The Interplay between Ferroptosis and Neuroinflammation in Central Neurological Disorders

Antioxidants, Journal Year: 2024, Volume and Issue: 13(4), P. 395 - 395

Published: March 26, 2024

Central neurological disorders are significant contributors to morbidity, mortality, and long-term disability globally in modern society. These encompass neurodegenerative diseases, ischemic brain traumatic injury, epilepsy, depression, more. The involved pathogenesis is notably intricate diverse. Ferroptosis neuroinflammation play pivotal roles elucidating the causes of cognitive impairment stemming from these diseases. Given concurrent occurrence ferroptosis due metabolic shifts such as iron ROS, well their critical central nervous disorders, investigation into co-regulatory mechanism has emerged a prominent area research. This paper delves mechanisms along with interrelationship. It specifically emphasizes core molecules within shared pathways governing neuroinflammation, including SIRT1, Nrf2, NF-κB, Cox-2, iNOS/NO·, how different immune cells structures contribute dysfunction through mechanisms. Researchers’ findings suggest that mutually promote each other may represent key factors progression disorders. A deeper comprehension common pathway between cellular holds promise for improving symptoms prognosis related

Language: Английский

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Deferasirox Causes Leukaemia Cell Death through Nrf2-Induced Ferroptosis

Antioxidants, Journal Year: 2024, Volume and Issue: 13(4), P. 424 - 424

Published: March 29, 2024

Acute lymphoblastic leukaemia (ALL) is the most prevalent cancer in children, and excessive iron buildup resulting from blood transfusions chemotherapy potentially has a negative impact on treatment outcomes prognosis patients with ALL. Therefore, initiating early chelation therapy during ALL logical approach. Ideally, selected chelator should also possess anti-leukaemia properties. The aim of present study was to explore potential underlying mechanism deferasirox (DFX) therapy. This proved that DFX, an chelator, capable inducing cell death through ferroptosis, which achievable by increasing expression acetylated nuclear factor erythroid 2-related 2 (NRF2). More specifically, NRF2 acetylation Lys599 facilitated acetyltransferase-p300/CBP. These findings indicate DFX could serve as potent adjunctive medication for Moreover, may offer dual benefits treatment, functioning both NRF2-modulating agent. Further research clinical trials are necessary fully elucidate therapeutic incorporate it into protocols.

Language: Английский

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Therapeutic approaches for UCPPS management: research advances, experimental targets, and future directions

Journal of Pharmacology and Experimental Therapeutics, Journal Year: 2024, Volume and Issue: 390(2), P. 222 - 232

Published: April 2, 2024

Urologic chronic pelvic pain syndrome (UCPPS) is a painful condition with persistent originating from the pelvis that often leads to detrimental lifestyle changes in affected patients. The develops both sexes, an estimated prevalence of 5.7% 26.6% worldwide. This narrative review summarizes currently recommended therapies for UCPPS, followed by latest animal model findings and clinical research advances field. diagnosis UCPPS clinicians has room improvement despite past decade aiming decrease time treatment. Therapeutic approaches targeting growth factors (i.e., nerve factor, vascular endothelial factor), amniotic bladder therapy, stem cell treatments gain more attention as experimental treatment options UCPPS. development novel diagnostic tests based on urinary biomarkers would be beneficial assist Future directions should address role psychologic stress mechanisms refractory conventional management strategies etiology. Testing applicability cognitive behavioral therapy this cohort patients might promising increase their quality life. search lead compounds innovative drug delivery systems requires clinically relevant translational models. autoimmune responses triggered environmental another direction clarify impact immune system pathophysiology. SIGNIFICANCE STATEMENT: minireview provides up-to-date summary therapeutic focus recent advancements disease, pathophysiological signaling pathways, molecular targets involved nociception.

