Temporal shifts in microRNAs signify the inflammatory state of primary murine microglial cells DOI Creative Commons
Keren Zohar, Elyad Lezmi,

Fanny Reichert

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

Abstract The primary function of microglia is to maintain brain homeostasis. However, in several neurodegenerative diseases, such as Alzheimer’s disease, the pathophysiological hallmarks that drive disease progression involve neurotoxicity and alterations neuroinflammation. In this study, we exposed murine neonatal microglial cultures external signals mimic vivo stimuli caused by pathogens, injury, or toxic agents. presence benzoyl ATP (bzATP) lipopolysaccharide (LPS), observed a coordinated increase expression interleukins chemokines. We focused on dynamics differentially expressed microRNAs (miRNAs) are statistically significant (DEMs) tracked their post-activation dynamics. Monitoring miRNAs 3 8 hours (h) revealed robust changes 33 57 DEMs, most which were upregulated. DEMs exhibiting strongest temporal regulation included miR-155, miR-132, miR-3473e, miR-222, miR-146b. Additionally, strong downregulation miR-3963 was attributed exposure bzATP. Through TNFα NFκB signaling pathways, identified reflect cellular response inflammatory signals. incubated activated cells with ladostigil, neuroprotective compound has been shown reduce oxidative stress, inflammation, cognitive decline. While there no effect h post-activation, at h, few implicated inflammation suppression miR-27a, miR-27b, miR-23b upregulated ladostigil-dependent manner. conclude miRNA profile provides sensitive indicator regulatory mechanisms underlying inflammation-related responses microglia. propose subjected controlled activation paradigms can serve model for states monitor aging along diseases.

Language: Английский

MicroRNAs in Parkinson’s disease: From pathogenesis to diagnostics and therapeutic strategies DOI

Dongying Zheng,

Jibing Chween

Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

2
The uptake of extracellular vesicles: research progress in cancer drug resistance and beyond DOI

Luomeng Qian,

Pangzhou Chen,

Shiwu Zhang

et al.

Drug Resistance Updates, Journal Year: 2025, Volume and Issue: 79, P. 101209 - 101209

Published: Feb. 1, 2025

Language: Английский

Citations

2
Exosomal miR-92a-3p modulates M2 macrophage polarization in colorectal cancer: implications for tumor migration and angiogenesis DOI
Wei Zhao,

Yudan Wu,

Yixiao Wang

et al.

Medical Oncology, Journal Year: 2025, Volume and Issue: 42(4)

Published: March 10, 2025

Language: Английский

Citations

2
Immunofluorescent analysis of exosomes using a microchip filled with transparent antibody-conjugated beads for breast cancer liquid biopsy DOI
Na Li,

Cheng Cheng,

Di Wu

et al.

Analytica Chimica Acta, Journal Year: 2025, Volume and Issue: 1345, P. 343743 - 343743

Published: Jan. 31, 2025

Language: Английский

Citations

1
Resveratrol-Enhanced Human Neural Stem Cell-Derived Exosomes Mitigate MPP+-Induced Neurotoxicity Through Activation of AMPK and Nrf2 Pathways and Inhibition of the NLRP3 Inflammasome in SH-SY5Y Cells DOI Creative Commons
Tony F. Chan, Yuping Yang, Christopher J.B. Nicol

et al.

