MicroRNA-22-3p ameliorates Alzheimer’s disease by targeting SOX9 through the NF-κB signaling pathway in the hippocampus

Journal of Neuroinflammation, Journal Year: 2022, Volume and Issue: 19(1)

Published: July 12, 2022

Abstract Background Studies have suggested that many down-regulated miRNAs identified in the brain tissue or serum of Alzheimer’s disease (AD) patients were involved formation senile plaques and neurofibrillary tangles. Specifically, our previous study revealed microRNA-22-3p (miR-22-3p) was significantly AD patients. However, molecular mechanism underlying down-regulation miR-22-3p has not been comprehensively investigated. Methods The ameliorating effect on apoptosis Aβ-treated HT22 cells detected by TUNEL staining, flow cytometry, western blotting. cognition mice with stereotaxic injection agomir antagomir assessed Morris water maze test. Pathological changes mouse hippocampus analyzed using hematoxylin eosin (HE) Nissl immunohistochemistry. Proteomics analysis performed to identify targets miR-22-3p, which further validated dual-luciferase reporter blotting analysis. Results played an important role cells. Increased levels improved mice. Although did cause decrease neuronal loss hippocampus, it reduced Aβ deposition. Sox9 protein as target verified luciferase experiments. Conclusion Our showed could improve reduce deposition acting through NF-κB signaling pathway We concluded ameliorated targeting hippocampus.

Language: Английский

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Virus‐Like Particle‐Induced cGAS‐STING Activation and AIM2 Inflammasome‐Mediated Pyroptosis for Robust Cancer Immunotherapy

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(24)

Published: April 11, 2023

Abstract cGAS‐STING‐mediated DNA sensing is demonstrated to be critical for launching antitumor immunity. However, DNA‐based cGAS‐STING agonists are rarely reported owing low cell permeability, poor biostability and, especially, limited length of exogenous DNA. Here, we present a virus‐like particle which self‐assembled from long building blocks generated through rolling‐circle amplification (RCA) and covered with cationic liposomes. Based on densely packed structure, it could efficiently induce liquid phase condensation cGAS activate STING signaling produce inflammatory cytokines. Moreover, this also trigger the formation AIM2 inflammasome gasdermin D‐mediated pyroptosis, boosting Thus, study provides simple robust strategy cancer immunotherapy clinical application. This first report intrinsic immunogenicity RCA products, thus facilitating their biomedical applications.

Language: Английский

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Imine-Linked Covalent Organic Framework Modulates Oxidative Stress in Alzheimer’s Disease

ACS Applied Materials & Interfaces, Journal Year: 2023, Volume and Issue: 15(4), P. 4947 - 4958

Published: Jan. 18, 2023

Oxidative stress due to Cu2+-triggered aggregation of β-amyloid protein (Aβ) and reactive oxygen species (ROS) overexpression in the brain is an important hallmark early stages Alzheimer's disease (AD) pathogenesis. The ideal modulator for improving oxidative microenvironment AD brains should take both Cu2+ ROS into consideration, which has been rarely reported. Here, a combined therapeutic strategy was achieved by co-encapsulating superoxide dismutase (SOD) catalase (CAT) imine-linked covalent organic frameworks (COFs), were modified with peptide KLVFF (T5). nanocomposite SC@COF-T5 exhibited eradicating ability through elimination chelation, inhibition Aβ42 monomer disaggregation fibrils. In vivo experiments indicated that high blood-brain barrier (BBB) penetration efficiency effective reduce Aβ deposition, expression pro-inflammatory cytokines, levels, neurologic damage model mice, consequently rescuing memory deficits mice. This work not only confirms feasibility merits regarding multiple targets treatment pathogenesis but also opens up novel direction COFs biomedical applications.

