In recent years,exosomes have garnered extensive attention as therapeutic agents and early diagnostic markers in neurodegenerative disease research.Exosomes are small and can effectively cross the blood-brain barrier,...In recent years,exosomes have garnered extensive attention as therapeutic agents and early diagnostic markers in neurodegenerative disease research.Exosomes are small and can effectively cross the blood-brain barrier,allowing them to target deep brain lesions.Recent studies have demonstrated that exosomes derived from different cell types may exert therapeutic effects by regulating the expression of various inflammatory cytokines,mRNAs,and disease-related proteins,thereby halting the progression of neurodegenerative diseases and exhibiting beneficial effects.However,exosomes are composed of lipid bilayer membranes and lack the ability to recognize specific target cells.This limitation can lead to side effects and toxicity when they interact with non-specific cells.Growing evidence suggests that surface-modified exosomes have enhanced targeting capabilities and can be used as targeted drug-delivery vehicles that show promising results in the treatment of neurodegenerative diseases.In this review,we provide an up-to-date overview of existing research aimed at devising approaches to modify exosomes and elucidating their therapeutic potential in neurodegenerative diseases.Our findings indicate that exosomes can efficiently cross the blood-brain barrier to facilitate drug delivery and can also serve as early diagnostic markers for neurodegenerative diseases.We introduce the strategies being used to enhance exosome targeting,including genetic engineering,chemical modifications(both covalent,such as click chemistry and metabolic engineering,and non-covalent,such as polyvalent electrostatic and hydrophobic interactions,ligand-receptor binding,aptamer-based modifications,and the incorporation of CP05-anchored peptides),and nanomaterial modifications.Research into these strategies has confirmed that exosomes have significant therapeutic potential for neurodegenerative diseases.However,several challenges remain in the clinical application of exosomes.Improvements are needed in preparation,characterization,and optimization methods,as well as in reducing the adverse reactions associated with their use.Additionally,the range of applications and the safety of exosomes require further research and evaluation.展开更多
Spinal cord injury is a critical event characterized by intricate pathogenic mechanisms.Although recent studies have highlighted tissue exosomes as key mediators of inflammatory responses in diverse organs and tissues...Spinal cord injury is a critical event characterized by intricate pathogenic mechanisms.Although recent studies have highlighted tissue exosomes as key mediators of inflammatory responses in diverse organs and tissues,their role in spinal cord injury has yet to be determined.In this study,we investigated the role and mechanisms of spinal cord tissue exosomes in the inflammatory response following spinal cord injury.We found morphological,concentration,and functional differences between exosomes extracted from injured and normal spinal cord tissues,and identified proinflammatory effects associated with spinal cord injury-generated tissue exosomes but not with exosomes derived from normal spinal cord tissue.Our in vivo and in vitro analyses showed that spinal cord injury-generated tissue exosomes promoted microglial M1 polarization and inflammatory cytokine expression,thereby exacerbating tissue and neuronal injury in the spinal cord.In addition,the combination of exosomal miRNA sequencing and experimental verification showed that the miR-155-5p level was higher in spinal cord injury-generated tissue exosomes than in spinal cord tissue.We further found that spinal cord injury-generated tissue exosomes-derived miR-155-5p induced a significant inhibition of forkhead box O3a phosphorylation and activated the nuclear factor-kappa B pathway,thereby promoting microglial M1 polarization and inflammatory cytokine expression.These findings suggest that injury-induced miR-155-5p-containing exosomes exacerbate spinal cord injury via the promotion of microglial M1 polarization and inflammatory responses.Thus,targeting miR-155-5p expression or exosome secretion could be a novel strategy for attenuating inflammation and reducing secondary injury post-spinal cord injury.展开更多
Exosomes have emerged as promising drug delivery carriers for targeting tumorigenesis,metastasis,and multidrug resistance,owing to their inherent therapeutic capabilities in regulating intercellular communications.Con...Exosomes have emerged as promising drug delivery carriers for targeting tumorigenesis,metastasis,and multidrug resistance,owing to their inherent therapeutic capabilities in regulating intercellular communications.Conventional exosome engineering involves sequential isolation and therapeutic cargo loading procedures,which complicate their functionalization and applications.In this study,we present an in situ engineering strategy of a photosensitizer(PS)-exosome nanoplatform for activating multiple programmed cell death(PCD)pathways in recipient cancer cells.The constructed PS DPNVP exhibits aggregation-induced emission characteristics and possesses prominent type Ⅰ and Ⅱ reactive oxygen species(ROS)generation capacity under white light irradiation.The suitable lipocationic nature enables DPNVP to precisely anchor onto plasma membranes.Upon light irradiation,lethal ROS generated by DPNVP compromise the integrity of the plasma membrane,trigger pyroptosis and apoptosis,and eventually lead to immunogenic cell death.More importantly,DPNVP specifically labels exosomes during their secretion from originating cells.These in-situ engineered PS-exosome nanocomplexes can be effectively internalized by recipient cancer cells,activating concurrent pyroptosis and apoptosis in recipient cancer cells through potent photodynamic therapy.展开更多
Diabetes mellitus is an escalating global health issue,with 463 million adults affected in 2019.Without intervention,this number is projected to increase to 578 million by 2030 and 700 million by 2045[1].Diabetic woun...Diabetes mellitus is an escalating global health issue,with 463 million adults affected in 2019.Without intervention,this number is projected to increase to 578 million by 2030 and 700 million by 2045[1].Diabetic wound,a significant complication,is characterized by delayed healing,high disability rates,and elevated mortality[2].The challenges of wound healing in diabetic patients,compounded by their high morbidity and mortality rates,have drawn growing attention in biomedical research.展开更多
We read with the great interest the study by Ababneh et al in which inducedmesenchymal stem cell-derived exosomes were shown to exhibit a stronger andmore sustained anti-proliferative effect by inducing a senescence-l...We read with the great interest the study by Ababneh et al in which inducedmesenchymal stem cell-derived exosomes were shown to exhibit a stronger andmore sustained anti-proliferative effect by inducing a senescence-like state withoutapoptosis.The results obtained by the authors highlight the features of theeffects of senescent drift induction in surrounding tissues.In the light of thesefindings,the role of the properties of extracellular matrix and cellular glycocalyxin responses of human tumors to therapy remain uninvestigated.These extracellularbarriers appear to be significant obstacles to effective cancer therapy,especiallyin relation to the use of unique properties of tumor microenvironment forthe immunotherapy-resistant cancer treatment.展开更多
