bims-oxygme 2025-03-30 papers

bims-oxygme

Biomed News

on Oxygen metabolism

Issue of 2025–03–30
twelve papers selected by
Onurkan Karabulut, Berkeley City College

Clinical Characteristics of Postpartum Women With Hypoxia: A Retrospective Analysis of 92 Cases.
Impact of hypoxia on the hippocampus: A review.
Electroacupuncture mitigates cognitive impairments in chronic hypoxia-induced mice by modulating neuroinflammation.
Comparison of the Effects of Endurance Training Conducted in Conditions of Normoxia and Artificial Hypoxia in Patients After Myocardial Infarction.
Small-molecule hypoxia therapy.
Molecular pathways in cardiovascular disease under hypoxia: Mechanisms, biomarkers, and therapeutic targets.
Hypoxia-associated genes as predictors of outcomes in gastric cancer: a genomic approach.
Phenothiazine Confers Neuroprotection via Dpp2/7 in High Altitude Traumatic Brain Injury Mouse Model.
Stabilization of Transcription Factor, HIF-1α by Prolylhydroxylase 1 Knockout Reduces Cardiac Injury After Myocardial Infarction in Mice.
Oxygen sensitive drug release using hemoglobin Microbubbles: A new approach to targeting hypoxia in Ultrasound-Mediated drug delivery.
Utilizing Hyperbaric Oxygen Therapy to Improve Cognitive Function in Patients With Alzheimer's Disease by Activating Autophagy-Related Signaling Pathways.
RETRACTION: Application of Hyperbaric Oxygen Therapy in Diabetic Foot Ulcers: A Meta-Analysis.

Int J Gen Med. 2025 ;18 1581-1590

Clinical Characteristics of Postpartum Women With Hypoxia: A Retrospective Analysis of 92 Cases.

Ting Wang, Rui Liu, Yuanpeng Li, Wei Qian, Man Niu.

   Purpose: Postpartum hypoxia is a significant concern among clinicians due to its association with fatal diseases such as amniotic fluid embolism. This study analyzed the clinical characteristics of patients with different etiologies of postpartum hypoxia.
Patients and Methods: Ninety-two postpartum cases with hypoxia, defined as oxygen saturation (SpO2) < 95% within 48 h postpartum without supplemental oxygen inhalation, and 100 normal gravidas were enrolled. All patients with postpartum hypoxia underwent 24 h vital sign monitoring and relevant examinations, including hematological tests, chest computed tomography (CT) scans, or CT pulmonary angiography, to determine the cause of hypoxia and received appropriate treatments. All patients were followed up for 1 month.
Results: Compared with normal gravidas, the patients with postpartum hypoxia had a higher occurrence rate of complications, including gestational hypertension (26.09% vs 8.00%), eclampsia (20.65% vs 4.00%), and a lower level of albumin (29.09 ± 0.57 vs 32.74 ± 0.94), thus tended to have longer hospitalization days (7.98 ± 0.40 vs 4.90 ± 0.16), with all P < 0.05. In all 92 cases, the most common cause of postpartum hypoxia was partial atelectasis with pleural effusion (65/92), followed by pulmonary edema (18/92), pneumonia (9/92), pulmonary embolism (6/92), and asthma (4/92). Among the five groups, patients with pneumonia had the longest hospital stay, whereas most patients with partial atelectasis accompanied by pleural effusion were asymptomatic. From the 1-month follow-up, all patients had a favorable prognosis with no apparent symptoms. Among those who underwent re-examination (27/92), no apparent imaging abnormalities were detected.
Conclusion: Postpartum hypoxia, which occurs more commonly in patients with gestational hypertension, is often caused by partial atelectasis with pleural effusion or pulmonary edema. The patient's prognosis was generally satisfactory after treatment.

Keywords:  partial atelectasis; postpartum hypoxia; prognosis; pulmonary edema

DOI:  https://doi.org/10.2147/IJGM.S508028
Medicine (Baltimore). 2025 Mar 21. 104(12): e41479

Impact of hypoxia on the hippocampus: A review.

