bims-oxygme 2025-05-11 papers

bims-oxygme

Biomed News

on Oxygen metabolism

Issue of 2025–05–11
eleven papers selected by
Onurkan Karabulut, Berkeley City College

Tumor hypoxia: Classification, detection, and its critical role in cancer progression.
Bubbler system design for regulating media oxygen levels in an open testing environment.
Defining the hypoxic thresholds that trigger blood-brain barrier disruption: the effect of age.
Effects of Heat and Hypoxia Training on the Fat Oxidation Capacity of Competitive Athletes.
Hypoxia and HIF-1 inhibition enhance lentiviral transduction efficiency: a novel strategy for gene delivery optimization.
Polarized macrophages modulate cardiac structure and contractility under hypoxia in novel immuno-heart on a chip.
Chronic Mountain Sickness: A Comprehensive Review of Current Management and Proposals for Novel Therapies.
Altitude and Paraganglioma.
[Progress on the mechanism and application of hyperbaric oxygen therapy for neurodegenerative diseases].
Electroacupuncture Inhibits Ferroptosis by Modulating Iron Metabolism and Oxidative Stress to Alleviate Cerebral Ischemia-Reperfusion Injury.
Gut microbiota modulates lung gene expression and metabolism to aid SD rats in adapting to low-pressure hypoxia.

Biomol Biomed. 2025 Apr 30.

Tumor hypoxia: Classification, detection, and its critical role in cancer progression.

Yan Zhao, Bing Zhong, Jing-Yi Cao, Qian Wang, Jie Liang, Ke Lu, Sheng-Ming Lu.

Hypoxia is a common feature of solid tumors and plays a critical role in cancer progression. A thorough understanding of tumor hypoxia is essential for gaining deeper insights into various aspects of cancer biology. This review examines the key factors contributing to tumor hypoxia, such as inadequate blood supply and oxygen delivery resulting from rapid tumor growth. We present a detailed classification of hypoxic regions and provide an overview of current methods used to identify these areas-from molecular techniques to imaging approaches-offering a comprehensive and multifaceted perspective. Additionally, we explore the mechanisms by which hypoxia drives tumor progression. Under low-oxygen conditions, tumor cells can alter their biological behavior, influencing processes such as cell proliferation, immune evasion, and the maintenance of tumor stem cells. By addressing these dimensions, we aim to enhance understanding of how hypoxia contributes to cancer development. Through this in-depth exploration, we hope this review will offer valuable insights to guide future research and clinical applications.

DOI: https://doi.org/10.17305/bb.2025.12318
J Biomech Eng. 2025 May 09. 1-23

Bubbler system design for regulating media oxygen levels in an open testing environment.

Margaret Capalbo, Spencer Szczesny.

Many biological processes are affected by hypoxia. For example, hypoxia has been suggested to be a driver of tendon degeneration especially in conjunction with mechanical stimulation. To better study the effects of both factors on tendon degeneration, tendon explant studies can be useful. However, such explant models are complicated by the need of an incubator to control the oxygen levels, limiting the types of experiments that can be done. In this paper, we describe the design of bubbler system to alter oxygen levels for experiments conducted in an open environment. The basin volume, basin surface area-to-volume ratio, total system volume, and pump flow rate were optimized to obtain the lowest possible oxygen level. Oxygen levels were most sensitive to the total system volume and pump flow rates with higher values for both parameters leading to lower oxygen readings. This bubbler system was able to reach and maintain hypoxic levels sufficient to conduct future tendon explant experiments to understand the mechanism driving tendinopathy.

DOI: https://doi.org/10.1115/1.4068635
Aging (Albany NY). 2025 May 01. null

Defining the hypoxic thresholds that trigger blood-brain barrier disruption: the effect of age.

Arjun Sapkota, Sebok K Halder, Richard Milner.

