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Cell Reports Apr 2023The mitochondrial response to changes in cellular energy demand is necessary for cellular adaptation and organ function. Many genes are essential in orchestrating this...
The mitochondrial response to changes in cellular energy demand is necessary for cellular adaptation and organ function. Many genes are essential in orchestrating this response, including the transforming growth factor (TGF)-β1 target gene Mss51, an inhibitor of skeletal muscle mitochondrial respiration. Although Mss51 is implicated in the pathophysiology of obesity and musculoskeletal disease, how Mss51 is regulated is not entirely understood. Site-1 protease (S1P) is a key activator of several transcription factors required for cellular adaptation. However, the role of S1P in muscle is unknown. Here, we identify S1P as a negative regulator of muscle mass and mitochondrial respiration. S1P disruption in mouse skeletal muscle reduces Mss51 expression and increases muscle mass and mitochondrial respiration. The effects of S1P deficiency on mitochondrial activity are counteracted by overexpressing Mss51, suggesting that one way S1P inhibits respiration is by regulating Mss51. These discoveries expand our understanding of TGF-β signaling and S1P function.
Topics: Animals; Mice; Cell Respiration; Mitochondria; Muscle, Skeletal; Signal Transduction; Transforming Growth Factor beta
PubMed: 37002920
DOI: 10.1016/j.celrep.2023.112336 -
Theranostics 2020
Topics: Cell Line; Drug Resistance, Neoplasm; Fluorodeoxyglucose F18; Glycolysis; Humans; Neoplasms; Oxygen; Positron-Emission Tomography; Radiopharmaceuticals; Tumor Microenvironment; Warburg Effect, Oncologic
PubMed: 32194847
DOI: 10.7150/thno.40599 -
Molecular Pharmaceutics Jul 2023Oxygen is a critical factor that can regulate the wound healing processes such as skin cell proliferation, granulation, re-epithelialization, angiogenesis, and tissue... (Review)
Review
Oxygen is a critical factor that can regulate the wound healing processes such as skin cell proliferation, granulation, re-epithelialization, angiogenesis, and tissue regeneration. However, hypoxia, a common occurrence in the wound bed, can impede normal healing processes. To enhance wound healing, oxygenation strategies that could effectively increase wound oxygen levels are effective. The present review summarizes wound healing stages and the role of hypoxia in wound healing and overviews current strategies to incorporate various oxygen delivery or generating materials for wound dressing, including catalase, nanoenzyme, hemoglobin, calcium peroxide, or perfluorocarbon-based materials, in addition to photosynthetic bacteria and hyperbaric oxygen therapy. Mechanism of action, oxygenation efficacy, and potential benefits and drawbacks of these dressings are also discussed. We conclude by highlighting the importance of design optimization in wound dressings to address the clinical needs to improve clinical outcomes.
Topics: Humans; Wound Healing; Bandages; Skin; Oxygen; Hypoxia
PubMed: 37338289
DOI: 10.1021/acs.molpharmaceut.3c00352 -
Sensors (Basel, Switzerland) Aug 2020Adequate oxygen delivery to a tissue depends on sufficient oxygen content in arterial blood and blood flow to the tissue. Oximetry is a technique for the assessment of... (Review)
Review
Adequate oxygen delivery to a tissue depends on sufficient oxygen content in arterial blood and blood flow to the tissue. Oximetry is a technique for the assessment of blood oxygenation by measurements of light transmission through the blood, which is based on the different absorption spectra of oxygenated and deoxygenated hemoglobin. Oxygen saturation in arterial blood provides information on the adequacy of respiration and is routinely measured in clinical settings, utilizing pulse oximetry. Oxygen saturation, in venous blood (SvO) and in the entire blood in a tissue (StO), is related to the blood supply to the tissue, and several oximetric techniques have been developed for their assessment. SvO can be measured non-invasively in the fingers, making use of modified pulse oximetry, and in the retina, using the modified Beer-Lambert Law. StO is measured in peripheral muscle and cerebral tissue by means of various modes of near infrared spectroscopy (NIRS), utilizing the relative transparency of infrared light in muscle and cerebral tissue. The primary problem of oximetry is the discrimination between absorption by hemoglobin and scattering by tissue elements in the attenuation measurement, and the various techniques developed for isolating the absorption effect are presented in the current review, with their limitations.