Guan Lu, Ge Rili, Ma Shuang.

Oxygen is the most abundant chemical substance and is a basic material for human activities. A decline in oxygen concentration affects many physiological processes in the body, leading to pathological changes and even the occurrence of diseases. Therefore, an increasing number of studies have focused on the pathological state of hypoxia. The hippocampus is the most sensitive tissue to oxygen in the brain. The reduction in oxygen concentration affects the morphology and functioning of the hippocampus, including a decline in learning and memory, immunity, and energy metabolism, causing great problems to people's physical and mental health. To keep people healthy in hypoxic environments, adapt to hypoxic environments, and avoid diseases, it is necessary to review the morphology and function of the hippocampus, as well as the effect of oxygen on the hippocampus.

DOI: https://doi.org/10.1097/MD.0000000000041479
IBRO Neurosci Rep. 2025 Jun;18 432-442

Electroacupuncture mitigates cognitive impairments in chronic hypoxia-induced mice by modulating neuroinflammation.

Fang Wan, Kun Zhuang, Ziyu Li, Xiaoqing Wang, Wenyan Li, Yunlong Hou, Wanhui You, Yibing Jiang, Mingye Wang, Pengyu Zhu.

  This study investigates the therapeutic effects and mechanisms of electroacupuncture (EA) on cognitive impairment induced by chronic hypoxia (CH) in mice. Chronic hypoxia was simulated by exposing mice to a 10 % oxygen environment for 8 hours daily over 3 months. The cognitive functions of the mice were assessed through behavioral tests, including the open field test (OFT), Y-maze, and Morris water maze (MWM). Results showed that CH induced significant anxiety-like behaviors and memory impairments in mice. EA treatment, targeting the Baihui (GV20), Shenting (GV24), and Zusanli (ST36) acupoints, significantly ameliorated these behavioral deficits. Histological analyses using HE staining, Nissl staining, and TUNEL assays demonstrated that EA reduced neuronal damage, apoptosis, and myelin loss in the cerebral cortex and hippocampus. Additionally, EA treatment significantly lowered the expression of the pro-inflammatory cytokine TNF-α in brain tissues, suggesting its anti-inflammatory effects. Immunofluorescence and Western blot analyses revealed that EA inhibited the overactivation of microglia and astrocytes in the CH model. Specifically, EA suppressed the expression of Iba1 and GFAP, markers of microglial and astrocytic activation, respectively. Furthermore, EA promoted the polarization of microglia towards the M2 anti-inflammatory phenotype by downregulating iNOS and upregulating Arg1. Similarly, EA reduced the expression of C3, a marker of A1 astrocytes, thereby preventing astrocytic polarization towards the pro-inflammatory state. Organotypic brain slice cultures subjected to oxygen-glucose deprivation (OGD) confirmed that electrical stimulation, akin to EA, inhibited the activation of microglia and astrocytes under hypoxic conditions. In conclusion, EA improves cognitive function in CH-induced mice by reducing neuroinflammation, inhibiting glial cell overactivation, and promoting anti-inflammatory phenotypes. These findings highlight EA's potential as a therapeutic intervention for cognitive impairments related to chronic hypoxia.

Keywords:  Astroglial Polarization; Chronic Hypoxia; Electroacupuncture; Microglial Polarization; Neuroinflammation

DOI:  https://doi.org/10.1016/j.ibneur.2025.03.001
J Clin Med. 2025 Mar 07. pii: 1790. [Epub ahead of print]14(6):

Comparison of the Effects of Endurance Training Conducted in Conditions of Normoxia and Artificial Hypoxia in Patients After Myocardial Infarction.

Agata Nowak-Lis, Zbigniew Nowak, Dominika Grzybowska-Ganszczyk, Paweł Jastrzębski, Anna Konarska-Rawluk.

