• Journal of Chest Surgery
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• v.56 no.4
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• pp.274-281
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• 2023

Background: Patients who require initial venoarterial extracorporeal membrane oxygenation (VA ECMO) support may need to undergo veno-arteriovenous ECMO (VAV ECMO) conversion. However, there are no definitive criteria for conversion to VAV ECMO. We report 9 cases of VAV ECMO at Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine. Methods: Of 158 patients who received ECMO support between January 2017 and June 2019, 82 were supported by initial VA ECMO. We retrospectively reviewed the medical records of 9 patients (7 men and 2 women; age, 53.1±19.4 years) who had differential hypoxia and required VAV ECMO support. Percutaneous transaortic catheter venting was used to detect the differential hypoxia. Results: Among the 82 patients who received VA ECMO support, 9 (10.9%) had differential hypoxia and required conversion to VAV ECMO support. The mean time from VA ECMO support to VAV ECMO support and the mean duration of the VAV support were 2.1±2.2 days and 1.9±1.5 days, respectively. The average peak inspiratory pressure before and after VAV ECMO application was 23.89±3.95 cmH₂O and 20.67±5.72 cmH₂O, respectively, decreasing by an average of 3.2±3.5 cmH₂O (p=0.040). The PaO₂/FiO₂ ratio was kept below 100 mm Hg in survivors and non-survivors for 116±65.4 and 250±124.9 minutes, respectively (p=0.016). Six patients underwent extracorporeal cardiopulmonary resuscitation, of whom 4 survived (67%). The overall survival rate of patients who underwent conversion from VA ECMO to VAV ECMO was approximately 56%. Conclusion: Rapid detection of differential hypoxia is required when VA ECMO is applied, and efficient conversion to VAV ECMO may be critical for patient survival.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.4
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• pp.183-186
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• 2002

Ischemic damage is one of the most serious problems. The openers of KATP channel have been suggested to have an effect to limit the ischemic damage. However, it is not yet clear how KATP channels of a cell correspond to hypoxic damage. To address the question, N2a cells were exposed to two different hypoxic conditions as follows: 6 hours hypoxia followed by 3 hours reperfusion and 12 hours hypoxia followed by 3 hours reperfusion. As the results, 6 hours hypoxic treatment increased glibenclamide- sensitive basal $K_{ATP}$ current activity (approximately 6.5-fold at 0 mV test potential) when compared with nomoxic condition. In contrast, 12 hours hypoxic treatment induced a relatively smaller change in the $K_{ATP}$ current density (2.5-fold at 0 mV test potential). Additionally, in experiments where $K_{ATP}$ channels were opened using diazoxide, the hypoxia for 6 hours significantly increased the current density in comparison to control condition (p＜0.001). Interestingly, the augmentation in the $K_{ATP}$ current density reduced after exposure to the 12 hours hypoxic condition (p＜0.001). Taken together, these results suggest that $K_{ATP}$ channels appear to be recruited more in cells exposed to the 6 hours hypoxic condition and they may play a protective role against hypoxia-reperfusion damage within the time range.

• Asian-Australasian Journal of Animal Sciences
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• v.22 no.3
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• pp.336-342
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• 2009

Avian embryos at high altitude are independent of maternal protection against hypoxia, which is contrary to mammals. It is well known that chronic hypoxic exposure at key points can significantly impact on avian development. Tibetan Chicken, a Chinese indigenous breed, living in Tibetan areas with an altitude of 2.2 to 4.1 thousand meters, has an adaptive mechanism to hypoxia. In the present study, fertilized eggs of Tibetan Chicken were incubated under 13% and 21% oxygen concentration. Two lowland chicken breeds, Shouguang Chicken, an indigenous chicken breed in Shandong Province of China, and Dwarf Recessive White Chicken, an imported breed in Beijing, were used as control groups. The embryo mass and some organs such as brain, heart, liver, stomach and eye weight in the three species were measured at Hamburger-Hamilton stage 39, 41, 43 and 45 under hypoxic and normal conditions. The results showed that in hypoxia Tibetan Chicken significantly differed from the two lowland chicken breeds in embryo mass at Hamburger-Hamilton stage 41, 43 and 45 (p<0.01). In particular, Dwarf Recessive White Chicken and Shouguang Chicken showed retarded growth in hypoxic incubation (p<0.01), whereas Tibetan Chicken showed no significant difference between hypoxic and normal conditions (p>0.05). In addition, heart and the other organs showed different susceptibility to hypoxia at the studied stages. In conclusion, chronic hypoxia induced a change in the embryo development of the three different species and Tibetan Chicken showed adaptation to hypoxia. Of note, the embryo developmental physiology of Tibetan Chicken in response to hypoxia will shed light on the process of physiological acclimation or evolutionary adaptation as well as the study of clinical disease.