Ischemic stroke remains a leading cause of disability and death,with mesenchymal stem cell-derived exosomes emerging as a promising therapeutic avenue.However,the optimal timing and underlying therapeutic mechanisms o...Ischemic stroke remains a leading cause of disability and death,with mesenchymal stem cell-derived exosomes emerging as a promising therapeutic avenue.However,the optimal timing and underlying therapeutic mechanisms of exosome treatment require further elucidation.In this study,we used a murine model of middle cerebral artery occlusion to investigate the therapeutic efficacy of human umbilical cord mesenchymal stem cell-derived exosomes administered intravenously at an early(6 hours)or delayed(3 days)time point post-ischemia.Compared with delayed treatment,early administration of exosomes resulted in significantly superior efficacy,as evidenced by improved neurological function scores and reduced infarct volumes.Transcriptomic analysis of brain tissues from mice receiving early exosome treatment revealed marked downregulation of inflammation-related genes,including Ccl2,Ccl5,Cxcl10,Il-1β,Il-6,Itgam,Itgax,and Tnf-α.Metabolomic profiling of these brain tissues further identified modulation of key metabolites,including trimethylamine N-oxide,glutathione,1-stearoyl-rac-glycerol,and phosphatidylcholine,suggesting that alteration of metabolic pathways contributes to the therapeutic effect.Integrated transcriptomic and metabolomic analysis pinpointed significant modulation of pathways involving metabolism of eicosapentaenoic acid,lysine,propanoate,and tyrosine.These findings suggest that umbilical cord mesenchymal stem cell-derived exosomes,particularly when administered early post-ischemia,exert their neuroprotective effects by broadly suppressing inflammatory pathways and modulating key metabolic processes in the ischemic brain,highlighting their potential as a therapeutic intervention for ischemic stroke.展开更多
The last research focuses on the role of exosomes in cancer treatment.Exosomes are extracellular vesicles.They can be secreted by cancer cells,and they can modulate chemotherapy sensitivity.Determining exosomal conten...The last research focuses on the role of exosomes in cancer treatment.Exosomes are extracellular vesicles.They can be secreted by cancer cells,and they can modulate chemotherapy sensitivity.Determining exosomal content opens the possibility for guiding treatment strategies for cancer diseases.Exosomal microRNA are considered one of the prime candidates for exosomal biomarkers.Exosomal circular RNAs represent excellent biomarkers for liquid biopsy because of their stability in many types of cancer.Exosomal proteins remain reliable biomarkers also.Exosomes have emerged as promising therapeutic candidates.Their biological properties render them ideal vectors for drug delivery.Genetic modification of exosomes is an effective way to deliver material capable of modulating cellular pathways involved in drug resistance.Furthermore,exosomes have been explored as carriers for metal-chelating agents.Integrating exosome-based therapies with traditional anticancer agents aims to exploit the natural targeting abilities of exosomes to enhance drug delivery.Despite the dynamic development of this field,many mechanisms of exosome action remain incompletely understood.Therefore,it is necessary to conduct further studies that will allow for a better understanding of their role in the process of resistance and will enable the development of effective therapeutic strategies.展开更多
Pancreatic cancer is known to have high metastatic potential and low survival rates due to the failure of the therapeutic agents to reach the cancer cells having the dense desmoplastic microenvironment.Exosomes are co...Pancreatic cancer is known to have high metastatic potential and low survival rates due to the failure of the therapeutic agents to reach the cancer cells having the dense desmoplastic microenvironment.Exosomes are considered to be a promising therapeutic agent carrier due to their advantages such as low immunogenicity and easy targeting.More researches and future developments are needed,although exosome-based therapies need further research and development before they can be translated into clinical applications.In this review,we aimed to discuss comparatively two main exosome sources as mesenchymal stem cell(MSC)-derived and macrophage-derived exosomes on pancreatic cancer in terms of the therapeutic potential,advantages,disadvantages and also other comprehensive details.In vitro,in vivo and clinical phase studies examining the therapeutic potential of MSC-derived and macrophage-derived exosomes in pancreatic cancer will be discussed.We strongly believe that this review will guide the new investigations related to exosome-based targeted therapy in pancreatic cancer.In the meantime,we aimed to provide an overview of ongoing research on MSC and macrophage exosome-based therapies,focusing on their role in cancer treatment,particularly for pancreatic cancer.By examining current findings,this review will provide a broad perspective on the therapeutic potential and limitations of exosomes.展开更多
Objective This study aims to investigate the exosome-derived metabolomics profiles in systemic lupus erythematosus(SLE),identify differential metabolites,and analyze their potential as diagnostic markers for SLE and l...Objective This study aims to investigate the exosome-derived metabolomics profiles in systemic lupus erythematosus(SLE),identify differential metabolites,and analyze their potential as diagnostic markers for SLE and lupus nephritis(LN).Methods Totally,91 participants were enrolled between February 2023 and January 2024 including 58 SLE patients[30 with nonrenal-SLE and 28 with Lupus nephritis(LN)]and 33 healthy controls(HC).Ultracentrifugation was used to isolate serum exosomes,which were analyzed for their metabolic profiles using liquid chromatography–tandem mass spectrometry(LC–MS/MS).Endogenous metabolites were identified via public metabolite databases.Random Forest,Lasso regression and Support Vector Machine Recursive Feature Elimination(SVM-RFE)algorithms were employed to screen key metabolites,and a prediction model was constructed for SLE diagnosis and LN discrimination.ROC curves were constructed to determine the potential of these differential exosome-derived metabolites for the diagnosis of SLE.Furthermore,Spearman’s correlation was employed to evaluate the potential links between exosome-derived metabolites and the clinical parameters which reflect disease progression.Results A total of 586 endogenous serum exosome-derived metabolites showed differential expression,with 225 exosome-derived metabolites significantly upregulated,88 downregulated and 273 exhibiting no notable changes in the HC and SLE groups.Machine learning algorithms revealed three differential metabolites:Pro-Asn-Gln-Met-Ser,C24:1 sphingolipid,and protoporphyrin IX,which exhibited AUC values of 0.998,0.992 and 0.969 respectively,for distinguishing between the SLE and HC groups,with a combined AUC of 1.0.In distinguishing between the LN and SLE groups,the AUC values for these metabolites were 0.920,0.893 and 0.865,respectively,with a combined AUC of 0.931,demonstrating excellent diagnostic performance.Spearman correlation analysis revealed that Pro-Asn-Gln-Met-Ser and protoporphyrin IX were positively correlated with the SLE Disease Activity Index(SLEDAI)scores,urinary protein/creatinine ratio(ACR)and urinary protein levels,while C24:1 sphingolipid exhibited a negative correlation.Conclusions This study provides the first comprehensive characterization of the exosome-derived metabolites in SLE and established a promising prediction model for SLE and LN discrimination.The correlation between exosome-derived metabolites and key clinical parameters strongly indicated their potential role in SLE pathological progression.展开更多
Mesenchymal stem cells are highly regarded for their potential in tissue repair and regenerative medicine due to their multipotency and self-renewal abilities.Recently,mesenchymal stem cells have been redefined as“me...Mesenchymal stem cells are highly regarded for their potential in tissue repair and regenerative medicine due to their multipotency and self-renewal abilities.Recently,mesenchymal stem cells have been redefined as“medical signaling cells,”with their primary biological effects mediated through exosome secretion.These exosomes,which contain lipids,proteins,RNA,and metabolites,are crucial in regulating various biological processes and enhancing regenerative therapies.Exosomes replicate the effects of their parent cells while offering benefits such as reduced side effects,low immunogenicity,excellent biocompatibility,and high drug-loading capacity.Dental stem cells,including those from apical papilla,gingiva,dental pulp,and other sources,are key contributors to exosome-mediated regenerative effects,such as tumor cell apoptosis,neuroprotection,angiogenesis,osteogenesis,and immune modulation.Despite their promise,clinical application of exosomes is limited by challenges in isolation techniques.Current methods face issues of complexity,inefficiency,and insufficient purity,hindering detailed analysis.Recent advancements,such as micro-electromechanical systems,alternating current electroosmosis,and serum-free three-dimensional cell cultures,have improved exosome isolation efficacy.This review synthesizes nearly 200 studies on dental stem cell-derived exosomes,highlighting their potential in treating a wide range of conditions,including periodontal diseases,cancer,neurodegenerative disorders,diabetes,and more.Optimized isolation methods offer a path forward for overcoming current limitations and advancing the clinical use of exosome-based therapies.展开更多
Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional recovery.Therefore,there is an urgent need to develop new methods for the treatment of this condition.E...Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional recovery.Therefore,there is an urgent need to develop new methods for the treatment of this condition.Exosomes are natural cell-derived vesicles that mediate signal transduction between cells under physiological and pathological conditions.They have low immunogenicity,good stability,high delivery efficiency,and the ability to cross the blood–brain barrier.These physiological properties of exosomes have the potential to lead to new breakthroughs in the treatment of ischemic stroke.The rapid development of nanotechnology has advanced the application of engineered exosomes,which can effectively improve targeting ability,enhance therapeutic efficacy,and minimize the dosages needed.Advances in technology have also driven clinical translational research on exosomes.In this review,we describe the therapeutic effects of exosomes and their positive roles in current treatment strategies for ischemic stroke,including their antiinflammation,anti-apoptosis,autophagy-regulation,angiogenesis,neurogenesis,and glial scar formation reduction effects.However,it is worth noting that,despite their significant therapeutic potential,there remains a dearth of standardized characterization methods and efficient isolation techniques capable of producing highly purified exosomes.Future optimization strategies should prioritize the exploration of suitable isolation techniques and the establishment of unified workflows to effectively harness exosomes for diagnostic or therapeutic applications in ischemic stroke.Ultimately,our review aims to summarize our understanding of exosome-based treatment prospects in ischemic stroke and foster innovative ideas for the development of exosome-based therapies.展开更多
“Peripheral nerve injury”refers to damage or trauma affecting nerves outside the brain and spinal cord.Peripheral nerve injury results in movements or sensation impairments,and represents a serious public health pro...“Peripheral nerve injury”refers to damage or trauma affecting nerves outside the brain and spinal cord.Peripheral nerve injury results in movements or sensation impairments,and represents a serious public health problem.Although severed peripheral nerves have been effectively joined and various therapies have been offered,recovery of sensory or motor functions remains limited,and efficacious therapies for complete repair of a nerve injury remain elusive.The emerging field of mesenchymal stem cells and their exosome-based therapies hold promise for enhancing nerve regeneration and function.Mesenchymal stem cells,as large living cells responsive to the environment,secrete various factors and exosomes.The latter are nano-sized extracellular vesicles containing bioactive molecules such as proteins,microRNA,and messenger RNA derived from parent mesenchymal stem cells.Exosomes have pivotal roles in cell-to-cell communication and nervous tissue function,offering solutions to changes associated with cell-based therapies.Despite ongoing investigations,mesenchymal stem cells and mesenchymal stem cell-derived exosome-based therapies are in the exploratory stage.A comprehensive review of the latest preclinical experiments and clinical trials is essential for deep understanding of therapeutic strategies and for facilitating clinical translation.This review initially explores current investigations of mesenchymal stem cells and mesenchymal stem cell-derived exosomes in peripheral nerve injury,exploring the underlying mechanisms.Subsequently,it provides an overview of the current status of mesenchymal stem cell and exosomebased therapies in clinical trials,followed by a comparative analysis of therapies utilizing mesenchymal stem cells and exosomes.Finally,the review addresses the limitations and challenges associated with use of mesenchymal stem cell-derived exosomes,offering potential solutions and guiding future directions.展开更多
Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)...Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.展开更多
Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease progression.The proteins,DNA,mRNA,and lipids carried by exosomes reflect...Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease progression.The proteins,DNA,mRNA,and lipids carried by exosomes reflect intracellular changes,and thus can serve as biomarkers for a variety of conditions.In this study,we investigated alterations in the protein content of plasma exosomes derived from patients with Parkinson’s disease and the potential therapeutic roles of these proteins in Parkinson’s disease.Using a tandem mass tag-based quantitative proteomics approach,we characterized the proteomes of plasma exosomes derived from individual patients,identified exosomal protein signatures specific to patients with Parkinson’s disease,and identified N-acetyl-alpha-glucosaminidase as a differentially expressed protein.N-acetyl-alpha-glucosaminidase expression levels in exosomes from the plasma of patients and healthy controls were validated by enzyme-linked immunosorbent assay and western blot.The results demonstrated that the exosomal N-acetyl-alpha-glucosaminidase concentration was not only lower in Parkinson’s disease,but also decreased with increasing Hoehn-Yahr stage,suggesting that N-acetyl-alpha-glucosaminidase could be used to rapidly evaluate Parkinson’s disease severity.Furthermore,western blot and immunohistochemistry analysis showed that N-acetyl-alpha-glucosaminidase levels were markedly reduced both in cells treated with 1-methyl-4-phenylpyridinium and cells overexpressingα-synuclein compared with control cells.Additionally,N-acetyl-alpha-glucosaminidase overexpression significantly increased cell viability and inhibitedα-synuclein expression in 1-methyl-4-phenylpyridinium-treated cells.Taken together,our findings demonstrate for the first time that exosomal N-acetyl-alpha-glucosaminidase may serve as a biomarker for Parkinson’s disease diagnosis,and that N-acetyl-alpha-glucosaminidase may reduceα-synuclein expression and 1-methyl-4-phenylpyridinium-induced neurotoxicity,thus providing a new therapeutic target for Parkinson’s disease.展开更多
Background:Lung cancer is a life-threatening disease that occurs worldwide,but is especially common in China.The crucial role of the tumour microenvironment(TME)in non-small cell lung cancer(NSCLC)has attracted recent...Background:Lung cancer is a life-threatening disease that occurs worldwide,but is especially common in China.The crucial role of the tumour microenvironment(TME)in non-small cell lung cancer(NSCLC)has attracted recent attention.Cancer-associated fibroblasts(CAFs)are the main factors that contribute to the TME function,and CAF exosomes are closely linked to NSCLC.Methods:The expression levels of miR-3124-5p and Toll-interacting protein(TOLLIP)were analysed by bioinformatics prediction combined with RT-qPCR/Western Blot detection.Fibroblasts were isolated and identified from clinical NSCLC tissues.Transmission electron microscopy and Western Blot were used to identify exosomes from these cells.Changes in proliferation(CCK-8 and clone formation),migration(wound healing),and invasion(transwell)of NSCLC cells were measured.The Luciferase reporter test was applied to clarify the binding of miR-3124-5p to TOLLIP.The TOLLIP/TLR4/MyD88/NF-κB pathway proteins were determined using Western blot analysis.Results:MiR-3124-5p is overexpressed in clinical tissues and cells of NSCLC.MiR-3124-5p was dramatically enriched in CAF-derived exosomes.Cellular experiments revealed that CAFs delivered miR-3124-5p into NSCLC cells via exosomes,stimulating cancer cell progression.MiR-3124-5p acted as a sponge to negatively regulate TOLLIP expression,which activated the TLR4/MyD88/NF-κB axis to promote the occurrence and development of NSCLC.Functional salvage tests were performed to determine whether CAF-exosome-derived miR-3124-5p plays a pro-cancer role in NSCLC by affecting the TOLLIP signalling pathway.Conclusions:These results provide an interesting direction for the diagnosis and therapy of NSCLC.展开更多
