Search Results (112)

Inflammatory lung diseases are characterized by complex immune dysregulation and structural tissue damage, demanding the development of novel therapeutic and diagnostic strategies. Exosomes (Exos) have emerged as promising alternatives to address these challenges by serving as key mediators and effective therapeutic nanocarriers. This review systematically analyzes the multifunctional roles of Exos derived from various sources, including immune cells, mesenchymal stem cells (MSCs), lung structural cells, and non-mammalian sources such as plants and milk, in the context of inflammatory lung diseases. These vesicles modulate critical pathological processes, such as macrophage polarization, oxidative stress, and programmed cell death, by delivering functional cargos, including miRNAs and proteins. Studies demonstrating the antioxidant properties of Exos are classified, and their roles in attenuating oxidative stress-mediated lung injury are discussed. Furthermore, engineering and priming strategies, as well as airway-directed delivery methods such as nebulization, are reported to enhance therapeutic efficacy and targeting. Evidence also indicates that plant-derived Exos could be scalable and safer alternatives to mammalian cell-derived Exos. Collectively, Exos represent a next-generation platform for precision medicine, functioning as potent therapeutic agents and efficient drug-delivery systems for the treatment of complex inflammatory lung diseases. Full article

Milk-derived exosomes (MDEs) are bioactive nanocarriers rich in microRNAs (miRNAs) that play critical roles in post-transcriptional regulation during neonatal development and immune adaptation. However, the dynamic changes in miRNA expression across lactation stages and their biological functions remain insufficiently explored. We hypothesized that the miRNA cargo of buffalo MDEs exhibits temporal specificity, thereby dynamically matching the immune requirements of the neonatal calves. Therefore, the present study aimed to systematically characterize the miRNA expression profiles of MDEs derived from colostrum, transitional milk, and mature milk. MDEs were isolated, purified using differential ultracentrifugation, and characterized via transmission electron microscopy, Western blotting, and nanoparticle-tracking analysis. A total of 370 miRNAs were identified in the MDEs, with 220 (59.5%) co-expressed across colostrum, transitional milk, and mature milk. Comparative analysis revealed that colostrum MDEs exhibited the greatest miRNA diversity. Expression patterns of miRNAs showed distinct stage-specific clustering as lactation progressed. Compared to mature milk, 100 differentially expressed miRNAs (DE-miRNAs) were identified in colostrum MDEs, including 39 upregulated and 61 downregulated miRNAs. Bioinformatics analyses indicated that predicted target genes were associated with transmembrane transport, immune response, cell development, and apoptosis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis identified pathways involved in immune regulation, inflammation, and apoptosis. Moreover, macrophages incubated with buffalo colostrum MDEs showed upregulation of proliferation-related genes and downregulation of pro-inflammatory factors, suggesting an anti-inflammatory effect through activation of the phosphoinositide 3-kinase-protein kinase B (PI3K-Akt) signaling pathway. These findings offer new insights into miRNA profiles of buffalo MDEs across the early postpartum transition and provide a preliminary basis for exploring immunomodulatory potential of buffalo MDEs. Full article

Lung cancer remains one of the leading causes of cancer-related mortality worldwide, with a five-year survival rate of only 26%, primarily due to late-stage diagnosis and limited treatment options. Exosomes, nanosized extracellular vesicles released by nearly all cell types, have emerged as promising tools in both diagnostics and therapeutics. Their unique composition containing proteins, lipids, and nucleic acids reflects the molecular profile of their cell of origin, making them excellent candidates for non-invasive early detection biomarkers. For therapeutic applications, exosomes offer biocompatible, low-immunogenicity platforms capable of delivering diverse therapeutic agents, including small molecules, siRNAs, and antimetabolites, directly to tumor cells while minimizing systemic toxicity. Functionalization strategies, such as folic acid tagging, have further enhanced tumor specificity, especially in cancers with high folate receptors. However, clinical translation is hindered by challenges including lack of standardized isolation and characterization methods, high production costs, and regulatory uncertainties. Despite these limitations, ongoing research continues to optimize exosome production, targeting, and integration with conventional therapies. Milk- and colostrum-derived exosomes have shown promising potential due to their abundance, scalability, oral bioavailability, and safety. Collectively, exosomes represent a transformative approach in lung cancer management, with the potential to improve early diagnosis, enhance therapeutic efficacy, and reduce adverse effects, thereby offering a path toward more personalized and effective cancer care. Full article

