Therapeutic Approaches and Potential Mechanisms of Small Extracellular Vesicles in Treating Vascular Dementia

Cells, Год журнала: 2025, Номер 14(6), С. 409 - 409

Опубликована: Март 11, 2025

Small extracellular vesicles (sEVs), including exosomes as a subtype, with diameter typically less than 200 nm and originating from the endosomal system, are capable of transporting diverse array bioactive molecules, proteins, nucleic acids, lipids, thereby facilitating intercellular communication modulating cellular functions. Vascular dementia (VaD) represents form cognitive impairment attributed to cerebrovascular disease, characterized by complex multifaceted pathophysiological mechanism. Currently, therapeutic approach VaD predominantly emphasizes symptom management, no specific pharmacological treatment exists cure condition. Recent investigations have illuminated significant role sEVs in pathogenesis vascular dementia. This review seeks provide comprehensive analysis characteristics functions sEVs, particular focus on their involvement its underlying mechanisms. The objective is advance understanding interplays between dementia, offering novel insights for future research strategies.

Язык: Английский

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Krüppel‐like factor 4 transcription factor in blood–brain barrier endothelial cells: A potential role in Alzheimer's disease

Animal Models and Experimental Medicine, Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

Alzheimer's disease is the most prevalent chronic neurodegenerative disorder worldwide, with no sufficient cure. Ongoing research focused on developing new therapies aimed at preventing or delaying onset of symptoms, slowing progression, and improving cognitive behavioral outcomes in individuals affected by disease. Among various pathological changes associated this condition, blood-brain barrier (BBB) leakage plays a crucial role as it serves vital boundary for maintaining central nervous system (CNS) health. Preserving integrity functionality BBB essential to protect brain from amyloid-β accumulation, neuroinflammation, neuronal degeneration. This review summarizes models characterized over time. More importantly, we introduce Krüppel-like factor 4 (KLF4), transcription involved vascular systems, discuss its relevance By elucidating functions KLF4 within both CNSs, highlights potential modulating pathology, which may contribute therapeutic strategies managing debilitating condition.

Язык: Английский

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Goat Milk Protein-Derived ACE Inhibitory Peptide SLPQ Exerts Hypertension Alleviation Effects Partially by Regulating the Inflammatory Stress of Endothelial Cells

Foods, Год журнала: 2024, Номер 13(21), С. 3392 - 3392

Опубликована: Окт. 25, 2024

Hypertension has always posed a severe threat to people's health. Food-derived angiotensin-converting enzyme (ACE)-inhibitory peptides have the potential both prevent and treat hypertension. In current investigation, two ACE-inhibitory (SLPQ PYVRYL) from goat milk were studied for their endothelial effects using EA.hy926 cells. PYVRYL outperformed SLPQ, yet neither impacted cell survival below 200 μg/mL. Investigation of SLPQ's impact on expression revealed 114 differentially expressed genes, with 65 downregulated 49 upregulated. The genes enriched in cytokine interactions, coagulation cascades, Hippo signaling, ECM-receptor interaction. Decreased c-x-c motif chemokine ligand 2 (CXCL2), integrin subunit beta (ITGB2), fbj murine osteosarcoma viral oncogene homologue (FOS) increased secreted phosphoprotein 1 (SPP1) may protect cells inflammation. Our findings suggest that beyond ACE inhibition, SLPQ aids blood pressure control by influencing function, paving way its use as an antihypertensive food ingredient.

Язык: Английский

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A Novel Cyanine-Based Fluorescent Dye for Targeted Mitochondrial Imaging in Neurotoxic Conditions and In Vivo Brain Studies

Опубликована: Окт. 26, 2024

Abstract Mitochondrial dysfunction is a key feature of neurodegenerative diseases, often preceding symptoms and influencing disease progression. However, real-time in vivo imaging mitochondria the brain limited by existing dyes like MitoTrackers, which struggle with poor tissue penetration, phototoxicity, inability to cross blood-brain barrier (BBB). This study introduces Cy5-PEG4, novel mitochondrial-targeting dye that overcomes these limitations, enabling high-resolution, non-invasive mitochondrial dynamics. Cy5-PEG4 effectively labels primary neuronal cells exposed SARS-CoV-2 RNYIAQVD peptide, revealing dose-dependent alterations function may contribute COVID-19-related neurodegeneration. Importantly, crosses BBB without causing neuroinflammation or toxicity, making it safe tool for detailed studies responses. In 3D cultured cells, captures dynamic changes distribution morphology as cell structures mature, highlighting its potential neurobiological research, diagnostics, therapeutic development. These findings support powerful studying progression, identifying early biomarkers, evaluating strategies disorders COVID-19.

Язык: Английский

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Dynamics of development of the systemic inflammatory response and disruption of endothelium-dependent vasodilation of cerebral arteries

Vestnik Moskovskogo universiteta Seria 16 Biologia, Год журнала: 2024, Номер 79(№4, 2024), С. 315 - 321

Опубликована: Янв. 1, 2024

Systemic chronic inflammation (SCI) can develop due to diabetes mellitus, coronary artery disease, atherosclerosis, autoimmune diseases, kidney, liver, and lung pathologies, cancer, etc. During the COVID-19 pandemic, there was clear evidence showing that damages endothelial cells of vascular wall, leading impaired microcirculation. Currently, mechanisms causing pathological changes in brain amid SCI are still unclear. In this work, we investigated how systemic affects vasodilatory function cerebral arteries. modeled using well-established cecal ligation puncture model, which involves tying off cecum below ileocecal valve puncturing it with a needle. For characterizing model animals, recorded body weight, blood pressure, analyzed levels leukocytes, ESR, hematocrit, erythrocyte aggregation arterial blood, number desquamated venous blood. The density network pial membrane reactivity studied vivo microvascular imaging. vessels per unit area diameter under influence vasoactive substances – aminoguanidine (an inducible NO-synthase inhibitor) acetylcholine were measured. From 7 days 3 months after onset SCI, leukocyte rat increased by 2.1–1.7 times compared control group. 1.8 control. Erythrocyte rose an average 1.3 times. decreased 1.7 constrictions arteries induced 1.5 3.7 expanded response 4.9 Thus, over period three leads decrease deterioration vasomotor

Язык: Английский

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Aging and Bioenergetics of Mitochondria

Advances in biochemistry in health and disease, Год журнала: 2024, Номер unknown, С. 285 - 303

Опубликована: Янв. 1, 2024

Язык: Английский

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