WHAMM Inhibits Type II Alveolar Epithelial Cell EMT by Mediating Autophagic Degradation of TGF‐β1 in Bronchopulmonary Dysplasia DOI Open Access

Shaodong Hua,

Jinghan Chi,

Ning Zhang

et al.

Journal of Cellular Physiology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 20, 2024

Bronchopulmonary dysplasia (BPD) is one of the most prevalent complication in preterm infants, primarily characterized by arrested alveolar growth. The involvement epithelial-mesenchymal transition (EMT) AECII cells proposed to have a crucial role pathogenesis BPD; however, underlying mechanism remains unclear. present study reveals significant reduction WHAMM (WASP homolog associated with actin, membranes, and microtubules) hyperoxia-induced BPD mice, highlighting its suppressing progression through inhibition EMT AECIIs. We demonstrated that downregulation leads accumulation TGF-β1 mediation autophagic degradation pathway. Mechanistically, enhanced autophagosomal localization concurrently promoted process autophagy, thereby comprehensively facilitating TGF-β1. These findings reveal important development BPD, WHAMM/autophagy/TGF-β1/EMT pathway may represent potential therapeutic strategy for treatment.

Language: Английский

Multimodal Metabolomics Analysis Reveals That Classic Decoction Mitigates Myocardial Ischemia‐Induced Damage by Modulating Energy and Branched‐Chain Amino Acid Metabolism DOI Open Access
Zhimin Ying, Jun Pu, Yingying Hu

et al.

Biomedical Chromatography, Journal Year: 2025, Volume and Issue: 39(2)

Published: Jan. 11, 2025

ABSTRACT Gualou‐Xiebai‐Banxia (GXB) decoction shows potential for treating myocardial ischemia (MI), although its underlying mechanism is not fully understood. In this study, a multimodal metabolomics approach, combining gas chromatography–mass spectrometry (GC–MS) and 1 H‐NMR, was employed to investigate the cardioprotective effects of GXB in rat model induced by ligation. ELISA assays HE staining demonstrated that effectively reduced injury, oxidative stress markers, fibrosis. Orthogonal partial least‐squares discriminant analysis identified 62 biomarkers, 20 which were confirmed using standard compounds. The GC–MS method showed excellent linearity across wide concentration range (0.004–29.7 μg/mL, R 2 > 0.9995), with intra‐ inter‐day precision RSD values below 4.72% 4.96%, respectively. Method recoveries ranged from 95.40% 104.83%, under 4.84%. Pathway enrichment revealed alleviates ischemia‐induced damage primarily modulating energy metabolism branched‐chain amino acid metabolism. These findings provide valuable support clinical application ischemia.

Language: Английский

Citations

0
The tryptophan metabolite 3-hydroxyanthranilic acid alleviates hyperoxia-induced bronchopulmonary dysplasia via inhibiting ferroptosis DOI Creative Commons

Qiqi Ruan,

Y. Peng, X. Yi

et al.

Redox Biology, Journal Year: 2025, Volume and Issue: 82, P. 103579 - 103579

Published: March 9, 2025

Bronchopulmonary dysplasia (BPD) is a prevalent chronic respiratory condition in preterm infants with an increasing incidence, severely affecting their survival rate and quality of life. Exploring the underlying mechanisms BPD helps to develop novel effective therapeutic strategies. In this study, integrated metabolomic analyses tracheal aspirates (TAs) from non-BPD infants, along lung tissues hyperoxia-induced experimental neonatal rats control rats, demonstrated that was associated significant reduction 3-hydroxyanthranilic acid (3-HAA), which confirmed be partly caused by tryptophan-metabolizing enzyme disorders. vivo vitro models were subsequently established assess efficacy 3-HAA relation BPD. Compared group, nebulization improved development suppressed inflammation rats. Limited proteolysis-small molecule mapping (LiP-SMap) proteomic analysis revealed involvement ferroptosis pathway mechanism alleviated injury. Ferroptosis identified detecting Fe2+ levels, malondialdehyde (MDA), 4-HNE, total aldehydes, mitochondrial morphology, ferroptosis-associated protein mRNA expression, dysregulation indeed ameliorated vivo. Furthermore, combination LiP-SMap, molecular docking, SPR Co-IP can bind directly FTH1 disrupt nuclear receptor coactivator 4 (NCOA4)-FTH1 interaction. conclusion, our study first reveal linked 3-HAA, could inhibit targeting FTH1, thereby alleviating injury alveolar type II epithelial cells, highlighting potential for clinical applications

Language: Английский

Citations

0
Ferroptosis and hyperoxic lung injury: insights into pathophysiology and treatment approaches DOI Creative Commons

Xiaoqiong Zhou,

Lei Tian, Zongde Zhang

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 18, 2025

Hyperoxia therapy is a critical clinical intervention for both acute and chronic illnesses. However, prolonged exposure to high-concentration oxygen can cause lung injury. The mechanisms of hyperoxic injury (HLI) remain incompletely understood, current treatment options are limited. Improving the safety hyperoxia has thus become an urgent priority. Ferroptosis, novel form regulated cell death characterized by iron accumulation excessive lipid peroxidation, been implicated in pathogenesis HLI, including diffuse alveolar damage, vascular endothelial injury, bronchopulmonary dysplasia. In this review, we analyze latest findings on ferroptosis therapeutic strategies HLI. Our aim provide new insights HLI facilitate translation these from bench bedside.

Language: Английский

Citations

0
Rescuing fertility: Itaconic acid prevents ovarian damage through NRF2-mediated pyroptosis pathways in diminished ovarian reserve models DOI
Ning Yang, Wenxiu Mo, Xin Lei

et al.

