{"title":"The Underexplored Landscape of Hypoxia-Inducible Factor 2 Alpha and Potential Roles in Tumor Macrophages: A Review.","authors":"Kayla J Steinberger, Timothy D Eubank","doi":"10.3390/oxygen3010005","DOIUrl":"10.3390/oxygen3010005","url":null,"abstract":"<p><p>Low tissue oxygenation, termed <i>hypoxia</i>, is a characteristic of solid tumors with negative consequences. Tumor-associated macrophages (TAMs) accumulate in hypoxic tumor regions and correlate with worse outcomes in cancer patients across several tumor types. Thus, the molecular mechanism in which macrophages respond to low oxygen tension has been increasingly investigated in the last decade. Hypoxia stabilizes a group of hypoxia-inducible transcription factors (HIFs) reported to drive transcriptional programs involved in cell survival, metabolism, and angiogenesis. Though both tumor macrophage HIF-1α and HIF-2α correlate with unfavorable tumor microenvironments, most research focuses on HIF-1α as the master regulator of hypoxia signaling, because HIF-1α expression was originally identified in several cancer types and correlates with worse outcome in cancer patients. The relative contribution of each HIFα subunit to cell phenotypes is poorly understood especially in TAMs. Once thought to have overlapping roles, recent investigation of macrophage HIF-2α has demonstrated a diverse function from HIF-1α. Little work has been published on the differential role of hypoxia-dependent macrophage HIF-2α when compared to HIF-1α in the context of tumor biology. This review highlights cellular HIF-2α functions and emphasizes the gap in research investigating oxygen-dependent functions of tumor macrophage HIF-2α.</p>","PeriodicalId":74387,"journal":{"name":"Oxygen (Basel, Switzerland)","volume":"3 1","pages":"45-76"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10137047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9399331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Igor A. Lavrinenko, G. Vashanov, J. L. Hernández Cáceres, Y. Nechipurenko
{"title":"Fitting Parameters of a Modified Hill’s Equation and Their Influence on the Shape of the Model Hemoglobin Oxygenation Curve","authors":"Igor A. Lavrinenko, G. Vashanov, J. L. Hernández Cáceres, Y. Nechipurenko","doi":"10.3390/oxygen3010007","DOIUrl":"https://doi.org/10.3390/oxygen3010007","url":null,"abstract":"Oxygen binds to hemoglobin cooperatively, and a correct description of this binding is relevant not only for understanding the mechanisms of involved molecular processes but also for clinical purposes. Hill’s equation, derived over a hundred years ago, is still the simplest and most efficient way to perform this description. However, in terms of accuracy, it is inferior to Adair´s equation, which contains more parameters. We proposed to use a modified Hill equation and showed that it allows a more accurate description of the binding of oxygen to hemoglobin than Adair’s equation. At the same time, unlike Adair’s equation, our model retains the physical meaning given to the original Hill equation. We considered and analyzed the influence of the equation parameters on the course of the oxygenation curve and presented the relationship between the fitting parameters and other parameters derived from them in the form of a diagram-graph, which, in our opinion, simplifies the perception of these estimates and can be useful in solving a number of problems for which the traditional way of analyzing the degree of cooperative interaction was via the Hill equation. We suggest that the newly proposed parameter hmax introduced in our model should be regarded as crucial for a better description of the oxygenation curve.","PeriodicalId":74387,"journal":{"name":"Oxygen (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45018528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Early History of Hydrogen and Other Gases in Respiration and Biological Systems: Revisiting Beddoes, Cavallo, and Davy","authors":"J. Hancock, Tyler W. LeBaron","doi":"10.3390/oxygen3010008","DOIUrl":"https://doi.org/10.3390/oxygen3010008","url":null,"abstract":"In 2007 a paper in Nature Medicine sparked a new wave of interest in the use of molecular hydrogen (H2) for medical treatments. Since then there has been a flurry of papers looking at a range of medical aspects, from neurodegenerative disease to sports injuries. Several methods of application have been developed, including breathing the gas, or making a hydrogen-rich solution that can be ingested, or administered as saline. H2 treatments are deemed to be safe and can be used in agricultural practice as well as in the biomedical arena. However, the first studies to investigate the use of H2 in medicine were carried out by those interested in the use of a range of gases and how this may affect respiration in humans. Beddoes was published in 1793 and Cavallo in 1798, with Davy following shortly after in 1800. With so many papers now appearing on H2 in biological systems, it seems timely, and interesting, to revisit the early papers, to humbly remind us of what these pioneers of respiratory research did.","PeriodicalId":74387,"journal":{"name":"Oxygen (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41547639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michał Szczepańczyk, Lea Paul, T. Ruzgas, Sebastian Björklund
