Search Results (1,772)

Sepsis-induced acute lung injury (SI-ALI) is a severe complication of sepsis characterized by dysregulated inflammatory responses and impaired immune homeostasis. Growing evidence indicates that extracellular vesicles (EVs), particularly exosomes, are important mediators of intercellular communication. Despite the heterogeneity of infectious sources underlying sepsis, EVs can regulate macrophage polarization and functional reprogramming by transferring diverse bioactive cargo. Consequently, EVs are involved in the pathophysiological progression of SI-ALI arising from sepsis of different etiologies. However, the mechanisms through which distinct EV cargos regulate macrophage function and contribute to SI-ALI pathogenesis remain incompletely understood. To address these issues, this review summarizes how different EV subtypes and their cargos, including RNAs, proteins, lipids, and DNA, modulate macrophage functional states through multiple signaling pathways. The effect of such processes further contributes to inflammatory reaction, immune balance, and tissue regeneration in acute lung injury caused by damage to the SI-ALI. Particularly, the EV-mediated modulation of macrophage function goes beyond the rigid M1/M2 dichotomy, being rather based on the dynamic functional repertoire involving both pro-inflammatory response and immune regulation as well as tissue regeneration. The article finally concludes with EV-based treatment approaches aimed at cargo delivery or blocking and the main problems related to translational medicine. Overall, the review article identifies the macrophage regulatory network controlled by EVs, thus helping to understand immunopathogenesis of SI-ALI as well as laying the theoretical foundation for developing EV-based precision medicine. Full article

Spinal cord injury (SCI) is a devastating neurological condition characterized by irreversible primary damage followed by a complex secondary injury cascade involving oxidative stress, neuroinflammation, iron dysregulation, and regulated cell death. Among these mechanisms, ferroptosis, a distinct, iron-dependent form of regulated cell death driven by lipid peroxidation and redox imbalance, is increasingly recognized as a critical mediator of neurodegeneration after SCI. The miRNAs play essential roles in neural injury responses by modulating inflammation, oxidative stress, and cell-death pathways. Growing evidence indicates that miRNAs closely regulate ferroptosis-related signaling networks following SCI, influencing key molecular targets including iron metabolism, antioxidant defense systems, and lipid peroxidation pathways. Conversely, ferroptotic stress may alter miRNA expression profiles, suggesting a bidirectional regulatory relationship. In addition, ferritinophagy, a selective autophagy pathway degrading ferritin via nuclear receptor coactivator 4 (NCOA4), has emerged as an important yet underexplored regulator of intracellular iron homeostasis and ferroptosis susceptibility in SCI. This review systematically summarizes current evidence on the molecular mechanisms linking miRNAs and ferroptosis in SCI, highlights how miRNA-mediated regulation of ferroptosis contributes to neuronal death, glial responses, and impaired regeneration, and discusses emerging therapeutic strategies targeting this axis to promote neuroprotection and functional recovery. By integrating recent experimental findings, we aim to provide mechanistic insight and identify translational opportunities for miRNA- and ferroptosis-based interventions in SCI. Full article

Extracellular vesicles (EVs), including exosomes and microvesicles, are nanoscale membrane-enclosed particles that transfer proteins, lipids, mRNAs, and microRNAs between cells. The same communication system is now being developed in two apparently opposing settings: mesenchymal stem/stromal cell (MSC)-derived EVs are explored as cell-free regenerative therapeutics, whereas tumor-derived EVs can promote metastasis, immune evasion, and treatment resistance while also serving as liquid-biopsy biomarkers. Rather than treating these studies separately, this review compares them along shared mechanistic axes: producer-cell identity and state, luminal cargo, membrane and surface composition (including the biomolecular corona), dose and administration route, biodistribution, and recipient-cell context. This cross-field perspective shows that angiogenesis, immunomodulation, matrix remodeling, and tissue tropism are not intrinsically regenerative or oncogenic; their consequences depend on where, how, and to which cells EV signals are delivered. We review EV biology and MISEV2023-aligned nomenclature, examine bidirectional regenerative and cancer-associated functions, and survey engineering strategies for cargo loading and surface modification together with plant-derived exosome-like nanovesicles. We further compare EVs with lipid nanoparticles, adeno-associated viruses, polymers, and virus-like particles, and discuss how engineering can improve potency and targeting while increasing manufacturing and characterization complexity. Finally, we address tumor-related safety considerations for regenerative EVs and the unresolved biological, technical, manufacturing, and regulatory questions that must be addressed for clinical translation. Full article

