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Journal of Nanobiotechnology Jun 2024Oxygen is necessary for life and plays a key pivotal in maintaining normal physiological functions and treat of diseases. Hemoglobin-based oxygen carriers (HBOCs) have... (Review)
Review
Oxygen is necessary for life and plays a key pivotal in maintaining normal physiological functions and treat of diseases. Hemoglobin-based oxygen carriers (HBOCs) have been studied and developed as a replacement for red blood cells (RBCs) in oxygen transport due to their similar oxygen-carrying capacities. However, applications of HBOCs are hindered by vasoactivity, oxidative toxicity, and a relatively short circulatory half-life. With advancements in nanotechnology, Hb encapsulation, absorption, bioconjugation, entrapment, and attachment to nanomaterials have been used to prepare nanomaterial-related HBOCs to address these challenges and pend their application in several biomedical and therapeutic contexts. This review focuses on the progress of this class of nanomaterial-related HBOCs in the fields of hemorrhagic shock, ischemic stroke, cancer, and wound healing, and speculates on future research directions. The advancements in nanomaterial-related HBOCs are expected to lead significant breakthroughs in blood substitutes, enabling their widespread use in the treatment of clinical diseases.
Topics: Humans; Hemoglobins; Blood Substitutes; Oxygen; Animals; Nanostructures; Liposomes; Nanocapsules; Wound Healing; Neoplasms; Shock, Hemorrhagic
PubMed: 38880905
DOI: 10.1186/s12951-024-02606-1 -
NPJ Microgravity Jun 2024Iron is essential for cell respiration, muscle metabolism, and oxygen transport. Recent research has shown that simulated microgravity rapidly affects iron metabolism in...
Iron is essential for cell respiration, muscle metabolism, and oxygen transport. Recent research has shown that simulated microgravity rapidly affects iron metabolism in men. However, its impact on women remains unclear. This study aims to compare iron metabolism alterations in both sexes exposed to 5 days of dry immersion. Our findings demonstrate that women, similarly to men, experience increased systemic iron availability and elevated serum hepcidin levels, indicative of iron misdistribution after short-term exposure to simulated microgravity.
PubMed: 38879550
DOI: 10.1038/s41526-024-00399-z -
Journal of Experimental & Clinical... Jun 2024Breast cancer (BC) is a complex disease, showing heterogeneity in the genetic background, molecular subtype, and treatment algorithm. Historically, treatment strategies...
BACKGROUND
Breast cancer (BC) is a complex disease, showing heterogeneity in the genetic background, molecular subtype, and treatment algorithm. Historically, treatment strategies have been directed towards cancer cells, but these are not the unique components of the tumor bulk, where a key role is played by the tumor microenvironment (TME), whose better understanding could be crucial to obtain better outcomes.
METHODS
We evaluated mitochondrial transfer (MT) by co-culturing Adipose stem cells with different Breast cancer cells (BCCs), through MitoTracker assay, Mitoception, confocal and immunofluorescence analyses. MT inhibitors were used to confirm the MT by Tunneling Nano Tubes (TNTs). MT effect on multi-drug resistance (MDR) was assessed using Doxorubicin assay and ABC transporter evaluation. In addition, ATP production was measured by Oxygen Consumption rates (OCR) and Immunoblot analysis.
RESULTS
We found that MT occurs via Tunneling Nano Tubes (TNTs) and can be blocked by actin polymerization inhibitors. Furthermore, in hybrid co-cultures between ASCs and patient-derived organoids we found a massive MT. Breast Cancer cells (BCCs) with ASCs derived mitochondria (ADM) showed a reduced HIF-1α expression in hypoxic conditions, with an increased ATP production driving ABC transporters-mediated multi-drug resistance (MDR), linked to oxidative phosphorylation metabolism rewiring.
CONCLUSIONS
We provide a proof-of-concept of the occurrence of Mitochondrial Transfer (MT) from Adipose Stem Cells (ASCs) to BC models. Blocking MT from ASCs to BCCs could be a new effective therapeutic strategy for BC treatment.
Topics: Humans; Breast Neoplasms; Female; Mitochondria; Drug Resistance, Neoplasm; Drug Resistance, Multiple; Stem Cells; Adipose Tissue; Cell Line, Tumor; Tumor Microenvironment
PubMed: 38877575
DOI: 10.1186/s13046-024-03087-8 -
BMC Cardiovascular Disorders Jun 2024In patients who experience out-of-hospital cardiac arrest (OHCA), it is important to assess the association of sub-phenotypes identified by latent class analysis (LCA)...
BACKGROUND
In patients who experience out-of-hospital cardiac arrest (OHCA), it is important to assess the association of sub-phenotypes identified by latent class analysis (LCA) using pre-hospital prognostic factors and factors measurable immediately after hospital arrival with neurological outcomes at 30 days, which would aid in making treatment decisions.