Exosomes have shown good potential in ischemic injury disease treatments.However,evidence about their effect and molecular mechanisms in osteonecrosis of femoral head(ONFH)treatment is still limited.Here,we revealed t...Exosomes have shown good potential in ischemic injury disease treatments.However,evidence about their effect and molecular mechanisms in osteonecrosis of femoral head(ONFH)treatment is still limited.Here,we revealed the cell biology characters of ONFH osteonecrosis area bone tissue in single cell scale and thus identified a novel ONFH treatment approach based on M2 macrophages-derived exosomes(M2-Exos).We further show that M2-Exos are highly effective in the treatment of ONFH by modulating the phenotypes communication between neutrophil and endothelium including neutrophil extracellular traps formation and endothelial phenotype transition.Additionally,we identified that M2-Exos’therapeutic effect is attributed to the high content of miR-93-5p and constructed miR-93-5p overexpression model in vitro and in vivo based on lentivirus and adenoassociated virus respectively.Then we found miR-93-5p can not only reduce neutrophil extracellular traps formation but also improve angiogenic ability of endothelial cells.These results provided a new theoretical basis for the clinical application of ONFH therapeutic exosomes.展开更多
Background Higher embryonic mortality,especially in aged breeding hens,is associated with insufficient hepatic functionality in maintaining redox homeostasis.Our previous study demonstrated that egg exosome-derived mi...Background Higher embryonic mortality,especially in aged breeding hens,is associated with insufficient hepatic functionality in maintaining redox homeostasis.Our previous study demonstrated that egg exosome-derived miRNAs may play a key role in modulating embryonic oxidation-reduction process,whereas the exact function and mechanism were still poorly understood.The present study aimed to investigate the roles of egg exosome miRNAs in maintaining dynamic equilibrium of free radicals and peroxide agents in embryonic liver,as well as demonstrate the specific mechanism using oxidative stress-challenged hepatocytes.Results Compared to 36-week-old breeding hens,decreased hatchability and increased embryonic mortality were observed in 65-week-old breeding hens.Meanwhile,the older group showed the increased MDA levels and decreased SOD and GSH-Px activities in embryonic liver,muscle and serum.Embryonic mortality was significantly positively correlated with MDA level and negatively correlated with GSH-Px activity in embryonic liver.In addition,363 differentially expressed genes(DEGs)were identified in embryonic liver,13 differentially expressed miRNAs(DE-miRNAs)were identified in egg exosomes.These DEGs and DE-miRNAs were involved in oxidoreductase activity,glutathione metabolic process,MAPK signaling pathway,apoptosis and autophagy.miRNA-mRNA network analysis further found that DEGs targeted by DE-miRNAs were mainly enriched in programmed cell death,such as apoptosis and autophagy.Wherein,MAPK10 with highest MCC and AUC values was significantly related to GSH-Px activity and MDA level,and served as the target gene of miR-145-5p based on dual luciferase reporter experiment and correlation analysis.Bioinformatics analysis found that miR-145-5p/MAPK10 axis might alleviate peroxide generation and apoptosis.In primary hepatocytes of chick embryos,miR-145-5p transfection significantly reversed H_(2)O_(2)-induced mitochondrial ROS increase,MAPK10,BAX and CASP3 overexpression and excessive apoptosis.Conclusion Exosome miR-145-5p in eggs could target MAPK10 and decrease mitochondrial ROS,attenuating oxidative damage and apoptosis in hepatocytes of chick embryos.These findings may provide new theoretical basis for the improvement of maternal physiological status to maintain embryonic redox homeostasis by nutritional or genetic modifications.展开更多
Lung cancer-derived exosomes are a kind of valuable and clinically-predictable biomarkers for lung cancer, but they have the limitations in individual differences when being applied in liquid biopsy. To improve their ...Lung cancer-derived exosomes are a kind of valuable and clinically-predictable biomarkers for lung cancer, but they have the limitations in individual differences when being applied in liquid biopsy. To improve their application value and accuracy in clinical diagnosis, a dual-labelled electrochemical method is herein reported for precise assessment of lung cancer-derived exosomes. To do so, two probes are prepared for the dual labeling of exosome membrane to run DNA assembly reactions: One is modified with cholesterol and can insert into exosome membrane through hydrophobic interaction;another one is linked with programmed death ligand-1(PD-L1) antibody and can bind to exosome surface-expressing PD-L1 via specific immunoreaction. Quantum dots-tagged signal strands are used to collect respective DNA products, and produce stripping signals corresponding to the amounts of total exosome and surfaceexpressing PD-L1, respectively. A wide linear relationship is established for the quantitative determination of lung cancer-derived exosomes in the range from 103to 1010particles/m L, whereas the ratiometric value of the two stripping signals is proven to have a better diagnostic use in screening and staging of lung cancer when being applied to clinical samples. Therefore, our method might provide a new insight into precise diagnosis of lung cancer, and offer sufficient information to refiect the biomarker level and guide the personalized treatment level even at an early stage in clinic.展开更多
Exosomes(Exos)are extracellular vesicles secreted by cells and serve as crucial mediators of intercellular communication.They play a pivotal role in the pathogenesis and progression of various diseases and offer promi...Exosomes(Exos)are extracellular vesicles secreted by cells and serve as crucial mediators of intercellular communication.They play a pivotal role in the pathogenesis and progression of various diseases and offer promising avenues for therapeutic interventions.Exos derived from mesenchymal stem cells(MSCs)have significant immunomodulatory properties.They effectively regulate immune responses by modulating both innate and adaptive immunity.These Exos can inhibit excessive inflammatory responses and promote tissue repair.Moreover,they participate in antigen presentation,which is essential for activating immune responses.The cargo of these Exos,including ligands,proteins,and microRNAs,can suppress T cell activity or enhance the population of immunosuppressive cells to dampen the immune response.By inhibiting lymphocyte proliferation,acting on macrophages,and increasing the population of regulatory T cells,these Exos contribute to maintaining immune and metabolic homeostasis.Furthermore,they can activate immune-related signaling pathways or serve as vehicles to deliver microRNAs and other bioactive substances to target tumor cells,which holds potential for immunotherapy applications.Given the immense therapeutic potential of MSC-derived Exos,this review comprehensively explores their mechanisms of immune regulation and therapeutic applications in areas such as infection control,tumor suppression,and autoimmune disease management.This article aims to provide valuable insights into the mechanisms behind the actions of MSC-derived Exos,offering theoretical references for their future clinical utilization as cell-free drug preparations.展开更多
基金supported by the National Natural Science Foundation of China,No.22103055(to JG)the Natural Science Foundation of Hebei Province,No.F2024110001(to HC)Open Project of Tianjin Key Laboratory of Optoelectronic Detection Technology and System,Nos.2024LODTS215(to NL),2024LODTS216(to XS).