Cellular Signalling, Journal Year: 2025, Volume and Issue: unknown, P. 111766 - 111766

Published: March 1, 2025

Language: Английский

Citations

0
The anti-inflammatory effects of itaconate and its derivatives in neurological disorders DOI Creative Commons
Xiangyi Kong, Xu Lin,

Zheng Mou

et al.

Cytokine & Growth Factor Reviews, Journal Year: 2024, Volume and Issue: 78, P. 37 - 49

Published: July 6, 2024

Almost 16 % of the global population is affected by neurological disorders, including neurodegenerative and cerebral neuroimmune diseases, triggered acute or chronic inflammation. Neuroinflammation recognized as a common pathogenic mechanism in wide array conditions Alzheimer's disease, Parkinson's postoperative cognitive dysfunction, stroke, traumatic brain injury, multiple sclerosis. Inflammatory process central nervous system (CNS) can lead to neuronal damage apoptosis, consequently exacerbating these diseases. Itaconate, an immunomodulatory metabolite from tricarboxylic acid cycle, suppresses neuroinflammation modulates CNS immune response. Emerging human studies suggest that itaconate levels plasma cerebrospinal fluid may serve biomarkers associated with inflammatory responses disorders. Preclinical have shown its highly cell-permeable derivatives are promising candidates for preventing treating neuroinflammation-related The underlying involve regulation cells signaling pathways molecules Nrf2/KEAP1 pathway, reactive oxygen species, NLRP3 inflammasome. Here, we introduce metabolism function synthesis development derivatives. We summarize potential impact therapeutic on molecules, based preclinical evidence via various disorder models. also discuss challenges solutions clinical translation promote further research

Language: Английский

Citations

1
The role and therapeutic potential of itaconate in lung disease DOI Creative Commons
Ruyuan He,

Yifan Zuo,

Ke Yi

et al.

Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)

Published: Oct. 1, 2024

Language: Английский

Citations

1
Itaconic acid ameliorates necrotizing enterocolitis through the TFEB-mediated autophagy-lysosomal pathway DOI

Baozhu Chen,

Yufeng Liu,

Shunchang Luo

et al.

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 226, P. 251 - 265

Published: Nov. 19, 2024

Language: Английский

Citations

1
Identification of a novel mitophagy-related signature for predicting clinical prognosis and immunotherapy of osteosarcoma DOI Creative Commons
Peichuan Xu,

Jiangminghao Zhao,

Wenrui Zhao

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: May 2, 2024

Abstract Background Osteosarcoma (OS) is a highly aggressive malignancy characterized by poor prognosis. Mitochondrial autophagy (mitophagy) has been implicated in tumor initiation, progression, and response to therapy, highlighting it potential prognostic indicator therapeutic target cancers. Despite this, the precise mechanisms underlying mitophagy osteosarcoma remain enigmatic. This research aims develop mitophagy-associated signature guide strategies prognosis estimations. Methods Clinical transcriptome data for patients with skeletal muscle tissue were retrieved from UCSC Xena GTEx. Mitophagy-related genes (MRGs) obtained Kyoto Encyclopedia of Genes Genomes (KEGG) website. A predictive risk model was constructed using Least Absolute Shrinkage Selection Operator (LASSO) algorithm Cox regression analysis. To delve into fundamental gene expression mechanisms, we employed Gene Ontology (GO), KEGG, Set Enrichment Analysis (GSEA). Moreover, different immune-related activities between two groups investigated ascertain efficacy immunotherapy. Lastly, functional analysis key MRAS carried out via vitro experiments pan-cancer small molecule drugs that may screened through molecular docking. Results Based on seven mitophagy-related signatures, stratified high- low-risk categories. The exhibited strong capability, as evidenced Kaplan-Meier analysis, time-dependent AUC, Nomogram. Notably, compared group, individuals high-risk group lower stromal, immune, estimate scores.The infiltration immune cells decreased. Further evidence supporting MRAS's protective role against shown in vitro, where upregulating its could suppress proliferation, migration, invasion while stimulating their apoptosis. Pan-cancer further demonstrated variety tumors. Conclusion study identified elucidated impact cells. Consequently, opened up fresh avenues clinical prediction established basis precision therapy osteosarcoma.

Language: Английский

Citations

0
Pulmonary Surfactant Biogenesis Blockage Mediated Polyhexamethylene Guanidine Disinfectant Induced Pulmonary Fibrosis DOI
Xin Li,

Jianzhong Zhang,

Mingyue Wang

et al.

Journal of Hazardous Materials, Journal Year: 2024, Volume and Issue: 480, P. 136307 - 136307

Published: Oct. 30, 2024

Language: Английский

Citations

0
WHAMM Inhibits Type II Alveolar Epithelial Cell EMT by Mediating Autophagic Degradation of TGF‐β1 in Bronchopulmonary Dysplasia DOI Open Access

Shaodong Hua,

Jinghan Chi,

Ning Zhang

et al.

Journal of Cellular Physiology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 20, 2024

Bronchopulmonary dysplasia (BPD) is one of the most prevalent complication in preterm infants, primarily characterized by arrested alveolar growth. The involvement epithelial-mesenchymal transition (EMT) AECII cells proposed to have a crucial role pathogenesis BPD; however, underlying mechanism remains unclear. present study reveals significant reduction WHAMM (WASP homolog associated with actin, membranes, and microtubules) hyperoxia-induced BPD mice, highlighting its suppressing progression through inhibition EMT AECIIs. We demonstrated that downregulation leads accumulation TGF-β1 mediation autophagic degradation pathway. Mechanistically, enhanced autophagosomal localization concurrently promoted process autophagy, thereby comprehensively facilitating TGF-β1. These findings reveal important development BPD, WHAMM/autophagy/TGF-β1/EMT pathway may represent potential therapeutic strategy for treatment.

Language: Английский

Citations

0