bims-oxygme 2025-08-17 papers

bims-oxygme

Biomed News

on Oxygen metabolism

Issue of 2025–08–17
ten papers selected by
Onurkan Karabulut, Berkeley City College

Global profiling of N-terminal cysteine-dependent degradation mechanisms.
Intermittent Hypoxia Induces Cognitive Dysfunction and Hippocampal Gene Expression Changes in a Mouse Model of Obstructive Sleep Apnea.
Effects of hyperbaric oxygen therapy on exercise-induced muscle injury and soreness: A systematic review and meta-analysis.
Brain Metastasis: A Literary Review of the Possible Relationship Between Hypoxia and Angiogenesis in the Growth of Metastatic Brain Tumors.
Engine-cargo structured nanotrucks for advanced phototherapy by alleviating hypoxia and penetration barriers via oxygen-propelled motion.
Gastrodin Attenuates Cerebral Ischemia-Reperfusion Injury by Enhancing Mitochondrial Fusion and Activating the AMPK-OPA1 Signaling Pathway.
Belzutifan-Associated Hypoxia: A Review of the Novel Therapeutic, Proposed Mechanisms of Hypoxia, and Management Recommendations.
Brief disruptions in capillary flow result in rapid onset of hypoxia.
Roles of hypoxia inducible factors in viral infection: Are they a potential therapeutic target?
Insight into the research frontier of hypoxia in skin health and diseases: a bibliometric analysis.

Proc Natl Acad Sci U S A. 2025 Aug 19. 122(33): e2501681122

Global profiling of N-terminal cysteine-dependent degradation mechanisms.

Aizat Bekturova, Yaara Makaros, Shahar Ben-David, Itay Koren.

  Hypoxia, a condition characterized by insufficient oxygen supply, challenges cellular homeostasis and energy production, triggering adaptive responses to promote survival under these stressful conditions. One key strategy involves enzymatic oxidation of N-terminal cysteine residues coupled with proteolysis through the Cys-Arg/N-degron pathway. Despite hundreds of human proteins possessing N-terminal cysteine, very few have been identified as substrates of this pathway, and its substrate selectivity remains unclear. Moreover, the biological role of this pathway in the cellular response to hypoxia is not well defined. Here, by systematically screening protein stability using an N-terminome library, we reveal a broad set of cysteine-initiating proteins regulated by this pathway. Mutagenesis experiments further revealed the specificity of Cys-Arg/N-degron pathway, showing a preference for hydrophobic and positively charged residues following cysteine. Additionally, we uncovered full-length substrates that are regulated by this pathway during hypoxia, including IP6K1. Loss of IP6K1 impaired glucose uptake, glycolytic ATP production, and overall mitochondrial function. Consequently, IP6K1-deficient cells exhibited disrupted metabolic adaptation under hypoxic conditions and reduced survival under stress. These findings underscore the importance of the Cys-Arg/N-degron pathway in regulating metabolic responses and highlight its potential importance in hypoxia-related disorders.

Keywords:  E3 ligases; N-degron; cysteine; hypoxia; protein degradation

DOI:  https://doi.org/10.1073/pnas.2501681122
Int J Mol Sci. 2025 Aug 03. pii: 7495. [Epub ahead of print]26(15):

Intermittent Hypoxia Induces Cognitive Dysfunction and Hippocampal Gene Expression Changes in a Mouse Model of Obstructive Sleep Apnea.

Kenta Miyo, Yuki Uchida, Ryota Nakano, Shotaro Kamijo, Masahiro Hosonuma, Yoshitaka Yamazaki, Hikaru Isobe, Fumihiro Ishikawa, Hiroshi Onimaru, Akira Yoshikawa, Shin-Ichi Sakakibara, Tatsunori Oguchi, Takuya Yokoe, Masahiko Izumizaki.

