Exosome-based targeted delivery of NF-κB ameliorates age-related neuroinflammation in the aged mouse brain

Experimental & Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Abstract Neuroinflammation, a significant contributor to various neurodegenerative diseases, is strongly associated with the aging process; however, date, no efficacious treatments for neuroinflammation have been developed. In aged mouse brains, number of infiltrating immune cells increases, and key transcription factor increased chemokine levels nuclear kappa B (NF-κB). Exosomes are potent therapeutics or drug delivery vehicles materials, including proteins regulatory genes, target cells. present study, we evaluated therapeutic efficacy exosomes loaded nondegradable form IκB (Exo-srIκB), which inhibits translocation NF-κB suppress age-related neuroinflammation. Single-cell RNA sequencing revealed that these anti-inflammatory targeted macrophages microglia, reducing expression inflammation-related genes. Treatment Exo-srIκB also suppressed interactions between macrophages/microglia T in brain. We demonstrated successfully alleviates by primarily targeting activated partially modulating functions interferon-responsive microglia Thus, our findings highlight as potential agent treating

Language: Английский

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Hydrogels with Essential Oils: Recent Advances in Designs and Applications

Gels, Journal Year: 2024, Volume and Issue: 10(10), P. 636 - 636

Published: Sept. 30, 2024

The innovative fusion of essential oils with hydrogel engineering offers an optimistic perspective for the design and development next-generation materials incorporating natural bioactive compounds. This review provides a comprehensive overview latest advances in use hydrogels containing biomedical, dental, cosmetic, food, food packaging, restoration cultural heritage applications. Polymeric sources, methods obtaining, cross-linking techniques, functional properties are discussed. unique characteristics polymer agents highlighted. These include biocompatibility, nontoxicity, effective antibacterial activity, control sustained prolonged release active substances, optimal porosity, outstanding cytocompatibility. Additionally, specific distinctive explored, along their extraction encapsulation methods. advantages disadvantages these also We have considered limitations due to volatility, solubility, environmental factors, stability. importance loading hydrogels, stability, biological activity is analyzed. highlights through in-depth analysis, recent innovations, challenges, future prospects encapsulated potential multiple applications including biomedicine, dentistry, cosmetics, conservation.

Language: Английский

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Exosomes Interactions with the Blood–Brain Barrier: Implications for Cerebral Disorders and Therapeutics

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(21), P. 15635 - 15635

Published: Oct. 26, 2023

The Blood-Brain Barrier (BBB) is a selective structural and functional barrier between the circulatory system cerebral environment, playing an essential role in maintaining homeostasis by limiting passage of harmful molecules. Exosomes, nanovesicles secreted virtually all cell types into body fluids, have emerged as major mediator intercellular communication. Notably, these vesicles can cross BBB regulate its physiological functions. However, precise molecular mechanisms which exosomes remain unclear. Recent research studies focused on effect BBB, particularly context their involvement onset progression various disorders, including solid metastatic brain tumors, stroke, neurodegenerative, neuroinflammatory diseases. This review focuses discussing summarizing current knowledge about pathological modulation BBB. A better understanding this regulation will improve our pathogenesis diseases enable design effective treatment strategies.

Language: Английский

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Gold Nanoparticles Downregulate IL-6 Expression/Production by Upregulating microRNA-26a-5p and Deactivating the RelA and NF-κBp50 Transcription Pathways in Activated Breast Cancer Cells

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1404 - 1404

Published: Jan. 24, 2024

MicroRNAs (miRNAs) are involved in the modulation of pathogenic genes by binding to their mRNA sequences’ 3′ untranslated regions (3′UTR). Interleukin-6 (IL-6) is known promote cancer progression and treatment resistance. In this study, we aimed explore therapeutic effects gold nanoparticles (GNP) against IL-6 overexpression miRNA-26a-5p breast (BC) cells. GNP were synthesized using trisodium citrate method characterized through UV-Vis spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM). To predict miR-26a-5p mRNA’s 3′UTR, utilized bioinformatics algorithms. Luciferase reporter clone assays anti-miRNA-26a-5p transfection employed validate miR26a-5p 3′UTR. The activity RelA NF-κBp50 was assessed confirmed Bay 11-7082. spherical with a mean size 28.3 nm, exhibiting high stability, suitable for BC cell treatment. We found that directly regulated MCF-7 cells activated PMA. Treatment resulted inhibition secretion increase miR26a-5p. Furthermore, deactivated NF-κBp65/NF-κBp50 transcription activity. newly engineered demonstrated safety showed promise as approach reducing overexpression. suppressed deactivating upregulating expression These findings suggest have potential intervention targeting associated pathways.

