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International Journal of Molecular... Dec 2020Oxygenated ex situ machine perfusion of donor livers is an alternative for static cold preservation that can be performed at temperatures from 0 °C to 37 °C. Organ... (Review)
Review
Oxygenated ex situ machine perfusion of donor livers is an alternative for static cold preservation that can be performed at temperatures from 0 °C to 37 °C. Organ metabolism depends on oxygen to produce adenosine triphosphate and temperatures below 37 °C reduce the metabolic rate and oxygen requirements. The transport and delivery of oxygen in machine perfusion are key determinants in preserving organ viability and cellular function. Oxygen delivery is more challenging than carbon dioxide removal, and oxygenation of the perfusion fluid is temperature dependent. The maximal oxygen content of water-based solutions is inversely related to the temperature, while cellular oxygen demand correlates positively with temperature. Machine perfusion above 20 °C will therefore require an oxygen carrier to enable sufficient oxygen delivery to the liver. Human red blood cells are the most physiological oxygen carriers. Alternative artificial oxygen transporters are hemoglobin-based oxygen carriers, perfluorocarbons, and an extracellular oxygen carrier derived from a marine invertebrate. We describe the principles of oxygen transport, delivery, and consumption in machine perfusion for donor livers using different oxygen carrier-based perfusion solutions and we discuss the properties, advantages, and disadvantages of these carriers and their use.
Topics: Animals; Erythrocytes; Humans; Liver; Oxygen; Perfusion; Temperature; Tissue Donors
PubMed: 33379394
DOI: 10.3390/ijms22010235 -
Scientific Reports Jan 2022An in vitro experiment on the dissolved oxygen transport during liquid ventilation by means of measuring global oxygen concentration fields is presented within this...
An in vitro experiment on the dissolved oxygen transport during liquid ventilation by means of measuring global oxygen concentration fields is presented within this work. We consider the flow in an idealized four generation model of the human airways in a range of peak Reynolds numbers of [Formula: see text]-3400 and Womersley numbers of [Formula: see text]-5. Fluorescence quenching measurements were employed in order to visualize and quantify the oxygen distribution with high temporal and spatial resolution during the breathing cycle. Measurements with varying tidal volumes and oscillating frequencies reveal short living times of characteristic concentration patterns for all parameter variations. Similarities to typical velocity patterns in similar lung models persist only in early phases during each cycle. Concentration gradients are quickly homogenized by secondary motions within the lung model. A strong dependency of peak oxygen concentration on tidal volume is observed with considerably higher relative concentrations for higher tidal volumes.
Topics: Humans; Liquid Ventilation; Models, Biological; Oxygen; Respiration
PubMed: 35075158
DOI: 10.1038/s41598-022-05105-1 -
Experimental Physiology Mar 2023What is the topic of this review? How the placenta, which transports nutrients and oxygen to the fetus, may alter its support of fetal growth developmentally and with... (Review)
Review
NEW FINDINGS
What is the topic of this review? How the placenta, which transports nutrients and oxygen to the fetus, may alter its support of fetal growth developmentally and with adverse gestational conditions. What advances does it highlight? Placental formation and function alter with the needs of the fetus for substrates for growth during normal gestation and when there is enhanced competition for substrates in species with multiple gestations or adverse gestational environments, and this is mediated by imprinted genes, signalling pathways, mitochondria and fetal sexomes.
ABSTRACT
The placenta is vital for mammalian development and a key determinant of life-long health. It is the interface between the mother and fetus and is responsible for transporting the nutrients and oxygen a fetus needs to develop and grow. Alterations in placental formation and function, therefore, have consequences for fetal growth and birthweight, which in turn determine perinatal survival and risk of non-communicable diseases for the offspring in later postnatal life. However, the placenta is not a static organ. As this review summarizes, research from multiple species has demonstrated that placental formation and function alter developmentally to the needs of the fetus for substrates for growth during normal gestation, as well as when there is greater competition for substrates in polytocous species and monotocous species with multiple gestations. The placenta also adapts in response to the gestational environment, integrating information about the ability of the mother to provide nutrients and oxygen with the needs of the fetus in that prevailing environment. In particular, placental structure (e.g. vascularity, surface area, blood flow, diffusion distance) and transport capacity (e.g. nutrient transporter levels and activity) respond to suboptimal gestational environments, namely malnutrition, obesity, hypoxia and maternal ageing. Mechanisms mediating developmentally and environmentally induced homeostatic responses of the placenta that help support normal fetal growth include imprinted genes, signalling pathways, subcellular constituents and fetal sexomes. Identification of these placental strategies may inform the development of therapies for complicated human pregnancies and advance understanding of the pathways underlying poor fetal outcomes and their consequences for health and disease risk.
