bims-oxygme 2025-10-26 papers

bims-oxygme

Biomed News

on Oxygen metabolism

Issue of 2025–10–26
eight papers selected by
Onurkan Karabulut, Berkeley City College

Hypoxia-Induced circPRELID2 Promotes Gastric Cancer Metastasis by Facilitating ZEB2 Translation via PCBP1 O-GlcNAcylation.
Monge's disease at 100 years: Revisiting the origins and endocrine mechanisms of chronic mountain sickness.
Effect of acute intermittent hypoxia to enhance motor functions in adults with incomplete spinal cord injury: A systematic review and meta-analysis.
Xingnao jianshen prescription reduces mitochondrial cristae breakage by protecting GPX1 from oxidation against cerebral ischemia-reperfusion injury.
Pseudohypoxia induced by chemical pollutants: Biochemical evidence of environmental vulnerability.
Metabolic alterations in erythrocytes associated with long-term hypoxia at high altitude.
Transgenerational adaptation to hypoxia.
Association between aging and in vivo mitochondrial oxygen tension (mitoPO2) and oxygen consumption (mitoVO2) in healthy volunteers.

Adv Sci (Weinh). 2025 Oct 21. e05396

Hypoxia-Induced circPRELID2 Promotes Gastric Cancer Metastasis by Facilitating ZEB2 Translation via PCBP1 O-GlcNAcylation.

Pengshan Zhang, Zai Luo, Yitian Xu, Yuan Zhang, Renchao Zhang, Nadina Paerhati, Shaopeng Zhang, Qianqian Cai, Zhengjun Qiu, Chen Huang.

  Circular RNAs (circRNAs) are involved in the occurrence and development of various carcinomas. However, the biogenesis, function and underlying mechanism of hypoxia-induced circRNA in gastric cancer (GC) are poorly understood. Here, a novel circRNA, circPRELID2, which is upregulated by HIF1A under hypoxic conditions, is identified. circPRELID2 is highly expressed in GC tissues, and positively correlates with lymph node invasion, vascular invasion in GC patients. Elevated circPRELID2 promotes the epithelial-mesenchymal transition (EMT) and metastasis of GC cells both in vitro and in vivo under hypoxic conditions. Mechanistically, HIF1A directly binds to the PRELID2 promoter to transcriptionally increase the expression of PRELID2 pre-mRNA in response to hypoxia. Moreover, protein kinase DYRK1A mediates SFPQ phosphorylation to promote the interaction between SFPQ and SAM68, further forming a DYRK1A-SFPQ-SAM68 ternary complex. Subsequently, the DYRK1A-SFPQ-SAM68 complex binds to Alu-containing introns flanking the circPRELID2-forming exons in the PRELID2 pre-mRNA to promote circPRELID2 circularization. Furthermore, circPRELID2 interacts with PCBP1 and promotes the cytoplasmic retention of PCBP1. CircPRELID2 enhances OGT-mediated PCBP1 O-GlcNAcylation at Threonine 99 site in the cytoplasm, which disrupts the binding of PCBP1 to the 3'-UTR of ZEB2, resulting in the reversal of ZEB2 translation silencing, and ultimately promoting the EMT and metastasis of GC cells. These findings reveal a new regulatory mechanism of circRNA biogenesis, and also uncover that circPRELID2 participates in the translation of ZEB2 during GC metastasis via the modulation of PCBP1 O-GlcNAcylation, which provides a promising prognostic biomarker and therapeutic target for GC metastasis.

Keywords:  O‐GlcNAcylation; PCBP1; ZEB2 translation; circPRELID2; gastric cancer

DOI:  https://doi.org/10.1002/advs.202505396
Sci Prog. 2025 Oct-Dec;108(4):108(4): 368504251387827

Monge's disease at 100 years: Revisiting the origins and endocrine mechanisms of chronic mountain sickness.

Gustavo F Gonzales.

