Periods Of Hypoxia Research Articles

Hypoxia-Induced Differences in the Expression of Pyruvate Dehydrogenase Kinase 1-Related Factors in the Renal Tissues and Renal Interstitial Fibroblast-like Cells of Yak (Bos Grunniens).

Hypoxia is one of the factors severely affect renal function, and, in severe cases, it can lead to renal fibrosis. Although much progress has been made in identifying the molecular mediators of fibrosis, the mechanisms that govern renal fibrosis remain unclear, and there have been no effective therapeutic anti-fibrotic strategies to date. Mammals exposed to low oxygen in the plateau environment for a long time are prone to high-altitude disease, while yaks have been living in the plateau for generations do not develop kidney fibrosis caused by low oxygen. It has been suggested that metabolic reprogramming occurs in renal fibrosis and that pyruvate dehydrogenase kinase 1 (PDK1) plays a crucial role in metabolic reprogramming as an important node between glycolysis and the tricarboxylic acid cycle. The aim of this study was to investigate the effects of hypoxia on the renal tissues and renal interstitial fibroblasts of yaks. We found that, at the tissue level, HIF-1α, PDK1, TGF-β1, Smad2, Smad3, and α-SMA were mainly distributed and expressed in tubular epithelial cells but were barely present in the renal mesenchymal fibroblasts of healthy cattle and yak kidneys. Anoptical density analysis showed that in healthy cattle kidneys, TGF-β1, Smad2, and Smad3 expression was significantly higher than in yak kidneys (p < 0.05), and HIF-1α and PDK1 expression was significantly lower than in yak kidneys (p < 0.05). The results at the protein and gene levels showed the same trend. At the cellular level, prolonged hypoxia significantly elevated PDK1 expression in the renal mesangial fibroblasts of cattle and yak kidneys compared with normoxia (p < 0.05) and was proportional to the degree of cellular fibrosis. However, PDK1 expression remained stable in yaks compared with renal interstitial fibroblast-like cells in cattle during the same hypoxic time period. At the same time, prolonged hypoxia also promoted changes in cellular phenotype, promoting the proliferation, activation, glucose consumption, lactate production, and anti-apoptosis in the both of cattle and yaks renal interstitial fibroblasts The differences in kidney structure and expression of PDK1 and HIF-1α in kidney tissue and renal interstitial fibroblasts induced by different oxygen concentrations suggest that there may be a regulatory relationship between yak kidney adaptation and hypoxic environment at high altitude. This provides strong support for the elucidation of the regulatory relationship between PDK1 and HIF-1α, as well as a new direction for the treatment or delay of hypoxic renal fibrosis; additionally, these findings provide a basis for further analysis of the molecular mechanism of hypoxia adaptation-related factors and the adaptation of yaks to plateau hypoxia.

Role of the telomeric factor TRF2 in post-hypoxic brain damages

The neuronal excitotoxicity that follows reoxygenation after a hypoxic period may contribute to epilepsy, Alzheimer's disease, Parkinson's disease and various disorders that are related to inadequate supplement of oxygen in neurons. Therefore, counteracting the deleterious effects of post-hypoxic stress is an interesting strategy to treat a large spectrum of neurodegenerative diseases. Here, we show that the expression of the key telomere protecting protein Trf2 decreases in the brain of mice submitted to a post-hypoxic stress. Moreover, downregulating the expression of Terf2 in hippocampal neural cells of unchallenged mice triggers an excitotoxicity-like phenotype including glutamate overexpression and behavioral alterations while overexpressing Terf2 in hippocampal neural cells of mice subjected to a post-hypoxic treatment prevents brain damages. Moreover, Terf2 overexpression in culture neurons counteracts the oxidative stress triggered by glutamate. Finally, we provide evidence that the effect of Terf2 downregulation on excitotoxicity involves Sirt3 repression leading to mitochondrial dysfunction. We propose that increasing the level of Terf2 expression is a potential strategy to reduce post-hypoxic stress damages.

Ocular Inflammation and Oxidative Stress as a Result of Chronic Intermittent Hypoxia: A Rat Model of Sleep Apnea.