Topics: Animals; Pregnancy; Female; Humans; Placenta; Fetal Development; Fetus; Membrane Transport Proteins; Oxygen; Mammals
PubMed: 36484327
DOI: 10.1113/EP090442 -
International Journal of Molecular... Jan 2022Higher concentration of protons in the mitochondrial intermembrane space compared to the matrix results in an electrochemical potential causing the back flux of protons... (Review)
Review
Higher concentration of protons in the mitochondrial intermembrane space compared to the matrix results in an electrochemical potential causing the back flux of protons to the matrix. This proton transport can take place through ATP synthase complex (leading to formation of ATP) or can occur via proton transporters of the mitochondrial carrier superfamily and/or membrane lipids. Some mitochondrial proton transporters, such as uncoupling proteins (UCPs), transport protons as their general regulating function; while others are symporters or antiporters, which use the proton gradient as a driving force to co-transport other substrates across the mitochondrial inner membrane (such as phosphate carrier, a symporter; or aspartate/glutamate transporter, an antiporter). Passage (or leakage) of protons across the inner membrane to matrix from any route other than ATP synthase negatively impacts ATP synthesis. The focus of this review is on regulated proton transport by UCPs. Recent findings on the structure and function of UCPs, and the related research methodologies, are also critically reviewed. Due to structural similarity of members of the mitochondrial carrier superfamily, several of the known structural features are potentially expandable to all members. Overall, this report provides a brief, yet comprehensive, overview of the current knowledge in the field.
Topics: Animals; Gene Expression Regulation; Humans; Ion Transport; Membrane Potential, Mitochondrial; Mitochondria; Mitochondrial Uncoupling Proteins; Models, Molecular; Protein Conformation
PubMed: 35163451
DOI: 10.3390/ijms23031528 -
Redox Biology May 2023The perils and promises of inspiratory hyperoxia (IH) in oncology are still controversial, especially for patients with lung cancer. Increasing evidence shows that...
The perils and promises of inspiratory hyperoxia (IH) in oncology are still controversial, especially for patients with lung cancer. Increasing evidence shows that hyperoxia exposure is relevant to the tumor microenvironment. However, the detailed role of IH on the acid-base homeostasis of lung cancer cells remains unclear. In this study, the effects of 60% oxygen exposure on intra- and extracellular pH were systematically evaluated in H1299 and A549 cells. Our data indicate that hyperoxia exposure reduces intracellular pH, which might be expected to reduce the proliferation, invasion, and epithelial-to-mesenchymal transition of lung cancer cells. RNA sequencing, Western blot, and PCR analysis reveal that monocarboxylate transporter 1 (MCT1) mediates intracellular lactate accumulation and intracellular acidification of H1299 and A549 cells at 60% oxygen exposure. In vivo studies further demonstrate that MCT1 knockdown dramatically reduces lung cancer growth, invasion, and metastasis. The results of luciferase and ChIP-qPCR assays further confirm that MYC is a transcription factor of MCT1, and PCR and Western blot assays confirm that MYC is downregulated under hyperoxic conditions. Collectively, our data reveal that hyperoxia can suppress the MYC/MCT1 axis and cause the accumulation of lactate and intracellular acidification, thereby retarding tumor growth and metastasis.
