Nasopharyngeal carcinoma derived exosomes regulate the proliferation and migration of nasopharyngeal carcinoma cells by mediating the miR-99a-5p BAZ2A axis

Abstract Objectives Nasopharyngeal Carcinoma (NPC) is a common malignant tumor of nasopharyngeal mucosal epithelium in clinical practice. Radiotherapy and chemotherapy are the main treatment methods at present, but the therapeutic effect is still unsatisfactory. Studies have shown that exosomes and microRNAs (miRNAs) play an important role in the development of cancer. Therefore, this study aimed to investigate the effects of NPC derived exosomes on NPC and their molecular mechanisms. Methods Serum was collected from healthy subjects, Epstein-Barr Virus (EBV) infected patients and NPC patients (n = 9 group) and exosomes were extracted separately. High-throughput sequencing of exosomes was performed to screen differentially expressed miRNAs. The function of the screened miRNA was identified by treating NPC cells with exosomes. The target gene of miRNA was identified using the dual-luciferase assay. Real-Time quantitative Polymerase Chain Reaction (RT-qPCR) was used to determine the levels of miR-99a-5p and Bromodomain Adjacent Tozinc finger domain protein 2A (BAZ2A). Cell Counting Kit-8 assay, flow cytometry, and wound healing assay were utilized to detect cell viability, cell cycle and apoptosis, and migration ability. The protein levels were evaluated by Western blot. Results MiR-99a-5p was identified as the most significant differentially expressed miRNA in exosomes (p< 0.05). The proliferation and migration of NPC cells were extremely facilitated by exosomes, accompanied by the suppressed apoptosis, upregulated BAZ2A, Monocyte Chemotactic Protein-1 (MCP1), and Vascular Endothelial Growth Factor A (VEGFA), and downregulation of Interleukin (IL)-1β and Nuclear Transcription Factor-κB (NF-κB) (p< 0.05). BAZ2A was a target gene of miR-99a-5p. Furthermore, the regulatory effect of exosomes on the proliferation, migration, and apoptosis was significantly abolished by overexpression of miR-99a-5p or downregulation of BAZ2A (p< 0.05). Conclusion NPC derived exosomes facilitated the proliferation and migration of NPC through regulating the miR-99a-5p/BAZ2A axis.

Effect of follicular fluid-derived exosomal mi RNAs on follicular dysplasia mediated via glycolysis of granulosa cells in patients with polycystic ovary syndrome and its mechanism / 中国生物制品学杂志

@#Objective To evaluate the effect of follicular fluid(FF)exosomal miRNAs on follicular dysplasia in patients with polycystic ovary syndrome(PCOS)mediated by glycolysis pathway of granulosa cells(GCs),and to explore the mechanism. Methods Three PCOS infertile patients and three non-PCOS infertile patients were recruited. The baseline hormone levels of the two groups were measured before ovulation induction. The bilateral FF was obtained by puncture after short-acting and long-term ovulation induction,and the exosomes were collected by ultracentrifugation and identified by transmission electron microscopy. The total exosomal RNA was extracted by Trizol method to construct the library,which was compared to the reference genome GRCh38 for statistical analysis after miRNA sequencing and quality control processing. Clustering Profiler R package was used to implement GO annotation analysis and KEGG pathway analysis of the differentially expressed genes(DEGs),and Omnipath software for miRNAs interaction analysis. A total of 16 miRNA were randomly selected and detected by qPCR to verify the accuracy of the miRNA sequencing results. Results Compared with the non-PCOS group,luteinizing hormone(LH),anti-Muerian hormone(AMH),testosterone and antral follicle counts in PCOS group increased significantly(t = 2. 479 ～ 9. 163,each P < 0. 05). The exosomes of FF in both groups showed the cup-shaped vesicles with clear edge and light staining in the center,with the diameters of 100 — 150 nm and intact structure,and the concentration was about 8 × 1010particles/mL. A total of 928 miRNAs were detected by miRNA sequencing. Compared with the non-PCOS group,59 differentially expressed miRNA(DEmiRNA)were screened out in exosomes of POCS group,of which 31 were up-regulated and 28 were down-regulated. The differential trend of gene expression detected by qPCR was highly similar to that of miRNA sequencing. In FF exosomes of PCOS patients,the glycolysis efficiency and apoptosis of GCs were significantly changed by miRNA regulating mRNA. PKM,PFKL and HK2 were the key target genes for miRNA to regulate GCs glycolysis,and SLC2A1 was the key target gene for miRNA to regulate GCs apoptosis. Conclusion The miRNAs in FF exosomes of PCOS patients can weaken the glycolysis of GCs while accelerate the apoptosis,thus reducing the production of ATP and lactic acid,resulting in follicular dysplasia.

