Search Results (997)

Neurodegenerative diseases (NDs), including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis (ALS), represent a growing global health challenge characterized by progressive neuronal loss and a lack of definitive disease-modifying treatments. This review explores the emerging potential of targeting non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and exosomal RNAs, to modulate pathogenic molecular pathways and address the underlying molecular origins of neurodegeneration. We evaluate the integration of advanced computational techniques for RNA structure prediction and gene regulatory network analysis, alongside chemical engineering strategies—such as Locked Nucleic Acids (LNAs) and phosphorothioate modifications—aimed at enhancing the stability and specificity of RNA-based molecules. Furthermore, we analyze cutting-edge delivery and editing technologies, including nanotechnology-driven solutions for precise neuronal targeting and the CRISPR/Cas13 system for direct ncRNA manipulation.The findings indicate that while challenges in delivery efficiency and long-term efficacy persist, the synergy of chemical engineering and computational modeling significantly improves the therapeutic profile of ncRNAs, with exosomal pathways offering a novel route for intercellular signaling modulation and biomarker discovery. Therapeutic interventions directed at specific clinical targets, such as miR-34a and BACE1-AS, demonstrate the capacity to influence protein aggregation and neuroinflammatory cascades. Although ncRNA-based therapies are currently in nascent stages, ongoing technological advancements in RNA editing and nanotechnology offer a transformative framework that could redefine the future of ND treatment and successfully halt disease progression rather than merely managing symptoms. Full article

Skin and hair follicles regenerate through coordinated stem cell niches and cyclic signaling associated with transitions among anagen, catagen, and telogen phases. In alopecia and chronic skin diseases, follicular miniaturization, immune dysregulation, persistent inflammation, impaired vascularization, and a compromised stratum corneum barrier limit the effectiveness of conventional topical and systemic therapies. Bio-nanovesicles (BNVs), including natural extracellular vesicles such as exosomes and microvesicles, as well as engineered artificial or hybrid nanovesicles, offer a targeted, cell-free delivery platform for miRNAs, proteins, and growth factors. By modulating key pathways—Wnt/β-catenin, PI3K/AKT, MAPK/ERK, and TGF-β/BMP—BNVs have the potential to restore regenerative crosstalk, enhance angiogenesis, and help initiate hair and skin repair. Full article

Chronic kidney disease (CKD) is a major global health burden leading to a loss of kidney function via podocyte damage, a non-regenerative renal cell type. Early detection of podocyte injury is crucial but remains limited, highlighting the need for non-invasive biomarkers. Therefore, we analysed urinary exosomal microRNAs (miRNAs) in relation to podocyte morphology in biopsies from 65 CKD patients, including focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD) and healthy controls. Global profiling distinguished CKD patients from controls, with miR-606 consistently upregulated and miR-431 downregulated. In podocytopathies, MCD displayed a predominantly suppressed miRNA profile, with miR-141, miR-429, and miR-660 as key candidates, whereas FSGS exhibited elevated miR-181c, miR-3610, miR-663b, miR-4651, and miR-429. Super-resolution morphometry revealed diffuse foot process effacement in MCD and heterogeneous, focally disrupted architecture in FSGS, providing a structural context for the molecular findings. Regression analyses linked these miRNAs to filtration slit density and length, proteinuria, and 25-Hydroxy-vitamin-D3 levels, integrating molecular, structural, and clinical readouts. These results define a coherent miRNA signature of podocyte injury that distinguishes CKD entities and correlates molecular changes with disease severity. Combining urinary exosomal miRNAs with morphometric analysis facilitates early, non-invasive identification of podocyte damage, enabling earlier therapeutic intervention in podocytopathies. Full article

