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Seminars in Fetal & Neonatal Medicine Oct 2023'Apnoeic oxygenation' describes the diffusion of oxygen across the alveolar-capillary interface in the absence of tidal respiration. Apnoeic oxygenation requires a... (Review)
Review
'Apnoeic oxygenation' describes the diffusion of oxygen across the alveolar-capillary interface in the absence of tidal respiration. Apnoeic oxygenation requires a patent airway, the diffusion of oxygen to the alveoli, and cardiopulmonary circulation. Apnoeic oxygenation has varied applications in adult medicine including facilitating tubeless anaesthesia or improving oxygenation when a difficult airway is known or anticipated. In the paediatric population, apnoeic oxygenation prolongs the time to oxygen desaturation, facilitating intubation. This application has gained attention in neonatal intensive care where intubation remains a challenging procedure. Difficulties are related to the infant's size and decreased respiratory reserve. In addition, policy changes have led to limited opportunities for operators to gain proficiency. Until recently, evidence of benefit of apnoeic oxygenation in the neonatal population came from a small number of infants recruited to paediatric studies. Evidence specific to neonates is emerging and suggests apnoeic oxygenation may increase intubation success and limit physiological instability during the procedure. The best way to deliver oxygen to facilitate apnoeic oxygenation remains an important question.
Topics: Adult; Infant; Infant, Newborn; Humans; Child; Respiration, Artificial; Lung; Oxygen; Oxygen Inhalation Therapy; Intubation, Intratracheal
PubMed: 38008598
DOI: 10.1016/j.siny.2023.101487 -
Chest Mar 2024
Topics: Humans; Oxygen; Pulmonary Embolism; Fibrinolytic Agents; Acute Disease; Thrombolytic Therapy
PubMed: 38461007
DOI: 10.1016/j.chest.2023.10.003 -
ELife Dec 2023Based on studies with a fluorescent reporter dye, Mito Thermo Yellow (MTY), and the genetically encoded gTEMP ratiometric fluorescent temperature indicator targeted to...
Based on studies with a fluorescent reporter dye, Mito Thermo Yellow (MTY), and the genetically encoded gTEMP ratiometric fluorescent temperature indicator targeted to mitochondria, the temperature of active mitochondria in four mammalian and one insect cell line was estimated to be up to 15°C above that of the external environment to which the cells were exposed. High mitochondrial temperature was maintained in the face of a variety of metabolic stresses, including substrate starvation or modification, decreased ATP demand due to inhibition of cytosolic protein synthesis, inhibition of the mitochondrial adenine nucleotide transporter and, if an auxiliary pathway for electron transfer was available via the alternative oxidase, even respiratory poisons acting downstream of oxidative phosphorylation (OXPHOS) complex I. We propose that the high temperature of active mitochondria is an inescapable consequence of the biochemistry of OXPHOS and is homeostatically maintained as a primary feature of mitochondrial metabolism.
Topics: Animals; Temperature; Mitochondria; Cell Respiration; Oxidative Phosphorylation; Body Temperature Regulation; Stress, Physiological; Mammals
PubMed: 38079477
DOI: 10.7554/eLife.89232 -
Cancer Letters May 2024A general feature of cancer is hypoxia, determined as low oxygen levels. Low oxygen levels may cause cells to alter in ways that contribute to tumor growth and... (Review)
Review
A general feature of cancer is hypoxia, determined as low oxygen levels. Low oxygen levels may cause cells to alter in ways that contribute to tumor growth and resistance to treatment. Hypoxia leads to variations in cancer cell metabolism, angiogenesis and metastasis. Furthermore, a hypoxic tumor microenvironment might induce immunosuppression. Moreover, hypoxia has the potential to impact cellular processes, such as autophagy. Autophagy refers to the catabolic process by which damaged organelles and toxic macromolecules are broken down. The abnormal activation of autophagy has been extensively recorded in human tumors and it serves as a regulator of cell growth, spread to other parts of the body, and resistance to treatment. There is a correlation between hypoxia and autophagy in human malignancies. Hypoxia can regulate the activity of AMPK, mTOR, Beclin-1, and ATGs to govern autophagy in human malignancies. Furthermore, HIF-1α, serving as an indicator of low oxygen levels, controls the process of autophagy. Hypoxia-induced autophagy has a crucial role in regulating the growth, spread, and resistance to treatment in human malignancies. Hypoxia-induced regulation of autophagy can impact other mechanisms of cell death, such as apoptosis. Chemoresistance and radioresistance have become significant challenges in recent years. Hypoxia-mediated autophagy plays a crucial role in determining the response to these therapeutic treatments.