Language: Английский

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Hybrid Membrane‐Coated Nanoparticles for Precise Targeting and Synergistic Therapy in Alzheimer's Disease

Advanced Science, Journal Year: 2024, Volume and Issue: 11(24)

Published: April 22, 2024

Abstract The blood brain barrier (BBB) limits the application of most therapeutic drugs for neurological diseases (NDs). Hybrid cell membrane‐coated nanoparticles derived from different types can mimic surface properties and functionalities source cells, further enhancing their targeting precision efficacy. Neuroinflammation has been increasingly recognized as a critical factor in pathogenesis various NDs, especially Alzheimer's disease (AD). In this study, novel membrane coating is designed by hybridizing platelets chemokine (C–C motif) receptor 2 (CCR2) cells are overexpressed to cross BBB target neuroinflammatory lesions. Past unsuccessful endeavors AD drug development underscore challenge achieving favorable outcomes when utilizing single‐mechanism drugs.Two with mechanisms actions into liposomes successfully loaded realize multitargeting treatment. transgenic mouse model familial (5xFAD), administration these drug‐loaded hybrid results significant reduction amyloid plaque deposition, neuroinflammation, cognitive impairments. Collectively, nanomaterials offer new opportunities precise delivery disease‐specific targeting, which represent versatile platform targeted therapy AD.

Language: Английский

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New Trends in Brain Shuttle Peptides

Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

The pharmacological treatment of central nervous system diseases faces significant challenges due to the presence blood–brain barrier (BBB). This naturally protects brain and prevents therapeutics from reaching their targets efficiently. However, BBB allows passage nutrients other molecules that guarantee homeostasis through selective transport mechanisms present at BBB. These provide an opportunity for delivering therapeutic agents into using shuttles. Here we review progress shuttle peptide development 2015 until 2025. We highlight most utilized peptides describe trends in strategies develop new shuttles enhance efficiency. Additionally, compared them with types emphasize toward clinical translation.

Language: Английский

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Self-Assembled DNA/SG-I Nanoflower: Versatile Photocatalytic Biosensors for Disease-Related Markers

Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

DNA nanostructures have recently attracted more attention with functionalities, programmability, and biocompatibility. Herein, a novel self-assembled photocatalytic DNA/SYBR Green I (SG-I) nanoflower (DSNF) was successfully synthesized by rolling circle amplification. DSNF through liquid crystallization of high concentration in the RCA products, without relying on Watson-Crick base-pairing principle. Interestingly, not only possessed larger specific surface area good stability but also exhibited excellent activity that generates singlet oxygen superoxide anion to oxidate 3,3',5,5'-tetramethylbenzidine. Meanwhile, combined an enzyme-linked immunosorbent assay develop new colorimetric sensor for highly specific, sensitive, visual detection carcinoembryonic antigens (CEAs). The achieved sensitive low-cost quantitative CEA linear range 0.5-80.0 ng/mL, LOD 0.5 ng/mL. In addition, three negative seven positive clinical serum samples were obtained 100% accuracy using proposed sensor, showing great potential application cancer diagnosis. We envision this is expected provide important perspectives fluorescence imaging, photosensitizing therapy, diagnosis fields.

Language: Английский

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Targeted Ganglion Delivery of CaV2.2-Mediated Peptide by DNA Nanoflowers for Relieving Myocardial Infarction and Neuropathic Pain

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

N-type calcium channel (CaV2.2) protein contributes to neuronal excitability and overactivation in sympathetic ganglion (SG) following myocardial infarction (MI), thereby easily triggering cardiac remodeling ventricular arrhythmias (VAs). Despite much advances the understanding of CaV2.2, a neuron-targeted modifying treatment is, yet, infrequently realized. Moreover, establishing specific delivery strategy stable probe architecture with an extensive molecular structure pursuit complex CaV2.2 regulation still remains challenge. Herein, we develop smart DNA nanoflower (sDNF) composite by utilizing customizable design scalable production from multifunctionality-encoded template that self-assembles into biomimetic nanoarchitecture. The nanoarchitecture contains neuron-targeting aptamer decorated mediator peptide-DNA bioconjugate. combined targeted release peptide synergistically led ∼31% reduction peak current neuron cells. sDNF alleviated MI-induced SG hyperactivity improved vivo outcomes, such as decreasing susceptibility VAs relieving neuropathic pain for 10 h. infarct size treated is reduced approximately 11.1%. It envisioned DNF-based nanostructure suppression inhibition along relief provides potential approach clinical sympathetic-associated cardiovascular diseases.