Topics: Humans; Monitoring, Physiologic; Oximetry; Oxygen; Spectroscopy, Near-Infrared
PubMed: 32867184
DOI: 10.3390/s20174844 -
Free Radical Biology & Medicine Aug 2019Metabolic processes in cells and chemical processes in the environment are fundamentally intertwined and have evolved in concert for most of Earth's existence. Here I... (Review)
Review
Metabolic processes in cells and chemical processes in the environment are fundamentally intertwined and have evolved in concert for most of Earth's existence. Here I argue that intrinsic properties of cellular metabolism imposed central constraints on the historical trajectories of biopsheric productivity and atmospheric oxygenation. Photosynthesis depends on iron, but iron is highly insoluble under the aerobic conditions produced by oxygenic photosynthesis. These counteracting constraints led to two major stages of Earth oxygenation. After a cyanobacteria-driven biospheric expansion near the Archean-Proterozoic boundary, productivity remained largely restricted to continental boundaries and shallow aquatic environments where weathering inputs made iron more accessible. The anoxic deep open ocean was rich in free iron during the Proterozoic, but this iron was largely inaccessible, partly because an otherwise nutrient-poor ocean was limiting to photosynthesis, but also because a photosynthetic expansion would have quenched its own iron supply. Near the Proterozoic-Phanerozoic boundary, bioenergetics innovations allowed eukaryotic photosynthesis to overcome these interconnected negative feedbacks and begin expanding into the deep open oceans and onto the continents, where nutrients are inherently harder to come by. Key insights into what drove the ecological rise of eukaryotic photosynthesis emerge from analyses of marine Synechococcus and Prochlorococcus, abundant marine picocyanobacteria whose ancestors colonized the oceans in the Neoproterozoic. The reconstructed evolution of this group reveals a sequence of innovations that ultimately produced a form of photosynthesis in Prochlorococcus that is more like that of green plant cells than other cyanobacteria. Innovations increased the energy flux of cells, thereby enhancing their ability to acquire sparse nutrients, and as by-product also increased the production of organic carbon waste. Some of these organic waste products had the ability to chelate iron and make it bioavailable, thereby indirectly pushing the oceans through a transition from an anoxic state rich in free iron to an oxygenated state with organic carbon-bound iron. Resulting conditions (and parallel processes on the continents) in turn led to a series of positive feedbacks that increased the availability of other nutrients, thereby promoting the rise of a globally productive biosphere. In addition to the occurrence of major biospheric expansions, the several hundred million-year periods around the Archean-Proterozoic and Proterozoic-Phanerozoic boundaries share a number of other parallels. Both epochs have also been linked to major carbon cycle perturbations and global glaciations, as well as changes in the nature of plate tectonics and increases in continental exposure and weathering. This suggests the dynamics of life and Earth are intimately intertwined across many levels and that general principles governed transitions in these coupled dynamics at both times in Earth history.
Topics: Biological Evolution; Cyanobacteria; Eukaryota; Iron; Oceans and Seas; Oxygen; Photosynthesis
PubMed: 31082508
DOI: 10.1016/j.freeradbiomed.2019.05.004 -
Biochimica Et Biophysica Acta.... May 2021Cytochrome bf (cytbf) lies at the heart of the light-dependent reactions of oxygenic photosynthesis, where it serves as a link between photosystem II (PSII) and... (Review)
Review
Cytochrome bf (cytbf) lies at the heart of the light-dependent reactions of oxygenic photosynthesis, where it serves as a link between photosystem II (PSII) and photosystem I (PSI) through the oxidation and reduction of the electron carriers plastoquinol (PQH) and plastocyanin (Pc). A mechanism of electron bifurcation, known as the Q-cycle, couples electron transfer to the generation of a transmembrane proton gradient for ATP synthesis. Cytbf catalyses the rate-limiting step in linear electron transfer (LET), is pivotal for cyclic electron transfer (CET) and plays a key role as a redox-sensing hub involved in the regulation of light-harvesting, electron transfer and photosynthetic gene expression. Together, these characteristics make cytbf a judicious target for genetic manipulation to enhance photosynthetic yield, a strategy which already shows promise. In this review we will outline the structure and function of cytbf with a particular focus on new insights provided by the recent high-resolution map of the complex from Spinach.
Topics: Cell Respiration; Cytochrome b6f Complex; Electron Transport; Electrons; Photosynthesis
PubMed: 33460588
DOI: 10.1016/j.bbabio.2021.148380 -
Med (New York, N.Y.) Jun 2021Several aquatic organisms such as loaches have evolved unique intestinal breathing mechanisms to survive under extensive hypoxia. To date, it is highly controversial...