Life, Journal Year: 2025, Volume and Issue: 15(2), P. 294 - 294

Published: Feb. 13, 2025

Parkinson's disease (PD) is a progressive neurodegenerative disorder primarily characterized by the loss of dopaminergic neurons in substantia nigra. Mitochondrial dysfunction, oxidative stress, and neuroinflammation are recognized as critical pathological mechanisms driving neurodegeneration PD. Exosome (Exo)-based therapies, particularly those derived from human neural stem cells (hNSCs), offer promising neuroprotective effects due to their ability transfer bioactive molecules that modulate cellular processes. Resveratrol (RES), polyphenolic compound with potent antioxidant anti-inflammatory properties, has been shown enhance therapeutic potential cell (SC)-derived Exos. This study investigated RES-treated hNSCs-derived Exos (RES-hNSCs-Exos) on SH-SY5Y exposed 1-methyl-4-phenylpyridinium (MPP+), neurotoxin commonly used model Parkinsonian neurotoxicity. Treating MPP+ led significant reductions viability, mitochondrial increased activation inflammatory pathways. Treatment RES-hNSCs-Exos rescued MPP+-induced toxicity improving enhancing ATP production, increasing biogenesis, reducing reactive oxygen species (ROS) generation. The findings also demonstrated expression essential genes involved such PGC1α, NRF1, Tfam, indicating improved function presence RES-hNSCs-Exos. Further analysis revealed these protective were mediated activating AMP-activated protein kinase (AMPK) Nrf2 signaling pathways, which promoted health reduced stress. Moreover, treatment suppressed downregulating NLRP3 inflammasome secretion pro-inflammatory cytokines IL-1β IL-18. In conclusion, results suggest exhibit against neurotoxicity function, inhibiting neuroinflammation. These highlight hNSCs-Exos novel strategy for diseases like PD, RES valuable enhancer efficacy.

Language: Английский

Citations

1
Scalable production of anti-inflammatory exosomes from three-dimensional cultures of canine adipose-derived mesenchymal stem cells: production, stability, bioactivity, and safety assessment DOI Creative Commons

Anatcha Thongsit,

Saranyou Oontawee, Parkpoom Siriarchavatana

et al.

BMC Veterinary Research, Journal Year: 2025, Volume and Issue: 21(1)

Published: Feb. 20, 2025

The therapeutic potential of exosomes derived from mesenchymal stem cells (MSCs) is increasingly recognized in veterinary medicine. This study explored the feasibility a microcarrier-based three-dimensional (3D) culture system for producing (cEXO). Investigations were conducted to enhance production efficiency, ensure stability, and evaluate cEXO anti-inflammatory applications while assessing their safety profile. 3D improved efficient cEXO, yielding with acceptable profiles, including size approximately 81.22 nm, negative surface charge, high particle concentration (1.32 × 109 particles/mL). Confocal imaging proved dynamic changes cell viability across phases, highlighting challenges maintaining during repeated exosome collection cycles. Characterization via transmission electron microscopy, nanoparticle tracking analysis, zeta-potential measurements confirmed stability functionality particularly when stored at -20 °C. Functional assays showed that exerted significant activity RAW264.7 macrophages an inverse dose-dependent manner, no observed cytotoxicity fibroblasts or macrophages. Acute toxicity testing rats revealed adverse effects on clinical parameters, organ health, body weight, supporting use. highlights scalable robust activity, profiles. These findings advance development cEXO-based therapies support application regenerative

Language: Английский

Citations

1
Unpacking Exosomes: A Therapeutic Frontier for Cardiac Repair DOI Creative Commons

Elena McMullan,

Darukeshwara Joladarashi,

Raj Kishore

et al.

Current Cardiology Reports, Journal Year: 2025, Volume and Issue: 27(1)

Published: March 20, 2025

Abstract Purpose of Review The rising global prevalence cardiovascular disease is driving the need for innovative biotherapeutics. Recently, exosomes-extracellular vesicles involved in paracrine signaling have shown promise aiding heart repair associated with conditions. Their therapeutic potential encompasses several beneficial mechanisms, including anti-fibrosis, anti-inflammation, pro-angiogenesis, anti-oxidation, and anti-apoptosis, all contributing to improved cardiac function. This review provides a comprehensive overview exosomes highlights latest research on their effectiveness addressing current challenges regenerative medicine. Recent Findings Current approaches revolve around elucidating enhancing how different cell types, cargo, delivery methods impact healing pathological environment. Summary emerging field exosome promising regeneration due effects exosomal cargo. expansion mechanistic knowledge optimization techniques are required before standard clinical application.