  Chronic mild hypoxia (CMH; 8% O2) triggers transient blood-brain barrier (BBB) disruption, an effect greatly increased with age. As BBB disruption predisposes to neuronal death and cognitive decline, here we defined the hypoxic thresholds that trigger BBB breakdown in young and aged mice, and then defined the age at which hypoxia-induced BBB disruption significantly increases. Dual-immunofluorescence of brain sections demonstrated that the thresholds required to trigger hypoxia-induced BBB disruption (CD31/fibrinogen) and endothelial proliferation (CD31/Ki67) were much lower in aged mice (15% O2) compared to young (13% O2). Hypoxia-induced endothelial proliferation was relatively constant across the age range, but advanced age strongly enhanced the degree of BBB disruption (4-6-fold greater in 23 months vs. 2 months old). While the BBB became more vulnerable to hypoxic disruption at 12-15 months, a large step-up also occurred at the surprisingly young age 2-6 months. Our data demonstrates that the aged BBB is far more sensitive to hypoxia-induced BBB disruption than the young and define the hypoxic thresholds that trigger hypoxia-induced BBB disruption in young and aged mice. This information has translational implications for people exposed to hypoxia and for those living with hypoxia-associated conditions such as asthma, emphysema, ischemic heart disease, and apnea.

Keywords:  blood-brain barrier integrity; chronic mild hypoxia; endothelial; hypoxic threshold; microglia; proliferation

DOI:  https://doi.org/10.18632/aging.206241
Eur J Sport Sci. 2025 Jun;25(6): e12312

Effects of Heat and Hypoxia Training on the Fat Oxidation Capacity of Competitive Athletes.

Zhizhong Geng, Xiaameng Wu, Jinhao Wang, Guohuan Cao, Chenhao Tan, Longji Li, Jun Qiu.

  This study aimed to evaluate the impact of a four-week heat and hypoxia training on the fat oxidation capacity of competitive athletes. Eight elite male modern pentathlon athletes completed a four-week aerobic endurance training program in three environments: normal (CON), high temperature and humidity (HOT), and hypoxia (HYP). Assessments were conducted in both the normal environment and the corresponding special environment before and after training. Gas exchange data were collected during exercise to assess aerobic capacity, and fat oxidation was measured using indirect calorimetry. Fat oxidation kinetics were modeled using the sinusoidal (SIN) mathematical model to determine the maximum fat oxidation (MFO) and the exercise intensity at which it occurred (FATmax). Under normal environment, HOT training had an increase in absolute V̇O2 (238.152 mL/min and p = 0.003), both the HOT (96.062 s and p = 0.006) and HYP (109.917 s and p = 0.002) trainings demonstrated increases in VT2@Time, both the HOT (0.126 g/min and p = 0.015) and HYP (0.157 g/min and p = 0.004) trainings showed increases in MFO, and the HOT training also exhibited an increase in FATmax (5.303 g/min and p = 0.005); both the HOT and HYP trainings showed dilatation of the fat oxidation curve, with the HOT training also displaying dilatation in the fat oxidation curve under heat conditions. Four-weeks of heat and hypoxia training significantly enhanced athletes' aerobic metabolism and fat oxidation capacity. The benefits of heat training on aerobic metabolism and fat oxidation may exceed those of hypoxia training.

Keywords:  competitive athletes; fat oxidation capacity; heat; hypoxia; training

DOI:  https://doi.org/10.1002/ejsc.12312
BMC Biotechnol. 2025 May 10. 25(1): 34

Hypoxia and HIF-1 inhibition enhance lentiviral transduction efficiency: a novel strategy for gene delivery optimization.

Qianyu Huo, Wentian Wang, Jiawen Dai, Xu Yuan, Dandan Yu, Bingqi Xu, Ying Chi, Huiyuan Li, Xiao Lei Pei, Guoqing Zhu, Lei Zhang.

  Lentiviral vectors are widely used for stable gene delivery, but their transduction efficiency can be limited by suboptimal experimental conditions. Here, we investigated the role of oxygen concentration and hypoxia-inducible factor 1 (HIF-1) signaling in lentiviral packaging and transduction. We found that packaging lentivirus under hypoxic conditions (10% O₂) significantly increased viral titers and transduction efficiency by approximately 10%. However, hypoxic conditions during viral entry impaired infection efficiency, likely due to HIF-1α-mediated cellular protective mechanisms. Pretreatment of cells with the HIF-1 inhibitor PX-478 reversed this effect, enhancing viral entry and genome integration in a dose-dependent manner. Combining hypoxic virus packaging with PX-478 pretreatment synergistically improved transduction efficiency by 20%. These findings suggest that HIF-1 inhibition and controlled hypoxia significantly enhance lentiviral transduction efficiency, establishing a versatile strategy with broad applicability across viral vector-dependent biomedical applications.