{"title":"Comparison of Oxygen Electrode Chronoamperometry and Spectrophotometry for Determination of Catalase Activity","authors":"Michał Szczepańczyk, Lea Paul, T. Ruzgas, Sebastian Björklund","doi":"10.3390/oxygen3010006","DOIUrl":"https://doi.org/10.3390/oxygen3010006","url":null,"abstract":"Catalase is a key antioxidative enzyme, and a deficiency or malfunction of catalase is hypothesized to be related to various diseases. To investigate catalase activity, it is important to use reliable methods and experimental protocols enabling consistent fallouts. One major problem, however, is that the activity values obtained with different techniques and procedures can vary to a large extent. The aim of this work was to identify experimental conditions that provide similar catalase activity values with two different methods based on either spectrophotometry or chronoamperometry. The investigated parameters include the concentration of catalase and its substrate (H2O2), as well as the effect of deoxygenation of the catalase medium by nitrogen (N2). Within the frame of investigated conditions, we show that spectrophotometry is strongly affected by the catalase concentration, whereas chronoamperometry is shown to be more dependent on the substrate concentration. Deoxygenation leads to elevated catalase activity values in the case of chronoamperometry, whereas it shows no influence on the results obtained with spectrophotometry. In particular, in the case of low substrate concentrations (i.e., low catalase reaction rates), higher and more accurate results are obtained with deoxygenation in the case of chronoamperometry measurements due to minimized oxygen escape. The effect of deoxygenation, giving rise to elevated catalase activity values, however, is not statistically significant at high substrate concentrations, implying that the protocol can be simplified by excluding this step as long as the other parameters are optimized. Finally, by comparing the two methods at different experimental conditions, we identified protocols resulting in similar results, i.e., 10 mM H2O2 and catalase activity of 4–5 U/mL. Based on this work, improved consistency of catalase activity data obtained with different methodologies and in different labs is expected.","PeriodicalId":74387,"journal":{"name":"Oxygen (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45851877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Valentina Membrino, Alice Di Paolo, Sonila Alia, Giulio Papiri, A. Vignini
{"title":"The Role of Oxidative Stress in Autism Spectrum Disorder: A Narrative Literature Review","authors":"Valentina Membrino, Alice Di Paolo, Sonila Alia, Giulio Papiri, A. Vignini","doi":"10.3390/oxygen3010004","DOIUrl":"https://doi.org/10.3390/oxygen3010004","url":null,"abstract":"Autism spectrum disorder (ASD) is a multifaceted neurodevelopmental disorder that comprises a complex aetiology, where a genetic component has been suggested, together with multiple environmental risk factors. Because of its increasing incidence in the paediatric population and the lack of successful curative therapies, ASD is one of the most puzzling disorders for medicine. In the last two decades and more, the relationship between oxidative stress (OS) and ASD has been recurrently documented. For this reason, the former hypothesis, according to which reactive oxygen and nitrogen species (ROS and RNS) play an important role in ASD, is now a certainty. Thus, in this review, we will discuss many aspects of the role of OS in ASD. In addition, we will describe, in the context of the most recent literature, the possibility that free radicals promote lipid peroxidation, as well as an increase in other OS biomarkers. Finally, we will outline the possibility of novel nutritional interventions aimed at counteracting ROS production in people with ASD. In fact, new strategies have investigated the possibility that ASD symptoms, as well behavioral anomalies, may be improved after interventions using antioxidants as supplements or included in foods.","PeriodicalId":74387,"journal":{"name":"Oxygen (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43918654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Acknowledgment to the Reviewers of Oxygen in 2022","authors":"","doi":"10.3390/oxygen3010003","DOIUrl":"https://doi.org/10.3390/oxygen3010003","url":null,"abstract":"High-quality academic publishing is built on rigorous peer review [...]","PeriodicalId":74387,"journal":{"name":"Oxygen (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44630971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Golenkina, S. Galkina, G. Viryasova, G. Sud’ina
{"title":"The Pro-Oxidant Effect of Class A CpG ODNs on Human Neutrophils Includes Both Non-Specific Stimulation of ROS Production and Structurally Determined Induction of NO Synthesis","authors":"E. Golenkina, S. Galkina, G. Viryasova, G. Sud’ina","doi":"10.3390/oxygen3010002","DOIUrl":"https://doi.org/10.3390/oxygen3010002","url":null,"abstract":"Synthetic CpG oligonucleotides are promising components of immunomodulatory drugs for the treatment and prophylaxis of infectious diseases, cancers, and allergies. Phosphorothioate modification stabilizes these compounds, contributing to the achievement of a clinical effect, but at the same time changes their immunomodulatory properties. We used the diffusible fluorescent dye dihydroethidium and the non-diffusible 6-carboxy-2′,7′dihydrochlorofluorescein diacetate and cytochrome c probes to demonstrate that it is the phosphorothioate backbones that determine the pronounced nonspecific pro-oxidant effect of CpG ODN on neutrophils. At the same time, as was shown using diaminofluorescein diacetate, the potentiation of nitric oxide synthesis in these leucocytes by CpG ODN class A strictly depends on the presence of CpG motifs and a palindromic “hairpin”. The results obtained will contribute to a more complete understanding of the physiological action of therapeutic agents based on synthetic CpG oligonucleotides.","PeriodicalId":74387,"journal":{"name":"Oxygen (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41883383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Savinova, T. Salimova, E. Proskurnina, I. V. Rodionov, O. Kraevaya, P. Troshin, L. Kameneva, E. Malinovskaya, O. Dolgikh, N. Veiko, S. Kostyuk
