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Journal of Thermal Biology Jul 2022Wood frogs, Rana sylvatica, endure the freezing of ∼65% of total body water while overwintering in cold climates, enduring not only internal ice formation but also...
Wood frogs, Rana sylvatica, endure the freezing of ∼65% of total body water while overwintering in cold climates, enduring not only internal ice formation but also long-term anoxia due to cessation of heartbeat and breathing. Thawing restores perfusion but rapid reoxygenation can increase vulnerability to reactive oxygen species and induce oxidative damage. This study provides a first assessment of antioxidant capacity, DNA damage, and DNA repair responses comparing freeze/thaw and anoxia/reoxygenation in liver and skeletal muscle of wood frogs. Oxidation of guanine resides in DNA did not change under either stress but total antioxidant capacity rose in both tissues under anoxia. Relative expression of eight proteins involved in double-stranded break repair (Mre11, Rad50, phospho-p95, XLF, DNA ligase IV, XRCC4, Ku70, Rad51) were assessed in both tissues. Freezing suppressed Ku70 and Rad51 in liver and Rad51 in muscle but levels rose again after thawing. Anoxia exposure suppressed XLF, Ku70 and Rad51 proteins in muscle. However, in liver, anoxia exposure led to elevated Mre11, Ku70 and DNA ligase IV, the former two belonging to the MRN complex that binds DNA and marks sites of double stranded breaks (DSBs). Large increases in Mre11 and Ku70 expression suggested DSB damage in liver under anoxia but not during freezing, whereas muscle was resistant to DSB damage under both stresses. These data indicate that DNA damage is minimal during whole body freezing due to tissue and stress specific regulation of antioxidant capacity and DNA damage repair to preserve genomic integrity.
Topics: Animals; Antioxidants; DNA; DNA Damage; DNA Ligase ATP; Freezing; Hypoxia; Muscle, Skeletal; Ranidae
PubMed: 35701025
DOI: 10.1016/j.jtherbio.2022.103274 -
Bulletin of Experimental Biology and... Sep 2021The phenomenon of ischemic preconditioning was discovered in 1986 in experiments with the heart, and then it was observed in almost all organs, the kidneys included.... (Review)
Review
The phenomenon of ischemic preconditioning was discovered in 1986 in experiments with the heart, and then it was observed in almost all organs, the kidneys included. This phenomenon is underlain by conditioning of the tissues with short ischemia/reperfusion cycles intended for subsequent exposure to pathological ischemia. Despite the kidneys are not viewed as so vital organs as the brain or the heart, the acute ischemic injury to kidneys is a widespread pathology responsible for the yearly death of almost 2 million patients, while the number of patients with chronic kidney disease is estimated as hundreds of millions or nearly 10% adult population the world over. Currently, it is believed that adaptation of the kidneys to ischemia by preconditioning is the most effective way to prevent the development of acute kidney injury, so deep insight into its molecular mechanisms will be a launch pad for creating the nephroprotective therapy by elevating renal tolerance to oxygen deficiency. This review focuses on the key signaling pathways of kidney ischemic preconditioning, the potential pharmacological mimetics of its key elements, and the limitations of this therapeutic avenue associated with age-related decline of ischemic tolerance of the kidneys.
Topics: Acute Kidney Injury; Adult; Animals; Humans; Hypoxia; Ischemic Preconditioning; Kidney; Reperfusion Injury
PubMed: 34617172
DOI: 10.1007/s10517-021-05270-9 -
The Veterinary Clinics of North... Mar 2017This article describes the calculation of the alveolar-arterial gas gradient and its clinical application in determining the cause of hypoxemia. It also outlines the... (Review)
Review
This article describes the calculation of the alveolar-arterial gas gradient and its clinical application in determining the cause of hypoxemia. It also outlines the analysis of arterial blood gases and the clinical approach toward diagnosis and treatment of respiratory disease.
Topics: Animals; Blood Gas Analysis; Hypoventilation; Hypoxia; Monitoring, Physiologic; Oximetry; Oxygen; Respiratory Distress Syndrome
PubMed: 27916285
DOI: 10.1016/j.cvsm.2016.10.004 -
Current Opinion in Critical Care Dec 2017To describe current evidence-based practice in the management of acute life-threatening hypoxemia in mechanically ventilated patients and some of the methods used to... (Review)
Review
PURPOSE OF REVIEW
To describe current evidence-based practice in the management of acute life-threatening hypoxemia in mechanically ventilated patients and some of the methods used to individualize the care of the patient.
RECENT FINDINGS
Patients with acute life-threatening hypoxemia will often meet criteria for severe ARDS, for which there are only a few treatment strategies that have been shown to improve survival outcomes. Recent findings have increased our knowledge of the physiological effects of spontaneous breathing and the application of PEEP. Additionally, the use of advanced bedside monitoring has a promising future in the management of hypoxemic patients to fine-tune the ventilator and to evaluate the individual patient response to therapy.
