Microglia morphological response to mesenchymal stromal cell extracellular vesicles demonstrates EV therapeutic potential for modulating neuroinflammation DOI Creative Commons

Kanupriya R. Daga,

Andrew M. Larey,

Maria G. Morfin

и другие.

Journal of Biological Engineering, Год журнала: 2024, Номер 18(1)

Опубликована: Окт. 17, 2024

Mesenchymal stromal cell derived extracellular vesicles (MSC-EVs) are a promising therapeutic for neuroinflammation. MSC-EVs can interact with microglia, the resident immune cells of brain, to exert their immunomodulatory effects. In response inflammatory cues, such as cytokines, microglia undergo phenotypic changes indicative function e.g. morphology and secretion. However, these in not well understood. Additionally, no disease-relevant screening tools assess MSC-EV bioactivity exist, which has further impeded clinical translation. Here, we developed quantitative, high throughput morphological profiling approach neuroinflammation- relevant signals whether this be used indicate MSC-EVs.

Язык: Английский

Advancing neurological disorders therapies: Organic nanoparticles as a key to blood-brain barrier penetration DOI Creative Commons
Zahra Razavi,

Seyed Sina Alizadeh,

F. S. Razavi

и другие.

International Journal of Pharmaceutics, Год журнала: 2025, Номер 670, С. 125186 - 125186

Опубликована: Янв. 8, 2025

The blood-brain barrier (BBB) plays a vital role in protecting the central nervous system (CNS) by preventing entry of harmful pathogens from bloodstream. However, this also presents significant obstacle when it comes to delivering drugs for treatment neurodegenerative diseases and brain cancer. Recent breakthroughs nanotechnology have paved way creation wide range nanoparticles (NPs) that can serve as carriers diagnosis therapy. Regarding their promising properties, organic NPs potential be used effective drug delivery across BBB based on recent advancements. These remarkable ability penetrate using various mechanisms. This review offers comprehensive examination intricate structure distinct properties BBB, emphasizing its crucial function preserving balance regulating transport ions molecules. disruption conditions such stroke, Alzheimer's disease, Parkinson's disease highlights importance developing creative approaches drugs. Through encapsulation therapeutic molecules precise targeting processes vasculature, NP formulations present hopeful strategy improve BBB. We explore changes pathological investigate factors affect successful into brain. In addition, we most systems associated with shown positive results treating ischemic disorders. opens up new possibilities nanotechnology-based therapies cerebral diseases.

Язык: Английский

Процитировано

12

Molecular heterogeneity in human stroke – What can we learn from the peripheral blood transcriptome? DOI Creative Commons
Boryana Stamova, Bodie Knepp, Fernando Rodríguez

и другие.

Journal of Cerebral Blood Flow & Metabolism, Год журнала: 2025, Номер unknown

Опубликована: Март 13, 2025

Stroke is a multifaceted disease with genetic and environmental components like diet lifestyle. The central nervous immune systems display complex interactions, the peripheral response participating in brain injury repair mechanisms following stroke. bidirectional communication between injured blood presents an opportunity to investigate molecular changes latter. There substantial heterogeneity stroke pathogenesis, pathophysiology, comorbidities, treatment outcome. This captured underscored by transcriptome. current review highlights role of human transcriptome architecture for phenotyping different etiologies identifying underlying correlates clinically important variables outcomes. Specific features can potentially provide targets clinical translation prioritizing genes pathways evaluation experimental models. We also propose approach study patient-specific transcriptional uncover combinatorial altered patients that guide search prevention targets. Deciphering tissue be easily accessed monitored, such as blood, may improve trial success.

Язык: Английский

Процитировано

1

Interaction between post-tumor inflammation and vascular smooth muscle cell dysfunction in sepsis-induced cardiomyopathy DOI Creative Commons
Rui Liu, Lina Jia, Yu Lin

