Search Results (695)

Objective: This study aimed to identify plasma exosomal microRNAs (miRNAs) associated with weight loss and type 2 diabetes (T2D) remission following low-calorie diet (LCD) intervention. Methods: A 6-month dietary intervention targeting T2D remission was conducted among individuals with T2D. Participants underwent a 3-month intensive weight loss phase consuming LCD (815–835 kcal/day) and a 3-month weight maintenance phase (N = 32). Sixteen participants were randomly selected for characterization of plasma-derived exosomal miRNA profiles at baseline, 3 months, and 6 months using small RNA sequencing. Linear mixed-effects models were used to identify differentially expressed exosomal miRNAs between responders and non-responders. Pathway enrichment analyses were conducted using target mRNAs of differentially expressed miRNAs. Logistic regression models assessed the predictive value of differentially expressed miRNAs for T2D remission. Results: Among the 16 participants, 6 achieved weight loss ≥10% and 12 achieved T2D remission. Eighteen exosomal miRNAs, including miR-92b-3p, miR-495-3p, and miR-452b-5p, were significantly associated with T2D remission and weight loss. Pathway analyses revealed enrichment in PI3K-Akt pathway, FoxO signaling pathway, and insulin receptor binding. The addition of individual miRNAs including miR-15b-3p, miR-26a-5p, and miR-3913-5p to base model improved the area under the curve values by 0.02–0.08 at 3 months and by 0.02–0.06 at 6 months for T2D remission. Conclusions: This study identified exosomal miRNAs associated with T2D remission and weight loss following LCD intervention. Several exosomal miRNAs might serve as valuable predictors of T2D remission in response to LCD intervention. Full article

Asthma, the most common chronic respiratory condition in children, involves airway inflammation, hyper-responsiveness, and frequent exacerbation that worsen the airflow and inflammation. Exosomes, extracellular vesicles carrying microRNAs (miRNAs), play a key role in cell communication alongside other types of communication and are promising markers of asthma severity. This study compares exosomal miRNA and long non-coding RNA (lncRNA) profiles in boys with asthma, focusing on differences between those with normal lung functions and those with severe airflow obstruction. This study enrolled 20 boys aged 9–18 years with asthma, split into two groups based on their lung function. Ten had normal lung function (NLF; FEV1/FVC > 0.84, FEF75% > 69% predicted), while ten had severe airflow obstruction (SAO; FEV1/FVC < 0.70, FEF75 < 50% predicted). Saliva and blood samples were collected. Exosomes were isolated, quantified, and analyzed via small RNA sequencing to identify differentially expressed (DE) miRNA and lncRNA profiles. Bioinformatic tools were then used to explore potential miRNA biomarkers linked to asthma severity. SAO subjects were more likely to exhibit allergen sensitization, higher IgE levels, and more eosinophils. We identified 27 DE miRNAs in plasma and 40 DE miRNAs in saliva. Additionally, five key miRNAs were identified in both saliva and plasma which underline important pathways such as neurotrophins, T-cell receptor, and B-cell receptor signaling. We further outlined key features and functions of miRNAs and long non-coding RNAS (lncRNAs) and their interactions in children with asthma. This study identified DE miRNAs and lncRNAs in children with SAO when compared to those with NLF. Exosomal miRNAs show strong potential as non-invasive biomarkers for personalized asthma diagnosis, treatment, and monitoring. These RNA markers may also aid in tracking disease progression and response to therapy, thereby supporting the need for future studies aimed at applications in precision medicine. Full article