Human breast milk harbors commensal lactic acid bacteria with probiotic potential, and microbial fermentation may enhance the bioactivity of plant-derived exosome-like nanovesicles (EVs); this study evaluated whether L. plantarum BMSE-HMP251 isolated from breast milk could safely ferment Hordeum vulgare L. and improve the anti-inflammatory activity of derived EVs. BMSE-HMP251 was identified by 16S rRNA sequencing and characterized by biochemical, safety, and genomic analyses. EVs derived from Hordeum vulgare L. extract and BMSE-HMP251-fermented broth were evaluated for physicochemical properties, antioxidant activity, cytotoxicity, and anti-inflammatory activity in LPS-stimulated HT-29 and RAW 264.7 cells. EVs derived from Hordeum vulgare L. fermentation exhibited a distinct size distribution and significantly enhanced bioactivity, including higher DPPH radical scavenging activity and greater suppression of nitric oxide production and proinflammatory cytokine (TNF-α and IL-1β) mRNA expression, compared with EVs from unfermented extracts. These effects were observed following fermentation with the human breast milk-derived strain L. plantarum BMSE-HMP251, which showed species-consistent phenotypic and genomic characteristics and no safety concerns. Overall, fermentation markedly enhances the anti-inflammatory potential of plant-derived EVs, supporting fermentation as a safe and effective strategy to improve their functional value. Full article

Androgenetic alopecia (AGA) and telogen effluvium (TE) are common hair loss disorders characterized by dysregulated hair follicle cycling and impaired dermal papilla cell function. Emerging evidence indicates that exosomes are key mediators of intercellular communication, largely through their microRNA (miRNA) cargo. Milk-derived exosomes (Mi-Exos) represent an accessible and biologically active source of regulatory miRNAs with potential relevance for hair disorders. This study evaluated the in vitro effects of bovine milk-derived exosomes (MEV-miRNAs) on human hair follicles. MEV-miRNAs were enriched in miRNA families (Let-7, miR-21, miR-30, miR-200, and miR-148/152) previously implicated in hair follicle regulation. Viability/metabolic activity of hair follicle dermal papilla (HFDP) cells was assessed, and human hair follicles were cultured ex vivo to measure shaft elongation and modulation of the WNT signaling pathway by qRT-PCR. MEV-miRNAs significantly increased HFDP cell viability after 24 h compared with controls. Human hair follicles showed a non-significant trend toward increased elongation following treatment. Gene expression analysis revealed significant up-regulation of key WNT pathway components, including WNT2, WNT5B, WNT10A, WNT11, MMP7, WISP1, and NKD1, indicating modulation of WNT-associated pathways implicated in hair follicle growth and cycling. Overall, MEV-miRNAs exhibit positive modulatory effects on signaling pathways, supporting their potential as a novel therapeutic strategy for AGA and TE. Full article

Background/Objectives: Hippocampal neuroinflammation (HNF) is a key pathological feature in neurodegenerative disorders. Milk-derived exosomes, as bioactive extracellular vesicles, have underexplored potential in regulating brain neuroinflammatory responses. This study aimed to characterize desert milk exosomes (D-Exo) and investigate their neuroprotective and anti-neuroinflammatory effects in LPS-induced HNF mice model and an LPS-stimulated BV2 microglia. Methods: Exosomes were isolated from desert and non-desert milk (ND-Exo) for proteomic analysis. After pretreating BV2 cells with exosomes and stimulating with LPS, their inflammatory responses and polarization were assessed by RT-PCR. Balb/c mice were orally gavaged with D-Exo or 0.9% NaCl for 28 days before LPS injection. Cognitive function was assessed via behavioral tests, with microglial/astrocyte activation analyzed by immunofluorescence. Results: D-Exo exhibited superior stability and a unique proteomic profile enriched with proteins linked to neuroinflammation and blood-brain barrier (BBB) integrity, notably within the AMPK signaling pathway. In vitro, D-Exo shifted LPS-stimulated microglia from the M1 to the M2 phenotype. In vivo, it alleviated HNF and cognitive decline, reduced Aβ_1-42 and Tau deposition, elevated BDNF and MAP2, and suppressed neuroinflammation and glial activation. Conclusions: D-Exo is enriched with specific proteins, attenuates neuroinflammation and cognitive decline by regulating microglial M1/M2 polarization and AMPK pathway, highlighting its preventive potential. Full article

