• Title/Summary/Keyword: Hypoxic

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Analysis of the global gene expression profiles in genomic instability-induced cervical cancer cells

  • Oh, Jung-Min
    • International Journal of Oral Biology
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    • v.47 no.2
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    • pp.17-24
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    • 2022
  • Preserving intact genetic material and delivering it to the next generation are the most significant tasks of living organisms. The integrity of DNA sequences is under constant threat from endogenous and exogenous factors. The accumulation of damaged or incompletely-repaired DNA can cause serious problems in cells, including cell death or cancer development. Various DNA damage detection systems and repair mechanisms have evolved at the cellular level. Although the mechanisms of these responses have been extensively studied, the global RNA expression profiles associated with genomic instability are not well-known. To detect global gene expression changes under different DNA damage and hypoxic conditions, we performed RNA-seq after treating human cervical cancer cells with ionizing radiation (IR), hydroxyurea, mitomycin C (MMC), or 1% O2 (hypoxia). Results showed that the expression of 184-1037 genes was altered by each stimulus. We found that the expression of 51 genes changed under IR, MMC, and hypoxia. These findings revealed damage-specific genes that varied differently according to each stimulus and common genes that are universally altered in genetic instability.

Histology and morphometry of the skin of the trident goby Tridentiger brevispinis (Perciformes, Gobiidae)

  • Hyun‑Tae Kim
    • Applied Microscopy
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    • v.52
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    • pp.8.1-8.7
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    • 2022
  • The Korean trident goby, Tridentiger brevispinis, lives in adverse habitats that can easily become hypoxic due to low precipitation, regional dry periods, and high amounts of solar radiation. Histological and morphometric studies revealed the goby's specialized skin (35.4-150.0㎛ in thickness), consisting of an epidermis and dermis. The thicker epidermis comprises an outermost surface layer (having taste buds, stratified fattened cells, mucous cells, pigment cells, and stratified polygonal cells), middle layer (having stratified polygonal cells), and stratum germinativum (stratified columnar cells). In particular, the dermis has scales, well-developed vascularization, and a few blood capillaries just above the basement membrane, and a reduced diffusion distance was present in the lateral body. Consequently, adaptations such as thicker epidermis, well-developed vascularization, few blood capillaries, and a reduced diffusion distance may provide cutaneous respiration for survival in poorly oxygenated water during the periodic dry season.

Laryngeal Paralysis in a Cat with Malignant Thymoma

  • Hyeona Bae;Il-Hwa Hong;Dong-In Jung;DoHyeon Yu
    • Journal of Veterinary Clinics
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    • v.40 no.1
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    • pp.68-72
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    • 2023
  • A 10-year-old castrated male Domestic Shorthair cat visited a veterinary medical teaching hospital for emergency dyspnea. The cat was hypoxic and hypotensive, and stridorous respiration was remarkable. Visual inspection confirmed laryngeal paralysis and a lack of mobility of the left larynx. Megaesophagus, aspiration pneumonia, cranial mediastinal mass, and positive Tensilon test results using neostigmine were observed, indicating acquired myasthenia gravis secondary to thymic neoplasia. After 10 minutes of neostigmine 0.02 mg/kg IV administration, laryngeal paralysis and dyspnea resolved. Histopathlogical examination for the cranial mediastinal mass after surgical resection confirmed malignant thymoma. Here, we report a case of acquired myasthenia gravis in a cat with a malignant thymoma that presented with life-threatening dyspnea due to laryngeal paralysis. Feline laryngeal paralysis is uncommon, and myasthenia gravis, a cause of laryngeal paralysis in cats, has not yet been reported. Myasthenia gravis should be considered in cats with laryngeal paralysis.

Synthetic Approach to 99mTc-labeled SPECT Radiotracers with Multi-nitroimidazoles for Hypoxia

  • Anh Thu Nguyen;Hee-Kwon Kim
    • The Korean Journal of Nuclear Medicine Technology
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    • v.28 no.1
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    • pp.1-11
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    • 2024
  • Hypoxia, defined as the deficiency of oxygen, is a significant hallmark of cancers presenting in the majority of solid tumors. Detection of tumor hypoxia is essential in cancer diagnosis to prevent cancer progression, metastasis, and resistance to cancer therapies in clinical practices. Single-photon emission computed tomography (SPECT) is one of the methods studied and applied for hypoxia detection with the use of radiolabeled imaging agents in which 99mTc is the common radioisotope used for radiolabeling. Nitroimidazoles are the hypoxia-targeting moieties presenting in numerous 99mTc-radiolabeled imaging agents due to their bio-reducible ability in hypoxic environments. Recently, in addition to 99mTc-labeled radiopharmaceuticals containing one nitroimidazole unit, there has been considerable attention given to 99mTc-radiopharmaceuticals bearing two or more nitroimidazole units. This review summarizes the synthesis of hypoxia-targeting chelators and radiolabeling processes to produce these 99mTc-radiopharmaceuticals for SPECT imaging.

