bims-oxygme 2025-05-25 papers

bims-oxygme

Biomed News

on Oxygen metabolism

Issue of 2025–05–25
ten papers selected by
Onurkan Karabulut, Berkeley City College

Response of cartilage explants to LPS cultured in normoxic and hypoxic conditions is modulated by Spirulina: implications for exercise recovery in vivo.
Reducing Diagnostic Bias in Oxygenation Assessments.
Training in normobaric hypoxia induces hematological changes that affect iron metabolism and immunity.
Carbonic anhydrase IX downregulation linked to disruption of HIF-1, NFκB and STAT3 pathways as a new mechanism of ibuprofen anti-cancer effect.
Cardiovascular Plasticity and Adaptation of High-Altitude Birds and Mammals.
Evolved changes in reflex control of the cardiovascular system in deer mice native to high altitude.
A novel peptide from yak ameliorates hypoxia-induced cardiac dysfunction via targeting gut microbiota and HIF-1α pathway.
High-fat diet-induced osteoporosis in mice under hypoxic conditions.
Multiple roles for iron in microbial physiology: Bacterial oxygen sensing by heme-based sensors.
Single-Cell RNA and Transcriptome Sequencing to Analyze the Role of Lactate Metabolism in Traumatic Brain Injury Astrocytes.

Connect Tissue Res. 2025 May 23. 1-14

Response of cartilage explants to LPS cultured in normoxic and hypoxic conditions is modulated by Spirulina: implications for exercise recovery in vivo.

Nadia Golestani, Wendy Pearson.

  Exercise-induced inflammation and free radical production are crucial for recovery, yet excess inflammation poses risks to equine athletes, leading to conditions like arthritis. Spirulina, recognized for its antioxidant and anti-inflammatory properties, could mitigate degenerative diseases without hindering post-exercise recovery. This study investigates Spirulina's direct impact on cartilage responses to LPS-induced inflammation in normoxic and hypoxic conditions, focusing on outcomes relevant to cartilage matrix turnover and exercise-induced inflammation. Spirulina underwent simulated digestion and liver metabolism, yielding a simulated biological extract (SPsim). In the normoxic experiment, porcine cartilage explants were cultured with SPsim (0, 30, or 90 μg/mL) for 72 h after 24 h in basal media, with LPS (0 or 10 μg/mL) added for the final 48 h. The hypoxic experiment mirrored this, with explants transferred to a hypoxia chamber for the final 48 h. Media samples collected at 0, 24, and 48 h were analyzed for biomarkers related to cartilage turnover (GAG), and exercise-induced inflammation (IL-6 and NO). Cell viability, assessed by live:dead staining, remained > 97% and unaffected by oxygen tension. In normoxic conditions, SPsim (30 μg/mL) significantly reduced GAG release at 48 h. Under hypoxia, SPsim (30 and 90 μg/mL) inhibited LPS-induced GAG release. SPsim (90 μg/mL) increased IL-6 and NO production in LPS-stimulated explants in normoxia, and a similar effect was observed with the lower SPsim dose (30 μg/mL) in hypoxic conditions. These results suggest that Spirulina may enhance cartilage mediators, potentially promoting healthy cartilage turnover during exercise recovery.

Keywords:  Arthritis; Cartilage; Spirulina; feed additives; modeling

DOI:  https://doi.org/10.1080/03008207.2025.2507239
Am J Nurs. 2025 Jun 01. 125(6): 10-11

Reducing Diagnostic Bias in Oxygenation Assessments.

Jacob Terrell, Kimberly Smith, Adrianna Ellice Philippe, Staja Q Booker.

Assessing for hypoxia in patients with dark skin tones to prevent disparities in care.

DOI: https://doi.org/10.1097/AJN.0000000000000086
Sci Rep. 2025 May 22. 15(1): 17757

Training in normobaric hypoxia induces hematological changes that affect iron metabolism and immunity.