Toxoplasma gondii (T. gondii) is an intracellular parasite known to modulate host immunity and cellular signaling, raising interest in its potential influence on cancer biology. A systematic review was conducted to evaluate experimental evidence on the antitumor or pro-tumor effects of T. gondii infection and parasite-derived antigens and to categorize the underlying mechanisms. PubMed was searched through 9 September 2024, and 54 eligible experimental studies were included (41 in vivo, 10 in vitro, and three combined). Forty-six studies reported antitumor effects, two pro-tumor effects, one stage-dependent divergent effects (acute infection/antitumor vs. chronic infection/pro-tumor), and five highlighted T. gondii-associated cancer-pertinent signaling pathways. Antitumor effects were observed following acute infection and exposure to parasite antigens, certain recombinant proteins, and exosomal microRNA miR-155-5p. Dominant mechanistic categories included activation of innate and adaptive immunity and reversal of tumor microenvironment immunosuppression (notably Th1-driven IL-12/IFN-γ responses, antitumor M1 macrophage polarization), induction of apoptosis, anti-angiogenesis, molecular mimicry and modulation of cancer-pertinent pathways. Conversely, pro-tumor effects were seen with chronic infection and exposure to ROP18 effector protein and miR-21. Future translational research should focus on rigorous evaluation of the safety and efficacy of attenuated non-replicating T. gondii strains and/or select recombinant antigens for potential cancer T. gondii-based immunotherapy. Full article

Pluripotent stem cell (PSC) differentiation is orchestrated by intricate autocrine and paracrine signaling networks. Among these, exosomes, key components of the cellular secretome, are implicated as crucial mediators of intercellular communication via delivery of bioactive molecules, including microRNAs (miRNAs). This study investigated the role of exosomal miRNAs in stem cell differentiation using Dgcr8-deficient mouse embryonic stem cells (mESCs), which are incapable of producing mature miRNAs. Although the differentiation capacity was markedly impaired in these cells, partial restoration was observed following treatment with exosomes derived from differentiating wild-type mESCs. Exosomal miRNA uptake was confirmed, and gene ontology analysis revealed significant enrichment of pathways associated with cell fate determination, morphogenesis, and apoptosis regulation. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that exosomal miRNAs modulated multiple osteoinductive signaling cascades, notably the MAPK and TGF-β pathways, in Dgcr8-deficient cells. Apoptotic markers were also downregulated, suggesting a protective effect conferred by the exosomal cargo. Collectively, our results suggest that exosome-mediated delivery of miRNAs may represent a fundamental mechanism by which pluripotent stem cells coordinate stress responses and differentiation trajectories, providing novel insights into the regulation of embryogenesis. Full article

Triple-negative breast cancer (TNBC) is an aggressive subtype lacking targeted therapies and characterized by pronounced heterogeneity and widespread dysregulation of microRNAs (miRNAs) that influence epithelial-to-mesenchymal transition (EMT) and metastasis. Tumor-derived extracellular vesicles (tEVs) further contribute to TNBC progression by transporting oncogenic cargo that can enhance pro-inflammatory signaling. The synthetic SMRwt peptide has been suggested to modulate oncogenic pathways; however, its effects on EV miRNA composition and inflammatory transcript profiles in TNBC remain unclear. Here, we investigated whether SMRwt alters tEV-associated miRNAs and cytokine transcript signatures relevant to EMT and inflammasome-linked pathways. Extracellular vesicles were isolated from SMR-treated and untreated MDA-MB-231 cells, followed by nanoparticle tracking analysis and small RNA sequencing. SMRwt treatment enriched 11 tumor-suppressive miRNAs (including Let-7a-5p, Let-7b-5p, miR-24-3p, miR-26b-5p, miR-92a-3p, miR-93-5p, and miR-496) previously associated with the regulation of proliferation, EMT, migration, and metastasis. We also observed modest, non-significant decreases (1.01–1.27-fold) in oncogenic miR-1200, miR-374a-5p, and miR-937-3p, which have been implicated in the progression of breast, lung, and bone malignancies. Complementary transcriptomic profiling using the NanoString nCounter Breast Cancer 360 Gene Expression Panel (NanoString Technologies, Inc., Seattle, CA, USA) demonstrated reduced expression of inflammasome-associated cytokines in TNBC cells relative to non-tumorigenic controls, including a log₂ fold change of −1.15 for IL 1β (MDA-MB-231 vs. MCF10A). These transcript-level changes suggest potential modulation. Additionally, SMRwt suppresses ASC-mediated caspase-1 activation and reduces IL-1β secretion, thereby inhibiting NLRP3 inflammasome signaling. Therefore, we infer that SMRwt simultaneously restores tumor-suppressive miRNA networks and suppresses inflammasome-driven inflammation, supporting its potential as a dual-target therapeutic strategy for TNBC. Full article

