bims-oxygme Biomed News
on Oxygen metabolism
Issue of 2025–08–31
twelve papers selected by
Onurkan Karabulut, Berkeley City College
  1. The uteroplacental circulation at high altitude: adaptation and maladaptation.
  2. Hypoxia-driven angiogenesis in breast cancer mechanisms and therapeutic targets: a narrative review.
  3. Pregnancy at high altitude: evolutionary and historical perspectives.
  4. Beyond blood flow: the multifaceted role of AMPK in regulating fetal growth at high altitudes.
  5. Pregnancy at high altitude: the challenge of hypoxia.
  6. A clinician's musings on oxygen: Too little or too much with life in the balance.
  7. High-altitude pregnancy adaptation: evidence from a Himalayan population in Leh.
  8. The Impact of a High-Fat Diet (HFD) on Mouse Behavior, Neurotransmitters, Inflammation, and Gut-Brain Axis Metabolism under Hypoxic Conditions.
  9. GSK-3α regulates miRNAs associated with transcriptional and metabolic processes in human cardiomyocytes under hypoxia.
  10. Tackling tumor hypoxia: advances in breaking the oncogenic HIF-1α-p300/CBP alliance.
  11. The Relationship Between Inflammation and the Development of Cerebral Ischaemia and Hypoxia in Traumatic Brain Injury-A Narrative Review.
  12. Accuracy of Pulse-Oximetry in Non-white Patients.
  1. Philos Trans R Soc Lond B Biol Sci. 2025 Aug 21. 380(1933): 20240179
    The uteroplacental circulation at high altitude: adaptation and maladaptation.
    Xiang-Qun Hu, Chiranjib Dasgupta, Yu Gao, Isaac Kremsky, Eugenia Mata-Greenwood, Lubo Zhang.
      The greatest challenge of living at high altitude is hypoxia. Hypoxia imposes immense impacts on reproduction. Gestation at high altitude is associated with high incidence of fetal growth restriction (FGR) and pre-eclampsia owing to maladaptation of uteroplacental circulation/placenta insufficiency and oxygen delivery to the fetus. Both disorders have been replicated in animal models at low altitude by hypoxic exposure. Intriguingly, high-altitude natives such as Tibetans and Andeans are relatively protected from FGR. Hypoxia constitutes a severe insult to the uteroplacental circulation. In response to hypoxia, a range of dynamic responses occurs in uteroplacental cells/tissues. To offset detrimental effects imposed by hypoxia, uteroplacental cells/tissues also develop countermeasure mechanisms. The uteroplacental circulation adaptation to high altitude depends on whether a novel homeostasis is achieved.This article is part of the discussion meeting issue 'Pregnancy at high altitude: the challenge of hypoxia'.
    Keywords:  adaptation; fetal growth restriction; high altitude; pre-eclampsia; uteroplacental circulation
    DOI:  https://doi.org/10.1098/rstb.2024.0179
  2. Ann Med Surg (Lond). 2025 Jul;87(7): 4246-4254
    Hypoxia-driven angiogenesis in breast cancer mechanisms and therapeutic targets: a narrative review.
    Emmanuel Ifeanyi Obeagu.
      Breast cancer remains a significant global health challenge, with hypoxia playing a crucial role in its progression. Hypoxia, defined as reduced oxygen availability, is a hallmark of solid tumors and particularly influences the tumor microenvironment in breast cancer. Under hypoxic conditions, tumors activate a variety of molecular responses that promote survival, including the stabilization of hypoxia-inducible factors (HIFs). These transcription factors regulate the expression of pro-angiogenic genes, such as vascular endothelial growth factor (VEGF), which drive angiogenesis and support tumor growth. However, the vasculature formed under hypoxic conditions is often dysfunctional, contributing to tumor progression, metastasis, and resistance to therapies. This review explores the mechanisms by which hypoxia drives angiogenesis in breast cancer, emphasizing the roles of HIFs, VEGF signaling, and metabolic reprogramming. Angiogenesis, a critical process for tumor survival and growth, is primarily mediated by the induction of VEGF under hypoxic conditions. VEGF acts on endothelial cells to promote blood vessel formation, ensuring the tumor receives sufficient oxygen and nutrients. However, the vessels formed are typically leaky and inefficient, exacerbating the hypoxic environment and perpetuating a cycle of tumor progression. The metabolic reprogramming that occurs in hypoxic tumor cells, such as the shift toward glycolysis (the Warburg effect), also plays a pivotal role in sustaining angiogenesis. The resulting acidic conditions further enhance VEGF production and endothelial cell migration, supporting continued tumor growth and metastasis.