Topics: Humans; Autophagy; Neoplasms; Tumor Microenvironment; Signal Transduction; Tumor Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Cell Hypoxia; Drug Resistance, Neoplasm; Animals
PubMed: 38521197
DOI: 10.1016/j.canlet.2024.216823 -
Experimental & Molecular Medicine Mar 2024Oxygen is crucial for life and acts as the final electron acceptor in mitochondrial energy production. Cells adapt to varying oxygen levels through intricate response... (Review)
Review
Oxygen is crucial for life and acts as the final electron acceptor in mitochondrial energy production. Cells adapt to varying oxygen levels through intricate response systems. Hypoxia-inducible factors (HIFs), including HIF-1α and HIF-2α, orchestrate the cellular hypoxic response, activating genes to increase the oxygen supply and reduce expenditure. Under conditions of excess oxygen and resulting oxidative stress, nuclear factor erythroid 2-related factor 2 (NRF2) activates hundreds of genes for oxidant removal and adaptive cell survival. Hypoxia and oxidative stress are core hallmarks of solid tumors and activated HIFs and NRF2 play pivotal roles in tumor growth and progression. The complex interplay between hypoxia and oxidative stress within the tumor microenvironment adds another layer of intricacy to the HIF and NRF2 signaling systems. This review aimed to elucidate the dynamic changes and functions of the HIF and NRF2 signaling pathways in response to conditions of hypoxia and oxidative stress, emphasizing their implications within the tumor milieu. Additionally, this review explored the elaborate interplay between HIFs and NRF2, providing insights into the significance of these interactions for the development of novel cancer treatment strategies.
Topics: Humans; Cell Hypoxia; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Neoplasms; NF-E2-Related Factor 2; Oxidative Stress; Oxygen; Tumor Microenvironment
PubMed: 38424190
DOI: 10.1038/s12276-024-01180-8 -
Current Opinion in Gastroenterology Jul 2023Hypoxia is a known contributor to inflammation in inflammatory bowel diseases (IBD), and a growing interest has emerged in pharmacologically targeting hypoxia response... (Review)
Review
PURPOSE OF REVIEW
Hypoxia is a known contributor to inflammation in inflammatory bowel diseases (IBD), and a growing interest has emerged in pharmacologically targeting hypoxia response pathways to treat IBD. The most basic form of treatment for hypoxia is delivering higher amounts of oxygen to the intestinal mucosa. In this review, we summarize the evidence in support of hyperbaric oxygen therapy (HBOT), a mechanism to deliver high amounts of oxygen to tissue, for treating IBD.
RECENT FINDINGS
Two phase 2 clinical trials in hospitalized ulcerative colitis patients suffering from moderate-to-severe flares have demonstrated that HBOT improves responsiveness to steroids and avoidance of rescue medical and surgical therapy. Outpatient cohort studies in perianal fistulizing Crohn's disease and fistulizing complications of the pouch have demonstrated improved healing, particularly for complex fistulae. Several systematic reviews have now been completed, and HBOT has been observed to be well tolerated with low rates of adverse events.
SUMMARY
HBOT may be considered as an adjunctive treatment for hospitalized ulcerative colitis flares and Crohn's disease-related fistulae. Higher quality trials are needed to confirm efficacy.
Topics: Humans; Colitis, Ulcerative; Crohn Disease; Hyperbaric Oxygenation; Inflammatory Bowel Diseases; Oxygen
PubMed: 37265170
DOI: 10.1097/MOG.0000000000000952 -
Science Advances Nov 2023Poor oxygenation (hypoxia) is a common spatially heterogeneous feature of human tumors. Biological responses to tumor hypoxia are orchestrated by the decreased activity... (Review)
Review
Poor oxygenation (hypoxia) is a common spatially heterogeneous feature of human tumors. Biological responses to tumor hypoxia are orchestrated by the decreased activity of oxygen-dependent enzymes. The affinity of these enzymes for oxygen positions them along a continuum of oxygen sensing that defines their roles in launching reactive and adaptive cellular responses. These responses encompass regulation of all steps in the central dogma, with rapid perturbation of the metabolome and proteome followed by more persistent reprogramming of the transcriptome and epigenome. Core hypoxia response genes and pathways are commonly regulated at multiple inflection points, fine-tuning the dependencies on oxygen concentration and hypoxia duration. Ultimately, shifts in the activity of oxygen-sensing enzymes directly or indirectly endow cells with intrinsic hypoxia tolerance and drive processes that are associated with aggressive phenotypes in cancer including angiogenesis, migration, invasion, immune evasion, epithelial mesenchymal transition, and stemness.