Nicotine damages the cardiovascular system in a variety of ways, from promoting inflammation to causing oxidative stress to prompting unnecessary autophagy. The alteration to the nervous system that yields nicotine dependence further exacerbates the negative impact that nicotine use has on public health. Nicotine use has also been found to cause alterations in exosome content, especially miRNA. Conversely, exosomes have also had promising results as treatments for nicotine-mediated alterations in protein and miRNA levels. However, although nicotine has been shown to both alter exosome content and exacerbate stroke outcomes, the relationship between these two functions is poorly understood. This review examines multiple sources to compare available data. Several factors in nicotine’s effect on exosome content were thus found that imply a correlation. Also, exosome contents are not only a viable biomarker for multiple conditions, including ischemic brain damage and tobacco use, but they are also able to influence the cells of test subjects, both as a treatment for ischemic stroke and as a regulator of healthy brain function in stroke-free test subjects. Taken together, previous evidence suggests that nicotine-mediated alterations in neuronal exosome content have an effect on the progression of stroke in nicotine users. Full article

Background/Objectives: Metabolic dysfunction-associated steatohepatitis (MASLD) represents a prevalent liver disease worldwide. It is crucial to maintain the stability of the gut–liver axis in order to inhibit the advancement of MASLD. Broccoli-derived exosome-like nanoparticles (BDENs) can alleviate constipation and improve colitis. This study investigated whether BDENs possess therapeutic potential for improving induced MASLD by the gut–liver axis. Methods: BDENs were fractionated from fresh broccoli using differential centrifugation, and the microRNAs were identified and analyzed. 24 male C57BL/6J mice (6 weeks old) were randomized into the control group, HFD group, and BDENs group, with 8 mice per group. After 8 weeks of high-fat diet modeling, the BDENs group accepted BDENs daily oral gavage of 100 mg/kg (B.W.), while the control and HFD groups accepted 1 × PBS. Four weeks after BDENs intervention, analysis was conducted on liver injury markers, liver tissue pathology, intestinal barrier, cecal content metabolomics and fecal 16S rRNA, serum inflammatory factors, and hepatic inflammation. Results: BDENs identified 1659 miRNAs associated with physiological processes such as immunity, antioxidant defense, and fatty acid biosynthesis. BDENs significantly reduced weight and ALT/AST ratio (p < 0.05). Furthermore, BDENs attenuated hepatic histopathological damage and lipid accumulation. For the gut–liver axis, BDENs maintained intestinal barrier, regulated intestinal bile acid metabolism and restored the gut microbiota. Additionally, BDENs reduced serum LPS level (p < 0.01) and suppressed hepatic inflammation, including F4/80 and IL-6, IL-1β (p < 0.0001). Conclusions: Oral BDENs therapy demonstrates potential for ameliorating MASLD. Full article