    Keywords:  VEGF; angiogenesis; breast cancer; hypoxia; therapeutic targets
    DOI:  https://doi.org/10.1097/MS9.0000000000003411
  3. Philos Trans R Soc Lond B Biol Sci. 2025 Aug 21. 380(1933): 20240168
    Pregnancy at high altitude: evolutionary and historical perspectives.
    Lorna G Moore.
      Pregnancy encompasses the portion of the life cycle subjected to among the strongest of evolutionary pressures owing to the nature of mammalian reproduction and the characteristics of the human species. The pioneering work of early investigators such as Joseph Barcroft, Donald Barron, Giacomo Meschia, James Metcalfe and others laid the groundwork for identifying constraints affecting each of the three major players in mammalian reproduction-fetus, placenta and mother-for meeting the increased oxygen and other nutrient demands required for fetal growth and maternal wellbeing. The papers comprising this special issue illustrate how each player responds under the conditions of the chronic hypoxia present at high altitude, as well as under other circumstances limiting oxygen supply. Recognizing the contributions of each player and the importance of their interactions can point the way towards actionable targets for developing new therapies for improving both immediate and later-in-life outcomes for both mother and child.This article is part of the discussion meeting issue 'Pregnancy at high altitude: the challenge of hypoxia'.
    Keywords:  evolution; fetal growth restriction; hypoxia; natural selection; pre-eclampsia
    DOI:  https://doi.org/10.1098/rstb.2024.0168
  4. Philos Trans R Soc Lond B Biol Sci. 2025 Aug 21. 380(1933): 20240173
    Beyond blood flow: the multifaceted role of AMPK in regulating fetal growth at high altitudes.
    Colleen G Julian.
      Over the past several decades, scientific advancements have propelled efforts towards identifying the mechanisms influencing uteroplacental and fetoplacental perfusion and their role in maintaining sufficient fetal growth. Despite substantial progress, many questions regarding the fundamental biological pathways regulating human fetal growth remain unanswered. High-altitude (HA) studies have long captured the attention of reproductive scientists interested in such questions, given the profound effect of ambient hypoxia on suppressing birth weight and the pregnancy-associated rise in uterine artery (UA) blood flow. However, the lower UA flows cannot be solely responsible for reduced fetal growth at HA, as uterine oxygen supply exceeds placental and fetal oxygen consumption. This suggests that reduced uteroplacental blood flow triggers metabolic responses within the maternal-placental-fetal unit to align fetal growth with oxygen availability. Through the presentation of molecular and physiological studies, this Review proposes that the adenosine monophosphate kinase signalling pathway coordinates uteroplacental perfusion and metabolism in HA pregnancy, regulating fetal growth through its dual roles as a potent vasodilator and a regulator of cellular energy homeostasis. Understanding the mechanisms orchestrating crosstalk between metabolism and perfusion within the maternal-placental-fetal unit at HA will provide deeper insight into the mechanisms by which hypoxia influences fetal growth more generally.This article is part of the discussion meeting issue 'Pregnancy at high altitude: the challenge of hypoxia'.
    Keywords:  AMPK; fetal growth; high altitude; maternal haemodynamics; oxidative metabolism; uteroplacental blood flow
    DOI:  https://doi.org/10.1098/rstb.2024.0173
  5. Philos Trans R Soc Lond B Biol Sci. 2025 Aug 21. 380(1933): 20240167
    Pregnancy at high altitude: the challenge of hypoxia.
    Graham J Burton, Lorna G Moore, Dino A Giussani, Andrew J Murray.
      
    Keywords:  high altitude; hypoxia; pregnancy
    DOI:  https://doi.org/10.1098/rstb.2024.0167
  6. J Perinatol. 2025 Aug 20.
    A clinician's musings on oxygen: Too little or too much with life in the balance.
    David K Stevenson, Ronald J Wong, Jonathan D Reiss, Ivana Marić, Anca M Paşca, Terence L Ahern.