文摘In recent years,exosomes have garnered extensive attention as therapeutic agents and early diagnostic markers in neurodegenerative disease research.Exosomes are small and can effectively cross the blood-brain barrier,allowing them to target deep brain lesions.Recent studies have demonstrated that exosomes derived from different cell types may exert therapeutic effects by regulating the expression of various inflammatory cytokines,mRNAs,and disease-related proteins,thereby halting the progression of neurodegenerative diseases and exhibiting beneficial effects.However,exosomes are composed of lipid bilayer membranes and lack the ability to recognize specific target cells.This limitation can lead to side effects and toxicity when they interact with non-specific cells.Growing evidence suggests that surface-modified exosomes have enhanced targeting capabilities and can be used as targeted drug-delivery vehicles that show promising results in the treatment of neurodegenerative diseases.In this review,we provide an up-to-date overview of existing research aimed at devising approaches to modify exosomes and elucidating their therapeutic potential in neurodegenerative diseases.Our findings indicate that exosomes can efficiently cross the blood-brain barrier to facilitate drug delivery and can also serve as early diagnostic markers for neurodegenerative diseases.We introduce the strategies being used to enhance exosome targeting,including genetic engineering,chemical modifications(both covalent,such as click chemistry and metabolic engineering,and non-covalent,such as polyvalent electrostatic and hydrophobic interactions,ligand-receptor binding,aptamer-based modifications,and the incorporation of CP05-anchored peptides),and nanomaterial modifications.Research into these strategies has confirmed that exosomes have significant therapeutic potential for neurodegenerative diseases.However,several challenges remain in the clinical application of exosomes.Improvements are needed in preparation,characterization,and optimization methods,as well as in reducing the adverse reactions associated with their use.Additionally,the range of applications and the safety of exosomes require further research and evaluation.
基金supported by the Joint Funds for the Innovation of Science and Technology,Fujian Province,No.2023Y9233(to HH)the QuanzhouScience and Technology Project,No.2022C036R(to HH)+1 种基金the Science and Technology Bureau of Quanzhou,No.2020CT003(to SL)the Quanzhou MunicipalMedical and Health Guiding Science and Technology Project,No.2023N066S(to YZhou).
文摘Spinal cord injury is a critical event characterized by intricate pathogenic mechanisms.Although recent studies have highlighted tissue exosomes as key mediators of inflammatory responses in diverse organs and tissues,their role in spinal cord injury has yet to be determined.In this study,we investigated the role and mechanisms of spinal cord tissue exosomes in the inflammatory response following spinal cord injury.We found morphological,concentration,and functional differences between exosomes extracted from injured and normal spinal cord tissues,and identified proinflammatory effects associated with spinal cord injury-generated tissue exosomes but not with exosomes derived from normal spinal cord tissue.Our in vivo and in vitro analyses showed that spinal cord injury-generated tissue exosomes promoted microglial M1 polarization and inflammatory cytokine expression,thereby exacerbating tissue and neuronal injury in the spinal cord.In addition,the combination of exosomal miRNA sequencing and experimental verification showed that the miR-155-5p level was higher in spinal cord injury-generated tissue exosomes than in spinal cord tissue.We further found that spinal cord injury-generated tissue exosomes-derived miR-155-5p induced a significant inhibition of forkhead box O3a phosphorylation and activated the nuclear factor-kappa B pathway,thereby promoting microglial M1 polarization and inflammatory cytokine expression.These findings suggest that injury-induced miR-155-5p-containing exosomes exacerbate spinal cord injury via the promotion of microglial M1 polarization and inflammatory responses.Thus,targeting miR-155-5p expression or exosome secretion could be a novel strategy for attenuating inflammation and reducing secondary injury post-spinal cord injury.
基金supported by the National Natural Science Foundation of China(22275119,22077077,21975149)the Fundamental Research Funds for the Central Universities(18QNGG007,GK202301010)。
文摘Exosomes have emerged as promising drug delivery carriers for targeting tumorigenesis,metastasis,and multidrug resistance,owing to their inherent therapeutic capabilities in regulating intercellular communications.Conventional exosome engineering involves sequential isolation and therapeutic cargo loading procedures,which complicate their functionalization and applications.In this study,we present an in situ engineering strategy of a photosensitizer(PS)-exosome nanoplatform for activating multiple programmed cell death(PCD)pathways in recipient cancer cells.The constructed PS DPNVP exhibits aggregation-induced emission characteristics and possesses prominent type Ⅰ and Ⅱ reactive oxygen species(ROS)generation capacity under white light irradiation.The suitable lipocationic nature enables DPNVP to precisely anchor onto plasma membranes.Upon light irradiation,lethal ROS generated by DPNVP compromise the integrity of the plasma membrane,trigger pyroptosis and apoptosis,and eventually lead to immunogenic cell death.More importantly,DPNVP specifically labels exosomes during their secretion from originating cells.These in-situ engineered PS-exosome nanocomplexes can be effectively internalized by recipient cancer cells,activating concurrent pyroptosis and apoptosis in recipient cancer cells through potent photodynamic therapy.
基金supported by a grant from General Scientific Research Project of Zhejiang Provincial Department of Education(No.Y202455614).
文摘Diabetes mellitus is an escalating global health issue,with 463 million adults affected in 2019.Without intervention,this number is projected to increase to 578 million by 2030 and 700 million by 2045[1].Diabetic wound,a significant complication,is characterized by delayed healing,high disability rates,and elevated mortality[2].The challenges of wound healing in diabetic patients,compounded by their high morbidity and mortality rates,have drawn growing attention in biomedical research.
文摘We read with the great interest the study by Ababneh et al in which inducedmesenchymal stem cell-derived exosomes were shown to exhibit a stronger andmore sustained anti-proliferative effect by inducing a senescence-like state withoutapoptosis.The results obtained by the authors highlight the features of theeffects of senescent drift induction in surrounding tissues.In the light of thesefindings,the role of the properties of extracellular matrix and cellular glycocalyxin responses of human tumors to therapy remain uninvestigated.These extracellularbarriers appear to be significant obstacles to effective cancer therapy,especiallyin relation to the use of unique properties of tumor microenvironment forthe immunotherapy-resistant cancer treatment.
基金supported by the National Key R&D Program of China,Nos.2021YFA1101703/2021YFA1101700(to YD).