Due to their therapeutic potential and effects on cells, exosomes derived from bovine colostrum (BCE) and milk (BME) are molecules that have been at the center of recent studies. Their properties include the ability to cross biological barriers, their natural biocompatibility, and their structure, which enable them to act as stable nanocarriers. Exosomes derived from milk and colostrum stand out in cancer prevention and treatment due to these properties. BMEs can be enriched with bioactive peptides, lipids, and nucleic acids. The targeted drug delivery capacity of BMEs can be made more efficient through these enrichment processes. For example, BME enriched with an iRGD peptide and developed using hypoxia-sensitive lipids selectively transported drugs and reduced the survival rate of triple-negative breast cancer (TNBC) cells. ARV-825-CME formulations increased antitumor activity in some cancer types. The anticancer effects of exosomes are supported by these examples. In addition to their anticancer activities, exosomes also exhibit effects that maintain immune balance. BME and BCE can regulate inflammatory responses with their miRNA and protein loads. These effects of BMEs have been demonstrated in studies on colon, breast, liver, and lung cancers. The findings support the safety and scalability of these effects. However, significant challenges remain in terms of their large-scale isolation, load heterogeneity, and regulatory standardization. Consequently, BMEs represent a new generation of biogenic nanoplatforms at the intersection of nutrition, immunology, and oncology, paving the way for innovative therapeutic approaches. Full article

Background/Objective: Milk and fermented dairy products are widely consumed functional foods and beverages, offering not only essential nutrients but also bioactive compounds with potential to modulate host immunity, metabolism, and the gut microbiome. This narrative review aims to synthesize current knowledge on the relationship between dairy consumption, gut microbiome, immune modulation, adverse reactions to food, physical performance and cardiometabolic health. Methods: An extensive literature analysis was conducted to explore how milk and fermented dairy products modulate the gut microbiome and influence the immune and cardiometabolic health. This study synthesis focused on key dairy bioactive compounds, such as probiotics, miRNAs, milk-derived peptides and exosomes and on evaluating their proposed mechanisms of action in inflammation and metabolic regulation, and their possible influence on physical performance through gut–microbiome interactions. Additionally, advances in metagenomic and metabolomic technologies were reviewed for their potential to uncover host–microbiota interactions relevant to precision nutrition strategies. Results: Fermented dairy products have shown potential in promoting beneficial bacteria growth such as Lactobacillus and Bifidobacterium, short-chain fatty acid synthesis and reduction in proinflammatory biomarkers. Specific dairy-derived peptides and exosomal components may further support gut barrier integrity, immune regulation and improve physical performance and reduce cardiometabolic risk factors. Additionally, emerging evidence links individual gut microbiota profiles to specific metabolic responses, including tolerance to lactose and bovine milk proteins. Conclusions: Integrating microbiome science with traditional nutritional paradigms enhances our understanding of how dairy influences immune and cardiometabolic health. Overall, current evidence suggests that investigating dairy-microbiome interactions, alongside lifestyle factors such as physical activity, may inform future personalized nutrition strategies aimed at supporting metabolic and immune health. Full article

Emerging evidence highlights extracellular vesicles (EVs), especially exosomes, as critical molecular messengers linking pediatric obesity to multi-organ complications. This scoping review synthesizes current knowledge on EVs-mediated intercellular communication that exacerbates inflammation, insulin resistance, endothelial dysfunction and organ-specific damage. Data demonstrate that adipose- and endothelial-derived EVs carry bioactive cargo, microRNAs, proteins, and lipids, that modulate key pathways driving metabolic derangements and vascular injury, often preceding detectable clinical biomarkers. Notably, maternal obesity influences EVs composition in breast milk, shaping early-life metabolic programming and offspring risk of obesity. Recent studies underscore the diagnostic and therapeutic potential of EVs in obesity-related conditions such as metabolic-associated fatty liver disease (MAFLD), early renal injury, and cardiovascular dysfunction in children. Furthermore, EVs released in response to exercise or bariatric surgery may mediate systemic metabolic improvements, offering a novel window into personalized interventions. Despite promising findings, standardization of EV isolation and profiling in pediatric research is lacking, and large-scale longitudinal studies are urgently needed. By deepening our understanding of EVs biology, clinicians may advance early detection, risk stratification, and targeted therapies to interrupt the progression from childhood obesity to lifelong metabolic and cardiovascular disease. Full article