  Background/Objective: Attention should be paid to the introduction of more functional training methods during the second stage of cardiac rehabilitation, which imitate everyday activities to some extent. The main purpose of this research was to analyze the effects of a 22-day training program carried out in normobaric hypoxic conditions corresponding to the altitude of 3000 m a.s.l. in patients after myocardial infarction and to compare it with the same training conducted in normoxic conditions. Material and Methods: This study included 36 patients after myocardial infarction who underwent percutaneous angioplasty with stent implantation. They were examined before and after 2 days of training sessions: day one, spiroergometric exercise test on a mechanical treadmill, blood collection for laboratory tests; day two, echocardiography of the heart. Than patients underwent 22 days of training in hypoxic conditions. At the end of experiment patients had the same examinations as day one and two. Results: Training conducted in hypoxic conditions had a wider impact on spiroergometrical parameters. Significant, beneficial changes were demonstrated in relation to test duration, distance covered, energy expenditure MET, respiratory exchange ratio RER, as well as resting values of systolic and diastolic blood pressure. There were no changes in parameters for morphology, cytokines, and fibrinogen. There were some differences in relation to echocardiography examinations. Conclusions: The conditions in which the rehabilitation training was conducted affect the level of exercise tolerance. The hypoxic conditions in which the training was conducted affected only two hemodynamic parameters: LVESd and e' septal. Rehabilitation training conducted in various environmental conditions had an impact only on the IL-10 value.

Keywords:  hypoxia; myocardial infarction; normobaric hypoxia; rehabilitation; training

DOI:  https://doi.org/10.3390/jcm14061790
Nat Rev Drug Discov. 2025 Mar 25.

Small-molecule hypoxia therapy.

Sarah Crunkhorn.

DOI: https://doi.org/10.1038/d41573-025-00056-4
J Biomed Res. 2025 Mar 20. 1-16

Molecular pathways in cardiovascular disease under hypoxia: Mechanisms, biomarkers, and therapeutic targets.

Izzatullo Ziyoyiddin O G Li Abdullaev, Ulugbek Gapparjanovich Gayibov, Sirojiddin Zoirovich Omonturdiev, Sobirova Fotima Azamjonovna, Sabina Narimanovna Gayibova, Takhir Fatikhovich Aripov.

  Chronic hypoxia is a key factor in the pathogenesis of cardiovascular diseases, including ischemia, heart failure, and hypertension. Under hypoxic conditions, oxygen deficiency disrupts oxidative phosphorylation in mitochondria, impairing ATP production and generating reactive oxygen species (ROS). These reactive species induce mitochondrial dysfunction, leading to oxidative stress, calcium imbalance, and activation of apoptosis pathways. Mitochondrial K-ATP (mitoK-ATP) and mitochondrial permeability transition pore (mPTP) channels are particularly affected, contributing to membrane potential loss, cytochrome C release, and cell death. This review explores the molecular mechanisms underlying hypoxia-induced cardiovascular diseases, with a focus on mitochondrial impairment, ion channel dysfunction, and ROS overproduction. Additionally, we examine hypoxia-inducible factor 1-alpha (HIF-1α) as a biomarker of cellular adaptation and discuss therapeutic strategies targeting mitochondrial function and oxidative stress. Antioxidants and compounds modulating key ion channels, such as K-ATP and mPTP, are highlighted as promising interventions for mitigating hypoxia-induced damage. Furthermore, we emphasize the potential of integrating in vitro, in vivo, and in silico studies to develop novel therapies aimed at preserving mitochondrial integrity and preventing cardiovascular diseases.

Keywords:  HIF-1α; K-ATP; heart ischemia; ion channel; mPTP; mitochondrion; oxidative stress; reactive oxygen species

DOI:  https://doi.org/10.7555/JBR.38.20240387
Front Immunol. 2025 ;16 1553477

Hypoxia-associated genes as predictors of outcomes in gastric cancer: a genomic approach.

Shuo Yang, Yuhao Jiang, Zhonghua Yang.

