Activated DRP1 promotes mitochondrial fission and induces glycolysis in ATII cells under hyperoxia DOI Creative Commons
T. Sun,

Haiyang Yu,

Dingning Zhang

et al.

Respiratory Research, Journal Year: 2024, Volume and Issue: 25(1)

Published: Dec. 26, 2024

Recent studies have reported mitochondrial damage and metabolic dysregulation in BPD, but the changes dynamics glucose reprogramming ATII cells their regulatory relationship not been reported. Neonatal rats this study were divided into model (FIO2:85%) control (FIO2: 21%) groups. Lung tissues extracted at 3, 7, 10 14 postnatal days then conducted HE staining for histopathological observation. We assessed expression of mitochondria dynamic associated proteins glycolysis enzymes lung tissues, primary RLE-6TN cells. Double immunofluorescence was used to confirm co-localization DRP1 Real-time analyses ECAR OCR performed with using Seahorse XF96. ATP concentration measured an kit. treated 85% hyperoxia 48 h fission inhibitor Mdivi-1 verify role regulating reprogramming. found that causes cells' morphological change. The p-DRP1 increased tissue neonatal exposed hyperoxia. Glycolysis related including PFKM, HK2, LDHA also increased. Hyperoxia inhibited production In cells, we verified administration could alleviate enhancement aerobic fragmentation caused by exposure leads mediates metabolism via signaling pathway. Inhibiting activation pathway may be a promising therapeutic target BPD.

Language: Английский

Itaconic acid regulation of TFEB-mediated autophagy flux alleviates hyperoxia-induced bronchopulmonary dysplasia DOI Creative Commons
Chengbo Liu, Changchang Fu,

Yazhou Sun

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 72, P. 103115 - 103115

Published: March 11, 2024

Premature infants often require oxygen supplementation, which can elicit bronchopulmonary dysplasia (BPD) and lead to mitochondrial dysfunction. Mitochondria play important roles in lung development, both normal metabolism apoptosis. Enhancing our comprehension of the underlying mechanisms BPD development facilitate effective treatments. Plasma samples from non-BPD were collected at 36 weeks post-menstrual age used for metabolomic analysis. Based on hyperoxia-induced animal cell models, changes mitophagy apoptosis evaluated following treatment with itaconic acid (ITA). Finally, mechanism action ITA was comprehensively demonstrated through rescue strategies administration corresponding inhibitors. An imbalance tricarboxylic (TCA) cycle significantly affected serving as a significant metabolic marker outcomes development. improved morphological rats, promoted SP-C expression, inhibited degree alveolar type II epithelial cells (AEC II) Mechanistically, mainly promotes nuclear translocation transcription factor EB (TFEB) dysfunctional clearance reduces AEC by regulating autophagic flux. The TCA is closely related improve flux promote TFEB TFEB, implying its potential therapeutic utility BPD.

Language: Английский

Citations

10
Impact of hyperoxia on the gut during critical illnesses DOI Creative Commons

Ninan Dai,

Juan Gu,

Yanhong Luo

et al.

Critical Care, Journal Year: 2024, Volume and Issue: 28(1)

Published: March 1, 2024

Abstract Molecular oxygen is typically delivered to patients via inhalation or extracorporeal membrane oxygenation (ECMO), potentially resulting in systemic hyperoxia from liberal localized the lower body peripheral venoarterial (VA) ECMO. Consequently, this exposes gastrointestinal tract excessive levels. Hyperoxia can trigger organ damage due overproduction of reactive species and associated with increased mortality. The gut microbiome play pivotal roles critical illnesses even small variations levels have a dramatic influence on physiology ecology microbes. Here, we reviewed emerging preclinical evidence which highlights how inhaled provoke diffuse villous damage, barrier dysfunction gut, dysbiosis. hallmark dysbiosis includes expansion oxygen-tolerant pathogens (e.g., Enterobacteriaceae ) depletion beneficial oxygen-intolerant microbes Muribaculaceae ). Furthermore, discussed potential impact various underlying involving inspiratory VA-ECMO. Currently, available findings area are somewhat controversial, consensus has not yet be reached. It appears that targeting near-physiological may offer means avoid hyperoxia-induced injury hypoxia-induced mesenteric ischemia. However, optimal target vary depending special clinical conditions, including acute hypoxia adults neonates, as well particular undergoing surgery VA-ECMO support. Last, outlined current challenges need for future studies area. Insights into vital ongoing research assist clinicians optimizing critically ill patients.

Language: Английский

Citations

7
Identification of serum metabolite biomarkers in premature infants with bronchopulmonary dysplasia: protocol for a multicentre prospective observational cohort study DOI Creative Commons
Yanping Guo, Wanxiang He,

Songzhou Xu

et al.