Background: Endothelial cell (EC) dysfunction is an early sign of compromised vascular integrity and is associated with various cardiovascular diseases (CVDs). Activation of Toll-like receptor 4 (TLR4) plays a central role in this process. Extracellular vesicles (EVs) derived from milk have known anti-inflammatory properties, particularly in suppressing TLR4 activation. This study investigates the therapeutic potential of human breast milk-derived EVs (HBM-EVs) in mitigating EC dysfunction related to CVDs. Methods: HBM-EVs were isolated from the breast milk of healthy nursing mothers using ultracentrifugation. HBM-EVs were applied to lipopolysaccharide (LPS)-treated human umbilical vein endothelial cells (HUVECs), and inflammatory marker expression was assessed through qPCR and Western blotting. Mitochondrial oxidative stress was measured using MitoSOX. The effects of HBM-EVs were further evaluated in ex vivo studies using mesenteric arteries from diet-induced obese mice. Additionally, the effect of HBM-EVs on angiogenesis was tested via a wound closure assay. Results: In HUVECs, pre-treatment with HBM-EVs inhibited LPS-induced expression of inflammatory markers, including IL-6 and VCAM-1, as well as the phosphorylation of NFκB. Additionally, HBM-EVs reduced LPS-induced mitochondrial oxidative stress. In animal studies, HBM-EV treatment restored EC-dependent vasorelaxation in mesenteric arteries from diet-induced obese mice. Furthermore, HBM-EVs enhanced EC migration, leading to improved wound closure in HUVECs. Conclusion: This study demonstrates the therapeutic potential of HBM-EVs in alleviating EC dysfunction, offering a promising new approach to the treatment of CVDs. Future research will focus on identifying the specific cargo of HBM-EVs and further exploring their therapeutic mechanisms in endothelial dysfunction. Full article

Background and Objectives: Human breast milk contains essential nutrients for infant growth, as well as bioactive molecules such as exosomes and miRNAs, which play a key role in the maturation of the infant’s immune system. Breast milk from mothers of preterm and term infants shows significant differences in its nutrient contents and bioactive components. This preliminary study aimed to compare the expressions of 13 immunomodulatory microRNAs present in breast milk from the mothers of preterm and term infants. Materials and Methods: Breast milk samples were obtained from 5 breastfeeding mothers of term infants and 5 breastfeeding mothers of preterm infants. Every mother provided morning, noon, and evening milk samples. The total protein, fat, and lactose concentrations were measured. In addition, miRNAs were extracted from the exosomal fraction of each sample. The expression levels of the 13 miRNAs were compared and analyzed at the three time points each day. Results: The preterm infants’ milk had higher average fat and lactose levels. There were no differences in the total protein concentrations. The expressions of miRNAs in the preterm infants’ milk showed significantly higher variations in miR-17-5p, miR-24, miR-29b, miR-30a-5p, and miR-146a. The other miRNAs did not show variations. Interestingly, the highest miRNA expression was only observed in breast milk from the nighttime. The morning and midday samples showed distinct expression patterns. Conclusions: We identified the immunomodulatory microRNA components and their changes in expression levels at different times of the day, as well as those most strongly expressed in breast milk consumed by preterm infants. Full article

