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European Archives of Psychiatry and... Jun 2024Proregenerative and neuroprotective effects of antidepressants are an important topic of inquiry in neuropsychiatric research. Oxygen-glucose deprivation (OGD) mimics...
Proregenerative and neuroprotective effects of antidepressants are an important topic of inquiry in neuropsychiatric research. Oxygen-glucose deprivation (OGD) mimics key aspects of ischemic injury in vitro. Here, we studied the effects of 24-h pretreatment with serotonin (5-HT), citalopram (CIT), fluoxetine (FLU), and tianeptine (TIA) on primary mouse cortical neurons subjected to transient OGD. 5-HT (50 μM) significantly enhanced neuron viability as measured by MTT assay and reduced cell death and LDH release. CIT (10 μM) and FLU (1 μM) did not increase the effects of 5-HT and neither antidepressant conferred neuroprotection in the absence of supplemental 5-HT in serum-free cell culture medium. By contrast, pre-treatment with TIA (10 μM) resulted in robust neuroprotection, even in the absence of 5-HT. Furthermore, TIA inhibited mRNA transcription of candidate genes related to cell death and hypoxia and attenuated lipid peroxidation, a hallmark of neuronal injury. Finally, deep RNA sequencing of primary neurons subjected to OGD demonstrated that OGD induces many pathways relating to cell survival, the inflammation-immune response, synaptic dysregulation and apoptosis, and that TIA pretreatment counteracted these effects of OGD. In conclusion, this study highlights the comparative strength of the 5-HT independent neuroprotective effects of TIA and identifies the molecular pathways involved.
Topics: Animals; Mice; Glucose; Neuroprotective Agents; Neurons; Thiazepines; Cells, Cultured; Cerebral Cortex; Citalopram; Fluoxetine; Serotonin; Mice, Inbred C57BL; Cell Hypoxia; Oxygen; Antidepressive Agents, Tricyclic
PubMed: 37653354
DOI: 10.1007/s00406-023-01685-9 -
Langmuir : the ACS Journal of Surfaces... Jul 2023As the key component of extracorporeal membrane oxygenation (ECMO), artificial lung membranes have low gas permeability and plasma leakage problems, and the contact...
As the key component of extracorporeal membrane oxygenation (ECMO), artificial lung membranes have low gas permeability and plasma leakage problems, and the contact between membrane materials and blood can cause coagulation, leading to the blockage of medical equipment and seriously threatening the safety of human life. In our work, poly(4-methyl-1-pentene) hollow fiber membranes (PMP HFMs) were prepared by the thermally induced phase separation (TIPS) method, the redox method was adopted for the surface hydroxylation of PMP HFMs, and then, heparin (Hep) and 2-(methacryloyloxy)ethyl(2-(trimethylammonio)ethyl) phosphate (MPC) were grafted to the surface of PMP HFMs to prepare anticoagulant coatings. The gas permeability and hemo-compatibility of the coatings were investigated by various characterization methods, such as gas flow meter, scanning electron microscope, extracorporeal circulation experiment, etc. The results show that PMP HFMs possess a bicontinuous pore structure with a dense surface layer, which could maintain good gas permeability with an oxygen permeance of 0.8 mL/bar·cm·min and stable gas selectivity. Furthermore, the whole blood circulation of rabbit indicated that a composite surface of bioactive Hep and biopassive MPC might be used as artificial lung membranes without the formation of thrombosis within 21 days.
Topics: Animals; Humans; Rabbits; Membranes, Artificial; Phosphorylcholine; Heparin; Lung; Oxygen
PubMed: 37427880
DOI: 10.1021/acs.langmuir.3c00945 -
Redox Biology May 2024We obviously agree with Wu et al. that HO might accumulate in the Archean land waters devoid of Fe. We do disagree on the topic of the half-life of HO, as the work cited...