Role of exosomes in intrahepatic cholangiocarcinoma / 临床肝胆病杂志

Intrahepatic cholangiocarcinoma （ICC） is a special type of liver cancer with atypical clinical symptoms in the early stage， and most patients are already in the advanced stage at the time of initial diagnosis. Due to a lack of effective molecular markers and treatment options， ICC patients tend to have an extremely low five-year survival rate. Exosomes are vesicles secreted by cells that contain proteins， RNA， and lipids， and they are important carriers of intercellular communication. Recent studies have shown that exosomes play a crucial role in the development and progression of ICC， and this article reviews the role and mechanism of exosomes in the diagnosis and treatment of ICC and looks into the future treatment prospect and potential clinical application of exosomes.

Research progress of mesenchymal stem cell-derived exosomes in the treatment of dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

Exosomes are extracellular vesicles that facilitate cellular communication by transmitting biomolecules and altering the biochemical characteristics of receptor cells. Mesenchymal stem cell-derived exosomes(MSC-Exos)are lipid bilayer vesicles secreted by mesenchymal stem cells(MSCs). These exosomes have similar functions to MSCs and contain bioactive substances such as proteins, lipids, and nucleic acids. MSC-Exos play a vital role in intercellular communication and are involved in essential physiological processes including immune regulation, tissue damage repair, and angiogenesis promotion. Consequently, they have gained significant attention in research, particularly in the treatment of immune inflammatory diseases, ischemic diseases, and other related fields. This article provides an in-depth analysis of the potential treatment mechanisms for dry eye, focusing on the pathogenesis of the condition, including inflammatory reactions, nerve regeneration, and tissue repair. The objective is to establish a foundation for the application of MSC-Exos in the treatment of dry eye, thereby offering a valuable reference for the future clinical applications.

Progress in the potential therapeutic mechanism of mesenchymal stem cell-derived exosomes for liver fibrosis / 中国临床药理学与治疗学

Liver fibrosis is pathological in most chronic liver diseases. Exosomes secreted by mesenchymal stem cells (MSCs) can regulate liver fibrosis through mechanisms such as inhibition of inflammatory response and proliferation of activated hepatic stellate cells, regulation of immune cells and metabolism. Therefore, MSC-derived exosomes can be used as a cell-free therapy for chronic liver disease, expanding new ideas for the treatment of chronic liver disease. Recent researches on MSC-derived exosomes in the treatment of liver fibrosis are reviewed in this article.

Research progress on exosome-based antitumor drug delivery system / 中国生物制品学杂志

@#Tumor is the main cause of global related death.Although the existing treatment methods have made significant progress,the lack of specificity and low bioavailability are still the challenge in the treatment.Exosomes are lipid bilayer extracellular vesicles that were released in the range of 30—150 nm when a multi vesicular body(MVB) fuses with plasma membrane,which are important mediators of intercellular communication,and can transport cellular components such as proteins,lipids and nucleic acids to neighboring or distant cells,thus changing the role of recipient cells.Exosomes have been used as natural nano-carriers for drug delivery.After being loaded with antitumor drugs,they can be delivered to the focus for targeted treatment of various tumors,and the therapeutic effect is good.In this paper,the advantages of exosomes-based antitumor drug delivery system,drug loading methods and the research progress of exosomes from different cells in cancer treatment are reviewed so as to provide important basis for the targeted treatment of cancer.

Role of mesenchymal stem cells and their exosomes in the treatment of drug-induced liver injury / 临床肝胆病杂志

The incidence rate of drug-induced liver injury （DILI） is increasing year by year with unknown mechanisms， and the treatment methods for DILI mainly include drugs， liver support systems， and liver transplantation， all of which have certain limitations. Therefore， the search for safer and more effective treatment methods has become a research hotspot at present. Studies have shown that mesenchymal stem cells and their exosomes can alleviate liver injury by reducing liver inflammation， promoting hepatocyte proliferation and regeneration， inhibiting the apoptosis of hepatocytes， improving oxidative stress， and regulating immunity. This article briefly reviews the role of mesenchymal stem cells and their exosomes in the treatment of DILI， so as to provide a reference for further research.