METHODS
This study retrospectively analyzed data obtained from the Japanese OHCA registry between June 2014 and December 2019. The registry included a complete set of data on adult patients with OHCA, which was used in the LCA. The association between the sub-phenotypes and 30-day survival with favorable neurological outcomes was investigated. Furthermore, adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by multivariate logistic regression analysis using in-hospital data as covariates.
RESULTS
A total of, 22,261 adult patients who experienced OHCA were classified into three sub-phenotypes. The factor with the highest discriminative power upon patient's arrival was Glasgow Coma Scale followed by partial pressure of oxygen. Thirty-day survival with favorable neurological outcome as the primary outcome was evident in 66.0% participants in Group 1, 5.2% in Group 2, and 0.5% in Group 3. The 30-day survival rates were 80.6%, 11.8%, and 1.3% in groups 1, 2, and 3, respectively. Logistic regression analysis revealed that the ORs (95% CI) for 30-day survival with favorable neurological outcomes were 137.1 (99.4-192.2) for Group 1 and 4.59 (3.46-6.23) for Group 2 in comparison to Group 3. For 30-day survival, the ORs (95%CI) were 161.7 (124.2-212.1) for Group 1 and 5.78 (4.78-7.04) for Group 2, compared to Group 3.
CONCLUSIONS
This study identified three sub-phenotypes based on the prognostic factors available immediately after hospital arrival that could predict neurological outcomes and be useful in determining the treatment strategy of patients experiencing OHCA upon their arrival at the hospital.
Topics: Humans; Out-of-Hospital Cardiac Arrest; Male; Female; Japan; Aged; Middle Aged; Retrospective Studies; Registries; Latent Class Analysis; Time Factors; Risk Factors; Cardiopulmonary Resuscitation; Aged, 80 and over; Treatment Outcome; Risk Assessment; Phenotype; Glasgow Coma Scale; Predictive Value of Tests; Prognosis
PubMed: 38877462
DOI: 10.1186/s12872-024-03975-z -
Cellular & Molecular Biology Letters Jun 2024Osteoarthritis (OA) is the most common degenerative joint disorder that causes disability in aged individuals, caused by functional and structural alterations of the...
Osteoarthritis (OA) is the most common degenerative joint disorder that causes disability in aged individuals, caused by functional and structural alterations of the knee joint. To investigate whether metabolic drivers might be harnessed to promote cartilage repair, a liquid chromatography-mass spectrometry (LC-MS) untargeted metabolomics approach was carried out to screen serum biomarkers in osteoarthritic rats. Based on the correlation analyses, α-ketoglutarate (α-KG) has been demonstrated to have antioxidant and anti-inflammatory properties in various diseases. These properties make α-KG a prime candidate for further investigation of OA. Experimental results indicate that α-KG significantly inhibited HO-induced cartilage cell matrix degradation and apoptosis, reduced levels of reactive oxygen species (ROS) and malondialdehyde (MDA), increased superoxide dismutase (SOD) and glutathione (GSH)/glutathione disulfide (GSSG) levels, and upregulated the expression of ETV4, SLC7A11 and GPX4. Further mechanistic studies observed that α-KG, like Ferrostatin-1 (Fer-1), effectively alleviated Erastin-induced apoptosis and ECM degradation. α-KG and Fer-1 upregulated ETV4, SLC7A11, and GPX4 at the mRNA and protein levels, decreased ferrous ion (Fe) accumulation, and preserved mitochondrial membrane potential (MMP) in ATDC5 cells. In vivo, α-KG treatment inhibited ferroptosis in OA rats by activating the ETV4/SLC7A11/GPX4 pathway. Thus, these findings indicate that α-KG inhibits ferroptosis via the ETV4/SLC7A11/GPX4 signaling pathway, thereby alleviating OA. These observations suggest that α-KG exhibits potential therapeutic properties for the treatment and prevention of OA, thereby having potential clinical applications in the future.
Topics: Ferroptosis; Animals; Osteoarthritis; Ketoglutaric Acids; Signal Transduction; Rats; Phospholipid Hydroperoxide Glutathione Peroxidase; Amino Acid Transport System y+; Male; Proto-Oncogene Proteins c-ets; Rats, Sprague-Dawley; Apoptosis; Reactive Oxygen Species
PubMed: 38877424
DOI: 10.1186/s11658-024-00605-6 -
Scientific Reports Jun 2024Intestinal preservation for transplantation is accompanied by hypoperfusion with long periods of ischemia with total blood cessation and absolute withdrawal of oxygen...