BMJ Open, Journal Year: 2025, Volume and Issue: 15(1), P. e089064 - e089064

Published: Jan. 1, 2025

Introduction Bronchopulmonary dysplasia (BPD) is one of the most common and significant complications preterm birth. It ultimately leads to a decrease in quality life for infants impacts their long-term health. Early prediction timely intervention are crucial halting development BPD. This study aims identify biomarkers that can predict early occurrence BPD by screening serum metabolites infants. will provide strong support targeted interventions future research. Methods analysis prospective, multicentre, open-label, observational cohort spanning 3 years. be conducted six major neonatal intensive care units Shenzhen, China, involving born at gestational ages <32 weeks. Demographic data treatment information collected prospectively. Serum samples five distinct time points: within 24 hours after birth, 1 week, 2 weeks, 28 days 36 weeks postmenstrual age. These undergo using liquid chromatography-tandem mass spectrometry untargeted metabolomics studies. Participants categorised into non-BPD groups based on final diagnosis, metabolite differences between these analysed. The enrol 1500 with over A three-step strategy—discovery, validation clinical testing—will used validate utility novel biomarkers. Additionally, nested case-control conducted, matching participants 1:1 control group sharing similar risk factors. Ethics dissemination Our protocol has been approved Medical Committees all participating hospitals, including Peking University Shenzhen Hospital, People’s Baoan Women’s Children’s Longgang District Maternity Child Healthcare Nanshan Hospital Luohu Hospital. We disseminate our results through academic conferences peer-reviewed public journals. Trial registration number ChiCTR2400081615.

Language: Английский

Citations

0
Preconception maternal hyperoxia exposure causes cardiac insufficiency through induction of mitochondrial toxicity in mice offspring DOI
Dan Chen, Xing Zhang,

Sheng-peng Li

et al.

Reproductive Toxicology, Journal Year: 2025, Volume and Issue: unknown, P. 108864 - 108864

Published: Feb. 1, 2025

Language: Английский

Citations

0
Glucagon-like peptide-1 receptor signaling activation in alveolar type II cells enhances lung development in neonatal rats exposed to hyperoxia DOI Creative Commons
T. Sun, Haiyang Yu, Dingning Zhang

et al.

Redox Biology, Journal Year: 2025, Volume and Issue: 82, P. 103586 - 103586

Published: March 6, 2025

Many studies have reported the important role of glucagon-like peptide-1 receptor (GLP-1R) in regulating glucose homeostasis. However, addition to pancreas, GLP-1R is distributed organs such as lungs. A few researches mechanism action acute and chronic lung diseases. Nevertheless, its effect on development remains unclear. In this research, we aimed explore potential mechanisms vivo vitro bronchopulmonary dysplasia (BPD) models. Neonatal Sprague-Dawley rats were divided into hyperoxia (FIO2 = 0.85) control 0.21) groups. Lung tissues extracted at 3, 7, 10, 14 postnatal days subjected hematoxylin eosin staining for histopathological morphological observation. Single-cell RNA sequencing was performed development. Western blotting conducted assess expression GLP-1R, dynamin-related protein 1 (DRP1), glycolysis-associated enzymes, including phosphofructokinase (PFKM), hexokinase 2 (HK2), lactate dehydrogenase (LDHA), tissues, primary alveolar type II (ATII) cells, RLE-6TN cells. Double immunofluorescence confirm co-localization DRP1, ATII Seahorse XF96 metabolic extracellular flux analyzer used perform real-time analyses acidification rate oxygen consumption cells isolated from The adenosine triphosphate (ATP) concentrations measured using an ATP kit. Mitochondria stained with MitoTracker observed HiS-SIM. gene levels tested RT-qPCR. We MeRIP-qPCR determine m6A modification level mRNA reporter verify site key methyltransferases. that signaling regulates plays a particularly after birth. Hyperoxia inhibits accelerates BPD production decreased glycolysis increased under hyperoxia. Activation promotes downregulates by DRP1 induced mitochondria fission. verified decreased; primarily methyltransferase-like (METTL14). expressed neonatal can promote during early period. pathway modulates mitochondrial fission metabolism inhibit activation inhibiting methylation pathogenesis.

Language: Английский

Citations

0
Mechanistic advances of hyperoxia-induced immature brain injury DOI Creative Commons
Yue Song, Changqiang Yang

Heliyon, Journal Year: 2024, Volume and Issue: 10(9), P. e30005 - e30005

Published: April 22, 2024

The impact of hyperoxia-induced brain injury in preterm infants is being increasingly investigated. However, the parameters and protocols used to study this condition animal models lack consistency. Research further hampered by fact that hyperoxia exerts both direct indirect effects on oligodendrocytes neurons, with precise underlying mechanisms remaining unclear. In article, we aim provide a comprehensive overview conditions induce immature injury. We discuss what known regarding injury, focusing briefly describe therapies may counteract hyperoxia. also identify studies required fully elucidate as well leading therapeutic options.