Topics: Humans; Hyperoxia; Symporters; Lung Neoplasms; Lactic Acid; Oxygen; Hydrogen-Ion Concentration; Glucose; Cell Line, Tumor; Tumor Microenvironment
PubMed: 36867943
DOI: 10.1016/j.redox.2023.102647 -
Journal of Applied Physiology... Feb 2022Pulmonary gas exchange during diving or in a dry hyperbaric environment is affected by increased breathing gas density and possibly water immersion. During free diving,... (Review)
Review
Pulmonary gas exchange during diving or in a dry hyperbaric environment is affected by increased breathing gas density and possibly water immersion. During free diving, there is also the effect of apnea. Few studies have published blood gas data in underwater or hyperbaric environments: this review summarizes the available literature and was used to test the hypothesis that arterial Po under hyperbaric conditions can be predicted from blood gas measurement at 1 atmosphere assuming a constant arterial/alveolar Po ratio (a:A). A systematic search was performed on traditional sources including arterial blood gases obtained on humans in hyperbaric or underwater environments. The a:A was calculated at 1 atmosphere absolute (ATA). For each condition, predicted arterial partial pressure of oxygen ([Formula: see text]) at pressure was calculated using the 1 ATA a:A, and the measured [Formula: see text] was plotted against the predicted value with Spearman correlation coefficients. Of 3,640 records reviewed, 30 studies were included: 25 were reports describing values obtained in hyperbaric chambers, and the remaining were collected while underwater. Increased inspired O at pressure resulted in increased [Formula: see text], although underlying lung disease in patients treated with hyperbaric oxygen attenuated the rise. [Formula: see text] generally increased only slightly. In breath-hold divers, hyperoxemia generally occurred at maximum depth, with hypoxemia after surfacing. The a:A adequately predicted the [Formula: see text] under various conditions: dry ( = 0.993, < 0.0001), rest versus exercise ( = 0.999, < 0.0001), and breathing mixtures ( = 0.995, < 0.0001). In conclusion, pulmonary oxygenation under hyperbaric conditions can be reliably and accurately predicted from 1 ATA a:A measurements.
Topics: Blood Gas Analysis; Diving; Humans; Hyperbaric Oxygenation; Oxygen; Partial Pressure; Pulmonary Gas Exchange
PubMed: 34941439
DOI: 10.1152/japplphysiol.00569.2021 -
American Journal of Physiology. Lung... Sep 2022The balance of gas exchange and lung ventilation is essential for the maintenance of body homeostasis. There are many ion channels and transporters in respiratory... (Review)
Review
The balance of gas exchange and lung ventilation is essential for the maintenance of body homeostasis. There are many ion channels and transporters in respiratory epithelial cells, including epithelial sodium channel, Na,K-ATPase, cystic fibrosis transmembrane conductance regulator, and some transporters. These ion channels/transporters maintain the capacity of liquid layer on the surface of respiratory epithelial cells and provide an immune barrier for the respiratory system to clear off foreign pathogens. However, in some harmful external environments and/or pathological conditions, the respiratory epithelium is prone to hypoxia, which would destroy the ion transport function of the epithelium and unbalance the homeostasis of internal environment, triggering a series of pathological reactions. Many respiratory diseases associated with hypoxia manifest an increased expression of hypoxia-inducible factor-1, which mediates the integrity of the epithelial barrier and affects epithelial ion transport function. It is important to study the relationship between hypoxia and ion transport function, whereas the mechanism of hypoxia-induced ion transport dysfunction in respiratory diseases is not clear. This review focuses on the relationship between hypoxia and respiratory diseases, as well as dysfunction of ion transport and tight junctions in respiratory epithelial cells under hypoxia.
Topics: Cystic Fibrosis Transmembrane Conductance Regulator; Epithelial Sodium Channels; Humans; Hypoxia; Ion Transport; Respiration Disorders; Respiratory Mucosa; Sodium-Potassium-Exchanging ATPase
PubMed: 35819839
DOI: 10.1152/ajplung.00065.2022 -
Proceedings of the National Academy of... Oct 2023Energy conversion by electron transport chains occurs through the sequential transfer of electrons between protein complexes and intermediate electron carriers, creating...
Energy conversion by electron transport chains occurs through the sequential transfer of electrons between protein complexes and intermediate electron carriers, creating the proton motive force that enables ATP synthesis and membrane transport. These protein complexes can also form higher order assemblies known as respiratory supercomplexes (SCs). The electron transport chain of the opportunistic pathogen is closely linked with its ability to invade host tissue, tolerate harsh conditions, and resist antibiotics but is poorly characterized. Here, we determine the structure of a SC that forms between the quinol:cytochrome oxidoreductase (cytochrome ) and one of the organism's terminal oxidases, cytochrome , which is found only in some bacteria. Remarkably, the SC structure also includes two intermediate electron carriers: a diheme cytochrome and a single heme cytochrome . Together, these proteins allow electron transfer from ubiquinol in cytochrome to oxygen in cytochrome . We also present evidence that different isoforms of cytochrome can participate in formation of this SC without changing the overall SC architecture. Incorporating these different subunit isoforms into the SC would allow the bacterium to adapt to different environmental conditions. Bioinformatic analysis focusing on structural motifs in the SC suggests that cytochrome - SCs also exist in other bacterial pathogens.
