As per the National Survey on Drug Use and Health, 10.5% of Americans aged 12 years and older are suffering from alcohol use disorder, with a wide range of neurological disorders. Alcohol-mediated neurological disorders can be linked to Alzheimer’s-like pathology, which has not been well studied. We hypothesize that alcohol exposure can induce astrocytic amyloidosis, which can be corroborated by the neurological disorders observed in alcohol use disorder. In this study, we demonstrated that the exposure of astrocytes to ethanol resulted in an increase in Alzheimer’s disease markers—the amyloid precursor protein, Aβ1-42, and the β-site-cleaving enzyme; an oxidative stress marker—4HNE; proinflammatory cytokines—TNF-α, IL1β, and IL6; lncRNA BACE1-AS; and alcohol-metabolizing enzymes—alcohol dehydrogenase, aldehyde dehydrogenase-2, and cytochrome P450 2E1. A gene-silencing approach confirmed the regulatory role of lncRNA BACE1-AS in amyloid generation, alcohol metabolism, and neuroinflammation. This report is the first to suggest the involvement of lncRNA BACE1-AS in alcohol-induced astrocytic amyloid generation and alcohol metabolism. These findings will aid in developing therapies targeting astrocyte-mediated neurological disorders and cognitive deficits in alcohol users.

Background: Colostrum extracellular vesicles (C-EVs) are nanoscale, bioactive vesicles with therapeutic potential. The mechanisms of action include the control of cellular and tissue homeostasis. These make C-EVs a novel means to control inflammatory and cellular dysfunctions. However, a limitation for their broad use is the ease of C-EV isolation and in ensuring their stability. Methods: Standard ultracentrifugation and gradient techniques used for EV recovery were employed, which included ultracentrifugation. Exodus dual-frequency ultrasonic nanofiltration (UNF) was a comparator used to overcome standard limitations by recovering pure vesicles at high concentrations. Both systems were evaluated for their abilities to recover clinical-grade C-EVs with optimal vesicle structural integrity and intact biological functions. Results: This study affirms UNF C-EV recovery by demonstrating intact Alix, CD63, Tsg101, and Flotillin antigens. The EVs maintained an intact bilayer structure with sizes ranging from to 50–200 nm. Functional tests showed preservation of their anti-inflammatory activities by suppression of pro-inflammatory cytokines and the NLRP3 inflammasome, caspase 1, interleukin-1, and 18 and maintaining cellular homeostasis. Processing time, high yield, and functional responses controlled cellular function. Conclusions: These data support the notion that UNF C-EVs can be recovered safely, at high yields, and reproducibly for future clinical applications.

Schematic representation of blood cell isolation by leukapharesis from Parkinson’s disease patients entered in the clinical trial. After centrifugal elutriation, enriched populations of monocytes and lymphocytes were recovered and then used to investigate key biomarkers associated with changes in movement-related functions. Tests were done at entry and after six and 12 months of treatment with Sargramostim. The image has been created by Biorendor.com. The online version contains supplementary material available at 10.1007/s10571-026-01717-7.

Colostrum extracellular vesicles (C-EVs) are nanoscale, bioactive vesicles with therapeutic potential. Mechanisms of action include their control of cellular and tissue homeostasis. These make C-EVs a novel means to control inflammatory and cellular dysfunctions. However, a limitation to their broad use is the ease of C-EV isolation and stability. Standard ultracentrifugation and gradient techniques used for EV isolation are costly, cumbersome, and time-consuming. Such isolation procedures require repeated ultracentrifugation. Exodus dual-frequency ultrasonic nanofiltration (UNF) isolation system can produce pure vesicles at high concentrations. Due to the need to recover C-EVs at clinical grade at high concentrations while preserving vesicle structural integrity and broad biological functions. Large-scale recovery is preserved within hours. We now affirm UNF C-EV purity by the presence of Alix, CD63, Tsg101, and Flotillin antigens. EVs’ sizes were from 50-200 nm, maintaining intact bilayer structures. Functional tests showed preservation of the vesicles’ anti-inflammatory activities with suppression of pro-inflammatory cytokines and the NLRP3 inflammasome, caspase 1, interleukin-1, and 18. These were maintained at baseline levels, sustaining cellular homeostasis. Processing time, high yields, and functional responses served to sustain cellular homeostasis. These data support that UNF-isolated C-EVs were recovered safely at high-yields and reproducibly for future clinical applications.