  Obstructive sleep apnea syndrome (OSAS) is characterized by cycles of decreased blood oxygen saturation followed by reoxygenation due to transient apnea. Cognitive dysfunction is a complication of OSAS, but its mechanisms remain unclear. Eight-week-old C57BL/6J mice were exposed to intermittent hypoxia (IH) to model OSAS, and cognitive function and hippocampal gene expression were analyzed. Three groups were maintained for 28 days: an IH group (oxygen alternating between 10 and 21% in 2 min cycles, 8 h/day), sustained hypoxia group (SH) (10% oxygen, 8 h/day), and control group (21% oxygen). Behavioral tests and RNA sequencing (RNA-seq) analysis were performed. While Y-maze test results showed no differences, the IH group demonstrated impaired memory and learning in passive avoidance tests compared to control and SH groups. RNA-seq revealed coordinated suppression of mitochondrial function genes and oxidative stress response pathways, specifically in the IH group. RT-qPCR showed decreased Lars2, Hmcn1, and Vstm2l expression in the IH group. Pathway analysis showed the suppression of the KEAP1-NFE2L2 antioxidant pathway in the IH group vs. the SH group. Our findings demonstrate that IH induces cognitive dysfunction through suppression of the KEAP1-NFE2L2 antioxidant pathway and downregulation of mitochondrial genes (Lars2, Vstm2l), leading to oxidative stress and mitochondrial dysfunction. These findings advance our understanding of the molecular basis underlying OSAS-related cognitive impairment.

Keywords:  Intermittent hypoxia; cognitive dysfunction; gene expression; hippocampus; obstructive sleep apnea syndrome

DOI:  https://doi.org/10.3390/ijms26157495
Arch Phys Med Rehabil. 2025 Aug 08. pii: S0003-9993(25)00824-X. [Epub ahead of print]

Effects of hyperbaric oxygen therapy on exercise-induced muscle injury and soreness: A systematic review and meta-analysis.

Xiaoqin Luo, Ying Yu, Shibin Zhang, Fengxue Qi.

   OBJECTIVE: This meta-analysis aimed to assess the efficacy of hyperbaric oxygen therapy (HBOT) in facilitating recovery from exercise-induced muscle injury and soreness.
DATA SOURCES: China Knowledge Network (CNKI), Embase, Web of Science, Cochrane Library, PubMed, and Scopus database inception until September 28, 2024.
DATA SELECTION: A randomized controlled trial (RCT) to assess the effects on patients with exercise-induced muscle damage and soreness.
DATA EXTRACTION: Mean difference (MD) and 95% CI for all outcome indicators were estimated using a fixed-effects model, adjusting for: (1) first author; (2) year of publication; (3) sample size; (4) age; (5) method of injury induction; (6) parameters of hyperbaric oxygen intervention; (7) outcome measure; and (8) risk of bias indicators.
DATA SYNTHESIS: A total of 10 articles comprising 299 subjects were included in the analysis. The meta-analysis identified that HBOT significantly accelerated recovery from exercise-induced muscle injury [95% CI: -76.19 to -33.11, P < 0.00001)]. Subgroup analyses further revealed that both higher (> 2.0 ATA(atmosphere absolute), 95% CI: -89.45 to -19.06, P = 0.003) and lower (≤ 2.0 ATA, 95% CI: -82.12 to -27.65, P < 0.0001) atmospheric pressures, as well as intervention durations of 60 minutes (95% CI: -76.87 to -25.51, P < 0.0001) and 100 minutes (95% CI: -102.41 to -23.29, P = 0.002), were effective in alleviating muscle injury. These beneficial effects were observed in both college students (95% CI: -82.00 to -9.56, P = 0.01) and elite athletes (95% CI: -86.28 to -32.71, P < 0.0001). In contrast, HBOT did not provide a significant therapeutic benefit for exercise-induced muscle soreness (95% CI: -0.91 to 0.48, P = 0.54). However, subgroup analyses revealed that muscle soreness was significantly reduced with an atmospheric pressure above 2.0 ATA (95% CI: -1.58 to -0.00, P = 0.05), a pressure at or below 2.0 ATA (95% CI: 0.17 to 1.28, P = 0.01), and with a 100-minute intervention (95% CI: -2.05 to -0.26, P = 0.01), whereas a 60-minute intervention did not show a significant effect (95% CI: -0.17 to 0.92, P = 0.17).
CONCLUSION: HBOT was statistically effective in promoting recovery from exercise-induced muscle injury. However, it did not enhance recovery from exercise-induced muscle soreness.

