bims-oxygme Biomed News
on Oxygen metabolism
Issue of 2025–06–22
eleven papers selected by
Onurkan Karabulut, Berkeley City College
  1. Hyperoxic recovery impacts on metabolic adaptations induced by hypoxic exercise: A lipidomics approach.
  2. Hypoxia regulates glycolysis through the HIF-1α/BMAL1/ALDOC axis to reduce oxaliplatin sensitivity in colorectal cancer.
  3. A 3D-printed multi-channel microfluidic device for precise dissolved oxygen regulation in cancer hypoxia research.
  4. Ginsenoside Rg5 alleviates hypoxia-induced myocardial apoptosis by targeting STAT3 to promote Tyr705 phosphorylation.
  5. Hypoxia-induced tRF-3Thr-CGT promotes hepatocellular carcinoma progression via mitochondrial energy metabolism remodeling dependent on the mtDNA-translation mechanism.
  6. Interplay of hypoxia, immune dysregulation, and metabolic stress in pathophysiology of type 1 diabetes.
  7. Light-Activated Hypoxia-Responsive Nanoparticles for Photodynamic Chemotherapy.
  8. The role of hypoxia-inducible factor-3α in human disease.
  9. RNA sequencing reveals circular RNA expression patterns in chronic intermittent hypoxia.
  10. Seven Hypoxia and Immune-Related Features Predict Prognosis in Patients with Hepatocellular Carcinoma.
  11. High-altitude physiology: Understanding molecular, pharmacological and clinical insights.
  1. Biochim Biophys Acta Mol Cell Biol Lipids. 2025 Jun 14. pii: S1388-1981(25)00055-1. [Epub ahead of print]1870(6): 159647
    Hyperoxic recovery impacts on metabolic adaptations induced by hypoxic exercise: A lipidomics approach.
    Simone Serrao, Eleonora Bossi, Vanna Denti, Johannes Burtscher, Martin Faulhaber, Günter Weiss, Wolfgang Schobersberger, Tobias Dünnwald, Giuseppe Paglia.
      This study investigates the effect of recovery phases in either hyperoxic air or hypoxic air during physical exercise in hypoxia on lipid metabolism in 11 male athletes. We observed a long-term effect leading to increased plasma triacylglycerols and diacylglycerols, along with a decrease in sphingomyelin when athletes received supplemental oxygen during recovery. In contrast, no significant changes in circulating lipids were detected in athletes trained under hypoxic recovery conditions after 7 days. We propose that hypoxic exercise induced potentially protective metabolic adaptations that might be disrupted by hyperoxic recovery.
    Keywords:  Acclimatization; Exercise; High altitude illnesses; Hyperoxia; Hypoxia; Lipidomics; Metabolism
    DOI:  https://doi.org/10.1016/j.bbalip.2025.159647
  2. J Cancer. 2025 ;16(8): 2503-2515
    Hypoxia regulates glycolysis through the HIF-1α/BMAL1/ALDOC axis to reduce oxaliplatin sensitivity in colorectal cancer.
    Jialing Ran, Feifei Li, Lei Zhan, Yue Jin, Qian Dong, Xiaoyan Li, XiaoXi Li, Qian Fei, Jingdong Zhang.
      Background: Oxaliplatin (L-OHP) is a first-line chemotherapy agent for advanced colorectal cancer (CRC), but the development of resistance often compromises its efficacy. Tumor hypoxia and metabolic reprogramming are known to influence chemotherapy sensitivity, yet their interrelationship remains inadequately explored. Methods: In vitro assays were conducted using human colorectal cancer cell lines (DLD1 and LoVo) under hypoxic conditions induced by cobalt chloride (CoCl2). The expression levels of key proteins involved in the HIF-1α/BMAL1/ALDOC pathway were assessed through Western blotting and quantitative real-time PCR (qPCR). Cell viability, apoptosis, and glycolytic activity were evaluated using CCK-8 assays, flow cytometry, and lactate/ATP measurements. Results: Hypoxia significantly enhanced glycolysis in CRC cells, decreasing sensitivity to L-OHP. The HIF-1α/BMAL1/ALDOC axis was identified as a crucial mediator in this process, with HIF-1α upregulating BMAL1, which increased ALDOC expression. This cascade promoted glycolytic activity and reduced apoptosis in hypoxic conditions. Notably, a positive correlation between HIF-1α and ALDOC expression was confirmed in clinical CRC samples. Conclusion: The findings reveal a novel mechanism by which hypoxia diminishes L-OHP sensitivity in CRC through the HIF-1α/BMAL1/ALDOC pathway. These insights provide potential biomarkers for predicting treatment outcomes and suggest new therapeutic strategies to enhance chemosensitivity in colorectal cancer.