Advances in the study of exosomes in ophthalmic applications / 国际眼科杂志(Guoji Yanke Zazhi)

Exosomes are commonly found in blood, urine, saliva, ascites, amniotic fluid and other body fluids, and are involved in intercellular communication, signal transduction, transport of genetic material, maintenance of internal environmental homeostasis and immune regulation, with a wide range of important biological functions. Exosomes transport proteins, lipids, and nucleic acids to target cells and facilitate intercellular communication.As research continues, they have been found to play important roles in physiological and pathological processes, and are important biomarkers for the diagnosis and treatment of diseases. It plays an important role in immunomodulation, inflammatory response, and angiogenesis in many diseases such as cancer, cardiovascular diseases, and brain diseases. More researches suggest that exosomes also play an important role in the development and progression of ophthalmic diseases. In this review, the research history and biological functions of exosomes, as well as their pathogenesis and prospects for the application in ophthalmic diseases, including corneal diseases, glaucoma, ocular trauma, age-related macular degeneration, uveitis and intraocular tumors, were discussed

Research Progress in Treatment of Malignant Tumors by Traditional Chinese Medicine Based on Exosomes / 肿瘤防治研究

Malignant tumor is still one of the malignant diseases with high morbidity and mortality in the world. Its occurrence and development are influenced by various factors. Exosomes are nanoscale secretory vesicles that play an important role in the occurrence and development of malignant tumors, and have intercellular communication functions. The mechanism of action of traditional Chinese medicine in prevention and treatment of tumors is not yet comprehensive enough. This article discusses the relationship between exosomes and tumor development, relapse, metastasis and drug resistance, and the application of exosomes in the treatment of malignant tumors by traditional Chinese medicine, to provide reference for finding new breakthroughs in the treatment of malignant tumors.

Effects of tumor derived exosomes on T cells markers expression

Abstract Exosomes are 30-120nm bio particles transferred from donor to recipient cells leading to modification in their regulatory mechanisms depending upon the coded message in the form of loaded biomolecule. Cancer cells derived exosomes the true representatives of the parent cells have been found to modify the tumor surrounding/distinct regions and participate in metastasis, angiogenesis and immune suppression. Tis study was aimed to study the effects of tumor mice derived exosomes on the normal mice spleen isolated T cells by using co-culture experiments and flow cytometer analysis. We mainly focused on some of the T cells population and cytokines including IFN-, FOXP3+ regulatory T (Treg) cells and KI67 (proliferation marker). Overall results indicated random changes in different set of experiments, where the cancer derived exosomes reduced the IFN- expression in both CD4 and CD8 T cells, similarly the Treg cells were also found decreased in the presence of cancer exosomes. No significant changes were observed on the Ki67 marker expression. Such studies are helpful in understanding the role of cancer exosomes in immune cells suppression in tumor microenvironment. Cancer exosomes will need to be validated in vivo and in vitro on a molecular scale in detail for clinical applications.

Resumo Os exossomos são biopartículas de 30-120 nm transferidas de células doadoras para células receptoras, levando à modificação em seus mecanismos reguladores, dependendo da mensagem codificada na forma de biomolécula carregada. Verificou-se que exossomos derivados de células cancerosas os verdadeiros representantes das células-mãe modificam as regiões circundantes / distintas do tumor e participam da metástase, angiogênese e imunossupressão. Este estudo teve como objetivo estudar os efeitos de exossomos derivados de camundongos com tumor nas células T isoladas de baço de camundongos normais, usando experimentos de cocultura e análise de citômetro de fluxo. Concentrou-se, principalmente, em algumas populações de células T e citocinas, incluindo IFN-, células T reguladoras FOXP3 + (Treg) e KI67 (marcador de proliferação). Os resultados gerais indicaram mudanças aleatórias em diferentes conjuntos de experimentos, em que os exossomos derivados de câncer reduziram a expressão de IFN- em células T CD4 e CD8, da mesma forma que as células Treg também foram encontradas diminuídas na presença de exossomos de câncer. Nenhuma mudança significativa foi observada na expressão do marcador Ki67. Esses dados são úteis para a compreensão do papel dos exossomos do câncer na supressão de células do sistema imunológico no microambiente tumoral. Exossomos de câncer precisarão ser validados in vivo e in vitro em escala molecular com detalhes para aplicações clínicas.

