able to be detected in the center of $CA_1$ area. The intensity and area of fluorescence indicating cell death correlated with the duration of oxygen deprivation. NMDA receptor and non-NMDA receptor blocking with MK-801(30 & $60{\mu}M$) and CNQX($100{\mu}M$) did not provide cellular protection to HOSC against damage induced by oxygen deprivation, but increased intracellular calcium buffering capacity with BAPTA-AM($10{\mu}M$) was effective in preventing neuronal death (p=0.01, Student's t-test). Cycloheximide($1{\mu}g/ml$, $10{\mu}g/ml$) provided no protection to HOSC against insult of complete oxygen deprivation for 60 minutes and combined therapy of MK-801(30 & $60{\mu}M$) and cycloheximide(1 & $10{\mu}g/ml$) was also ineffective in preventing neuronal death. Conclusion : The results of this study show that the another mechanism not associated with glutamate receptor(NMDA & non NMDA) may play major role in cell death mechanisms induced by complete oxygen deprivation and increased intracellular calcium during anoxia may participate in the neuronal death mechanism of oxygen deprivation. Further investigation of the calcium entry channel activated during oxygen deprivation is necessary to understand the neuronal death of anoxia.

• Journal of Embryo Transfer
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• v.30 no.4
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• pp.305-313
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• 2015

Xenotransplantation of pig islet regarded as a good alternative to allotransplantation. However, cellular death mediated by hypoxia-reoxygenation injury after transplantation disturb success of this technique. In the present study, we produce transgenic pig expressing human heme oxygenase 1 (HO1) genes to overcome cellular death for improving efficiency of islet xenotransplantation. Particularly, Korean miniature pig breed, Micro-Pig, was used in the present study. Somatic cell nuclear transfer (SCNT) technique was used to produce the HO1 transgenic pig. Six alive transgenic piglets were produced and all the transgenic pigs were founded to have transgene in their genomic DNA and the gene was expressed in all tested organs. Also, in vitro cultured fibroblasts derived from the HO1 transgenic pig showed low reactive oxygen species level, improved cell viability and reduced apoptosis level.