Anoxia ; Brain ; Brain Ischemia ; Cell Death ; Cognition ; Hippocampus ; Ischemia ; Neuregulin-1 ; Neurons ; Neuroprotection ; Neuroprotective Agents

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 ; Biology ; Calcium ; Hypoxia-Inducible Factor 1 ; Karyopherins ; Metabolism ; Microtubules ; Stem Cells ; Transcription Factors

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 ; Anoxia ; Apoptosis ; Biological Processes ; Cell Cycle ; Cell Cycle Checkpoints ; Cell Survival ; Culture Media, Conditioned ; Fibroblasts ; Gene Ontology ; Genome ; HeLa Cells ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; Membrane Potential, Mitochondrial ; Mesenchymal Stromal Cells ; Tissue Inhibitor of Metalloproteinase-2 ; Uterine Cervical Neoplasms

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 ; Apnea ; Diabetes Mellitus ; Humans ; Incidence ; Logistic Models ; Nocturia ; Oxygen ; Polysomnography ; Prostate ; Quality of Life ; Sleep Apnea, Obstructive

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 ; Chronic Disease ; Exercise Therapy ; Extremities ; Humans ; Inflammation ; Lung Diseases ; Muscle Strength ; Nutritional Support ; Oxidative Stress ; Oxygen ; Prevalence ; Pulmonary Disease, Chronic Obstructive ; Rehabilitation ; Sarcopenia ; Vitamin D

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 ; Apoptosis ; Biopsy ; Breast Neoplasms ; Breast ; Homeostasis ; Humans ; Metabolism ; Molecular Imaging ; Oxygen ; Phenotype ; Physiological Processes ; Prognosis ; Tumor Microenvironment

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

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 ; Anoxia ; Apnea ; Child ; Conscious Sedation ; Endoscopy ; Endoscopy, Digestive System ; Endoscopy, Gastrointestinal ; Heart Arrest ; Hospital Records ; Humans ; Hypnotics and Sedatives ; Hypotension ; Laryngismus ; Midazolam ; Propofol ; Retrospective Studies ; Vital Signs

BACKGROUND: This study was conducted to investigate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the mobilization of mesenchymal stem cells (MSCs) from the bone marrow (BM) into the peripheral blood (PB) in rats. METHODS: GM-CSF was administered subcutaneously to rats at 50 µg/kg body weight for 5 consecutive days. The BM and PB of rats were collected at 1, 3, and 5 days during the administration for analysis. RESULTS: Upon GM-CSF administration, the number of mononuclear cells increased rapidly at day 1 both in the BM and PB. This number decreased gradually over time in the BM to below the initial amount by day 5, but was maintained at a high level in the PB until day 5. The colony-forming unit-fibroblasts were increased in the PB by 10.3-fold at day 5 of GM-CSF administration, but decreased in the BM. Compared to GM-CSF, granulocyte-colony stimulating factor (G-CSF) stimulated lower levels of MSC mobilization from the BM to the PB. Immunohistochemical analysis revealed that GM-CSF induced a hypoxic and proteolytic microenvironment and increased C-X-C chemokine receptor type 4 (CXCR4) expression in the BM. GM-CSF added to BM MSCs in vitro dose-dependently increased CXCR4 expression and cell migration. G-CSF and stromal cell derived factor-1 (SDF-1) showed similar results in these in vitro assays. Know-down of CXCR4 expression with siRNA significantly abolished GM-CSF- and G-CSF-induced MSC migration in vitro, indicating the involvement of the SDF-1-CXCR4 interaction in the mechanism. CONCLUSION: These results suggest that GM-CSF is a useful tool for mobilizing BM MSCs into the PB.
Animals ; Anoxia ; Body Weight ; Bone Marrow ; Cell Movement ; Granulocyte Colony-Stimulating Factor ; Granulocyte-Macrophage Colony-Stimulating Factor ; In Vitro Techniques ; Mesenchymal Stromal Cells ; Rats ; RNA, Small Interfering ; Stromal Cells

BACKGROUND/AIMS: Many systems including the cardiovascular system (ischemic heart diseases, heart failure, and hypertension) may act as comorbidities that can be seen during the course of chronic obstructive pulmonary disease (COPD). Comorbidities affect the severity and prognosis of COPD negatively. Nearly 25% of patients with COPD die due to cardiovascular diseases. In this study, we aimed to evaluate the relationship between the blood pressure, inflammation, hypoxia, hypercapnia, and the severity of airway obstruction. METHODS: We included 75 COPD patients in the study with 45 control cases. We evaluated age, sex, body mass index, smoking history, C-reactive protein levels, 24-hour ambulatory blood pressure Holter monitoring, arterial blood gas, and respiratory function tests of the patient and the control groups. RESULTS: In COPD patients, the night time systolic, diastolic blood pressures and pulse per minute and the mean blood pressures readings were significantly elevated compared to the control group (p < 0.05). In the correlation analysis, night time systolic pressure was associated with all the parameters except forced expiratory volume in 1 second (FEV₁%). Diastolic blood pressure was associated with pH and HCO₃ levels. The mean night time, day time pulse pressures and 24-hour pulse per minute values were also associated with all the parameters except FEV₁%. CONCLUSIONS: In this study we found that parameters of systolic and diastolic blood pressures and pulse pressures were significantly elevated in COPD patients compared to the control groups. Blood pressure was associated blood gas parameters and inflammation parameters in COPD patients. This, in turn, may cause understanding of the pathophysiology of COPD and its complications.
Airway Obstruction ; Anoxia ; Blood Pressure* ; Body Mass Index ; C-Reactive Protein ; Cardiovascular Diseases ; Cardiovascular System ; Comorbidity ; Electrocardiography, Ambulatory ; Forced Expiratory Volume ; Heart Diseases ; Heart Failure ; Humans ; Hydrogen-Ion Concentration ; Hypercapnia ; Inflammation* ; Prognosis ; Pulmonary Disease, Chronic Obstructive* ; Reading ; Respiratory Function Tests ; Smoke ; Smoking ; Spirometry*