      The most abundant element on Earth, oxygen (O2) is essential for all complex, eukaryotic life. Because under- (hypoxia) or overexposure (hyperoxia) to O2 can be detrimental, achieving the ideal balance is crucial for human survival. In this perspective, we discuss the fundamental role of hemoglobin in O2 transport and tissue oxygenation. We also discuss the role that O2. can play in oxidative stress, sometimes initiating inflammatory cascades in vulnerable individuals, such as those with deficiencies in antioxidant defenses or with immune dysregulation. Preterm newborns may be especially prone to such oxidative injury.
    DOI:  https://doi.org/10.1038/s41372-025-02398-8
  7. Philos Trans R Soc Lond B Biol Sci. 2025 Aug 21. 380(1933): 20240396
    High-altitude pregnancy adaptation: evidence from a Himalayan population in Leh.
    Sara L Hillman, Padma Dolma.
      Leh, Ladakh, is situated at an altitude of more than 3500 metres above sea level (masl) and serves as a natural hypoxic environment for studying the effects of a low-oxygen environment on pregnancy. Over a 10 year collaboration, pregnant women in Leh were recruited and studied, alongside their partners and offspring at birth. The aim was to better elucidate underlying mechanisms that might both protect from, as well as predispose to, poor fetal growth. Phenotypic data were analysed alongside genomic data generated by the Infinium™ Global Screening Array-24 BeadChip. Patient records from low-altitude sites (Bylakuppe 850 m a.s.l) and Delhi (200 m) were compared with data from Leh. A cohort of 318 pregnant women in Ladakh were studied, with an average birthweight for those born at term of 3.15 kg. Compared with women who delivered an appropriate for gestational age (AGA) baby in Leh, those who delivered a small for gestational age (SGA) (<10th birth weight centile) were statistically older and lighter and had smaller maternal uterine artery diameters at 18-22 weeks of gestation. This difference was not maintained between AGA and SGA babies at low altitude in the Delhi cohort. Genetic analysis of Ladakh babies suggested a genetic history most closely related to neighbouring Tibeto-Burman-speaking populations and birth weight analysis replicated previous identified SNPs related to metabolic, skeletal and height genes, offering novel avenues of investigation.This article is part of the discussion meeting issue 'Pregnancy at high altitude: the challenge of hypoxia'.
    Keywords:  Ladakh; birth weight; hypoxia
    DOI:  https://doi.org/10.1098/rstb.2024.0396
  8. Behav Brain Res. 2025 Aug 19. pii: S0166-4328(25)00369-9. [Epub ahead of print] 115782
    The Impact of a High-Fat Diet (HFD) on Mouse Behavior, Neurotransmitters, Inflammation, and Gut-Brain Axis Metabolism under Hypoxic Conditions.
    Yajun Qiao, Ruiying Cheng, Huimin Zheng, Juan Guo, Lin Rong, Guoqiang Li, Lixin Wei, Tingting Gao, Hongtao Bi.
      In the context of the increasing global prevalence of mental health disorders, depression and anxiety have emerged as significant public health challenges. Notably, the incidence rates are higher in plateau regions. This study aimed to investigate the effects and underlying mechanisms of a high-fat diet (HFD) and hypoxic conditions on mouse behavior. The mice were subjected to different diets (a HFD or a normal diet) and placed in a hypoxic environment. This study explored relevant mechanisms through the measurement of physical and behavioral indicators, pathological assessments, biochemical analyses, evaluation of gut microbiota diversity, and metabolomics. The results indicated that a HFD induced obesity in mice under hypoxic conditions, leading to abnormal behavior and reduced synthesis of neurotransmitters such as 5-hydroxytryptaminergic (5-HT), norepinephrine (NE), dopamine (DA), and gamma-aminobutyric acid (GABA). Additionally, a HFD may synergize with increased hypoxia-inducible factor (HIF) expression under hypoxic conditions, exacerbating multitissue inflammation, increasing proinflammatory factor levels, decreasing anti-inflammatory factor levels, and causing systemic inflammation due to gut injury, thereby damaging brain and gut tissues. Furthermore, a HFD altered the gut microbiota diversity, reducing beneficial bacteria while increasing harmful bacteria. KEGG pathway analysis and metabolomics revealed that the brain-gut metabolic pathway clustered around kynurenine metabolism, with metabolites such as kynurenic acid, 2-oxoadipic acid, (2-oxo-2,3-dihydro-1 h-indol-3-yl) acetic acid, and D-kynurenine being reduced, which are associated with inflammatory and depressive/anxious behaviors. Subsequent Spearman correlation analysis revealed an interaction network among all factors, with kynurenic acid positioned at the core, serving as a key hub for interactions. Under dual stimulation from hypoxia and a HFD, this network becomes imbalanced, inducing cerebral and gut metabolic disorders and abnormal behaviors. This study elucidates the multifactorial mechanisms underlying abnormal behavior caused by a HFD and hypoxia in mice, providing a foundation for future research and prevention and treatment strategies for mental health disorders in plateau regions.