Svenja Nolte, Deeksha Malhan, Anna Klemmer, Tom Kastner, Nico Walter, Daniel Fleckenstein, Johannes Keck, Simon Klügel, Celina Maier, Kristina Gebhardt, Tobias Stauber, Angela Relógio, Karsten Krüger, Karsten Hollander.

  Altitude training is a method among endurance athletes to enhance performance via hypoxia-induced adaptations. However, individual responses vary significantly, with some athletes even showing performance decrements. Iron metabolism and immune function may influence these adaptations, as hypoxia-induced erythropoiesis increases systemic iron demand, potentially affecting immune cells reliant on iron. This study investigated the interplay between hematological, iron, and immunological variables under controlled normobaric hypoxia. 15 highly trained athletes participated in a 21-day live-high-train-low training camp in a normobaric altitude house. Blood samples were collected pre- and post-camp and at four intermediate time points to measure hematological variables, iron metabolism variables, and immunological variables. Pre- and post-performance was assessed via VO2max tests. Statistical analyses included paired t-tests, Wilcoxon rank-sum test, Spearman correlations, and Granger causality analysis to explore systemic temporal interactions. VO2max increased significantly (p < 0.05) with large interindividual variability (2.4 ± 3.5 ml/min/kg). Hemoglobin concentration, erythrocytes, and the soluble transferrin receptor (sTfR) showed significant increases over time (p < 0.05), while ferritin peaked early and declined post-camp. Myeloperoxidase and lactoferrin exhibited dynamic correlations with iron variables (p < 0.05), reflecting competition between erythropoiesis and immune function for iron. The structure of the Granger causality network places transferrin in a central role, highlighting iron metabolism as one key regulator of these adaptations. Normobaric hypoxia training induces systemic physiological changes involving hematological, iron, and immune systems. Controlled hypoxic conditions enable detailed exploration of these interactions, providing insights into optimizing altitude training strategies for endurance performance enhancement.

Keywords:  Athletes; Hypoxia; Lactoferrin; Neutrophils; Transferrin

DOI:  https://doi.org/10.1038/s41598-025-01542-w
PLoS One. 2025 ;20(5): e0323635

Carbonic anhydrase IX downregulation linked to disruption of HIF-1, NFκB and STAT3 pathways as a new mechanism of ibuprofen anti-cancer effect.

Katarina Grossmannova, Petra Belvoncikova, Barbora Puzderova, Veronika Simko, Lucia Csaderova, Jaromir Pastorek, Monika Barathova.

Numerous studies have highlighted the anti-cancer effects of nonsteroidal anti-inflammatory drugs (NSAIDs), although the underlying mechanisms remain unclear. This study focuses on elucidating the impact of the NSAID ibuprofen (IBU) on cancer cells exposed to hypoxia, as the hypoxic microenvironment significantly influences tumor progression, metastatic potential, and therapy resistance. Given that carbonic anhydrase IX (CA IX) is a key hypoxia-associated protein and a promising therapeutic target due to its tumor-specific expression, we primarily examined the impact of IBU on CA IX and the transcription factors regulating CA IX expression. We found that IBU downregulates expression and protein level of CA IX in hypoxic colon carcinoma and head and neck cancer cells, resulting in a reduction of membranous CA IX. To elucidate the mechanism of this phenomenon, we analyzed the key CA IX-regulating transcription factor HIF-1 and found decreased levels of the HIF-1α subunit in IBU-treated cells, leading to its impaired binding to the CA9 promotor. Analysis of another transcription factor involved in CA IX expression, NFκB, showed suppressed NFκB pathway under IBU treatment. Moreover, we demonstrated IBU-mediated induction in apoptosis in cancer cells, as well as a decrease in their ability to migrate. Our study is the first to demonstrate that ibuprofen downregulates carbonic anhydrase IX expression in hypoxic colon and head and neck tumor cells by decreasing HIF-1α levels. Additionally, ibuprofen impairs key transcription factors NFκB and STAT3, leading to reduced adaptation to hypoxic stress, decreased tumor cell viability, and migration. This indicates its potential as a therapeutic agent in combination therapy for colon carcinoma or head and neck cancer.