BACKGROUND
Several aquatic organisms such as loaches have evolved unique intestinal breathing mechanisms to survive under extensive hypoxia. To date, it is highly controversial whether such capability can be adapted in mammalian species as another site for gas exchange. Here, we report the advent of the intestinal breathing phenomenon in mammalians by exploiting EVA (enteral ventilation via anus).
METHODS
Two different modes of EVA were investigated in an experimental model of respiratory failure: intra-rectal oxygen O gas ventilation (g-EVA) or liquid ventilation (l-EVA) with oxygenated perfluorocarbon. After induction of type 1 respiratory failure, we analyzed the effectiveness of g-EVA and I-EVA in mouse and pig, followed by preclinical safety analysis in rat.
FINDINGS
Both intra-rectal O gas and oxygenated liquid delivery were shown to provide vital rescue of experimental models of respiratory failure, improving survival, behavior, and systemic O level. A rodent and porcine model study confirmed the tolerable and repeatable features of an enema-like l-EVA procedure with no major signs of complications.
CONCLUSIONS
EVA has proven effective in mammalians such that it oxygenated systemic circulation and ameliorated respiratory failure. Due to the proven safety of perfluorochemicals in clinics, EVA potentially provides an adjunctive means of oxygenation for patients under respiratory distress conditions.
FUNDING
This work is funded by the Research Program on Emerging and Re-emerging Infectious Diseases, Research Projects on COVID-19 (JP20fk0108278, 20fk0108506h0001), from the Japan Agency for Medical Research and Development (AMED), to T.T.; Strategic Promotion for Practical Application of Innovative Medical Technology, Seeds A (A145), to T.T.; and KAKENHI 19K22657, to T.C.-Y. This research is partially supported by the AMED Translational Research Program; Strategic Promotion for Practical Application of Innovative Medical Technology (TR-SPRINT), to T.C.-Y.; and AMED JP18bm0704025h0001 (Program for Technological Innovation of Regenerative Medicine), to T.T.
Topics: Animals; COVID-19; Humans; Lung; Mammals; Mice; Oxygen; Rats; Respiration; Respiration, Artificial; Respiratory Insufficiency; Swine
PubMed: 35590139
DOI: 10.1016/j.medj.2021.04.004 -
Biomolecules Jul 2021Nanomaterial-mediated cancer therapeutics is a fast developing field and has been utilized in potential clinical applications. However, most effective therapies, such as... (Review)
Review
Nanomaterial-mediated cancer therapeutics is a fast developing field and has been utilized in potential clinical applications. However, most effective therapies, such as photodynamic therapy (PDT) and radio therapy (RT), are strongly oxygen-dependent, which hinders their practical applications. Later on, several strategies were developed to overcome tumor hypoxia, such as oxygen carrier nanomaterials and oxygen generated nanomaterials. Among these, oxygen species generation on nanozymes, especially catalase (CAT) mimetic nanozymes, convert endogenous hydrogen peroxide (HO) to oxygen (O) and peroxidase (POD) mimetic nanozymes converts endogenous HO to water (HO) and reactive oxygen species (ROS) in a hypoxic tumor microenvironment is a fascinating approach. The present review provides a detailed examination of past, present and future perspectives of POD mimetic nanozymes for effective oxygen-dependent cancer phototherapeutics.
Topics: Animals; Biomimetic Materials; Humans; Nanostructures; Neoplasms; Oxygen; Peroxidase; Photochemotherapy; Tumor Hypoxia; Tumor Microenvironment
PubMed: 34356639
DOI: 10.3390/biom11071015 -
The Journal of Extra-corporeal... Mar 2024The optimal timing for extracorporeal membrane oxygenation (ECMO) circuit change-out is crucial for the successful management of patients with severe cardiopulmonary... (Review)
Review
INTRODUCTION
The optimal timing for extracorporeal membrane oxygenation (ECMO) circuit change-out is crucial for the successful management of patients with severe cardiopulmonary failure. This comprehensive review examines the various factors that influence the timing of oxygenator replacement in the ECMO circuit. By considering these factors, clinicians can make informed decisions to ensure timely and effective change-out, enhancing patient outcomes and optimizing the delivery of ECMO therapy.
METHODOLOGY
A thorough search of relevant studies on ECMO circuits and oxygenator change-out was conducted using multiple scholarly databases and relevant keywords. Studies published between 2017 and 2023 were included, resulting in 40 studies that met the inclusion criteria.