• Animal cells and systems
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• v.8
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• pp.72-72
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• 2004

• Biomolecules & Therapeutics
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• v.26 no.5
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• pp.487-493
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• 2018

Cluster of differentiation 44 (CD44), a cell surface receptor for hyaluronic acid (HA), is involved in aggressive cancer phenotypes. Herein, we investigated the role of the CD44 standard isoform (CD44s) in hypoxia-inducible $factor-1{\alpha}$ ($HIF-1{\alpha}$) regulation using MCF7 overexpressing CD44s (pCD44s-MCF7). When pCD44s-MCF7 was incubated under hypoxia, levels of $HIF-1{\alpha}$, vascular endothelial growth factor, and the $HIF-1{\alpha}$ response element-derived luciferase activity were significantly increased compared to those in the control MCF7. Incubation of pCD44s-MCF7 cells with HA further increased $HIF-1{\alpha}$ accumulation, and the silencing of CD44s attenuated $HIF-1{\alpha}$ elevation, which verifies the role of CD44s in $HIF-1{\alpha}$ regulation. In addition, the levels of phosphorylated extracellular signal-regulated kinase (ERK) was higher in hypoxic pCD44s-MCF7 cells, and $HIF-1{\alpha}$ accumulation was diminished by the pharmacological inhibitors of ERK. CD44s-mediated $HIF-1{\alpha}$ augmentation resulted in two functional outcomes. First, pCD44s-MCF7 cells showed facilitated cell motility under hypoxia via the upregulation of proteins associated with epithelial-mesenchymal transition, such as SNAIL1 and ZEB1. Second, pCD44s-MCF7 cells exhibited higher levels of glycolytic proteins, such as glucose transporter-1, and produced higher levels of lactate under hypoxa. As a consequence of the enhanced glycolytic adaptation to hypoxia, pCD44s-MCF7 cells exhibited a higher rate of cell survival under hypoxia than that of the control MCF7, and glucose deprivation abolished these differential responses of the two cell lines. Taken together, these results suggest that CD44s activates hypoxia-inducible $HIF-1{\alpha}$ signaling via ERK pathway, and the $CD44s-ERK-HIF-1{\alpha}$ pathway is involved in facilitated cancer cell viability and motility under hypoxic conditions.

• International Journal of Oral Biology
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• v.46 no.4
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• pp.190-199
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• 2021

Despite evidence that bacteria-sensing Toll-like receptors (TLRs) are activated in salivary gland tissues of Sjogren syndrome (SS) patients, the role of oral bacteria in SS etiopathogenesis is unclear. We previously reported that two SS-associated oral bacteria, Prevotella melaninogenica (Pm) and Rothia mucilagenosa (Rm), oppositely regulate the expression of major histocompatibility complex class I (MHC I) in human salivary gland (HSG) cells. Here, we elucidated the mechanisms underlying the differential regulation of MHC I expression by these bacteria. The ability of Pm and Rm to activate TLR2, TLR4, and TLR9 was examined using TLR reporter cells. HSG cells were stimulated by the TLR ligands, Pm, and Rm. The levels of MHC I expression, bacterial invasion, and viability of HSG cells were examined by flow cytometry. The hypoxic status of HSG cells was examined using Hypoxia Green. HSG cells upregulated MHC I expression in response to TLR2, TLR4, and TLR9 activation. Both Pm and Rm activated TLR2 and TLR9 but not TLR4. Rm-induced downregulation of MHC I strongly correlated with bacterial invasion and cell death. Rm-induced cell death was not rescued by inhibitors of the diverse cell death pathways but was associated with hypoxia. In conclusion, Pm upregulated MHC I likely through TLR2 and TLR9 activation, while Rm-induced hypoxia-associated cell death and the downregulation of MHC I, despite its ability to activate TLR2 and TLR9. These findings may provide new insight into how oral dysbiosis can contribute to salivary gland tissue damage in SS.

• 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.