Effects of tumor derived exosomes on T cells markers expression / Efeitos de exossomos derivados de tumor na expressão de marcadores de células T

Exosomes are 30-120nm bio particles transferred from donor to recipient cells leading to modification in their regulatory mechanisms depending upon the coded message in the form of loaded biomolecule. Cancer cells derived exosomes the true representatives of the parent cells have been found to modify the tumor surrounding/distinct regions and participate in metastasis, angiogenesis and immune suppression. Tis study was aimed to study the effects of tumor mice derived exosomes on the normal mice spleen isolated T cells by using co-culture experiments and flow cytometer analysis. We mainly focused on some of the T cells population and cytokines including IFN-γ, FOXP3+ regulatory T (Treg) cells and KI67 (proliferation marker). Overall results indicated random changes in different set of experiments, where the cancer derived exosomes reduced the IFN-γ expression in both CD4 and CD8 T cells, similarly the Treg cells were also found decreased in the presence of cancer exosomes. No significant changes were observed on the Ki67 marker expression. Such studies are helpful in understanding the role of cancer exosomes in immune cells suppression in tumor microenvironment. Cancer exosomes will need to be validated in vivo and in vitro on a molecular scale in detail for clinical applications.

Os exossomos são biopartículas de 30-120 nm transferidas de células doadoras para células receptoras, levando à modificação em seus mecanismos reguladores, dependendo da mensagem codificada na forma de biomolécula carregada. Verificou-se que exossomos derivados de células cancerosas ­ os verdadeiros representantes das células-mãe ­ modificam as regiões circundantes / distintas do tumor e participam da metástase, angiogênese e imunossupressão. Este estudo teve como objetivo estudar os efeitos de exossomos derivados de camundongos com tumor nas células T isoladas de baço de camundongos normais, usando experimentos de cocultura e análise de citômetro de fluxo. Concentrou-se, principalmente, em algumas populações de células T e citocinas, incluindo IFN-γ, células T reguladoras FOXP3 + (Treg) e KI67 (marcador de proliferação). Os resultados gerais indicaram mudanças aleatórias em diferentes conjuntos de experimentos, em que os exossomos derivados de câncer reduziram a expressão de IFN-γ em células T CD4 e CD8, da mesma forma que as células Treg também foram encontradas diminuídas na presença de exossomos de câncer. Nenhuma mudança significativa foi observada na expressão do marcador Ki67. Esses dados são úteis para a compreensão do papel dos exossomos do câncer na supressão de células do sistema imunológico no microambiente tumoral. Exossomos de câncer precisarão ser validados in vivo e in vitro em escala molecular com detalhes para aplicações clínicas.

Mesenchymal stem cells-derived exosomal miR-653-5p suppresses laryngeal papilloma progression by inhibiting BZW2

Abstract Objectives: Although miR-653-5p has been validated to participate in the progression of multiple types of cancer, the functional role of exosomal miR-653-5p derived from Mesenchymal Stem Cells (MSCs) in Laryngeal Papilloma (LP) has still remained elusive. Hence, this study aimed to investigate the role of MSCs-derived exosomal miR-653-5p in LP. Methods: LP tissues (n = 15) and adjacent normal tissues (n = 10) were collected to examine the expression level of miR-653-5p. The expression level of miR-653-5p in LP cells and normal cells was also detected. Then, miR-653-5p was overexpressed or silenced to explore its effects on the proliferation, migration, invasion, and apoptosis of LP cells. Thereafter, the effects of exosomal miR-653-5p derived from MSCs on LP cell progression and the potential regulatory mechanism of miR-653-5p were assessed. Results: It was revealed that the expression level of miR-653-5p was downregulated in LP tissues and cells. In addition, miR-653-5p suppressed the proliferation, migration, invasion, and apoptosis of LP cells. Exosomes derived from MSCs played a suppressive role in LP development and mediated the transmission of miR-653-5p to LP cells. Further exploration identified Basic leucine Zipper and W2 domains 2 (BZW2) as the target of miR-653-5p. More importantly, the rescue experiments revealed that MSCs-secreted exosomal miR-653-5p efficiently inhibited the aggressive phenotypes of LP cells, which could be significantly reversed by BZW2 overexpression in LP cells. Conclusion: MSCs-derived exosomal miR-653-5p exerted inhibitory effects on LP progression through targeting BZW2, which provided a novel idea for the therapy of LP. Clinical Trial registration number: chictr-ior-17011021.