We obviously agree with Wu et al. that HO might accumulate in the Archean land waters devoid of Fe. We do disagree on the topic of the half-life of HO, as the work cited in support for a longer half-live is not relevant to the conditions in the Archean ocean. While the existence of radicals in quartz is not in doubt, we do question the hypothesis that these radicals oxidize water to HO and HO.
Topics: Hydrogen Peroxide; Oxygen; Photosynthesis; Hydroxyl Radical; Oxidation-Reduction
PubMed: 38492556
DOI: 10.1016/j.redox.2024.103110 -
Journal of Applied Physiology... Aug 2023We tested the hypothesis that ingestion of cocoa flavanols would improve cognition during acute hypoxia equivalent to 5,500 m altitude (partial pressure of end-tidal... (Randomized Controlled Trial)
Randomized Controlled Trial
We tested the hypothesis that ingestion of cocoa flavanols would improve cognition during acute hypoxia equivalent to 5,500 m altitude (partial pressure of end-tidal oxygen = 45 mmHg). Using placebo-controlled double-blind trials, 12 participants ingested 15 mg·kg of cocoa flavanols 90 min before completing cognitive tasks during normoxia and either poikilocapnic or isocapnic hypoxia (partial pressure of end-tidal carbon dioxide uncontrolled or maintained at the baseline value, respectively). Cerebral oxygenation was measured using functional near-infrared spectroscopy. Overall cognition was impaired by poikilocapnic hypoxia (main effect of hypoxia, = 0.008). Cocoa flavanols improved a measure of overall cognitive performance by 4% compared with placebo (effect of flavanols, = 0.033) during hypoxia, indicating a change in performance from "low average" to "average." The hypoxia-induced decrease in cerebral oxygenation was two-fold greater with placebo than with cocoa flavanols (effect of flavanols, = 0.005). Subjective fatigue was increased by 900% with placebo compared with flavanols during poikilocapnic hypoxia (effect of flavanols, = 0.004). Overall cognition was impaired by isocapnic hypoxia (effect of hypoxia, = 0.001) but was not improved by cocoa flavanols (mean improvement = 1%; effect of flavanols, = 0.72). Reaction time was impaired by 8% with flavanols during normoxia and further impaired by 11% during isocapnic hypoxia (effect of flavanols, = 0.01). Our findings are the first to show that flavanol-mediated improvements in cognition and mood during normoxia persist during severe oxygen deprivation, conferring a neuroprotective effect. We show for the first time that cocoa flavanols exert a neuroprotective effect during severe hypoxia. Following acute cocoa flavanol ingestion, we observed improvements in cognition, cerebral oxygenation, and subjective fatigue during normoxia and severe poikilocapnic hypoxia. Cocoa flavanols did not improve cognition during severe isocapnic hypoxia, suggesting a possible interaction with carbon dioxide.
Topics: Humans; Cacao; Carbon Dioxide; Cognition; Hypoxia; Mental Fatigue; Neuroprotective Agents; Oxygen; Polyphenols; Double-Blind Method
PubMed: 37471213
DOI: 10.1152/japplphysiol.00219.2023 -
International Immunopharmacology Aug 2023
Topics: Oxygen; Ozone; Mitomycin
PubMed: 37455171
DOI: 10.1016/j.intimp.2023.110598 -
Journal of Sport and Health Science Jul 2024Near-infrared spectroscopy (NIRS) technology has allowed for the measurement of cerebral and skeletal muscle oxygenation simultaneously during exercise. Since this... (Review)
Review
BACKGROUND
Near-infrared spectroscopy (NIRS) technology has allowed for the measurement of cerebral and skeletal muscle oxygenation simultaneously during exercise. Since this technology has been growing and is now successfully used in laboratory and sports settings, this systematic review aimed to synthesize the evidence and enhance an integrative understanding of blood flow adjustments and oxygen (O) changes (i.e., the balance between O delivery and O consumption) within the cerebral and muscle systems during exercise.
