1.Research progress on the effect of mitochondrial and endoplasmic reticulum stress caused by hypoxia during pregnancy on preeclampsia and intrauterine growth restriction.
Hui-Fang LIU ; Ri-Li GE ; Ta-Na WUREN
Acta Physiologica Sinica 2023;75(5):714-726
Preeclampsia and intrauterine growth restriction (IUGR) of the fetus are the two most common pregnancy complications worldwide, affecting 5%-10% of pregnant women. Preeclampsia is associated with significantly increased maternal and fetal morbidity and mortality. Hypoxia-induced uteroplacental dysfunction is now recognized as a key pathological factor in preeclampsia and IUGR. Reduced oxygen supply (hypoxia) disrupts mitochondrial and endoplasmic reticulum (ER) function. Hypoxia has been shown to alter mitochondrial reactive oxygen species (ROS) homeostasis and induce ER stress. Hypoxia during pregnancy is associated with excessive production of ROS in the placenta, leading to oxidative stress. Oxidative stress occurs in a number of human diseases, including high blood pressure during pregnancy. Studies have shown that uterine placental tissue/cells in preeclampsia and IUGR show high levels of oxidative stress, which plays an important role in the pathogenesis of both the complications. This review summarizes the role of hypoxia-induced mitochondrial oxidative stress and ER stress in the pathogenesis of preeclampsia/IUGR and discusses the potential therapeutic strategies targeting oxidative stress to treat both the pregnancy complications.
Pregnancy
;
Female
;
Humans
;
Placenta
;
Fetal Growth Retardation/etiology*
;
Pre-Eclampsia/pathology*
;
Reactive Oxygen Species
;
Hypoxia/pathology*
;
Pregnancy Complications/pathology*
;
Endoplasmic Reticulum Stress
2.Effect of Hypoxia-Supported Umbilical Cord Mesenchymal Stem Cells on the Expansion of Cord Blood Mononuclear Cells in vitro.
Journal of Experimental Hematology 2023;31(1):227-232
OBJECTIVE:
To explore the effect of hypoxia-supported umbilical cord mesenchymal stem cell (UC-MSC) on the expansion of cord blood mononuclear cell (MNC) in vitro.
METHODS:
The isolated cord blood mononuclear cells were inoculated on the preestablished umbilical cord mesenchymal stem cell layer and cultured under hypoxic conditions (3% O2) and the experimental groups were normoxia (MNCs were cultured under normoxic conditions), hypoxia (MNCs were cultured under hypoxic conditions), UC-MSC (MNCs were cultured with UC-MSC under normoxic conditions), and UC-MSC+hypoxia (MNCs were cultured with UC-MSC under hypoxic conditions). To further investigate the combinational effect of 3 factors of SCF+FL+TPO (SFT) on expansion of cord blood MNCs in vitro in hypoxia-supported UC-MSC culture system, the experiments were further divided into group A (MNCs were cultured with UC-MSC and SFT under normoxic conditions), group B (MNCs were cultured with UC-MSC under hypoxic conditions), group C (MNCs were cultured with UC-MSC and SFT under hypoxic conditions). The number of nucleated cells (TNC), CD34+ cell, CFU and CD34+CXCR4+, CD34+CD49d+, CD34+CD62L+ cells of each groups were detected at 0, 7, 10 and 14 days, respectively.
RESULTS:
Compared with group hypoxia and UC-MSC, group UC-MSC+hypoxia effectively promoted the expansion of TNC, CD34+ cell and CFU, and upregulated the expression level of adhesion molecule and CxCR4 of the cord blood CD34+ cell(P<0.05). After culturing for 14 days, compared with group A and group B, group C effectively promoted the expansion of cord blood MNC at different time points(P<0.05), and the effect of group A was better than that of group B at 7 and 10 days(P<0.05).
CONCLUSION
Hypoxia-supported UC-MSC efficiently promoted the expansion and expression of adhesion molecule and CXCR4 of cord blood CD34+ cell, and the effect of expansion could be enhanced when SFT 3 factors were added.
