Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 14, 2024

Iron, an essential mineral in the body, is involved numerous physiological processes, making maintenance of iron homeostasis crucial for overall health. Both overload and deficiency can cause various disorders human diseases. Ferroptosis, a form cell death dependent on iron, characterized by extensive peroxidation lipids. Unlike other kinds classical unprogrammed death, ferroptosis primarily linked to disruptions metabolism, lipid peroxidation, antioxidant system imbalance. Ferroptosis regulated through transcription, translation, post-translational modifications, which affect cellular sensitivity ferroptosis. Over past decade or so, diseases have been as part their etiology, including cancers, metabolic disorders, autoimmune diseases, central nervous cardiovascular musculoskeletal Ferroptosis-related proteins become attractive targets many major that are currently incurable, some regulators shown therapeutic effects clinical trials although further validation potential needed. Therefore, in-depth analysis its molecular mechanisms may offer additional strategies prevention treatment. In this review, we discuss significance contribution etiology development along with evidence supporting targeting approach. Importantly, evaluate recent promising interventions, providing guidance future targeted treatment therapies against

Language: Английский

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The influence of microbiota on ferroptosis in intestinal diseases

Gut Microbes, Journal Year: 2023, Volume and Issue: 15(2)

Published: Oct. 5, 2023

Ferroptosis is a distinctive form of iron-dependent necrotic cell death, characterized by excessive lipid peroxidation on cellular membranes and compromised antioxidant defenses. Multiple metabolic pathways, including iron metabolism, as well systems, contribute to the execution ferroptosis. The gut microbiota exerts regulatory effects ferroptosis through its microbial composition, biological functions, metabolites. Notably, most pathogenic bacteria tend promote ferroptosis, thereby inducing or exacerbating diseases, while probiotics have been shown protect against death. Given colonization in gut, an intimate association found between intestinal diseases microbiota. This review consolidates essential aspects ferroptotic processes, emphasizing key molecules delineating intricate interplay Moreover, this underscores potential utility modulation regulating for treatment diseases.

Language: Английский

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Amino acid transporters within the solute carrier superfamily: Underappreciated proteins and novel opportunities for cancer therapy

Molecular Metabolism, Journal Year: 2024, Volume and Issue: 84, P. 101952 - 101952

Published: May 3, 2024

Solute carrier (SLC), a diverse family of membrane proteins, are instrumental in orchestrating the intake and efflux nutrients including amino acids, vitamins, ions, nutrients, etc, across cell membranes. This dynamic process is critical for sustaining metabolic demands cancer cells, promoting their survival, proliferation, adaptation to tumor microenvironment. Amino acids fundamental building blocks playing essential roles not only protein synthesis but also nutrient sensing, signaling pathways that can promote tumorigenesis. As key transporters SLCs have emerged as crucial players maintaining cellular acid homeostasis, dysregulation implicated various types. Thus, understanding intricate connections between SLCs, pivotal unraveling novel therapeutic targets strategies. uptake by positively affects progression. However, some studies revealed suppressor function SLCs. Although body evaluated SLC7A11 SLC1A5, SLC proteins studied sufficiently cancer. In this review, we delve into significant impact carriers on growth progression explore current state knowledge field, shedding light molecular mechanisms underlie these relationships highlighting potential avenues future research clinical interventions. comprehensive review provides insights rapidly evolving area biology focusing one most important materials cells need, within superfamily.

Language: Английский

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GSH and Ferroptosis: Side-by-Side Partners in the Fight against Tumors

Antioxidants, Journal Year: 2024, Volume and Issue: 13(6), P. 697 - 697

Published: June 6, 2024

Glutathione (GSH), a prominent antioxidant in organisms, exhibits diverse biological functions and is crucial safeguarding cells against oxidative harm upholding stable redox milieu. The metabolism of GSH implicated numerous diseases, particularly the progression malignant tumors. Consequently, therapeutic strategies targeting regulation synthesis to modulate levels represent promising avenue for future research. This study aimed elucidate intricate relationship between ferroptosis, highlighting how modulation can impact cellular susceptibility ferroptosis consequently influence development tumors other diseases. paper provides comprehensive overview physiological GSH, including its structural characteristics, physicochemical properties, sources, metabolic pathways, as well investigate molecular mechanisms underlying potential interventions. Unraveling role holds promise individuals afflicted with

Language: Английский

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Short Chain Fatty Acids: Essential Weapons of Traditional Medicine in Treating Inflammatory Bowel Disease

Molecules, Journal Year: 2024, Volume and Issue: 29(2), P. 379 - 379

Published: Jan. 12, 2024

Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal inflammatory disease, mainly including Crohn's (CD) ulcerative colitis (UC). In recent years, the incidence prevalence of IBD have been on rise worldwide become significant concern health huge economic burden patients. The occurrence development involve variety pathogenic factors. changes in short-chain fatty acids (SCFAs) are considered to be an important mechanism this disease. SCFAs metabolites microbial environment, which closely involved regulating immune, anti-tumor, anti-inflammatory activities. Changes metabolite levels can reflect homeostasis microflora. Recent studies shown that provide energy for host cells microflora, shape regulate immune system, thereby physiology. effectively reduce enteritis, cardiovascular colon cancer, obesity, diabetes, also play role maintaining balance metabolism (mainly glucose metabolism) improving insulin tolerance. many numerous decoctions natural compounds traditional Chinese medicine promising therapeutic activities multiple animal models thus attracted increasing attention from scientists study treatment. Some these medicines or alleviate colonic inflammation clinical symptoms by generation SCFAs. This reviews effects various bioactive substances production their potential impacts severity inflammation. On basis, we discussed IBD-associated inflammation, as well related regulatory factors signaling pathways. addition, our understanding limitations current research prospects future new therapies targeting review may widen effect view alleviating models, contributing researchers.

