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

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*

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 ; Ischemia ; Neuregulin-1 ; Neurons ; Neuroprotection ; Neuroprotective Agents

BACKGROUND: This study was conducted to identify the types and incidence of adverse events associated with midazolam, which is the most widely used drug to induce conscious sedation during gastrointestinal endoscopy, and to analyze the factors associated with hypoxemia and sedation failure.METHODS: Of 87,740 patients who underwent gastrointestinal endoscopy between February 2015 and May 2017, the electronic medical records of 335 who reportedly developed adverse events were retrospectively reviewed, and analysis was performed to determine the risk factors for hypoxemia and sedation failure, the two most frequent adverse events among those manifested during gastrointestinal endoscopy.RESULTS: The overall adverse event rate was 0.38% (n = 335); hypoxemia was most frequent, accounting for 40.7% (n = 90), followed by sedation failure (34.8%, n = 77), delayed discharge from the recovery room (22.1%, n = 49), and hypotension (2.2%, n = 5). Compared with the control group, the hypoxemia group did not show any significant differences in sex and body weight, but mean age was significantly older (P < 0.001) and a significantly lower dose of midazolam was administered (P < 0.001). In the group with sedation failure, the mean rate was higher in men (P < 0.001) and a significantly higher dose of midazolam was administered (P < 0.001), but no age difference was found.CONCLUSIONS: Midazolam-based conscious sedation during gastrointestinal endoscopy can lead to various adverse events. In particular, as elderly patients are at higher risk of developing hypoxemia, midazolam dose adjustment and careful monitoring are required in this group.
Aged ; Anoxia ; Body Weight ; Conscious Sedation ; Electronic Health Records ; Endoscopy, Gastrointestinal ; Humans ; Hypotension ; Incidence ; Male ; Midazolam ; Recovery Room ; Retrospective Studies ; Risk Factors

OBJECTIVE: Assessing the severity of injury and predicting outcomes are essential in traumatic brain injury (TBI). However, the respiratory rate and Glasgow Coma Scale (GCS) of the Revised Trauma Score (RTS) are difficult to use in the prehospital setting. This investigation aimed to develop a new prehospital trauma score for TBI (NTS-TBI) to predict mortality and disability.METHODS: We used a nationwide trauma database on severe trauma cases transported by fire departments across Korea in 2013 and 2015. NTS-TBI model 1 used systolic blood pressure < 90 mmHg, peripheral capillary oxygen saturation < 90% measured via pulse oximeter, and motor component of GCS. Model 2 comprised variables of model 1 and age >65 years. We assessed discriminative power via area under the curve (AUC) value for in-hospital mortality and disability defined according to the Glasgow Outcome Scale with scores of 2 or 3. We then compared AUC values of NTS-TBI with those of RTS.RESULTS: In total, 3,642 patients were enrolled. AUC values of NTS-TBI models 1 and 2 for mortality were 0.833 (95% confidence interval [CI], 0.815 to 0.852) and 0.852 (95% CI, 0.835 to 0.869), respectively, while AUC values for disability were 0.772 (95% CI, 0.749 to 0.796) and 0.784 (95% CI, 0.761 to 0.807), respectively. AUC values of NTS-TBI model 2 for mortality and disability were higher than those of RTS (0.819 and 0.761, respectively) (P < 0.01).CONCLUSION: Our NTS-TBI model using systolic blood pressure, motor component of GCS, oxygen saturation, and age was feasible for prehospital care and showed outstanding discriminative power for mortality.
Anoxia ; Area Under Curve ; Blood Pressure ; Brain Injuries ; Capillaries ; Fires ; Glasgow Coma Scale ; Glasgow Outcome Scale ; Hospital Mortality ; Humans ; Hypotension ; Korea ; Mortality ; Observational Study ; Oxygen ; Quality Improvement ; Respiratory Rate

Oxygen is required to sustain aerobic organisms. Reactive oxygen species (ROS) are constantly released during mitochondrial oxygen consumption for energy production. Any imbalance between ROS production and its scavenger system induces oxidative stress. Oxidative stress, a critical contributor to tissue damage, is well-known to be associated with various diseases. The kidney is susceptible to hypoxia, and renal hypoxia is a common final pathway to end stage kidney disease, regardless of the underlying cause. Renal hypoxia aggravates oxidative stress, and elevated oxidative stress, in turn, exacerbates renal hypoxia. Oxidative stress is also enhanced in chronic kidney disease, especially diabetic kidney disease, through various mechanisms. Thus, the vicious cycle between oxidative stress and renal hypoxia critically contributes to the progression of renal injury. This review examines recent evidence connecting chronic hypoxia and oxidative stress in renal disease and subsequently describes several promising therapeutic approaches against oxidative stress.
Anoxia ; Diabetic Nephropathies ; Kidney ; Kidney Failure, Chronic ; Oxidative Stress ; Oxygen ; Oxygen Consumption ; Reactive Oxygen Species ; Renal Insufficiency, Chronic