Keywords:  hyperbaric oxygen therapy; muscle injury; muscle soreness; recovery

DOI:  https://doi.org/10.1016/j.apmr.2025.07.017
Int J Mol Sci. 2025 Aug 05. pii: 7541. [Epub ahead of print]26(15):

Brain Metastasis: A Literary Review of the Possible Relationship Between Hypoxia and Angiogenesis in the Growth of Metastatic Brain Tumors.

Lara Colby, Caroline Preskitt, Jennifer S Ho, Karl Balsara, Dee Wu.

  Brain metastases are a common and deadly complication of many primary tumors. The progression of these tumors is poorly understood, and treatment options are limited. Two important components of tumor growth are hypoxia and angiogenesis. We conducted a review to look at the possibility of a symbiotic relationship between two transcription factors, Hypoxia-Inducible Factor 1α (HIF1α) and Vascular Endothelial Growth Factor (VEGF), and the role they play in metastasis to the brain. We delve further into this possible relationship by examining commonly used chemotherapeutic agents and their targets. Through an extensive literature review, we identified articles that provided evidence of a strong connection between these transcription factors and the growth of brain metastases, many highlighting a symbiotic relationship. Further supporting this, combinations of chemotherapeutic drugs with varying targets have increased the efficacy of treatment. Angiogenesis and hypoxia have long been known to play a large role in the invasion, growth, and poor outcomes of tumors. However, it is not fully understood how these factors influence one another during metastases. While prior studies have investigated the effects separately, we specifically delve into the synergistic and compounding effects that may exist between them. Our findings underscore the need for greater research allocation to investigate the possible symbiotic relationship between angiogenesis and hypoxia in brain metastasis.

Keywords:  HIF1α; VEGF; angiogenesis; brain metastasis; hypoxia

DOI:  https://doi.org/10.3390/ijms26157541
J Colloid Interface Sci. 2025 Aug 06. pii: S0021-9797(25)02043-0. [Epub ahead of print]700(Pt 3): 138652

Engine-cargo structured nanotrucks for advanced phototherapy by alleviating hypoxia and penetration barriers via oxygen-propelled motion.

Tonghan Zhao, Yue Hu, Ziyue Xu, Jing Wang, Zijian Xu, Hejingying Niu, Xiaohui Zhu.

  Photodynamic therapy (PDT) holds significant promise for tumor treatment, yet its efficiency is still limited by shallow light penetration and tumor hypoxia. Herein, this study develops a Janus-typed nanotruck with an "engine-cargo" structure, where an upconversion nanoparticle is asymmetrically coated by a mesoporous silica shell using a special surfactant-templating method. Upon further loading with catalase (CAT) and photosensitizer (MC540), the obtained nanotruck enables to convert tumor-overexpressed H2O2 into oxygen gas, which not only propels the nanoparticle to enhance cellular uptake and tissue penetration but also alleviates tumor hypoxia. Thanks to the synergistic effect of particle motion and oxygen production, both in vitro and in vivo results showed that the ROS (reactive oxygen species) generation was significantly amplified under 980 NIR light illumination, which greatly enhanced PDT efficiency in tumor treatment. It is believed that this study demonstrates a promising strategy to alleviate limitations of traditional PDT and provides a more effective and targeted approach to tumor therapy.

Keywords:  Hypoxia; Nanotruck; Oxygen generation; Phototherapy; Upconversion nanoparticle

DOI:  https://doi.org/10.1016/j.jcis.2025.138652
CNS Neurosci Ther. 2025 Aug;31(8): e70559

Gastrodin Attenuates Cerebral Ischemia-Reperfusion Injury by Enhancing Mitochondrial Fusion and Activating the AMPK-OPA1 Signaling Pathway.

Zihan Liu, Zeyu Han, Wenshuai Bao, Yihan Guo, Yuan Yuan, Jianming Cheng, Jie Zhang, Yang Hu.