Humans
;
Cells, Cultured
;
Fetal Blood
;
Cell Proliferation
;
Umbilical Cord/metabolism*
;
Mesenchymal Stem Cells
;
Antigens, CD34/metabolism*
;
Hypoxia/metabolism*
3.Neuregulin 1/ErbB4 signaling attenuates neuronal cell damage under oxygen-glucose deprivation in primary hippocampal neurons
Ji Young YOO ; Han Byeol KIM ; Seung Yeon YOO ; Hong Il YOO ; Dae Yong SONG ; Tai Kyoung BAIK ; Jun Ho LEE ; Ran Sook WOO
Anatomy & Cell Biology 2019;52(4):462-468
hypoxia and ischemia. Neuregulin-1 (NRG1) has been shown to be able to protect against focal cerebral ischemia. The aim of the present study was to investigate the neuroprotective effect of NRG1 in primary hippocampal neurons and its underlying mechanism. Our data showed oxygen-glucose deprivation (OGD)-induced cytotoxicity and overexpression of ErbB4 in primary hippocampal neurons. Moreover, pretreatment with NRG1 could inhibit OGD-induced overexpression of ErbB4. In addition, NRG1 significantly attenuated neuronal death induced by OGD. The neuroprotective effect of NRG1 was blocked in ischemic neurons after pretreatment with AG1478, an inhibitor of ErbB4, but not after pretreatment with AG879, an inhibitor of ErbB2. These results indicate an important role of ErbB4 in NRG1-mediated neuroprotection, suggesting that endogenous ErbB4 might serve as a valuable therapeutic target for treating global cerebral ischemia.]]>
Anoxia
;
Brain
;
Brain Ischemia
;
Cell Death
;
Cognition
;
Hippocampus
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Ischemia
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Neuregulin-1
;
Neurons
;
Neuroprotection
;
Neuroprotective Agents
4.Role of HIF1α Regulatory Factors in Stem Cells
Hyun Jik LEE ; Young Hyun JUNG ; Gee Euhn CHOI ; Jun Sung KIM ; Chang Woo CHAE ; Ho Jae HAN
International Journal of Stem Cells 2019;12(1):8-20
Hypoxia-inducible factor 1 (HIF1) is a master transcription factor that induces the transcription of genes involved in the metabolism and behavior of stem cells. HIF1-mediated adaptation to hypoxia is required to maintain the pluripotency and survival of stem cells under hypoxic conditions. HIF1 activity is well known to be tightly controlled by the alpha subunit of HIF1 (HIF1α). Understanding the regulatory mechanisms that control HIF1 activity in stem cells will provide novel insights into stem cell biology under hypoxia. Recent research has unraveled the mechanistic details of HIF1α regulating processes, suggesting new strategies for regulating stem cells. This review summarizes recent experimental studies on the role of several regulatory factors (including calcium, 2-oxoglutarate-dependent dioxygenase, microtubule network, importin, and coactivators) in regulating HIF1α activity in stem cells.
Anoxia
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Biology
;
Calcium
;
Hypoxia-Inducible Factor 1
;
Karyopherins
;
Metabolism
;
Microtubules
;
Stem Cells
;
Transcription Factors
5.Enhanced Anti-Cancer Effects of Conditioned Medium from Hypoxic Human Umbilical Cord–Derived Mesenchymal Stem Cells
Kyu Hyun HAN ; Ae Kyeong KIM ; Gun Jae JEONG ; Hye Ran JEON ; Suk Ho BHANG ; Dong Ik KIM
International Journal of Stem Cells 2019;12(2):291-303
BACKGROUND AND OBJECTIVES: There have been contradictory reports on the pro-cancer or anti-cancer effects of mesenchymal stem cells. In this study, we investigated whether conditioned medium (CM) from hypoxic human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) (H-CM) showed enhanced anti-cancer effects compared with CM from normoxic hUC-MSCs (N-CM). METHODS AND RESULTS: Compared with N-CM, H-CM not only strongly reduced cell viability and increased apoptosis of human cervical cancer cells (HeLa cells), but also increased caspase-3/7 activity, decreased mitochondrial membrane potential (MMP), and induced cell cycle arrest. In contrast, cell viability, apoptosis, MMP, and cell cycle of human dermal fibroblast (hDFs) were not significantly changed by either CM whereas caspase-3/7 activity was decreased by H-CM. Protein antibody array showed that activin A, Beta IG-H3, TIMP-2, RET, and IGFBP-3 were upregulated in H-CM compared with N-CM. Intracellular proteins that were upregulated by H-CM in HeLa cells were represented by apoptosis and cell cycle arrest terms of biological processes of Gene Ontology (GO), and by cell cycle of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. In hDFs, negative regulation of apoptosis in biological process of GO and PI3K-Akt signaling pathway of KEGG pathways were represented. CONCLUSIONS: H-CM showed enhanced anti-cancer effects on HeLa cells but did not influence cell viability or apoptosis of hDFs and these different effects were supported by profiling of secretory proteins in both kinds of CM and intracellular signaling of HeLa cells and hDFs.