Language: Английский

Citations

1
Exosome-based immunotherapy as an innovative therapeutic approach in melanoma DOI Creative Commons

Shabnam Babaei,

Manouchehr Fadaee, Hajar Abbasi‐Kenarsari

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Oct. 31, 2024

The malignant form of melanoma is one the deadliest human cancers that accounts for almost all skin tumor-related fatalities in its later stages. Achieving an exhaustive understanding reliable cancer-specific markers and molecular pathways can provide numerous practical techniques direct way toward development rational curative medicines to increase lifespan patients. Immunotherapy has significantly enhanced treatment metastatic late-stage melanoma, resulting incredible positive responses therapy. Despite increasing occurrence median survival rate patients with advanced, inoperable terminal disease increased from around six months years. current knowledge tumor microenvironment (TME) interaction immune system resulted swift growth innovative immunotherapy treatments. Exosomes are small extracellular vesicles (EVs), ranging 30 150 nm size, majority cells released them. possess natural advantages such as high compatibility living organisms low potential causing reactions, making them delivering therapeutic agents like chemotherapy drugs, nucleic acids, proteins. This review highlights recent advancements using exosomes approach providing medications melanoma.

Language: Английский

Citations

8
Pyroptosis in Endothelial Cells and Extracellular Vesicle Release in Atherosclerosis via NF-κB-Caspase-4/5-GSDM-D Pathway DOI Creative Commons
Salman Shamas,

Razia Rashid Rahil,

Laveena Kaushal

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(12), P. 1568 - 1568

Published: Nov. 22, 2024

Background: Pyroptosis, an inflammatory cell death, is involved in the progression of atherosclerosis. Pyroptosis endothelial cells (ECs) and its underlying mechanisms atherosclerosis are poorly understood. Here, we investigated role a caspase-4/5-NF-κB pathway pyroptosis palmitic acid (PA)-stimulated ECs EVs as players pyroptosis. Methods: Human umbilical vein (HUVECs) were cultured medium, treated with Ox-LDL, PA, caspase-4/5 inhibitor, NF-κB sEV release inhibitor for 24 h, respectively. The cytotoxicity PA was determined using MTT assay, migration scratch-wound-healing morphology bright field microscopy, lipid deposition oil red O staining. mRNA protein expression GSDM-D, CASP4, CASP5, NF-κB, NLRP3, IL-1β, IL-18 RT-PCR Western blot. Immunofluorescence used to determine NLRP3 ICAM-1 expressions. Extracellular vesicles (EVs) isolated exosome isolation kit characterized by blot scanning electron microscopy. Results: stimulation significantly changed HUVECs swelling, plasma membrane rupture, increased LDH release, which features accumulation reduced migration. also triggered inflammation dysfunction, evidenced activation, upregulation (endothelial activation marker), pyroptotic markers (NLRP3, IL-18). Inhibition (Ac-FLTD-CMK) (trifluoroacetate salt (TFA)) resulted significant reduction caspase-4/5, gasdermin D (GSDM-D) PA-treated HUVECs. Furthermore, GW4869, markedly PA-stimulated derived from exacerbated pyroptosis, indicated augmented NF-κB. Conclusions: present study revealed that inflammatory, non-canonical signaling may be one crucial mechanistic pathways associated ECs, facilitated normal during

Language: Английский

Citations

5
The role of exosomal hsa-miR-125b-5p and hsa-miR-320c as non-invasive biomarkers in high-radon areas of Kazakhstan DOI
Akmaral Aripova, Assiya Kussainova, Milana Ibragimova

et al.

Biomarkers, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 12

Published: Jan. 17, 2025

Radon, a radioactive gas, is significant risk factor for lung cancer, especially in non-smokers. This study examines the expression of exosomal microRNAs (miRNAs) as potential biomarkers radon-induced effects. A total 109 participants from high- and low-radon areas Kazakhstan were included. Exosomal hsa-miR-125b-5p hsa-miR-320c levels quantified using real-time PCR. Results revealed 25.4-fold increase 12.5-fold decrease exposed to high radon compared controls. Bioinformatic analysis identified key target genes, such PRDM1 IRF4, which are implicated cancer development. These findings suggest that miRNAs could serve non-invasive exposure, offering early diagnosis monitoring cancer. The underscores need further research validate these reliable diagnostic tools.

Language: Английский

Citations

0