   Objective: To investigate the effects of hypoxia-related genes in stomach adenocarcinoma (STAD) and construct an excellent prognostic model.
Methods: RNA expression data and clinical details were retrieved from the TCGA and GEO database dataset. scRNA-seq analysis was conducted on primary gastric cancer samples from GSE183904. Cellular hypoxia status was predicted using the CHPF software. WGCNA and GO-BP/KEGG enrichment of module genes analyses were performed to identify gene modules associated with hypoxia and biological pathway enrichment. A prognostic model was developed employing the LassoCox algorithm. GES-1, AGS, BGC823, and MGC803 cell lines were obtained for qRT-PCR analysis to identify the expression of model genes.
Results: Single-cell atlas within STAD delineated that most of neoplastic cells, fibroblasts, endothelial cells, and myeloid cells were hypoxic. Further analysis of neoplastic cell subpopulations identified four hypoxic subpopulations (H1-H4) and four non-hypoxic subpopulations (N1-N4), with H1 subpopulation had the highest degree of hypoxia. The prognostic model constructed by five H1-specific transcription factors EHF, EIF1AD, GLA, KEAPI, and MAGED2, was demonstrated efficacy in predicting overall survival (OS), with significantly worse OS in high-risk patients. qRT-PCR analysis determined the higher expression level of five H1-specific transcription factors in gastric cancer cell lines than that in normal gastric epithelial cell line.
Conclusion: Hypoxia exerts a profound influence on STAD due to the overexpression of hypoxic cellular subpopulations-specific transcription factors EHF, EIF1AD, GLA, KEAPI, and MAGED2. The novel prognostic model developed by these hypoxia-associated genes presents a novel approach to risk stratification, exhibiting an excellent prognostic value for STAD patients.

Keywords:  hypoxia; prognostic model; qRT-PCR; single-cell RNA sequencing; stomach adenocarcinoma; transcription factor

DOI:  https://doi.org/10.3389/fimmu.2025.1553477
High Alt Med Biol. 2025 Mar 26.

Phenothiazine Confers Neuroprotection via Dpp2/7 in High Altitude Traumatic Brain Injury Mouse Model.

Wenxin Zhang, Yuting Yang, Jing Guo, Fei Hu, Yuan Ma, Qing Ouyang.

  Zhang, Wenxin, Yuting Yang, Jing Guo, Fei Hu, Yuan Ma, and Qing Ouyang. Phenothiazine confers neuroprotection via Dpp2/7 in high altitude traumatic brain injury mouse model. High Alt Med Biol. 00:00-00, 2025. Background: Traumatic brain injury (TBI) in high altitude areas can lead to more severe cerebral edema, higher disability, and mortality than in low altitude areas. This study was designed to evaluate the neuroprotective effects and underlying mechanisms of phenothiazine on TBI at high altitudes. Methods: Mice were kept in a hypobaric chamber for 7 days under simulated conditions of 5,000 m above sea level. A controlled cortical impact (CCI) model was established and followed by phenothiazine (chlorpromazine and promethazine) and Dpp2/7 inhibitor UAMC00039 treatment. Hematoxylin-eosin (HE) staining, immunohistochemistry (IHC), western blot, label-free quantitative proteomics, and real-time quantitative polymerase chain reaction (RT-qPCR) assays were performed to assess the effects of phenothiazine and UAMC00039 on TBI. Results: HE staining confirmed that phenothiazine treatment could ameliorate CCI-induced brain injury. IHC, western blot, and RT-qPCR showed that cell apoptosis was alleviated by phenothiazine after high altitude TBI, as proved by the reduction of cleaved-Caspase-3 and increased Bcl-2 expression. Label-free quantitative proteomics, IHC, and western blot showed that phenothiazine significantly upregulated Dpp2/7 after high altitude TBI. Western blot and IHC showed that UAMC00039 treatment significantly reversed phenothiazine-mediated Bcl-2 upregulation and cleaved-Caspase-3 downregulation after high altitude TBI. Conclusions: The results indicated that phenothiazine offers neuroprotective effects via antiapoptosis after high altitude TBI, and this protective mechanism is associated with Dpp2/7-mediated Bcl-2 expression and Caspase-3 cleaving.

Keywords:  Dpp2/7; TBI; apoptosis; high altitude; neuroprotection; phenothiazine

DOI:  https://doi.org/10.1089/ham.2024.0096
Cells. 2025 Mar 13. pii: 423. [Epub ahead of print]14(6):

Stabilization of Transcription Factor, HIF-1α by Prolylhydroxylase 1 Knockout Reduces Cardiac Injury After Myocardial Infarction in Mice.