Streptococcus salivarius-derived extracellular vesicles (SsEVs) have emerged as important mediators of host–microbe communication, but their role in oral squamous cell carcinoma (OSCC) remains unclear. In this study, SsEVs were isolated and characterized by transmission electron microscopy and nanoparticle tracking analysis, and their uptake by CAL-27 cells was confirmed by fluorescence imaging. Functional assays demonstrated that SsEVs inhibited the proliferation, migration, and invasion of CAL-27 cells in a concentration-dependent manner. RNA sequencing revealed substantial transcriptional reprogramming following SsEV treatment, with enrichment analyses indicating the suppression of pathways associated with cell adhesion, extracellular matrix remodeling, lipid metabolism, and particularly Notch signaling. Gene set enrichment analysis (GSEA) and gene set nariant analysis (GSVA) consistently identified Notch signaling as significantly downregulated. Further validation showed that SsEVs markedly decreased the expression of JAG1, NOTCH1, and HEYL at both the mRNA and protein levels. In a CAL-27 xenograft model, SsEV treatment significantly inhibited tumor growth and reduced JAGGED1, NOTCH1, and HEYL expression in tumor tissues, as confirmed by immunohistochemistry. Collectively, these findings demonstrate that SsEVs suppress OSCC progression both in vitro and in vivo by inhibiting the JAG1–NOTCH1–HEYL signaling axis, suggesting that microbiota-derived extracellular vesicles may represent a promising therapeutic approach for OSCC. Full article

Nanomedicine has yielded clinically useful platforms, including liposomes, albumin-bound nanoparticles, and lipid nanoparticles; yet, many systems translate poorly because of nonspecific biodistribution, limited target-site accumulation, inefficient cellular uptake and intracellular delivery, immune clearance, and off-target toxicity. These bottlenecks are often shaped at cell membrane interfaces, where therapeutic materials are recognized, retained, internalized, or cleared and may elicit unsafe responses. Here, we frame cell membrane biophysics as a therapeutic interface for nanomedicine. We examine how lipid organization and fluidity, mechanics, electrochemical state, glycocalyx architecture, and membrane protein identity shape recognition, adhesion, endocytosis, fusion, trafficking, immune responses, and drug release. We assess how disease-associated membrane remodeling can create candidate therapeutic entry points and delivery barriers across cancer, neurodegeneration, inflammation, infection, and vascular disease. We then analyze receptor-mediated targeting, lipid-domain-associated uptake, membrane-coated nanocarriers, engineered extracellular vesicles, and hybrid platforms, with explicit context-of-use definitions and design boundaries. Finally, we propose translational qualification through function-linked critical quality attributes, mechanism-relevant potency assays, context-matched models, in vivo pharmacology and immune safety, scalable manufacturing, and regulatory evaluation. Progress will depend less on descriptive membrane mimicry than on measurable, reproducible, and qualified membrane-dependent functions. Full article

Background: Cerebrovascular diseases have complex pathogenesis and pose a serious threat to human health; thus, novel diagnostic and therapeutic strategies are needed. Small extracellular vesicles (sEVs), commonly referred to as exosomes, are 30–150 nm lipid-bilayer vesicles that shield long noncoding RNAs (lncRNAs) from degradation. Because exosomal lncRNAs are more stable than free lncRNAs in blood and cerebrospinal fluid and can cross the blood–brain barrier, they are promising as biomarkers and therapeutic vectors. This review summarizes the roles and mechanisms of exosomal lncRNAs in cerebrovascular diseases. Methods: This narrative review is based on the experimental literature and focuses on the biological functions and regulatory mechanisms of exosomal lncRNAs in cerebrovascular disorders. Results: As competing endogenous RNAs (ceRNAs), they sequester microRNAs (miRNAs), thereby derepressing downstream target-gene expression and modulating neuronal injury (oxidative stress, apoptosis, neuroinflammation) through the nuclear factor kappa-B (NF-κB) and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathways. They show altered profiles in acute stroke (ischemic/hemorrhagic) correlated with neurological deficits, and are relevant to the early diagnosis of chronic diseases (atherosclerosis, aneurysm) and vascular dementia. Conclusions: Exosomal lncRNAs demonstrate promising translational potential in preclinical studies because they combine exosome delivery capabilities with lncRNA regulatory functions, although clinical validation remains limited. Full article