Intestinal preservation for transplantation is accompanied by hypoperfusion with long periods of ischemia with total blood cessation and absolute withdrawal of oxygen leading to structural damage. The application of intraluminal oxygen has been successfully tested in small-animal series during storage and transport of the organ but have been so far clinically unrelatable. In this study, we tested whether a simple and clinically approachable method of intraluminal oxygen application could prevent ischemic damage in a large animal model, during warm ischemia time. We utilised a local no-flow ischemia model of the small intestine in pigs. A low-flow and high-pressure intraluminal oxygen deliverance system was applied in 6 pigs and 6 pigs served as a control group. Mucosal histopathology, hypoxia and barrier markers were evaluated after two hours of no-flow conditions, in both treatment and sham groups, and in healthy tissue. Macro- and microscopically, the luminal oxygen delivered treatment group showed preserved small bowel's appearance, viability, and mucosal integrity. A gradual deterioration of histopathology and barrier markers and increase in hypoxia-inducible factor 1-α expression towards the sites most distant from the oxygen application was observed. Intraluminal low-flow, high oxygen delivery can preserve the intestinal mucosa during total ischemia of the small intestine. This finding can be incorporated in methods to overcome small bowel ischemia and improve intestinal preservation for transplantation.
Topics: Animals; Intestinal Mucosa; Intestine, Small; Oxygen; Swine; Ischemia; Disease Models, Animal; Organ Preservation; Hypoxia-Inducible Factor 1, alpha Subunit
PubMed: 38877069
DOI: 10.1038/s41598-024-64660-x -
Cell Metabolism Jun 2024Mitochondria house many metabolic pathways required for homeostasis and growth. To explore how human cells respond to mitochondrial dysfunction, we performed...
Mitochondria house many metabolic pathways required for homeostasis and growth. To explore how human cells respond to mitochondrial dysfunction, we performed metabolomics in fibroblasts from patients with various mitochondrial disorders and cancer cells with electron transport chain (ETC) blockade. These analyses revealed extensive perturbations in purine metabolism, and stable isotope tracing demonstrated that ETC defects suppress de novo purine synthesis while enhancing purine salvage. In human lung cancer, tumors with markers of low oxidative mitochondrial metabolism exhibit enhanced expression of the salvage enzyme hypoxanthine phosphoribosyl transferase 1 (HPRT1) and high levels of the HPRT1 product inosine monophosphate. Mechanistically, ETC blockade activates the pentose phosphate pathway, providing phosphoribosyl diphosphate to drive purine salvage supplied by uptake of extracellular bases. Blocking HPRT1 sensitizes cancer cells to ETC inhibition. These findings demonstrate how cells remodel purine metabolism upon ETC blockade and uncover a new metabolic vulnerability in tumors with low respiration.
PubMed: 38876105
DOI: 10.1016/j.cmet.2024.05.014 -
Redox Biology Aug 2024The pathogenesis of epilepsy remains unclear; however, a prevailing hypothesis suggests that the primary underlying cause is an imbalance between neuronal excitability...
Glucose-6-phosphate dehydrogenase alleviates epileptic seizures by repressing reactive oxygen species production to promote signal transducer and activator of transcription 1-mediated N-methyl-d-aspartic acid receptors inhibition.
The pathogenesis of epilepsy remains unclear; however, a prevailing hypothesis suggests that the primary underlying cause is an imbalance between neuronal excitability and inhibition. Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway, which is primarily involved in deoxynucleic acid synthesis and antioxidant defense mechanisms and exhibits increased expression during the chronic phase of epilepsy, predominantly colocalizing with neurons. G6PD overexpression significantly reduces the frequency and duration of spontaneous recurrent seizures. Furthermore, G6PD overexpression enhances signal transducer and activator of transcription 1 (STAT1) expression, thus influencing N-methyl-d-aspartic acid receptors expression, and subsequently affecting seizure activity. Importantly, the regulation of STAT1 by G6PD appears to be mediated primarily through reactive oxygen species signaling pathways. Collectively, our findings highlight the pivotal role of G6PD in modulating epileptogenesis, and suggest its potential as a therapeutic target for epilepsy.
