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

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Окт. 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

Язык: Английский

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Nrf2 activation: a key mechanism in stem cell exosomes-mediated therapies

Cellular & Molecular Biology Letters, Год журнала: 2024, Номер 29(1)

Опубликована: Март 2, 2024

Abstract Exosomes are nano-sized membrane extracellular vesicles which can be released from various types of cells. originating inflammatory or injured cells have detrimental effects on recipient cells, while exosomes derived stem not only facilitate the repair and regeneration damaged tissues but also inhibit inflammation provide protective against diseases, suggesting they may serve as an alternative strategy transplantation. a fundamental role in communication between through transfer proteins, bioactive lipids nucleic acids (like miRNAs mRNAs) This significantly impacts both physiological pathological functions Nuclear factor erythroid 2–related 2 (Nrf2), transcription factor, is able to mitigate damage caused by oxidative stress signaling pathways. The positive resulting activation Nrf2 pathway different disorders been documented literature. Studies confirmed that could act effective agonists. However, limited studies explored therapeutic cell-derived exosomes. review provides comprehensive overview existing knowledge concerning pathways impact exerted cell some common diseases. Graphical

Язык: Английский

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Tumor-derived extracellular vesicles regulate macrophage polarization: role and therapeutic perspectives

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Апрель 16, 2024

Extracellular vesicles (EVs) are important cell-to-cell communication mediators. This paper focuses on the regulatory role of tumor-derived EVs macrophages. It aims to investigate causes tumor progression and therapeutic directions. Tumor-derived can cause macrophages shift M1 or M2 phenotypes. indicates they alter M1/M2 cell ratio have pro-tumor anti-inflammatory effects. discusses several key points: first, factors that stimulate macrophage polarization cytokines released as a result; second, an overview methods used isolate them; third, how from various cancer sources, such hepatocellular carcinoma, colorectal lung breast glioblastoma sources promote development by inducing in macrophages; fourth, pancreatic lungs carcinoma also contribute promoting Modified sourced breast, pancreatic, repolarize exhibits anti-tumor activities offers novel approaches for treatment. Therefore, we discovered either phenotypes regulate development. is based description altering vesicle contents.

Язык: Английский

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Micro electrical fields induced MSC-sEVs attenuate neuronal cell apoptosis by activating autophagy via lncRNA MALAT1/miR-22-3p/SIRT1/AMPK axis in spinal cord injury

Journal of Nanobiotechnology, Год журнала: 2023, Номер 21(1)

Опубликована: Ноя. 27, 2023

Язык: Английский

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Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Potential Therapy for Diabetes Mellitus and Diabetic Complications

Pharmaceutics, Год журнала: 2022, Номер 14(10), С. 2208 - 2208

Опубликована: Окт. 17, 2022

As a novel cell-free strategy, mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) inherit the therapeutic potential of donor cells, and are widely used for treatment many diseases. Increasing studies have shown that MSC-EVs transfer various bioactive molecules to create beneficial microenvironment, thus exerting protective roles in diabetic mellitus (DM) complications. To overcome limitations natural such as heterogeneity insufficient function, several modification methods been established constructing engineered with elevated repairing efficiency. In this review, PubMed library was searched from inception August 2022, using combination Medical Subject Headings (MeSH) keywords related MSC-EVs, DM, We provide an overview major characteristics summarize recent advances MSC-EV-based therapy hyperglycemia-induced tissue damage emphasis on MSC-EV-mediated delivery functional components. Moreover, applications DM-related diseases discussed by presenting examples, opportunities challenges clinical translation especially evaluated.

Язык: Английский

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Small extracellular vesicles: a novel drug delivery system for neurodegenerative disorders

Frontiers in Aging Neuroscience, Год журнала: 2023, Номер 15

Опубликована: Июнь 19, 2023

Neurodegenerative diseases (NDs) have a slow onset and are usually detected late during disease. NDs often difficult to cure due the presence of blood–brain barrier (BBB), which makes it find effective treatments drugs, causing great stress financial burden families society. Currently, small extracellular vesicles (sEVs) most promising drug delivery systems (DDSs) for targeted molecules specific sites in brain as therapeutic vehicle their low toxicity, immunogenicity, high stability, efficiency, biocompatibility trans-BBB functionality. Here, we review application sEVs several NDs, including Alzheimer’s disease, Parkinson’s Huntington’s discuss current barriers associated with brain-targeted DDS, suggest future research directions.

