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Environmental Pollution (Barking, Essex... Dec 2023Extracellular superoxide radical (O) is ubiquitous in microbial environments and has significant implications for pollutant transformation. Microbial extracellular O can... (Review)
Review
Extracellular superoxide radical (O) is ubiquitous in microbial environments and has significant implications for pollutant transformation. Microbial extracellular O can be produced through multiple pathways, including electron leakage from the respiratory electron transport chain (ETC), NADPH oxidation by the transmembrane NADPH oxidase (NOX), and extracellular reactions. Extracellular O significantly influences the geochemical processes of various substances, including toxic metals and refractory organic pollutants. On one hand, extracellular O can react with variable-valence metals and detoxify certain highly toxic metals, such as As(III), Cr(VI), and Hg(II). On the other hand, extracellular O can directly or indirectly (via Bio-Fenton) degrade many organic pollutants, including a variety of emerging contaminants. In this work, we summarize the production mechanisms of microbial extracellular O, review its roles in the transformation of environmental pollutants, and discuss the potential applications, limiting factors, and future research directions in this field.
Topics: Superoxides; NADPH Oxidases; Cell Respiration; Metals; Environmental Pollutants; Oxidation-Reduction
PubMed: 37717891
DOI: 10.1016/j.envpol.2023.122563 -
Advanced Healthcare Materials Jan 2024Hypoxia in chronic wounds impairs the activities of reparative cells, resulting in tissue necrosis, bacterial infections, decreased angiogenesis, and delayed wound... (Review)
Review
Hypoxia in chronic wounds impairs the activities of reparative cells, resulting in tissue necrosis, bacterial infections, decreased angiogenesis, and delayed wound healing. To achieve effective oxygenation therapy and restore oxygen homeostasis, oxygen-generating hydrogels based on different oxygen sources have been developed to release dissolved oxygen in the wound bed, which not only alleviate hypoxia, but also accelerate chronic wound healing. This review first discusses the vital role of oxygen and hypoxia in the wound healing process. The advancements in oxygen-generating hydrogels, which produce oxygen through the decomposition of hydrogen peroxide, metal peroxides, glucose-activated cascade reactions, and photosynthesis of algae microorganisms for chronic wound healing, are discussed and summarized. The therapeutic effects and challenges of using oxygen-generating hydrogels for the clinical treatment of chronic wounds are concluded and prospected.
Topics: Humans; Oxygen; Hydrogels; Wound Healing; Hypoxia; Peroxides
PubMed: 37899694
DOI: 10.1002/adhm.202302391 -
American Journal of Respiratory Cell... Oct 2023
Topics: Oxygen; Hypoxia-Inducible Factor 1, alpha Subunit; Cell Hypoxia; Organogenesis; Lung
PubMed: 37478332
DOI: 10.1165/rcmb.2023-0247ED -
Cells Aug 2023Mitochondria play a crucial role in cellular respiration, ATP production, and the regulation of various cellular processes. Mitochondrial dysfunctions have been directly... (Review)
Review
Mitochondria play a crucial role in cellular respiration, ATP production, and the regulation of various cellular processes. Mitochondrial dysfunctions have been directly linked to pathophysiological conditions, making them a significant target of interest in toxicological research. In recent years, there has been a growing need to understand the intricate effects of xenobiotics on human health, necessitating the use of effective scientific research tools. (), a nonpathogenic nematode, has emerged as a powerful tool for investigating toxic mechanisms and mitochondrial dysfunction. With remarkable genetic homology to mammals, has been used in studies to elucidate the impact of contaminants and drugs on mitochondrial function. This review focuses on the effects of several toxic metals and metalloids, drugs of abuse and pesticides on mitochondria, highlighting the utility of as a model organism to investigate mitochondrial dysfunction induced by xenobiotics. Mitochondrial structure, function, and dynamics are discussed, emphasizing their essential role in cellular viability and the regulation of processes such as autophagy, apoptosis, and calcium homeostasis. Additionally, specific toxins and toxicants, such as arsenic, cadmium, and manganese are examined in the context of their impact on mitochondrial function and the utility of in elucidating the underlying mechanisms. Furthermore, we demonstrate the utilization of as an experimental model providing a promising platform for investigating the intricate relationships between xenobiotics and mitochondrial dysfunction. This knowledge could contribute to the development of strategies to mitigate the adverse effects of contaminants and drugs of abuse, ultimately enhancing our understanding of these complex processes and promoting human health.