  Chronic mountain sickness (CMS), first described by Carlos Monge Medrano in 1925, is characterized by excessive erythrocytosis (EE), hypoxemia, and neurocognitive disturbances in long-term high-altitude residents. This narrative review revisits Monge's contribution in the light of modern research. CMS is now recognized worldwide, where genetic predisposition and environmental stressors jointly shape susceptibility to high-altitude life. Although hypoxia-driven erythropoietin (EPO) stimulation has long been considered the primary mechanism, recent evidence highlights the critical role of sex hormones in modulating erythropoiesis. EE, once the defining feature, is now complemented by symptom-based scoring systems that better capture the syndrome. Testosterone promotes erythroid expansion by stimulating progenitors, enhancing EPO sensitivity, and suppressing hepcidin, whereas estrogens counteract these effects by downregulating GATA1 and modulating hypoxia-inducible pathways. Elevated testosterone or high testosterone-to-estradiol ratios correlate with hemoglobin, hematocrit, and EE in CMS, explaining its greater prevalence and severity in men. Advances in molecular biology have identified the hypoxia-testosterone-EPO axis, with regulators such as SENP1 and GATA1, as central to disease susceptibility. Excessive androgenic signaling also worsens sleep-disordered breathing and cognitive dysfunction, while estrogenic modulation appears protective, opening avenues for prevention and therapy. In conclusion, CMS should be regarded as a multifactorial disorder shaped by hypoxia, hormones, gene-environment interactions, and cellular stress. Despite progress, underdiagnosis and limited healthcare attention in South American highlands remain major challenges, underscoring the relevance of Monge's seminal description.

Keywords:  GATA-1; SENP1; Testosterone; chronic mountain sickness; erythropoiesis; hypoxia

DOI:  https://doi.org/10.1177/00368504251387827
Clin Rehabil. 2025 Oct 21. 2692155251388395

Effect of acute intermittent hypoxia to enhance motor functions in adults with incomplete spinal cord injury: A systematic review and meta-analysis.

Emmanuel Segnon Sogbossi, Bastien Bouffanet, Julien Pincede, Alexandra Ribon-Demars, Gauthier Everard.

  ObjectiveThis systematic review aimed to assess the safety and effectiveness of acute intermittent hypoxia to improve motor outcomes in individuals with incomplete spinal cord injury.Data sourcePubmed, Embase, Scopus, and Cochrane Library databases were searched.Review methodsWe only included randomized controlled trials (published up to September 2025) that met the following criteria: participants were adults with incomplete spinal cord injury; the intervention involved acute intermittent hypoxia with or without motor training; the control group received sham acute intermittent hypoxia with or without motor training; outcomes included motor functions. Risk of bias was evaluated using RoB2 tool. Risk and mean differences were computed, with a random-effects model.ResultsNine randomized controlled trials (n = 114) were included. Overall risk of bias was with some concerns. The review indicates that acute intermittent hypoxia is safe and has good treatment adherence, with low drop-out rates for acute intermittent hypoxia alone (RD = 0.08; 95% confidence interval (CI): -0.11-0.26; I2 = 0%; n = 66) or with gait training (RD = 0.04; 95% CI: -0.11-0.18; I2 = 0%; n = 57). Acute intermittent hypoxia was found to have beneficial effects on walking speed (MD = 5.97; 95% CI: 1.4-10.54; I2 = 0%; n = 53), endurance (MD = 39.39; 95% CI: 1.92-76.86; I2 = 50%; n = 54), muscle strength, and manual dexterity. However, no significant effects were observed on balance functions.ConclusionAcute intermittent hypoxia may be a promising adjunctive therapy to enhance motor function in individuals with incomplete spinal cord injury. Further research with standardized protocols and larger sample sizes is needed to optimize its use in clinical practice.

Keywords:  Spinal cord injuries; gait; hypoxia; meta-analysis; rehabilitation

DOI:  https://doi.org/10.1177/02692155251388395
Phytomedicine. 2025 Oct 10. pii: S0944-7113(25)01007-4. [Epub ahead of print]148 157369

Xingnao jianshen prescription reduces mitochondrial cristae breakage by protecting GPX1 from oxidation against cerebral ischemia-reperfusion injury.

Xinna Wang, Kai Tao, Li Sun, Dongni Ren, Song Xie, Kaige Zhang, Xiao Li, Dexi Zhao, Qian Yang.

