Hypoxia reduces mouse urine output via HIF1α–mediated up–regulation of renal AQP1 DOI Creative Commons
Rongfang Qiao, Xiaohui Cui, Yitong Hu

et al.

Kidney Diseases, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 15

Published: Oct. 22, 2024

Patients with acute mountain sickness (AMS) due to hypoxia at high altitudes often exhibit abnormal water metabolism. Hypoxia-inducible factors (HIFs) are major regulators of adaptive responses hypoxia. As transcription factors, HIFs involved in the regulation erythropoiesis, iron metabolism, angiogenesis, energy and cell survival by promoting transcriptional expression hundreds target genes. Roxadustat, a novel drug for treatment anemia associated chronic kidney disease (CKD), acts inhibiting degradation increase their protein levels. However, clinical use roxadustat is frequently peripheral edema, suggesting involvement regulating body's balance possibly modulating reabsorption kidney.

Language: Английский

Remote ischemic preconditioning prevents high‐altitude cerebral edema by enhancing glucose metabolic reprogramming DOI Creative Commons
Rongrong Han,

Xiaoyan Yang,

Xunming Ji

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(9)

Published: Sept. 1, 2024

Abstract Aims Incidence of acute mountain sickness (AMS) ranges from 40%–90%, with high‐altitude cerebral edema (HACE) representing a life‐threatening end stage severe AMS. However, practical and convenient preventive strategies for HACE are lacking. Remote ischemic preconditioning (RIPC) has demonstrated effects on ischemia‐ or hypoxia‐induced cardiovascular cerebrovascular diseases. This study aimed to investigate the potential molecular mechanism application RIPC in preventing onset. Methods A hypobaric hypoxia chamber was used simulate environment 7000 meters. Metabolomics metabolic flux analysis were employed assay metabolite levels. Transcriptomics quantitative real‐time PCR (q‐PCR) gene expression Immunofluorescence staining performed neurons label cellular proteins. The fluorescent probes Mito‐Dendra2, iATPSnFR1.0, CMTMRos observe mitochondria, ATP, membrane cultured neurons, respectively. TUNEL detect quantify apoptotic cell death. Hematoxylin eosin (H&E) utilized analyze pathological changes, such as tissue swelling cortex samples. Rotarod test assess motor coordination balance rats. Oxygen–glucose deprivation (OGD) cells an vitro model hypoglycemia induced by animal experiments. Results We revealed causative perturbation glucose metabolism brain preceding edema. Ischemic treatment significantly reprograms metabolism, ameliorating apoptosis energy deprivation. Notably, improves mitochondrial ATP production through enhanced glucose‐coupled metabolism. In vivo studies confirm that alleviates edema, reduces hypoxia, dysfunction resulting Conclusions Our elucidates basis pathogenesis. provides new strategy reprogramming highlighting targeting neuroprotective interventions neurological diseases caused ischemia hypoxia.

Language: Английский

Citations

6
Closing the loop: Autonomous intelligent control for hypoxia pre-acclimatization and high-altitude health management DOI Creative Commons
Dawei Shi, Jing Chen, Miao Li

et al.

National Science Review, Journal Year: 2025, Volume and Issue: 12(5)

Published: March 7, 2025

Hypobaric hypoxia at high altitudes threatens the health of high-altitude residents. The development effective methods to guarantee safety frequent human activities in locations is therefore needed. Pre-acclimatization sea level an approach mitigate subsequent altitude sickness for rapid ascent, which offers a viable substitute on-site acclimatization, minimizes associated risks that are linked prolonged exposure environments and can be personalized individual hypoxic responses. Another critical aspect prevent long-term physical damage management altitudes, enabled by emerging technologies wearable sensors, Internet Medical Things artificial intelligence. In this review, we outline progress pre-acclimatization management, as well understanding physiological mechanisms under hypoxia, highlighting important role played sensors closed-loop control systems developing intelligent solutions. We also discuss challenges prospects deploying autonomous monitoring management.