Mahesh Thirunavukkarasu, Seetur R Pradeep, Babatunde Oriowo, Sue Ting Lim, Monica Maloney, Shayan Ahmed, Nicole Taylor, David M Russell, Pavayee Socrates, Ethan Batko, Matan Berkovsky, John Alexander Palesty, Nilanjana Maulik.

  Inhibition of HIF-prolyl hydroxylases (PHD1, PHD2, and PHD3) causes the stabilization of hypoxia-inducible factor-1α and -2α (HIF-1α and HIF-2α) to regulate various cell signaling pathways. Hypoxia-inducible factor (HIF) is crucial in regulating signal responses mediated by hypoxia. HIF regulates the transcription of many genes involved in the response to hypoxia and ischemic insult. Our current work investigates the protective effects of PHD1 knockout in mice against myocardial infarction. Study Design: Myocardial infarction (MI) was induced by left anterior descending coronary artery (LAD) ligation (8-12-week-old mice) in both wild-type (WT) and PHD1 knockout (PHD1-/-) mice. WT sham (S) and PHD1-/-S group mice underwent surgery without LAD ligation. Thirty days post-surgery, cardiac functions were measured by echocardiogram. Mice in all the groups were euthanized at various time points for tissue collection post-MI 8 h (gel shift and microarray analysis), 4 days (Western blot analysis), 7 days (blood vessel density), or 30 days (histological analysis). For microarray analysis, WTMI and PHD1-/-MI group mices' heart tissue was used for RNA isolation, then hybridization to a GeneChip™ Mouse Gene 1.0 ST Array as per the manufacturer's instructions. Bioinformatic analysis was performed using the transcriptome analysis console (TAC) to generate a list of differentially regulated genes, followed by ingenuity pathway analysis. Results: The study findings revealed a significant increase in vessel density (capillary and arteriolar density) in the PHD1-/-MI mice compared to those with WTMI. The echocardiographic examination demonstrated that the PHD1-/-MI mice group had an increased ejection fraction and fractional shortening than the WT mice 30 days post-MI. HIF-1α DNA binding activity was higher in PHD1-/-MI mice than in WTMI. The Western blot analysis showed a significant increase in the expression of HSPA12B in the PHD1-/-MI compared to WTMI mice. Bioinformatic analysis using TAC software, Version 4.0.2.15 (1.5 fold, p < 0.05) showed 174 differentially regulated genes. Conclusions: In conclusion, our study showed PHD1 knockout activates several important molecules and signaling pathways, resulting in increased angiogenesis and cardioprotection against myocardial infarction.

Keywords:  HIF-1α; cardiac functions; myocardial infarction; pathway analysis; prolyl hydroxylase-1

DOI:  https://doi.org/10.3390/cells14060423
Int J Pharm. 2025 Mar 24. pii: S0378-5173(25)00358-8. [Epub ahead of print] 125521

Oxygen sensitive drug release using hemoglobin Microbubbles: A new approach to targeting hypoxia in Ultrasound-Mediated drug delivery.

Ghazal Rastegar, Mohammad Musa Salman, Shashank R Sirsi.

  Targeted drug delivery strategies using focused ultrasound (FUS) are gaining prominence in clinical application. FUS offers deep tissue penetration and precise targeting capabilities. The capabilities of FUS in targeted drug delivery are greatly enhanced by the introduction of ultrasound contrast agents (UCAs - also known as microbubbles). This study introduces a novel hypoxia-targeting drug delivery system using hemoglobin microbubbles (HbMBs) conjugated with doxorubicin-loaded liposomes (LDOX). Previously, we reported that HbMBs exhibit significant acoustic response differences between oxygenated and deoxygenated environments due to hemoglobin's conformational changes, which alters the MBs' shell elasticity as well as resonance frequency. In this study, we coated the surface of HBMBs with LDOX to create Lip-HBMB complex and subsequently investigated its drug release at different oxygen partial pressures (pO2) when exposed to an ultrasound field. Results showed significantly higher drug release at lower oxygen levels, with about 10-times higher release at 5 mmHg pO2 than 160 mmHg pO2 at 0.5 W/cm2 US intensity and 3 MHz frequency. This highlights Lip-HbMBs' potential for targeted drug delivery to hypoxic tumor regions, marking a significant advancement in focused ultrasound-mediated drug delivery. This study marks the first-ever report of ultrasound-mediated oxygen-sensitive drug uncaging, which holds promise in enhancing FUS specificity and addressing the challenges posed by metastatic cancer.