Exosomes are membranous vesicles that play a crucial role as intercellular messengers. Cells secrete exosomes, which can be found in a variety of bodily fluids such as amniotic fluid, semen, breast milk, tears, saliva, urine, blood, bile, ascites, and cerebrospinal fluid. Exosomes have a distinct bilipid protein structure and can be as small as 30–150 nm in diameter. They may transport and exchange multiple cellular messenger cargoes across cells and are used as a non-invasive biomarker for various illnesses. Due to their unique features, exosomes are recognized as the most effective biomarkers for cancer and other disease detection. We give a review of the most current applications of exosomes derived from various sources in the prognosis and diagnosis of multiple diseases. This review also briefly examines the significance of exosomes and their applications in biomedical research, including the use of aptamers and antibody–antigen functionalized biosensors. Full article

Heat stress in dairy cows, caused by high temperature and humidity during summer, has led to significant declines in milk production and severe economic losses for farms. Exosomes—extracellular vesicles carrying bioactive molecules—are critical for intercellular communication and immunity but remain understudied in heat-stressed Holstein cows. In this study, we extracted exosomes from three heat-stressed (HS) cows and three non-heat-stressed (Ctr) cows and employed proteomics to analyze plasma exosomes. We identified a total of 28 upregulated and 18 downregulated proteins in the HS group compared to the control group. Notably, we observed a significant upregulation of key protein groups, including cytoskeletal regulators, signaling mediators, and coagulation factors, alongside the downregulation of HP-25_1. These differentially expressed proteins demonstrate strong potential as heat stress biomarkers. GO and KEGG analyses linked the differentially expressed proteins to actin cytoskeleton regulation and endoplasmic reticulum pathways. Additionally, protein–protein interaction (PPI) analysis revealed the PI3K-Akt signaling pathway as a central node in the cellular response to heat stress. These findings establish plasma exosomes as valuable biospecimens, provide valuable insights into the molecular mechanisms of heat stress response, and may contribute to the development of precision breeding strategies for enhanced thermal resilience in dairy herds. Full article

The global obese population accounts for approximately 30% of the total population and continues to increase. White adipocytes, which accumulate in the body for energy storage, are associated with obesity. Mechanisms that activate browning of white adipocytes are an attractive therapeutic target for obesity and metabolic disorders. Exosomes are nano-sized biovesicles that play a role in cell-to-cell communication though the transfer of cargos such as microRNAs. Although milk exosomes contain many endogenous microRNA molecules, the role of microRNAs in milk exosomes is limited. Therefore, the aim of this study was to investigate the effects of milk exosomes on the browning of white adipocyte. Mouse pre-adipocytes (3T3-L1) and human adipose-derived stem cells (hADSCs) were differentiated and exposed to milk exosomes. Compared to control, milk exosomes promoted the expression of thermogenic genes and cellular mitochondrial energy metabolism in both 3T3-L1 cells and hADSCs. Additionally, milk exosomes were orally administered to mice fed a high-fat diet. As the intake of milk exosomes increased, the mice’s body weight decreased. Milk exosomes also increased the protein levels of thermogenic genes and mitochondrial-related genes in mouse adipose tissue. The overexpression of miR-11987, which is abundant in milk exosomes, in both 3T3-L1 cells and hADSCs led to the increased expression of thermogenic genes and mitochondrial activity. Our results support that bovine-specific miR-11987 in milk exosomes promotes the browning of white adipocytes. Therefore, milk exosome and milk exosomal miR-11987 could have significant clinical implications for obesity and metabolic syndrome. Full article

Exosomes, nanoscale vesicles involved in intercellular communication, have garnered significant attention for their potential in drug delivery and therapeutic applications. This review provides a comparative analysis of mammalian-derived exosomes, particularly milk-derived exosomes, and plant-derived exosome-like nanoparticles (PDENs). It explores their biogenesis, bioactivities, and functional similarities, including their roles in cellular communication, immune modulation, and disease therapy. While milk-derived exosomes exhibit promising biocompatibility and stability for targeted delivery, PDENs offer distinct advantages, such as scalability and inherent bioactivities, derived from their plant sources. Despite similarities in their structure and cargo, PDENs differ in lipid composition and protein profiles, reflecting plant-specific functions. Emerging research highlights the therapeutic potential of PDENs in managing inflammation, oxidative stress, and other diseases, emphasizing their utility as functional food components and nanocarriers. However, challenges related to their chemical stability and large-scale production require further investigation. This review underscores the need for advanced studies to fully harness the potential of these natural nanocarriers in drug-delivery systems and therapeutic interventions. Full article