Language: Английский

Citations

0
Multi-omics analysis reveals phenylalanine enhance mitochondrial function and hypoxic endurance via LKB1/AMPK activation DOI Creative Commons
Yi‐Long Wu, Yi Ma, Qiang Li

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Oct. 10, 2024

Many studies have focused on the effects of small molecules, such as amino acids, metabolism under hypoxia. Recent findings indicated that phenylalanine levels were markedly elevated in adaptation to chronic This raises possibility treatment could improve hypoxic endurance. However, importance hypoxia-regulated is still unclear. study investigates role hypoxia using a zebrafish model and multi-omics analysis. We found phenylalanine-related metabolic pathways are significantly up-regulated hypoxia, contributing enhanced Phenylalanine reduced ROS levels, improved mitochondrial oxygen consumption rate (OCR), extracellular acidification (ECAR) cells. Western blotting revealed increased uptake via L-type transporters (LAT1), activating LKB1/AMPK signaling pathway. activation peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) Bcl-2/Bax ratio, while down-regulating uncoupling protein 2 (UCP2), thereby improving function first comprehensive analysis demonstrate phenylalanine's crucial adaptation, providing insights for development anti-hypoxic drugs.

Language: Английский

Citations

3
Th1/Th2 Immune Imbalance in the Spleen of Mice Induced by Hypobaric Hypoxia Stimulation and Therapeutic Intervention of Astragaloside IV DOI Open Access

Rong Gao,

Zhenhui Wu,

Wanyun Dang

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2584 - 2584

Published: March 13, 2025

This study aims to establish a hypobaric hypoxia-induced immune injury model and investigate the intervention therapeutic effects of Astragaloside IV (AS-IV). simulated hypoxia stimulation in mice at an altitude 7000 m on plateau for 1, 3, 5, 7 days. HE staining transcriptomic analysis were performed mouse spleens. In addition, AS-IV was selected prevention treatment, validated by flow cytometry, ELISA, Q-PCR. The results showed that under hypoxic conditions 5 days, peripheral blood lymphocytes decreased, CD45+ cells, CD3+ T CD3+CD4+ CD4+/CD8+ cell ratio spleen all decreased. can significantly alleviate pathological damage spleen, decrease serum levels IL-2 IL-6, increase IL-4 IL-10, raise cells while increasing CD4+IFN-γ+cells reducing ROS apoptosis content relevant mRNA Th1/Th2 pathway. summary, simulating days stable model, effectively injury.

Language: Английский

Citations

0
RIPC improves myocardial injury by promoting mitochondrial protection via the PGC-1α/Nrf2 pathway DOI Creative Commons
Zhenzhou Zhao, Zhiwen Zhang, Xuejie Li

et al.

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108476 - 108476

Published: April 1, 2025

Myocardial infarction (MI) is a common condition with high morbidity and mortality rates. Remote ischemic preconditioning (RIPC) activates the endogenous protective mechanisms by promoting tolerance mitigating subsequent damage caused fatal ischemia. Maintaining mitochondrial function imperative for prevention of myocardial The current study aims to evaluate therapeutic effects RIPC on MI focus involved in function. In our study, patients who underwent coronary angiography were randomly assigned either group (n = 20) or control 20). intervention was administered preoperatively inflating blood pressure cuff upper arm 200 mmHg four cycles 5 min each, interspersed 5-min reperfusion intervals. process alleviated injury among participants, accompanied significant elevation serum concentrations PGC-1α Nrf2 levels serum. In-vitro studies showed that can protect cardiomyocytes against preserving morphology, maintaining membrane integrity, reducing oxidative stress. In-vivo experimental findings illustrated mitigated structural mice augmenting function, leading cardiac protection, as evidenced improved reduced infarct size. Moreover, abolished upon silencing PGC-1α. Collectively, results indicated PGC-1α/Nrf2 signaling pathway rescue during insult, suggesting promising strategy preventing ischemia injury.

Language: Английский

Citations

0
Hypoxia reduces mouse urine output via HIF1α–mediated up–regulation of renal AQP1 DOI Creative Commons
Rongfang Qiao, Xiaohui Cui, Yitong Hu

et al.

Kidney Diseases, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 15

Published: Oct. 22, 2024

Patients with acute mountain sickness (AMS) due to hypoxia at high altitudes often exhibit abnormal water metabolism. Hypoxia-inducible factors (HIFs) are major regulators of adaptive responses hypoxia. As transcription factors, HIFs involved in the regulation erythropoiesis, iron metabolism, angiogenesis, energy and cell survival by promoting transcriptional expression hundreds target genes. Roxadustat, a novel drug for treatment anemia associated chronic kidney disease (CKD), acts inhibiting degradation increase their protein levels. However, clinical use roxadustat is frequently peripheral edema, suggesting involvement regulating body's balance possibly modulating reabsorption kidney.

Language: Английский

Citations

0