Background: Glioblastoma is the most lethal primary brain tumor, being characterized not only by marked intratumoral heterogeneity but also by strong systemic immunosuppression. Circulating extracellular vesicles (EVs) have gained growing recognition during the past decade as important mediators of intercellular communication, particularly through their microRNA (miRNA) cargo. However, the global EV miRNA landscape of circulating EV-associated miRNAs in glioblastoma patients and their relation with gene expression patterns in peripheral immune cells remain incompletely defined. Methods: To investigate these systemic associations, we profiled EV-associated miRNA expression in plasma samples from glioblastoma patients and matched healthy controls using the small RNA sequencing method, followed by differential expression and pathway analyses. Based on these findings and literature evidence, identified changes in selected EV miRNA levels were validated by qPCR in an extended cohort. In parallel, expression of their predicted immune-related mRNA targets was analyzed in peripheral blood mononuclear cells (PBMCs) obtained from the same individuals, allowing for the assessment of EV miRNA–PBMC mRNA correlation patterns. Results: Small RNA sequencing revealed a distinct circulating EV-associated miRNA profile in glioblastoma patients compared to controls. The validation analysis of relative expression of the identified DEmiRNAs has shown a statistically significant upregulation of hsa-miR-142-3p, hsa-miR-19b-3p, and hsa-miR-98-5p in circulating EVs of glioblastoma patients compared to controls. PBMCs from glioblastoma patients exhibited increased expression of the regulatory genes SOCS1, SOCS3, and PTEN, while CCND1 was downregulated. Correlation analyses suggested that certain EV miRNA changes parallel with alterations in PBMC gene expression in glioblastoma patients, suggesting early immune priming in the circulation. Conclusions: Our findings indicate that circulating EV miRNAs in glioblastoma patients are associated with specific gene expression patterns in peripheral immune cells, suggesting a complex regulatory balance between pro-inflammatory and anti-inflammatory cues, potentially preceding full tumor-associated macrophage polarization. These molecular interactions may offer opportunities for developing early biomarkers or new therapeutic approaches. Full article

Exosomes are nanoscale extracellular vesicles that carry disease-associated microRNAs (miRNAs) and represent promising biomarkers for cancer diagnosis. Triple-negative breast cancer (TNBC) lacks well-defined molecular markers, necessitating sensitive and integrable analytical approaches for TNBC-related exosomal miRNAs. In this study, exosomes were isolated from MDA-MB-231 TNBC cells using a paddle screw-based system designed to enhance mass transfer through active rotation, providing a mechanically driven isolation strategy that is compatible with miniaturized and microfluidic platforms. This dynamic isolation process enabled rapid and efficient exosome recovery within a short processing time. Three TNBC-associated miRNAs encapsulated in the isolated exosomes were quantitatively analyzed using polyadenylation tailing (poly(A) tailing) and specific bidirectional extension sequence-based assays combined with reverse transcription quantitative real-time PCR (RT-qPCR). The bidirectional extension (BDE) assay generated highly specific PCR templates, leading to improved amplification specificity and reduced background signals. The RT-qPCR analysis exhibited high sensitivity, wide dynamic range, and good reproducibility for all target miRNAs. Overall, these results demonstrate that the integration of a paddle screw-based exosome isolation module with an extension-based nucleic acid detection strategy provides a scalable and biosensor-compatible analytical framework for profiling TNBC-associated exosomal miRNAs, with potential applications in microfluidic liquid biopsy platforms and exosome-based cancer diagnostics. Full article

Purpose: Due to the lack of effective local therapeutic strategies for oral squamous cell carcinoma (OSCC), this study aimed to develop a novel gelatin/lignin hydrogel loaded with mesenchymal stem cell (MSC)-derived exosomes enriched in microRNA-185 (miR-185 EV) for intraoral delivery, followed by systematic evaluation of its therapeutic efficacy and underlying molecular mechanisms. Materials and Methods: The gelatin/lignin hydrogel was prepared and subsequently loaded with miR-185 EV. The physicochemical properties of the hydrogel, including microstructure, swelling behavior, chemical composition, and rheological characteristics, were systematically evaluated. Next, the stability, viscosity, biocompatibility, and exosome release kinetics of the hydrogel were further assessed. A 4-nitroquinoline-1-oxide (4NQO)-induced mouse tongue carcinogenesis model was established to assess the in vivo antitumor activity of the hydrogel via intraoral administration. Moreover, a proteomic analysis was conducted to investigate the molecular mechanisms of miR-185 EV on OSCC. Results: The miR-185 EV-loaded gelatin/lignin hydrogel exhibited favorable physicochemical properties, stability, and biocompatibility while prolonging the tissue retention time of miR-185 EV. In vivo antitumor efficacy experiments showed that the miR-185 EV-loaded hydrogel significantly inhibited tumor occurrence and alleviated epithelial dysplasia. Immunohistochemical analyses revealed significant suppression of tumor proliferation and epithelial–mesenchymal transition (EMT) of the hydrogel. Proteomic analysis indicated that miR-185 EV suppressed OSCC progression by downregulating interleukin-1β (IL-1β), consequently inhibiting the NF-κB signaling pathway. Conclusion: The findings demonstrate the successful development of the miR-185 EV-loaded gelatin/lignin hydrogel that represents an effective nanomedicine platform for intraoral drug delivery, providing a promising strategy for the clinical treatment of OSCC. Full article

