Search Results (97)

Cancer remains one of the leading causes of morbidity and mortality worldwide, with lung, breast, and colorectal cancers among the most prevalent and lethal malignancies. In recent years, extracellular vesicles (EVs) have emerged as important mediators of intercellular communication and promising tools in oncology. EVs are membrane-bound vesicles released by most cell types and carry diverse biomolecules, including nucleic acids, proteins, lipids, and metabolites derived from their parent cells. Their presence in biological fluids makes them attractive candidates for liquid biopsy applications and minimally invasive cancer diagnosis. In addition, EVs have gained considerable attention as therapeutic platforms due to their biocompatibility, stability, and ability to deliver functional cargo to recipient cells. Beyond mammalian EVs, plant-derived extracellular vesicles (PDEVs) are increasingly being investigated as scalable and potentially safe nanocarriers for biomedical applications. This review summarizes current advances in the use of EVs for cancer diagnosis and therapy, with particular emphasis on their role as biomarkers, drug-delivery systems, and emerging therapeutic agents. Furthermore, the review discusses current challenges and future perspectives related to EV isolation, characterization, and clinical translation in oncology. Full article

Extracellular vesicles (EVs) are key mediators of intercellular communication across biological kingdoms, with central roles in immune regulation and disease processes. Despite shared structural features, EVs derived from bacteria, plants, and mammalian cells differ substantially in their biogenesis, molecular composition, and immunological functions. EV formation pathways generate vesicles with distinct cargo profiles, including pathogen-associated molecular patterns (PAMPs) in bacterial EVs, regulatory small RNAs in plant-derived vesicles, and cytokines, microRNAs, and antigen-presenting complexes in mammalian EVs. Differences in cargo result in divergent immune outcomes. Bacterial EVs predominantly activate innate immunity via pattern recognition receptors such as Toll-like receptors, whereas plant-derived EVs exhibit low immunogenicity and mediate cross-kingdom RNA interference. In contrast, mammalian EVs primarily regulate immune responses by modulating antigen presentation and cytokine signaling. These findings support a framework in which EV origin determines immunological function and therapeutic applicability. This perspective highlights the importance of selecting appropriate EV sources for vaccine development, regenerative medicine, and targeted delivery strategies, while addressing current challenges related to heterogeneity, standardization, and safety. Full article

Plant-derived exosome-like nanoparticles (PELNs), a subset of extracellular vesicle (EV) secreted by plant cells, have emerged as revolutionary biomaterial with broad applications in biomedicine, agriculture, and nanotechnology. Structurally, PELNs feature a phospholipid bilayer homologous to plant cell membranes, encapsulating bioactive components such as proteins, nucleic acids, lipids, and secondary metabolites. The native structure of PELNs endows them with enhanced bioavailability, reduced immunogenicity, and improved barrier penetration for precise tissue delivery. Recent studies highlight the cross-kingdom therapeutic potential of PELNs in mammals, including antitumor, anti-inflammatory, tissue repair, immunomodulation and so on. This review comprehensively summarized recent advancements in PELN research, including innovative isolation techniques, molecular characterization, their roles in drug delivery and disease therapy. We also discussed challenges in standardization, scalability, and regulatory frameworks which could provide future perspectives for translating PELNs into clinical and industrial applications. Full article

Objectives: Plant extracellular vesicles (EVs) mediate intercellular communication and carry tissue-specific metabolites, yet tissue-resolved EV metabolomics in non-model medicinal plants remains poorly explored. Hibiscus syriacus is a valuable medicinal and ornamental species rich in bioactive compounds, but the metabolic profiles of flower- and leaf-derived EVs are unknown. This study aimed to characterize tissue-specific EV metabolomes of H. syriacus and reveal their functional implications. Methods: EVs were isolated from flowers (MJH) and leaves (MJY) of H. syriacus and verified by TEM and DLS. Untargeted LC-MS/MS metabolomics was applied to profile EV metabolites. Multivariate statistics (PCA, OPLS-DA), differential metabolite screening (VIP > 1, p < 0.05), and KEGG pathway enrichment were performed. Results: MJH- and MJY-EVs exhibited typical EV morphology and high purity. In total, 3338 metabolites were identified, dominated by lipids (29.43%). Clear metabolic separation was observed between MJH- and MJY-EVs. Thirty-nine differential metabolites were identified: 31 upregulated in MJH-EVs (lipids, pentadecanoic acid) and eight in MJY-EVs (nucleotides, secondary metabolites). Glycerophospholipid metabolism was the most enriched pathway in MJH-EVs, while MJY-EVs were linked to energy and defensive metabolism. Conclusions: H. syriacus EVs display strong tissue-specific metabolic signatures. Leaf EVs prioritize lipid metabolism for photosynthetic function and stress tolerance, while flower EVs accumulate secondary and energy-related metabolites for reproduction and defense. These findings advance plant EV biology and support potential applications of H. syriacus EVs in cosmetics and agriculture. Full article