   BACKGROUND: Cerebral ischemia-reperfusion (I/R) injury is a critical pathological process in stroke, characterized by disrupted energy metabolism, inflammatory responses, and mitochondrial dysfunction. Targeting mitochondrial dynamics presents promising strategies for alleviating brain injury. This study investigates the role and mechanism of Gastrodin (Gas) in regulating mitochondrial dynamics and mitigating cerebral I/R injury via activation of the AMPK-OPA1 signaling pathway.
METHODS: An in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model and an in vivo middle cerebral artery occlusion/reperfusion (MCAO/R) model were used to assess the effects of Gas on inflammation, mitochondrial function, and energy metabolism. Immunofluorescence, western blotting (WB), reverse-transcription PCR (RT-PCR), JC-1 staining, and molecular docking techniques were employed for analysis.
RESULTS: Gas activated the AMPK-OPA1 signaling pathway, promoting mitochondrial fusion, restoring membrane potential, enhancing ATP production, and rebalancing NAD+/NADH levels. Additionally, Gas significantly suppressed I/R-induced inflammatory responses, reduced neuronal damage, and decreased infarct volume. Notably, its protective effects on mitochondrial fusion and neuroprotection were abolished under AMPK silencing, highlighting the critical role of the AMPK-OPA1 pathway.
CONCLUSION: Gas alleviates cerebral I/R injury by regulating mitochondrial dynamics via the AMPK-OPA1 signaling pathway. These findings provide a theoretical basis for the therapeutic application of Gas in stroke and offer new insights into mitochondrial-targeted treatment strategies.

Keywords:  AMPK‐OPA1; Gastrodin; cerebral ischemia–reperfusion injury; mitochondrial fusion; oxygen–glucose deprivation/reperfusion

DOI:  https://doi.org/10.1111/cns.70559
Int J Mol Sci. 2025 Jul 23. pii: 7094. [Epub ahead of print]26(15):

Belzutifan-Associated Hypoxia: A Review of the Novel Therapeutic, Proposed Mechanisms of Hypoxia, and Management Recommendations.

John Kucharczyk, Anshini Bhatt, Laura Bauer, Minas Economides.

  Belzutifan is a hypoxia-inducible factor-2α (HIF-2α) inhibitor that received FDA approval in 2021 for treating cancers resulting from von Hippel-Lindau (VHL) disease, including clear cell renal cell carcinoma (ccRCC), followed by approval in 2023 for sporadic ccRCC that has progressed through multiple lines of therapy. HIF-2α is a promising drug target, as VHL is commonly inactivated in ccRCC, which results in HIF-2α-mediated signaling that is considered central to tumorigenesis. Belzutifan has demonstrated efficacy in clinical trials in the first-line and subsequent line settings, and in combination with tyrosine kinase inhibitors. Despite being overall well tolerated, belzutifan has a distinct safety profile because of its unique mechanism of action. Anemia was the most common adverse event observed in clinical trials and is considered an on-target effect. Hypoxia is also frequently observed and commonly results in dose reductions, treatment discontinuation, and supplemental oxygen use. This review summarizes the rates of hypoxia seen in clinical trials of belzutifan in ccRCC. As the cause of hypoxia is not well understood, this review also discusses possible mechanisms of hypoxia based on preclinical studies of the HIF pathway and HIF-2α inhibitors. Finally, this review proposes monitoring and management recommendations for clinicians prescribing belzutifan to ccRCC patients.

Keywords:  adverse events; belzutifan; hypoxia; hypoxia-inducible factor-2α (HIF-2α); renal cell carcinoma

DOI:  https://doi.org/10.3390/ijms26157094
Neurophotonics. 2025 Jun;12(Suppl 2): S22803

Brief disruptions in capillary flow result in rapid onset of hypoxia.

John T Giblin, Sreekanth Kura, Gülce Küreli, John Jiang, Kıvılcım Kılıç, Baoqiang Li, Sava Sakadžić, Anna Devor, David A Boas.