Background: Myocardial ischemic injury, encompassing acute myocardial infarction (MI) and ischemia/reperfusion (I/R) injury, remains a major cause of cardiac morbidity and mortality worldwide, and is driven by interconnected molecular and cellular processes, including cardiomyocyte apoptosis, inflammatory activation, mitochondrial dysfunction, oxidative stress, and impaired angiogenesis. Mesenchymal stem cell (MSC)-derived exosomes have emerged as a promising cell-free nanotherapeutic strategy for cardiac repair due to their ability to transfer bioactive molecules that modulate multiple signaling networks involved in myocardial survival and regeneration. This systematic review aimed to synthesize evidence on the mechanistic basis of MSC-derived exosome mediated cardioprotection in myocardial ischemic injury. Methods: A systematic search of Ovid MEDLINE, Scopus, and Web of Science was conducted to identify studies investigating the effects of MSC-derived exosomes on myocardial ischemic injury. Eligible studies included clinical and preclinical models of MI or I/R injury assessing functional, biochemical, and molecular outcomes. Results: Seven preclinical studies published between 2015 and 2025 met the inclusion criteria. Exosome administration consistently improved cardiac function, reduced infarct size, and preserved myocardial architecture. Biochemical analyses revealed decreased cardiac injury markers, alongside suppressed apoptosis, inflammation, and oxidative stress. Mechanistically, MSC-derived exosomes delivered regulatory miRNAs (e.g., miR-19a, miR-125b, miR-205, miR-294) and lncRNAs (HAND2-AS1) that modulated key signaling pathways including PI3K/Akt, JAK2/STAT3, HAND2-AS1/miR-17-5p/Mfn2, and HIF-1α/VEGF. These molecular effects collectively inhibited apoptotic and inflammatory responses, enhanced mitochondrial integrity, and promoted angiogenesis and myocardial repair. Conclusions: MSC-derived exosomes confer robust cardioprotection against myocardial ischemic injury through integrated anti-apoptotic, anti-inflammatory, antioxidant, and pro-angiogenic mechanisms. Their multifaceted bioactivity, low immunogenicity, and potential for targeted delivery highlight their potential as a next-generation nanomedicine for ischemic heart disease. Future studies should emphasize standardized exosome production, mechanistic profiling, and translational validation in large-animal and clinical models. Full article

