Pinoresinol Diglucoside Attenuates Nuclear Receptor Coactivator 4‐Mediated Ferritinophagy Associated with Cisplatin‐Induced Hearing Loss

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

Cisplatin can cause irreversible hearing loss. However, effective approaches to its prevention are not established. In this study, the effect of traditional Chinese medicine monomer pinoresinol diglucoside (PDG) is evaluated on cisplatin-induced ototoxicity and underlying mechanism action. PDG significantly increases cell viability inhibits reactive oxygen species production ferroptosis in cisplatin-treated House Ear Institute-Organ Corti 1 cells basilar membranes. partially restores loss caused by cisplatin. Transcriptome sequencing identifies Suppressor Cytokine Signaling (SOCS1), which elevated cisplatin-only group but reduced after application. SOCS1 a ferroptosis-promoting factor, knocking it down nuclear receptor coactivator 4 (NCOA4) ferritinophagy. Transmission electron microscopy reveals that reduces number autophagic lysosomes induced Co-immunoprecipitation performed confirm interaction between NCOA4. Taken together, these results indicate NCOA4-mediated ferritinophagy downregulating SOCS1, ototoxicity. This study provides new clinical option for

Language: Английский

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Exploring Ferroptosis in Allergic Inflammatory Diseases: Emerging Mechanisms and Therapeutic Perspectives

Cell Biology International, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

ABSTRACT Ferroptosis, a unique form of regulated cell death driven by iron accumulation and lipid peroxidation, has emerged as critical process in various diseases. Recent evidence suggests its involvement the pathogenesis allergic diseases, including asthma, rhinitis, atopic dermatitis. These conditions are characterized chronic inflammation, oxidative stress, immune dysregulation, all which intersect with molecular mechanisms ferroptosis. Key regulators, such glutathione peroxidase 4 (GPX4), cystine/glutamate antiporter system Xc‐, metabolism pathways, play pivotal roles ferroptotic processes their contribution to disease progression. This review explores mechanistic link between ferroptosis emphasizing how damage overload exacerbate inflammation tissue injury. We also highlight emerging diagnostic biomarkers, peroxidation products could improve monitoring stratification. Therapeutic strategies targeting ferroptosis, GPX4 activators, chelators, inhibitors, show promise preclinical\ studies, offering potential new avenues for treating However, challenges remain translating these findings into clinical applications. By integrating current knowledge, this underscores need further research both biomarker therapeutic target

Language: Английский

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JAK/STAT signaling as a key regulator of ferroptosis: mechanisms and therapeutic potentials in cancer and diseases

Cancer Cell International, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 7, 2025

Ferroptosis is a distinct form of regulated cell death characterized by iron-dependent lipid peroxidation, playing critical role in various diseases, including cancer, neurodegeneration, and tissue damage. This study reviews the intricate relationship between ferroptosis Janus kinase/signal transducer activator transcription (JAK/STAT) signaling pathway, highlighting its regulatory functions across multiple biological processes. Dysregulation JAK/STAT pathway implicated promoting or inhibiting ferroptosis, depending on context. JAK2 promotes activating STAT proteins, modulating expression key regulators like SLC7A11 GPX4, influencing iron homeostasis through pathways such as ferritinophagy hepcidin regulation. STAT1 activation primarily enhances suppression cystine-glutamate antiporter (System Xc-), leading to glutathione depletion contributing conditions Sjogren's syndrome age-related macular degeneration. In contrast, STAT3 plays protective upregulating which inhibits survival, particularly cancers hepatocellular carcinoma, prostate renal carcinoma. also discusses STAT6's involvement diseases asthma lung injury regulating antioxidant defenses. Furthermore, review explores potential therapeutic strategies targeting manipulate for disease treatment. cancer therapy, this can enhance effectiveness inducers, offering promising avenues overcome drug resistance. Additionally, interplay immune responses, oxidative stress, metabolism underscores significance progression intervention. By exploring these mechanisms, provides insights into development novel treatments modulation, with implications inflammatory neurodegenerative conditions.

Language: Английский

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Therapeutic Potential of Platycodon Saponin D in Allergic Asthma through Anti-Inflammatory and Anti-Remodeling Effects

Phytomedicine, Journal Year: 2025, Volume and Issue: unknown, P. 156728 - 156728

Published: April 1, 2025

Language: Английский

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Targeting glutamate metabolism in chronic lung diseases

Clinical and Translational Discovery, Journal Year: 2024, Volume and Issue: 4(2)

Published: April 1, 2024

Abstract Amino acids are necessary for all life forms, which play various roles. Disorder of amino acid metabolism is now considered an important driving mechanism in diverse pulmonary conditions, particularly chronic lung diseases like obstructive disease, idiopathic fibrosis and cancer. Glutamate actively participates multiple vital biological processes, while the intricate glutamate metabolism, receptors transporters assume crucial regulatory functions development diseases. This review aims to discuss relationship between dysfunction By discussing physiological pathological function glutamate, we probe potential drug targets pathway.