Keywords:  Chemotherapy; Drug delivery; Microbubble; Oxygen-sensitive drug release; Targeting drug release; Ultrasound

DOI:  https://doi.org/10.1016/j.ijpharm.2025.125521
Physiol Res. 2025 Mar 24. 74(1): 141-147

Utilizing Hyperbaric Oxygen Therapy to Improve Cognitive Function in Patients With Alzheimer's Disease by Activating Autophagy-Related Signaling Pathways.

B Li, H Li, H Chen, Y Sui, J Zeng, X Lin, Q Fan, Z Song.

To investigate the impact of hyperbaric oxygen therapy (HBOT) on the cognitive function of mice with Alzheimer's disease (AD), while also identifying the cellular pathways associated with autophagy involved in the treatment. Twenty-four APP/PSl double transgenic mice were randomly assigned to either Group A or Group B, while another 24 C57 mice were randomly allocated to Group C or Group D. HBOT was administered to mice in Group B and Group D, and the Morris water maze test was used to assess changes in mice behavior. Histological examination using hematoxylin and eosin staining was conducted to observe pathological alterations in the hippocampus of the mice brain tissue. Polymerase chain reaction (PCR) was employed to analyze autophagy-related gene pathways in the hippocampus of the mice. Following HBOT, mice in Group B exhibited a significant reduction in escape latency and a notable increase in residence time within the target quadrant compared with Group A (P<0.05), as well as Group C and Group D (P<0.01). The hippocampal neurons in Group A and Group B mice exhibited disorganized arrangements, characterized by pyknosis and margination. Conversely, neurons in Group C displayed orderly arrangements, retaining intact structures with round nuclei demonstrating clear nuclear staining and normal morphology. The cellular morphology of mice in Group D remained unaffected. PCR analysis revealed no notable disparity in autophagy-related gene expression between Group A and Group C. However, the expression levels of five genes including Tgfb1, Mapk14, Bid, Atg7, and Akt1, were significantly elevated in Group B compared to Group A. HBOT has the potential to improve the cognitive function in mice modeled with AD. This improvement of cognitive function appears to be mediated by the up-regulation of autophagy-related genes, specifically Tgfb1, Mapk14, Bid, Atg7, and Akt1. These results indicate that HBOT may offer a therapeutic strategy for treating AD by enhancing autophagy mechanisms. Key words Alzheimer's disease, Autophagy, Hyperbaric oxygen, Morris water maze, PCR.
Int Wound J. 2025 Apr;22(4): e70437

RETRACTION: Application of Hyperbaric Oxygen Therapy in Diabetic Foot Ulcers: A Meta-Analysis.

RETRACTION: H.-R. Chen, S.-J. Lu, Q. Wang, M.-L. Li, X.-C. Chen, and B.-Y. Pan, "Application of Hyperbaric Oxygen Therapy in Diabetic Foot Ulcers: A Meta-Analysis," International Wound Journal 21, no. 42024): e14621, https://doi.org/10.1111/iwj.14621. The above article, published online on 26 March 2024, in Wiley Online Library (http://onlinelibrary.wiley.com/), has been retracted by agreement between the journal Editor in Chief, Professor Keith Harding; and John Wiley & Sons Ltd. Following an investigation by the publisher, all parties have concluded that this article was accepted solely on the basis of a compromised peer review process. The editors have therefore decided to retract the article. The authors did not respond to our notice regarding the retraction.

DOI: https://doi.org/10.1111/iwj.70437