Plant-derived extracellular vesicles (PDEVs) are emerging as promising bioactive materials for biomedical and dermatological applications. In this study, we isolated and characterized exosome-like vesicles derived from Rosa damascena callus culture medium (RSC-EXO) and evaluated their molecular features and biological activities in skin-related cellular models. Nanoparticle tracking analysis and cryo-electron microscopy showed that RSC-EXO exhibited a nanoscale size distribution and spherical morphology. Western blotting confirmed enrichment of the plant EV-associated markers PEN1 and TET8. RSC-EXO were efficiently internalized by human dermal fibroblasts and showed markedly improved biocompatibility compared with crude conditioned medium (RSC-CM). Functionally, RSC-EXO significantly increased collagen synthesis and showed a trend toward enhanced wound closure in fibroblasts. In addition, RSC-EXO reduced melanin production in α-MSH-stimulated B16F10 melanoma cells and suppressed the secretion of pro-inflammatory cytokines, including IL-1α, IL-6, and TNF-α, in LPS-stimulated RAW 264.7 macrophages. Proteomic analysis revealed a distinct cargo enriched in stress-, defense-, and metabolism-related proteins, while small RNA sequencing identified a heterogeneous small RNA population containing a limited fraction of miRNA-sized reads. Collectively, these findings suggest that RSC-EXO represents a biologically active plant-derived vesicle population with regenerative and anti-inflammatory activity observed in vitro in skin-related cellular models and support its potential as a promising platform for future cosmeceutical and dermatological applications. Full article

Plant-derived nanovesicles (PDNVs) are a class of nanoscale vesicles derived from plant tissues; they are particles with a lipid bilayer and no ability to replicate autonomously. As a type of bioactive natural nanocarrier, they demonstrate immense potential for application in 21st-century nanomedicine, skincare and nutritional health, owing to their excellent biocompatibility, low immunogenicity and targeted delivery capabilities. However, the clinical translation of PDNVs still faces key bottlenecks, including low extraction efficiency, complex purification processes, and immature engineering modification techniques. Compared to the wealth of systematic reviews in the field of Mammalian Extracellular Vesicles (M-EVs), research on PDNVs still lacks a comprehensive exposition of its multifaceted research progress. This review endeavours to comprehensively summarise the shortcomings over the last 60 years regarding PDNV purification processes, research progress, composition and characterisation, engineering modifications, functional mechanisms, clinical translation and market regulation. It discusses the feasibility of innovative approaches such as AI deep learning technologies, interdisciplinary integration and cross-application, and outlines the latest frontiers in PDNV research. It provides comprehensive and reliable reference material for future research and application strategies regarding PDNVs, offering theoretical support and practical guidance to overcome barriers to their industrialisation. This will facilitate the transition from limited laboratory research to clinical application and drive technological innovation in the next generation of naturally derived nanomedicines. Full article