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 10, 2025

Sepsis-induced cardiomyopathy (SIC) presents a critical complication in cancer patients, contributing notably to heart failure and elevated mortality rates. While its clinical relevance is well-documented, the intricate molecular mechanisms that link sepsis, tumor-driven inflammation, cardiac dysfunction remain inadequately explored. This study aims elucidate interaction between post-tumor intratumor heterogeneity, of VSMC SIC, as well evaluate therapeutic potential exercise training specific pharmacological interventions. Transcriptomic data from NCBI GEO databases were analyzed identify differentially expressed genes (DEGs) associated with SIC. Weighted gene co-expression network analysis (WGCNA), ontology (GO), KEGG pathway enrichment analyses utilized biological significance these genes. Molecular docking dynamics simulations used investigate drug-target interactions, immune infiltration mutation carried out by means platforms like TIMER 2.0 DepMap comprehend influence DVL1 on responsiveness. Through utilization datasets, we discovered core exhibited remarkable up-regulated expression both SIC diverse kinds cancers, which poor prognosis inflammatory responses. revealed Digoxin could bind reduce oxidative stress The module related was identified WGCNA, demonstrated distinctive cell patterns impact immunotherapeutic resistance. regulator other cancers and, therefore, can serve target. present suggests targeted therapies enhance response regimens may be novel tool during particularly patients. drugs, Digoxin, require further vivo studies confirm their effects efforts improve outcomes immunotherapy-resistant

Язык: Английский

Процитировано

0

Microglia Morphological Response to Mesenchymal Stromal Cell Extracellular Vesicles Demonstrates EV Therapeutic Potential for Modulating Neuroinflammation DOI

Kanupriya R. Daga,

Andrew M. Larey,

Maria G. Morfin

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 3, 2024

ABSTRACT Background Mesenchymal stromal cell derived extracellular vesicles (MSC-EVs) are a promising therapeutic for neuroinflammation. MSC-EVs can interact with microglia, the resident immune cells of brain, to exert their immunomodulatory effects. In response inflammatory cues, such as cytokines, microglia undergo phenotypic changes indicative function e.g. morphology and secretion. However, these in not well understood. Additionally, no disease-relevant screening tools assess MSC-EV bioactivity exist, which has further impeded clinical translation. Here, we developed quantitative, high throughput morphological profiling approach neuroinflammation-relevant signals whether this be used indicate MSC-EVs. Results Using an immortalized human cell-line, observed increased size (perimeter, major axis length) complexity (form factor) upon stimulation interferon-gamma (IFN-γ) tumor necrosis factor-alpha (TNF-α). Upon treatment MSC-EVs, overall score (determined using principal component analysis) shifted towards unstimulated morphology, indicating that bioactive modulate microglia. The effects TNF-γ/IFN-α stimulated were concomitant reduced secretion 14 chemokines/cytokines (e.g. CXCL6, CXCL9) 12 CXCL8, CXCL10). Proteomic analysis lysates revealed significant increases 192 proteins HIBADH, MEAK7, LAMC1) decreases 257 PTEN, TOM1, MFF) treatment. Of note, many involved regulation migration. Gene Set Variation Analysis upregulation pathways associated response, cytokine production, infiltration T cells, NK cells) Semaphorin, RHO/Rac signaling). mitochondrial measured suggesting metabolism. Conclusion This study comprehensively demonstrates on microglial secretion, cellular proteome, content. Our high-throughput, rapid, low-cost enables batches manufacturing conditions enhance EV mitigate functional heterogeneity disease relevant manner. is highly generalizable adapted refined based selection signal, target cell, product.

Язык: Английский

Процитировано

1

Microglia morphological response to mesenchymal stromal cell extracellular vesicles demonstrates EV therapeutic potential for modulating neuroinflammation DOI Creative Commons

Kanupriya R. Daga,

Andrew M. Larey,

Maria G. Morfin

и другие.

Journal of Biological Engineering, Год журнала: 2024, Номер 18(1)

Опубликована: Окт. 17, 2024

Mesenchymal stromal cell derived extracellular vesicles (MSC-EVs) are a promising therapeutic for neuroinflammation. MSC-EVs can interact with microglia, the resident immune cells of brain, to exert their immunomodulatory effects. In response inflammatory cues, such as cytokines, microglia undergo phenotypic changes indicative function e.g. morphology and secretion. However, these in not well understood. Additionally, no disease-relevant screening tools assess MSC-EV bioactivity exist, which has further impeded clinical translation. Here, we developed quantitative, high throughput morphological profiling approach neuroinflammation- relevant signals whether this be used indicate MSC-EVs.

Язык: Английский

Процитировано

0