    Keywords:  ALDOC; HIF-1α; chemotherapy; glycolysis; hypoxia
    DOI:  https://doi.org/10.7150/jca.108582
  3. Talanta. 2025 Jun 16. pii: S0039-9140(25)00959-2. [Epub ahead of print]296 128469
    A 3D-printed multi-channel microfluidic device for precise dissolved oxygen regulation in cancer hypoxia research.
    Chenchen Zhang, Ziyi Yu, Haiyang Tang, Kuo Tian, Min Jiang, Zhoumin Li, Danke Xu.
      Hypoxia plays a critical role in cancer progression, therapy resistance, and metastasis, yet establishing precise, physiologically relevant dissolved oxygen (DO) gradients for in vitro cell studies remains technically challenging. Here, we developed a novel 3D-printed microfluidic platform that generates eight parallel DO gradients (0-100 % saturation) for multiplexed hypoxia research. The integrated system combines a modular microplate adapter with a precise DO concentration gradient generation chip, creating stable linear oxygen profiles that faithfully mimic different in vivo tumor microenvironments. DO concentration gradient generation is validated with online electrochemical detection showed great linearity (R2 > 0.99) and accuracy. The microfluidic perfusion system demonstrated excellent biocompatibility, supporting robust cellular proliferation and maintaining >95 % viability across all cell lines during 72-h continuous culture periods. Using renal (A498) and colorectal (SW480/SW620) cancer cell lines, we demonstrate concentration-dependent cellular responses to hypoxia. Compared to conventional microplates and microfluidic chips, this system enables stable perfusion culture of cells, and high-resolution analysis of spatiotemporal hypoxia adaptations. This technology provides a versatile, cost-effective tool for investigating hypoxia-driven mechanisms in cancer biology and therapeutic development.
    Keywords:  3D printing; Cell viability; Concentration gradient; Dissolved oxygen; Hypoxia; Microfluidic chip; Tumor
    DOI:  https://doi.org/10.1016/j.talanta.2025.128469
  4. Chin Med. 2025 Jun 13. 20(1): 86
    Ginsenoside Rg5 alleviates hypoxia-induced myocardial apoptosis by targeting STAT3 to promote Tyr705 phosphorylation.
    Fang-Yang Li, Yi-Hao Wang, Cheng Zhang, Wan-Yun Dang, Ze-Kun Wu, Zhen-Hui Wu, Jia-Lu Cui, Xiang-Jun Wu, Chun-Qi Yang, Xue-Cong Tian, Cheng-Rong Xiao, Yu-Guang Wang, Yue Gao.
       BACKGROUND: The heart, as the body's blood-pumping organ, is extremely sensitive to changes in oxygen levels. Myocardial injury caused by hypoxia is a challenging issue, and there are currently no definitive specific drugs available for its treatment. Ginsenoside Rg5, one of the main rare saponins in ginseng, has shown significant efficacy in treating myocardial injury. This study aims to investigate the role and mechanisms of Rg5 in the treatment of hypoxic myocardial injury.
    METHODS: The cardioprotective effect against acute hypoxia of Rg5 was studied by assessing heart function, myocardial injury markers, inflammation, and oxidative stress in C57 mice, as well as apoptosis and reactive oxygen species (ROS) levels in H9c2 cardiomyocytes. Thermal proteome and target validation techniques were used to confirm the target protein of Rg5. The further protective mechanisms against hypoxia-induced damage were explored using immunocoprecipitation, immunofluorescence and rescue experiments in vivo and in vitro.
    RESULTS: The experimental results demonstrated that Rg5 effectively improved cardiac function in mice, reduced inflammation, oxidative stress, and the release of myocardial injury markers, decreased cardiomyocyte apoptosis, and lowered ROS levels. Further, using target protein screening and validation techniques, Signal transducer and activator of transcription 3 (STAT3) was verified as a direct target for Rg5's cardioprotective effect. It was observed that Rg5 specifically promoted the phosphorylation of Tyr705 in STAT3 via the JAK2/STAT3 pathway, leading to the translocation of phosphorylated STAT3 into the nucleus where they induce the expression of anti-apoptotic protein and protect cells from hypoxic damage.
    CONCLUSION: Rg5 could be a potential therapeutic agent for preventing and treating myocardial hypoxic injury, providing scientific evidence for its application in anti-hypoxic therapy.
