Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)
Опубликована: Фев. 2, 2025
Язык: Английский
Процитировано
3Ferroptosis and pyroptosis are connected through autophagy: a new perspective of overcoming drug resistance
Molecular Cancer, Год журнала: 2025, Номер 24(1)
Опубликована: Янв. 17, 2025
Drug resistance is a common challenge in clinical tumor treatment. A reduction drug sensitivity of cells often accompanied by an increase autophagy levels, leading to autophagy-related resistance. The effectiveness combining chemotherapy drugs with inducers/inhibitors has been widely confirmed, but the mechanisms are still unclear. Ferroptosis and pyroptosis can be affected various types autophagy. Therefore, ferroptosis have crosstalk via autophagy, potentially switch cell death under certain conditions. As two forms inflammatory programmed death, different effects on inflammation, cGAS-STING signaling pathway also involved. it plays important role progression some chronic diseases. This review discusses relationship between pyroptosis, attempts uncover reasons behind evasion nature
Язык: Английский
Процитировано
1Targeted temperature management alleviates post-resuscitation myocardial dysfunction by inhibiting ferroptosis
Cell Death Discovery, Год журнала: 2025, Номер 11(1)
Опубликована: Фев. 21, 2025
Abstract Targeted temperature management (TTM) is a vital intervention for cardiac arrest survivors to mitigate post-resuscitation myocardial dysfunction (PRMD). However, the optimal TTM remains topic of debate. This study investigates effects at different temperatures and explores underlying mechanisms using in vivo vitro models ischemia/reperfusion (I/R) injury following (CA) cardiopulmonary resuscitation (CPR). We found that 33 °C significantly improved hemodynamics function, reducing both mitochondrial damage rat model CA/CPR. Additionally, Deferoxamin (DFO), as an iron chelating agent, also demonstrated protective against PRMD. Both experiments confirmed hypothermia DFO mitigated damage, oxidative stress, lipid peroxidation, overload, while suppressing ferritinophagy ferroptosis. Furthermore, facilitated nuclear translocation factor erythroid 2-related 2 (Nrf2), with Nrf2 activation leading inhibited enhanced export. Our findings indicate 33° C, opposed 36° alleviates PRMD reduced by inhibiting Theses are associated modulation homeostasis. Moreover, not only suppressed ferroptosis through its chelation properties but activating axis.
Язык: Английский
Процитировано
1Mitochondria-mediated ferroptosis contributes to the inflammatory responses of bovine viral diarrhea virus (BVDV) in vitro
Journal of Virology, Год журнала: 2024, Номер 98(2)
Опубликована: Янв. 16, 2024
Bovine viral diarrhea virus (BVDV) threatens a wide range of domestic and wild cattle population worldwide. BVDV causes great economic loss in industry through its immunosuppression persistent infection. Despite extensive research, the mechanism underlying pathogenesis remains elusive. Our data provide first direct evidence that mitochondria-mediated ferroptosis mitophagy are involved inflammatory responses both biotypes BVDV-infected cells. Importantly, we demonstrate different degrees injury mitochondria may attribute to pathways induced by BVDV. Overall, our findings uncover interaction between infection ferroptosis, which shed novel light on physiological impacts infection, promising therapeutic strategy treat this important infectious disease with worldwide distribution.
Язык: Английский
Процитировано
5Disease and brain region specific immune response profiles in neurodegenerative diseases with pure and mixed protein pathologies
Acta Neuropathologica Communications, Год журнала: 2024, Номер 12(1)
Опубликована: Апрель 5, 2024
Abstract The disease-specific accumulation of pathological proteins has long been the major focus research in neurodegenerative diseases (ND), including Alzheimer’s disease (AD) and related dementias (RD), but recent identification a multitude genetic risk factors for ND immune-associated genes highlights importance immune processes pathogenesis progression. Studies animal models have characterized local response to AD ADRD, due complexity co-existence multiple protein pathologies human donor brains, precise role is far from understood. To better characterize interplay between different extracellular intracellular brain’s intrinsic system ND, we set out comprehensively profile postmortem brain samples individuals with “pure” beta-Amyloid tau pathology (AD), α-Synuclein Lewy body (LBD), as well cases neuropathological changes (ADNC) (MIX). Combining immunohistochemical profiling microglia digital image analysis, along deep immunophenotyping using gene expression on NanoString nCounter® platform spatial GeoMx® identified robust activation signature samples. This maintained persons mixed pathologies, irrespective (LB) pathology, while LBD LB exhibit an attenuated distinct signature. Our studies highlight disease- region-specific profiles further underscore neuroimmune interactions ND.