Keywords:  Gene delivery optimization; HIF-1 inhibitor; Hypoxia; Lentiviral transduction; Oxygen tension; Transduction efficiency

DOI:  https://doi.org/10.1186/s12896-025-00969-3
APL Bioeng. 2025 Jun;9(2): 026114

Polarized macrophages modulate cardiac structure and contractility under hypoxia in novel immuno-heart on a chip.

Andrew A Schmidt, Li-Mor David, Nida T Qayyum, Khanh Tran, Cassandra Van, Ali H S H A Hetta, Ronit L Shrestha, Ashley O Varatip, Sergei Butenko, Daniela Enriquez-Ochoa, Christy Nguyen, Marcus M Seldin, Wendy F Liu, Anna Grosberg.

Cardiac adaptation to hypoxic injury is regulated by dynamic interactions between cardiomyocytes and macrophages, yet the impacts of immune phenotypes on cardiac structure and contractility remain poorly understood. To address this, we developed the immuno-heart on a chip, a novel in vitro platform to investigate cardiomyocyte-macrophage interactions under normoxic and hypoxic conditions. By integrating neonatal rat ventricular myocytes (NRVMs) and bone marrow-derived macrophages-polarized to pro-inflammatory (M1) or pro-healing (M2/M2*) phenotypes-we elucidated the dual protective and detrimental roles macrophages play in modulating cardiomyocyte cytoskeletal architecture and contractility. Pro-inflammatory stimulation reduced cardiomyocyte structural metrics (z-line length, fraction, and integrity) in normoxic co-cultures. Under hypoxia, M1-stimulated NRVM monocultures exhibited declines in cytoskeletal organization-quantified by actin and z-line orientational order parameters. Relative to monocultures, M1-stimulated co-cultures attenuated hypoxia-induced active stress declines but produced weaker normoxic stresses. In contrast, pro-healing stimulation improved normoxic z-line metrics and preserved post-hypoxia cytoskeletal organization but reduced normoxic contractility. Notably, M2-stimulated macrophages restored normoxic contractility and preserved post-hypoxia systolic stress, albeit with increased diastolic stress. RNAseq analysis of M2-stimulated co-cultures identified upregulated structural and immune pathways driving these hypoxia-induced changes. Cytokine profiles revealed stimulation-specific and density-dependent tumor necrosis factor-alpha and interleukin-10 secretion patterns. Together, these findings quantitatively link clinically relevant macrophage phenotypes and cytokines to distinct changes in cardiac structure and contractility, offering mechanistic insights into immune modulation of hypoxia-induced dysfunction. Moreover, the immuno-heart on a chip represents an innovative framework to guide the development of future therapies that integrate immune and cardiac targets to enhance patient outcomes.

DOI: https://doi.org/10.1063/5.0253888
High Alt Med Biol. 2025 May 07.

Chronic Mountain Sickness: A Comprehensive Review of Current Management and Proposals for Novel Therapies.

Edmund Adams, Tamlyn Peel.

  Chronic mountain sickness (CMS) is an acquired condition affecting 5%-10% of high-altitude residents. Lifelong exposure to chronic hypoxia triggers excessive erythrocytosis, resulting in an expanded hematocrit. Patients present with symptoms such as dyspnea, fatigue, and palpitations. Complications such as pulmonary hypertension and heart failure are often fatal. Relocation to sea level remains the only definitive management of CMS but poses an unacceptable personal burden. Long-term oxygen therapy provides symptomatic relief, but dependency issues remain a concern. Phlebotomy reduces hematocrit and offers short-term symptom relief. However, side effects and cultural conflicts continue to pose challenges. Acetazolamide, enalapril, and medroxyprogesterone have lowered hematocrit and alleviated symptoms in human trials. Further research into systemic side effects, application in women, and long-term use is required. Methylxanthines, adrenergic blockers, almitrine, and dopamine antagonists showed promise in murine and/or short-term human trials, highlighting the need for further long-term human trials. Inhibition of hypoxia-inducible factor and Janus Kinase-signal transducer and activator of transcription pathways is currently used to suppress hematocrit in polycythemia vera, demonstrating potential application in CMS. Topiramate may stimulate ventilation via acid-base modulation, thus providing therapeutic value. Similarly, the effect of aspirin and caffeine on ventilation may provide a low-cost, accessible intervention.