Background/Objectives: Thermal injuries represent a significant global health burden, often complicated by hypertrophic scarring, chronic inflammation, and delayed re-epithelialization. While Mesenchymal Stem Cell (MSC) transplantation has shown promise, its clinical translation is hindered by risks of tumorigenicity and immunological concerns. This study evaluates the efficacy of cell-free Extracellular Vesicle (EV) therapy—derived from both mammalian MSCs and plant sources (PDNVs)—as standardized, off-the-shelf alternatives. This study synthesizes evidence focusing on re-epithelialization velocity, angiogenic activity, and anti-fibrotic outcomes, while assessing the impact of second-generation delivery scaffolds on therapeutic durability. Methods: Conducted in accordance with PRISMA 2020 guidelines and registered in PROSPERO (CRD420261305379), this review interrogated PubMed, Scopus, Embase, and Web of Science for studies published between 2015 and 2026. Eligible studies included in vivo animal models of thermal injury using purified vesicles from mammalian MSC sources or plant-derived nanovesicles compared with placebo, standard care, or untreated controls. Data were synthesized narratively; methodological quality was appraised using the SYRCLE risk of bias tool and compliance with MISEV guidelines. Results: Synthesis of 50 studies revealed that vesicle-based interventions consistently accelerate wound closure and improve histological healing. Mammalian ADSC-derived vesicles demonstrated superior anti-fibrotic effects via the miR-192-5p and miR-125b-5p axes, while hUC-MSC vesicles attenuated systemic inflammatory signaling via miR-181c. Plant-derived nanovesicles (PDNVs) showed potent antioxidant and re-epithelialization effects, with emerging potential as engineered genetic carriers. Crucially, advanced delivery systems, including bioactive hydrogels and microneedle patches, were repeatedly associated with improved local retention and more durable effects than bolus injections. Conclusions: Vesicle-based therapies show consistent pro-healing signals in preclinical models, suggesting source-dependent profiles: MSC-derived vesicles excel in immunomodulation and anti-fibrotic remodeling, while PDNVs provide a scalable, low-immunogenicity platform. As a cell-free strategy, these therapies circumvent the safety risks of live cell transplantation. This review identifies a critical shift toward second-generation delivery scaffolds to overcome the clearance crisis of topical applications, emphasizing the need for harmonized MISEV-aligned characterization in future clinical translation. Full article

Combining plant-derived bioactives could produce effective anti-inflammatory interventions for myofascial inflammation. This study evaluated in vitro synergy and computational mechanisms of curcumin–evodiamine activity against TNF-α, IL-1β, iNOS and COX-2, with frontier molecular orbital analysis to inform putative mechanisms. Evodiamine and curcumin were identified/quantified by HPLC–PDA and LC–MS (λmax 226 nm and 426 nm; RT 8.61 and 9.53 min; [M−H]⁻m/z 302.2 and 367.2). Purities were 98.08 ± 1.92% and 98.04 ± 1.86%. Noncytotoxic concentrations in RAW264.7 cells were determined, then LPS-stimulated cells were treated with evodiamine (0.01 µM), curcumin (0.01 µM) and a 1:1 mixture (0.001 µM). Molecular docking against TNF-α, IL-1β, iNOS and COX-2 and HOMO–LUMO calculations were performed. Curcumin and the combination significantly reduced TNF-α and NO; curcumin and the combination reduced IL-1β, whereas evodiamine alone showed limited effects. Docking predicted stronger binding for curcumin and evodiamine than ibuprofen across targets (e.g., curcumin ΔG −10.18 kcal·mol⁻¹ for TNF-α; evodiamine ΔG −10.02 kcal·mol⁻¹ for COX-2). Frontier orbital energies indicated differing electronic profiles (ibuprofen ΔE 8.62 eV; evodiamine 9.65 eV; curcumin 9.89 eV), suggesting complementary reactivity. The curcumin–evodiamine combination exhibits in vitro anti-inflammatory activity with supportive docking and orbital data, providing mechanistic rationale for further development. Full article

The gut microbiota takes charge in a pivotal role in metabolic equilibrium, immune response, and modulating gut lining stability and has become the main focus of nutrition and functional food research. In this regard, the definition of prebiotics has progressed past the traditional approach limited to indigestible dietary fibers, embracing more targeted, biologically active, and functional delivery systems. In recent years, plant-derived exosomes (PDEs), a subclass of exosomes defined as extracellular vesicles (EVs) in the 30–150 nm size range, have emerged as an innovative class of nanostructures supporting this transformation. Plant-derived exosome-like nanoparticles (PELNs) have been taken into account as natural nanocarriers which are suitable for the gastrointestinal system with the help of their high biocompatibility, low immunogenicity profiles and rich bioactive cargo contents. This review discusses structural features of PELNs, molecular cargo content, and biological roles comprehensively and focuses especially on gut microbiota interactions. MicroRNAs, proteins, lipids, polyphenols, and glycans which PELNs contain are discussed with regard to shaping the microbial composition, regulating microbial metabolic activity, and modulating host-microbe communication. Findings derived from in vitro, in vivo, and limited translational studies indicate that PELNs can modulate specific microbial taxa, increase short-chain fatty acid (SCFA) yield, strengthen mucosal immune homeostasis, and induce source-dependent responses in the gut microbiota. In their traditional definition, prebiotics are taken into account as food components which selectively support proliferation and metabolism of helpful microbes, especially Bifidobacteria and Lactobacilli. Within this framework, PELNs are not only passive carriers of functional components but also evaluated as active systems which can directly affect microbiota composition and metabolic functions. Thus, they are repositioned as “prebiotic nanocarriers.” Also this review evaluates the potential of functional food and integration of major edible PELNs into synbiotic formulations by discussing their isolation and characterization methods and stabilities in the gastrointestinal environment. Limitations of clinical applications and lack of research from a prebiotic nanocarrier perspective of PELNs show that this field still contains important research gaps. The novelty of the study lies in its integration of PELN research with nutrition-based approaches to microbiota modulation and innovative functional food strategies under a single multidisciplinary conceptual framework. Full article