Язык: Английский
Процитировано
4Realgar Transforming Solution Triggered Ferroptosis in Leukemia Cells by Disrupting Iron Homeostasis Through the Slc7a11/Gpx4 Axis
Опубликована: Янв. 1, 2025
Clinical investigations have demonstrated that the progression of acute myeloid leukemia (AML) is particularly susceptible to iron overload and dysregulation homeostasis, which can trigger ferroptosis. Consequently, regulating homeostasis may positively impact AML treatment. This study aimed investigate anticancer properties potential mechanisms realgar transforming solution (RTS) in inducing ferroptosis disrupting NB4 cells. Cell viability was assessed using Counting Kit-8 (CCK-8) assay. Transcriptomic analysis conducted identify differentially expressed genes (DEGs) predict pathways through RTS exerts its antitumor effects. Ferroptosis evaluated BODIPY C11 lipid ROS probe, T-SOD, MDA, GSH assay kits, along with JC-1 fluorescent probe Western blot analysis. Iron Fe2+ kits metabolism. Transcriptome sequencing revealed 819 DEGs, HO-1 PML-RARα Regulated Adaptor Molecule 1 (PRAM1) being most prominent. KEGG indicated significant enrichment pathway. In vitro studies treatment resulted increased levels depletion SLC7A11 GPX4 expression Additionally, TFR1 NCOA4 increased, while FPN1 (SLC40A1), FTH1, IREB2 decreased under led intracellular accumulation, ultimately Pretreatment inhibitors, such as Ferrostatin-1 (Fer-1) or Deferoxamine mesylate (DFOM), attenuated RTS-induced The demonstrates induce cells by via regulation SLC7A11/GPX4 axis. These findings suggest a therapeutic agent for AML.
Язык: Английский
Процитировано
0Nuclear receptor coactive 4-mediated ferritinophagy: a key role of heavy metals toxicity
Archives of Toxicology, Год журнала: 2025, Номер unknown
Опубликована: Фев. 10, 2025
Язык: Английский
Процитировано
0Advances in understanding the role and mechanism of the cGAS-STING signaling pathway in ocular diseases
Immunological Medicine, Год журнала: 2025, Номер unknown, С. 1 - 15
Опубликована: Март 8, 2025
The cGAS-STING signaling pathway plays a critical role in the immune defense against DNA viruses and autoimmunity, coordinating cascade of events that enhance cytokine production, particularly type I interferons. This review summarizes recent advancements understanding pathway's impact on various ocular diseases, including age-related macular degeneration (AMD), diabetic retinopathy, uveitis. Activation this by cytoplasmic from either damaged retinal cells or external pathogens induces inflammatory responses may accelerate disease progression. Moreover, paper explores new therapeutic approaches target pathway, offering insights into how modulation could reduce inflammation improve clinical outcomes. emerging research area suggests potential for innovative treatments degenerative conditions.
Язык: Английский
Процитировано
0Smaller-Sized Silica Nanoparticles Exacerbated Cardiomyocyte Pyroptosis by Impairing Mitophagy to Activate mtDNA-cGAS-STING Signaling
Journal of Agricultural and Food Chemistry, Год журнала: 2025, Номер unknown
Опубликована: Апрель 8, 2025
Silica nanoparticles (SiNPs) are a nanometer powder widely used in various consumer products, engineering, the food industry, and medical applications. Environmental SiNPs have attracted attention owing to their exposure cardiovascular adverse events. Here, we exposed C57/BL6 mouse HL-1 cells with different-sized (50, 300 nm, 1 μm) investigate underlying mechanism of its toxicity. Mice three-sized showed significant weight loss after 21 days treatment. Heart tibia length ratio histopathology staining indicated increased heart volume cross-sectional area myocardial fibers mice SiNPs. In vivo vitro experiments results that causes size-dependent mitochondrial damage initiates mitophagy. Notably, compared caused by nm μm exposure, 50 blocked autophagy flux, leading excessive accumulation DNA (mtDNA) cytoplasm, ultimately exacerbating downstream cGAS-STING pathway-mediated pyroptosis. This study revealed potential health risks helped understand differences cytotoxicity different sizes.
Язык: Английский
Процитировано
0Identification of ferroptosis-related key genes associated with immune infiltration in sepsis by bioinformatics analysis and in vivo validation
Gene, Год журнала: 2024, Номер 918, С. 148482 - 148482
Опубликована: Апрель 21, 2024
Sepsis is a life-threatening infectious disease in which an immune inflammatory response triggered. The potential effect of ferroptosis-related genes (FRGs) inflammation sepsis remained unclear. We focused on identifying and validating core FRGs their association with infiltration blood from currently all patients sepsis. All current raw data septic were obtained Gene Expression Omnibus. After removing the batch merging into complete dataset obtaining Diferentially expressed (DEGs). Common cross-talk identified DEGs FRGs. WGCNA, GO, KEGG, PPI, GESA, ROC curves, LASSO regression analysis performed to indentify validate key based external datasets. Infiltrated cells 2 hub (MAPK14 ACSL4) conducted using CIBERSORT algorithm Spearman correlation analysis. Further, expressions verified LPS-induced ALI cardiac injury mice. MAPK14 ACSL4 identified, mostly enriched T cell through NOD-like receptor signaling pathway according high or low expression. upregulated validated mice, accompanied by upregulation NLRP3 pathway. could become robustly reliable promising biomarkers for regulating ferroptosis pathway, mainly associated T-cell infiltration.
Язык: Английский
Процитировано
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