    Keywords:  Ginsenoside Rg5; Hypoxia; Myocardial apoptosis; Stat3; Tyr705 phosphorylation
    DOI:  https://doi.org/10.1186/s13020-025-01128-8
  5. Front Pharmacol. 2025 ;16 1549373
    Hypoxia-induced tRF-3Thr-CGT promotes hepatocellular carcinoma progression via mitochondrial energy metabolism remodeling dependent on the mtDNA-translation mechanism.
    Xianzhi Qu, Buhan Liu, Duo Jin, Yue Ma, Mingjun Liu, Xiaoyu Yan, Jing Su, Lei Zhou.
      Hypoxia is one of the major characteristics of the tumor microenvironment, and it promotes mitochondrial energy metabolic remodeling for hepatocellular carcinoma (HCC) progression. It is believed that under dual control of the mitochondrial genome (mtDNA) and the nuclear genome (nDNA) mitochondria coordinate multiple signals to alter energy metabolism under hypoxic stress. Currently, it has been found that hypoxia promotes tRNA cleavage to produce tRFs (tRNA-derived fragment), which have attracted attention as potential biomarkers and therapeutic targets. In this study, we found that hypoxic stress could drive HCC cell invasion and migration. Furthermore, the expression of core oxidative phosphorylation (OXPHOS) proteins encoded by nDNA and mtDNA were uncoordinated under hypoxia. Therefore, the human mitochondrial peptide deformylase (HsPDF) which was essential for mtDNA-encoded protein translation and respiratory chain maintenance has been brought into focus. We found that hypoxic stress significantly suppressed HsPDF which was responsible for mtDNA-encoded protein inhibition. To further explore the possible mechanism, high-throughput sequencing was used to map tRF expression patterns in HCC cells under hypoxia. We found that hypoxic stress altered their subtype distributions and that the high expression of tRF-3Thr-CGT, which has functions in transcription and translation regulation, may potentially bind to the 3'-UTR of HsPDF. Upregulated tRF-3Thr-CGT could inhibit HsPDF and mitochondrial OXPHOS function. Furthermore, the orthotopic liver cancer model in mice also indicated that the tRF-3Thr-CGT inhibitor significantly suppressed tumor progression. These results collectively suggested that tRFs may have roles in mitochondrial protein coordination and become novel pharmacological targets for mitochondrial remodeling under tumor microenvironment remodeling of HCC therapy.
    Keywords:  energy metabolism remodeling; hepatocellular carcinoma; hypoxia; mitochondrial; oxidative phosphorylation; tRNA-derived fragment
    DOI:  https://doi.org/10.3389/fphar.2025.1549373
  6. Front Immunol. 2025 ;16 1599321
    Interplay of hypoxia, immune dysregulation, and metabolic stress in pathophysiology of type 1 diabetes.
    Rahul Mittal, Joana R N Lemos, Prem Chapagain, Khemraj Hirani.
      Type 1 diabetes (T1D) is an autoimmune disease characterized by the progressive destruction of pancreatic β-cells, leading to insulin deficiency and chronic hyperglycemia. While immune-mediated mechanisms of β-cell destruction are well-recognized, emerging evidence highlights hypoxia as a silent yet critical contributor to T1D pathogenesis. Hypoxia in the pancreatic islets arises from inflammation, vascular dysfunction, hyperglycemia, and immune cell infiltration, creating a microenvironment that exacerbates β-cell dysfunction and amplifies autoimmune responses. Hypoxia-inducible factors (HIFs) play a dual role in regulating adaptive and maladaptive responses to hypoxia, influencing β-cell survival, immune activation, and oxidative stress. Specifically, hypoxia promotes the polarization of macrophages toward a pro-inflammatory M1 phenotype, enhances the differentiation of Th17 cells, and impairs the function of regulatory T cells (Tregs), thereby shifting the immune landscape toward sustained autoimmunity. This perspective discusses the multifaceted role of hypoxia in driving immune dysregulation and β-cell vulnerability in T1D as well as highlights the need for innovative research approaches to target this pathway. We propose future directions that emphasize the development of advanced experimental models to mimic the interplay between hypoxia, hyperglycemia, and immune responses in clinically relevant conditions. Furthermore, we highlight the potential of therapeutic strategies that target hypoxia and its downstream effects to preserve β-cell function and modulate autoimmunity. Collaborative efforts across disciplines will be crucial to translating these insights into clinical innovations that improve outcomes for individuals with T1D.