Exosomes, small extracellular vesicles secreted by various cell types, have gained significant attention in cancer investigations. Isolation and characterization of exosomes derived from DOK (dysplastic oral keratinocyte), SCC (squamous cell carcinoma) and HaCaT (normal skin keratinocyte) cell lines and microRNA profiling were conducted. Magnetic sorting was applied to obtain pure exosomes. Morphology and size were characterized by transmission electron microscopy and nanoparticle tracking analysis. Validation of membrane exosomal markers (CD9, CD63) was performed via Western blotting. MiR-21, miR-31, and miR-133 levels were analyzed in exosomes and parent cells by qPCR. Biological effects of the exosomes were tested by adding them to fibroblast cultures and determining the expression of relevant carcinogenesis markers by qPCR. Exosomes appeared as cup-shaped nano-sized particles, and there was no difference regarding particle diameter and concentration between the three types of exosomes. The oncogenic miR-21 was significantly upregulated both in SCC and SCC-derived exosomes compared to DOK and HaCaT cells and their respective exosomes. However, miR-31 unexpectedly showed the highest expression in normal cells and the lowest in HaCaT exosomes. MiR-133, the tumor suppressor miRNA, was downregulated in both SCC and DOK cells compared to normal (HaCaT) cells, while the opposite situation was observed in exosomes, with HaCaT cells showing the lowest levels of miR-133. The differences in exosome content were reflected in signaling pathway activation in exosome-treated fibroblasts, with SCC exosomes exerting the most potent effect on several cancer-related pathways, notably PIK3/AKT, PTEN, and NOTCH signaling cascades. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by dopaminergic neuronal loss, α-synuclein aggregation, and chronic neuroinflammation. Recent evidence suggests that exosomal microRNAs (miRNAs)—small, non-coding RNAs encapsulated in extracellular vesicles—are key regulators of PD pathophysiology and promising candidates for biomarker development and therapeutic intervention. Exosomes facilitate intercellular communication, cross the blood–brain barrier, and protect miRNAs from degradation, rendering them suitable for non-invasive diagnostics and targeted delivery. Specific exosomal miRNAs modulate neuroinflammatory cascades, oxidative stress, and synaptic dysfunction, and their altered expression in cerebrospinal fluid and plasma correlates with disease onset, severity, and progression. Despite their translational promise, challenges persist, including methodological variability in exosome isolation, miRNA profiling, and delivery strategies. This review integrates findings from preclinical models, patient-derived samples, and systems biology to delineate the functional impact of exosomal miRNAs in PD. We propose mechanistic hypotheses linking miRNA dysregulation to molecular pathogenesis and present an interactome model highlighting therapeutic nodes. Advancing exosomal miRNA research may transform the clinical management of PD by enabling earlier diagnosis, molecular stratification, and the development of disease-modifying therapies. Full article

Mesenchymal stem cell (MSC) transplantation has emerged as a potential therapeutic strategy for systemic sclerosis (SSc), a rare autoimmune disease characterized by inflammation, fibrosis, and vasculopathy. Recent evidence suggests that the therapeutic benefits of MSCs do not depend directly on their ability to proliferate but rather on their capacity to release extracellular nanovesicles known as exosomes (MSC-Exos). MSC-Exos are rich in bioactive molecules such as microRNAs, which can modulate gene expression and trigger significant biological responses, playing a central role in modulating immune responses, inhibiting fibrotic pathways and promoting tissue repair and angiogenesis. Preclinical studies have demonstrated that MSC-Exos can attenuate fibrosis, modulate macrophage polarization, suppress autoreactive lymphocyte activity, and even reverse pulmonary arterial hypertension in animal models of SSc. Compared to cell-based therapies, MSC-Exos offer several advantages, including lower immunogenicity and better safety profile. This review provides an overview of the immunomodulatory, antifibrotic, and angiogenic properties of MSC-Exos and explores their potential as novel cell-free therapy for SSc. Full article