文摘Ischemic stroke remains a leading cause of disability and death,with mesenchymal stem cell-derived exosomes emerging as a promising therapeutic avenue.However,the optimal timing and underlying therapeutic mechanisms of exosome treatment require further elucidation.In this study,we used a murine model of middle cerebral artery occlusion to investigate the therapeutic efficacy of human umbilical cord mesenchymal stem cell-derived exosomes administered intravenously at an early(6 hours)or delayed(3 days)time point post-ischemia.Compared with delayed treatment,early administration of exosomes resulted in significantly superior efficacy,as evidenced by improved neurological function scores and reduced infarct volumes.Transcriptomic analysis of brain tissues from mice receiving early exosome treatment revealed marked downregulation of inflammation-related genes,including Ccl2,Ccl5,Cxcl10,Il-1β,Il-6,Itgam,Itgax,and Tnf-α.Metabolomic profiling of these brain tissues further identified modulation of key metabolites,including trimethylamine N-oxide,glutathione,1-stearoyl-rac-glycerol,and phosphatidylcholine,suggesting that alteration of metabolic pathways contributes to the therapeutic effect.Integrated transcriptomic and metabolomic analysis pinpointed significant modulation of pathways involving metabolism of eicosapentaenoic acid,lysine,propanoate,and tyrosine.These findings suggest that umbilical cord mesenchymal stem cell-derived exosomes,particularly when administered early post-ischemia,exert their neuroprotective effects by broadly suppressing inflammatory pathways and modulating key metabolic processes in the ischemic brain,highlighting their potential as a therapeutic intervention for ischemic stroke.
文摘The last research focuses on the role of exosomes in cancer treatment.Exosomes are extracellular vesicles.They can be secreted by cancer cells,and they can modulate chemotherapy sensitivity.Determining exosomal content opens the possibility for guiding treatment strategies for cancer diseases.Exosomal microRNA are considered one of the prime candidates for exosomal biomarkers.Exosomal circular RNAs represent excellent biomarkers for liquid biopsy because of their stability in many types of cancer.Exosomal proteins remain reliable biomarkers also.Exosomes have emerged as promising therapeutic candidates.Their biological properties render them ideal vectors for drug delivery.Genetic modification of exosomes is an effective way to deliver material capable of modulating cellular pathways involved in drug resistance.Furthermore,exosomes have been explored as carriers for metal-chelating agents.Integrating exosome-based therapies with traditional anticancer agents aims to exploit the natural targeting abilities of exosomes to enhance drug delivery.Despite the dynamic development of this field,many mechanisms of exosome action remain incompletely understood.Therefore,it is necessary to conduct further studies that will allow for a better understanding of their role in the process of resistance and will enable the development of effective therapeutic strategies.
文摘Pancreatic cancer is known to have high metastatic potential and low survival rates due to the failure of the therapeutic agents to reach the cancer cells having the dense desmoplastic microenvironment.Exosomes are considered to be a promising therapeutic agent carrier due to their advantages such as low immunogenicity and easy targeting.More researches and future developments are needed,although exosome-based therapies need further research and development before they can be translated into clinical applications.In this review,we aimed to discuss comparatively two main exosome sources as mesenchymal stem cell(MSC)-derived and macrophage-derived exosomes on pancreatic cancer in terms of the therapeutic potential,advantages,disadvantages and also other comprehensive details.In vitro,in vivo and clinical phase studies examining the therapeutic potential of MSC-derived and macrophage-derived exosomes in pancreatic cancer will be discussed.We strongly believe that this review will guide the new investigations related to exosome-based targeted therapy in pancreatic cancer.In the meantime,we aimed to provide an overview of ongoing research on MSC and macrophage exosome-based therapies,focusing on their role in cancer treatment,particularly for pancreatic cancer.By examining current findings,this review will provide a broad perspective on the therapeutic potential and limitations of exosomes.
基金funded by National Natural Science Foundation of China to Ping Yang with Grant number No.82202600by Nanjing Drum Tower Hospital to Ping Yang with Grant number No.2024-LCYJ-MS-11then to Shou-bin Zhan with Grant number No.2023-JCYJ-QP-25.
文摘Objective This study aims to investigate the exosome-derived metabolomics profiles in systemic lupus erythematosus(SLE),identify differential metabolites,and analyze their potential as diagnostic markers for SLE and lupus nephritis(LN).Methods Totally,91 participants were enrolled between February 2023 and January 2024 including 58 SLE patients[30 with nonrenal-SLE and 28 with Lupus nephritis(LN)]and 33 healthy controls(HC).Ultracentrifugation was used to isolate serum exosomes,which were analyzed for their metabolic profiles using liquid chromatography–tandem mass spectrometry(LC–MS/MS).Endogenous metabolites were identified via public metabolite databases.Random Forest,Lasso regression and Support Vector Machine Recursive Feature Elimination(SVM-RFE)algorithms were employed to screen key metabolites,and a prediction model was constructed for SLE diagnosis and LN discrimination.ROC curves were constructed to determine the potential of these differential exosome-derived metabolites for the diagnosis of SLE.Furthermore,Spearman’s correlation was employed to evaluate the potential links between exosome-derived metabolites and the clinical parameters which reflect disease progression.Results A total of 586 endogenous serum exosome-derived metabolites showed differential expression,with 225 exosome-derived metabolites significantly upregulated,88 downregulated and 273 exhibiting no notable changes in the HC and SLE groups.Machine learning algorithms revealed three differential metabolites:Pro-Asn-Gln-Met-Ser,C24:1 sphingolipid,and protoporphyrin IX,which exhibited AUC values of 0.998,0.992 and 0.969 respectively,for distinguishing between the SLE and HC groups,with a combined AUC of 1.0.In distinguishing between the LN and SLE groups,the AUC values for these metabolites were 0.920,0.893 and 0.865,respectively,with a combined AUC of 0.931,demonstrating excellent diagnostic performance.Spearman correlation analysis revealed that Pro-Asn-Gln-Met-Ser and protoporphyrin IX were positively correlated with the SLE Disease Activity Index(SLEDAI)scores,urinary protein/creatinine ratio(ACR)and urinary protein levels,while C24:1 sphingolipid exhibited a negative correlation.Conclusions This study provides the first comprehensive characterization of the exosome-derived metabolites in SLE and established a promising prediction model for SLE and LN discrimination.The correlation between exosome-derived metabolites and key clinical parameters strongly indicated their potential role in SLE pathological progression.
文摘Mesenchymal stem cells are highly regarded for their potential in tissue repair and regenerative medicine due to their multipotency and self-renewal abilities.Recently,mesenchymal stem cells have been redefined as“medical signaling cells,”with their primary biological effects mediated through exosome secretion.These exosomes,which contain lipids,proteins,RNA,and metabolites,are crucial in regulating various biological processes and enhancing regenerative therapies.Exosomes replicate the effects of their parent cells while offering benefits such as reduced side effects,low immunogenicity,excellent biocompatibility,and high drug-loading capacity.Dental stem cells,including those from apical papilla,gingiva,dental pulp,and other sources,are key contributors to exosome-mediated regenerative effects,such as tumor cell apoptosis,neuroprotection,angiogenesis,osteogenesis,and immune modulation.Despite their promise,clinical application of exosomes is limited by challenges in isolation techniques.Current methods face issues of complexity,inefficiency,and insufficient purity,hindering detailed analysis.Recent advancements,such as micro-electromechanical systems,alternating current electroosmosis,and serum-free three-dimensional cell cultures,have improved exosome isolation efficacy.This review synthesizes nearly 200 studies on dental stem cell-derived exosomes,highlighting their potential in treating a wide range of conditions,including periodontal diseases,cancer,neurodegenerative disorders,diabetes,and more.Optimized isolation methods offer a path forward for overcoming current limitations and advancing the clinical use of exosome-based therapies.