Keywords:  Andean populations; Tibetan Plateau; acetazolamide; chronic mountain sickness; high-altitude populations; novel therapies

DOI:  https://doi.org/10.1089/ham.2024.0127
Ann Endocrinol (Paris). 2025 May 06. pii: S0003-4266(25)00091-5. [Epub ahead of print] 101772

Altitude and Paraganglioma.

Julie Sanceau, Rebecca Westbrook, Judith Favier.

  The relationship between altitude and the development of paragangliomas (PGLs), rare tumors within the sympathetic nervous system has been suggested since the early 1970's. Here, we discuss how altitude, marked by lower barometric pressure and hypoxia (reduced oxygen partial pressure), may influence cancer rates. Chronic hypoxia triggers physiological changes, such as carotid body (CB) hyperplasia and a higher incidence of head and neck paragangliomas (HN-PGL) has been reported in high-altitude populations, with a predominance of females among affected individuals. The involvement of hypoxia signalling in PGL tumorigenesis is further reinforced by the demonstration that genetic mutations, (particularly in VHL, SDHx and EPAS1 genes) cause a pseudo-hypoxic response. Furthermore, somatic mutations in EPAS1 are also linked to an increased risk of PGL in individuals with chronic hypoxemic conditions sur as cyanotic congenital heart disease or haemoglobin diseases. Altogether, this review emphasizes the unique sensitivity of paragangliomas to hypoxic signalling, and shows that whether due to low environmental oxygen at high altitudes, diseases, or genetic mutations, hypoxia plays a pivotal role in PGL formation.

Keywords:  EPAS1; SDHx; VHL; altitude; hypoxia; paraganglioma

DOI:  https://doi.org/10.1016/j.ando.2025.101772
Sheng Li Xue Bao. 2025 Apr 25. 77(2): 318-326

[Progress on the mechanism and application of hyperbaric oxygen therapy for neurodegenerative diseases].

Fang-Fang Wang, Nan Wang, Heng-Rong Yuan, Ji Xu, Jun Ma, Xiao-Chen Bao, Yi-Qun Fang.

In 2040, neurodegenerative diseases (NDD) will overtake cancer as the second leading cause of death after cardiovascular and cerebrovascular diseases. Therefore, the search for effective intervention measures has become the top priority to deal with this difficult burden. Hyperbaric oxygen therapy (HBOT) has been used for the past 50 years to treat conditions such as decompression sickness, carbon monoxide poisoning and radiation damage. In recent years, studies have confirmed that HBOT has good effects in improving cognitive impairment after brain injury and stroke, and alleviating neurodegeneration and dysfunction related to NDD. Here we reviewed the pathogenesis and treatment state of NDD, introduced the application of HBOT in animal models and clinical studies of NDD, and expounded the application potential of HBOT in the treatment of NDD from the perspective of mitochondrial function, neuroinflammation, neurogenesis and angiogenesis, oxidative stress, apoptosis, microcirculation and epigenetics.

DOI: https://doi.org/10.13294/j.aps.2025.0033
J Mol Neurosci. 2025 May 03. 75(2): 63

Electroacupuncture Inhibits Ferroptosis by Modulating Iron Metabolism and Oxidative Stress to Alleviate Cerebral Ischemia-Reperfusion Injury.

Yaoyao Liu, Qi Wang, Ziwen Hou, Ying Gao, Peng Li.