Acute and chronic inflammation underlies the pathogenesis of numerous diseases, including autoimmune disorders, atherosclerosis, infections, and cancer. Although non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids are widely used to control inflammation, their clinical utility is limited by adverse effects such as gastrointestinal toxicity and immunosuppression. Specialized pro-resolving mediators (SPMs), a family of endogenous lipid mediators derived from omega-3 fatty acids, have emerged as promising therapeutics because they actively promote the resolution of inflammation without suppressing host immunity. However, their clinical translation is hindered by poor chemical stability, rapid metabolic degradation, and short circulation half-lives. To overcome these limitations, a variety of delivery platforms—including liposomes, extracellular vesicles, PLGA nanoparticles, and hydrogels—have been developed to improve SPM stability, pharmacokinetics, and therapeutic efficacy. This review summarizes the cellular targets of SPMs, current delivery challenges, and emerging strategies for cell- and tissue-specific SPM delivery. We also discuss future opportunities for targeted SPM therapies in the treatment of inflammatory diseases and cancer. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the most prevalent chronic liver diseases worldwide, involving multiple pathological mechanisms such as lipid metabolism disorders, oxidative stress, chronic inflammation, insulin resistance, and dysregulation of the gut–liver axis. Currently, there remains a lack of effective and long-term safe therapeutic strategies for MASLD, necessitating the development of novel interventions. Plant-derived exosome-like nanovesicles (PELNs) represent naturally secreted nanoscale vesicles derived from plant cells. Their advantages, including extensive availability, high biocompatibility, low immune activation, remarkable stability, and convenient oral administration, make them attractive platforms for therapeutic delivery. PELNs can not only encapsulate natural bioactive compounds such as polyphenols, alkaloids, terpenoids, and polysaccharides but also serve as drug delivery vehicles to achieve liver-targeted transport and synergistic therapy. Current evidence for PELNs in MASLD is predominantly preclinical. In vitro studies have provided mechanistic insights into their effects on lipid metabolism, oxidative stress, inflammatory signaling, and hepatocellular injury, whereas animal studies have demonstrated improvements in hepatic steatosis and related metabolic abnormalities for selected PELNs. A smaller number of studies have investigated tissue distribution, oral uptake, or preliminary biosafety. However, systematic pharmacokinetic, long-term toxicological, and target-species clinical evidence remains insufficient. Accordingly, the therapeutic effects discussed in this review should be interpreted primarily as preclinical findings, and the applicability of PELNs in veterinary practice remains to be established. Full article

Exosomes have emerged as key mediators of intercellular and inter-organ communication. Although substantial advances have expanded the understanding of the biology of extracellular vesicles, exosome biogenesis and their role in the disease progression of systemic diseases have not yet been fully elucidated. In this review, we present a comprehensive overview of the molecular pathways responsible for exosome biogenesis, emphasizing how the selective incorporation of proteins, lipids, metabolites, messenger RNAs, and microRNAs (miRs) determines the composition and biological activity of exosomes. We also discuss how exosome-mediated inter-organ communication functions as an integrated biological network that connects the kidney, the cardiovascular system, the brain, the liver, the immune system, and tumors, thereby coordinating the pathological responses underlying the progression of chronic diseases. Additionally, we demonstrate the recent advances in the potential of exosomes as minimally invasive biomarkers and clinical translational implantation. Finally, we discussed the methodological and biological challenges that limit the clinical application of exosomes. Overall, this review presents an integrated framework for understanding exosome biology and supports the concept that exosomes function as dynamic platforms for systemic signaling that link molecular mechanisms to disease pathogenesis and translational medicine. Full article