Topics: Humans; Tumor Hypoxia; Neoplasms; Hypoxia; Oxygen; Phenotype
PubMed: 37992163
DOI: 10.1126/sciadv.adj6409 -
Nature Communications Nov 2023Implantable cell therapies and tissue transplants require sufficient oxygen supply to function and are limited by a delay or lack of vascularization from the transplant...
Implantable cell therapies and tissue transplants require sufficient oxygen supply to function and are limited by a delay or lack of vascularization from the transplant host. Previous exogenous oxygenation strategies have been bulky and had limited oxygen production or regulation. Here, we show an electrocatalytic approach that enables bioelectronic control of oxygen generation in complex cellular environments to sustain engineered cell viability and therapy under hypoxic stress and at high cell densities. We find that nanostructured sputtered iridium oxide serves as an ideal catalyst for oxygen evolution reaction at neutral pH. We demonstrate that this approach exhibits a lower oxygenation onset and selective oxygen production without evolution of toxic byproducts. We show that this electrocatalytic on site oxygenator can sustain high cell loadings (>60k cells/mm) in hypoxic conditions in vitro and in vivo. Our results showcase that exogenous oxygen production devices can be readily integrated into bioelectronic platforms, enabling high cell loadings in smaller devices with broad applicability.
Topics: Humans; Oxygen; Hypoxia; Cell Hypoxia; Respiratory Physiological Phenomena
PubMed: 37945597
DOI: 10.1038/s41467-023-42697-2 -
Journal of Artificial Organs : the... Mar 2024Hollow fiber membrane is incorporated into an extracorporeal membrane oxygenator (ECMO), and the function of the membrane determines the ECMO's functions, such as gas... (Review)
Review
Hollow fiber membrane is incorporated into an extracorporeal membrane oxygenator (ECMO), and the function of the membrane determines the ECMO's functions, such as gas transfer rate, biocompatibility, and durability. In Japan, the membrane oxygenator to assist circulation and ventilation is approved for ECMO support. However, in all cases, the maximum use period has been only 6 h, and so-called 'off-label use' is common for ECMO support of severely ill COVID-19 patients. Under these circumstances, the HLS SET Advanced (Getinge Group Japan K.K.) was approved in 2020 for the first time in Japan as a membrane oxygenator with a two-week period of use. Following this membrane oxygenator, it is necessary to establish a domestic ECMO system that is approved for long-term use and suitable for supporting patients. Looking back on the evolution of ECMO so far, Japanese researchers and manufacturers have also contributed to the developments of ECMO globally. Currently, excellent membrane oxygenators and systems have been marketed by Japanese manufacturers and some of them are globally acclaimed, but in fact, most of the ECMO membranes are not made in Japan. Fortunately, Japan has led the world in the fields of membrane separation technology and hollow fiber membrane production. In the wake of this pandemic, from the perspective of medical and economic security, the practical use of purely domestic hollow fiber membranes and membrane oxygenators for long-term ECMO is imperative in anticipation of the next pandemic.
Topics: Humans; Oxygenators, Membrane; Extracorporeal Membrane Oxygenation; Equipment Design; Japan
PubMed: 36914927
DOI: 10.1007/s10047-023-01389-w -
Redox Biology May 2024Mitochondrial respiration extends beyond ATP generation, with the organelle participating in many cellular and physiological processes. Parallel changes in components of...
Mitochondrial respiration extends beyond ATP generation, with the organelle participating in many cellular and physiological processes. Parallel changes in components of the mitochondrial electron transfer system with respiration render it an appropriate hub for coordinating cellular adaption to changes in oxygen levels. How changes in respiration under functional hypoxia (i.e., when intracellular O levels limit mitochondrial respiration) are relayed by the electron transfer system to impact mitochondrial adaption and remodeling after hypoxic exposure remains poorly defined. This is largely due to challenges integrating findings under controlled and defined O levels in studies connecting functions of isolated mitochondria to humans during physical exercise. Here we present experiments under conditions of hypoxia in isolated mitochondria, myotubes and exercising humans. Performing steady-state respirometry with isolated mitochondria we found that oxygen limitation of respiration reduced electron flow and oxidative phosphorylation, lowered the mitochondrial membrane potential difference, and decreased mitochondrial calcium influx. Similarly, in myotubes under functional hypoxia mitochondrial calcium uptake decreased in response to sarcoplasmic reticulum calcium release for contraction. In both myotubes and human skeletal muscle this blunted mitochondrial adaptive responses and remodeling upon contractions. Our results suggest that by regulating calcium uptake the mitochondrial electron transfer system is a hub for coordinating cellular adaption under functional hypoxia.
Topics: Humans; Calcium; Oxygen Consumption; Cell Respiration; Hypoxia; Muscle, Skeletal; Oxygen
PubMed: 38401291
DOI: 10.1016/j.redox.2024.103037