Topics: Humans; Animals; Caenorhabditis elegans; Xenobiotics; Mitochondria; Cell Respiration; Apoptosis; Mammals
PubMed: 37681856
DOI: 10.3390/cells12172124 -
Journal of Neurochemistry May 2024During transient brain activation cerebral blood flow (CBF) increases substantially more than cerebral metabolic rate of oxygen consumption (CMRO) resulting in blood...
Neurovascular coupling is optimized to compensate for the increase in proton production from nonoxidative glycolysis and glycogenolysis during brain activation and maintain homeostasis of pH, pCO, and pO.
During transient brain activation cerebral blood flow (CBF) increases substantially more than cerebral metabolic rate of oxygen consumption (CMRO) resulting in blood hyperoxygenation, the basis of BOLD-fMRI contrast. Explanations for the high CBF versus CMRO slope, termed neurovascular coupling (NVC) constant, focused on maintenance of tissue oxygenation to support mitochondrial ATP production. However, paradoxically the brain has a 3-fold lower oxygen extraction fraction (OEF) than other organs with high energy requirements, like heart and muscle during exercise. Here, we hypothesize that the NVC constant and the capillary oxygen mass transfer coefficient (which in combination determine OEF) are co-regulated during activation to maintain simultaneous homeostasis of pH and partial pressure of CO and O (pCO and pO). To test our hypothesis, we developed an arteriovenous flux balance model for calculating blood and brain pH, pCO, and pO as a function of baseline OEF (OEF), CBF, CMRO, and proton production by nonoxidative metabolism coupled to ATP hydrolysis. Our model was validated against published brain arteriovenous difference studies and then used to calculate pH, pCO, and pO in activated human cortex from published calibrated fMRI and PET measurements. In agreement with our hypothesis, calculated pH, pCO, and pO remained close to constant independently of CMRO in correspondence to experimental measurements of NVC and OEF. We also found that the optimum values of the NVC constant and OEF that ensure simultaneous homeostasis of pH, pCO, and pO were remarkably similar to their experimental values. Thus, the high NVC constant is overall determined by proton removal by CBF due to increases in nonoxidative glycolysis and glycogenolysis. These findings resolve the paradox of the brain's high CBF yet low OEF during activation, and may contribute to explaining the vulnerability of brain function to reductions in blood flow and capillary density with aging and neurovascular disease.
Topics: Humans; Homeostasis; Brain; Hydrogen-Ion Concentration; Glycolysis; Carbon Dioxide; Neurovascular Coupling; Protons; Glycogenolysis; Cerebrovascular Circulation; Oxygen; Oxygen Consumption; Magnetic Resonance Imaging
PubMed: 37150946
DOI: 10.1111/jnc.15839 -
Autophagy Jun 2024BRAF is the most prevalent mutation in thyroid cancer and correlates with poor prognosis and therapy resistance. Although selective inhibitors of BRAF have been...