DISCUSSION
Thrombosis within the membrane oxygenator and its impact on dysfunction were identified as significant contributors, highlighting the importance of monitoring coagulation parameters and gas exchange. Several factors, including fibrinogen levels, pre and post-membrane blood gases, plasma-free hemoglobin, D-dimers, platelet function, flows and pressures, and anticoagulation strategy, were found to be important considerations when determining the need for an oxygenator or circuit change-out. The involvement of a multidisciplinary team and thorough preparation were also highlighted as crucial aspects of this process.
CONCLUSION
In conclusion, managing circuit change-outs in ECMO therapy requires considering factors such as fibrinogen levels, blood gases, plasma-free hemoglobin, D-dimers, platelet function, flows, pressures, and anticoagulation strategy. Monitoring these parameters allows for early detection of issues, timely interventions, and optimized ECMO therapy. Standardized protocols, personalized anticoagulation approaches, and non-invasive monitoring techniques can improve the safety and effectiveness of circuit change-outs. Further research and collaboration are needed to advance ECMO management and enhance patient outcomes.
Topics: Humans; Extracorporeal Membrane Oxygenation; Oxygenators, Membrane; Anticoagulants; Hemoglobins; Gases
PubMed: 38488715
DOI: 10.1051/ject/2023047 -
International Journal of Radiation... Jun 2021Preclinical radiation replicating clinical intensity modulated radiation therapy (IMRT) techniques can provide data translatable to clinical practice. For this work,...
PURPOSE
Preclinical radiation replicating clinical intensity modulated radiation therapy (IMRT) techniques can provide data translatable to clinical practice. For this work, treatment plans were created for oxygen-guided dose-painting in small animals using inverse-planned IMRT. Spatially varying beam intensities were achieved using 3-dimensional (3D)-printed compensators.
METHODS AND MATERIALS
Optimized beam fluence from arbitrary gantry angles was determined using a verified model of the XRAD225Cx treatment beam. Compensators were 3D-printed with varied thickness to provide desired attenuation using copper/polylactic-acid. Spatial resolution capabilities were investigated using printed test-patterns. Following American Association of Physicists in Medicine TG119, a 5-beam IMRT plan was created for a miniaturized (∼1/8th scale) C-shape target. Electron paramagnetic resonance imaging of murine tumor oxygenation guided simultaneous integrated boost (SIB) plans conformally treating tumor to a base dose (Rx) with boost (Rx) based on tumor oxygenation. The 3D-printed compensator intensity modulation accuracy and precision was evaluated by individually delivering each field to a phantom containing radiochromic film and subsequent per-field gamma analysis. The methodology was validated end-to-end with composite delivery (incorporating 3D-printed tungsten/polylactic-acid beam trimmers to reduce out-of-field leakage) of the oxygen-guided SIB plan to a phantom containing film and subsequent gamma analysis.
RESULTS
Resolution test-patterns demonstrate practical printer resolution of ∼0.7 mm, corresponding to 1.0 mm bixels at the isocenter. The miniaturized C-shape plan provides planning target volume coverage (V = 95%) with organ sparing (organs at risk D < 50%). The SIB plan to hypoxic tumor demonstrates the utility of this approach (hypoxic tumor V = 91.6%, normoxic tumor V = 95.7%, normal tissue V = 7.1%). The more challenging SIB plan to boost the normoxic tumor rim achieved normoxic tumor V = 90.9%, hypoxic tumor V = 62.7%, and normal tissue V = 5.3%. Average per-field gamma passing rates using 3%/1.0 mm, 3%/0.7 mm, and 3%/0.5 mm criteria were 98.8% ± 2.8%, 96.6% ± 4.1%, and 90.6% ± 5.9%, respectively. Composite delivery of the hypoxia boost plan and gamma analysis (3%/1 mm) gave passing results of 95.3% and 98.1% for the 2 measured orthogonal dose planes.
CONCLUSIONS
This simple and cost-effective approach using 3D-printed compensators for small-animal IMRT provides a methodology enabling preclinical studies that can be readily translated into the clinic. The presented oxygen-guided dose-painting demonstrates that this methodology will facilitate studies driving much needed biologic personalization of radiation therapy for improvements in patient outcomes.
Topics: Animals; Copper; Electron Spin Resonance Spectroscopy; Fibrosarcoma; Mice; Organ Sparing Treatments; Oxygen; Phantoms, Imaging; Polyesters; Printing, Three-Dimensional; Proof of Concept Study; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated; Tumor Hypoxia; X-Ray Film
PubMed: 33373659
DOI: 10.1016/j.ijrobp.2020.12.028