Topics: Glucosephosphate Dehydrogenase; Reactive Oxygen Species; Animals; Receptors, N-Methyl-D-Aspartate; Seizures; STAT1 Transcription Factor; Epilepsy; Signal Transduction; Mice; Humans; Neurons; Male; Rats; Disease Models, Animal
PubMed: 38875958
DOI: 10.1016/j.redox.2024.103236 -
European Journal of Sport Science Jun 2024Blood flow restriction (BFR) is increasingly being used to enhance aerobic performance in endurance athletes. This study examined physiological responses to BFR applied... (Randomized Controlled Trial)
Randomized Controlled Trial
Blood flow restriction (BFR) is increasingly being used to enhance aerobic performance in endurance athletes. This study examined physiological responses to BFR applied in recovery phases within a high-intensity interval training (HIIT) session in trained cyclists. Eleven competitive road cyclists (mean ± SD, age: 28 ± 7 years, body mass: 69 ± 6 kg, peak oxygen uptake: 65 ± 9 mL · kg · min) completed two randomised crossover conditions: HIIT with (BFR) and without (CON) BFR applied during recovery phases. HIIT consisted of six 30-s cycling bouts at an intensity equivalent to 85% of maximal 30-s power (523 ± 93 W), interspersed with 4.5-min recovery. BFR (200 mmHg, 12 cm cuff width) was applied for 2-min in the early recovery phase between each interval. Pulmonary gas exchange (V̇O, V̇CO, and V̇E), tissue oxygen saturation index (TSI), heart rate (HR), and serum vascular endothelial growth factor concentration (VEGF) were measured. Compared to CON, BFR increased V̇CO and V̇E during work bouts (both p < 0.05, dz < 0.5), but there was no effect on V̇O, TSI, or HR (p > 0.05). In early recovery, BFR decreased TSI, V̇O, V̇CO, and V̇E (all p < 0.05, dz > 0.8) versus CON, with no change in HR (p > 0.05). In late recovery, when BFR was released, V̇O, V̇CO, V̇E, and HR increased, but TSI decreased versus CON (all p < 0.05, dz > 0.8). There was a greater increase in VEGF at 3-h post-exercise in BFR compared to CON (p < 0.05, dz > 0.8). Incorporating BFR into HIIT recovery phases altered physiological responses compared to exercise alone.
Topics: Humans; Bicycling; High-Intensity Interval Training; Adult; Heart Rate; Oxygen Consumption; Cross-Over Studies; Male; Young Adult; Pulmonary Gas Exchange; Vascular Endothelial Growth Factor A; Regional Blood Flow; Athletic Performance; Oxygen Saturation
PubMed: 38874956
DOI: 10.1002/ejsc.12107 -
International Journal of Molecular... Jul 2024In paraquat (PQ)‑induced acute lung injury (ALI)/ acute respiratory distress syndrome, PQ disrupts endothelial cell function and vascular integrity, which leads to...
Anthrahydroquinone‑2,6‑disulfonate attenuates PQ‑induced acute lung injury through decreasing pulmonary microvascular permeability via inhibition of the PI3K/AKT/eNOS pathway.
In paraquat (PQ)‑induced acute lung injury (ALI)/ acute respiratory distress syndrome, PQ disrupts endothelial cell function and vascular integrity, which leads to increased pulmonary leakage. Anthrahydroquinone‑2,6‑disulfonate (AH2QDS) is a reducing agent that attenuates the extent of renal injury and improves survival in PQ‑intoxicated Sprague‑Dawley (SD) rats. The present study aimed to explore the beneficial role of AH2QDS in PQ‑induced ALI and its related mechanisms. A PQ‑intoxicated ALI model was established using PQ gavage in SD rats. Human pulmonary microvascular endothelial cells (HPMECs) were challenged with PQ. Superoxide dismutase, malondialdehyde, reactive oxygen species and nitric oxide (NO) fluorescence were examined to detect the level of oxidative stress in HPMECs. The levels of TNF‑α, IL‑1β and IL‑6 were assessed using an ELISA. Transwell and Cell Counting Kit‑8 assays were performed to detect the migration and proliferation of the cells. The pathological changes in lung tissues and blood vessels were examined by haematoxylin and eosin staining. Evans blue staining was used to detect pulmonary microvascular permeability. Western blotting was performed to detect target protein levels. Immunofluorescence and immunohistochemical staining were used to detect the expression levels of target proteins in HPMECs and lung tissues. AH2QDS inhibited inflammatory responses in lung tissues and HPMECs, and promoted the proliferation and migration of HPMECs. In addition, AH2QDS reduced pulmonary microvascular permeability by upregulating the levels of vascular endothelial‑cadherin, zonula occludens‑1 and CD31, thereby attenuating pathological changes in the lungs in rats. Finally, these effects may be related to the suppression of the phosphatidylinositol‑3‑kinase (PI3K)/protein kinase B (AKT)/endothelial‑type NO synthase (eNOS) signalling pathway in endothelial cells. In conclusion, AH2QDS ameliorated PQ‑induced ALI by improving alveolar endothelial barrier disruption via modulation of the PI3K/AKT/eNOS signalling pathway, which may be an effective candidate for the treatment of PQ‑induced ALI.
Topics: Animals; Acute Lung Injury; Proto-Oncogene Proteins c-akt; Nitric Oxide Synthase Type III; Rats, Sprague-Dawley; Capillary Permeability; Phosphatidylinositol 3-Kinases; Humans; Male; Signal Transduction; Lung; Paraquat; Rats; Endothelial Cells; Oxidative Stress
PubMed: 38874017
DOI: 10.3892/ijmm.2024.5387