Obstructive sleep apnea (OSA) is a sleep disorder characterized by intermittent complete or partial occlusion of the airway. Despite a recognized association between OSA and glaucoma, the nature of the underlying link remains unclear. In this study, we investigated whether mild OSA induces morphological, inflammatory, and metabolic changes in the retina resembling those seen in glaucoma using a rat model of OSA known as chronic intermittent hypoxia (CIH). Rats were randomly assigned to either normoxic or CIH groups. The CIH group was exposed to periodic hypoxia during its sleep phase with oxygen reduction from 21% to 10% and reoxygenation in 6 min cycles over 8 h/day. The eyes were subsequently enucleated, and then the retinas were evaluated for retinal ganglion cell number, oxidative stress, inflammatory markers, metabolic changes, and hypoxic response modulation using immunohistochemistry, multiplex assays, and capillary electrophoresis. Statistically significant differences were observed between normoxic and CIH groups for oxidative stress and inflammation, with CIH resulting in increased HIF-1α protein levels, higher oxidative stress marker 8-OHdG, and increased TNF-α. Pyruvate dehydrogenase kinase-1 protein was significantly reduced with CIH. No significant differences were found in retinal ganglion cell number. Our findings suggest that CIH induces oxidative stress, inflammation, and upregulation of HIF-1α in the retina, akin to early-stage glaucoma.

Effects of Hypoxia on the Antibacterial Activity of Epidermal Mucus from Chilean Meagre (Cilus gilberti).

Comprehending the immune defense mechanisms of new aquaculture species, such as the Chilean meagre (Cilus gilberti), is essential for sustaining large-scale production. Two bioassays were conducted to assess the impact of acute and intermittent hypoxia on the antibacterial activity of juvenile Chilean meagre epidermal mucus against the potential pathogens Vibrio anguillarum and Vibrio ordalii. Lysozyme and peroxidase activities were also measured. In general, fish exposed to hypoxia showed a 9-30% reduction in mucus antibacterial activity at the end of hypoxic periods and after stimulation with lipopolysaccharide. However, following water reoxygenation, the activity of non-stimulated fish was comparable to that of fish in normoxic conditions, inhibiting bacterial growth by 35-52%. In the case of fish exposed to chronic hypoxia, the response against V. anguillarum increased by an additional 19.8% after 6 days of control inoculation. Lysozyme exhibited a similar pattern, while no modulation of peroxidase activity was detected post-hypoxia. These results highlight the resilience of C. gilberti to dissolved oxygen fluctuations and contribute to understanding the potential of mucus in maintaining the health of cultured fish and the development of future control strategies.

Temporal Phosphorus Dynamics in Shallow Eutrophic Lake Suwa, Japan

It can be difficult to decrease the water phosphorus (P) concentration in eutrophic shallow lakes, even if the external P loading is reduced, owing to a high level of internal P loading to surface water from sediment. However, in shallow Lake Suwa, Japan, lake water P concentration has largely decreased in recent years owing to low levels of internal P loading, as well as declining external P loading. We measured water/sediment P and iron (Fe) concentrations and the P release rate from sediment in Lake Suwa, and then compared it with data from the 1970s. In the 1970s, the P concentration throughout the lake water was high during the hypoxic period. Recently, however, the P concentration has increased only in the hypolimnion during the hypoxic period. This suggests that internal P loading from sediment to surface water has largely been suppressed during the hypoxic period in recent years. This may be due to (i) stronger water stratification from global warming, (ii) a greater decrease in the P release rate from the sediment owing to a decline in sediment P concentration from the 1970s to 2020, and (iii) stronger formation of the Fe–P cycle in Lake Suwa recently, compared with that in the 1970s. Our results indicated the need to reduce both external P loading, and internal P loading from sediment to water, for effective water quality improvement in shallow lakes.

Nitric oxide and mitochondria injuries in kidney tissue upon a simulation of cardiopulmonary bypass and circulatory arrest: an experimental study