METHODS
A systematic review was conducted using PubMed, Embase, Scopus, and Web of Science databases to search for relevant studies that simultaneously investigated cerebral and muscle hemodynamic changes using the near-infrared spectroscopy system during exercise. This review considered manuscripts written in English and available before February 9, 2023. Each step of screening involved evaluation by 2 independent authors, with disagreements resolved by a third author. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess the methodological quality of the studies.
RESULTS
Twenty studies were included, of which 80% had good methodological quality, and involved 290 young or middle-aged adults. Different types of exercises were used to assess cerebral and muscle hemodynamic changes, such as cycling (n = 11), treadmill (n = 1), knee extension (n = 5), isometric contraction of biceps brachii (n = 3), and duet swim routines (n = 1). The cerebral hemodynamics analysis was focused on the frontal cortex (n = 20), while in the muscle, the analysis involved vastus lateralis (n = 18), gastrocnemius (n = 3), biceps brachii (n = 5), deltoid (n = 1), and intercostal muscle (n = 1). Overall, muscle deoxygenation increases during exercise, reaching a plateau in voluntary exhaustion, while in the brain, oxyhemoglobin concentration increases with exercise intensity, reaching a plateau or declining at the exhaustion point.
CONCLUSION
Muscle and cerebral oxygenation respond differently to exercise, with muscle increasing O utilization and cerebral tissue increasing O delivery during exercise. However, at the exhaustion point, both muscle and cerebral oxygenation become compromised. This is characterized by a reduction in blood flow and a decrease in O extraction in the muscle, while in the brain, oxygenation reaches a plateau or decline, potentially resulting in motor failure during exercise.
Topics: Humans; Muscle, Skeletal; Oxygen Consumption; Spectroscopy, Near-Infrared; Exercise; Brain; Hemodynamics; Oxygen; Cerebrovascular Circulation; Adult
PubMed: 38462172
DOI: 10.1016/j.jshs.2024.03.003 -
Nature Communications Nov 2023The inability to inspect metabolic activities within distinct subcellular compartments has been a major barrier to our understanding of eukaryotic cell metabolism....
The inability to inspect metabolic activities within distinct subcellular compartments has been a major barrier to our understanding of eukaryotic cell metabolism. Previous work addressed this challenge by analyzing metabolism in isolated organelles, which grossly bias metabolic activity. Here, we describe a method for inferring physiological metabolic fluxes and metabolite concentrations in mitochondria and cytosol based on isotope tracing experiments performed with intact cells. This is made possible by computational deconvolution of metabolite isotopic labeling patterns and concentrations into cytosolic and mitochondrial counterparts, coupled with metabolic and thermodynamic modelling. Our approach lowers the uncertainty regarding compartmentalized fluxes and concentrations by one and three orders of magnitude compared to existing modelling approaches, respectively. We derive a quantitative view of mitochondrial and cytosolic metabolic activities in central carbon metabolism across cultured cell lines without performing cell fractionation, finding major variability in compartmentalized malate-aspartate shuttle fluxes. We expect our approach for inferring metabolism at a subcellular resolution to be instrumental for a variety of studies of metabolic dysfunction in human disease and for bioengineering.