DOI: https://doi.org/10.1371/journal.pone.0323635
Integr Zool. 2025 May 21.

Cardiovascular Plasticity and Adaptation of High-Altitude Birds and Mammals.

Huishang She, Yanhua Qu.

  Exposure to a hypoxic environment at high altitudes imposes severe pressure on animals living there, which utilize substantial cardiovascular and respiratory responses to meet the physiological challenge of oxygen requirement. These responses may result from phenotypic plasticity through short-term exposure (i.e., within a generation) to a new environment or shaped by adaptation (i.e., many generations) through long-term evolution. For example, plasticity triggers a sympathetic-mediated adrenergic response, resulting in an elevation of heart rate and hypoxia-induced pulmonary vasoconstriction that eventually contributes to pulmonary hypertension in some animals. Adaptation to high altitudes can drive an increase in muscular capillarization and adaptive cardiac growth, which promote oxygen diffusion and transportation. Exposure to a high-altitude hypoxic environment stimulates excessive erythropoiesis, which has maladaptive effects and contributes to chronic mountain sickness. Maladaptation caused by plasticity at early stages can be reversed during adaptation. Despite extensive research on high-altitude adaptation, the phenotypic changes and genetic variations in cardiovascular systems responding to high-altitude hypoxia remain insufficiently integrated across taxa. While genomic and transcriptomic studies have advanced our understanding, a cross-taxa comparison of cardiovascular adaptations is still incomplete. We here review recent literature on phenotypic plasticity, adaptations, and genetic and transcriptional basis of cardiovascular systems of mammals and birds living in high altitudes with respect to their duration of exposure at high altitudes. By integrating and comparing data across mammalian and avian species, we aim to provide a framework for understanding the plasticity and adaptation of the cardiovascular system in high-altitude environments.

Keywords:  cardiovascular system; genetic adaptations; high altitudes; mammals and birds; phenotypic plasticity; transcriptional basis

DOI:  https://doi.org/10.1111/1749-4877.12996
J Exp Biol. 2025 May 22. pii: jeb.249483. [Epub ahead of print]

Evolved changes in reflex control of the cardiovascular system in deer mice native to high altitude.

Oliver H Wearing, John J McGuire, Graham R Scott.

  The cold and hypoxic conditions at high altitude place high demands on the cardiovascular system to sustain circulatory O2 transport. High-altitude natives have evolved to overcome cold hypoxia, but the cardiovascular mechanisms involved remain poorly understood in most taxa. Here, we investigated the evolved changes in reflex control of cardiovascular function in deer mice (Peromyscus maniculatus) native to high altitude. High- and low-altitude populations of deer mice were each bred in captivity and then chronically acclimated to warm normoxia (25˚C, ∼20 kPa O2) or cold hypoxia (5˚C, 12 kPa O2) for 6-8 weeks. Cardiovascular function was measured in vivo using physiological telemeters, complemented by wire myography to examine vascular function ex vivo. High-altitude mice acclimated to cold hypoxia exhibited greater heart rates and were better able to maintain blood pressure in moderate and severe hypoxia, in association with less pronounced depression of metabolism and body temperature. High-altitude mice also exhibited greater baroreflex sensitivity than low-altitude mice across acclimation environments, as reflected by greater changes in heart rate and smaller changes in arterial blood pressure during pharmacological manipulations. Mesenteric arteries from each population exhibited similar ex vivo smooth muscle contractions in response to phenylephrine (α1-adrenoceptor agonist), and similar endothelium-dependent relaxation in response to acetylcholine, suggesting that evolved changes in the baroreflex arise from adjustments in autonomic control of the heart and/or other resistance vessels. These evolved changes in cardiovascular function and reflex control may be valuable for supporting high metabolic rates in the cold and hypoxic environment at high altitude.

Keywords:  Acclimatization; Autonomic control; High-altitude adaptation; Mammal; Systemic vascular resistance; Vasomotor function

DOI:  https://doi.org/10.1242/jeb.249483
J Dairy Sci. 2025 May 16. pii: S0022-0302(25)00358-3. [Epub ahead of print]

A novel peptide from yak ameliorates hypoxia-induced cardiac dysfunction via targeting gut microbiota and HIF-1α pathway.