Introduction: Surgical interventions under cardiopulmonary bypass and circulatory arrest are complicated by impaired microcirculation in tissues; during hypoxic period the mitochondria dysfunction becomes the leading pathogenetic factor of ischemia-reperfusion injuries. In this regard, the search for methods of organ protection seems to be an extremely urgent task. The using of nitric oxide can be a promising technique given its pluripotent properties.Objective: The study was aimed to examining of mitochondria injuries in kidney biopsies stipulated by cardiopulmonary bypass and circulatory arrest when simulating cardiac surgery, as well as to assessing the potentials of organ protection with nitric oxide in the experiment.Methods: The study was carried out on Altai breed sheep and included simulating of cardiopulmonary bypass and circulatory arrest. The first group (n = 6) was provided with intraoperative nitric oxide donation. The second group (n = 6) served as a control (without nitric oxide donation). Mitochondria injuries were assessed in kidney biopsies by measuring transmembrane potential and Ca2+-binding capacity of organelles, as well as by determining ATP and lactate concentrations.Results: Nitric oxide therapy was associated with less mitochondria dysfunction in kidney biopsies compared with the control group. There was a steady trend to the amelioration of the energy maintenance in the renal parenchyma in the nitric oxide donation group.Conclusion: A steady trend towards optimizing the energy supply of tissues under cardiopulmonary bypass and circulatory arrest was revealed in an experiment against the background of NO donation at a concentration of 80 ppm. Received 11 February 2024. Revised 28 March 2024. Accepted 29 March 2024. Funding: The The study was carried out within the framework of the state assignment “Protection of organs by nitric oxide in cardiovascular surgery: technological support (synthesis and delivery devices), mechanisms for implementing protective effects and impact on clinical outcomes” (topic No. 122123000017-3). Conflict of interest: The authors declare no conflict of interest. Contribution of the authors Conception and study design: A.M. Boyko, N.O. Kamenshchikov, Yu.K. Podoksenov, L.N. Maslov, B.N. Kozlov Data collection and analysis: A.M. Boyko, Yu.S. Svirko, V.A. Lugovskiy, A.V. Mukhomedzyanov, B.A. BazarbekovaStatistical analysis: I.V. KravchenkoDrafting the article: A.M. Boyko Critical revision of the article: N.O. Kamenshchikov, A.G. Miroshnichenko, Yu.K. Podoksenov, M.L. Diakova, K.A. Petlin, D.S. Panfilov, B.N. KozlovFinal approval of the version to be published: A.M. Boyko, N.O. Kamenshchikov, A.G. Miroshnichenko, Yu.K. Podoksenov, Yu.S. Svirko, V.A. Lugovskiy, M.L. Diakova, I.V. Kravchenko, A.V. Mukhomedzyanov, L.N. Maslov, B.A. Bazarbekova, K.A. Petlin, D.S. Panfilov, B.N. Kozlov

Evolution of a novel regulatory mechanism of hypoxia inducible factor in hypoxia-tolerant electric fishes

Hypoxia is a significant source of metabolic stress that activates many cellular pathways involved in cellular differentiation, proliferation, and cell death. Hypoxia is also a major component in many human diseases and a known driver of many cancers. Despite the challenges posed by hypoxia, there are animals that display impressive capacity to withstand lethal levels of hypoxia for prolonged periods of time and thus offer a gateway to a more comprehensive understanding of the hypoxic response in vertebrates. The weakly electric fish genus Brachyhypopomus inhabits some of the most challenging aquatic ecosystems in the world, with some species experiencing seasonal anoxia, thus providing a unique system to study the cellular and molecular mechanisms of hypoxia tolerance. In this study, we use closely related species of Brachyhypopomus that display a range of hypoxia tolerances to probe for the underlying molecular mechanisms via hypoxia inducible factors (HIFs)-transcription factors known to coordinate the cellular response to hypoxia in vertebrates. We find that HIF1⍺ from hypoxia tolerant Brachyhypopomus species displays higher transactivation in response to hypoxia than that of intolerant species, when overexpressed in live cells. Moreover, we identified two SUMO-interacting motifs near the oxygen-dependent degradation and transactivation domains of the HIF1⍺ protein that appear to boost transactivation of HIF1, regardless of the genetic background. Together with computational analyses of selection, this shows that evolution of HIF1⍺ are likely to underlie adaptations to hypoxia tolerance in Brachyhypopomus electric fishes, with changes in two SUMO-interacting motifs facilitating the mechanism of this tolerance.

In situ forming, mechanically resilient hydrogels prepared from 4a-[PEG-b-PTMC-Ac] and thiolated chondroitin sulfate for nucleus pulposus cell delivery.