Language: Английский

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The Blood–CSF Barrier in Oncological Research

Current human cell research and applications, Journal Year: 2025, Volume and Issue: unknown, P. 195 - 206

Published: Jan. 1, 2025

Language: Английский

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Astrocytes: a potential avenue for depression and cancer

Brain Behavior and Immunity Integrative, Journal Year: 2025, Volume and Issue: unknown, P. 100124 - 100124

Published: April 1, 2025

Language: Английский

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Astrocyte plasticity shapes brain metastasis progression through tumor-astrocyte crosstalk

Published: Jan. 13, 2025

Brain metastases are ten times more common than primary brain tumors and pose a significant clinical challenge. How metastatic tumor cells adapt to the unique hostile microenvironment remains unclear. Astrocytes, most abundant glial in brain, emerging as key mediators regulating development of metastases. Initially anti-metastatic, astrocytes reprogrammed by tumor-derived signals, transitioning into pro-metastatic phenotype. Here, we review roles metastasis describe evidence for their phenotypic plasticity, basis astrocyte-tumor interactions, potential therapeutic strategies targeting these processes.

Language: Английский

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Immunotherapy revolutionizing brain metastatic cancer treatment: personalized strategies for transformative outcomes

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: July 29, 2024

Brain metastatic cancer poses a significant clinical challenge, with limited treatment options and poor prognosis for patients. In recent years, immunotherapy has emerged as promising strategy addressing brain metastases, offering distinct advantages over conventional treatments. This review explores the evolving landscape of tumor in context cancer, focusing on intricate interplay between microenvironment (TME) immunotherapeutic approaches. By elucidating complex interactions within TME, including role immune cells, cytokines, extracellular matrix components, this highlights potential to reshape paradigm metastases. Leveraging checkpoint inhibitors, cellular immunotherapies, personalized strategies, holds promise overcoming challenges posed by blood-brain barrier immunosuppressive Through comprehensive analysis current research findings future directions, underscores transformative impact management new insights opportunities precise therapeutic interventions.

Language: Английский

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Multifaceted interactions between cancer cells and glial cells in brain metastasis

Cancer Science, Journal Year: 2024, Volume and Issue: 115(9), P. 2871 - 2878

Published: July 11, 2024

Abstract Cancer brain metastasis has a poor prognosis, is commonly observed in clinical practice, and the number of cases increasing as overall cancer survival improves. However, experiments mouse models have shown that itself an inefficient process. One reason for this inefficiency microenvironment, which differs significantly from other organs, making it difficult cells to adapt. The microenvironment consists unique resident cell types such neurons, oligodendrocytes, astrocytes, microglia. Accumulating evidence over past decades suggests interactions between glial can positively or negatively influence development metastasis. Nevertheless, elucidating complex remains challenging, part due limitations existing experimental culture. In review, we first provide overview culture methods then examine recent discoveries regarding metastatic surrounding cells, with special focus on astrocytes Finally, discuss future perspectives understanding multifaceted treatment tumors.

Language: Английский

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Exosomes as a Nano-Carrier for Chemotherapeutics: A New Era of Oncology

Cells, Journal Year: 2023, Volume and Issue: 12(17), P. 2144 - 2144

Published: Aug. 25, 2023

Despite the considerable advancements in oncology, cancer remains one of leading causes death worldwide. Drug resistance mechanisms acquired by cells and inefficient drug delivery limit therapeutic efficacy available chemotherapeutics drugs. However, studies have demonstrated that nano-drug carriers (NDCs) can overcome these limitations. In this sense, exosomes emerge as potential candidates for NDCs. This is because better organotropism, homing capacity, cellular uptake, cargo release ability than synthetic addition, serve NDCs both hydrophilic hydrophobic chemotherapeutic Thus, review aimed to summarize latest advances cell-free therapy, describing how contribute each step carcinogenesis process discussing nanosized vesicles could be explored chemotherapeutics.

Language: Английский

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