  Ischemic stroke (IS) is one of the leading causes of mortality and long-term disability worldwide. Electroacupuncture (EA) is commonly used in the treatment of IS, meaning that may reduce cerebral ischemia-reperfusion injury (CIRI). The middle cerebral artery occlusion/reperfusion (MCAO/R) rat models were created by the modified Zea Longa suture method. EA treatment was performed for 7 consecutive days at the acupoints Neiguan (PC6), Shuigou (GV26), and Sanyinjiao (SP6). The neurological function was assessed using the Zausinger six-point neurological deficiency score. The cerebral infarct volume was detected by 2,3,5-triphenyl tetrazolium chloride (TTC) staining. Hematoxylin and eosin (HE) staining was employed to observe the pathological changes in brain tissues. Prussian blue staining was employed to investigate iron deposition within the brain tissues. Transmission electron microscopy (TEM) was utilized to examine the morphological characteristics of mitochondria. Simultaneously, flow cytometry was utilized to detect the fluorescence intensity of reactive oxygen species (ROS). Assay kits were employed to measure the levels of Fe2+ and glutathione (GSH). Additionally, western blot (WB) and real-time quantitative polymerase chain reaction (RT-qPCR) assays were performed to evaluate the expression levels of proteins associated with ferroptosis. Compared with the MCAO/R group, both the MCAO/R + EA and MCAO/R + DFO groups exhibited significant improvements in neurological function following cerebral ischemia-reperfusion (CIR), attenuated the pathological brain tissue injury, and reduced the cerebral infarct volume and iron deposition in brain tissue. Furthermore, both the MCAO/R + EA and MCAO/R + DFO groups displayed a marked reduction in mitochondrial injury. There was a substantial decrease in Fe2+ and ROS levels, accompanied by a notable increase in GSH level and glutathione peroxidase 4 (GPX4) activity. Compared with the MCAO/R group, the levels of ferroportin1 (FPN1) protein and mRNA expression were significantly increased in the MCAO/R + EA and MCAO/R + DFO groups, and the expression levels of transferrin (TF), transferrin receptor 1 (TFR1), divalent metal transporter 1 (DMT1) protein and mRNA, as well as ferritin (FER) protein, were significantly decreased. EA inhibits ferroptosis by modulating iron metabolism and oxidative stress to alleviate CIRI, exerting neuroprotective effects.

Keywords:  Cerebral ischemia–reperfusion injury; Electroacupuncture; Ferroptosis; Iron metabolism; Oxidative stress

DOI:  https://doi.org/10.1007/s12031-025-02355-2
Microbiol Spectr. 2025 May 06. e0004525

Gut microbiota modulates lung gene expression and metabolism to aid SD rats in adapting to low-pressure hypoxia.

Zheng Chen, Shatuo Chai, Yuxia Ding, Kaiyue Pang, Tanqin Dong, Dongwen Dai, Jianmei Wang, Shuxiang Wang, Shujie Liu.

  Hypoxia has long posed a serious threat to the health of both animals and humans, causing respiratory acidosis, metabolic disorders, systemic inflammation, oxidative stress damage, and other issues, thereby endangering life and limiting development in high-altitude areas. Gut microbiota plays a crucial role in life activities and hypoxia adaptation. We transplanted the gut microbiota from small mammals, plateau zokors (Myospalax baileyi), from the Qinghai-Tibetan plateau (3,500 m) to Sprague-Dawley (SD) rats housed in a hypobaric chamber (equivalent to 6,000 m altitude) for 30 days. The results showed that microbiota transplantation significantly reshaped the gut microbiota structure of the rats, notably increasing the abundance of short-chain fatty acid-producing bacteria Lachnospiraceae and Prevotellaceae, alleviating hypoxia and acidosis, reducing pulmonary hypertension and right ventricular hypertrophy, increasing the production of anti-inflammatory substances like indole-3-lactic acid, and reducing the generation of pro-inflammatory substances, such as histamine and uric acid. It also decreased the expression of inflammatory genes like lgE, TNFα, and IFN-γ in the lung. Fecal microbiota transplantation from plateau-specific species to low-altitude SD rats effectively altered metabolism, changed gene expression, decreased pulmonary artery pressure, and enhanced plateau adaptability. This study demonstrates the potential effectiveness of treating hypoxic pulmonary hypertension through microbiota transplantation and offers insights into improving hypoxia adaptation.
IMPORTANCE: We report the beneficial effects of FMT on respiratory capacity, lung metabolism, and lung gene expression in SD rats under hypoxic conditions. We revealed the inhibitory effects of gut microbiota on lung mast cells and histamine expression under hypoxic conditions. The study demonstrated the potential effectiveness of treating HPH through FMT and offers insights into improving hypoxia adaptation.

Keywords:  SCFAs; gut microbiota; hypoxia adaptation; hypoxic pulmonary hypertension; inflammation

DOI:  https://doi.org/10.1128/spectrum.00045-25