Synthesis of Novel 18F-Labeled-Nitroimidazole-Based Imaging Agents for Hypoxia: Recent Advances

  • Anh Thu Nguyen;Hee-Kwon Kim
    • The Korean Journal of Nuclear Medicine Technology
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    • v.27 no.2
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    • pp.83-93
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    • 2023
  • Hypoxia indicates the condition of low oxygen levels in tissues. In oncology, hypoxia can induce cancer progression and metastasis, as well as cause resistance to cancer therapies. The detection of hypoxia by using molecular imaging, particularly, positron emission tomography (PET) has been extensively studied due to many advantages. Nitroimidazoles, the moieties that can be trapped in hypoxic tissues due to selective reduction, have been used to design and synthesize of hypoxia-targeting radiopharmaceuticals. This review provides a summary of synthetic routes towards 18F-labeled-nitroimidazole radiotracers for PET imaging of hypoxia.

A Study of Endothelium-dependent Pulmonary Arterial Relaxation and the Role of Nitric oxide on Acute Hypoxic Pulmonary Vasoconstriction in Rats (흰쥐 폐동맥의 내피세포의존성 혈관이완과 급성 저산소성 폐동맥수축에서 산화질소의 역할)

  • In, Kwang-Ho;Lee, Jin-Goo;Cho, Jae-Youn;Shim, Jae-Jung;Kang, Kyung-Ho;Yoo, Se-Hwa
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.3
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    • pp.231-238
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    • 1994
  • Backgroud: Since the demonstration of the fact that vascular relaxation by acetylcholine(Ach) results from the release of relaxing factor from the endothelium, the identity and physiology of this endothelium-derived relaxing factor(EDRF) has been the target for many researches. EDRF has been identified as nitric oxide(NO). With the recent evidences that EDRF is an important mediator of vascular tone, there have been increasing interests in defining the role of the EDRF as a potential mediator of hypoxic pulmonary vasoconstriction. But the role of EDRF in modulating the pulmonary circulation is not compeletely clarified. To investigate the endothelium-dependent pulmonary vasodilation and the role of EDRF during hypoxic pulmonary vasoconstriction, we studied the effects of $N^G$-monomethyl-L-arginine(L-NMMA) and L-arginine on the precontracted pulmonary arterial rings of the rat in normoxia and hypoxia. Mothods: The pulmonary arteries of male Sprague Dawley(300~350g) were dissected free of surrounding tissue, and cut into rings. Rings were mounted over fine rigid wires, in organ chambers filled with 20ml of Krebs solution bubbled with 95 percent oxygen and 5 percent carbon dioxide and maintained at $37^{\circ}C$. Changes in isometric tension were recorded with a force transducer(FT.03 Grass, Quincy, USA) Results: 1) Precontraction of rat pulmonry artery with intact endothelium by phenylephrine(PE, $10^{-6}M$) was relaxed completely by acetylcholine(Ach, $10^{-9}-10^{-5}M$) and sodium nitroprusside(SN, $10^{-9}-10^{-5}M$), but relaxing response by Ach in rat pulmonary artery with denuded endothelium was significantly decreased. 2) L-NMMA($10^{-4}M$) pretreatment inhibited Ach($10^{-9}-10^{-5}M$)-induced relaxation, but L-NMMA ($10^{-4}M$) had no effect on relaxation induced by SN($10^{-9}-10^{-5}M$). 3) Pretreatment of the L-arginine($10^{-4}M$) significantly reversed the inhibition of the Ach ($10^{-9}-10^{-5}M$)-induced relaxation caused by L-NMMA($10^{-4}M$) 4) Pulmonary arterial contraction by PE($10^{-6}M$) was stronger in hypoxia than normoxia but relaxing response by Ach($10^{-9}-10^{-5}M$) was decreased, 5) With pretreatment of L-arginine($10^{-4}M$), pulmonary arterial relaxation by Ach($10^{-9}-10^{-5}M$) in hypoxia was reversed to the level of relaxation in normoxia. Conclusion: It is concluded that rat pulmonary arterial relaxation by Ach is dependent on the intact endothelium and is largely mediated by NO. Acute hypoxic pulmonary vasoconstriction is related to the suppression on NO formation in the vascular endothelium.