Circulating cell-free nucleic acids (NAs), in particular plasma-derived cell-free DNA, have evolved into promising clinical analytes for prenatal diagnostics, cancer analysis, and cancer surveillance and therapy monitoring. Nevertheless, salivary extracellular and extracellular vesicle (EV)-derived DNA and microRNA have recently gained attention as potential non-invasive biomarkers for a variety of diseases, including cancer, cardiovascular, autoimmune, and infectious diseases. Our goal in this study was therefore to evaluate and optimize commercially available approaches for cell-free nucleic acid isolation, focusing specifically on DNA and miRNA present in cell-free saliva or saliva-derived EVs. Along these lines, we investigated various commercially available kits, which enable parallel isolation of cell-free DNA and RNA in separate fractions from cell-free saliva and salivary EVs, respectively, and compared them to single analyte extraction kits. The efficiency of all tested nucleic acid extraction methods was determined by comparing DNA and RNA fluorescence spectroscopy measurements and quantitative PCR values obtained from a selection of different DNA- and microRNA targets. We found the Norgen Plasma/Serum RNA/DNA Purification Mini kit in combination with the miRCURY exosome isolation kit to work best in our hands and to provide the highest yields of EV-derived nucleic acids. Having tested and identified effective protocols for isolating salivary extracellular nucleic acids, we present with this comparison study, among others, a sound basis for future circulating small nucleic acid and epigenetic biomarker research aiming for early disease diagnosis, prognosis, and prediction from cell-free saliva, representing an easy-to-collect and readily available diagnostic fluid. Full article

Circular RNAs (circRNAs) are single-stranded noncoding RNAs with a covalently closed loop structure. They are known for their stability, abundance, and highly conserved nature. Their expression is often specific to tissues or developmental stages. They interact with microRNAs (miRNAs) and RNA-binding proteins (RBPs) and they undergo N⁶-methyladenosine (m⁶A) modifications, further affecting gene transcription and translation. Increasing evidence over the past decades has revealed that dysregulated circRNA expression is associated with various neurological disorders, particularly the glioma, one of the most malignant tumors with a poor prognosis. Due to the presence of the blood–brain barrier (BBB) and drug resistance, conventional therapeutic approaches have shown limited efficacy. Recently, increasing attention has been directed toward precisely targeted therapies, with circRNAs emerging as promising molecules for cancer treatment. Studies indicate that circRNAs play a key role in glioma proliferation and metastasis. Substantial evidence indicates that exosomes can package circRNAs and facilitate their transport across the BBB into brain tissue, highlighting the potential of circRNAs as therapeutic targets for glioma. This review summarizes circRNAs’ functional mechanisms, clinical application relevance, and current limitations. It offers future research directions in this evolving field, aiming to encourage further research on circRNAs’ therapeutic applications and contribute to the development of novel glioma-treatment strategies. Full article

Background: As the prevalence of diabetes continues to rise each year, increasing attention is focused on its complications, including erectile dysfunction (ED). However, effective therapeutic agents for diabetes mellitus erectile dysfunction (DMED) are often inadequate. Exosomes, which are extracellular vesicles containing proteins and microRNAs, demonstrated remarkable capabilities in modulating pathophysiological processes related to tissue repair, anti-inflammatory responses, and immune regulation. Methods: Transcriptomic analysis was conducted to investigate gene alterations and associated pathways in the penile smooth muscle of DMED rats, both before and after exosome treatment. And the genes (Rxra, PPAR-γ, and CPt1a) related to the PPAR pathway were verified through qRT-PCR. Results: Results show that 13,947 genes were expressed in both the DMED group and the Exo group. Analysis of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways revealed significant enrichment in the Exo group for molecular pathways including PPAR and cAMP signaling. These genes are primarily involved in immune regulation and collagen deposition biological processes within the smooth muscle of the penis in DMED rats. Conclusions: Transcriptome analysis revealed important genes and pathways that regulate various biological processes. These findings offer a novel approach for decreasing collagen deposition in this tissue. 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