基金supported by the National Natural Science Foundation of China,Nos.82071291(to YY),82301464(to HM)the Norman Bethune Health Science Center of Jilin University,No.2022JBGS03(to YY)+2 种基金a grant from Department of Science and Technology of Jilin Province,Nos.YDZJ202302CXJD061(to YY),20220303002SF(to YY)a grant from Jilin Provincial Key Laboratory,No.YDZJ202302CXJD017(to YY)Talent Reserve Program of First Hospital of Jilin University,No.JDYYCB-2023002(to ZNG)。
文摘Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional recovery.Therefore,there is an urgent need to develop new methods for the treatment of this condition.Exosomes are natural cell-derived vesicles that mediate signal transduction between cells under physiological and pathological conditions.They have low immunogenicity,good stability,high delivery efficiency,and the ability to cross the blood–brain barrier.These physiological properties of exosomes have the potential to lead to new breakthroughs in the treatment of ischemic stroke.The rapid development of nanotechnology has advanced the application of engineered exosomes,which can effectively improve targeting ability,enhance therapeutic efficacy,and minimize the dosages needed.Advances in technology have also driven clinical translational research on exosomes.In this review,we describe the therapeutic effects of exosomes and their positive roles in current treatment strategies for ischemic stroke,including their antiinflammation,anti-apoptosis,autophagy-regulation,angiogenesis,neurogenesis,and glial scar formation reduction effects.However,it is worth noting that,despite their significant therapeutic potential,there remains a dearth of standardized characterization methods and efficient isolation techniques capable of producing highly purified exosomes.Future optimization strategies should prioritize the exploration of suitable isolation techniques and the establishment of unified workflows to effectively harness exosomes for diagnostic or therapeutic applications in ischemic stroke.Ultimately,our review aims to summarize our understanding of exosome-based treatment prospects in ischemic stroke and foster innovative ideas for the development of exosome-based therapies.
基金supported by the Key Research and Development Project of Hubei Province of China,2022BCA028(to HC)。
文摘“Peripheral nerve injury”refers to damage or trauma affecting nerves outside the brain and spinal cord.Peripheral nerve injury results in movements or sensation impairments,and represents a serious public health problem.Although severed peripheral nerves have been effectively joined and various therapies have been offered,recovery of sensory or motor functions remains limited,and efficacious therapies for complete repair of a nerve injury remain elusive.The emerging field of mesenchymal stem cells and their exosome-based therapies hold promise for enhancing nerve regeneration and function.Mesenchymal stem cells,as large living cells responsive to the environment,secrete various factors and exosomes.The latter are nano-sized extracellular vesicles containing bioactive molecules such as proteins,microRNA,and messenger RNA derived from parent mesenchymal stem cells.Exosomes have pivotal roles in cell-to-cell communication and nervous tissue function,offering solutions to changes associated with cell-based therapies.Despite ongoing investigations,mesenchymal stem cells and mesenchymal stem cell-derived exosome-based therapies are in the exploratory stage.A comprehensive review of the latest preclinical experiments and clinical trials is essential for deep understanding of therapeutic strategies and for facilitating clinical translation.This review initially explores current investigations of mesenchymal stem cells and mesenchymal stem cell-derived exosomes in peripheral nerve injury,exploring the underlying mechanisms.Subsequently,it provides an overview of the current status of mesenchymal stem cell and exosomebased therapies in clinical trials,followed by a comparative analysis of therapies utilizing mesenchymal stem cells and exosomes.Finally,the review addresses the limitations and challenges associated with use of mesenchymal stem cell-derived exosomes,offering potential solutions and guiding future directions.
基金supported by the National Natural Science Foundation of China,No.8227050826(to PL)Tianjin Science and Technology Bureau Foundation,No.20201194(to PL)Tianjin Graduate Research and Innovation Project,No.2022BKY174(to CW).
文摘Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.
基金supported by the Science and Technology(S&T)Program of Hebei Province,No.22377798D(to YZ).
文摘Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease progression.The proteins,DNA,mRNA,and lipids carried by exosomes reflect intracellular changes,and thus can serve as biomarkers for a variety of conditions.In this study,we investigated alterations in the protein content of plasma exosomes derived from patients with Parkinson’s disease and the potential therapeutic roles of these proteins in Parkinson’s disease.Using a tandem mass tag-based quantitative proteomics approach,we characterized the proteomes of plasma exosomes derived from individual patients,identified exosomal protein signatures specific to patients with Parkinson’s disease,and identified N-acetyl-alpha-glucosaminidase as a differentially expressed protein.N-acetyl-alpha-glucosaminidase expression levels in exosomes from the plasma of patients and healthy controls were validated by enzyme-linked immunosorbent assay and western blot.The results demonstrated that the exosomal N-acetyl-alpha-glucosaminidase concentration was not only lower in Parkinson’s disease,but also decreased with increasing Hoehn-Yahr stage,suggesting that N-acetyl-alpha-glucosaminidase could be used to rapidly evaluate Parkinson’s disease severity.Furthermore,western blot and immunohistochemistry analysis showed that N-acetyl-alpha-glucosaminidase levels were markedly reduced both in cells treated with 1-methyl-4-phenylpyridinium and cells overexpressingα-synuclein compared with control cells.Additionally,N-acetyl-alpha-glucosaminidase overexpression significantly increased cell viability and inhibitedα-synuclein expression in 1-methyl-4-phenylpyridinium-treated cells.Taken together,our findings demonstrate for the first time that exosomal N-acetyl-alpha-glucosaminidase may serve as a biomarker for Parkinson’s disease diagnosis,and that N-acetyl-alpha-glucosaminidase may reduceα-synuclein expression and 1-methyl-4-phenylpyridinium-induced neurotoxicity,thus providing a new therapeutic target for Parkinson’s disease.
文摘Background:Lung cancer is a life-threatening disease that occurs worldwide,but is especially common in China.The crucial role of the tumour microenvironment(TME)in non-small cell lung cancer(NSCLC)has attracted recent attention.Cancer-associated fibroblasts(CAFs)are the main factors that contribute to the TME function,and CAF exosomes are closely linked to NSCLC.Methods:The expression levels of miR-3124-5p and Toll-interacting protein(TOLLIP)were analysed by bioinformatics prediction combined with RT-qPCR/Western Blot detection.Fibroblasts were isolated and identified from clinical NSCLC tissues.Transmission electron microscopy and Western Blot were used to identify exosomes from these cells.Changes in proliferation(CCK-8 and clone formation),migration(wound healing),and invasion(transwell)of NSCLC cells were measured.The Luciferase reporter test was applied to clarify the binding of miR-3124-5p to TOLLIP.The TOLLIP/TLR4/MyD88/NF-κB pathway proteins were determined using Western blot analysis.Results:MiR-3124-5p is overexpressed in clinical tissues and cells of NSCLC.MiR-3124-5p was dramatically enriched in CAF-derived exosomes.Cellular experiments revealed that CAFs delivered miR-3124-5p into NSCLC cells via exosomes,stimulating cancer cell progression.MiR-3124-5p acted as a sponge to negatively regulate TOLLIP expression,which activated the TLR4/MyD88/NF-κB axis to promote the occurrence and development of NSCLC.Functional salvage tests were performed to determine whether CAF-exosome-derived miR-3124-5p plays a pro-cancer role in NSCLC by affecting the TOLLIP signalling pathway.Conclusions:These results provide an interesting direction for the diagnosis and therapy of NSCLC.