    Keywords:  behavioral abnormalities; brain gut axis; high-fat diet; hypoxic environment; inflammatory response
    DOI:  https://doi.org/10.1016/j.bbr.2025.115782
  9. Biochem J. 2025 Aug 14. pii: BCJ20253208. [Epub ahead of print]
    GSK-3α regulates miRNAs associated with transcriptional and metabolic processes in human cardiomyocytes under hypoxia.
    Firdos Ahmad, Hezlin Marzook, Musa Idris, Omama Dawuod, Megna Srinivas, Asima Karim, Mohamed Saleh, Rizwan Qaisar.
      Glycogen synthase kinase-3α (GSK-3α) is a multifunctional kinase plays roles in the pathogenesis of various cardiac diseases, including ischemia and pressure overload and ischemia-reperfusion-induced injury. It regulates key cellular processes such as cardiac cell proliferation, apoptosis, metabolism, and inflammation. However, its role in regulating cardiac microRNAs (miRNAs) remains unknown. To explore the role of GSK-3α in regulating miRNAs, we conducted an unbiased miRNA sequencing analysis in human GSK-3α overexpressing AC16 cardiomyocytes (GOC) under hypoxic conditions. Transcriptomic analysis demonstrated numerous differentially expressed miRNAs crucial for transcriptional, inflammatory, and various metabolic processes of the cell. Amongst 184 differentially expressed miRNAs, hsa-miR-3934-5p, hsa-miR-139-5p and hsa-miR-185-5p were the most upregulated and hsa-miR-193b-3p, hsa-miR-181a-2-3p and hsa-miR-369-3p were the most downregulated in GOC vs. control cells subjected to hypoxia. Gene Ontology (GO) term analysis demonstrated a significant set of genes associated with the terms regulation of transcription, cellular protein modification process, and cellular aromatic compound metabolic process and nucleotide binding in GOC. KEGG pathway analysis further revealed enrichment of key pathways including metabolic, cytokine-cytokine receptor interaction, cAMP and MAPK signaling pathways in GOC challenged with hypoxia. Collectively, these findings reveal a novel mechanism by which GSK-3α regulates a network of miRNAs in human cardiomyocytes required for critical transcriptional, metabolic, and signaling responses including MAPK and inflammatory pathways under hypoxic stress. GSK-3α-mediated miRNA dysregulation may contribute to the pathophysiological changes observed in ischemia-induced cardiac injury.
    Keywords:  Cardiomyocytes; GSK-3alpha; Hypoxia; Inflammation; Ischemia; Metabolism; microRNA
    DOI:  https://doi.org/10.1042/BCJ20253208
  10. Invest New Drugs. 2025 Aug 21.
    Tackling tumor hypoxia: advances in breaking the oncogenic HIF-1α-p300/CBP alliance.
    Emadeldin M Kamel, Sally Mostafa Khadrawy, Ahmed A Allam, Noha A Ahmed, Faris F Aba Alkhayl, Al Mokhtar Lamsabhi.