Tissue repair is a finely organized process that progresses via a series of phases, including hemostasis, inflammation, proliferation, and remodeling, which are coordinated by immune–stromal interactions. Aging profoundly dysregulates these processes through mechanisms such as immunosenescence and inflammaging, cellular senescence, chronic inflammation, and extracellular matrix alterations, ultimately contributing to typical age-related progression. This review discusses the immune mechanisms that govern physiological tissue healing, as well as the age-related perturbations that lead to ulcerative and fibrotic diseases. It also highlights the potential application of extracellular vesicles (EVs), both mammalian and plant-derived, as a stable and low-immunogenicity mediator to modulate and re-establish repair homeostasis. Translational hurdles such as EV standardization, dosing, safety assessment, and manufacturing are critically discussed to promote their use in geroscience, regenerative medicine, and dermatology. Full article

Plant-based biomaterials are increasingly recognized as bio-instructive platforms capable of actively modulating immune responses rather than functioning solely as passive structural supports. In this context, the term plant-based refers to photosynthetic biomass-derived platforms, including both terrestrial plants and marine macroalgae, reflecting their shared richness in polysaccharides and secondary metabolites relevant to immune engineering and regenerative medicine. This review critically synthesizes current evidence on plant-derived polysaccharides and phytochemicals, including algal sulfated polysaccharides (fucoidan, alginate, carrageenan, and ulvan), terrestrial plant polysaccharides (e.g., Lycium barbarum and Aloe vera derivatives), polyphenols, and other secondary metabolites such as terpenoids and alkaloids, highlighting their roles as immunomodulators in biomedical contexts. Key mechanisms include macrophage polarization along an M1–M2 continuum, pattern recognition receptor engagement, redox and metabolic regulation, and crosstalk between innate and adaptive immunity, with emphasis on context-dependent signaling and structural heterogeneity. Material design parameters, including molecular weight and chemical functionalization, are critical determinants of immune responses. Advanced delivery systems, such as hydrogels, nanocomposites, phytosomes, and plant-derived extracellular vesicles (EVs), enable improved stability and spatiotemporal control. Applications in wound and musculoskeletal regeneration are discussed alongside translational challenges, including variability, reproducibility, regulatory issues, and the need for standardized characterization and immune validation. Full article

Virtual power plants (VPPs) aggregate flexible resources, such as distributed photovoltaics (PV), energy storage, and flexible loads, to provide substantial reserve capacity for grid operation. However, the combined effects of renewable energy output uncertainty, load forecast errors, and user-bounded rationality responses lead to significant errors in traditional deterministic VPP reserve assessment methods, severely affecting the balance between system supply and demand. To address this challenge, this paper proposes a credible reserve assessment method that accounts for user-bounded rationality. First, thermodynamic models with on–off constraints for air conditioning loads, energy feasible region, and power constraint models for electric vehicles (EVs) and energy storage systems (ESSs), as well as PV forecast error models are established to characterize physical reserve boundaries. Second, prospect theory is introduced to describe user-bounded rationality and a logit-based response probability model is developed. Monte Carlo sampling and kernel density estimation are employed to derive credible reserve sets under different confidence levels, achieving a probabilistic quantification of VPP reserve capacity distribution. Case studies demonstrate that the proposed method accurately characterizes the probabilistic distribution characteristics of VPP reserve provision under multiple uncertainties, providing comprehensive and reliable assessment information for power dispatching agencies. Full article