The neurobiological mechanisms underlying methamphetamine use disorder (MUD) remain elusive, and specific treatment modalities as well as diagnostic markers are scarce. The emergence of exosomes has opened up possibilities for developing diagnostic and assessment biomarkers for neuropsychiatric disorders. Hence, the present study aimed to preliminarily explore the alterations in exosomal miRNA expression in MUD patients and the potential mechanisms involved in MUD. First, miRNA sequencing and RT-qPCR were used to verify the differential expression of peripheral blood exosomal miR-184-3p and miR-4433a-5p in MUD patients. Subsequently, the diagnostic ability of these two miRNAs for MUD was evaluated using ROC analysis. Finally, the regulatory relationship between miRNA-184-3p and its downstream target gene CRTC1 was verified by dual luciferase reporter assay. The results demonstrated that exosomal miR-184-3p and miR-4433a-5p were markedly decreased in MUD patients. However, the expression level of miR-4433a-5p was influenced by anxiety-depressive symptoms. The ROC analysis revealed that the AUCs of exosomal miRNA-184-3p in the training and validation sets of MUD patients were 0.902 and 0.823, respectively. In conclusion, exosomal miR-184-3p levels in peripheral blood may be a potential biomarker for the diagnosis and assessment of MUD, and it may be involved in the pathophysiological process of MUD through the targeted regulation of the CRTC1/CREB pathway. Full article

Berberis kaschgarica Rupr.-derived exosome-like nanovesicles (BELNs), a type of plant-derived extracellular vesicle, consist of proteins, lipids, and nucleic acids. In this research, we employed differential centrifugation and ultracentrifugation techniques to isolate and purify BELNs. Subsequently, we conducted a comprehensive multi-omics analysis to systematically determine their physicochemical properties. Experiments were conducted in vitro with Human Umbilical Vein Endothelial Cells (HUVECs) to verify the therapeutic impact of BELNSs on atherosclerosis. The isolated BELNs exhibited a distinctive teacup-shaped exosome morphology. The extraction yield was approximately 2.1 × 10¹³ particles per milliliter, and the average particle size was measured to be 179.1 nm. These nanovesicles were lipid-rich. The protein content predominantly comprised cytoplasmic proteins. In-depth analysis revealed the presence of five highly conserved plant microRNAs: miR166, miR156, miR399, miR171, and miR395. These miRNAs are involved in regulating plant growth and responses to both biotic and abiotic stresses. Functional assays demonstrated that Berberis kaschgarica Rupr.-derived exosome-like nanovesicles substantially decreased the lipid deposition in HUVECs that was triggered by Palmitic Acid (PA). This research establishes the inaugural utilization of multi-omics platforms to systematically elucidate the bioactivity profile of BELNs from Berberis kaschgarica Rupr., thereby laying the groundwork for advancing its therapeutic potential. Full article

MicroRNAs (miRNAs) are key regulators of gene expression and play essential roles in physiological processes such as cell proliferation, apoptosis, and metabolism. They have emerged as promising biomarkers for the early diagnosis, prognosis, and treatment of Metabolic Syndrome (MetS). In recent years, exosome-derived miRNAs, known as “xeno-miRNAs”, which are derived from food, as well as circulating miRNAs, have emerged as areas of intense research due to their potential effects on metabolic disorders. miRNAs influence fasting blood glucose and insulin resistance through mechanisms such as β-cell differentiation, insulin gene transcription, and PI3K–AKT pathway activation. Additionally, miRNAs play important roles in regulating MetS components, as follows: obesity through adipogenesis and lipogenesis; hypertension through regulation of the renin–angiotensin system and vascular tone; and dyslipidemia by modulating lipid metabolism. Emerging evidence suggests that nutrients such as polyphenols and specific dietary patterns can alter miRNA expression, potentially impacting metabolic health. Understanding the interactions between diet and miRNA regulation offers novel insights into the prevention and treatment of MetS. This review explores the mechanisms by which miRNAs influence MetS components, and highlights the growing potential of nutrient-regulated miRNAs as therapeutic targets within the framework of precision nutrition and personalized metabolic disease management. Full article