Topics: Humans; Cytosol; Mitochondria; Cell Respiration; Cell Line; Isotopes; Isotope Labeling
PubMed: 37980339
DOI: 10.1038/s41467-023-42824-z -
Tumor hypoxia and radiotherapy: A major driver of resistance even for novel radiotherapy modalities.Seminars in Cancer Biology Jan 2024Hypoxia in solid tumors is an important predictor of poor clinical outcome to radiotherapy. Both physicochemical and biological processes contribute to a reduced... (Review)
Review
Hypoxia in solid tumors is an important predictor of poor clinical outcome to radiotherapy. Both physicochemical and biological processes contribute to a reduced sensitivity of hypoxic tumor cells to ionizing radiation and hypoxia-related treatment resistances. A conventional low-dose fractionated radiotherapy regimen exploits iterative reoxygenation in between the individual fractions, nevertheless tumor hypoxia still remains a major hurdle for successful treatment outcome. The technological advances achieved in image guidance and highly conformal dose delivery make it nowadays possible to prescribe larger doses to the tumor as part of single high-dose or hypofractionated radiotherapy, while keeping an acceptable level of normal tissue complication in the co-irradiated organs at risk. However, we insufficiently understand the impact of tumor hypoxia to single high-doses of RT and hypofractionated RT. So-called FLASH radiotherapy, which delivers ionizing radiation at ultrahigh dose rates (> 40 Gy/sec), has recently emerged as an important breakthrough in the radiotherapy field to reduce normal tissue toxicity compared to irradiation at conventional dose rates (few Gy/min). Not surprisingly, oxygen consumption and tumor hypoxia also seem to play an intriguing role for FLASH radiotherapy. Here we will discuss the role of tumor hypoxia for radiotherapy in general and in the context of novel radiotherapy treatment approaches.
Topics: Humans; Tumor Hypoxia; Neoplasms; Radiation Dose Hypofractionation; Hypoxia; Treatment Outcome
PubMed: 38040401
DOI: 10.1016/j.semcancer.2023.11.006 -
Physiology & Behavior Aug 2023This systematic review, meta-analysis and meta-regression examined the effect of acute normobaric hyperoxic breathing on cognition in healthy humans. 23 studies were... (Meta-Analysis)
Meta-Analysis Review
This systematic review, meta-analysis and meta-regression examined the effect of acute normobaric hyperoxic breathing on cognition in healthy humans. 23 studies were included providing 76 effect estimates (EE). Hyperoxic breathing improved memory accuracy (22 EEs; g = 0.34) and speed (9 EEs; g = 0.59), attention accuracy (7 EEs; g = 0.59) and speed (7 EEs; g = 0.51), reaction speed (8 EEs; g = 0.82), crystallised intelligence (7 EEs; g = 0.73), executive function (6 EEs; g = 0.88) and information processing (10 EEs; g = 0.62). However, the overall quality of evidence was low (average Rosendal score of 47%) and there was a large range of study heterogeneity, with prediction intervals often crossing 0; therefore, reducing the reliability of the magnitude of these favourable effects. Oxygen percentage, 100% compared with 22-99% oxygen, temporal position of administration to task performance, and study quality did not influence the overall weighted mean effects for most cognitive domains. Altogether, despite beneficial results, further high quality research is required prior to recommending hyperoxic breathing to enhance cognition.
Topics: Humans; Hyperoxia; Reproducibility of Results; Cognition; Executive Function; Oxygen
PubMed: 37121344
DOI: 10.1016/j.physbeh.2023.114208 -
Bioorganic Chemistry Mar 2024Hypoxia, as a prevalent feature of solid tumors, is correlated with tumorigenesis, proliferation, and invasion, playing an important role in mediating the drug... (Review)
Review
Hypoxia, as a prevalent feature of solid tumors, is correlated with tumorigenesis, proliferation, and invasion, playing an important role in mediating the drug resistance and affecting the cancer treatment outcomes. Due to the distinct oxygen levels between tumor and normal tissues, hypoxia-targeted therapy has attracted significant attention. The hypoxia-activated compounds mainly depend on reducible organic groups including azo, nitro, N-oxides, quinones and azide as well as some redox-active metal complex that are selectively converted into active species by the increased reduction potential under tumor hypoxia. In this review, we briefly summarized our current understanding on hypoxia-activated compounds with a particular highlight on the recently developed prodrugs and fluorescent probes for tumor treatment and diagnosis. We have also discussed the challenges and perspectives of small molecule-based hypoxia-activatable prodrug for future development.
Topics: Humans; Hypoxia; Neoplasms; Prodrugs; Cell Hypoxia; Tumor Hypoxia; Cell Line, Tumor
PubMed: 38306826
DOI: 10.1016/j.bioorg.2024.107161