Language: Английский

Citations

2
Dysfunction of astrocytic glycophagy exacerbates reperfusion injury in ischemic stroke DOI Creative Commons
Haiyun Guo, Yumeng Li,

Shiquan Wang

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 74, P. 103234 - 103234

Published: June 7, 2024

Glycophagy has evolved from an alternative glycogen degradation pathway into a multifaceted pivot to regulate cellular metabolic hemostasis in peripheral tissues. However, the pattern of glycophagy brain and its potential therapeutic impact on ischemic stroke remain unknown. Here, we observed that dysfunction astrocytic was caused by downregulation GABA type A receptor-associated protein like 1 (GABARAPL1) during reperfusion patients mice. PI3K-Akt activation is involved driving GABARAPL1 cerebral reperfusion. Moreover, dysfunction-induced glucosamine deficiency suppresses nuclear translocation specificity TATA binding protein, transcription factors for GABARAPL1, decreasing their O-GlcNAcylation levels, accordingly feedback inhibits astrocytes Restoring overexpressing decreases DNA damage oxidative injury improves survival surrounding neurons In addition, hypocaloric diet acute phase after can enhance glycophagic flux accelerate neurological recovery. summary, links autophagy, metabolism, epigenetics together, exacerbates stroke.

Language: Английский

Citations

2
Analysis of variable metabolites in preterm infants with bronchopulmonary dysplasia: a systematic review and meta-analysis DOI Creative Commons
Yanping Guo, Ying Liu, Ruolin Zhang

et al.

˜The œItalian Journal of Pediatrics/Italian journal of pediatrics, Journal Year: 2024, Volume and Issue: 50(1)

Published: Nov. 14, 2024

Abstract Numerous studies have attempted to identify potential biomarkers for early detection of bronchopulmonary dysplasia (BPD) in preterm infants using metabolomics techniques. However, the presence consistent evidence remains elusive. Our study aimed conduct a systematic review and meta-analysis differences small-molecule metabolites between BPD non-BPD infants. Through meticulous screening numerous samples, we identified promising candidates, providing valuable insights future research. We searched PubMed, Cochrane Library, Embase, Web Science, China National Knowledge Internet, Wan-fang database, Chinese Science Technique Journal Database Biomedical Literature from inception until January 16, 2024. Studies were comprehensively reviewed against inclusion criteria. included case-control adhered Preferred Reporting Items Systematic Reviews Meta-Analysis guidelines. Study quality was assessed with Newcastle-Ottawa scale. compared changes metabolite levels A conducted on targeted research data based strategy standardized mean (MD) 95% confidence intervals (CI).Fifteen (1357 participants) included. These clinical-based clarified 110 differential The revealed higher glutamate concentration group (MD = 1, CI 0.59 1.41, p < 0.00001). Amino acids as key distinguishing without BPD, potentially serving predictor this population.

Language: Английский

Citations

1
Genetic Ablation of Pyruvate Dehydrogenase Kinase Isoform 4 Gene Enhances Recovery from Hyperoxic Lung Injury: Insights into Antioxidant and Inflammatory Mechanisms DOI Creative Commons

Keisuke Watanabe,

Akie Kato,

Hiroyuki Adachi

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(4), P. 746 - 746

Published: March 27, 2024

Background: Pyruvate dehydrogenase kinase isoform 4 (PDK4) plays a pivotal role in the regulation of cellular proliferation and apoptosis. The objective this study was to examine whether genetic depletion PDK4 gene attenuates hyperoxia-induced lung injury neonatal mice. Methods: Neonatal PDK4−/− mice wild-type (WT) were exposed oxygen concentrations 21% (normoxia) 95% (hyperoxia) for first days life. Pulmonary histological assessments performed, mRNA levels PDK4, monocyte chemoattractant protein (MCP)-1 interleukin (IL)-6 assessed. inflammatory cytokines tissue quantified. Results: Following convalescence from hyperoxia, exhibited improved alveolarization. Notably, displayed significantly elevated MCP-1 pulmonary tissues following hyperoxic exposure, whereas WT showed increased IL-6 under similar conditions. Furthermore, subjected hyperoxia demonstrated markedly higher expression at age compared mice, while remained unaffected Conclusions: Newborn notable recovery injury, suggesting potential protective mitigating damage.

Language: Английский

Citations

0
Analysis of blood metabolite characteristics at birth in preterm infants with bronchopulmonary dysplasia: an observational cohort study DOI Creative Commons
Yanping Guo, Jingjing Chen, Zhen Zhang

et al.

Frontiers in Pediatrics, Journal Year: 2024, Volume and Issue: 12

Published: Oct. 31, 2024

To analyze the characteristics of blood metabolites within 24 h after birth in preterm infants with bronchopulmonary dysplasia (BPD) and to identify biomarkers for predicting occurrence BPD.

Language: Английский

Citations

0