Activins
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Anoxia
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Apoptosis
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Biological Processes
;
Cell Cycle
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Cell Cycle Checkpoints
;
Cell Survival
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Culture Media, Conditioned
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Fibroblasts
;
Gene Ontology
;
Genome
;
HeLa Cells
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Humans
;
Insulin-Like Growth Factor Binding Protein 3
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Membrane Potential, Mitochondrial
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Mesenchymal Stromal Cells
;
Tissue Inhibitor of Metalloproteinase-2
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Uterine Cervical Neoplasms
6.Effect of Nocturnal Hypoxia on Nocturia in Patients With Obstructive Sleep Apnea
Jae Hoon CHUNG ; Hong Sang MOON ; Sung Yul PARK ; Kyung Rae KIM ; Seok Hyun CHO ; Yong Tae KIM
International Neurourology Journal 2019;23(2):161-168
PURPOSE: To identify the association between nocturia and obstructive sleep apnea (OSA), we compared results of polysomnography (PSG) with the presence or absence of nocturia in patients with suspected OSA. METHODS: Patients underwent PSG for suspected OSA. The International Prostate Symptom Score and quality of life (IPSS/QoL) questionnaire was evaluated to assess voiding symptoms that may affect sleep quality. The results of PSG were compared between patient groups with or without nocturia. RESULTS: In logistic regression analysis, age (odds ratio [OR], 1.052; P=0.004), diabetes mellitus (OR, 6.675; P<0.001), mean O₂ saturation (OR, 0.650; P=0.017), oxygen desaturation index (ODI) 3 (OR, 1.193; P=0.010), and ODI4 (OR, 1.136; P=0.014) affected nocturia independently among the OSA-suspected patients. CONCLUSIONS: Hypoxia caused by OSA affects the incidence of nocturia. Less desaturated OSA patients with nocturia may require more urological evaluation and treatment for nocturia even after the correction of OSA.
Anoxia
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Apnea
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Diabetes Mellitus
;
Humans
;
Incidence
;
Logistic Models
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Nocturia
;
Oxygen
;
Polysomnography
;
Prostate
;
Quality of Life
;
Sleep Apnea, Obstructive
7.Sarcopenia Associated with Chronic Obstructive Pulmonary Disease
Sang Hun KIM ; Myung Jun SHIN ; Yong Beom SHIN ; Ki Uk KIM
Journal of Bone Metabolism 2019;26(2):65-74
Sarcopenia is frequently associated with chronic diseases such as chronic obstructive pulmonary disease (COPD) and cancer. COPD, which is characterized by an irreversible airflow limitation, exacerbates respiratory distress as the disease progresses. The prevalence of sarcopenia in stable COPD was reported to be 15% to 25% in previous foreign studies and 25% in a Korean study. As the amount of activity decreases, muscle mass decreases and eventually oxygen cannot be used effectively, resulting in a vicious cycle of deterioration of exercise capacity. Deconditioning due to decreased activity is a major cause of limb muscle dysfunction in patients with COPD. In these patients, the factors that decrease muscle strength and endurance include chronic inflammation, oxidative stress, inactivity, hypoxemia, hormone abnormality, deficits of nutrients such as protein and vitamin D, and the use of systemic corticosteroid. Therefore, treatment and management should either inhibit this process or should be directed toward supplementing the deficiency, such as with exercise, nutritional support, and medications and supplements. The relationship between sarcopenia and COPD is increasingly being reported, with some overlap in clinical features and treatments. We are fascinated to be able to diagnose 2 diseases through similar physical performance tests and to improve both diseases using the same treatment such as exercise. Therefore, this review summarizes the clinical relevance and integrative management of the 2 diseases.
Anoxia
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Chronic Disease
;
Exercise Therapy
;
Extremities
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Humans
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Inflammation
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Lung Diseases
;
Muscle Strength
;
Nutritional Support
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Oxidative Stress
;
Oxygen
;
Prevalence
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Pulmonary Disease, Chronic Obstructive
;
Rehabilitation
;
Sarcopenia
;
Vitamin D
8.Insights into Hypoxia: Non-invasive Assessment through Imaging Modalities and Its Application in Breast Cancer
Journal of Breast Cancer 2019;22(2):155-171
Oxygen is crucial to maintain the homeostasis in aerobic cells. Hypoxia is a condition in which cells are deprived of the oxygen supply necessary for their optimum performance. Whereas oxygen deprivation may occur in normal physiological processes, hypoxia is frequently associated with pathological conditions. It has been identified as a stressor in the tumor microenvironment, acting as a key mediator of cancer development. Numerous pathways are activated in hypoxic cells that affect cell signaling and gene regulation to promote the survival of these cells by stimulating angiogenesis, switching cellular metabolism, slowing their growth rate, and preventing apoptosis. The induction of dysregulated metabolism in cancer cells by hypoxia results in aggressive tumor phenotypes that are characterized by rapid progression, treatment resistance, and poor prognosis. A non-invasive assessment of hypoxia-induced metabolic and architectural changes in tumors is advisable to fully improve breast cancer (BC) patient management, by potentially reducing the need for invasive biopsy procedures and evaluating tumor response to treatment. This review provides a comprehensive overview of the molecular changes in breast tumors secondary to hypoxia and the non-invasive imaging alternatives to evaluate oxygen deprivation, with an emphasis on their application in BC and the advantages and limitations of the currently available techniques.