{"title":"Effect of Water-Soluble Chlorine-Containing Buckminsterfullerene Derivative on the Metabolism of Reactive Oxygen Species in Human Embryonic Lung Fibroblasts","authors":"E. Savinova, T. Salimova, E. Proskurnina, I. V. Rodionov, O. Kraevaya, P. Troshin, L. Kameneva, E. Malinovskaya, O. Dolgikh, N. Veiko, S. Kostyuk","doi":"10.3390/oxygen3010001","DOIUrl":"https://doi.org/10.3390/oxygen3010001","url":null,"abstract":"The development of novel biologically active nanopharmaceuticals is a topical problem of medicine. Water-soluble fullerene derivatives are of particular interest due to their ability to regulate intracellular metabolism of reactive oxygen species (ROS) by direct oxidation or effects on oxidative and signaling enzymes. Here, we studied the effect of a water-soluble chlorine-containing derivative of C60 fullerene on human embryonic lung fibroblasts. MTT tests, intracellular ROS visualization, detection of the ROS-associated gene and protein expression, repair, cell proliferation and cell cycle regulation, and quantitation of oxidative DNA damage were used. Within the first three hours after exposure, antioxidant effects were revealed. Later, oxidative damage appeared. Thus, the studied compound had an ambiguous effect on ROS metabolism associated with a switch in the regulatory effect, which must be taken into account when assessing its biological activity and toxicity.","PeriodicalId":74387,"journal":{"name":"Oxygen (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48055733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Manoel Rios, V. Reis, Susana Soares, D. Moreira-Gonçalves, R. Fernandes
{"title":"Pros and Cons of Two Methods of Anaerobic Alactic Energy Assessment in a High-Intensity CrossFit® Workout","authors":"Manoel Rios, V. Reis, Susana Soares, D. Moreira-Gonçalves, R. Fernandes","doi":"10.3390/oxygen2040042","DOIUrl":"https://doi.org/10.3390/oxygen2040042","url":null,"abstract":"The current study aimed to evidence the strengths and weaknesses of two indirect methods for assessing the anaerobic alactic contribution to a specific CrossFit® workout. Thirty experienced crossfitters performed the Fran workout at maximal intensity, and ventilatory data were collected during the recovery period using a telemetric portable gas analyser to assess the oxygen uptake (VO2) of the off-kinetics fast component (Anarecovery). The kinetics of maximal phosphocreatine splitting (AnaPCr) were determined based on the literature. No differences between the two methods were observed (31.4 ± 4.0 vs. 30.4 ± 4.1 kJ for Anarecovery and AnaPCr, respectively). Despite the existence of some caveats (e.g., errors derived from a delay at the onset of VO2 recovery and the assumption of given values in the concentration of phosphocreatine per kilogram of wet muscle, respectively) in both methods, the data indicate that they yield similar results and allow for estimations of alactic energy contribution from a short-duration and high intensity CrossFit® routine. The current data contributes to CrossFit® workout evaluations and training strategies, helping researchers to evaluate crossfitters more accurately. The advantage of the two methods used in the current study is that they are non-invasive, which differs greatly from muscle biopsies.","PeriodicalId":74387,"journal":{"name":"Oxygen (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47873834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Complete Recovery of an Iatrogenic Venous Gaseous Embolism (VGE) Clinical Presentation Thanks to a Timely Hyperbaric Oxygen Therapy (HBOT) Treatment","authors":"V. Zanon, S. Magri, G. Bonera, E. Camporesi","doi":"10.3390/oxygen2040041","DOIUrl":"https://doi.org/10.3390/oxygen2040041","url":null,"abstract":"Gas embolism is a potentially fatal occurrence in which bubbles are introduced into the arterial/venous circulation. A multifocal ischemia could be the life-threatening scenario of that and occurring after diving-related activities, or pulmonary barotrauma, or even iatrogenic procedure capable to cause an accidental introduction of gas into the vasculature. The case here reported concerns the good outcome of one of these rare occurrences thanks to a prompt diagnosis and proper management of the ongoing gaseous lesion. Unfortunately, it remains ethically and technically complex to consider feasible Randomized Clinical Trials (RCTs) in hyperbaric medicine in general, and even more so in this type of eventuality. We are happy to share this further favorable result as we believe it is just thanks to growing documented clinical evidence that now anyone, if ever had to be suffering from gas embolism, in presence of a RCT would widely prefer to be included in the arm that can take advantage of oxygen hyperbaric (HBO) therapy.","PeriodicalId":74387,"journal":{"name":"Oxygen (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43251016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}