Language: Английский

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Salvianolic Acid A Attenuates Lipopolysaccharide‐Induced Acute Lung Injury by Activating AMPK/SIRT1/Nrf2 Signaling Pathway

Journal of Biochemical and Molecular Toxicology, Journal Year: 2025, Volume and Issue: 39(5)

Published: April 24, 2025

ABSTRACT Salvianolic acid A (Sal A) has been reported to have anti‐inflammatory and antioxidant properties. The present study aimed explore the potential mechanisms of Sal on lipopolysaccharide (LPS)‐induced acute lung injury (ALI). results indicated that pretreatment attenuated LPS induced injury, shown by alleviated histopathological damage alveolar‐capillary barrier dysfunction, as well reduced inflammatory response oxidative stress. Moreover, effectively increased expression p‐AMPK SIRT1 promoted Nrf2 nuclear translocation in tissues. However, these effects were remarkably blunted Compound C. Molecular docking experiments further confirmed bound active sites AMPK SIRT1. In conclusion, exerted its protective LPS‐induced ALI through suppressing inflammation stress, which was mainly dependent activation AMPK/SIRT1/Nrf2 signaling pathway.

Language: Английский

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Protective effect of roflumilast on cyclophosphamide-induced ovarian toxicity in rats: role of SIRT1/Nrf2/nF-ĸB pathway

Immunopharmacology and Immunotoxicology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 10

Published: March 25, 2025

This study aimed to investigate the possible protective effect of roflumilast (RFL) on cyclophosphamide (CP)-induced ovarian toxicity as well underlying mechanism. Female Wistar rats received vehicle (n = 6) or CP (200 mg/kg, i.p.). The other 2 groups 6 for each) were orally pretreated with RFL at dosages 0.5 and 1 respectively, 14 days then after one hour administration 14th day, intraperitoneally administered a single dose CP. Serum tissue samples collected. Biochemical, real-time polymerase chain reaction, histopathological immunohistopathological examination carried out. significantly elevated serum follicle-stimulating hormone (FSH) luteinizing (LH) compared group. remarkably contents Sirtuin-1 (SIRT1), heme oxygenase-1 (HO-1), reduced nuclear factor-kappa B (NF-ĸb) p65/NF-ĸB ratio control Compared group, Nrf2 gene expression, malondialdehyde (MDA), glutathione (GSH) content. It also protein expression TNF-α caspase-3. can be concluded that (0.5 mg/kg) protected against CP-induced via altering SIRT1/Nrf2/NF-ĸB pathway, ameliorating changes in addition its anti-apoptotic effect.

Language: Английский

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Umbilical cord mesenchymal stem cells: a powerful fighter against colon cancer?

Tissue and Cell, Journal Year: 2024, Volume and Issue: 90, P. 102523 - 102523

Published: Aug. 14, 2024

Language: Английский

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High Salt Exacerbates Myocardial Dysfunction In Vitro and In Vivo by Promoting SIRT1/Nrf2‐Mediated Ferroptosis

Clinical and Experimental Pharmacology and Physiology, Journal Year: 2024, Volume and Issue: 52(2)

Published: Dec. 29, 2024

Myocardial dysfunction is a crucial determinant of the development heart failure in salt-sensitive hypertension. Ferroptosis, programmed iron-dependent cell death, has been increasingly recognised as an important contributor to pathophysiology various cardiovascular diseases. This study aims investigate role and underlying mechanism ferroptosis high-salt (HS)-induced myocardial damage. Our results reveal that HS stimulation inhibited proliferation promoted apoptosis cardiomyocyte HL-1 cells dose-dependent manner. Ferroptotic features were observed HS-induced cells, including ferric iron accumulation, decreased glutathione levels, increased oxidative stress upregulation marker proteins PTGS2, 4HNE FTH1 downregulation GPX4, all which reversed by treatment with suppressor Fer-1. Furthermore, administration Fer-1 ameliorated damage Dahl SS rats. Additionally, we found diet suppressed SIRT1/Nrf2 signalling pathway activation our vivo experiments. Activation SIRT1 overexpression significantly attenuated cells. In conclusion, findings demonstrate levels induce injury promoting via deactivation pathway, highlighting potential for therapeutic targeting hypertension-related disorders.