Feiyan Yang, Guangfan Qu, Yuchi Wu, Pingsheng Zhong, Zhongxing Chu, Zeyu He, Yuyan Wang, Yiping Tang, Shuguo Sun, Feijun Luo.

  Due to the high altitude and low oxygen levels, individuals residing or traveling in high-altitude regions often experience hypoxic cardiac dysfunction, which significantly affects their overall well-being and quality of life. Our previous investigations showed that peptide from yak milk residue exhibits notable antioxidant, anti-inflammatory, and anti-apoptotic properties that may have a good regulatory effect on hypoxic cardiac dysfunction. In this study, our results suggest that oral administration of yak milk peptide T3 improves the cardiac dysfunction of mice by the hypoxia-inducible factor 1α (HIF-1α) pathway, and these results may be related to the regulation of T3 on the gut microbiota of mice. Additionally, oral administration T3 enhances the permeability of the intestinal barrier and reduces intestinal inflammation. Further analysis revealed that the genera Oscillospira, Clostridium, and Staphylococcus are associated with aspartate aminotransferase, lactate dehydrogenase, and reactive oxygen species levels in heart tissues, which could ameliorate hypoxia-induced myocardial injury in mice. In vitro cell models have also confirmed that T3 intervention can activate the HIF-1α pathway and inhibit myocardial inflammation and cardiomyocyte apoptosis. These findings suggest that T3 may be a potential candidate for developing functional foods to reduce hypoxia-induced cardiac dysfunction.

Keywords:  HIF-1α; apoptosis; hypoxia; microbiota; myocarditis

DOI:  https://doi.org/10.3168/jds.2024-26058
BMC Musculoskelet Disord. 2025 May 16. 26(1): 487

High-fat diet-induced osteoporosis in mice under hypoxic conditions.

Yajun Qiao, Huimin Zheng, Ruiying Cheng, Juan Guo, Li Ji, Zhibin Liu, Lixin Wei, Hongtao Bi, Zhongshu Shan.

  In the context of global aging, osteoporosis has emerged as a significant public health concern, with a relatively high prevalence observed in plateau regions. This study aimed to investigate the effects and underlying mechanisms of high-fat diet (HFD) and hypoxic conditions on bone metabolism in mice. The mice were subjected to different dietary regimens (a HFD versus a normal diet) and placed in a hypoxic environment. This study explored relevant mechanisms through comprehensive assessments, including body and bone morphological indices, pathological examinations, biochemical analyses, evaluation of gut microbiota diversity, and metabolomics approaches. The results indicated that, compared with those in the control group, the body weight, Lee's index, body mass index (BMI), and body fat percentage of the HFD-fed group were significantly greater. Additionally, the femoral microstructure was compromised, bone metabolic markers were disrupted, inflammatory responses were heightened, gut microbiota diversity was altered, and specific intestinal metabolites such as Anserine were downregulated, whereas L-carnosine was upregulated. Spearman correlation analysis and network visualization elucidated the multifactorial influence mechanism of a HFD on bone metabolism under hypoxic conditions. These factors interconnect to form a complex network that drives osteoporosis development. Notably, L-carnosine occupies a central position within this network, serving as a key hub for interactions among various factors. Under the dual stressors of hypoxia and a HFD, this network becomes imbalanced, leading to bone metabolic disorders and osteoporosis. This study provides insights into the multifactorial mechanisms of osteoporosis induced by a HFD and hypoxia in mice, offering a foundation for subsequent research and preventive strategies for osteoporosis in plateau areas.

Keywords:  Bone metabolism; Gut; HFD; Hypoxia

DOI:  https://doi.org/10.1186/s12891-025-08725-6
Adv Microb Physiol. 2025 ;pii: S0065-2911(24)00032-8. [Epub ahead of print]86 257-329

Multiple roles for iron in microbial physiology: Bacterial oxygen sensing by heme-based sensors.