Intervertebral disk degeneration (IVDD) is a common condition that causes severe back pain and affects patients' mobility and life quality considerably. IVDD originates within the central region of the disk called the nucleus pulposus (NP). Removing the damaged tissue and replacing it with NP cells (NPCs) delivered within an in situ forming hydrogel is a promising treatment approach. Herein we describe a hydrogel formulation based on 4-arm [poly(ethylene glycol)-b-poly(trimethylene carbonate)-acrylate] (4a[PEG-b-PTMC-Ac]) crosslinked with thiolated chondroitin sulfate via Michael-type reaction for this purpose. A library of hydrogels based on 15 kDa 4a-[PEG] with PTMC blocks of varying molecular weight were prepared and characterized. The instantaneous moduli of the hydrogels were adjustable from 24 to 150 kPa depending on the length of the PTMC block and the polymer volume fraction. The influence of each of these parameters was effectively explained using both scaling or mean field theories of polyelectrolyte hydrogels. The hydrogels were resistant to cyclic compressive loading and degraded gradually over 70 days in vitro. A hydrogel formulation with an instantaneous modulus at the high end of the range of values reported for human NP tissue was chosen to assess the ability of these hydrogels for delivering NPCs. The prepolymer solution was injectable and formed a hydrogel within 30 minutes at 37 °C. Bovine NPCs were encapsulated within this hydrogel with high viability and proliferated throughout a 28 day, hypoxic culture period. The encapsulated NPCs formed clusters and deposited collagen type II but no collagen type I within the hydrogels. Despite an initial gradual decrease, a steady-state modulus was reached at the end of the 28 day culture period that was within the range reported for healthy human NP tissue. This in situ forming hydrogel formulation is a promising approach and with further development could be a viable clinical treatment for IVDD.

DEVELOPMENT AND EXPERIMENTAL REPLICATION OF THE MODEL OF PARTIAL TRACHEAL STENOSIS IN YOUNG SEXUALLY IMMATURE WHITE RATS

This work is devoted to the development of two models of experimental replication of stenosis in the upper part of the trachea with different degrees of compression of this organ in sexually immature (one-month-old) white Wistar rats. Considering the different degrees of laryngomalacia in newborns, we developed two models: with a lower (20%) and higher (30%) degree of airway obstruction. In the first version of modeling, this was achieved by applying the ligature at the level between 1 and 2, or 2 and 3 cartilaginous semi-rings of the trachea, in the second – by applying it directly to the 2 cartilaginous semi-ring of the trachea. Both models were performed to study the state of the organism in conditions of hypoxic hypoxia in laboratory animals.&#x0D; The developed modeling methods differ from each other not only in the place of application of the compressing ligature, but also in the mechanism of compression development. In the case of applying a ligature to the intercartilaginous ligaments (20% stenosis), soft tissues are compressed and both semi-rings of the trachea are brought together. In the second variant of modeling, the pathophysiological mechanism of stenosis consists not only in the compression of the cartilaginous semi-ring of the trachea, but also in the process of invagination of the dorsal, i.e., elastic part of the trachea into the lumen of this hollow organ. As a result, a more intense variant of tracheal stenosis in experimental animals is achieved. Another important component of the developed models is the possibility at different stages of the experiment to eliminate the compressive effect of the ligature on the trachea and to study the state of various organs and tissues of animals in the early or delayed post-hypoxic periods. This leads to a significant increase in the value or efficiency of conducting this kind of experiments, taking into account the fact that hypoxic and posthypoxic periods can be studied on the same experimental animal. Both exotracheal modeling methods are fundamentally different from the endotracheal variant of experimentally reproducing stenosis. With the latter, pathological structural and functional disorders of the cells of the mucous membrane, the connective apparatus of the trachea and smooth muscle elements, the development of inflammation, and the progression of irreversible changes in the cellular and organ structures of the trachea are observed. In addition, simulation of the specified variant of stenosis requires the use of expensive equipment – a laryngoscope and some other modern technologies. Both variants of exotracheal modeling of tracheal stenosis, proposed by us, are devoid of all these shortcomings. At the same time, they enable to achieve the same degree of stenosis of this organ in animals as with the endotracheal variant.

Protists in hypoxic waters of Jinhae Bay and Masan Bay, Korea, based on metabarcoding analyses: emphasizing surviving dinoflagellates

Hypoxia can indeed impact the survival of protists, which play a crucial role in marine ecosystems. To better understand the protistan community structure and species that can thrive in hypoxic waters, we collected samples from both the surface and bottom waters during the hypoxic period in Jinhae and Masan Bays and the non-hypoxic period in Jinhae Bay. Subsequently, we utilized metabarcoding techniques to identify the protistan species. During hypoxia, with dissolved oxygen concentrations of 0.8 mg L&lt;sup&gt;-1&lt;/sup&gt; in Jinhae Bay and 1.8 mg L&lt;sup&gt;-1&lt;/sup&gt; in Masan Bay within the bottom waters, the phylum Dinoflagellata exhibited the highest amplicon sequence variants richness among the identified protist phyla. Following the Dinoflagellata, Ochrophyta and Ciliophora also displayed notable presence. In hypoxic waters of Jinhae and Masan Bays, we identified a total of 36 dinoflagellate species that exhibited various trophic modes. These included one autotrophic species, 14 mixotrophic species, 9 phototrophic species with undetermined trophic modes (either autotrophic or mixotrophic), 2 kleptoplastidic species, and 10 heterotrophic species. Furthermore, the hypoxic bottom water exhibited a greater number of heterotrophic dinoflagellate species compared to the non-hypoxic surface water within the same water column or the non-hypoxic bottom water. Therefore, feeding by mixotrophic and heterotrophic dinoflagellates may be partially responsible for their dominance in terms of the number of species surviving in hypoxic waters. This study not only introduces the initial documentation of 26 dinoflagellate species surviving in hypoxic conditions but also establishes a foundation for a more comprehensive understanding of the ecophysiology of dinoflagellates in hypoxic marine environments.