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of upper and lower motor neurons, leading to muscle weakness, paralysis, and ultimately respiratory failure. Despite advances in understanding its genetic basis, particularly mutations in Chromosome 9 Open Reading Frame 72 (C9orf72), superoxide dismutase 1 (SOD1), TAR DNA-binding protein (TARDBP), and Fused in Sarcoma (FUS) gene, current diagnostic methods result in delayed intervention, and available treatments offer only modest benefits. This review examines innovative approaches transforming ALS research and clinical management. We explore emerging biomarkers, including the fluid-based markers such as neurofilament light chain, exosomes, and microRNAs in biological fluids, alongside the non-fluid-based biomarkers, including neuroimaging and electrophysiological markers, for early diagnosis and patient stratification. The integration of multi-omics data reveals complex molecular mechanisms underlying ALS heterogeneity, potentially identifying novel therapeutic targets. We highlight current gene therapy strategies, including antisense oligonucleotides (ASOs), RNA interference (RNAi), and CRISPR/Cas9 gene editing systems, alongside advanced delivery methods for crossing the blood–brain barrier. By bridging molecular neuroscience with bioengineering, these technologies promise to revolutionize ALS diagnosis and treatment, advancing toward truly disease-modifying interventions for this previously intractable condition. Full article

Systemic cancer progression culminating in metastatic disease is implicitly dependent on tumour cell interactions with the vascular system. Indeed, different facets of the micro- and macro-vasculature can be regarded as rate-limiting ‘vascular checkpoints’ in the process of cancer dissemination. The underlying complex communication networks drive tumour neovascularization, angiogenesis, immunoregulation, activation of the coagulation system, angiocrine interactions, and non-angiogenic vascular responses across multiple cancer types. Yet, each cancer may represent a unique vascular interaction scenario raising a prospect of targeted modulation of blood and lymphatic vessels for therapeutic purposes, beyond the traditional notion of tumour anti-angiogenesis. While the emphasis of studies aiming to understand this circuitry has traditionally been on soluble, or ‘mono-molecular’ mediators, the rise of the particulate secretome encompassing heterogeneous subpopulations of extracellular vesicles (EVs; including exosomes) and particles (EPs) brings another dimension into the tumour–vascular communication web during the process of metastasis. EVs and EPs are nanosized cellular fragments, the unique nature of which lies in their ability to encapsulate, protect and deliver to target cells a range of bioactive molecular entities (proteins, RNA, DNA) assembled in ways that enable them to exert a wide spectrum of biological activities. EVs and EPs penetrate through biological barriers and are capable of intracellular uptake. Their emerging vascular functions in metastatic or infiltrative cancers are exemplified by their roles in pre-metastatic niche formation, thrombosis, vasectasia or angiocrine regulation of cancer stem cells. Here, we survey some of the related evidence supporting the biological, diagnostic and interventional significance of EVs/EPs (EVPs) in disseminated neoplastic disease. Full article

Oral squamous cell carcinoma (OSCC), a major subtype of head and neck squamous cell carcinoma (HNSCC), is a significant global health burden owing to its late-stage diagnosis and poor prognosis. Recent advancements in molecular biology, genomics, and imaging have transformed the landscape of OSCC diagnosis and treatment. This review provides a comprehensive synthesis of early molecular diagnostic strategies, including biomarker discovery using next-generation sequencing, liquid biopsy, and salivary exosomal microRNAs. In addition, we highlight the emerging role of non-invasive optical imaging technologies and their clinical integration for improved surgical precision and early lesion detection. This review also discusses evolving therapeutic approaches, including immunotherapy, neoadjuvant chemotherapy, and patient-centered multimodal regimens tailored through molecular profiling. We emphasized balancing therapeutic efficacy with the quality of life in patients undergoing chemoradiotherapy. The convergence of multi-omics, artificial intelligence, and precision medicine holds promise for revolutionizing early detection and personalized treatment of OSCC, ultimately improving patient survival and clinical outcomes. Full article