Postbiotic preparations contain inanimate microbial cells and a diverse mixture of cell-wall structures, proteins, polysaccharides, lipids, metabolites, and vesicle-associated materials. Although many of these components have been proposed as key bioactives, most are identified through compositional profiling, enrichment in active fractions, or testing of purified molecules. Such findings demonstrate biological activity but do not necessarily show that a candidate contributes to the effect of the original preparation. This review examines the experimental approaches used to narrow candidate lists and evaluate functional contribution, including phenotype-guided comparison, activity-guided fractionation, selective depletion, multi-omics profiling, structural characterization, dose–response testing, mechanistic intervention, and reconstitution. A structured narrative search of Web of Science Core Collection, PubMed, and Scopus through 30 March 2026, supplemented by citation tracking, identified the relevant literature; 15 representative primary studies that examined defined candidates and provided evidence beyond compositional detection were selected and appraised across seven preparation-level attribution domains. An appraisal of representative studies shows that current evidence largely supports the activity of individual candidates, whereas preparation-level attribution remains uncommon. Stronger evidence requires quantification of the candidate in the source material, selective removal with appropriate controls, and restoration at a preparation-relevant dose. Structural heterogeneity, processing history, molecular state, dose, and experimental context must also be considered. This evidence-based approach can support bioactive-component validation, batch consistency, and the design of future preclinical and human studies. Full article

Thyroid cancer (TC) is one of the most common endocrine malignancies and ranks among the ten most frequently diagnosed cancers worldwide, highlighting the need for improved diagnostic and monitoring strategies. Extracellular vesicles (EVs) are nano-sized, membrane-enclosed particles released by nearly all cell types that carry selectively sorted bioactive cargo capable of influencing the behavior and fate of recipient cells. Although their molecular composition is shaped by their cells of origin, cargo loading is a regulated process that contributes to EV-mediated intercellular communication and cell-specific targeting. In TC, EVs have emerged as important mediators of tumor progression and microenvironment modulation. Recent advances underscore the diagnostic and prognostic value of EVs as non-invasive biomarkers, particularly through the detection of EV-associated non-coding RNAs, proteins, lipids, and other molecular signatures. However, methodological variability and limited clinical validation remain key barriers to clinical translation. Further preclinical and clinical studies are needed to establish the role of EVs in liquid biopsy and personalized targeted therapy for TC. This review provides a comprehensive and systematic overview of EVs in TC, with particular emphasis on methodological factors influencing EV research, including sample-specific isolation and characterization strategies. Based on a systematic literature survey, this review integrates current knowledge on EV-associated cargo, biological functions, biomarker and therapeutic potential while critically evaluating methodological challenges and outlining future directions for clinical translation. Full article

Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide despite advances in screening, surgical techniques, and systemic therapies. In recent years, exosomes—nanoscale extracellular vesicles involved in intercellular communication—have emerged as critical regulators of CRC biology. Exosomes mediate tumor progression, metastatic dissemination, immune evasion, and therapeutic resistance through the transfer of bioactive molecules including proteins, lipids, and non-coding RNAs. Moreover, exosomes have gained increasing attention as promising liquid biopsy tools and therapeutic platforms due to their stability, biocompatibility, and ability to reflect tumor molecular dynamics. This review provides a comprehensive overview of exosome biogenesis, molecular composition, and their functional roles in CRC pathogenesis. We further discuss their diagnostic and prognostic value, involvement in therapeutic resistance, and emerging therapeutic applications, with particular emphasis on translational and surgical oncology implications. Finally, we highlight current limitations and future perspectives for clinical integration of exosome-based strategies in CRC management. Full article

Prostate cancer (PCa) is one of the most prevalent malignancies in men worldwide. Established clinicopathological parameters do not fully describe the biological heterogeneity of PCa or consistently predict its clinical course after radical prostatectomy, supporting the investigation of additional prognostic markers. Stroma AReactive Invasion Front Areas (SARIFA) is a recently described histomorphological pattern characterized by direct contact between tumor cells and adipocytes without intervening desmoplastic or inflammatory stroma at the invasion front. Limited retrospective evidence from prostatectomy specimens indicates that SARIFA positivity is associated with adverse pathological features. However, its independent prognostic value and clinical utility remain to be established. Because SARIFA can potentially be assessed on routinely prepared hematoxylin and eosin-stained sections without additional molecular assays or immunohistochemical staining, it represents a potentially accessible candidate marker, although its reproducibility, standardization, and cost-effectiveness require formal evaluation. This review summarizes current evidence concerning lipid metabolic remodeling and tumor–adipocyte interactions that may contribute to the SARIFA phenotype in PCa. Androgen receptor-regulated lipid metabolism, uptake of adipocyte-derived fatty acids, adipokine signaling, and extracellular vesicle-mediated communication provide a plausible mechanistic framework. Nevertheless, direct experimental evidence linking several of these processes specifically to SARIFA in PCa remains limited, and some proposed relationships are based on indirect evidence or findings from other tumor types. Further studies should establish standardized scoring criteria, intra- and interobserver reproducibility, external validation, and incremental prognostic value before the clinical implementation of SARIFA can be considered. Full article