Evaluation of vestibular functions in patients with obstructive sleep apnea syndrome

Background To determine the anatomical proximity of the vestibular nuclei to the respiratory nuclei and the effect of susceptibility of the posterior labyrinth to a hypoxic state on the vestibular system. Objective It was aimed to evaluate the possible effects of periodic hypoxia on vestibular reflexes and proprioceptive perception in patients with obstructive sleep apnea syndrome (OSAS). Material and methods The study was conducted with 40 patients diagnosed with moderate and severe OSAS and 21 healthy individuals. All individuals were evaluated with Dizziness Handicap Inventory, ocular vestibular evoked myogenic potential (oVEMP), cervical vestibular evoked myogenic potential (cVEMP), video head impulse test (vHIT), videonystagmography (VNG) and sportKAT 3000. Results In the vHIT, a statistically significant difference was found between the groups in terms of anterior and posterior semicircular canal vestibulo-ocular reflex gains (p < .05). A negative correlation was found between the lateral gain asymmetry and RALP gain asymmetry and the awake blood oxygen level in the OSAS groups. There was a statistically significant difference between the groups in terms of wave response rates cVEMP 100 dB nHL and oVEMP 100–110 dB nHL (p < .05). Conclusion and Significance It was concluded that vestibular reflexes and proprioceptive perception were affected due to periodic/chronic hypoxia in patients with moderate and severe OSAS.

Dynamic defence? Intertidal triplefin species show better maintenance of mitochondrial membrane potential than subtidal species at low oxygen pressures.

Oxygen is essential for most eukaryotic lifeforms, as it supports mitochondrial oxidative phosphorylation to supply ∼90% of cellular adenosine triphosphate (ATP). Fluctuations in O2 present a major stressor, with hypoxia leading to a cascade of detrimental physiological changes that alter cell operations and ultimately induce death. Nonetheless, some species episodically tolerate near-anoxic environments, and have evolved mechanisms to sustain function even during extended hypoxic periods. While mitochondria are pivotal in central metabolism, their role in hypoxia tolerance remains ill defined. Given the vulnerability of the brain to hypoxia, mitochondrial function was tested in brain homogenates of three closely related triplefin species with varying degrees of hypoxia tolerance (Bellapiscis medius, Forsterygion lapillum and Forsterygion varium). High-resolution respirometry coupled with fluorometric measurements of mitochondrial membrane potential (mtMP) permitted assessment of differences in mitochondrial function and integrity in response to intermittent hypoxia and anoxia. Traditional steady-state measures of respiratory flux and mtMP showed no differences among species. However, in the transition into anoxia, the tolerant species B. medius and F. lapillum maintained mtMP at O2 pressures 7- and 4.4-fold lower, respectively, than that of the hypoxia-sensitive F. varium and exhibited slower rates of membrane depolarisation. The results indicate that dynamic oxic-hypoxic mitochondria transitions underlie hypoxia tolerance in these intertidal fish.

Effects of diel-cycling hypoxia and salinity on lipid metabolism and fatty acid composition of the oyster Crassostrea hongkongensis