Language: Английский

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Hemin-incorporating DNA nanozyme enabling catalytic oxygenation and GSH depletion for enhanced photodynamic therapy and synergistic tumor ferroptosis

Journal of Nanobiotechnology, Journal Year: 2022, Volume and Issue: 20(1)

Published: Sept. 15, 2022

Photodynamic therapy (PDT) has emerged as a promising tumor treatment method via light-triggered generation of reactive oxygen species (ROS) to kill cells. However, the efficacy PDT is usually restricted by several biological limitations, including hypoxia, excess glutathione (GSH) neutralization, well resistance. To tackle these issues, herein we developed new kind DNA nanozyme realize enhanced and synergistic ferroptosis. The was constructed rolling circle amplification, which contained repeat AS1411 G quadruplex (G4) units form multiple G4/hemin DNAzymes with catalase-mimic activity. Both hemin, an iron-containing porphyrin cofactor, chlorine e6 (Ce6), photosensitizer, were facilely inserted into G4 structure high efficiency, achieving in-situ catalytic oxygenation photodynamic ROS production. Compared other self-oxygen-supplying tools, such advantageous for stability compatibility. Moreover, nanostructure could achieve cells targeting internalization intranuclear transport Ce6 virtue specific nucleolin binding AS1411. catalyze decomposition intracellular H2O2 hypoxia relief evidenced suppression hypoxia-inducible factor-1α (HIF-1α), moreover, GSH depletion cell ferroptosis also achieved therapy. Upon intravenous injection, effectively accumulate tumor, impose multi-modal excellent biocompatibility. Therefore, integrating capabilities O2 depletion, nanoplatform PDT/ferroptosis combination

Language: Английский

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Surface engineering Salmonella with pH‐responsive polyserotonin and self‐activated DNAzyme for better microbial therapy of tumor

Exploration, Journal Year: 2023, Volume and Issue: 3(6)

Published: Oct. 5, 2023

Abstract Bacteria‐based microbial immunotherapy shows various unique properties for tumor therapy owing to their active tropism and multiple anti‐tumor mechanisms. However, its clinical benefit is far from satisfactory, which limited by rapid systemic clearance neutrophils‐mediated immune restriction compromise the efficacy, as well non‐specific distribution cause toxicity. To address all these limitations, herein we reported a polyserotonin (PST) coated Salmonella ( Sal ) with surface adsorption of DNAzyme (Dz)‐functionalized MnO 2 nanoparticles (DzMN) therapy. PST could facilely coat on via oxidation self‐polymerization serotonin monomer, enabled stealth avoid while maintaining homing effect. Upon targeting tumor, was degraded exfoliated in response acidic microenvironment, thus liberating recover activities. Meanwhile, DzMN also delivered into hitchhiking , release Dz Mn 2+ after cells internalization. The then activated cofactor cleave target PD‐L1 mRNA, serving self‐activated system gene silencing. Combining activation knockdown, respectively, achieved enhanced efficacy. Notably, coating significantly decrease infection potential colonization at normal organs, achieving high vivo biosafety. This work addresses key limitations application biomaterials modification, provides promising platform better immunotherapy.

Language: Английский

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Nanomedicines for Alzheimer's disease: Therapies based on pathological mechanisms

Brain‐X, Journal Year: 2023, Volume and Issue: 1(3)

Published: July 28, 2023

Abstract Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. Because of complex pathogenesis AD and unique location lesions, effective clinical treatment strategies for this remain elusive. However, development nanotechnology has allowed a new era to emerge. nanomedicines are products interdisciplinary research that enable high precision targeted delivery. Additionally, they can specifically regulate various pathogenic factors. This review focuses on based pathological mechanisms target lesions. We also discuss precise regulatory effects (including nanomaterials themselves) proteins, neuroinflammatory molecules, other summarize trials have examined drugs, highlighting progress in their translation. Nanotechnology‐based nascent field, complete cure distant at present; therefore, we elaborate shortcomings current nanomedicines. Finally, prospects guide future

Language: Английский

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