    Keywords:  autoimmune response; hyperglycemia; hypoxia; hypoxia-inducible factors; immune dysregulation; inflammation; regulatory T cells; type 1 diabetes
    DOI:  https://doi.org/10.3389/fimmu.2025.1599321
  7. ACS Omega. 2025 Jun 10. 10(22): 22719-22724
    Light-Activated Hypoxia-Responsive Nanoparticles for Photodynamic Chemotherapy.
    Dan Zhao, Shunliang Zheng, Xinyi Zuo, Hongyang Xu, Yue Ding, Fengming Liang.
      Hypoxia is a characteristic of solid tumors, and it significantly impedes cancer treatment. Here, we report light-activated hypoxia-responsive nanoparticles NPs-TPZ consisting of 5,10,5,20-tetrakis-(4-aminophenyl)-porphine (TAPP) modified with four azobenzene groups, cyclodextrin (CD), and 3-aminobenzotriazine-1,4-di-N-oxide tirapazamine (TPZ) by the synergy of π-π stacking, host-guest, and hydrophobic interactions for synergistic photodynamic chemotherapy (PDT-CT). Under near-infrared (NIR) irradiation, the process of PDT depletes oxygen and generates singlet oxygen (1O2). The induced hypoxia exacerbation further accelerates the release and activation of TPZ. As a result, this hypoxia-responsive nanoparticle provides an effective strategy for the ablation of hypoxic solid tumors by synergistic PDT-CT.
    DOI:  https://doi.org/10.1021/acsomega.4c11283
  8. Biochim Biophys Acta Mol Cell Res. 2025 Jun 11. pii: S0167-4889(25)00112-0. [Epub ahead of print] 120007
    The role of hypoxia-inducible factor-3α in human disease.
    Alejandro López-Mejía, Paola Briseño-Díaz, Martha Robles-Flores.
      Hypoxia-inducible factors (HIFs) are master regulators of cellular adaptation to hypoxia in both disease and normal physiological conditions. HIFs consist of two subunits: the oxygen-sensitive alpha (α) and the constitutively expressed beta (β). The three oxygen-dependent alpha subunits-HIF-1α, HIF-2α, and HIF-3α-encoded by distinct genes are crucial for regulating cellular responses to hypoxia in various vertebrates, including humans. Much of our understanding of HIFs is based on studies on HIF-1α and HIF-2α subunits. Recent studies have shown that, although HIF-3α is the least studied member, it may also play essential roles in the development of human diseases, including cancer, cardiovascular and respiratory diseases, metabolic disorders, and other pathological processes. In this review, we focus on how HIF-3α overexpression is associated with various human diseases, aiming to better understand its role in human pathophysiology and its potential use as a therapeutic target.
    Keywords:  HIF-1α; HIF-2α; HIF-3α; HIF-3α in disease; Hypoxia; Hypoxia inducible factors
    DOI:  https://doi.org/10.1016/j.bbamcr.2025.120007
  9. Sleep Biol Rhythms. 2025 Jul;23(3): 295-303
    RNA sequencing reveals circular RNA expression patterns in chronic intermittent hypoxia.
    Cong Li, Tiantian Su, Yuqin Chen, Lei Yue, Yu Zhang, Song Shi, Wenjia Wei.
      Circular RNAs (circRNAs) participate in diverse biological processes. However, whether circRNAs exhibit distinct expression patterns under obstructive sleep apnea (OSA)-induced chronic intermittent hypoxia (CIH) remains unexplored. We conducted RNA sequencing to compare expression profiles between CIH rats (n = 4) and normoxic controls (n = 4), identifying differentially expressed (DE) circRNAs. After filtering candidate circRNAs, we validated their expression in four OSA patients and four controls using qRT-PCR. Principal component analysis (PCA) was employed to confirm the diagnostic potential of these circRNAs. The miRanda software predicted target microRNAs (miRNAs), and the circRNA-miRNA regulatory network was visualized using Cytoscape software. In total, we identified 43 DE circRNAs, primarily enriched in functions like protein binding, cytoskeleton organization, and supramolecular complexes. We selected eight DE circRNAs associated with CIH for validation in OSA patients (n = 4) and controls (n = 4), with five displaying significant expression differences. These eight circRNAs showed distinct expression patterns between CIH and control groups, suggesting potential utility in distinguishing CIH conditions. Notably, our analysis identified mir-466b-3p as associated with DE circRNAs in the context of CIH. In conclusion, this study described circRNA expression profiles in CIH rats and identified several circRNAs with altered expression in CIH conditions. These findings suggest areas for further research into the relationship between circRNA expression and CIH.
    Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-025-00577-w.