Endometriosis affects approximately 10% of women of reproductive age and is associated with infertility in up to half of those diagnosed. Despite decades of research, the molecular basis of its reproductive consequences remains poorly defined. Among the pathophysiological features most consistently documented in affected women, chronic oxidative stress within the peritoneal cavity has attracted sustained attention, yet its relationship to the extracellular vesicle biology that has emerged as central to endometriosis pathogenesis has never been systematically examined. Iron-catalyzed radical chemistry, macrophage-derived superoxide, and mitochondrial electron leak in ectopic stromal cells collectively sustain a peritoneal redox burden that modifies exosomal biogenesis, alters microRNA sorting, and reprograms vesicle lipid and protein cargo. Oxidatively conditioned exosomes skew peritoneal macrophages toward an immunosuppressive M2 phenotype through miR-301a-3p, miR-146a-5p, and miR-196a-5p, suppress natural killer cell cytotoxicity through NKG2D ligand decoy delivery, facilitate peritoneal dissemination and neuroangiogenesis, and compromise oocyte developmental competence through ferroptosis-derived vesicles carrying aberrant miR-122-5p, oxidized phosphatidylethanolamines, and damaged mitochondria. These mechanisms map directly onto the clinical deficits observed in women with endometriosis undergoing assisted reproduction, including reduced oocyte yield, lower fertilization rates, elevated embryo aneuploidy, and impaired implantation. Follicular and peritoneal fluid exosomal microRNA profiles represent promising non-invasive biomarkers, while combinatorial strategies targeting the iron-ROS-exosome axis offer a more coherent therapeutic framework than the single-antioxidant approaches that have so far shown limited benefit. Full article

Ovarian cancer (OC) remains the most lethal gynecological malignancy, mostly due to its frequent diagnosis at advanced stages, early peritoneal dissemination, ascites formation, and limited sensitivity of currently available approaches for early detection. Extracellular vesicles (EVs), particularly exosomes, mediate intercellular communication through the transfer of proteins, lipids, metabolites, and nucleic acids. In OC, EV-associated protein profiles reflect both tumor-cell-intrinsic programs and the complex interactions between malignant cells and the peritoneal microenvironment. This review summarizes current evidence regarding the involvement of exosomal proteins in OC progression, with particular emphasis on epithelial–mesenchymal transition, mesothelial reprogramming, extracellular matrix remodeling, angiogenesis, immune suppression, peritoneal dissemination, and platinum resistance. Mechanistic studies indicate that exosomal proteins, including CD44, the integrin α5β1/asparaginyl endopeptidase complex, annexin A2, low-density lipoprotein receptor-related protein 1, and programmed death-ligand 1, can directly contribute to metastatic niche formation and tumor progression. In parallel, proteomic studies of plasma-, serum-, ascites-, peritoneal-fluid-, and uterine-lavage-derived EVs have identified candidate liquid-biopsy biomarkers, including MUC1, EpCAM, FOLR1, integrins, complement- and coagulation-related proteins, and proteins associated with treatment resistance. To integrate the biological significance of proteins reported in OC-associated exosomes, we additionally performed protein–protein interaction and functional enrichment analyses. These analyses revealed interconnected protein groups associated with cell adhesion, oxidative stress adaptation, secretory remodeling, lipid metabolism, extracellular matrix organization, and inflammatory signaling. Taken together, the available evidence supports exosomal proteome profiling as a promising approach for investigating OC dissemination and developing minimally invasive diagnostic and prognostic tools. However, standardized EV isolation, quantitative proteomics, functional validation, and independent clinical cohorts remain essential for translation into clinical practice. Full article