For marine animals living in estuarine, coastal, and intertidal areas, salinity changes and periodic hypoxia are typical stressors; however, how the varying salinity and dissolved oxygen affect the quality and nutrition of marine aquaculture species, such as oysters remains unknown. In this study, we evaluated the diel-cycling hypoxia under different salinities on fatty acid composition and lipid metabolism in oyster Crassostrea hongkongensis digestive glands. After 28 days of exposure, both hypoxia and elevated salinity caused a decrease in the saturated fatty acid (SFA)/polyunsaturated fatty acid (PUFA) ratio of C. hongkongensis, salinity mainly causes changes in C17:0, C17:1, C18:1n9, C20:1n9, C20:4n6, C21:5n3, C22:5n3, with high salinity being more damaging to the fatty acid fractions. Also, Hypoxia accelerates the synthesis of C18:1n9 and C20:4n6. Fatty acid synthase (FAS) synthesis is increased by reduced salinity or hypoxia, but Acetyl CoA carboxylase (ACC) only weakly promotes fatty acid synthesis. Under hypoxic conditions, the activity of both hepatic lipase (HL) and lipoprotein lipase activity (LPL) decreases, which is contrary to the results for dissolved oxygen. The increase in salinity under dissolved oxygen leads to a decrease in LPL activity and an increase in HL activity. Our findings highlighted that exposure to a combination of salinity and hypoxia stressors, can disrupt the protective mechanisms of the oyster and affect the function of its lipid metabolism. Therefore, long-term exposure to periodic hypoxia with salinity changes poses a risk to the nutritional quality of C. hongkongensis, affecting oyster aquaculture and the coastal ecosystem.

Effectiveness of Continuous Positive Airway Pressure in Treating Hypertension in Obstructive Sleep Apnea: A Traditional Review.

Almost one billion individuals worldwide suffer from obstructive sleep apnea (OSA). The most widely used treatment for OSA has been continuous positive airway pressure (CPAP), but its effect on blood pressure (BP) has been challenged. Our review aims to evaluate the effects of treating OSA with CPAP on BP and BP-related morbidities in adult hypertensive patients. Medical subject headings (MeSH) terminology was used to search the PubMed Central, MEDLINE, and PubMed databases for articles on the use of CPAP in OSA patients with hypertension. We selected various forms of academic writing, encompassing complete texts that were published in the English language. The study included a total of 21 papers. OSA is a serious health concern associated with a higher risk of cardiovascular disease, kidney disease, pulmonary hypertension, and aortic stiffness, which is brought on by the periodic hypoxia caused by nocturnal respiratory episodes. For individuals with moderate-to-severe OSA, CPAP therapy has been shown to have a considerable long-term benefit with a median drop of 11 mm Hg, and high adherence results in a decrease in diastolic BP. CPAP therapy directly lowers BP in OSA patients with a body mass index (BMI) of more than 30 kg/m2 and has also demonstrated improvement in early signs of atherosclerosis with lower nocturnal systolic BP levels. OSA patients with resistant hypertension also experienced lower BP after using CPAP for a year. Therefore, our findings suggest that obesity, hypersomnolence, high nocturnal BP, prolonged CPAP usage, and resistant hypertension may all have a major impact on the BP response to CPAP therapy in individuals with severe OSA.

Microglial exosomes alleviate intermittent hypoxia-induced cognitive deficits by suppressing NLRP3 inflammasome

Intermittent hypoxia is the best predictor of developing cognitive decline and Alzheimer’s disease progression in patients with obstructive sleep apnea. The nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome has been poorly studied as a regulator of neuroinflammation in cognitive impairment caused by intermittent hypoxia. As critical inflammatory cells, exosomes secreted by microglia have been found to affect the spread of pathologic proteins and neuropathology in neurodegenerative diseases. However, the effects of microglial exosomes on neuroinflammation and cognitive outcomes after intermittent hypoxia remain unclear. In this study, the role of miRNAs in microglial exosomes in improving cognitive deficits in mice exposed to intermittent hypoxia was investigated. We demonstrated that miR-146a-5p fluctuated over time in microglial exosomes of mice exposed to intermittent hypoxia for different periods of time, which could regulate neuronal NLRP3 inflammasome and neuroinflammation. In primary neurons, we found that miR-146a-5p regulated mitochondrial reactive oxygen species by targeting HIF1α, thus affecting the NLRP3 inflammasome and secretion of inflammatory factors. Similarly, further studies showed that inhibition of NLRP3 by administering overexpressed miR-146a-5p in microglial exosomes and MCC950 has improved neuroinflammation and cognitive dysfunction in mice after intermittent hypoxia. In conclusion, NLRP3 inflammasome may be a regulatory target for ameliorating cognitive impairment caused by intermittent hypoxia, and microglial exosomal miR-146a-5p may be a promising therapeutic strategy.