Language: Английский

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Identification of oxidative stress-related diagnostic marker genes and immune landscape in interstitial cystitis by bioinformatics and machine learning

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

Published: July 19, 2024

Background Interstitial cystitis (IC) is a chronic inflammatory disease with autoimmune associations that challenging to diagnose and treat. Recent findings indicate oxidative stress (OS) crucial pathophysiological mechanism in IC. Moreover, the interactions between OS, inflammation, immune cell infiltration are highly complex. Therefore, this study aims identify biomarkers linked OS development of IC elucidate their relationship infiltration. These could provide new research directions for diagnosis treatment Methods The GSE711783 dataset from GEO database was utilized differentially expressed genes IC, while OS-related were obtained GeneCards database. Hub associated identified through integrated analysis using WGCNA protein-protein interaction networks. Gene regulatory networks involving transcription factors, TF-miRNA gene-disease analyzed relevant databases. Diagnostic marker refined machine learning algorithms. Subsequently, nomogram diagnostic prediction model developed validated vitro experiments. Potential drug candidates DSigDB database, landscape explored CIBERSORT algorithm. Results We total 68 related alongside 15 hub genes. Among these, four genes—BMP2, MMP9, CCK NOS3—were further selected as markers. Using ANN model, ROC curve analysis, all demonstrated excellent efficacy. Additionally, these exhibited strong T cells CD4 memory resting, activated, Eosinophils. Finally, decitabine emerged most promising molecule treatment. Conclusion pivotal pathogenesis influencing both responses. highlight avenues

Language: Английский

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Cell Sheets Formation Enhances Therapeutic Effects of Human Umbilical Cord Mesenchymal Stem Cells on Spinal Cord Injury

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(12)

Published: Dec. 1, 2024

ABSTRACT Background In recent years, the utilization of stem cell therapy and sheet technology has emerged as a promising approach for addressing spinal cord injury (SCI). However, most appropriate type mechanism action remain unclear at this time. This study sought to develop an SCI rat model evaluate therapeutic effects human umbilical mesenchymal (hUC‐MSC) sheets in model. Furthermore, mechanisms underlying vascular repair effect hUC‐MSC following were investigated. Methods A temperature‐responsive culture method was employed preparation sheets. The extracellular matrix (ECM) produced by hUC‐MSCs serves two distinct yet interrelated purposes. Firstly, it acts biologically active scaffold transplanted cells, facilitating their attachment proliferation. Secondly, provides mechanical support bridges stumps, thereby restoration function. formation cavity within evaluated using Hematoxylin Eosin (H&E) staining method. Subsequently, endothelial cells cultivated with conditioned medium (CM) obtained from or pro‐angiogenic impact (MSC‐CM) (CS‐CM) through CCK‐8 assay, wound healing tube assay vitro context. development glial scars, blood vessels, neurons, axons assessed immunofluorescence staining. Results comparison hUC‐MSCs, demonstrated more pronounced capacity facilitate induce regeneration newborn neurons site, while also reducing scar significantly enhancing motor function rats. Notably, under identical conditions, been associated paracrine increase ability themselves secrete growth factors. During course experiment, observed that secretion uPAR among factors present MSC‐CM CS‐CM. finding subsequently corroborated subsequent experiments, wherein promote angiogenesis via PI3K/Akt signaling pathway. Conclusion creation not only enhances biological but effectively retains locally injury. Therefore, transplantation can maximize greatly formation, promoting axons. Additionally, research findings prove activate pathway enhance angiogenesis. transfer entire sheets, absence introduction additional exogenous synthetic biomaterials, further augment potential clinical application.

Language: Английский

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