High-flow nasal oxygenation (HFNO) is a promising new technique for anesthesiologists. The use of HFNO during the induction of anesthesia and during upper airway surgeries has been initiated, and its applications have been rapidly growing ever since. The advantages of this technique include its easy set-up, high tolerability, and its abilities to produce positive airway pressure and a high fraction of inspired oxygen and to influence the clearance of carbon dioxide to some extent. HFNO, via a nasal cannula, can provide oxygen both to patients who can breathe spontaneously and to those who are apneic; further, this technique does not interfere with bag-mask ventilation, attempts at laryngoscopy for tracheal intubation, and surgical procedures conducted in the airway. In this review, we describe the techniques associated with HFNO and the advantages and disadvantages of HFNO based on the current state of knowledge.
Airway Management ; Anesthesia ; Anoxia ; Carbon Dioxide ; Catheters ; Humans ; Intubation ; Intubation, Intratracheal ; Laryngoscopy ; Oxygen ; Ventilation

OBJECTIVES: Hypoxia—a characteristic of almost all types of solid tumors—has been associated with poor outcomes in several human malignancies. Genipin—an active constituent of Gardenia fruit— has been reported to exert an anti-tumor effect in several cancers. In this study, we investigated inhibition of angiogenesis using Genipin-mediated hypoxia-induced hypoxia inducible factor (HIF-1) and VEGF expression in human cervical cancer cells.METHODS: Under normoxic and hypoxic conditions, the expression of HIF-1α and VEGF in cervical cancer HeLa cells was detected by quantitative reverse transcription polymerase chain reaction and western blotting. Luciferase reporter assays were used to investigate the molecular mechanisms underlying the hypoxia-induced survivin activation.RESULTS: Surprisingly, we found that Genipin suppressed the HIF-1α accumulation during hypoxia in human liver cancer cell line (HepG2), human prostate cancer cell line (LNCaP), colon cancer cell line (HCT116), and breast cancer cell line (MDA231). Genipin treatment also significantly reduced hypoxia-induced secretion of VEGF.CONCLUSIONS: Suppression of HIF-1α accumulation following treatment with Genipin under hypoxia was associated with PI3K and MAPK pathways. Taken together, these results suggested that Genipin inhibits HIF-1α expression through inhibition of PI3K and MAPK signaling pathways. These results provide new insights into a potential mechanism of the anticancer properties of Genipin.
Anoxia ; Blotting, Western ; Breast Neoplasms ; Cell Line ; Colonic Neoplasms ; Gardenia ; HeLa Cells ; Humans ; Liver Neoplasms ; Luciferases ; Polymerase Chain Reaction ; Prostatic Neoplasms ; Reverse Transcription ; Uterine Cervical Neoplasms ; Vascular Endothelial Growth Factor A

BACKGROUND: Low temperature plasma (LTP) was recently shown to be potentially useful for biomedical applications such as bleeding cessation, cancer treatment, and wound healing, among others. Keratinocytes are a major cell type that migrates directionally into the wound bed, and their proliferation leads to complete wound closure during the cutaneous repair/regeneration process. However, the beneficial effects of LTP on human keratinocytes have not been well studied. Therefore, we investigated migration, growth factor production, and cytokine secretion in primary human keratinocytes after LTP treatment.METHODS: Primary cultured keratinocytes were obtained from human skin biopsies. Cell viability was measured with the EZ-Cytox cell viability assay, cell migration was evaluated by an in vitro wound healing assay, gene expression was analyzed by quantitative real-time polymerase chain reaction, and protein expression was measured by enzyme-linked immunosorbent assays and western blotting after LTP treatment.RESULTS: Cell migration, the secretion of several cytokines, and gene and protein levels of angiogenic growth factors increased in LTP-treated human keratinocytes without associated cell toxicity. LTP treatment also significantly induced the expression of hypoxia inducible factor-1α (HIF-1α), an upstream regulator of angiogenesis. Further, the inhibition of HIF-1α expression blocked the production of angiogenic growth factors induced by LTP in human keratinocytes.CONCLUSION: Our results suggest that LTP treatment is an effective approach to modulate wound healing-related molecules in epidermal keratinocytes and might promote angiogenesis, leading to improved wound healing.
Anoxia ; Biopsy ; Blotting, Western ; Cell Migration Assays ; Cell Movement ; Cell Survival ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Gene Expression ; Hemorrhage ; Humans ; In Vitro Techniques ; Intercellular Signaling Peptides and Proteins ; Keratinocytes ; Plasma ; Real-Time Polymerase Chain Reaction ; Skin ; Wound Healing ; Wounds and Injuries

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*