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EFFECT OF OXYGEN TENSION ON THE ACTIVITY AND FUNCTION OF THE CELLS DERIVED FROM HUMAN PERIODONTAL LIGAMENT (산소 장력이 치주인대에서 유래한 세포의 활성과 기능에 미치는 영향)

  • Sa, Muyng-Hee;Yang, Won-Sik
    • The korean journal of orthodontics
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    • v.27 no.3 s.62
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    • pp.503-513
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    • 1997
  • This study was undertaken to investigate the effect of oxygen tension on the activity and function of the cells derived from human periodontal ligament by measuring cell activity, total protein synthesis, collagen synthesis, $IL-1{\beta},\;IL-6,\;TNF-{\alpha}$ Human periodontal ligament fibroblasts were collected from premolars extracted for orthodontic treatment and incubated in the environment of $37^{\circ}C,\;5\%\;CO_2,\100\%$ humidity. After the fifth to sixth passage they were used for the experiment. Gaspack system to which $0.2{\mu}m$ Millipore filter was attached was connected to mixed-gas tanks. The mixed gases were composed of $10\%\;O_2,\;5\%\;CO_2,\;85\%\;N_2$ in hyoxic group or $90\%\;O_2,\;5\%\;CO_2,\;5\%\;N_2$ in hyperoxic group and $5\%\;CO_2,\;95\%$ air for control. After incubation in $37^{\circ}C$ for 2, 4, 6 days, cell activity was determined by tetrazolium(MTT) assay and total protein synthesis was assayed using sulforhodamine B(SRB). And measurement of 4-hydroxyproline was performed to assess collagen synthesis md $IL-1{\beta},\;IL-6,\;and\;TNF-{\alpha}$ were measured by enzymeimmunoassay. The results were as follows. 1. The cell activity and total protein synthesis in hypoxic group were a little higher than or almost the same with those in control group. 2. In hyperoxic group, the cell activity was lower than that in control group and total protein synthesis was decreased. 3. Collagen synthesis was significantly decreased initially in both hypoxic and hyperoxic group and increased nearly to the level of control group as the duration of cell incubation was longer 4. As a result of enzymeimmunoassay, the amount of cytokines was $IL-6,\;TNF-{\alpha}\;and\;IL-1{\beta}$ in order. 5. $IL-6,\;TNF-{\alpha}\;and\;IL-1{\beta}$ were increased more rapidly in both hypoxic and hyperoxic group than in control group as the duration of cell incubation was longer. 6. There were more $IL-6\;and\;TNF-{\alpha}$ in hyperoxic group than in control group after 6 days, and there were more $IL-6\;and\;TNF-{\alpha}$ after 6 days than after 2 or 4 days in hyperoxic group. These results suggested that oxygen tension might modulate the production of extracellular matrix and cytokines in the cells derived from human periodontal ligament.

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Hypoxia-dependent mitochondrial fission regulates endothelial progenitor cell migration, invasion, and tube formation

  • Kim, Da Yeon;Jung, Seok Yun;Kim, Yeon Ju;Kang, Songhwa;Park, Ji Hye;Ji, Seung Taek;Jang, Woong Bi;Lamichane, Shreekrishna;Lamichane, Babita Dahal;Chae, Young Chan;Lee, Dongjun;Chung, Joo Seop;Kwon, Sang-Mo
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.2
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    • pp.203-213
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    • 2018
  • Tumor undergo uncontrolled, excessive proliferation leads to hypoxic microenvironment. To fulfill their demand for nutrient, and oxygen, tumor angiogenesis is required. Endothelial progenitor cells (EPCs) have been known to the main source of angiogenesis because of their potential to differentiation into endothelial cells. Therefore, understanding the mechanism of EPC-mediated angiogenesis in hypoxia is critical for development of cancer therapy. Recently, mitochondrial dynamics has emerged as a critical mechanism for cellular function and differentiation under hypoxic conditions. However, the role of mitochondrial dynamics in hypoxia-induced angiogenesis remains to be elucidated. In this study, we demonstrated that hypoxia-induced mitochondrial fission accelerates EPCs bioactivities. We first investigated the effect of hypoxia on EPC-mediated angiogenesis. Cell migration, invasion, and tube formation was significantly increased under hypoxic conditions; expression of EPC surface markers was unchanged. And mitochondrial fission was induced by hypoxia time-dependent manner. We found that hypoxia-induced mitochondrial fission was triggered by dynamin-related protein Drp1, specifically, phosphorylated DRP1 at Ser637, a suppression marker for mitochondrial fission, was impaired in hypoxia time-dependent manner. To confirm the role of DRP1 in EPC-mediated angiogenesis, we analyzed cell bioactivities using Mdivi-1, a selective DRP1 inhibitor, and DRP1 siRNA. DRP1 silencing or Mdivi-1 treatment dramatically reduced cell migration, invasion, and tube formation in EPCs, but the expression of EPC surface markers was unchanged. In conclusion, we uncovered a novel role of mitochondrial fission in hypoxia-induced angiogenesis. Therefore, we suggest that specific modulation of DRP1-mediated mitochondrial dynamics may be a potential therapeutic strategy in EPC-mediated tumor angiogenesis.