High metabolism and periodic hypoxia associated with drifting macrophyte detritus in the shallow subtidal Baltic Sea

Abstract. Macrophytes form highly productive habitats that export a substantial proportion of their primary production as particulate organic matter. As the detritus drifts with currents and accumulates in seafloor depressions, it constitutes organic enrichment and can deteriorate O2 conditions on the seafloor. In this study, we investigate the O2 dynamics and macrobenthic biodiversity associated with a shallow ∼ 2300 m2 macrophyte detritus field in the northern Baltic Sea. The detritus, primarily Fucus vesiculosus fragments, had a biomass of ∼ 1700 g dry weight m−2, approximately 1.5 times larger than nearby intact F. vesiculosus canopies. A vertical array of O2 sensors placed within the detritus documented that hypoxia ([O2] &lt; 63 µmol L−1) occurred for 23 % of the time and terminated at the onset of wave-driven hydrodynamic mixing. Measurements in five other habitats nearby, spanning bare sediments, seagrass, and macroalgae, indicate that hypoxic conditions were unique to detritus canopies. Fast-response O2 sensors placed above the detritus documented pulses of hypoxic waters originating from within the canopy. These pulses triggered a rapid short-term (∼ 5 min) deterioration of O2 conditions within the water column. Eddy covariance measurements of O2 fluxes indicated high metabolic rates, with daily photosynthetic production offsetting up to 81 % of the respiratory demands of the detritus canopy, prolonging its persistence within the coastal zone. The detritus site had a low abundance of crustaceans, bivalves, and polychaetes when compared to other habitats nearby, likely because their low O2 tolerance thresholds were often exceeded.

Hpgd affects the progression of hypoxic pulmonary hypertension by regulating vascular remodeling

BackgroundHypoxic pulmonary hypertension (HPH) is a syndrome of abnormally elevated pulmonary artery pressure, and it is mostly caused by vasoconstriction and remodeling of the pulmonary artery induced by long-term chronic hypoxia. There is a high incidence of HPH, a short survival time of the patients, but currently no effective treatments.MethodsIn this study, HPH-related single cell sequencing (scRNA-seq) and bulk RNA sequencing (RNA-seq) data were downloaded from the public database of Gene Expression Omnibus (GEO) for bioinformatics analysis in order to find out genes with important regulatory roles in the development of HPH. 523 key genes were identified through cell subpopulation identification and trajectory analysis of the downloaded scRNA-seq data, and 41 key genes were identified through weighted correlation network analysis (WGCNA) of the bulk RNA-seq data. Three key genes: Hpgd, Npr3 and Fbln2 were identified by taking intersection of the key genes obtained above, and Hpgd was finally selected for subsequent verification. The human pulmonary artery endothelial cells (hPAECs) were treated with hypoxia for different periods of time, and it was found that the expression of Hpgd decreased in hypoxia-treated hPAECs in a time-dependent manner. In order to further confirm whether Hpgd affects the occurrence and development of HPH, Hpgd was overexpressed in hPAECs.ResultsHpgd was confirmed to regulate the proliferation activity, apoptosis level, adhesiveness and angiogenesis ability of hypoxia-treated hPAECs through multiple experiments.ConclusionsDownregulation of Hpgd can improve the proliferation activity, reduce apoptosis, and enhance adhesion and angiogenesis in endothelial cells (ECs), thus promoting the occurrence and development of HPH.

320 Oxygenated Peritoneal Perfluorodecalin Improves Response to Normobaric Hypoxic Exposure in Swine

OBJECTIVES/GOALS: Patients suffering from respiratory failure have few options to support oxygenation and carbon dioxide removal aside from mechanical ventilation. Our objective was to test a novel extrapulmonary mechanism of gas exchange via peritoneal oxygenated perfluorocarbon (PFC) in a large animal model. METHODS/STUDY POPULATION: Using two 50 kg swine, hypoxia was modeled with subatmospheric oxygen and hypercarbia induced with acute hypoventilation. Through a midline laparotomy, cannulas were placed into the peritoneal space to allow for PFC infusion and circulation. After abdominal closure, these cannulas were connected to a device capable of draining, oxygenating, and infusing PFC. One animal was subjected to acute hypoxia (12% FiO2) and another animal to acute hypoventilation (4 breaths per minute). Primary outcomes were times for SpO2 to reach 75 mmHg, respectively. Trials were performed without PFC and with PFC dwelling or circulating through the peritoneal space, during which abdominal and bladder pressures were monitored and maintained under 20 mmHg by regulation of the PFC volume contained in the animal. RESULTS/ANTICIPATED RESULTS: In the animal subjected to acute hypoxia (12% FiO2), survival time improved from 5:55 to 20:00 (min:sec) after 2.5 liters of oxygenated PFC was instilled in the peritoneal space. Oxygen percent saturation of PFC before and after dwelling in the peritoneal space was measured at 100% before and 70% after dwelling in the animal during this hypoxic period corresponding with a gas transfer of 300 mL of oxygen over the 20-minute trial (i.e., 15 mL/min). Continual PFC circulation did not further extend the survival time during hypoxic conditions over PFC dwelling in the abdomen. In the animal that was acutely hypoventilated, there were no detectable differences in the rate of CO2 accumulation as measured by EtCO2 or direct blood pCO2 measurements with PFC dwelling or circulating through the peritoneal space. DISCUSSION/SIGNIFICANCE: Oxygenated PFC dwelling in the peritoneal space increased the duration of systemic arterial blood saturation remaining greater than 50% during normobaric hypoxic (12% FiO2) conditions but did not appreciably clear blood carbon dioxide during hypoventilation. Future experiments will focus on maximizing the rate of systemic oxygen uptake.