BRAF is the most prevalent mutation in thyroid cancer and correlates with poor prognosis and therapy resistance. Although selective inhibitors of BRAF have been developed, more advanced tumors such as anaplastic thyroid carcinomas show a poor response in clinical trials. Therefore, the study of alternative survival mechanisms is needed. Since metabolic changes have been related to malignant progression, in this work we explore metabolic dependencies of thyroid tumor cells to exploit them therapeutically. Our results show that respiration of thyroid carcinoma cells is highly dependent on fatty acid oxidation and, in turn, fatty acid mitochondrial availability is regulated through macroautophagy/autophagy. Furthermore, we show that both lysosomal inhibition and the knockout of the essential autophagy gene, , lead to enhanced lipolysis; although this effect is not essential for survival of thyroid carcinoma cells. We also demonstrate that following inhibition of either autophagy or fatty acid oxidation, thyroid tumor cells compensate oxidative phosphorylation deficiency with an increase in glycolysis. In contrast to lipolysis induction, upon autophagy inhibition, glycolytic boost in autophagy-deficient cells is essential for survival and, importantly, correlates with a higher sensitivity to the BRAF selective inhibitor, vemurafenib. In agreement, downregulation of the glycolytic pathway results in enhanced mitochondrial respiration and vemurafenib resistance. Our work provides new insights into the role of autophagy in thyroid cancer metabolism and supports mitochondrial targeting in combination with vemurafenib to eliminate BRAF-positive thyroid carcinoma cells.: AMP: adenosine monophosphate; ATC: anaplastic thyroid carcinoma; ATG: autophagy related; ATP: adenosine triphosphate; BRAF: B-Raf proto-oncogene, serine/threonine kinase; Cas9: CRISPR-associated protein; CREB: cAMP responsive element binding protein; CRISPR: clustered regularly interspaced short palindromic repeats; 2DG: 2-deoxyglucose; FA: fatty acid; FAO: fatty acid oxidation; FASN: fatty acid synthase; FCCP: trifluoromethoxy carbonyl cyanide phenylhydrazone; LAMP1: lysosomal associated membrane protein 1; LIPE/HSL: lipase E, hormone sensitive type; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; OCR: oxygen consumption rate; OXPHOS: oxidative phosphorylation; PRKA/PKA: protein kinase cAMP-activated; PTC: papillary thyroid carcinoma; SREBF1/SREBP1: sterol regulatory element binding transcription factor 1.
Topics: Humans; Autophagy; Thyroid Neoplasms; Mitochondria; Cell Line, Tumor; Proto-Oncogene Proteins B-raf; Drug Resistance, Neoplasm; Fatty Acids; Glycolysis; Proto-Oncogene Mas; Vemurafenib; Lipolysis; Cell Respiration; Autophagy-Related Protein 7; Sulfonamides; Oxidative Phosphorylation; Lysosomes; Indoles
PubMed: 38436206
DOI: 10.1080/15548627.2024.2312790 -
Cells Dec 2023Hypoxia-inducible factor (HIF)-1α represents an oxygen-sensitive subunit of HIF transcriptional factor, which is usually degraded in normoxia and stabilized in hypoxia...
Hypoxia-inducible factor (HIF)-1α represents an oxygen-sensitive subunit of HIF transcriptional factor, which is usually degraded in normoxia and stabilized in hypoxia to regulate several target gene expressions. Nevertheless, in the skeletal muscle satellite stem cells (SCs), an oxygen level-independent regulation of HIF-1α has been observed. Although HIF-1α has been highlighted as a SC function regulator, its spatio-temporal expression and role during myogenic progression remain controversial. Herein, using biomolecular, biochemical, morphological and electrophysiological analyses, we analyzed HIF-1α expression, localization and role in differentiating murine C2C12 myoblasts and SCs under normoxia. In addition, we evaluated the role of matrix metalloproteinase (MMP)-9 as an HIF-1α effector, considering that MMP-9 is involved in myogenesis and is an HIF-1α target in different cell types. HIF-1α expression increased after 24/48 h of differentiating culture and tended to decline after 72 h/5 days. Committed and proliferating mononuclear myoblasts exhibited nuclear HIF-1α expression. Differently, the more differentiated elongated and parallel-aligned cells, which are likely ready to fuse with each other, show a mainly cytoplasmic localization of the factor. Multinucleated myotubes displayed both nuclear and cytoplasmic HIF-1α expression. The MMP-9 and MyoD (myogenic activation marker) expression synchronized with that of HIF-1α, increasing after 24 h of differentiation. By means of silencing HIF-1α and MMP-9 by short-interfering RNA and MMP-9 pharmacological inhibition, this study unraveled MMP-9's role as an HIF-1α downstream effector and the fact that the HIF-1α/MMP-9 axis is essential in morpho-functional cell myogenic commitment.