Topics: Pseudomonas aeruginosa; Electron Transport; Biological Transport; Cytochromes c; Anti-Bacterial Agents
PubMed: 37751552
DOI: 10.1073/pnas.2307093120 -
Mathematical Biosciences Nov 2020Elevated intraocular pressure is the primary risk factor for glaucoma, yet vascular health and ocular hemodynamics have also been established as important risk factors...
Elevated intraocular pressure is the primary risk factor for glaucoma, yet vascular health and ocular hemodynamics have also been established as important risk factors for the disease. The precise physiological mechanisms and processes by which flow impairment and reduced tissue oxygenation relate to retinal ganglion cell death are not fully known. Mathematical modeling has emerged as a useful tool to help decipher the role of hemodynamic alterations in glaucoma. Several previous models of the retinal microvasculature and tissue have investigated the individual impact of spatial heterogeneity, flow regulation, and oxygen transport on the system. This study combines all three of these components into a heterogeneous mathematical model of retinal arterioles that includes oxygen transport and acute flow regulation in response to changes in pressure, shear stress, and oxygen demand. The metabolic signal (S) is implemented as a wall-derived signal that reflects the oxygen deficit along the network, and three cases of conduction are considered: no conduction, a constant signal, and a flow-weighted signal. The model shows that the heterogeneity of the downstream signal serves to regulate flow better than a constant conducted response. In fact, the increases in average tissue PO due to a flow-weighted signal are often more significant than if the entire level of signal is increased. Such theoretical work supports the importance of the non-uniform structure of the retinal vasculature when assessing the capability and/or dysfunction of blood flow regulation in the retinal microcirculation.
Topics: Animals; Biological Transport, Active; Computer Simulation; Glaucoma, Open-Angle; Hemodynamics; Humans; Mathematical Concepts; Mice; Microcirculation; Models, Biological; Oxygen; Oxygen Consumption; Regional Blood Flow; Retina; Retinal Vessels
PubMed: 32920096
DOI: 10.1016/j.mbs.2020.108476 -
British Journal of Cancer Feb 2021In tumours, hypoxia-a condition in which the demand for oxygen is higher than its availability-is well known to be associated with reduced sensitivity to radiotherapy... (Review)
Review
In tumours, hypoxia-a condition in which the demand for oxygen is higher than its availability-is well known to be associated with reduced sensitivity to radiotherapy and chemotherapy, and with immunosuppression. The consequences of hypoxia on tumour biology and patient outcomes have therefore led to the investigation of strategies that can alleviate hypoxia in cancer cells, with the aim of sensitising cells to treatments. An alternative therapeutic approach involves the design of prodrugs that are activated by hypoxic cells. Increasing evidence indicates that hypoxia is not just clinically significant in adult cancers but also in paediatric cancers. We evaluate relevant methods to assess the levels and extent of hypoxia in childhood cancers, including novel imaging strategies such as oxygen-enhanced magnetic resonance imaging (MRI). Preclinical and clinical evidence largely supports the use of hypoxia-targeting drugs in children, and we describe the critical need to identify robust predictive biomarkers for the use of such drugs in future paediatric clinical trials. Ultimately, a more personalised approach to treatment that includes targeting hypoxic tumour cells might improve outcomes in subgroups of paediatric cancer patients.
Topics: Antineoplastic Agents; Biomarkers; Carbonic Anhydrase IX; Cell Hypoxia; Child; Combined Modality Therapy; Glucose Transporter Type 1; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Magnetic Resonance Imaging; Neoplasms; Nitroimidazoles; Oxygen Consumption; Prodrugs; Tumor Hypoxia; Vascular Endothelial Growth Factor A
PubMed: 33106581
DOI: 10.1038/s41416-020-01107-w