Language: Английский

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Microbial metabolite sodium butyrate enhances the anti-tumor efficacy of 5-fluorouracil against colorectal cancer by modulating PINK1/Parkin signaling and intestinal flora

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: June 6, 2024

Abstract Colorectal cancer (CRC) is a prevalent global health issue, with 5-fluorouracil (5-FU) being commonly used chemotherapeutic agent for its treatment. However, the efficacy of 5-FU often hindered by drug tolerance. Sodium butyrate (NaB), derivative intestinal flora, has demonstrated anti-cancer properties both in vitro and vivo through pro-apoptotic effects shown promise improving outcomes when conjunction traditional chemotherapy agents. This study seeks to evaluate impact potential mechanisms NaB combination on CRC. We employed comprehensive set assays, including CCK-8, EdU staining, Hoechst 33258 flow cytometry, ROS assay, MMP immunofluorescence, mitophagy detect effect biological function CRC cells vitro. Western blotting immunohistochemistry were verify above experimental results. The xenograft tumor model was established anti-CRC activity NaB. Subsequently, 16S rRNA gene sequencing analyze flora. findings our demonstrate that sodium (NaB) exerts inhibitory cell proliferation promotes apoptosis vitro, while also impeding progression enhancement pathway. Furthermore, combined treatment yielded superior therapeutic compared monotherapy either agent. Moreover, this therapy resulted specific enrichment Bacteroides, LigiLactobacillus, butyric acid-producing bacteria, acetic bacteria microbiota. improvement microbiota contributed enhanced reduced adverse 5-FU. Taken together, these indicate NaB, histone acetylation inhibitor synthesized flora fermentation, significantly enhance improve prognosis patients.

Language: Английский

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The lactate metabolism and protein lactylation in epilepsy

Frontiers in Cellular Neuroscience, Journal Year: 2025, Volume and Issue: 18

Published: Jan. 14, 2025

Protein lactylation is a new form of post-translational modification that has recently been proposed. Lactoyl groups, derived mainly from the glycolytic product lactate, have linked to protein in brain tissue, which shown correlate with increased neuronal excitability. Ischemic stroke may promote glycolysis, leading lactate accumulation tissue. This heighten excitability by upregulating levels, potentially triggering post-stroke epilepsy. Although current clinical treatments for seizures advanced significantly, approximately 30% patients epilepsy remain unresponsive medication, and prevalence continues rise. study explores mechanisms epilepsy-associated death mediated metabolism lactylation. also examines potential histone deacetylase inhibitors alleviate modifying thereby offering fresh perspectives future research into pathogenesis treatment

Language: Английский

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Establishment of a prognostic signature and immune infiltration characteristics for uterine corpus endometrial carcinoma based on a disulfidptosis/ferroptosis-associated signature

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

Published: Jan. 27, 2025

Background Disulfidptosis and ferroptosis are two different programmed cell death pathways, their potential therapeutic targets have important clinical prospects. Although there is an association between the two, role of genes associated with these forms in development endometrial cancer remains unclear. Methods In this study, RNA sequencing (RNA-seq) data were obtained from public databases, comprehensive analysis methods, including difference analysis, univariate Cox regression, Least Absolute Shrinkage Selection Operator (LASSO) used to construct a disulfidptosis/ferroptosis-related (DFRGs) prognostic signature. To further explore new feature, pathway functional analyses performed, differences gene mutation frequency level immune infiltration high- low-risk groups studied. Finally, we validated expression profile samples. Results We identified five optimal DFRGs that differentially expressed prognosis uterine corpus carcinoma (UCEC). These include CDKN2A, FZD7, LCN2, ACTN4, MYH10. Based on DFRGs, constructed robust model significantly lower overall survival high-risk group than group, tumor burden invasion risk groups. The key genes, ACTN4 was verified by immunohistochemistry RT-qPCR. Conclusion This study established characteristics assessment disulfidptosis provides insights guide patient management personalized treatment.

Language: Английский

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Design, Synthesis, and Antitumor Activity of NSDs Inhibitors Targeting Lung Squamous Cell Carcinoma

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 289, P. 117388 - 117388

Published: Feb. 13, 2025

Language: Английский

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Exploring the causal associations of the gut microbiota and plasma metabolites with ovarian cancer: an approach of mendelian randomization analysis combined with network pharmacology and molecular docking

Journal of Ovarian Research, Journal Year: 2025, Volume and Issue: 18(1)

Published: Feb. 13, 2025

Language: Английский

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