SOD and Inorganic Nutrient Fluxes from Sediment in the Downstream of the Nagdong River (낙동강 하류 수계에서 저질퇴적층의 SOD와 영양염 용출)

  • Jung, Ha-Young;Cho, Kyung-Je
    • Korean Journal of Ecology and Environment
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    • v.36 no.3 s.104
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    • pp.322-335
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    • 2003
  • Nutrient fluxes and sediment oxygen demands (SOD) were measured with intact sediment cores collected from three stations in the downstream of Nagdong River. The sediments were subjected to controlled oxic and hypoxic conditions and temperature gradients (from $10^{\circ}C$ to $30^{\circ}C$) of the overlying waters in laboratory batch system. The effect of temperature and labile layer thickness of the sediment on SOD were examined. $PO_4\;^{3-}$ and $NH_4\;^+$ fluxes were elevated above $20^{\circ}C$ and large mobilities were observed when they were coupled with a hypoxic and high-temperature condition. In the well oxygenated conditions, $PO_4\;^{3-}$ fluxes were negative or negligible but $NH_4\;^+$ fluxes ranged from 1.3 mg N $m^{-2}\;hr^{-1}$ to 2.3 $m^{-2}\;hr^{-1}$. Temperature quotients($Q_{10}$) of $PO_4\;^{3-}$ fluxes were 3.7 ${\sim}$ 7.3 ranges to have the most high values. $PO_4\;^{3-}$ and $NH_4\;^+$ fluxes had the logarithmic increase with temperature, while $NO_3\;^-$ was negatively absorbed to the sediment and linearly correlated with the temperature. $SiO_2$ fluxes showed no difference among oxic and hypoxic conditions and sediment texture. The nutrient fluxes would be closely correlated with pore water chemistry of sediments and activated by the top sediment layer composition such as labile organic matters or algal detritus. The ecological implications of the nutrient fluxes were discussed in terms of sources and sinks of nutrients coupled to algal productions in the Nagdong River.

The Correlation between the Severity of Hypoxic Ischemic Encephalopathy and the Development of Acute Renal Failure in Asphyxiated Neonates (신생아 질식 환아에서 저산소성 허혈 뇌증의 정도와 급성신부전 발생과의 연관성)

  • Park, Sung-Shin;Chung, Sung-Hoon;Song, Jun-Hyuk;Kim, Sun-Kyoung;Cho, Byoung-Soo;Kim, Sung-Do
    • Childhood Kidney Diseases
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    • v.11 no.1
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    • pp.32-40
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    • 2007
  • Purpose : We performed this study to determine the incidence of acute renal failure(ARF) in birth asphyxia and to correlate the severity of asphyxia and hypoxic-ischemic encephalopathy (HIE) and ARF in asphyxiated neonates. Methods : Data was retrospectively collected from the medical records of 33 patients with neonatal asphyxia and of 33 neonates with no asphyxia. On the basis the 5-minute Apgar score, the asphyxiated neonates were further grouped into mild(6 or 7), moderate(4 or 5), and severe asphyxia(3 or less). Asphyxiated neonates with HIE were staged by the Sarnat and Sarnat scoring system. We compared serum creatinine, blood urea nitrogen, electrolytes, and urine output on day 3 of life and the incidence and severity of intraventricular hemorrhage(IVH) between each group. Results : ARF occurred in 8(24.2%) asphyxiated neonates. Of these, 3(37.5%) were oliguric, while 1(10.0%) patient with mild asphyxia, 2(18.2%) of moderate asphyxia, and 5(41.7%) with of severe asphyxia had ARF(P>0.05). One(25%) patient with stage I HIE, 4(50%) with stage II HIE, and 3(75%) of HIE with stage III HIE developed ARF(P<0.01). There was no statistical correlation between the severity of asphyxia and HIE stage. One(7.7%) patient with grade 1 IVE, 0(0.0%) with grade 2 IVH, 2(66.7%) with grade 3 IVH, and 2(100.0%) with grade 4 IVH had ARF(P<0.01). Mortality was higher in asphyxiated neonates with ARF(P<0.05). There was no significant difference between the oliguric and non-oliguric renal failure. Conclusion : We found that the greater the degree of HIE, the higher was the incidence of ARF. Asphyxiated neonates with ARF had a poorer prognosis.

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