基金the support of the National Natural Science Foundation of China (Grant No.82272503)Natural Science Foundation of Zhejiang Province (Grant No. LQN25H060006)
文摘Exosomes have shown good potential in ischemic injury disease treatments.However,evidence about their effect and molecular mechanisms in osteonecrosis of femoral head(ONFH)treatment is still limited.Here,we revealed the cell biology characters of ONFH osteonecrosis area bone tissue in single cell scale and thus identified a novel ONFH treatment approach based on M2 macrophages-derived exosomes(M2-Exos).We further show that M2-Exos are highly effective in the treatment of ONFH by modulating the phenotypes communication between neutrophil and endothelium including neutrophil extracellular traps formation and endothelial phenotype transition.Additionally,we identified that M2-Exos’therapeutic effect is attributed to the high content of miR-93-5p and constructed miR-93-5p overexpression model in vitro and in vivo based on lentivirus and adenoassociated virus respectively.Then we found miR-93-5p can not only reduce neutrophil extracellular traps formation but also improve angiogenic ability of endothelial cells.These results provided a new theoretical basis for the clinical application of ONFH therapeutic exosomes.
基金supported by China Agriculture Research System of MOF and MARA(CARS-40)the National Natural Science Foundation of China(32302776)。
文摘Background Higher embryonic mortality,especially in aged breeding hens,is associated with insufficient hepatic functionality in maintaining redox homeostasis.Our previous study demonstrated that egg exosome-derived miRNAs may play a key role in modulating embryonic oxidation-reduction process,whereas the exact function and mechanism were still poorly understood.The present study aimed to investigate the roles of egg exosome miRNAs in maintaining dynamic equilibrium of free radicals and peroxide agents in embryonic liver,as well as demonstrate the specific mechanism using oxidative stress-challenged hepatocytes.Results Compared to 36-week-old breeding hens,decreased hatchability and increased embryonic mortality were observed in 65-week-old breeding hens.Meanwhile,the older group showed the increased MDA levels and decreased SOD and GSH-Px activities in embryonic liver,muscle and serum.Embryonic mortality was significantly positively correlated with MDA level and negatively correlated with GSH-Px activity in embryonic liver.In addition,363 differentially expressed genes(DEGs)were identified in embryonic liver,13 differentially expressed miRNAs(DE-miRNAs)were identified in egg exosomes.These DEGs and DE-miRNAs were involved in oxidoreductase activity,glutathione metabolic process,MAPK signaling pathway,apoptosis and autophagy.miRNA-mRNA network analysis further found that DEGs targeted by DE-miRNAs were mainly enriched in programmed cell death,such as apoptosis and autophagy.Wherein,MAPK10 with highest MCC and AUC values was significantly related to GSH-Px activity and MDA level,and served as the target gene of miR-145-5p based on dual luciferase reporter experiment and correlation analysis.Bioinformatics analysis found that miR-145-5p/MAPK10 axis might alleviate peroxide generation and apoptosis.In primary hepatocytes of chick embryos,miR-145-5p transfection significantly reversed H_(2)O_(2)-induced mitochondrial ROS increase,MAPK10,BAX and CASP3 overexpression and excessive apoptosis.Conclusion Exosome miR-145-5p in eggs could target MAPK10 and decrease mitochondrial ROS,attenuating oxidative damage and apoptosis in hepatocytes of chick embryos.These findings may provide new theoretical basis for the improvement of maternal physiological status to maintain embryonic redox homeostasis by nutritional or genetic modifications.
基金supported by the National Natural Science Foundation of China (Nos. 81972799, 82202834, and 81871449)。
文摘Lung cancer-derived exosomes are a kind of valuable and clinically-predictable biomarkers for lung cancer, but they have the limitations in individual differences when being applied in liquid biopsy. To improve their application value and accuracy in clinical diagnosis, a dual-labelled electrochemical method is herein reported for precise assessment of lung cancer-derived exosomes. To do so, two probes are prepared for the dual labeling of exosome membrane to run DNA assembly reactions: One is modified with cholesterol and can insert into exosome membrane through hydrophobic interaction;another one is linked with programmed death ligand-1(PD-L1) antibody and can bind to exosome surface-expressing PD-L1 via specific immunoreaction. Quantum dots-tagged signal strands are used to collect respective DNA products, and produce stripping signals corresponding to the amounts of total exosome and surfaceexpressing PD-L1, respectively. A wide linear relationship is established for the quantitative determination of lung cancer-derived exosomes in the range from 103to 1010particles/m L, whereas the ratiometric value of the two stripping signals is proven to have a better diagnostic use in screening and staging of lung cancer when being applied to clinical samples. Therefore, our method might provide a new insight into precise diagnosis of lung cancer, and offer sufficient information to refiect the biomarker level and guide the personalized treatment level even at an early stage in clinic.
基金Supported by the National Natural Science Foundation of China,No.82072537the General Project of Hunan Natural Science Foundation,No.2022JJ30412 and No.2021JJ30464.
文摘Exosomes(Exos)are extracellular vesicles secreted by cells and serve as crucial mediators of intercellular communication.They play a pivotal role in the pathogenesis and progression of various diseases and offer promising avenues for therapeutic interventions.Exos derived from mesenchymal stem cells(MSCs)have significant immunomodulatory properties.They effectively regulate immune responses by modulating both innate and adaptive immunity.These Exos can inhibit excessive inflammatory responses and promote tissue repair.Moreover,they participate in antigen presentation,which is essential for activating immune responses.The cargo of these Exos,including ligands,proteins,and microRNAs,can suppress T cell activity or enhance the population of immunosuppressive cells to dampen the immune response.By inhibiting lymphocyte proliferation,acting on macrophages,and increasing the population of regulatory T cells,these Exos contribute to maintaining immune and metabolic homeostasis.Furthermore,they can activate immune-related signaling pathways or serve as vehicles to deliver microRNAs and other bioactive substances to target tumor cells,which holds potential for immunotherapy applications.Given the immense therapeutic potential of MSC-derived Exos,this review comprehensively explores their mechanisms of immune regulation and therapeutic applications in areas such as infection control,tumor suppression,and autoimmune disease management.This article aims to provide valuable insights into the mechanisms behind the actions of MSC-derived Exos,offering theoretical references for their future clinical utilization as cell-free drug preparations.