Topics: Animals; Mice; Cell Differentiation; Matrix Metalloproteinase 9; Myoblasts, Skeletal; Oxygen; Hypoxia-Inducible Factor 1, alpha Subunit; Cell Hypoxia
PubMed: 38132171
DOI: 10.3390/cells12242851 -
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 -
JAMA Apr 2024
Topics: Oxygen; Oxygen Inhalation Therapy; Precision Medicine; Respiration, Artificial; Critical Care; Hypoxia; Machine Learning; Randomized Controlled Trials as Topic; Treatment Effect Heterogeneity
PubMed: 38501204
DOI: 10.1001/jama.2024.0972 -
Accounts of Chemical Research Aug 2023In this Account, we overview and highlight synthetic bioinorganic chemistry focused on initial adducts formed from the reaction of reduced ligand-copper(I) coordination...
In this Account, we overview and highlight synthetic bioinorganic chemistry focused on initial adducts formed from the reaction of reduced ligand-copper(I) coordination complexes with molecular oxygen, reactions that produce ligand-Cu(O) complexes (O ≡ superoxide anion). We provide mostly a historical perspective, starting in the Karlin research group in the 1980s, emphasizing the ligand design and ligand effects, structure, and spectroscopy of these O adducts and subsequent further reactivity with substrates, including the interaction with a second ligand-Cu complex to form binuclear species. The Account emphasizes the approach, evolution, and results obtained in the Karlin group, a synthetic bioinorganic research program inspired by the state of knowledge and insights obtained on enzymes possessing copper ion active sites which process molecular oxygen. These constitute an important biochemistry for all levels/types of organisms, bacteria, fungi, insects, and mammals, including humans.Copper is earth abundant, and its redox properties in complexes allow for facile Cu/Cu interconversions. Simple salts or coordination complexes have been well known to serve as oxidants for the stoichiometric or catalytic oxidation or oxygenation (i.e., O-atom insertion) of organic substrates. Thus, copper dioxygen- or peroxide-centered synthetic bioinorganic studies provide strong relevance and potential application to synthesis or even the development of cathodic catalysts for dioxygen reduction to hydrogen peroxide or water, as in fuel cells. The Karlin group's focus however was primarily oriented toward bioinorganic chemistry with the goal to provide fundamental insights into the nature of copper-dioxygen adducts and further reduced and/or protonated derivatives, species likely occurring in enzyme turnover or related in one or more aspects of formation, structure, spectroscopic properties, and scope of reactivity toward organic/biochemical substrates.Prior to this time, the 1980s, O adducts of redox-active first-row transition-metal ions focused on iron, such as the porphyrinate-Fe centers occurring in the oxygen carrier proteins myoglobin and hemoglobin and that determined to occur in cytochrome P-450 monooxygenase turnover. Deoxy (i.e., reduced Fe(II)) heme proteins react with O, giving Fe-superoxo complexes (preferably referred to by traditional biochemists as ferrous-oxy species). And, it was in the 1970s that great strides were made by synthetic chemists in generating hemes capable of forming O adducts, their physiochemical characterization providing critical insights to enzyme (bio)chemistry and providing ideas and important goals leading to countless person years of future research.
Topics: Ligands; Copper; Oxygen; Superoxides; Models, Molecular; Metalloendopeptidases; Mixed Function Oxygenases; Catalytic Domain; Hydrogen Bonding
PubMed: 37527056
DOI: 10.1021/acs.accounts.3c00297