Enrichment of miR-17-5p enhances the protective effects of EPC-EXs on vascular and skeletal muscle injury in a diabetic hind limb ischemia model

BACKGROUND/AIMS: Diabetes mellitus (DM) is highly susceptible to diabetic hind limb ischemia (DHI). MicroRNA (MiR)-17-5p is downregulated in DM and plays a key role in vascular protection. Endothelial progenitor cell (EPC)-released exosomes (EPC-EXs) contribute to vascular protection and ischemic tissue repair by transferring their contained miRs to target cells. Here, we investigated whether miR-17-5p-enriched EPC-EXs (EPC-EXsmiR-17-5p) had conspicuous effects on protecting vascular and skeletal muscle in DHI in vitro and in vivo. METHODS: EPCs transfected with scrambled control or miR-17-5p mimics were used to generate EPC-EXs and EPC-EXsmiR-17-5p. Db/db mice were subjected to hind limb ischemia. After the surgery, EPC-EXs and EPC-EXsmiR-17-5p were injected into the gastrocnemius muscle of the hind limb once every 7 days for 3 weeks. Blood flow, microvessel density, capillary angiogenesis, gastrocnemius muscle weight, structure integrity, and apoptosis in the hind limb were assessed. Vascular endothelial cells (ECs) and myoblast cells (C2C12 cells) were subjected to hypoxia plus high glucose (HG) and cocultured with EPC-EXs and EPC-EXsmiR-17-5p. A bioinformatics assay was used to analyze the potential target gene of miR-17-5p, the levels of SPRED1, PI3K, phosphorylated Akt, cleaved caspase-9 and cleaved caspase-3 were measured, and a PI3K inhibitor (LY294002) was used for pathway analysis. RESULTS: In the DHI mouse model, miR-17-5p was markedly decreased in hind limb vessels and muscle tissues, and infusion of EPC-EXsmiR-17-5p was more effective than EPC-EXs in increasing miR-17-5p levels, blood flow, microvessel density, and capillary angiogenesis, as well as in promoting muscle weight, force production and structural integrity while reducing apoptosis in gastrocnemius muscle. In Hypoxia plus HG-injured ECs and C2C12 cells, we found that EPC-EXsmiR-17-5p could deliver their carried miR-17-5p into target ECs and C2C12 cells and subsequently downregulate the target protein SPRED1 while increasing the levels of PI3K and phosphorylated Akt. EPC-EXsmiR-17-5p were more effective than EPC-EXs in decreasing apoptosis and necrosis while increasing viability, migration, and tube formation in Hypoxia plus HG-injured ECs and in decreasing apoptosis while increasing viability and myotube formation in C2C12 cells. These effects of EPC-EXsmiR-17-5p could be abolished by a PI3K inhibitor (LY294002). CONCLUSION: Our results suggest that miR-17-5p promotes the beneficial effects of EPC-EXs on DHI by protecting vascular ECs and muscle cell functions.

Exosomes secreted from human umbilical cord mesenchymal stem cells promote pancreatic ductal adenocarcinoma growth by transferring miRNAs / 中华肿瘤杂志

Objective: To observe the effects of exosomes derived from human umbilical cord mesenchymal stem cells on the proliferation and invasion of pancreatic cancer cells, and to analyze the contents of exosomes and explore the mechanisms affecting pancreatic cancer cells. Methods: Exosomes extracted from human umbilical cord mesenchymal stem cells were added to pancreatic cancer cells BxPC3, Panc-1 and mouse models of pancreatic cancer, respectively. The proliferative activity and invasion abilities of BxPC3 and Panc-1 cells were measured by cell counting kit-8 (CCK-8) and Transwell assays. The expressions of miRNAs in exosomes were detected by high-throughput sequencing. GO and KEGG were used to analyze the related functions and the main metabolic pathways of target genes with high expressions of miRNAs. Results: The results of CCK-8 cell proliferation assay showed that the absorbance of BxPC3 and Panc-1 cells in the hucMSCs-exo group was significantly higher than that in the control group [(4.68±0.09) vs. (3.68±0.01), P<0.05; (5.20±0.20) vs. (3.45±0.17), P<0.05]. Transwell test results showed that the number of invasion cells of BxPC3 and Panc-1 in hucMSCs-exo group was significantly higher than that in the control group (129.40±6.02) vs. (89.40±4.39), P<0.05; (134.40±7.02) vs. (97.00±6.08), P<0.05. In vivo experimental results showed that the tumor volume and weight in the exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs-exo) group were significantly greater than that in the control group [(884.57±59.70) mm(3) vs. (695.09±57.81) mm(3), P<0.05; (0.94±0.21) g vs. (0.60±0.13) g, P<0.05]. High-throughput sequencing results showed that miR-148a-3p, miR-100-5p, miR-143-3p, miR-21-5p and miR-92a-3p were highly expressed. GO and KEGG analysis showed that the target genes of these miRNAs were mainly involved in the regulation of glucosaldehylation, and the main metabolic pathways were ascorbic acid and aldehyde acid metabolism, which were closely related to the development of pancreatic cancer. Conclusion: Exosomes derived from human umbilical cord mesenchymal stem cells can promote the growth of pancreatic cancer cells and the mechanism is related to miRNAs that are highly expressed in exosomes.