• Molecules and Cells
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• v.37 no.2
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• pp.178-186
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• 2014

Differential transcription of the clusterin (CLU) gene yields two CLU isoforms, a nuclear form (nCLU) and a secretory form (sCLU), which play crucial roles in prostate tumorigenesis. Pro-apoptotic nCLU and anti-apoptotic sCLU have opposite effects and are differentially expressed in normal and cancer cells; however, their regulatory mechanisms at the transcriptional level are not yet known. Here, we examined the transcriptional regulation of nCLU in response to hypoxia. We identified three putative hypoxia response elements (HREs) in the human CLU promoter between positions -806 and +51 bp. Using a luciferase reporter, electrophoretic gel mobility shift, and chromatin immunoprecipitation assays, we further showed that hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) bound directly to these sites and activated transcription. Exposure to the hypoxia-mimetic compound $CoCl_2$, incubation under 1% $O_2$ conditions, or overexpression of HIF-$1{\alpha}$ enhanced nCLU expression and induced apoptosis in human prostate cancer PC3M cells. However, LNCaP prostate cancer cells were resistant to hypoxia-induced cell death. Methylation-specific PCR analysis revealed that the CLU promoter in PC3M cells was not methylated; in contrast, the CLU promoter in LNCap cells was methylated. Co-treatment of LNCaP cells with $CoCl_2$ and a demethylating agent promoted apoptotic cell death through the induction of nCLU. We conclude that nCLU expression is regulated by direct binding of HIF-$1{\alpha}$ to HRE sites and is epigenetically controlled by methylation of its promoter region.

• Advances in pediatric surgery
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• v.1 no.2
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• pp.204-208
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• 1995

Neonatal adrenal hemorrhage is frequently associated with birth trauma or perinatal hypoxia. Hemorrhagic necrosis of the adrenal glands is often found at autopsy and many small lesions are usually asymptomatic. A palpable abdominal mass and jaundice are the usual presenting signs. Ultrasound is very useful in the diagnosis of this lesion; however, if the mass has mixed echoic pattern, magnetic resonance imaging (MRl) is helpful for the differential diagnosis from neuroblastoma. We present the case of a female newborn who was found to have a abdominal mass on physical examination. The patient showed anemia and hyperbilirubinemia. An ultrasonogram disclosed a $3.8{\times}3.0$ cm suprarenal mass with mixed echoic pattern. The mass was initially suspected to be neuroblastoma. An abdominal computed tomogram was not able to differentiate the mass. Magnetic resonance imaging revealed markedly increased signal intensity on T1 and T2-weighted sequences. This finding was consistent with adrenal hemorrhage. Serial sonogram demonstrated the mass that resolved completely by 12 weeks of age.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1901-1906
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• 2012

Background: The discovery that microRNA (miRNA) regulates metastasis provide a principal molecular basis for tumor heterogeneity. A characteristic of solid tumors is their heterogenous distribution of blood vessels, with significant hypoxia occurring in regions (centers of tumor) of low blood flow. It is necessary to discover the mechanism of breast cancer metastasis in relation to the fact that there is a differential distribution of crucial microRNA in tumors from centers to edges. Methods: Breast tissues from 48 patients (32 patients with breast cancer) were classified into the high invasive and metastatic group (HIMG), low invasive and metastatic group (LIMG), and normal group. Samples were collected from both the centers and edges of all tumors. The first six specimens were detected by microRNA array, and the second ten specimens were detected by real-time qRT-PCR and Western blot analyses. Correlation analysis was performed between the miRNAs and target proteins. Results: The relative content of miR-20a and miR-20b was lower in the center of the tumor than at the edge in the LIMG, lower at the edge of the tumor than in the center in the HIMG, and lower in breast cancer tissues than in normal tissues. VEGF-A and HIF-1alpha mRNA levels were higher in the HIMG than in the LIMG, and levels were higher in both groups than in the normal group; there was no difference in mRNA levels between the edge and center of the tumor. VEGF-A and HIF-1alpha protein levels were higher in the HIMG than in the LIMG, and protein levels in both groups were higher than in the normal group; there was a significant difference in protein expression between the edge and center of the tumor. Correlation analysis showed that the key miRNAs (miR-20a and miR-20b) negatively correlated with the target proteins (VEGF-A and HIF-1alpha). Conclusions: Our data suggest that miR-20a and miR-20b are differentially distributed in breast cancer, while VEGF-A and HIF-1alpha mRNA had coincident distributions, and VEGF-A and HIF-1alpha proteins had uneven and opposing distributions to the miRNAs. It appears that one of the most important facets underlying metastatic heterogeneity is the differential distribution of miR-20a and miR-20b and their regulation of target proteins.