Language: Английский

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Ferroptosis in Cancer: A new perspective on T cells

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 143, P. 113539 - 113539

Published: Nov. 1, 2024

Language: Английский

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Silencing SMAD4 inhibits inflammation and ferroptosis in asthma by blocking the IL-17A signaling pathway

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

Published: Dec. 6, 2024

The TGF-β/SMAD signaling pathway is crucial in the pathogenesis of asthma. However, SMAD family member 4 (SMAD4), a key mediator TGF-β, its roles and underlying mechanisms asthma remain unclear. vivo vitro SMAD4 were investigated through an ovalbumin (OVA)-induced mouse model interleukin-13 (IL-13)-induced cell model. molecular mechanism influenced was examined using transcriptome sequencing, followed by feedback experiments involving recombinant human interleukin 17 A (rhIL-17 A), IL-17 activator. highly expressed models. silencing alleviated damage to lung tissue decreased inflammatory infiltration. Expression levels Caspase-3, IgG, factors reduced after SMAD4. Silencing suppressed ferroptosis. also enhanced IL-13-induced BEAS-2B proliferation apoptosis. Furthermore. promoted models, as evidenced elevated IL-17RA, A, Act1 protein levels. inhibited expression these pathway-associated proteins. Moreover, rhIL-17 treatment notably reversed impacts on OVA-induced model, indicating that inflammation ferroptosis blocking pathway. prevents inhibiting pathway, which provides novel potential approach for therapy.

Language: Английский

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Quercetin inhibits ferroptosis through the SIRT1/Nrf2/HO-1 signaling pathway and alleviates asthma disease

Translational Pediatrics, Journal Year: 2024, Volume and Issue: 13(10), P. 1747 - 1759

Published: Oct. 1, 2024

Quercetin (QCT) is a bioflavonoid derived from vegetables and fruits that has anti-inflammatory anti-ferroptosis effects against various diseases. Previous studies have shown QCT modulates the production of cellular inflammatory factors in asthma models delays development chronic airway inflammation. However, regulatory mechanism QCT, traditional Chinese medicine, treatment not been elucidated. The aim present study to investigate whether can inhibit ferroptosis via SIRT1/Nrf2 pathway play therapeutic role asthma.

Language: Английский

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Au/FeNiPO₄‐Based Multiple Spectra Optoacoustic Tomography/CT Dual‐Mode Nanoprobe for Systemic Screening of Atherosclerotic Vulnerable Plaque

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(44)

Published: May 29, 2024

Abstract Current diagnostic technique in direct identification of multi‐site plaques and simultaneous assessment plaque vulnerability remains a challenge, which is crucial for indicating the risk atherosclerotic cardiovascular diseases (ASCVD). Herein, an osteopontin (OPN)‐specific nanoprobe (OPN Ab‐Au/FeNiPO 4 @ICG) with both multiple spectra optoacoustic tomography (MSOT) computed (CT) imaging, constructed successfully realizing systemic screening vulnerable plaque. OPN @ICG specifically targeted OPN‐overexpressed foam cells recognized at molecular level. In AS mice, CT imaging exhibits that effectively avoid interference from calcification accurately visualized MSOT functional results reveals after injection nanoprobe, carotid exhibited much higher signal than aortic arch ( P = 0.0291). Further pathological analysis displays possessed score 0.0247), agreement signals. More importantly, linear regression confirms high correlation between signals R 0.7095 0.0216), demonstrating potential proposed systematic evaluation vulnerability. This work employs dual‐model strategy localization assessment, greatly advancing accurate diagnosis ASCVD.

Language: Английский

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Characterization of dipyridamole as a novel ferroptosis inhibitor and its therapeutic potential in acute respiratory distress syndrome management

Theranostics, Journal Year: 2024, Volume and Issue: 14(18), P. 6947 - 6968

Published: Oct. 21, 2024

Rationale: Ferroptosis in lung epithelium and endothelium contributes to the pathogenesis of acute respiratory distress syndrome (ARDS), a critical often fatal condition marked by inflammation elevated pulmonary vascular permeability. Despite this, there are currently no FDA-approved therapeutics specifically targeting ferroptosis for ARDS management. Methods: A screening 259 drugs was conducted identify an effective inhibitor epithelial endothelial cells. The anti-ferroptotic therapeutic efficacy this screened drug rigorously evaluated using two distinct mouse models (LPS-induced injury CLP-induced sepsis) human airway organoids (hAOs). regulatory mechanism on inhibition investigated via RNA-sequencing, qRT-PCR, western blotting, IF, luciferase reporter assay, chromatin immunoprecipitation limited proteolysis-mass spectrometry cellular thermal shift affinity responsive target stability assay. Furthermore, proof-of-concept clinical trial conducted, wherein patients were administered with as adjunctive therapy. Results: Dipyridamole (DIPY) identified potent DIPY effectively mitigated damage both hAOs, primarily downregulating heme oxygenase 1 (HMOX1). transcription factor cAMP element binding protein (CREB1) key transactivator HMOX1, which downregulated. Mechanistically, binds activates superoxide dismutase (SOD1), turn inhibits CREB1/HMOX1 pathway, thereby suppressing ferroptosis. Notably, further corroborated potential patients, demonstrating improved outcomes Conclusions: These findings provide compelling evidence that cells modulating SOD1/CREB1/HMOX1 signaling axis suggest promising strategy treatment.

Language: Английский

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