INTERVAL HYPOXIC HYPEROXIC TREATMENT IN THE REHABILITATION OF POST-COVID-19 PATIENTS

The aim of the study is to reveal the main pathogenetic mechanisms of the effectiveness of interval hypoxic hyperoxic treatment in the rehabilitation of post-COVID-19 patients.&#x0D; Materials and Methods. Hypo-Oxy, hypoxic therapy device produced by Oxyterra (Russia) was used to generate a hypoxic mixture with different oxygen content. Hypoxic periods followed the hyperoxic ones (30 % O2). To determine individual sensitivity to hypoxia, patients underwent a hypoxic test, the results of which were used to select the optimal oxygen content in the hypoxic mixture, the duration of hypoxic effects and the number of sessions. The authors determined the parameters of the functional respiratory system, oxygen regimen, lipid peroxidation, antioxidant system, exhaled air condensate and coagulation system. Statistical processing was carried out in accordance with the rules of mathematical statistics using Microsoft Excel and Statistica 6.0 for Windows. When conducting parametric analysis, paired and unpaired Student's t-tests were used. All numerical data were presented as the arithmetic mean and standard error of the mean (M±m). Differences were considered statistically significant at p&lt;0.05. &#x0D; Results. Interval hypoxic hyperoxic treatment has proven to be an effective way to rehabilitate post-COVID-19 patients (medium severity). After hypoxic therapy, there was a decrease in respiratory, circulatory, hemic and tissue hypoxia, and an improvement in the parameters of the prooxidant and antioxidant systems. Hypoxic therapy had a normalizing effect on the hemostasis system: platelet count in the blood increased (p&lt;0.05) (it was low before hypoxic therapy). Activated partial thromboplastin time, international normalized ratio, and antithrombin III content also increased. Prothrombin index, fibrinogen and D-dimer content in the blood serum showed a decreased risk of thrombosis. &#x0D; Conclusion. The conducted studies have proven the high efficiency of interval hypoxic hyperoxic treatment in the rehabilitation of post-COVID-19 patients.

Periodic hypoxia, intermittent pain, and caffeine in male and female neonatal rats: corticosterone, insulin resistance, and hepatic gene expression.

Preterm infants experience multiple stressors including periodic neonatal hypoxia, maternal/caregiver separation, and acute pain from clinical procedures. Although neonatal hypoxia or interventional pain are associated with sexually dimorphic effects that may last into adulthood, the interaction of these common preterm stressors and caffeine pretreatment remains unknown. We hypothesize that an interaction of acute neonatal hypoxia, isolation, and pain modeling the experience of the preterm infant will augment the acute stress response and that caffeine routinely given to preterm infants will alter this response. Male and female rat pups were isolated and exposed to six cycles of periodic hypoxia (10% O2) or normoxia (room air control) and/or intermittent pain by administering needle pricks (or touch control) to the paw on postnatal (PD) days 1-4. An additional set of rat pups was pretreated with caffeine citrate (80 mg/kg ip) and studied on PD1. Plasma corticosterone, fasting glucose, and insulin were measured to calculate homeostatic model assessment for insulin resistance (HOMA-IR) (index of insulin resistance). Glucocorticoid-, insulin-, and caffeine-sensitive gene mRNAs were analyzed in the PD1 liver and hypothalamus to evaluate downstream markers of glucocorticoid action. Acute pain with periodic hypoxia led to a large increase in plasma corticosterone, which was attenuated by pretreatment with caffeine. Pain with periodic hypoxia led to a 10-fold increase in hepatic Per1 mRNA expression in males, which was attenuated with caffeine. The augmentation of corticosterone and HOMA-IR at PD1 after periodic hypoxia with pain suggests early intervention to attenuate the stress response may mitigate the programming effects of neonatal stress.