      The ability of tumor cells to survive under low-oxygen conditions is largely attributed to the hypoxia-inducible factor-1 (HIF-1) pathway, in which HIF-1α forms a functional complex with the transcriptional co-activators p300/CBP. This interaction drives the expression of genes that promote angiogenesis, metabolic reprogramming, and immune evasion and correlates with advanced disease and poor outcomes in diverse cancer types. In recent years, extensive efforts have sought to disrupt the HIF-1α-p300/CBP axis, leveraging strategies that include blocking protein-protein binding, inhibiting acetyltransferase activity, and modulating post-translational modifications that stabilize HIF-1α. A range of small-molecule inhibitors, derived either synthetically or from natural sources such as fungal metabolites and plant polyphenols, have demonstrated efficacy in preclinical cancer models by attenuating tumor hypoxia adaptations and sensitizing malignant cells to chemotherapies and radiotherapies. Although many of these compounds exhibit favorable anti-tumor activity, issues of specificity, drug delivery, toxicity, and potential resistance mechanisms remain. This review highlights the current understanding of HIF-1α-p300/CBP biology, examines small-molecule compounds that target this critical transcriptional interface, and evaluates preclinical evidence validating their therapeutic promise. We also discuss emerging challenges in translating these findings to clinical practice, emphasizing combination treatment strategies, biomarker-driven patient selection, and refined drug formulations to optimize efficacy and safety. By offering a detailed overview of the HIF-1α-p300/CBP landscape, this review underscores the potential of disabling tumor hypoxia responses as an innovative approach to combat cancer progression.
    Keywords:  HIF-1α– p300/CBP; Hypoxia-inducible factor-1; Protein-Protein Interaction; Tumor hypoxia
    DOI:  https://doi.org/10.1007/s10637-025-01570-3
  11. Int J Mol Sci. 2025 Aug 20. pii: 8066. [Epub ahead of print]26(16):
    The Relationship Between Inflammation and the Development of Cerebral Ischaemia and Hypoxia in Traumatic Brain Injury-A Narrative Review.
    Alan Nimmo, Alexander Younsi.
      Traumatic brain injuries (TBI) represent a leading cause of morbidity and mortality globally. Whilst clinical care has significantly improved in recent years, there is still significant scope to improve patient outcomes, particularly in relation to quality of life. However, there is a window of opportunity for clinical intervention, since most of the mortality and morbidity is associated with secondary injury processes that arise after the initial trauma. In the brain, as with any tissue, inflammation plays an important role in the response to injury. However, particularly with severe injuries, an excessive inflammatory response can have detrimental effects. Following TBI, inflammation can lead to the development of cerebral oedema and a rise in intracranial pressure. Without effective control, these processes can rapidly lead to patient deterioration. This narrative review focusses on the role of inflammation in TBI in order to examine the strategies that may help improve patient outcomes. Whilst there is clearly a relationship between the development of cerebral oedema, rising intracranial pressure (ICP), and poor patient prognosis, there are also discrepancies in terms of their impact on patient outcomes. In addition to causing a rise in ICP, this review examines in what other ways inflammation and the development of cerebral oedema may contribute to the injury process. The potential for these factors to impact upon microvascular function and reduce cerebral tissue perfusion and oxygenation is explored. In addition, the impact of TBI on glymphatic function is discussed. Following an evaluation of the potential injury processes, the scope for intervention and the development of novel therapeutic approaches is explored.
    Keywords:  blood-brain barrier; capillary stalling; cerebral oedema; glymphatic system; inflammation; intracranial hypertension; neuroinflammation; thrombo-inflammation; traumatic brain injury; vascular stasis
    DOI:  https://doi.org/10.3390/ijms26168066
  12. Crit Care Nurs Clin North Am. 2025 Sep;pii: S0899-5885(25)00035-8. [Epub ahead of print]37(3): 447-460
    Accuracy of Pulse-Oximetry in Non-white Patients.
    John J Gallagher, Jennifer Lynn Adamski.
      Pulse oximeters are widely used to monitor saturation of peripheral oxygen (SpO2) in the clinical setting. Patients with dark skin pigmentation are at risk for hidden hypoxemia due to overestimation of SpO2 compared to true arterial oxygen saturation resulting from melanin absorption of the red and infrared light sources. Clinicians must be aware of this potential inaccuracy when interpreting SpO2 value, considering the overall assessment of the patient. Ongoing improvement of current and emerging oxygen monitoring technology is essential to improve accuracy and equitable care for all patients.
    Keywords:  Functional oxygen saturation; Melanin; Occult hypoxemia; Pulse oximetry; Skin Tone; Skin pigmentation
    DOI:  https://doi.org/10.1016/j.cnc.2025.05.006
This page is being maintained by Thomas Krichel. It was last updated on 2025‒09‒11 at 0:38.