   BACKGROUND: Ischemic stroke (IS) is a common cerebrovascular disease. Inhibiting oxidative stress is a recognized therapeutic mechanism for this disease. Xingnao Jianshen prescription (Xnjs) has been clinically applied since its creation in the 1990s, and it has a significant effect in the conservative treatment of acute IS. However, due to a lack of objective studies, the mechanism underlying its pharmacological effects has not been elucidated.
METHODS: LC‒MS and GC‒MS were employed to analyze the chemical components of Xnjs. A rat model of middle cerebral artery occlusion (MCAO) was constructed to explore the mechanism underlying its pharmacological efficacy. Concurrently, we examined the possible pathways and targets of Xnjs using network pharmacological analysis and proteomics. This included methods such as transmission electron microscopy, Western blotting, flow cytometry, fluorescent probe live cell labeling, and lentiviral stable cell lines, which aims to validate mitochondrial oxidative stress both in vivo and in vitro. Molecular docking analysis and surface plasmon resonance were applied jointly to determine the binding affinity between the potential active ingredients and target proteins RESULTS: Xnjs was found to be composed of a total of 398 natural monomer products by a chemical composition test. In the MCAO model, Xnjs has demonstrated efficacy in alleviating cerebral ischemia-reperfusion-induced neurological dysfunction and enhancing mitochondrial integrity, particularly in the high-dose group. This has been achieved by inhibiting excessive oxidative stress responses in the central nervous system and mitigating apoptotic damage. This study has successfully identified GPX1 as the core target of Xnjs, which has the potential to promote active expression of GPX1, thereby contributing to the maintenance of a more complete mitochondrial cristae structure. In GPX1-knockdown cell lines, Xnjs was observed to protect neuronal cells from entering the damaging apoptotic stage, reduce GSH depletion and inhibit ROS production on mitochondria to mitigate mitochondrial cristae rupture. The results of this study also screened out six active monomeric components in Xnjs, all of which appeared to bind to GPX1 to varying degrees. While detecting their relative content in Xnjs compounds, the antioxidant stress effects of the mixed active ingredient group (6CP) were also preliminarily verified.
CONCLUSION: The findings of the research indicate that Xnjs has the capacity to enhance the biological activity of the GPX1 protein, thereby ensuring the preservation of mitochondrial cristae. This results in the augmentation of antioxidative stress and the mitigation of the extent of pathological apoptosis in cells. Based on the above drug target proteins, potential active ingredients in Xnjs were screened to lay the foundation for further pharmacological research.

Keywords:  GPX1; Ischemia‒reperfusion injury; Mitochondrion; Oxidative stress; Xingnao Jianshen prescription

DOI:  https://doi.org/10.1016/j.phymed.2025.157369
Ecotoxicol Environ Saf. 2025 Oct 18. pii: S0147-6513(25)01588-X. [Epub ahead of print]305 119243

Pseudohypoxia induced by chemical pollutants: Biochemical evidence of environmental vulnerability.

Chenxu Hu, Zehua Tao, Yanli Lin, Jian Chen, Ngwa Adeline Ngeng, Michael Aschner, Alexey A Tinkov, Rongzhu Lu.

  Chemical pollutants can abnormally elevate hypoxia-inducible factor 1-alpha (HIF-1α) levels under normoxic conditions, leading to pseudohypoxia. This condition disrupts normal cellular energy metabolism, gene expression, and signal transduction, thereby inducing detrimental physiological effects. Pseudohypoxia can also increase the risk of various diseases, including cancer, cardiovascular diseases, and chronic respiratory diseases, while adversely affecting disease treatment and prognosis. Focusing on the intersection between environmental pollution and hypoxia signaling pathways, this review proposes a novel concept that chemical pollutants can induce pseudohypoxia and elucidates its underlying mechanisms. We also identify various environmental pollutants that induce pseudohypoxia, including but not limited to metals and metalloids (e.g., cadmium, cobalt, arsenic), persistent organic pollutants (e.g., BPA, dioxins, PCBs), and atmospheric particulate pollutants (e.g., PM2.5, diesel exhaust particles), and examine the complex interplay between these pollutants, pseudohypoxia, and various diseases. This review aims to offer novel strategies for managing pseudohypoxia caused by environmental exposures, thereby offering new insights into the prevention and treatment of environmental exposure-related disease and susceptibility.

Keywords:  Atmospheric particulate matter; Chemical pollutants; Environmental vulnerability; HIF-1α; Heavy metals; Hypoxia; Hypoxic response; Pseudohypoxia

DOI:  https://doi.org/10.1016/j.ecoenv.2025.119243
BMC Genomics. 2025 Oct 21. 26(1): 940

Metabolic alterations in erythrocytes associated with long-term hypoxia at high altitude.

Teng Yu, Chengning Tan, Chao Zhou, Lanyue Hu, Xiaojie Wang, Qian Ran, Yanni Xiao, Lixin Xiang, Yangzhou Jiang, Xiaoliang Li, Peipei Xue, Maoshan Chen, Li Chen, Zhongjun Li.