Язык: Английский

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Alleviation of ischemia-reperfusion induced renal injury by chemically modified SOD2 mRNA delivered via lipid nanoparticles

Molecular Therapy — Nucleic Acids, Год журнала: 2023, Номер 34, С. 102067 - 102067

Опубликована: Окт. 27, 2023

Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury, which serious clinical condition with no effective pharmacological treatment. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) significantly alleviate IRI; however, the underlying mechanisms and key molecules conferring renoprotection remain elusive. In this study, we characterized protein composition MSC-EVs using proteomics approach found that mitochondrial superoxide dismutase 2 (SOD2) was enriched in MSC-EVs. Using lipid nanoparticles (LNP), successfully delivered chemically modified SOD2 mRNA into cells mice IRI. We demonstrated mRNA-LNP treatment decreased cellular reactive oxygen species (ROS) cultured ameliorated renal damage IRI mice, as indicated by reduced levels serum creatinine restored tissue integrity compared control mRNA-LNP-injected group. Thus, modulation ROS through upregulation delivery could be novel therapeutic method for ischemia-reperfusion-induced injury.

Язык: Английский

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Neural stem cell-derived small extracellular vesicles: a new therapy approach in neurological diseases

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 16, 2025

Neural stem cells (NSCs) possess pluripotent characteristics, proliferative capacity, and the ability to self-renew. In context of neurological diseases, transplantation NSCs has been shown facilitate repair through paracrine mechanisms. NSC-derived small extracellular vesicles (NSC-sEVs), a prominent component NSC secretome, play crucial role in modulating various physiological pathological processes, such as regulating microenvironment, promoting endogenous differentiation, facilitating maturation neurons glial cells. Moreover, NSC-sEVs exhibit reduced immunogenicity, decreased tumorigenic potential, enhanced traverse blood-brain barrier. Consequently, present novel therapeutic approaches non-cellular treatments for disorders are poised serve viable alternative cell therapies. Furthermore, can be manipulated enhance production efficiency, improve biological activity, optimize targeting specificity, thereby significantly advancing utilization clinical settings conditions. This review provides comprehensive overview functions NSC-sEVs, their implications underlying molecular mechanisms diverse disorders, well potential engineering drug delivery platforms. Additionally, limitations challenges faced by practical applications were discussed depth, targeted solutions proposed.

Язык: Английский

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Bibliometric and visualization analysis of kidney repair associated with acute kidney injury from 2002 to 2022

Frontiers in Pharmacology, Год журнала: 2023, Номер 14

Опубликована: Апрель 20, 2023

Background: Renal repair is closely related to the prognosis of acute kidney injury (AKI) and has attracted increasing attention in research field. However, there a lack comprehensive bibliometric analysis this area. This study aims at exploring current status hotspots renal AKI from perspective bibliometrics. Methods: Studies published between 2002 2022 after were collected Web Science core collection (WoSCC) database. Bibliometric measurement knowledge graph predict latest trends field performed using bibliometrics software CiteSpace VOSviewer. Results: The number documents steadily increased over 20 years. United States China contribute more than 60% are main drivers Harvard University most active academic institution that contributes documents. Humphreys BD Bonventre JV prolific authors co-cited American Journal Physiology-Renal Physiology Society Nephrology popular journals with greatest “exosome”, “macrophage polarization”, “fibroblast”, and” aki-ckd transition” high-frequency keywords recent Extracellular vesicles (including exosomes), macrophage polarization, cell cycle arrest, hippo pathway, sox9 potential targets Conclusion: first on structure development trend AKI-related results comprehensively summarize identify frontiers repair.

Язык: Английский

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Naïve or Engineered Extracellular Vesicles from Different Cell Sources: Therapeutic Tools for Kidney Diseases

Pharmaceutics, Год журнала: 2023, Номер 15(6), С. 1715 - 1715

Опубликована: Июнь 12, 2023

Renal pathophysiology is a multifactorial process involving different kidney structures. Acute injury (AKI) clinical condition characterized by tubular necrosis and glomerular hyperfiltration. The maladaptive repair after AKI predisposes to the onset of chronic diseases (CKD). CKD progressive irreversible loss function, fibrosis that could lead end stage renal disease. In this review we provide comprehensive overview most recent scientific publications analyzing therapeutic potential Extracellular Vesicles (EV)-based treatments in animal models CKD. EVs from multiple sources act as paracrine effectors involved cell-cell communication with pro-generative low immunogenic properties. They represent innovative promising natural drug delivery vehicles used treat experimental acute diseases. Differently synthetic systems, can cross biological barriers deliver biomolecules recipient cells inducing physiological response. Moreover, new methods for improving carriers have been introduced, such engineering cargo, modification proteins on external membrane, or pre-conditioning cell origin. nano-medicine approaches based bioengineered are an attempt enhance their capacity applications.

Язык: Английский

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