The generation from decentralized energy resources strongly depends on weather conditions, which causes fluctuations and degrades power grid quality. One of the most effective solutions in modern power systems to mitigate this issue is the use of energy storage systems (ESSs). These systems enhance the network performance by reducing power fluctuations. In this scope, and for frequency analysis, a model consisting of two interconnected microgrids was considered in this work. The frequency of these microgrids varies due to sudden changes in load or generation (or both). The frequency regulation was performed by an efficient load frequency controller (LFC). This regulation was essential and was employed to improve control performance, reduce the impact of load disturbances on frequency, and minimize power deviations in the power flow tie-lines. A fuzzy logic-based optimizer was installed in each microgrid to optimize the proposed proportional–integral–derivative (PID) controllers by generating their optimal parameters. The main objective of the LFC was to ensure zero steady-state error for system frequency and power deviations in the tie-lines. However, with the increasing integration of renewable energies and the intermittent nature of their production due to climate change, frequency fluctuations arise. To mitigate this issue, a coordinated AGC–PMS (automatic generation control–power management system) regulation with hybrid energy storage systems and interconnected microgrids was designed to enhance the quality and stability of the power network. This paper focuses on the load frequency control (LFC) technique applied to interconnected microgrids integrating renewable energy sources (RESs). It presents an optimization study based on artificial intelligence (AI) combined with the use of energy storage systems (ESSs) and high-voltage direct current (HVDC) transmission link for power management and control. The renewable energy sources used in this work are photovoltaic generators, wind turbines, and a solar thermal power plant. A hybrid energy storage system has been installed to ensure energy management and control. It consists of redox flow batteries (RFBs), a superconducting magnetic energy storage (SMES) system, electric vehicles (EVs), and fuel cells (FCs).The system behavior was analyzed through several case studies to improve frequency regulation and power management under renewable energy integration and load variation conditions. Full article

The immune microenvironment critically influences bone healing, particularly in the oral cavity where inflammation and microbial biofilms can compromise regeneration. Plant-derived extracellular vesicles (PDEVs) offer a biocompatible means to modulate immune responses, and apple-derived extracellular vesicles (ADEVs) have shown antioxidant and anti-inflammatory activity, although their osteoregenerative potential remains unclear. Here, we investigate the indirect effects of ADEVs on bone regeneration by assessing how their immunomodulatory action on macrophages influences the osteogenic commitment of human dental pulp stem cells (DPSCs). ADEVs were isolated, characterized, and applied to THP-1-derived macrophages to evaluate polarization via morphology and immunofluorescence for M1 (iNOS) and M2 (ARG1) markers. Then, the extracellular vesicles (EVs) from untreated and ADEV-treated macrophages were isolated and applied to DPSCs. All EVs were efficiently internalized by both macrophages and DPSCs. Treated macrophages shifted toward an M2-like phenotype, and macrophage-derived EVs (MDEVs) promoted stem cell morphological features consistent with osteogenic activation. These findings suggest that ADEVs promote osteoregeneration indirectly by influencing macrophage polarization and modifying the osteoactive cargo of MDEVs, thereby supporting their potential in cell-free, immunomodulatory approaches for oral bone regeneration. Full article

The skin, the largest organ in the human body, serves as a crucial barrier against external stimuli. With the acceleration of social industrialization and the worsening of global climate change, the risk of physical, chemical and biological damage to the skin has significantly increased. Among these, surgical wounds, accidental injuries, diabetic wounds, and ultraviolet (UV)-radiation-induced photoaging are particularly common. Cutaneous wound healing is a complex and dynamic process that requires precise coordination of numerous molecular events to effectively repair damaged skin. Skin photoaging, a phenomenon of premature aging caused by long-term UV exposure, is characterized by pigmentary abnormalities, telangiectasia, epidermal roughness, wrinkle formation, and precancerous lesions, all of which seriously affect skin health and appearance. Extracellular vesicles (EVs), a class of nano-sized vesicles secreted by various cells, play important regulatory roles in tissue regeneration. Although cell-culture-medium-derived EVs (C-EVs) have been proven to effectively promote skin wound healing and photodamage repair, their origin from a single cell type and challenges in large-scale production severely limit their broad application. In contrast, EVs derived from natural biological resources, including tissue-derived EVs (Ti-EVs) and plant-derived EVs (PDEVs), have emerged as novel therapeutic strategies for skin wounds and photoaging. These EVs better reflect the physiological microenvironment and demonstrate considerably higher production efficiencies. Ti-EVs, obtained from mammalian tissues composed of multiple cell types and extracellular matrix, contain more abundant regulatory factors, thus exhibiting superior bioactivity compared with C-EVs. PDEVs have also garnered significant attention due to their favorable stability, low immunogenicity, unique natural antioxidant components, and feasibility of large-scale extraction. This review will systematically elaborate on the characteristics and isolation methods of both Ti-EVs and PDEVs, as well as their therapeutic roles and underlying mechanism in wound healing and skin photoaging. Full article