    Keywords:  Chronic intermittent hypoxia; Circular RNAs; MicroRNAs; Obstructive sleep apnea; RNA sequencing
    DOI:  https://doi.org/10.1007/s41105-025-00577-w
  10. Dig Dis Sci. 2025 Jun 18.
    Seven Hypoxia and Immune-Related Features Predict Prognosis in Patients with Hepatocellular Carcinoma.
    Yun Lu, Xiangyu Li, Kai Zhao, Peng Qiu, Wei Yao.
       BACKGROUND: The role of hypoxia and immunity in the progression of hepatocellular carcinoma (HCC) was highly critical. However, there were few application-based studies on hypoxia and immune molecules in HCC prognosis prediction. This study aims to reveal the prognostic significance of hypoxia- and immune-related genes in HCC.
    METHODS: We identified the hypoxia- and immune-related differentially expressed genes (HIDEGs) from the Cancer Genome Atlas (TCGA). Seven HIDEGs associated with the prognosis of HCC were identified with the Cox regression and LASSO analysis. The prognosis model was validated in both the TCGA (n = 420) and Gene Expression Omnibus (GEO) (GSE14520-GPL3921, n = 222) databases. CIBERSORT was applied to measure the fractions of immune cell types. The drug sensitivity analysis was used to evaluate the applicability of drug treatment to HCC patients. The effect of ADM on the malignant biological behaviors of HCC was measured by plate colony formation assay, Cell Counting Kit-8 (CCK-8) assay, scratch wound assay and Transwell migration and invasion assays.
    RESULTS: We identified 78 HIRDEGs associated with survival time in HCC, among them, seven genes were chosen to construct a prognosis model. The prognosis model showed good performance in predicting prognosis in HCC patients in both the TCGA (n = 420) and Gene Expression Omnibus (GEO) (GSE14520-GPL3921, n = 222) databases. Based on the median risk score, HCC patients were classified into high- and low-risk groups. The high-risk group suffered worse survival time and contained higher proportions of M0/M1 macrophages and monocytes, and showed greater expression of classical immune checkpoints, including PD-1, PD-L1, and CTLA4. Furthermore, we presented that ADM was up-regulated by hypoxia, and silencing its expression suppressed HCC cells proliferation, migration, and invasion in vitro.
    CONCLUSION: The hypoxia- and immune-related signatures are promising biomarkers for HCC prognosis. ADM might be a novel target for HCC treatment.
    Keywords:  Hepatocellular carcinoma; Hypoxia; Immune; Prognostic; Risk score; TCGA
    DOI:  https://doi.org/10.1007/s10620-025-09152-2
  11. Pathol Res Pract. 2025 Jun 11. pii: S0344-0338(25)00273-0. [Epub ahead of print]272 156080
    High-altitude physiology: Understanding molecular, pharmacological and clinical insights.
    B M Redwan Matin Zidan, Mehrukh Zehravi, Shaik Kareemulla, Kallam Sudha Divya Madhuri, Jeetendra Kumar Gupta, Voleti Vijaya Kumar, Jishan Khan, Ali G Alkhathami, Hamid Osman, Mayeen Uddin Khandaker, Talha Bin Emran.
      Acute mountain sickness (AMS), high-altitude pulmonary edema (HAPE), and high-altitude cerebral edema (HACE) are three common forms of altitude sickness. These conditions can be life-threatening, with symptoms like fatigue, dizziness, and headaches. Ascending to high elevations increases the likelihood of developing these conditions, with some individuals adapting quickly while others need to descend. Early acclimatization is beneficial for avoiding AMS and HACE, but it takes weeks to months to improve job performance and performance at high altitudes. HAPE is a leading cause of mortality from altitude sickness, characterized by foamy mucus, coughing, and difficulty breathing. Treatment is most effective when it is administered quickly, with mild cases resolving with additional time spent at altitude. Oxygen therapy and chemicals such as acetazolamide, spironolactone, and dexamethasone are used to restore fluid balance and prevent complications. Genes and environmental factors influence genetic reactions to low oxygen levels at high altitudes. This review explores pharmacological interventions currently used or under investigation, such as acetazolamide, dexamethasone, and novel HIF stabilizers. By integrating molecular insights with pharmacological data, we aim to provide a comprehensive understanding of altitude-related illnesses. Studying altitude sickness is highly relevant not only for climbers and high-altitude workers but also for broader medical contexts like hypoxia-related diseases. This manuscript aims to bridge the gap between basic science and clinical practice, facilitating improved strategies for management and prevention of high-altitude disorders.
    Keywords:  HACE; HAPE; High altitudes; oxygen therapy
    DOI:  https://doi.org/10.1016/j.prp.2025.156080
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