Anoxia
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Apoptosis
;
Biopsy
;
Breast Neoplasms
;
Breast
;
Homeostasis
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Humans
;
Metabolism
;
Molecular Imaging
;
Oxygen
;
Phenotype
;
Physiological Processes
;
Prognosis
;
Tumor Microenvironment
9.Effects of Bicycle Ergometer Exercise on Cerebral Blood Flow Velocity and Electroencephalogram Response in Normoxia and Hypoxia
Seong Dae KIM ; Myung Wha KIM ; Il Gyu JEONG
Korean Journal of Health Promotion 2019;19(1):59-67
BACKGROUND: The cerebral blood flow velocity (CBFV) has been known to increase in response to acute hypoxia. However, how CBFV might respond to exercise in hypoxic conditions and be associated with electroencephalogram (EEG) remains unclear. The purpose of this study was to evaluate the effect of exercise in hypoxic conditions corresponding to altitudes of 4,000 m on CBFV and EEG. METHODS: In a randomized, double-blind, balanced crossover study, ten healthy volunteers (19.8±0.4 years) were asked to perform the incremental bicycle ergometer exercise twice in hypoxic and control (sea level) conditions with a 1-week interval, respectively. Exercise intensity was set initially at 50 W and increased by 25 W every 2 minutes to 125 W. Acute normobaric hypoxic condition was maintained for 45 minutes using low oxygen gas mixture. CBFV in the middle cerebral artery (MCA) and EEG were measured at rest 5 minutes, rest 15 minutes, immediately after exercise, and 15 minutes recovery using transcranial-Doppler sonography and EEG signal was recorded from 6 scalp sites leading to analysis of alpha and beta wave relative activities. All data were analyzed using two-way repeated-measures analysis of variance and Pearson's correlation. RESULTS: CBFV in the MCA in the hypoxic condition was significantly higher than that in the control condition at rest 5 minutes (83±9 vs. 69±9 cm/s, P<0.01), rest 15 minutes (87±8 vs. 67±7 cm/s, P<0.001), immediately after exercise (112±9 vs. 97±9 cm/s, P<0.01), and 15 minutes recovery (91±11 vs. 74±7 cm/s, P<0.01). However, no significant correlation was found between the changes of CBFV and EEG wave activities. CONCLUSIONS: These results suggest that the drastic change of CBFV observed during exercise with hypoxia might appear independently with EEG wave activities.
Altitude
;
Anoxia
;
Cerebrovascular Circulation
;
Cross-Over Studies
;
Electroencephalography
;
Healthy Volunteers
;
Middle Cerebral Artery
;
Oxygen
;
Scalp
10.Propofol with and without Midazolam for Diagnostic Upper Gastrointestinal Endoscopies in Children
Ulas Emre AKBULUT ; Seyfi KARTAL ; Ufuk DOGAN ; Gulgun Elif AKCALI ; Serap KALAYCI ; Hulya KIRCI
Pediatric Gastroenterology, Hepatology & Nutrition 2019;22(3):217-224
PURPOSE: Various publications on the use of sedation and anesthesia for diagnostic procedures in children have demonstrated that no ideal agent is available. Although propofol has been widely used for sedation during esophagogastroduodenoscopy in children, adverse events including hypoxia and hypotension, are concerns in propofol-based sedation. Propofol is used in combination with other sedatives in order to reduce potential complications. We aimed to analyze whether the administration of midazolam would improve the safety and efficacy of propofol-based sedation in diagnostic esophagogastroduodenoscopies in children. METHODS: We retrospectively reviewed the hospital records of children who underwent diagnostic esophagogastroduodenoscopies during a 30-month period. Demographic characteristics, vital signs, medication dosages, induction times, sedation times, recovery times, and any complications observed, were examined. RESULTS: Baseline characteristics did not differ between the midazolam-propofol and propofol alone groups. No differences were observed between the two groups in terms of induction times, sedation times, recovery times, or the proportion of satisfactory endoscopist responses. No major procedural complications, such as cardiac arrest, apnea, or laryngospasm, occurred in any case. However, minor complications developed in 22 patients (10.7%), 17 (16.2%) in the midazolam-propofol group and five (5.0%) in the propofol alone group (p=0.010). CONCLUSION: The sedation protocol with propofol was safe and efficient. The administration of midazolam provided no additional benefit in propofol-based sedation.
Anesthesia
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Anoxia
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Apnea
;
Child
;
Conscious Sedation
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Endoscopy
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Endoscopy, Digestive System
;
Endoscopy, Gastrointestinal
;
Heart Arrest
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Hospital Records
;
Humans
;
Hypnotics and Sedatives
;
Hypotension
;
Laryngismus
;
Midazolam
;
Propofol
;
Retrospective Studies
;
Vital Signs

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