SUMMARY
Treating the patient with acute life-threatening hypoxemia during mechanical ventilation should begin with an evidence-based approach, with the goal of improving oxygenation and minimizing the harmful effects of mechanical ventilation. The use of advanced monitoring and the application of simple maneuvers at the bedside may assist clinicians to better individualize treatment and improve clinical outcomes.
Topics: Critical Care; Early Diagnosis; Electric Impedance; Humans; Hypoxia; Neuromuscular Blocking Agents; Positive-Pressure Respiration; Practice Guidelines as Topic; Prone Position; Respiratory Distress Syndrome
PubMed: 29016366
DOI: 10.1097/MCC.0000000000000459 -
Biochimica Et Biophysica Acta. General... Jan 2022The discovery of humanin (HN/MTRNR2) 20 years ago blazed a trail to identifying mitochondrial derived peptides with biological function. (Review)
Review
BACKGROUND
The discovery of humanin (HN/MTRNR2) 20 years ago blazed a trail to identifying mitochondrial derived peptides with biological function.
SCOPE
Humanin is associated with pro-survival, cytoprotective, anti-inflammatory, and anti-oxidative properties and may play a role in reducing neurodegenerative and metabolic disease progression. Although the role of humanin in vitro and in vivo laboratory models is well characterized, the regulation of humanin in natural models that encounter lethal cytotoxic and oxidative insults, as part of their natural history, require immediate research. In this review, we discuss the conservation of humanin-homologues across champion hibernators, anoxia and freeze-tolerant vertebrates and postulate on the putative roles of humanin in non-model species.
SIGNIFICANCE
We hope characterization of humanin in animals that are naturally immune to cellular insults, that are otherwise lethal for non-tolerant species, will elucidate key biomarkers and cytoprotective pathways with therapeutic potential and help differentiate pro-survival mechanisms from cellular consequences of stress.
Topics: Animals; Cold-Shock Response; Hibernation; Humans; Hypoxia; Intracellular Signaling Peptides and Proteins; Nervous System Physiological Phenomena; Stress, Physiological
PubMed: 34626747
DOI: 10.1016/j.bbagen.2021.130022 -
Journal of Controlled Release :... Dec 2015One of the most challenging and clinically important goals in nanomedicine is to deliver imaging and therapeutic agents to solid tumors. Here we discuss the recent... (Review)
Review
One of the most challenging and clinically important goals in nanomedicine is to deliver imaging and therapeutic agents to solid tumors. Here we discuss the recent design and development of stimuli-responsive smart nanoparticles for targeting the common attributes of solid tumors such as their acidic and hypoxic microenvironments. This class of stimuli-responsive nanoparticles is inactive during blood circulation and under normal physiological conditions, but is activated by acidic pH, enzymatic up-regulation, or hypoxia once they extravasate into the tumor microenvironment. The nanoparticles are often designed to first "navigate" the body's vascular system, "dock" at the tumor sites, and then "activate" for action inside the tumor interstitial space. They combine the favorable biodistribution and pharmacokinetic properties of nanodelivery vehicles and the rapid diffusion and penetration properties of smaller drug cargos. By targeting the broad tumor habitats rather than tumor-specific receptors, this strategy has the potential to overcome the tumor heterogeneity problem and could be used to design diagnostic and therapeutic nanoparticles for a broad range of solid tumors.
Topics: Animals; Enzyme Activation; Humans; Hydrogen-Ion Concentration; Hypoxia; Nanoparticles; Neoplasms; Tumor Microenvironment
PubMed: 26341694
DOI: 10.1016/j.jconrel.2015.08.050 -
Advanced Drug Delivery Reviews Dec 2017In addition to immunological and wound healing cell and platelet delivery, ion stasis and nutrient supply, blood delivers oxygen to cells and tissues and removes... (Review)
Review
In addition to immunological and wound healing cell and platelet delivery, ion stasis and nutrient supply, blood delivers oxygen to cells and tissues and removes metabolic wastes. For decades researchers have been trying to develop approaches that mimic these two immediately vital functions of blood. Oxygen is crucial for the long-term survival of tissues and cells in vertebrates. Hypoxia (oxygen deficiency) and even at times anoxia (absence of oxygen) can occur during organ preservation, organ and cell transplantation, wound healing, in tumors and engineering of tissues. Different approaches have been developed to deliver oxygen to tissues and cells, including hyperbaric oxygen therapy (HBOT), normobaric hyperoxia therapy (NBOT), using biochemical reactions and electrolysis, employing liquids with high oxygen solubility, administering hemoglobin, myoglobin and red blood cells (RBCs), introducing oxygen-generating agents, using oxygen-carrying microparticles, persufflation, and peritoneal oxygenation. Metabolic waste accumulation is another issue in biological systems when blood flow is insufficient. Metabolic wastes change the microenvironment of cells and tissues, influence the metabolic activities of cells, and ultimately cause cell death. This review examines advances in blood mimicking systems in the field of biomedical engineering in terms of oxygen delivery and metabolic waste removal.
