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: Congenital central hypoventilation syndrome (CCHS) is a rare disorder characterized by alveolar hypoventilation and autonomic dysregulation. Patients with CCHS have adequate ventilation while awake but exhibit hypoventilation while asleep. More severely affected patients exhibit hypoventilation both when awake and when asleep. CASE: Here, we report a case of successful spinal anesthesia and postoperative epidural analgesia in a patient with CCHS who underwent orthostatic surgery. CONCLUSIONS: In patients with CCHS, anesthesia is used with the goal of minimizing respiratory depression to avoid prolonged mechanical ventilation. Regional anesthesia should be considered where appropriate. Continuous oxygen saturation and end-tidal carbon dioxide monitoring must be available.
Analgesia, Epidural ; Anesthesia ; Anesthesia, Conduction ; Anesthesia, Spinal ; Anoxia ; Carbon Dioxide ; Humans ; Hypoventilation ; Oxygen ; Respiration, Artificial ; Respiratory Insufficiency ; Ventilation

Whole body ultrasound can be used to improve the speed and accuracy of evaluation of an increasing number of organ systems in the critically ill. Cardiac and abdominal ultrasound can be used to identify the mechanisms and etiology of hemodynamic instability. In hypoxemia or hypercarbia, lung ultrasound can rapidly identify the etiology of the condition with an accuracy that is equivalent to that of computed tomography. For encephalopathy, ocular ultrasound and transcranial Doppler can identify elevated intracranial pressure and midline shift. Renal and bladder ultrasound can identify the mechanisms and etiology of renal failure. Ultrasound can also improve the accuracy and safety of percutaneous procedures and should be currently used routinely for central vein catheterization and percutaneous tracheostomy.
Anoxia ; Brain Diseases ; Catheterization ; Catheters ; Critical Care ; Critical Illness ; Hemodynamics ; Intensive Care Units ; Intracranial Hypertension ; Lung ; Operating Rooms ; Renal Insufficiency ; Tracheostomy ; Ultrasonography ; Urinary Bladder ; Veins

We present the case of a 48-year-old woman who complained of sustained dyspnea and newly developed dyspnea, who then suddenly and unexpectedly expired during bronchoscopy. On postmortem examination, the deceased had advanced gastric cancer as a primary tumor. Frequent lymphatic tumor emboli were observed with some pulmonary lymphangitic carcinomatosis (PLC), and pulmonary tumor thrombotic microangiopathy (PTMA). PLC and PTMA are lethal forms of pulmonary metastasis, and PTMA can lead to sudden death. The characteristic findings of PLC and PTMA in the deceased were not predominant, however, and the clinical manifestation was not acutely deteriorating. These findings are, therefore, insufficient to explain the deceased's sudden death. Clinically, the deceased manifested hypoxemia, bradycardia and cardiac arrest during bronchoscopy and then soon expired, suggesting the possibility of cardiovascular complication related to bronchoscopy. Despite several limitations, we assumed that the sudden unexpected death might have been induced by cardiovascular complications related to bronchoscopy and due to the underlying pathologic condition by PLC and PTMA.
Anoxia ; Autopsy ; Bradycardia ; Bronchoscopy ; Carcinoma ; Death, Sudden ; Dyspnea ; Female ; Forensic Pathology ; Heart Arrest ; Humans ; Middle Aged ; Neoplasm Metastasis ; Stomach Neoplasms ; Thrombotic Microangiopathies

Hypoxia inducible factor (HIF)-stabilizers are being developed for the renal anemia treatment. This small molecules inhibit prolyl hydroxylase domain (PHD)-containing enzymes, causing HIF activation instead of degradation under the state of normoxia, finally increase production of intrinsic erythropoiesis. Current treatment guidelines suggest that renal anemia should be treated mainly with iron and erythropoiesis stimulating agents (ESAs). But there are several complications and concerns such as hypertension, ESA refractory anemia and increased cardiovascular mortality in using ESAs. Advantages of HIF stabilizers over ESAs are orally available, no dose-up requirement for inflammation. So far new HIF stabilizers showed efficacy and safety in renal anemia treatment. This new therapeutic agent may emerge as a standard treatment option for renal anmia treatment.
Anemia ; Anemia, Refractory ; Anoxia ; Erythropoiesis ; Hematinics ; Hepcidins ; Humans ; Hypertension ; Inflammation ; Iron ; Mortality ; Prolyl Hydroxylases ; Renal Insufficiency, Chronic

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