Artur Sergunin, Jakub Vávra, Dominik Pašek, Toru Shimizu, Markéta Martínková.

  Bacterial oxygen sensing embodies a fascinating interplay between evolutionary pressures and physiological adaptations to varying oxygen levels. Throughout Earth's history, the composition of the atmosphere has undergone significant changes, from anoxic conditions to the gradual accumulation of oxygen. In response, microbial life has evolved diverse strategies to cope with these shifting oxygen levels, ranging from anaerobic metabolism to oxygen-dependent pathways crucial for energy production and cellular processes typical for eukaryotic, multicellular organisms. Of particular interest is the role of iron in bacterial oxygen sensing systems, which play pivotal roles in adaptation to changing oxygen levels. Only free iron, heme-iron, and non-heme iron directly sense oxygen. These iron-containing proteins, such as heme-containing sensors and iron-sulfur cluster proteins, regulate the expression of genes and activity of enzymes involved in oxidative stress defence, virulence, and biofilm formation, highlighting their significance in bacterial pathogenesis and environmental adaptation. Special attention in the review is paid to the mechanisms of oxygen detection and signal transduction from heme-containing sensing to functional domains in the case of bacterial heme-based oxygen sensors.

Keywords:  Heme-based sensor; Intramolecular catalytic regulation; Oxygen sensing; Signal transduction

DOI:  https://doi.org/10.1016/bs.ampbs.2024.10.001
Brain Behav. 2025 May;15(5): e70428

Single-Cell RNA and Transcriptome Sequencing to Analyze the Role of Lactate Metabolism in Traumatic Brain Injury Astrocytes.

Zhang Bu, Yuqian Zhou, Feng Xu, Shan Xu.

   PURPOSE: After traumatic brain injury (TBI), ischemia and hypoxia of brain tissue, glucose undergoes anaerobic fermentation, leading to a large accumulation of lactic acid. Our aim was to explore the role of lactate metabolism in brain cells after TBI.
METHOD: In scRNA-seq dataset, 10-week-old male C57BL/6 J mice were randomized to undergo mild fluid percussion injury or sham surgery, and we analyzed frontal cortex tissue during the acute (24 h) and subacute (7 days) phases of TBI at single-cell resolution. Cell cycle phases were evaluated, and principal component analysis was performed. Cell populations were identified and visualized using the UMAP downscaling technique. Differentially expressed genes (DEGs) were analyzed using the "FindAllMarkers" algorithm. In addition, the set of genes related to lactate metabolism was evaluated using the AUCell score. GO and KEGG enrichment analyses were performed to investigate the functional pathways of DEGs in astrocytes in the acute and subacute phases of TBI.
RESULTS: A total of 13 cell populations were distinguished, including neurons, astrocytes, and oligodendrocyte progenitors. The number of neurons, astrocytes, and endothelial cells was reduced in the TBI group compared with the sham group. During the acute phase of TBI, enhanced interactions between brain-associated cells, especially astrocytes and oligodendrocyte precursor cells, were observed. Several signaling pathways, including EGF, CSF, MIF inflammatory factors as well as PSAP and PTN neurotrophic factor signaling were significantly enhanced after TBI. Lactate metabolism scores were elevated in the TBI group, especially in astrocytes. During the subacute phase, the frequency of intercellular communication increased but its intensity decreased. Astrocytes and oligodendrocyte precursor cells remained at high levels during both phases. PSAP signaling was closely associated with the subacute phase of TBI. Subsequently, NADH:ubiquinone oxidoreductase subunit B9 (Ndufb9) and cytochrome c oxidase subunit 8A (Cox8a) were identified as key players in lactate metabolism associated with TBI. Ndufb9 and Cox8a showed a consistent upward trend in brain tissue following TBI with transcriptomic data.
CONCLUSION: Lactate metabolism genes play an important role in TBI. These findings provide new insights into the cellular and molecular mechanisms following TBI.

Keywords:  astrocytes; lactate metabolism; traumatic brain injury

DOI:  https://doi.org/10.1002/brb3.70428