Background/Objectives: Despite recent advances in breast cancer diagnostics, therapies and personalized medicine through genetic profiling, effective treatment of aggressive subtypes, particularly triple-negative breast cancer (TNBC), remains a considerable clinical challenge. MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that influence tumor progression and are detectable extracellularly in biofluids, where they are typically protected within extracellular vesicles (e.g., exosomes) or associated with RNA-binding proteins and lipoprotein complexes. This review integrates current evidence on oncogenic and tumor-suppressive extracellular miRNAs in breast cancer, with emphasis on subtype-specific functions and potential clinical relevance as liquid-biopsy biomarkers and therapeutic targets. Methods: A PubMed-based literature review (January 2000–February 2026) was conducted using search terms combining “breast cancer” with “miRNA/microRNA” and “circulating/plasma/serum/exosomal/extracellular vesicle.” Studies were prioritized if they provided validated targets/mechanisms and/or human clinical evidence for diagnostic, prognostic, or predictive utility; discrepant findings were evaluated in a subtype-aware framework. Findings were organized into functional categories (e.g., EMT/metastasis, cell-cycle/DNA damage, immune modulation, and hormone/growth factor signaling). Clinical and translational studies evaluating circulating miRNAs for diagnosis, prognosis, treatment response, and toxicity prediction were synthesized, together with key pre-analytical and analytical variables that affect reproducibility. Results: Across mechanistic and clinical studies, miR-21 and miR-155 recur as prominent oncogenic miRNAs, whereas miR-205 is frequently reported as a tumor-suppressive miRNA that is reduced in breast cancer and in circulation in several cohorts. Panels combining these miRNAs show promise for sensitive and specific breast cancer diagnostics. Additionally, several miRNAs show context- or subtype-dependent effects, with opposing activities reported between TNBC and estrogen receptor (ER)-positive disease (e.g., miR-17-92, miR-425, miR-181 family members, miR-31, and miR-24). Conclusions: Circulating miRNAs represent a promising class of minimally invasive biomarkers and potential therapeutic targets; however, translation is constrained by biological context dependence and by pre-analytical and analytical variability. Standardized protocols and rigorously validated, subtype-aware biomarker panels will be essential for clinical implementation and for enabling miRNA-informed precision oncology in breast cancer. Full article

Gamma-aminobutyric acid (GABA) has been implicated in gut–brain interactions and neuronal activation. We hypothesized that GABA could ameliorate memory decline. We investigated whether oral GABA administration ameliorated age-related cognitive decline in aged mice (C57BL/6J, male) and explored the role of circulating exosomes in mediating these effects. Aged mice that drank water containing 0.5% GABA exhibited significantly improved discrimination index scores compared with that of controls, indicating enhanced memory function. Their plasma-derived exosomes induced neurite outgrowth and mitochondrial activation and restored neuronal activity in SH-SY5Y cells. GABA enhanced the exosomal expression of several miRNAs linked to neuronal activation, longevity, and anti-senescence pathways. Plasma-derived exosomes also restored object recognition memory, reduced hippocampal neuroinflammation, and decreased senescent cell markers (p21 and γH2AX) in aged mice. Additionally, mitochondria- and neurite-related genes were upregulated, and pathways associated with oxidative phosphorylation and Alzheimer’s disease were enriched. Collectively, long-term GABA administration was found to improve cognitive function of aged mice through the secretion of functional exosomes. Full article

Depressive disorders (DDs), especially treatment-resistant depression (TRD), pose a significant challenge worldwide, largely because their underlying biological mechanisms are complicated and treatments often fall short. There is growing evidence pointing to factors like disrupted neuroplasticity, neuroinflammation, irregularities in the hypothalamic–pituitary–adrenal (HPA) axis, and glutamatergic system imbalances as contributors to the onset and persistence of depressive symptoms. Exosomes (small extracellular vesicles involved in communication between cells) have recently gained attention for their potential role in connecting peripheral and central nervous system (CNS) changes. They carry proteins, lipids, and nucleic acids and are even capable of crossing the blood–brain barrier. Because of this, exosomes might provide a window into molecular changes in the brain and serve as accessible biomarkers of disease status and treatment response. Recent research points out that the contents of exosomes, especially microRNAs (miRNAs) and neurotrophic factors like brain-derived neurotrophic factor (BDNF), might play a part in disrupting synaptic plasticity and could be linked to resistance to antidepressants. At the same time, there is growing interest in using engineered exosomes as targeted drug carriers aimed at the CNS. That said, there are still quite a few hurdles to overcome. Methods vary widely between studies, protocols for isolating exosomes are not sufficiently standardized, safety data are limited, and we do not fully understand how drugs and exosomes interact or how they behave pharmacokinetically. This review brings together current findings regarding exosomes in DDs (with particular emphasis on TRD), highlights their promise for diagnosis and treatment, and sets out some of the main questions that need to be answered before clinical application becomes feasible. Full article