Topics: Animals; Biomedical Engineering; Biomimetics; Blood; Humans; Hyperbaric Oxygenation; Hypoxia; Oxygen; Wound Healing
PubMed: 28214553
DOI: 10.1016/j.addr.2017.02.001 -
Food Chemistry Mar 2022This study investigated the dynamic changes in the anaerobic metabolism end products (ethanol, acetaldehyde and ethyl acetate) of different apple cultivars during...
This study investigated the dynamic changes in the anaerobic metabolism end products (ethanol, acetaldehyde and ethyl acetate) of different apple cultivars during 84-days of regular air (RA) and controlled atmosphere (CA) storage after 0-, 3-, 7- and 14-days of anoxia. Increasing the length of exposure to anoxia increased the anaerobic metabolites concentrations (AMC) in all cultivars. Fruit could recover from anoxia, and the AMC dissipated after 84-days of storage under both storage systems when the duration of anoxia was <7-days. The rate of metabolite dissipation following 14-days of anoxia differed among cultivars and storage systems. The reduction in AMC was faster under CA than RA-storage for 'Golden Delicious' and 'Jonagold' fruit, while the opposite trend was observed for 'Kanzi'. These results indicate that storage under CA post anoxia maintains better fruit quality during 84-days of storage than RA and effectively reduces the AMC.
Topics: Anaerobiosis; Atmosphere; Fruit; Hypoxia; Malus
PubMed: 34583177
DOI: 10.1016/j.foodchem.2021.131152 -
Birth Defects Research Oct 2017Hypoxia may influence normal and different pathological processes. Low oxygenation activates a variety of responses, many of them regulated by hypoxia-inducible factor 1... (Review)
Review
Hypoxia may influence normal and different pathological processes. Low oxygenation activates a variety of responses, many of them regulated by hypoxia-inducible factor 1 complex, which is mostly involved in cellular control of O consumption and delivery, inhibition of growth and development, and promotion of anaerobic metabolism. Hypoxia plays a significant physiological role in fetal development; it is involved in different embryonic processes, for example, placentation, angiogenesis, and hematopoiesis. More recently, fetal hypoxia has been associated directly or indirectly with fetal programming of heart, brain, and kidney function and metabolism in adulthood. In this review, the role of hypoxia in fetal development, placentation, and fetal programming is summarized. Hypoxia is a basic mechanism involved in different pregnancy disorders and fetal health developmental complications. Although there are scientific data showing that hypoxia mediates changes in the growth trajectory of the fetus, modulates gene expression by epigenetic mechanisms, and determines the health status later in adulthood, more mechanistic studies are needed. Furthermore, if we consider that intrauterine hypoxia is not a rare event, and can be a consequence of unavoidable exposures to air pollution, nutritional deficiencies, obesity, and other very common conditions (drug addiction and stress), the health of future generations may be damaged and the incidence of some diseases will markedly increase as a consequence of disturbed fetal programming. Birth Defects Research 109:1377-1385, 2017.© 2017 Wiley Periodicals, Inc.
Topics: Embryonic Development; Female; Fetal Development; Health; Humans; Hypoxia; Placentation; Pregnancy
PubMed: 29105382
DOI: 10.1002/bdr2.1142 -
Comparative Biochemistry and... Feb 2020Evolution has produced animals that survive extreme fluctuations in environmental conditions including freezing temperatures, anoxia, desiccating conditions, and... (Review)
Review
Evolution has produced animals that survive extreme fluctuations in environmental conditions including freezing temperatures, anoxia, desiccating conditions, and prolonged periods without food. For example, the wood frog survives whole-body freezing every winter, arresting all gross physiological functions, but recovers functions upon thawing in the spring. Likewise, many small mammals hibernate for months at a time with minimal metabolic activity, organ perfusion, and movement, yet do not suffer significant muscle atrophy upon arousal. These conditions and the biochemical adaptations employed to deal with them can be viewed as Nature's answer to problems that humans wish to answer, particularly in a biomedical context. This review focuses on recent advances in the field of animal environmental stress adaptation, starting with an emphasis on new areas of research such as epigenetics and microRNA. We then examine new and emerging technologies such as genome editing, novel sequencing applications, and single cell analysis and how these can push us closer to a deeper understanding of biochemical adaptation. Next, evaluate the potential contributions of new high-throughput technologies (e.g. next-generation sequencing, mass spectrometry proteomics) to better understanding the adaptations that support these extreme phenotypes. Concluding, we examine some of the human applications that can be gained from understanding the principles of biochemical adaptation including organ preservation and treatments for conditions such as ischemic stroke and muscle disuse atrophy.
Topics: Adaptation, Physiological; Animals; Epigenesis, Genetic; Extreme Environments; Gene Editing; Hibernation; High-Throughput Nucleotide Sequencing; Hypoxia
PubMed: 31778815
DOI: 10.1016/j.cbpa.2019.110623