   BACKGROUND: Red blood cell (RBC) plays a vital role in the adaptations to hypoxia at high altitudes, however, the metabolic pattern of RBC under long-term hypoxia remains unknown. Here, we employed broad- and energy-targeted metabolomics approaches to study the differences in the RBC among the three groups: lowlanders living in plain areas, lowlanders acclimatized to plateaus for more than 10 years, and native Tibetans.
RESULTS: Compared with lowlanders, the glycolytic flux remained stable in acclimatized lowlanders and adapted Tibetans, and purine metabolism did not correspondingly increase. Notably, the oxidative pentose phosphate pathway was reduced in both acclimatized lowlanders and adapted Tibetans, and a consistent decrease was observed in the reduced glutathione, a key metabolite of the redox system. Next, reduced Superoxide dismutase activity and enhanced catalase activity exhibited distinct pattern in the antioxidant system. Further validation using proteomics confirmed that the major antioxidant enzymes have undergone extensive adaptive changes under long-term hypoxia, including a decrease in Superoxide dismutase 1, peroxiredoxin 1/2, and thioredoxin reductase 1, while catalase has increased.
CONCLUSIONS: In conclusion, metabolomics and validation measurements reveal a distinct remodeling of the antioxidant defense system in erythrocytes under long-term hypoxia and suggest a pronounced influence of environmental factors on erythrocyte metabolism, offering new insights into hypoxic adaptations.

Keywords:  High altitude; Hypoxia; Metabolomics; Oxidative damage; Red blood cell

DOI:  https://doi.org/10.1186/s12864-025-12107-6
Sci Adv. 2025 Oct 24. 11(43): eadv9451

Transgenerational adaptation to hypoxia.

Kathleen Kim, Ariel Telger, Gautam Sarkar, Sharan Surya, M Hafiz Rothi, Michael P Meers, Simon Yuan Wang, Eric Lieberman Greer.

Epigenetic inheritance alerts naïve descendants to prepare for stresses that could still be present, whereas distant descendants return to a basal state after several generations without stress. However, organisms are frequently exposed to stresses successively across generations. We found that parental hypoxia exposure increased P0 longevity, caused intergenerational lipid reduction, and elicited transgenerational fertility reduction that was dependent on generationally transmitted small RNAs. Here, we find that Caenorhabditis elegans adapt to repeated generational stresses. We show that, upon two repeated generational hypoxia exposures, the life-span extension is eliminated, and after four repeated generational hypoxia exposures, the reduced fertility is eliminated. Transgenerational adaptation also occurred in response to changes in glucose availability. Transgenerational hypoxia adaptation is dependent on the H3K27 trimethyltransferase PRC2 complex, and we identified transgenerationally adapted genes. Our findings reveal that transgenerational adaptation occurs and suggest that H3K27me3 is a critical modification for adapting to repeated generational stresses.

DOI: https://doi.org/10.1126/sciadv.adv9451
J Appl Physiol (1985). 2025 Oct 20.

Association between aging and in vivo mitochondrial oxygen tension (mitoPO2) and oxygen consumption (mitoVO2) in healthy volunteers.

Calvin J de Wijs, Annika M van Smaalen, Lucia W J M Streng, Robert J Stolker, Egbert G Mik, Floor A Harms.

  The Cellular Oxygen METabolism (COMET®) device provides validated bedside in vivo measurements of mitochondrial oxygen tension (mitoPO2) and consumption (mitoVO2). Because mitochondrial function has been shown in experimental in vivo and ex vivo studies to potentially alter with age, it is important to establish whether age itself influences these in vivo measurements. The aim of this single-center prospective observational study was to determine whether mitoPO2 and mitoVO2 values are influenced by age, thereby ensuring their validity for use across age groups. The aim of the study was not to evaluate COMET® as monitor of aging. Using the COMET® device, mitoPO2 and mitoVO2 were measured at the upper arm and sternum in 176 healthy participants aged 18-90 years. The mean arm mitoPO2 was 75.3 ± 28.7 mmHg (mean ± SD), while the mean sternal mitoPO2 was 65.8 ± 23.6 mmHg. Multivariable linear regression did not demonstrate a significant age-related change in mitoPO2. Conversely, the mean arm mitoVO2 was 6.37 ± 2.07 mmHgꞏs-1, and the median sternal mitoVO2 was 7.16 mmHgꞏs-1 [IQR 5.63-9.17]. Multivariable linear models at both sites demonstrated a significant negative association between age and mitoVO2. No significant sex differences were observed for either parameter. These findings reveal that while mitoPO2 remains unaffected by age, mitoVO2 shows a significant negative association with increasing age. This distinction suggests that mitoPO2 can be interpreted independent of age, whereas mitoVO2 requires age-informed consideration. By profiling healthy volunteers across four decades, we establish preliminary age-informed normative ranges for epidermal mitoPO2 and mitoVO2.

Keywords:  Aging; Mitochondria; Mitochondrial Oxygen Consumption; Mitochondrial Oxygen Tension; Sex

DOI:  https://doi.org/10.1152/japplphysiol.00270.2025