   Significance: Capillaries are the critical site of vascular exchange with the local tissue, with continuous flow to meet the brain's unique and steep energetic demands. However, transient stalls in capillary flow have been observed and at elevated levels in preclinical models of disease. Systematic measurements have not been made to quantify the acute effects of individual capillary stalls on local oxygen.
Aim: We aim to quantify oxygen dynamics around capillary stalls as they occur in vivo.
Approach: We use high-resolution two-photon phosphorescent lifetime microscopy (2PLM) to monitor capillary flux and pO2 in the mouse cortex, allowing us to capture acute oxygen dynamics around capillary stalling.
Results: All stalls cause rapid drops in intra-capillary oxygen that likely extend to local tissue based on estimates using the erythrocyte-associated transient (EAT). This includes a subset of capillaries, which reach critically hypoxic levels (<10 mmHg), which could not be predicted by the capillaries' normal flux and oxygen levels, nor local vessel density or proximity to diving arterioles and venules.
Conclusion: Our findings indicate that a subset of capillary stalls reach extremely low local oxygen, resulting in transient hypoxia in the surrounding tissue. This reveals a new potential pathological mechanism due to stalled capillary flow.

Keywords:  capillary stalling; cerebral oxygen; phosphorence lifetime; two photon microscopy

DOI:  https://doi.org/10.1117/1.NPh.12.S2.S22803
Virulence. 2025 Dec;16(1): 2546680

Roles of hypoxia inducible factors in viral infection: Are they a potential therapeutic target?

Sikai Jia, Shuo Pan, Zhiyun Gao, Hongxiu Qiao, Yan Zhao, Xia Chuai, Jian Li.

  As a crucial nuclear transcription factor, hypoxia-inducible factor (HIF) serves essential functions in mediating cellular responses to hypoxic stress. Through oxygen-sensing mechanisms, HIF initiates downstream signaling cascades that coordinate metabolic reprogramming, immune modulation, and oncogenic progression in oxygen-deficient microenvironments. Current evidence positions HIF at the convergence of various pathologies, including microbial pathogenesis, carcinogenesis, and inflammatory disorders. This systematic review summarizes recent advances in HIF-mediated immunomodulation and virological mechanisms. The analysis emphasizes the fundamental importance of investigating HIF-related molecular pathways to address significant gaps in basic research.

Keywords:  Hypoxia inducible factor; hypoxia; immunization; normoxia; virus infection

DOI:  https://doi.org/10.1080/21505594.2025.2546680
Ann Med Surg (Lond). 2025 Aug;87(8): 4949-4962

Insight into the research frontier of hypoxia in skin health and diseases: a bibliometric analysis.

Cancan Huang, Xiang Li, Jieyu Li, Wenjun Wang, Xingzhu Mou, Wuda Huoshen, Ni Liu, Xia Xiong, Sha Yi, Guishu Zhong, Yan Chen.

  Research has demonstrated that hypoxia, a decrease in intracellular oxygen, is linked to multiple processes in the skin, including metabolic adaptation, cell survival, pathogenic microbe infection, immune response, tumorigenesis, and various diseases. This paper aims to perform a thorough bibliometric analysis of studies of hypoxia in skin health and disease to identify the frontiers, hotspots, and evolution of these studies. Articles about hypoxia in skin health and disease in the Web of Science Core Collection were gathered as of December 31, 2023. To find bursting keywords and references, VOSviewer was used to look at co-authorship and phrase co-occurrences and make visualizations of them. A total of 1511 papers on hypoxia in skin health and disease were examined in this study. China, the United States, and Japan were the top three countries contributing to this topic, while the International Journal of Molecular Sciences was the journal with the most articles. In terms of prolific authors in the publications, Yuesheng Huang from China contributed the most articles. The terms "hypoxia," "angiogenesis," and "wound healing" were the ones that were used the most frequently. In this study, a bibliometric analysis was performed on the last 10 years' worth of research on hypoxia in skin health and disease. The analysis identified the publications, nations, authors, institutions, and journals that were involved in this subject. These data offer a more comprehensive understanding of the area of research that has been conducted on hypoxia in skin health and disease.

Keywords:  CiteSpace; VOS viewer; bibliometrics; hypoxia; skin

DOI:  https://doi.org/10.1097/MS9.0000000000003303