Expression and clinical significance of plasma exosomal miR-34-5p and miR-142-3p in systemic sclerosis / 北京大学学报(医学版)

OBJECTIVE@#To detect the expression of plasma exosomal microRNA (miRNA) in systemic sclerosis (SSc), and to investigate its clinical significance.@*METHODS@#A total of 20 patients who were initially diagnosed with SSc and did not receive medication in Department of Rheumatology and Immunology of Meizhou People' s Hospital from January 2020 to January 2022 were recruited, as well as 15 healthy individuals whose gender and age matched with those of the SSc patients. Plasma exosomes were isolated using ultracentrifugation method. The expression levels of exosomal miR-34-5p, miR-92-3p and miR-142-3p were detected by quantative real-time polymerase chain reaction (qRT-PCR). Correlations between the expression levels of exosomal miRNAs and clinical characteristic were analyzed by Spearman's rank correlation coefficient test.@*RESULTS@#The mean age of 20 patients with SSc was (52.6±12.6) years, including 7 males and 13 females. Among the 20 SSc patients, 13 cases were diagnosed as limited cutaneous systemic sclerosis (lcSSc) and 7 cases were diagnosed as diffuse cutaneous systemic sclerosis (dcSSc) according to the extent of skin involvement. According to the findings of high resolution chest CT, 7 of 20 SSc patients were diagnosed with interstitial lung disease (ILD) and 13 SSc patients were diagnosed with non-ILD. The expression levels of exosomal miR-34-5p, miR-92-3p and miR-142-3p were significantly elevated in the SSc patients compared with those in the healthy controls group (P=0.003, P=0.000 1, and P=0.016, respectively). Compared with the SSc patients without ILD, the expression levels of miR-34-5p and miR-142-3p were significantly lower in the SSc patients with ILD (P=0.037 and P=0.015, respectively). The expression levels of exosomal miR-34-5p and miR-142-3p showed negative correlation with ILD (r=-0.48, P=0.031 and r=-0.55, P=0.011, respectively), and arthritis (r=-0.46, P=0.040 and r=-0.48, P=0.032, respectively). The expression levels of exosomal miR-142-3p showed a negative correlation with erythrocyte sedimentation rate (ESR) (r=-0.55, P=0.012).@*CONCLUSION@#Plasma exosomal miR-34-5p, miR-92-3p and miR-142-3p were dysregulated in SSc. The dyregulation of exosomal miR-34-5p and miR-142-3p showed correlation with SSc associated ILD (SSc-ILD).

Research Progress in Exosomes in the Pathogenesis of Bronchial Asthma / 中国医学科学院学报

Bronchial asthma is a heterogeneous chronic inflammatory disease involving multiple immune cells and structural cells.It is characterized by airflow limitation,airway hyperresponsiveness,and airway remodeling,with complex pathogenesis.In recent years,the research on exosomes has developed rapidly.Exosomes are small vesicles secreted by a variety of cells and are naturally found in various biological fluids,with stability and biocompatibility.Exosomes from different cells are involved in pathophysiological processes such as airway inflammation,remodeling,and hyperresponsiveness through specific mechanisms and play a regulatory role in multiple links in bronchial asthma.This review focuses on the role of exosomes from different cells in the pathogenesis of bronchial asthma.

Sciatic nerve derived exosomes in promotion of axon regeneration and functional recovery following peripheral nerve injury in rat / 中华显微外科杂志

Objective:To explore the effect of sciatic nerve derived exosomes(SN-EXO) on axon regeneration and functional recovery after peripheral nerve injury(PNI).Methods:From March 2021 to October 2022, the Department of Orthopedics of the First Affiliated Hospital of Zhengzhou University studied the effect of SN-EXO on the proliferation of Schwann cells(SCs) through EdU cell proliferation experiment. Twenty-one healthy male SD rats were randomly divided into 3 groups of sham operation, peripheral nerve injury(PNI) and SN-EXO treatment, with 7 rats in each group. The right sciatic nerves of rat models in sham group were exposed without injury. In the rat in PNI group and SN-EXO treatment group, PBS and SN-EXO were injected under the epineurium of right sciatic nerves following sciatic nerve crush. Sciatic nerve function index(SFI) was performed at 28 days after operation, and then sacrificed. Right sciatic nerves were removed for further exploration of nerve regeneration. The histopathological changes and axon arrangement of sciatic nerves were evaluated by HE staining. Regeneration efficiency of neurofilaments and SCs were obserred by NF200 and S100β double staining of sciatic nerve. The data obtained were statistically analyzed, and P<0.05 was statistically significant. Results:It was found that SN-EXO can significantly enhance the proliferation ability of SCs, with statistically significant difference( P<0.05). SFI in SN-EXO treatment group and PNI group were(-27.65±4.36) and(-57.33±7.49), respectively, and the difference was statistically significant( P<0.05). Axons in SN-EXO treatment group were arranged more closely and orderly than those in the PNI group at 28 days after operation, and there were less injury induced axon disintegration and vacuolation. Immunofluorescence assay indicated that NF200 and S100β fluorescence intensity in SN-EXO treatment group was significantly higher than that in the PNI group, and the difference was statistically significant( P<0.05). Conclusion:SN-EXO could enhance the proliferation of SCs to promote axon regeneration following peripheral nerve injury.

Progress in the regulatory effects of tumor-derived exosomes on macrophage polarization / 中华微生物学和免疫学杂志

Mononuclear macrophages are versatile cells that can have different responses to various microenvironmental signals. Under different stimuli of circumstances, macrophages can be fully polarized into classically activated macrophages (M1) and alternatively activated macrophages (M2), which are the extremes of a continuum of functional states. Nuclear factor-κB, cyclooxygenase 2, anoxia status, proto-oncogene MYC, Toll-like receptor signaling pathway, Notch signaling pathway and cytokines are all closely involved in the transition of tumor-associated macrophages from M1 to M2 phenotype. Macrophages that infiltrate tumor tissues are driven by tumor-derived cytokines to acquire a polarized M2 phenotype. These functionally polarized cells play a key role in the subversion of adaptive immunity and in inflammatory circuits that promote tumor development and progression. Exosomes derived from tumors have the characteristics of tumor cells and could participate in multiple processes of tumorigenesis and development. This review focused on exosomes derived from various cancer cells and discussed the role of the payloads of tumor-derived exosomes in modulating macrophage polarization in the tumor immune microenvironment and the intracellular signal mechanisms involved.

Research progress of human milk exosomes and their effects on intestinal mucosal barrier in neonates / 中华围产医学杂志

Human breast milk-derived exosomes (HMDEs) are newly discovered active signaling vesicles in breast milk, which are rich in nucleic acids, proteins, and lipids. These exosomes play an essential role in the development and maturation of the intestinal mucosal barrier in newborns. In addition, HMDEs possess distinctive properties that allow for remodeling and modification, thereby are expected to provide more efficient prevention and treatment strategies for neonatal intestinal diseases. This article aims to provide a comprehensive review of the origin, isolation, identification, labeling, structural features, composition, and biological functions, and their unique impact on the intestinal mucosal barrier function in newborns.

Progress in therapeutic potential of human breast milk-derived exosomes in neonate necrotizing enterocolitis / 中华围产医学杂志

Neonatal necrotizing enterocolitis (NEC) is one of the leading causes of neonatal death and no effective therapeutic drugs are currently available. Breastfeeding is a safe and effective preventive measure for NEC. Human breast milk-derived exosomes (HM-exos), which are membranous vesicles in breast milk, play an important role in maintaining the integrity of the intestinal barrier and promoting the repair of intestinal epithelial cells (IECs) damage through protecting IECs from oxidative stress, improving the proliferation and migration of IECs, maintaining the tight connection between IECs, inhibiting inflammatory response and regulating immune response.